Kurdistan Regional Governorate Ministry of Higher Education and Scientific Research University of Sulaimani Faculty of Medical Sciences/School of Medicine Department of Physiology

The Utility of Different Electrophysiological and Biochemical Parameters with Magnetic Resonance Imaging in the Diagnosis of Suspected Radiculopathy in Sulaimani Province A Thesis Submitted to the Faculty of Medical Sciences/Council of School of Medicine-Sulaimani University in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Medical Physiology

By Hiwa S. Namiq M.B.Ch.B, MSc (Physiology)

Supervisor

Supervisor

Dr. Qasim H. Abdullah

Dr. Ari S. Hussain

PhD (Physiology)

FICMS (Neurosurgery)

Assistant Prof. (Physiology)

Assist.Prof. of Neurosurgery

2013 A.C

1434 H

2713 K

‫حكومة اقليم كوردستان‪ /‬العراق‬ ‫وزارة التعليم العالي والبحث العلمي‬ ‫جامعة السليمانية‬ ‫فاكلتي العلوم الطبية‪/‬المدرسة الطبية‬ ‫تقييم المتغيرات الفسيولوجية العصبية مع فحص الرنين المغناطيسي في تشخيص‬ ‫الضغط على الجذور العصبية‬ ‫االطروحة مقدمة إلى مجلس المدرسة الطبية‪ ,‬جامعة السليمانية ضمن جزء من‬ ‫المتطلبات للحصول على درجة الدكتوراه الفلسفة في الفسلجة الطبية‬ ‫من قبل‬ ‫هيوا شفيق نامق‬ ‫بكالوريوس في طب و جراحة العامة‬ ‫ماجستير في الفسلجة‬ ‫باشرا ف‬ ‫الدكتور‬

‫الدكتور‬

‫ئاري سامي حسين‬

‫قاسم حسو عبدهللا‬

‫أستاذ مساعد في جراحة العصبية‬

‫ماجستير ودكتوراه في الفسلجة‬

‫طبيب استشاري بالجراحة العصبية‬

‫أستاذ مساعد في الفسلجة‬

‫تشرين االول ‪3102‬‬

‫حكومةتى هةريَمى كوردستان‪/‬عيَراق‬ ‫وةزارةتى خويَندنى باآلو تويَذينوةى زانستى‬ ‫زانكؤى سليَمانى‪/‬فاكةلَتى زانستة ثزيشكيةكان‬ ‫سكولَى ثزيشكى‪/‬بةشى كارئةندامزانى‬ ‫سوودى طؤرِانة كارئةندامزاني ية دةماريةكان و ثشكنينى تيشكى موكناتيسى لةو‬ ‫نةخؤشانةى كة ثةستان ضوةتة سةر رِةكى دةمارةكانى درِكة ثةتك‬

‫تويَذينةوةيةكة ثيَشكةش بة ئةجنومةنى سكووىل ثزيشكى ‪/‬زانكؤى سليمانى كراوة بؤ تةواو كردنى بةشيَك‬ ‫لة ثيَداويستى ثلةى دكتؤراى فةلسةفة لة كارئةندامزانى‬

‫لة اليةن‬

‫هيوا شفيق نامق‬ ‫بةكالؤريؤس لة ثزيشكى و نةشتةرطةرى طشتى‬ ‫ماستةر لة كارئةندامزانى‬

‫بة سةرثةرشتى‬

‫د‪.‬ئارى سامى حسني‬

‫د‪.‬قاسم حةسؤ عبداللة‬ ‫ماستةرو دكتؤرا لة كارئةندامزانى‬

‫ثرؤفيسؤرى ياريدةدةر لة نةشتةرطةرى ميَشك‬

‫ثرؤفيسؤرى ياريدةدةر لة كارئةندامزانى‬

‫ثزيشكى رِاويَذكارى نةشتةركةرى ميَشك‬

‫‪ 3172‬كوردى‬

‫‪ 7121‬كؤضى‬

‫‪ 3172‬زايينى‬

‫بسم هللا الرحمن الرحيم‬

‫َ‬ ‫ُ‬ ‫َو ه‬ ‫ُون َشيْئا ً‬ ‫ْ‬ ‫ُ‬ ‫ُط‬ ‫ب‬ ‫ِّن‬ ‫م‬ ‫م‬ ‫ك‬ ‫ج‬ ‫ر‬ ‫خ‬ ‫هللاُ أ‬ ‫ون أ ُ َّم َها ِت ُك ْم الَ َتعْ َلم َ‬ ‫َ‬ ‫َ‬ ‫ِ‬ ‫ار َواألَ ْف ِئدَ َة َل َعلَّ ُك ْم‬ ‫ْص َ‬ ‫َو َج َع َل َل ُك ُم ْالسَّمْ َع َواألَب َ‬ ‫ُون }‬ ‫َت ْش ُكر َ‬ ‫النحل‪87‬‬ ‫صدق هللا العظيم‬

Acknowledgements First of all great and continuous thanks to God for giving me life, believes, patience and strength to achieve this study. Special thanks and gratitude to my supervisor Dr. Qasim H. Abdulla for his patience and endless support throughout the period of achieving this research I'm also grateful to my supervisor Dr. Ari Sami for his help and guidance in this study and for recruiting patients for the study. I am also thankful to Dr. Ahmad Alnuaimi and Dr. Abdulfatah Hawrami for their help in statistical analysis. I would like also to thank the Schools of Medicine and Pharmacy at University of Sulaimani in providing me research requirements. I have special thanks to the staff of laboratory of Shaheed Dr. Aso's hospital that were very cooperative in completion of blood investigations and lastly I am thankful to all patients who participated in this study.

- VII -

PhD research Questionnaire for Patients with Suspected

Lumbosacral Radiculopathy Name: Age:

Sex:

Phone No. Height: Yes

Rheumatoid A. DM Thyroid disease Other diseases Hx of atherosclerosis and intermittent claudication 6- Hx of Hip disorders 7- Drug Hx and alcohol consumption

past medical diseases

  

1. 2. 3. 4. 5. 6. 7.

Neurological findings

Weight:

Yes No

No

12345-

Hx of current and

Chief complaint

ID: BMI:

1. Local injury/lesion in the back

Hx of

3. Myopathy

4. Neuromuscular

Back pain/lower limb pain Lower limb Parasthesia/numbness Altered sensation in groin, buttocks, or inner thighs Dermatomal involvment Decreased or absent muscle stretch reflex Increased reflex Impaired bowel and bladder function Foot drop, weakness of dorsiflexor muscles, SLRT Vibration/position sense

2. Neuropathy

disorders < 3 weeks

Duration of symptoms Other (indicate exact duration):

> 3 weeks

Investigations Value

Normal

Abnormal

MRI Findings 1. WBC 2. ESR 3. FBS Blood

4. S.GOT 5. S.GPT 6. S. creatinine 7. S.CPK 8. Hs-CRP

PhD research Questionnaire for Patients with Suspected

Cervical Radiculopathy Name: Age:

Phone No. Height:

Sex:

Yes Rheumatoid A. DM Thyroid disease Hx of atherosclerosis Hx of shoulder disorders 6- Other diseases 7- Drug Hx and alcohol consumption

Yes No

No

12345-

Hx of current and past medical diseases

Chief complaint

Weight:

ID: BMI:

1. Local injury/lesion in the back

Hx of

2. Neuropathy 3. Myopathy 4. Neuromuscular

Neck /upper limb pain

disorders Upper limb parasthesia/numbness

< 3 weeks

1. 2. 3. 4. 5.

Neurological findings

Dermatomal involvment Decreased or absent muscle stretch reflex Increased reflex Wrist drop, weakness of extensor muscles Vibration/position sense

Duration of symptoms Other (indicate exact duration):

> 3 weeks

Investigations Value

1. WBC 2. ESR 3. FBS 4. S.GOT Blood

5. S.GPT 6. S. creatinine 7. S.CPK 8. Hs-CRP

Normal

Abnormal

MRI Findings

Committee Certificate We, the examining committee, certify that we have read this thesis and discussed the graduate student Hiwa Shafiq Namiq in its contents and what is relevant to it on 5/12/2013, and in our opinion it deserves to be accepted for granting the degree of Doctor of Philosophy in Medical Physiology.

Professor Dr. Omar A. Al-Habib Ph.D. Physiology Chairman

Professor Dr. Salahaddin M.A. Al-Merani Ph.D. Physiology Member

Assistant Professor Dr. Raed S. Al-Nuaemi Ph.D. Physiology Member

Associate Professor Dr. Ahmad D.H. Al-Saffar Ph.D. Physiology Member

Assistant Professor Dr. Omar A. R. Barawi F.I.C.M.S (ortho.) M.D.O.A (The Netherlands) Member

Assistant Professor Dr. Qasim H. Abdullah Ph.D in Clinical Physiology Member and Supervisor

Assistant Professor Dr. Ari Sami H. Nadhim FICMS (Neurosurgery) Member and Supervisor

Approved by the Council of School of Medicine

Dr. Ari Sami Husain Nadhim Assistant Professor in Neurosurgery Head of School of Medicine/University of Sulaimani / / 2013

List of Abbreviations: ALT (SGOT) AST (SGOT) ATP BMI CK CMAP CRP CSF CT CR DDD DRG EDX ELISA EMG ESR HK HNP Hs-CRP IFCC LDH LSR MCV MRI NCS NCV nEMG PLID ROC SLRT SNAP SNCV TNF

Alanine aminotransferase (serum glutamic pyruvate transaminase) Aspartate aminotransferase (serum glutamate oxaloacetic transaminase)

Adenosine triphosphate Body mass index Creatine kinase Compound muscle action potential C- reative protein Cerebrospinal fluid Computed tomography Cervical radiculopathy Degenerative disc disease Dorsal root ganglion Electodiagnostic parametere Enzyme-linked immunosorbent assay Electromyography Erythrocyte sedimentation rate Hexokinase Herniated nucleus palposus High sensitivity C-reactive protein International federation of clinical chemistry Lumbar disc herniation Lumbosacral radiculopathy Motor conduction velocity Magnetic resonance imaging Nerve conduction study Nerve conduction velocity Needle electromyopathy Prolapsed lumbar intervertebral disc Receiver operating characteristic Straight leg raising test Sensory nerve action potential Sensory nerve conduction velocity Tumor necrosis factor

XVIII

LIST OF CONTENTS

Contents

Page No.

Abstract Acknowledgments List of centents List of figures

III VII VIII VIII

List of tables List of abbreviations

VIII XVIII

Chapter one Introduction Aim of the study Review of literature

1 3 4

1.1 Definition and causes

4

1.2 Lumbosacral radiculopathy

5

1.3 Cervical radiculopathy

5

1.4: History:

6

1.5: Epidemiology

7



1.5.1: Lumbosacral radiculopathy

7



1.5.2: Cervical radiculopathy

7

1.6: Risk factors:

8



1.6.1: Lumbosacral radiculopathy:

8



1.6.2: Cervical radiculopathy

8

1.7: Anatomy

9



1.7.1: Lumbar spine

9



1.7.2: Cervical spine

11

1.8: Pathophysiology of Radiculopathy

13



1.8.1: Role of mechanical factors

13



1.8.2: Role of inflammation in Radiculopathy

16



1.8.3: Pain generation and centralization

20

1.9: Diagnosis: 

22 22

1.9.1: Lumbosacral Radiculopathy - VIII -



24

1.9.2: Cervical radiculopathy:

1.10: Blood tests in radiculopathy:

29



1.10.1: High-sensitivity C-reactive protein

29



1.10.2: Creatine phosphokinase

29



1.10.3: Aminotransferases

30



1.10.4: Erythrocyte sedimentation rate (ESR)

30

1.11: Imaging studies

30



1.11.1: Discography

30



1.11.2: Myelography

31



1.11.3: Plain Radiography

31



1.11.4: Computed tomography (CT) Scanning

33



1.11.5: MRI in radiculopathy:

34

1.12: Electrodiagnosis (EDX) in radiculopathy

36



1.12.1: Nerve conduction studies in radiculopathy.

37



1.12.2: Needle EMG:

40

1.13: Utility of Electrodiagnostic parameters and MRI in radiculopathy

43

2: Subjects materials and method

46

2.1: Subjects and study design:

46

2.2: Patient selection:

46



2.2.1: Inclusion criteria

46



2.2.2: Exclusion criteria

47

2.3: Study protocol

47

2.4: Blood samples

48

2.5: Clinical assessment

48

2.5.1 Diabetes mellitus

49 - IX -

2.5.2. Thyroid disease 2.5.3 Rheumatoid arthritis 2.5.4 Drug history and Alcohol consumption 2.5.5 Body Mass Index Measurement (BMI) 2.6: Interpretation of results of MRI

50

2.7: Assessment of biochemical parameters

51



2.7.1: Serum High Sensitivity C - reactive protein (Hs-CRP)

51



2.7.2: Serum Creatine phosphokinase (CPK)

52



2.7.3: Serum glutamate oxaloacetic transaminase (GOT-AST)

53



2.7.4: Serum glutamic pyruvate transaminase (GPT-ALT)

53

2.8: Nerve Conduction Study Protocol

54



2.8.1: Sensory Nerve Conduction Study

56



2.8.2: Motor Nerve Conduction Study

57

2.9: Recording Methods

58



2.9.1: Sensory Nerve Conduction Study Procedure

58



2.9.2: Motor Nerve Conduction Study Procedure

61



2.9.3: Late responses

64

2.10: Needle Electromyography

66

2.11: Statistical analysis

70



2.11.1. Test Performance Characteristics

70



2.11.2. Limitations for the use of ROC results

71

3. Results

73

3.1 Demographic parameters

73

3.2 Blood test parameters for patients with suspected lumbosacral radiculopathy (LSR) and cervical radiculopathy (CR) compared with control group

73

-X-

3.3: Nerve conduction parameters in patients suspected of LSR and CR compared with the control group

74

3.4 Correlation between selected parameters (NCS and blood parameters) in the

76

control group 3.5 Correlation between selected parameters (Blood and NCS parameters) in

76

LSR and CR patients. 3.6: Receiver operating characteristic (ROC) curve analysis for NCS parameters

77

of upper limb to predict cervical radiculopathy 3.7: Receiver operating characteristic (ROC) curve analysis for NCS parameters

78

of lower limb to predict lumbosacral radiculopathy 3.8: Validity parameters for tibial CMAP amplitude when used to predict LSR

79

3.9 ROC area for BMI and Hs-CRP when used to predict radiculopathy

80

(cervical or lumbosacral radiculopathy) 3.10. Validity parameters of BMI and Hs-CRP when used as test to predict

82

radiculopathy. 3.11 Electrodiagnostic results according to duration of symptoms (DOS)

83

3.12: Electrodiagnostic results and foot drop/weak dorsiflexion

85

3.13: Electrodiagnostic results and straight leg raising test (SLRT) in LSR group

86

3.14: Electrodiagnostic results and vibration and position senses

87

3.15. Different electrodiagnostic results according to dermatomal distribution.

88

3.16. Electrodiagnostic results and stretch reflex

90

3.17. Association between types of EMG abnormality with types of MRI

91

abnormality

3.18. Association between Needle EMG, NCS, late responses and root/thecal - XI -

93

compression in MRI. 3.19. Electrodiagnostic results according to MRI root level

96

3.20. Consistency of abnormal needle EMG with abnormal MRI findings

99

regardless the root level 3.21. Consistency of abnormal needle EMG with abnormal MRI regarding the

99

root level 3.22. Comparison of rate of positive (Abnormal) electrodiagnostic tests, MRI

100

findings and clinical findings between patients with cervical and lumbosacral radiculopathy 3.23. Case-control comparison in positivity rate of selected tests for cervical and

102

lumbosacral radiculopathy 4. Discussion

103

4.1 Blood test parameters in patients with suspected lumbosacral radiculopathy (LSR) and cervical radiculopathy (CR) compared with control group

4.2. Nerve conduction parameters in patients suspected of LSR and CR

103

compared with the control groups 4.3. Correlation between selected parameters (NCS and blood parameters) in

105

the control group 4.4 Correlation between selected parameters (Blood and NCS parameters) in

106

LSR and CR patients. 4.5: Validity parameters for tibial CMAP amplitude when used to predict LSR

106

4.6 Validity parameters of BMI and Hs-CRP when used as test to predict

107

radiculopathy. 4.7 Electrodiagnostic results according to duration of symptoms (DOS)

107

4.8 Electrodiagnostic test results according to different clinical test findings:

108

- XII -

4.9 Association between types of EMG abnormality with types of MRI

111

abnormality 4.10 Electrodiagnostic (EDX) results according to MRI root level

112

4.11 Consistency of abnormal needle EMG with abnormal MRI findings

114

regardless/regarding the root level 4.12 Comparison of positive (Abnormal) electrodiagnostic tests, MRI findings

115

and clinical findings between patients with cervical and lumbosacral radiculopathy 4.13 Case-control comparison in positivity rate of selected tests for cervical and

117

lumbosacral radiculopathy 5.1: Conclusions

119

5.2: Recommendations

121

- XIII -

List of Figures Figure No. Figure 1.1

Title

Page

Examples of intervertebral disc problems

4

Cross section of lumbar spine Axial representation of C5 vertebra looking cephalad to caudal Inflammatory Cascade following mechanical injury of nerve root Causes of cervical radiculopathy Calibration curve for Hs-CRP standards against absorbance at 450nm. Photograph of NIHON KOHDEN EMG/EP machine Sensory nerve action potential parameters recorded in this study Compound muscle action potential parameters Median sensory nerve conduction study Ulnar sensory nerve conduction study Sural nerve conduction study

9 11

Figure 2.8 Figure 2.9 Figure 2.10

Median motor nerve conduction study Peroneal motor nerve conduction study Normal minimal F-wave latency of tibial nerve in one control subject.

62 63 64

Figure 2.11 Figure 2.12

H-reflex recorded from soleus muscle A: optimal location for G1 placement (double arrows). B: H-reflex response.

65 66

Figure 2.13

Muscle fiber motor unit potential parameters (A), Recruitment and interference pattern (B) Tibial distal and proximal motor responses recorded from abductor hallucis brevis muscle. A: Normal tibial CMAP amplitude recorded from a control subjetc. B: Decreased tibial CMAP amplitude recorded from a patient with chronic S1 radiculopathy.

69

ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls.

77

ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for

79

Figure 1.2 Figure 1.3 Figure 1.4 Figure 1.5 Figure 2.1 Figure 2.2 Figure 2.3 Figure2.4 Figure 2.5 Figure 2.6 Figure 2.7

Figure 3.1

Figure 3.2

Figure 3.3

Figure 3.4

- XIV -

14 15 52 55 57 58 59 60 61

75

78

selected nerve conduction study parameters when used as test to predict cases with lumbosacral radiculopathy differentiating them from healthy controls.

Figure 3.5

Figure 3.6

Figure 3.7

ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for BMI when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls. ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for HsCRP when used as test to predict cases with radiculopathy (cervical and LSR) differentiating them from healthy controls.

81

Neuropathic motor unit potentials and its parameters recorded from medial gastrocnemius muscle in a patient with chronic S1 sacral radiculopathy.

92

- XV -

82

List of Tables Table No.

Title

Page

Table 1.1

Non-skeletal causes of lumbosacral radiculopathy

6

Table 1.2

Differential diagnosis of lumbosacral radiculopathy

22

Table 1.3

Clinical attributes of solitary root lesions

23

Table 1.4

Physical findings in common cervical radiculopathy

26

Table 1.5

Differential diagnosis of cervical radiculopathy

28

Table 1.6

Electromyography in lower extremity radiculopathy: Most useful muscles to sample Electromyography in upper extremity radiculopathy: Most useful muscles to sample

40

Table 2.1

EMG measuring machine settings for NCS

55

Table 3.1

Demographic parameters of the study groups

73

Table 3.2

Comparison of blood test parameters between LSR and CR patients with control group

74

Table 3.3

NCS parameters of LSR and CR patients compared with control groups

74

Table 3.4

Correlation between selected parameters in control groups

76

Table 3.5

Correlation between selected parameters in LSR and CR group

76

Table 3.6

77

Table 3.11-A

ROC area for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls ROC area for selected nerve conduction study parameters when used as test to predict cases with lower limb radiculopathy differentiating them from healthy controls Validity indices for selected nerve conduction study parameters when used as test to predict cases with lumbosacral radiculopathy differentiating them from healthy controls. ROC area for BMI and Hs-CRP when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls. Validity indices for BMI and Hs-CRP when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls. Different Electrodiagnostic results according to duration of symptoms

Table 3.11-B

Different Electrodiagnostic results according to DOS

84

Table 3.12

Electrodiagnostic results and foot drop

85

Table 3.13

Electrodiagnostic test results according to SLRT

86

Table 3.14-A

Electrodiagnostic test results according to abnormal vibration and position

87

Table 1.7

Table 3.7

Table 3.8

Table 3.9

Table 3.10

- XVI -

42

78

80

80

83

80

List of Tables Table 3.14-B

sense in LSR group Electrdiagnostic results and vibration and position senses in CR group

88

Table 3.15-A

Electrodiagnostic results according to dermatomal distribution in LSR

89

Table 3.15-B

Electrodiagnostic results according to dermatomal distribution in CR

89

Table 3.16-A

Electrodiagnostic and stretch reflex in LSR group

90

Table 3.16-B

Electrodiagnostic results according to stretch reflex in CR group

91

Table 3.17-A

Types of EMG abnormality with types of MRI abnormality in LSR group

92

Table 3.17-B

Types of EMG abnormality with types of MRI abnormality in CR group

92

Table 3.18-A

94

Table 3.19-A

Association of different Electrodiagnostic result and root/thecal compression in MRI Association of different Electrodiagnostic result and root/thecal compression in MRI Different EDX results according to level of MRI abnormality in LSR group

Table 3.19-B

Different EDX results according to level of MRI abnormality in CR group

98

Table 3.20

Consistency of abnormal needle EMG findings with abnormal MRI findings regardless the root level in LSR and CR groups Consistency of abnormal needle EMG with abnormal MRI regarding the root level The difference between cervical and lumbosacral radiculopathy in rate of positive tests findings Case-control comparison in positivity rate of selected tests for LSR and CR groups

99

Table 3.18-B

Table 3.21 Table 3.22 Table 3.23

- XVII -

95 97

100 101 102

Chapter 1

Introduction and Literature Review

Introduction: Radicular pain is one of the most common complaints referred to the electromyography (EMG) laboratory. Even with the wide spread use of magnetic resonance imaging; EMG continues to play an important role in the evaluation of radiculopathy. Although imaging studies are diagnostic in the more common radiculopathies caused by structural lesions, they are often unrevealing in radiculopathies caused by infection, infiltration, demyelination, or infarction. Whereas imaging studies do well in visualizing the spinal cord and nerve roots and their relationship to the vertebrae and intervertebral discs, they yield no information about how the nerve is functioning. In this regard EMG complements imaging with its ability not only to localize the lesion but also to functionally assess the nerve (Preston and Shapiro, 2005). Electrophysiologic and MRI studies are used together in the evaluation of suspected radiculopathy. Studies have shown that both are useful diagnostic tools (Albeck et al., 1995,). However, both procedures have their limitations. For instance, EMG is likely to be negative if performed early and may remain negative in radiculopathies that are mild or predominantly sensory (Wilbourn and Aminoff, 1988, Nardin et al., 1999) on the other hand MRI may reveal structural spinal abnormalities in asymptomatic subjects (Boden et al., 1990, Jensen et al., 1994). One important factor affecting EMG is the timing of the studies. EMG changes of denervation (e.g., fibrillations and positive sharp waves) develop first in the paraspinals (7– 10 days), and then in the limb muscles of the affected myotome (2–3 weeks); reinnervation changes may be seen at around 3–6 months. Thus, EMG may be negative if performed before evidence of denervation has developed or if denervation has resolved and reinnervation is incomplete. Furthermore, EMG also tests only anterior nerve root function, and may be normal in root injuries that affect the dorsal root fibers predominantly (Wilbourn and Aminoff, 1988). 1

Chapter 1 Introduction and Literature Review Magnetic resonance imaging (MRI) has largely replaced computed tomography (CT) as the primary diagnostic imaging modality in the evaluation of suspected radiculopathy, while needle electromyography (EMG) remains the mainstay of the electrodiagnostic evaluation. The EMG provides a measure of the physiologic integrity of the nerve roots, while MRI provides structural details of the nerve roots and surrounding structures (Nardin et al., 1999). Although they are commonly used in the diagnosis of cervical and lumbosacral radiculopathy, but the agreement between the two studies in relation to the clinical status is still controversial especially when comparing their results with an asymptomatic subjects. A correct diagnosis of radiculopathy is important for implementation of timely and appropriate treatments (Charles et al., 2010). Nerve-root compression by itself does not always lead to pain unless the dorsal-root ganglion is also compressed (Song et al., 1999). Hypoxia of the nerve root and dorsal ganglion can aggravate the effect of compression (Sugawara et al., 1996). Evidence from the past decade indicates that inflammatory mediators — including matrix metalloproteinases, prostaglandin E2, interleukin-6, and nitric oxide are released by herniated cervical intervertebral disks (Kang et al., 1995, Kang et al., 1997, Furusawa et al., 2001). These observations provide a rationale for treatment with antiinflammatory agents (Miyamoto et al., 2002). In patients with disk herniation, the resolution of symptoms with nonsurgical management correlates with attenuation of the herniation on imaging studies (Mochida et al., 1998, Matsumoto et al., 2001). C-reactive protein (CRP) is an acute phase reactant for trauma and infections and is mainly produced in the liver in response to systemic inflammations, resulting in increased blood CRP levels. It has long been recognized that CRP is closely related to immunology, inflammation and host defense and as a result it has been used as an inflammatory marker (Bharadwaj et al., 1999; Thompson, 2004). 2

Chapter 1 Introduction and Literature Review Till now to the best of our knowledge, there have been no such studies comparing EMG and MRI in the diagnosis of radiculopathy in our locality. Accordingly, the present project was adopted to examine the EMG and MRI findings in patients with cervical and lumbar radiculopathies in order to determine how they are correlated with one another and with the clinical symptoms.

Aims of the study 1. To evaluate the diagnostic utility of different electrophysiologic tests in patients with suspected radiculopathy 2. To compare the diagnostic value of MRI with electrophysiologic examination in patients with lumbosacral and cervical radiculopathies. 3. To investigate the role of inflammation in radiculopathy.

3

Chapter 1

Introduction and Literature Review

1: Literature Review 1.1: Definition and causes Cervical and lumbosacral radiculopathies are conditions that involve a pathologic process which affect the spinal nerve roots. Commonly, this process is a herniated nucleus pulposus that anatomically compresses a nerve root within the spinal canal. Another common cause of radiculopathy is spinal stenosis resulting

from a

combination

of degenerative

spondylosis,

ligament

hypertrophy, and spondylolisthesis (figure 1.1). Inflammatory radiculitis is another pathophysiologic process that can cause radiculopathy (Dillingham, 2002, Regan, 2012). Radiculopathy can also occur on a microscopic level without evidence of a mass lesion. The cause can be infiltration by tumor (carcinomatous or lymphomatous meningitis), infiltration by granulomatous tissue (e.g. sarcoid), or infection (e.g. Lyme disease, herpes zoster, cytomegalovirus, herpes simplex). Rare cases of pure radiculopathy or polyradiculopathy may be due to acquired demyelinating neuropathy (e.g. Guillain-Barr'e syndrome) (Preston and Shapiro, 2005).

Figure 1.1: Examples of intervertebral disc problems (Regan, 2012) 4

Chapter 1 Introduction and Literature Review In addition, radiculopathy can be seen as a result of infarction of the nerve root which may occur in vasculitic neuropathy and presumably occurs commonly in diabetic polyradiculopathy (Caridi, 2005). 1.2: Lumbosacral radiculopathy: Lumbosacral radiculopathy is a condition in which a disease process affects the function of one or more lumbosacral nerve roots (Tarulli and Raynor, 2007). Causes of lumbosacral radiculopathy include both skeletal and nonskeletal factors (Table 1.1). Intervertebral disc herniations commonly cause nerve root compression from the anterior aspect of the foramen (Bush et al., 1997). Disc herniations can either be acute or chronic. Chronic herniations occur when the intervertebral disc becomes degenerated and desiccated. This causes collapse of the disc space and bulging of the annulus into the neural foramen. Chronic herniations and facet spondylosis generally cause symptoms with an insidious onset that tend to be less severe. An acute herniation occurs when a fragment of the nucleus pulposus extrudes through a defect in the annulus fibrosis. This generally is associated with the sudden onset of severe symptoms, in contrast to those associated with a chronic disc herniation. Researchers hypothesize that pain syndromes and deficits arise as a result of both ischemia and inflammation notions that would explain why acute insults tend to result in more profound symptoms than slow, adaptable processes (Humphreys et al., 1998, Buttermann, 2008). 1.3: Cervical radiculopathy: Cervical radiculopathy is a pain and/or sensorimotor deficit syndrome that is defined as being caused by compression of a cervical nerve root (Carette and Fehlings, 2005, Fouyas et al., 2002). The compression can occur as a result of disc herniation, spondylosis, instability, trauma, or rarely, tumors. Patient presentations can range from complaints of pain, numbness, and/or tingling in the upper extremity to electrical type pains or even weakness (John et al., 2011). 5

Chapter 1 Introduction and Literature Review Table1.1: Non-skeletal causes of lumbosacral radiculopathy (Hsu et al., 2011) Diabetes mellitus Single or multiple radiculopathies Inflammatory disorders Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) Sarcoidosis Infectious diseases Borrelia burgdorferi (Lyme disease) Cytomegalovirus Epstein Barr Herpes simplex virus Human immunodeficiency virus (HIV) Mycobacterium Varicella zoster virus (Herps zoster or shingles) Malignancy Lymphoma Metastasis Multiple myeloma Vascular Arteriovenous malformation Radiation-induced vascular occulusion Vasculitis (nerve root infarction)

1.4: History Compression of the lumbosacral nerve roots arising in the setting of degenerative stenosis was described as early as 1931(Towne and Reichert, 1931).The relationship between lumbar intervertebral disc rupture and ‘‘sciatica’’ initially was described by Mixter and Barr in 1934 (Mixter and Barr, 6

Chapter 1 Introduction and Literature Review 1934). Semmes and Murphey described similar acute cervical disc pathology resulting in ‘‘radiculitis’’ in 1943. Verbiest drew attention to the role of developmental narrowing of the lumbar canal in radicular syndromes in 1954. Stenotic upper extremity pain syndromes occurring in the setting of degenerative ‘‘cervical arthritis’’ with resultant irritation of the cervical nerve roots was recognized by Semmes and Murphey (1943).

1.5: Epidemiology 1.5.1: Lumbosacral radiculopathy Lumbosacral radiculopathy is one of the most common disorders evaluated by neurologists and is a leading referral cause for the performance of electromyography. Although precise epidemiologic data are difficult to establish, the prevalence of lumbosacral radiculopathy is approximately 3-5%, distributed equally in men and women. Degenerative spondyloarthropathies are the principal underlying cause of these clinical syndromes and are increasingly commonplace with age. Men are most likely to develop symptoms in their 40s, whereas women are affected most commonly between ages 50 and 60 years (Tarulli and Raynor, 2007). 1.5.2: Cervical radiculopathy Population-based data from Rochester and Minnesota indicate that cervical radiculopathy has an annual incidence rate of 107.3 per 100,000 for men and 63.5 per 100,000 for women, with a peak at 50 to 54 years of age. A history of physical exertion or trauma preceded the onset of symptoms in only 15 percent of cases. A study from Sicily reported a prevalence of 3.5 cases per 1000 population (Salemi et al., 1996). In North America, the Saskatchewan Health and Back Pain Survey reported 54% of respondents experienced neck pain in the previous 6 months, of which almost 5% said pain was highly disabling (Cote et al., 2000).

7

Chapter 1

Introduction and Literature Review

1.6: Risk factors: 1.6.1: Lumbosacral radiculopathy: Several occupational factors are believed to be associated with an increased risk of sciatica and disc herniation (Mundt et al., 1993): 1.

Frequent heavy lifting

2.

Frequent twisting and bending

3.

Exposure to vibration

4.

Sedentary activity

5.

Driving

1.6.2: Cervical radiculopathy Risk factors that have been identified for cervical disc degeneration and radiculopathy include the following (Roth et al., 2009): Strongly Implicated 1. Cigarette smoking 2. Axial load-bearing 3. High-risk occupation: meat carriers, dentists, professional drivers 4. Prior lumbar radiculopathy Possibly Implicated 1. Metabolic disturbance 2. Prior cervical trauma 3. Vibrational exposure 4. Diet/nutritional factors 5. Genetic factors 6. Racial factors 7. Gender 8. Atherosclerosis 9. Auto-immune factors No Role Identified 1. Repeated turning of the neck 8

Chapter 1 2. Sports

Introduction and Literature Review

3. Sedentary occupations

1.7: Anatomy 1.7.1: Lumbar spine The lumbar spine has 5 vertebrae with an intervertebral disc interposed between adjacent vertebral bodies. A cartilaginous endplate exists between the disc and the adjacent vertebral bodies and it is considered part of the disc. The disc itself is composed of a central nucleus pulposus surrounded peripherally by the annulus fibrosis (Windsor and Sullivan, 2008) (Fig. 1.2).

Figure 1.2: Cross section of lumbar spine (Williams and Park, 2003) In normal young adults, the nucleus is a semifluid mass of mucoid material. The nucleus is composed of approximately 70-90% water in a young healthy disc, but this percentage generally decreases with age. The primary nuclear constituents include glycosaminoglycans, proteoglycans, and collagen. Type II collagen predominates in the nucleus. Proteoglycans are the largest 9

Chapter 1 Introduction and Literature Review molecules in the body and possess an enormous capacity to attract water through oncotic forces. These forces increase their weight by 250% and result in a gellike composition. The nucleus pulposus is embedded in a gelatinous matrix of various glucosaminoglycans, water, and salts. This material usually is under considerable pressure and is restrained by the crucible-like annulus (Williams and Park, 2003). In adults, the spinal cord terminates at the L1-2 intervertebral level as the conus medullaris. The nerve roots descend from this point through the spinal canal as the cauda equina and exit eventually through the neural foramina at their respective intervertebral levels. Ventral roots, containing primarily motor fibers, arise from rootlets, which extend from the ventral gray matter of the spinal cord. Dorsal rootlets, carrying sensory information, extend centrally from the dorsal root ganglia that lie outside the spinal cord, within the neural foramen. Just distal to the intervertebral foramen, the dorsal and ventral roots unite to form a mixed spinal nerve, which divides into dorsal and ventral primary rami. The dorsal rami supply the paraspinal muscles and skin overlying the paraspinal region, whereas the ventral rami give rise to the lumbosacral plexus and, eventually, the individual nerves supplying the lower limbs and sacral region. The muscles supplied by a single spinal segment constitute a myotome; the skin region supplied by a single spinal segment is a dermatome (Tarulli and Raynor, 2007). The principal functions of the disc are to allow movement between vertebral bodies and to transmit loads from one vertebral body to the next. When axial loads are transmitted to the spine, the annulus and nucleus display a complex intertwined role, allowing for pressure dispersal. The nucleus has the capacity to sustain and transmit pressure. The annular lamellae are capable of sustaining an axial load on the basis of its bulk. When an axial load is applied to the nucleus, it tends to shorten. The nucleus attempts to radially expand, thereby exerting pressure on the annulus. Annular resistance efficiently opposes this outward pressure, creating a hoop-tension effect. The intervertebral disc is so 11

Chapter 1 Introduction and Literature Review effective at resisting these axial loads that a 40-kg load to a disc causes only 1 mm of vertical compression and only 0.5 mm of radial expansion. During movement, the annulus acts like a ligament to restrain movements and partially stabilize the interbody joint. The oblique orientation of the annular fibers provides resistance to vertical, horizontal, and sliding movement. The alternation in the direction of the annular fibers in consecutive lamellae causes the annulus to resist twisting motions poorly (Windsor and Sullivan, 2008). 1.7.2: Cervical spine The cervical spine has 7 vertebrae (C1-C7) and 8 spinal nerves (C1-C8). The C1 vertebra is called the atlas and is a ring of bone, which rotates around the odontoid process of the axis, or the C2 vertebra. The cervical spinal nerves are named corresponding to the vertebral body below the nerve. The C8 nerve exits between C7 and T1 vertebra (Drake and Gray, 2008). Between 2 vertebrae is the foramen where a spinal nerve, blood vessels, and the sinuvertebral nerves pass through. The superior and inferior borders of this foramen are the pedicles, the anterior border is the intervertebral disk and vertebral bodies, and the posterior border is the facet, or zygapophyseal joint (Benzel, 2005) (Fig. 1.3).

Figure 1.3: Axial representation of C5 vertebra looking cephalad to caudal (Caridi, 2011). 11

Chapter 1 Introduction and Literature Review In 1-15% of the population, a bony arch may form converting the groove on C1 for the vertebral artery and the first cervical nerve into an arcuate foramen (Clark, 2005). There is also a spinal canal that is bordered by the laminae and the ligamentum flavum posteriorly and anteriorly by the vertebral bodies and intervertebral disks. The midsagittal (anteroposterior) diameter of the canal in the upper cervical spine (C1-3) is about 21 mm, whereas the lower cervical spine (C4-7) is 18 mm. The cervical spinal cord usually occupies about 40% of the cervical canal. Cervical extension decreases the canal diameter by 2-3 mm (Devereaux, 2007). The neural foramen is made up of the facet joint posteriorly and the intervertebral disc anteriorly. The superior and inferior borders are comprised of the pedicles of the vertebral bodies above and below, respectively. The foramina are largest in the upper cervical spine and gradually narrow distally, with the C7/T1 foramina being the narrowest (Caridi, 2011). The C1-C2 joint, or the atlanto-axial joint, has no disk between them and has about 1/2 of rotational range of motion. The transverse ligament of the atlas holds the odontoid process in place and is stronger than the odontoid process itself. There is also a pair of alar ligaments on both sides of the occipital condyles, which limit rotation. Normal cervical spine has a shallow lordosis, which can be decreased or even reversed in patients with degenerative changes and increased in patients with increased thoracic kyphosis (Roth et al, 2009). Each cervical spinal nerve has a ventral and a dorsal spinal root. The ventral horn of the spinal cord contains alpha motor neurons, which give off efferent motor fibers in the ventral root. The dorsal root ganglion and its afferent sensory fibers travel in the dorsal root. The ventral and dorsal root combine to form a spinal nerve, which then divides into the dorsal primary ramus and the ventral primary ramus. The dorsal ramus supplies the posterior neck structures, whereas the ventral ramus supplies prevertebral and paraspinal muscles and then forms the brachial plexus, which then go on to innervate the upper limb. A 12

Chapter 1 Introduction and Literature Review myotome is a group of muscles innervated by 1 spinal nerve. A dermatome is the sensory distribution of a dorsal root. The myotome, dermatome, and muscle stretch reflexes can help localize the level of the cervical radiculopathy and radiculitis (Levin et al., 2001).

1.8: Pathophysiology of Radiculopathy 1.8.1: Role of mechanical factors  Lumbosacral radiculopathy The most common etiology of lumbosacral radiculopathy is nerve root compression caused by a disc herniation or spondylosis (ie, spinal stenosis due to degenerative arthritis affecting the spine). Additional etiologies include nonskeletal causes of nerve root compression and noncompressive mechanisms such as infection, inflammation, neoplasm, and vascular disease (Philip, 2011). Spinal nerve roots and their nutrient vessels lack a perineurium and demonstrate a poorly developed epineurium, rendering them particularly vulnerable to mechanical injury. Additionally, the blood supply to spinal nerve roots is not as secure as that to their peripheral nerve counterparts. It is likely that the most pertinent mechanical effect of herniated disc material or degenerative stenosis on neural tissue is one of increased pressure (Robinson et al., 1995). In vivo studies of the effect of pressure on nerve roots have revealed that the first effect probably is one of impaired venous blood flow within the vasa nervorum, which can be observed initially with compressive pressures as low as 5 to 10 mm Hg. At these levels, capillary stasis and ischemia have been observed. Partial blockage of axonal transport also can be observed with pressure as low as 10 mm Hg (Olmarker et al., 1990). Nerve conduction failure first occurs when pressures of 50 to 75 mm Hg are sustained for 1 to 2hours, and neural ischemia can be complete with compressive exposures that reach 70 to 130 mm Hg (Rydevik and Holm, 1990)

13

Chapter 1 Introduction and Literature Review Although local compression of neural tissue may induce direct structural insults, including deformation of the nodes of Ranvier and paranodal myelin, such effects typically occur with higher sustained pressures. The injuries more commonly observed in association with lower compressive exposures (i.e, less than 200 mm Hg) likely arise in the setting of impaired blood and nutritional supply to neural tissue (Rydevik and Holm, 1990) Degenerative disc disease (DDD) can also cause mechanical nerve root compression in the intervertebral foramen from decreased disk height, foraminal hypertrophy, ligamentum hypertrophy, spondylolisthesis, and periradicular fibrous tissue. Degenerative changes affect all levels but are relatively less common above C3-C4 disk (Montgomery and Brower, 1992). Most commonly the C5-6 disk space (affect C6 nerve root) followed by C6-7 (C7 nerve root) are affected. Cervical spondylotic radiculopathy starts about 10 years after the disk starts to degenerate, and the mechanical incompetence of the motion segment leads to spondylotic degeneration of facets and uncovertebral joints .As the disk loses height, uncovertebral joints come into contact leading to osteophyte formation.

Figure 1.4: Inflammatory Cascade following mechanical injury of nerve root (Montgomery and Brower, 1992). 14

Chapter 1 Introduction and Literature Review The zygapophyseal joints override and also form osteophytes. These osteophytes are also called “hard” disk protrusions and can themselves compress nerves (Montgomery and Brower, 1992).  Cervical radiculopathy: The most common cause of cervical radiculopathy (in 70 to 75 percent of cases) is foraminal encroachment of the spinal nerve due to a combination of factors, including decreased disc height and degenerative changes of the uncovertebral joints anteriorly and zygapophyseal joints posteriorly (i.e., cervical spondylosis) (Fig. 1.5). In contrast to disorders of the lumbar spine, herniation of the nucleus pulposus is responsible for only 20 to 25 percent of cases (Roth, 2009, Shelerud and Paynter, 2002).

Figure 1.5: Causes of cervical radiculopathy (Daniel et al., 2009)

15

Chapter 1

Introduction and Literature Review

1.8.2: Role of inflammation in Radiculopathy The mechanisms underlying radicular pain are poorly understood. Nerveroot compression by itself does not always lead to pain unless the dorsal-root ganglion is also compressed. Hypoxia of the nerve root and dorsal ganglion can aggravate the effect of compression. Evidence from the past decade indicates that

inflammatory

mediators

—

including

matrix

metalloproteinases,

prostaglandin E 2, interleukin- 6, and nitric oxide — are released by herniated cervical intervertebral disks. These observations provide a rationale for treatment with antiinflammatory agents (Furusawa et al., 2001, Miyamoto et al., 2002).

Although the mechanical stressors that contribute to radicular syndromes were well described by the 1940s, it was not until the early 1970s that the chemical and inflammatory components of neural injury were first identified. In 1973, Marshall and Trethewie stated: ‘‘we consider the acute pain in disc is due to local irritation of the nerve-root producing oedema and release of protein and H-substances at the site of disc injury. Relief of pain by cortisone accords with these findings….’’ (Marshall and Trethewie, 1973). Various theories have been proposed as the sources of pain generation in disc injury, involving an intervertebral disc that is degenerative, bulging, or protruding. Mechanical compression and an immunologic or inflammatory response are possibly related to pain from a disc injury. Mechanical compression of a nerve alone is not necessarily painful; however, if that nerve is inflamed, it can produce severe pain with a small amount of mechanical compression (Windsor and Sullivan, 2008). Central to this idea is the arachidonic cascade. Phospholipase A2 (PLA2) is the rate-limiting step in this pathway, controlling the release of prostaglandins and leukotrienes. It has been reported that human 16

Chapter 1 Introduction and Literature Review PLA2 levels in the intervertebral disc are many times more active than the PLA2 found in other human tissues. This research has led to the investigation of PLA2 and other biochemicals as putative mediators of the inflammatory response to intervertebral disc injury and, thus, inducing back pain (Saal et al., 1990).

The epidural application of nucleus pulposus to cauda equina nerve roots in pigs, without associated mechanical nerve root compression, was observed to result in a pronounced reduction in nerve conduction when compared with the similar application of a fat control. The application of nuclear material also resulted in a more pronounced histologic injury than that observed in controls. Such findings suggest that there may be a direct biochemical effect of nucleus pulposus material on neural tissue that results in inflammatory, microvascular, and structural injury (Olmarker et al., 1993). Herniated nucleus palposus (HNP) causes radicular pain through chemical radiculitis from proteoglycans and phospholipases released from the nucleus pulposus, which propagate an inflammatory cascade, and from direct nerve injury/compression, which can lead to nerve demyelination and neurologic symptoms (Shigeru et al., 2004). In a dog model, the effects on nerve roots after the incision of an adjacent annulus fibrosus were similarly investigated. Once again, without a more apparent mechanical stressor, resultant capillary stasis, significantly reduced conduction velocity, and structural axonal change were observed. These findings suggest that an annular tear, which might not be radiologically visible, and the subsequent leakage of nucleus pulposus can contribute to the pathophysiology of radiculopathy (Kayama et al., 1996). Similarly, synovial cytokines have been shown to impair sciatic nerve function in a rat model, raising the possibility that leakage of synovial fluid from an adjacent zygapophyseal joint might contribute to radicular pathology (Wehlig et al., 1990). In a controlled behavioral study using a rat model, chromic gut sutures were applied loosely to the lower lumbar nerve roots. In these animals, the 17

Chapter 1 Introduction and Literature Review recovery from thermal hyperalgesia seemed to depend, in part, on the reduction of local phospholipase A2 activity after ligature introduction. In those groups in which corticosteroid was introduced epidurally, a more pronounced reduction of phospholipase A2 activity and a more rapid return to normal behavior were observed (Lee et al., 1998). Several studies identified multiple known inflammatory mediators at the site of disc herniation and nerve injury. Increased levels of cytokines, leukotrienes, nitric oxide, immunoglobulins, and interleukins also have been detected at the site of disc injury (Goupille et al., 1998). An award-winning study specifically investigated the potential role of tumor necrosis factor (TNF)-a in sciatica associated with herniated lumbar discs. Exogenous TNF-a was applied in an in vivo rat model and resulted in neuropathologic and behavioral changes markedly similar to those observed with the application of nucleus pulposus. These findings suggest that TNF-a may be a key player in the pathophysiologic processes leading to radicular pain (Igarashi et al., 2000). Immunohistologic studies of herniated lumbar disc tissue have identified increased levels of cyclo-oxygenase 2 (Cox -2) and prostaglandin E2 (PGE-2) (Deleo et al., 2000, Miyamoto et al., 2000). Through the selective blocking of Cox-2, PGE-2 synthesis also pain was distinctly suppressed; suggesting that Cox-2and associated inflammatory cytokines might contribute to radiculopathy through an upregulation of prostaglandin synthesis. It was observed that introduction of a Cox-2 inhibitor in a rat model of radiculopathy resulted in a reduction in mechanical allodynia. Pain behavior was significantly lower in both the systemically and the intrathecally treated groups when compared with a control. The intrathecal treatment group demonstrated a great and statistically significant attenuation of allodynia (Miyamoto et al., 2000). Studies of the role of inflammation in radicular syndromes have also shed light on a potentially associated systemic inflammatory process and elevated plasma C-reactive protein levels in response to local nerve root injury (Le Gars 18

Chapter 1 Introduction and Literature Review et al., 2000). Although multiple inflammatory mediators have been identified at the site of disc injury, the relationship between clinical symptoms and the presence of inflammatory cells such as macrophages, leukocytes, and neutrophils remains less clear (Kawakami et al., 2000). An immunohistochemical analysis of 96 transligamentous disc herniations was performed and correlated with patients’ motor weakness and response to straight leg–raise maneuvers. No significant relationship between the presence of inflammatory cells and clinical symptoms was observed and activated T cells demonstrated a limited correlation with straight leg–raise limitation. The authors concluded that macrophages were probably more active in disc resorption than in the pathologic processes contributing to sciatica (Gronblad et al., 2000). A study of 179 disc samples from patients who had undergone discectomy also attempted to correlate preoperative clinical data with macrophage infiltration. After statistical analysis no significant correlation between macrophage presence and the recorded clinical data was identified although varying amounts of inflammatory cells were identified, (Rothoerl et al., 1998). Mast cells are known to play an important role in inflammatory processes; their presence in herniated lumbar disc samples has also been studied. Fifty herniated lumbar disc samples were obtained from patients who had undergone discectomy and compared with control disc samples. Only a minority of disc herniations demonstrated mast cells after toluidine blue staining and immunocytochemical analysis. This finding suggests a limited role for mast cells in the inflammatory processes of radiculopathy after disc herniation (Habtemariam et al., 1999). A study of cervical disc specimens removed after discectomy for radiculopathy also has been performed. These samples were compared with a control group of disc material removed during anterior surgery after traumatic burst fractures. Significantly increased matrix metalloproteinase, nitric oxide, PGE-2, and interleukin-6 were identified compared with control group. These observations were similar to those made in previous studies of lumbar disc 19

Chapter 1 Introduction and Literature Review material, suggesting that similar pathophysiologic processes likely were contributing in patients with cervical radiculopathy (Kobayashi, 1995).

1.8.3: Pain generation and centralization Pain and parasthesias often are referred to as positive symptoms of radiculopathy, whereas weakness and numbness are considered negative symptoms. Positive symptoms are believed to reflect neuronal hyperactivity, and negative symptoms may stem from diminished neural firing occurring in the setting of axonal loss or conduction block (Robinson et al., 1995, Thomas and Ochoa, 1993). Using the technique

of microneurography,

in which

microelectrodes are placed within the fascicles of peripheral nerves, it has been suggested that the more distal parasthesias of lumbar radiculopathy arise when activity in large sensory afferent fibers is generated ectopically. Such ectopic activity is presumed to occur from irritation of the nerve root or dorsal root ganglion (DRG) (Nordin et al., 1995). DRG is a unique component of the spinal nerve, containing the cell bodies for the sensory neurons. The DRG is particularly sensitive to mechanical irritation and is suspected to be a key player in radicular pain syndromes. Because the DRG typically is located within the neural foramen, foraminal disc pathology or stenosis might be more likely to result in a burning or dysesthetic type of pain involving the affected limb (Cohen et al., 1992). In addition to the positive and negative symptoms originating from direct involvement of the spinal nerve and DRG, symptoms also may arise from activation of those surrounding pain generators that most likely are intimately involved in radiculopathy (Robinson et al., 1995). The spinal nerve dura mater is richly innervated by an extensive intraspinal neural plexus derived from the sinuvertebral nerves. This innervation is particularly pronounced over the ventral aspect of the thecal sac and around the nerve root sleeves (Bogduk , 1997). The dura mater is both mechanically and 21

Chapter 1 Introduction and Literature Review chemically sensitive, and its stimulation can result in lumbar and lower extremity pain (Groen et al., 1990). In radicular pain syndromes, in addition to those symptoms arising from direct nerve root involvement, irritation of the surrounding dura may result in local somatic and more distally referred symptoms to the extremity (Bogduk, 1997). It has been suggested that the dysesthetic pain in nerve root injury stems from volleys of impulses beginning in damaged afferent fibers of the spinal nerve roots, whereas the associated deeper aching discomfort might be caused by the activation of the nervi nervorum that innervate the neural and meningeal tissues (Janig and Koltzenburg, 1991). Several pathologies can cause pain originating from the cervical spine. Herniated nucleus pulposus (HNP) is a condition in which the central part of an intervertebral disk gets pushed out, which can cause neck pain from the inflammatory response or nerve dysfunction from the inflammation or mechanical compression of spinal nerves.In HNP, the disk is thought to start degenerating in the second decade with repetitive strain causing posterolateral annular tear, circumferential tears causing radial fissures, and nuclear material extrusion through these tears causing disk desiccation and nuclear degradation. Spinal stenosis is a narrowing of the spinal canal or the intervertebral foramina, which is usually a result of spondylosis or cervical degenerative disk disease (DDD). Spinal stenosis can occur from bone spurs, or osteophytes, from spondylolisthesis, or slipping of 1 vertebral body on another, or from ligamentous thickening causing compression. If the narrowing causes spinal nerve dysfunction, patients can acquire radicular symptoms. If there is cord compression, or myelopathy, bowel and bladder dysfunction, as well as motor and sensory deficits, may result (Roth et al., 2009).

21

Chapter 1

Introduction and Literature Review

1.9: Diagnosis: The diagnosis of radiculopathy is based on history and clinical examination, imaging studies, and electrodiagnostic (EDX) testing. 1.9.1: Lumbosacral Radiculopathy 1. Clinical history: Pain

and

sensory

symptoms

such

as

paresthesia,

dysesthesia,

hyperesthesia, or anaesthesia that involve a specific lumbosacral dermatome are suggestive of a radicular process. Similarly, weakness confined to the muscles in a particular lumbosacral myotome should raise suspicion for radiculopathy. Inability to get up from a chair suggests iliopsoas or quadriceps weakness, while buckling of the knee is consistent with quadriceps weakness, and dragging of the toe points to tibialis anterior weakness. Elucidation of triggering and alleviating factors may also be helpful. Radicular pain that worsens with Valsalva or improves while lying down suggests a compressive etiology. Conversely, radicular pain that worsens with lying down suggests an inflammatory or neoplastic etiology. The acute onset of symptoms with bending, lifting, or trauma may herald a radiculopathy. However, none of these factors is specific for

radiculopathy.

Bowel/bladder

symptoms,

particularly

new

urinary

incontinence, suggest a cauda equina syndrome (Hsu, 2011). Sometimes disc herniation does not cause radicular symptoms (Jensen et al., 1994). In addition, the clinical presentation itself may be inconclusive. For example, injuries affecting the sacroiliac and zygapophysial joints, ligaments, muscles, and the peripheral disk annulus may cause referred pain suggestive of radiculopathy (Park et al., 1993, Schwarzer et al., 1994, Schwarzer et al., 1995). Disorders that mimic lumbosacral radiculopathy are illustrated in table 1.2: Table 1.2: Differential diagnosis of lumbosacral radiculopathy Neurologic  Lumbosacral plexopathy  Herps zoster

Foot and ankle abnormalities  Planter fasciiatis Muscle and connective tissue 22

Chapter 1

Introduction and Literature Review

 Peripheral mononeuropathy (e.g.  Myofacial pain syndrome sciatic neuropathy)  Fibromyalgia  Multiple sclerosis  Polymyalgia rhrumatica Hip abnormalities  Ankylosing spondylitis  Hip and pelvic bone and joint Vascular pathology  Gluteal artery syndrome  Greater trochanteric bursitis Other  Piriformis syndrome.  Catamenial sciatica  Ileopsoas bursitis (endometriosis) Knee abnormlaities  Nephrolithiasis  Ileotibial band syndrome  Pes anserine bursitis 2. Physical Examination Evaluation for lumbosacral radiculopathy requires a careful neurologic examination. A summary of findings for specific nerve root levels of involvement is found in the Table1.3. Table 1.3: Physical findings of LSR (solitary root lesions) (Hsu, 2011) Root

Pain

Sensory loss

Weakness

Reflex loss

L1

Inguinal region

Inguinal region

Rarely hip flexion

None

L2-L3-

Back, radiating Anterior

L4

to

thigh, Hip

anterior occasionally

thigh

adduction,

and median lower leg

medial

flexion,

hip Patellar tendon knee

extension

lower

leg Back,

L5

radiating

Lateral

to dorsum foot, web flexion,

buttock, lateral space thigh, calf dorsum

calf, Hip abduction, knee Semimembranosus/

between dorsiflexion,

lateral first and second extension and toe foot,

great toe.

toe tendon and

flexion,

foot

eversion

and

inversion

23

foot semitendinosus

Chapter 1

Introduction and Literature Review Back, radiating Posterior

S1

to

calf, Hip extension, knee Achilles tendon

buttock, lateral or planter and planter flexion

lateral

and foot

posterior thigh, posterior

calf,

lateral

or

planter foot S2-S3-S4

Sacral

or Medial

buttock radiating

pain, perineal

buttock, Weakness may be Bulbocavernosus, and minimal

to perianal regions.

urinary and fecal

posterior aspect

incontinence

of

well

leg

or

perineum

with anal wink

as

as sexual

dysfunction

Additional procedures (eg, straight leg raising test, reverse straight leg raising test) may be useful but their specificity, sensitivity, and reproducibility are variably limited. Vertebral tenderness is suggestive of infection but is not specific enough to be clinically useful. Deep tendon reflexes should be assessed at both the quadriceps (L2/L3/L4) and Achilles (S1). There is no reliable reflex to assess L5, the most common root compressed in mechanical lumbosacral radicular disease. The sensory examination is more subjective than other parts of the neurologic examination and is further confounded by dermatomal overlap and variability. However, it can provide important information for localization (Deyo and Weinstein, 2001). 1.9.2: Cervical radiculopathy: 1. Clinical history: The patient history alone can diagnose cervical radiculopathy in over 75% of cases. The most common symptom associated with cervical radiculopathy is arm pain or paresthesias in the dermatomal distribution of the affected nerve. Typical patient with cervical radiculopathy or stenosis presents with an insidious onset of neck and arm pain. Discomfort can range from a dull ache to a severe burning pain. Typically, pain is referred to the medial border of the 24

Chapter 1 Introduction and Literature Review scapula, and the patient’s chief complaint is lower neck or shoulder pain. As the condition progresses, the pain radiates to the upper or lower arm and into the hand, along the sensory distribution of the nerve root(s) that is involved. Older patient may have had previous episodes of neck pain or give a history of having spondylosis of the cervical spine that may have been previously diagnosed by another physician (Wainner and Gill, 2000). It is important to recognize that acute disk herniations, and sudden narrowing of the neural foramen, may also occur in injuries involving cervical extension, lateral bending, or rotation with axial loading. These patients usually complain of increased pain with neck positions that cause foraminal narrowing including extension, lateral bending, or rotating toward the symptomatic side. Some patients report a reduction in their radicular-type symptoms by abducting their shoulder and placing their hand behind their head. This relief in symptoms is thought to occur by decreasing tension at the nerve root. Patients may complain of sensory changes along the involved nerve root dermatome, which can include tingling, numbness, or loss of sensation. Some patients may complain of motor weakness. A very small percentage of patients will present only with weakness, without significant pain or sensory complaints (Polston, 2007). 2. Physical examination: Sensory examination can distinguish between a C8 radiculopathy and ulnar neuropathy, as there will be splitting of the hypalgesia in either the third or fourth digit with ulnar neuropathy. With C8 radiculopathy, the entire digit will be affected. Motor examination may or may not show a grade of weakness in the myotome that corresponds to the pathologic nerve. No myotome corresponds to the upper four cervical nerve roots. C5 radiculopathy may show weakness in the deltoids; C6 will show weakness in the biceps and flexor carpi ulnaris (evaluated by testing for wrist extension); C7 weakness occurs in the triceps, as well as the brachioradialis; C8 pathology causes weakness in the intrinsic muscles of the hand, as evaluated by finger abduction and grip. Muscle stretch reflexes also 25

Chapter 1 Introduction and Literature Review tend to be decreased in the setting of radiculopathy. Biceps hyporeflexia is indicative of C6 radiculopathy, while decrease in the triceps and brachioradialis reflexes corresponds to pathology at C7. Cervical range of motion is often tested in patients who complain of neck pain and radicular symptoms (Youdas et al., 1991). Patients often have impairment in their range of motion and limitation in their function. This is most commonly seen in extension, since the foramina tend to narrow significantly when the spine is extended. This has been shown by both anatomic in vitro studies as well as CT studies of the spine in vivo (Humphreys et al., 1998). Table1. 4: Physical findings in common cervical radiculopathy (Wainner et al., 2003)

Observation. Typically, the patient exhibits a head tilt away from the side of injury and may hold his or her neck stiffly. Active range of motion is usually reduced, particularly in extension, rotation, and lateral bending, either toward or away from the affected nerve root. Increased pain with lateral bending away from the affected side can cause increased displacement of a disk herniation on a nerve root, whereas ipsilateral pain would suggest an impingement of a nerve root at the site of the neural foramen (Dvorak, 1998).A patient with cervical 26

Chapter 1 Introduction and Literature Review radiculopathy and/or stenosis may have a change in the normal cervical lordosis or thoracic kyphosis (Rao et al., 2007). Palpation. On palpation, tenderness is usually noted along the cervical paraspinal muscles, usually more pronounced along the ipsilateral side of the affected nerve root. Muscle tenderness may be present along the muscles where the symptoms are referred (eg, medial scapula, proximal arm, lateral epicondyle). Associated hypertonicity or spasm on palpation in these painful muscles may occur (Rao et al., 2007, Carette and Fehlings, 2005). Motor. Manual muscle testing is an important aspect of determining an affected nerve root level on physical examination. Manual muscle testing is performed to detect subtle weakness in a myotomal distribution. Motor weakness is usually the last symptom seen in cervical radiculopathy or stenosis. It is very important that if any clinical weakness is noted in the affected limb, that this be compared with the unaffected side (Rhee et al., 2007, Carette and Fehlings, 2005). Sensory. On sensory examination, a dermatomal decrease or loss of sensation should be noted in patients with a single nerve root radiculopathy. In addition, patients with radiculopathy may have hyperesthesia to light touch and pinprick examination (Rhee et al., 2007). However, the sensory examination can be quite subjective because it requires a response by the patient. The sensory examination should be performed with both light touch and pinprick. In cases of mild radiculopathy, the pinprick examination may be the only sensory test that is positive, and this is more reliable (Wainner and Gill, 2000). Deep Tendon Reflexes. The deep tendon reflexes, or muscle stretch reflexes, are helpful in the evaluation of patients who present with limb symptoms that are suggestive of a radiculopathy or stenosis. Any grade of reflex can be normal, so it is the asymmetry of the reflexes that is most helpful. The biceps brachii reflex is obtained by tapping the distal tendon in the antecubital fossa. This reflex occurs at the C5-C6 level. The brachioradialis 27

Chapter 1 Introduction and Literature Review reflex is another C5-C6 reflex that can be obtained by tapping the radial aspect of the wrist. The triceps reflex can be obtained by tapping the distal tendon at the posterior aspect of the elbow, with the elbow relaxed at about 90° of flexion. This tests the C7-C8 nerve roots.The pronator reflex can be helpful in differentiating C6 and C7 nerve root problems. If this reflex is abnormal in conjunction with an abnormal triceps reflex, then the level of involvement is more likely to be C7 (Wainner and Gill, 2000, Dvorak, 1998). Disorders that mimic cervical radiculopathy are illustrated in table 1.5 (Lauder, 1999) Table 1.5: Differential diagnosis of cervical radiculopathy Neurologic  Neurogenic

Elbow abnormalities thoracic

 Medial epicondylitis

outlet

 Lateral epicondylitis

syndrome  Pancoast tumor

Wrist or hand abnormalities

 Brachial plexopathy

 Wrist/finger flexor or extensor

 Peripheral mononeuropathy (e.g. suprascapular,

long

tendonitis

thoracic, Muscle or connective tissue disease  Myofacial pain syndrome

ulnar neuropathy etc)  Syringomyelia

 Fibromyalgia

 Intracranial tumors

 Polymyalgia rheumatic

Shoulder abnormalities

Vascular

 Impingement syndrome (Rotator cuff tendinitis)

 Vascular

thoracic

syndrome

 Rotator cuff tears

 Aortic arch syndrome

 Biceps tendonitis

 Vertebral artery dissection

 Glenohumoral instability  Glenoid cyst

28

outlet

Chapter 1

Introduction and Literature Review

1.10: Blood tests in radiculopathy: Inflammation

plays

an

important

role

in

radiculopathy.

Once

inflammation has been established, the nerves become exquisitely sensitive to pressure, producing prolonged and pain-generating discharge with either gentle manipulation or pressure (Refshauge and Maher, 2006) 1.10.1: High-sensitivity C-reactive protein Lumbar disc herniation (LDH) induces an inflammatory reaction around the nerve roots which may cause radicular pain (Sugimori et al., 2003). In histological studies, inflammatory cells, predominantly macrophages have been found in herniated disc tissue harvested during surgery (Kawaguchi et al., 2002). These cells spontaneously produce inflammatory mediators such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor (TNF)-α, leukotriene B4 (LTB4), thromboxane B2 (TxB2), phospholipase A2, nitric oxide (NO) (Kang et al., 1996, Takahashi et al., 1996, Nygaard et al., 1997)

resulting in an

inflammatory response in the area surrounding the disc herniation (Kawaguchi et al., 2002, Kawaguchi et al., 2001, Doita et al., 2001, Virri et al., 2001, Woertgen et al., 2000, Gronblad et al., 2000). Pro-inflammatory cytokines, such as IL-6 and IL-1, are largely responsible for the induction of CRP synthesis in the liver and stimulate the liver resulting in an increase in the concentration of CRP in the serum (Gabay and Kushner, 1999). 1.10.2: Creatine phosphokinase Creatine kinase (CK) is an enzyme found in skeletal muscle, myocardium, and brain that catalyzes the reaction of creatine phosphate and adenosine diphosphate to creatine and adenosine triphosphate, thus generating energy (Bais and Edwards, 1982). An important clinical use of serum CK is in the diagnosis of neuromuscular disease. CK elevation is commonly associated with myopathies, but elevations may also occur in neurogenic disorders, such as motor neuron disease (Nardin et al., 2009). Many neurogenic disorders can present with elevated serum creatine kinase (CK) (Chahin and sorenson, 2009). 29

Chapter 1 1.10.3: Aminotransferases

Introduction and Literature Review

Alanine aminotransferase (ALT, formerly serum glutamic pyruvate transaminase-SGPT) and aspartate aminotransferase (AST, formerly serum glutamate oxaloacetic transaminase-SGOT ) are the most commonly used indicators of hepatic cell necrosis. They are present in high concentration in liver cells where they catalyze the transfer of alanine and aspartate a-amino groups to the a-keto groups of ketoglutaric acid to produce pyruvic and oxaloacetic acids. Injury to liver cell membranes causes leakage of aminotransferases into the circulation (Dufour et al., 2000, Kew, 2000). Normal ALT levels are 10-55 IU/L (international units per liter) and normal range for AST is 10 to 40 IU/L (Thapa and Anuj, 2007). Aminotransferases are sensitive but relatively nonspecific indicators of liver cell injury. ALT is the more specific of the two because, for the most part, it is confined to liver, whereas AST is present not only in liver but also in skeletal and cardiac muscle, brain and kidney and red blood cells (Dufour et al., 2000, Kamath, 1996, Kew, 2000). 1.10.4: Erythrocyte sedimentation rate (ESR) A more non-specific measure of inflammation is the erythrocyte sedimentation rate (ESR), a common hematology test that tracks the rate of red blood cell precipitation for 1 hour. There are little clinical studies that have examined any correlation between ESR level and chronic low back or radicular pain patients (Park and Lee, 2010).

1.11: Imaging studies 1.11.1: Discography Discography provides information about the structure of discs that may not be learned from other sources. Discographic pain provocation is a very important part of the evaluation. Discography is also indicated in the assessment of patients in whom surgery has failed and in the assessment of discs before fusion or minimally invasive interventions (Windsor and Sullivan, 2008). 31

Chapter 1 Introduction and Literature Review Much of the controversy surrounding discography centers on the unfavorable results reported by Earl Holt in 1968 (Holt, 1968). He examined 30 prison inmates (70-72 discs) and reported a 37% false-positive rate in asymptomatic volunteers. Also Walsh and associates reported on lumbar discography in normal subjects (Walsh et al., 1990). In asymptomatic subjects, the discogram alone was abnormal in 17%. When the criteria for a positive discogram included a concordant pain response, none of the subjects were positive. 1.11.2: Myelography The value of myelography is the ability to check all disc levels for abnormality and to define intraspinal lesions; it may be unnecessary if clinical and CT findings are in complete agreement. The primary indications for myelography are suspicion of an intraspinal lesion or questionable diagnosis resulting from conflicting clinical findings and other studies. In addition, myelography is of value in a previously operated spine and in patients with marked bony degenerative change that may be underestimated on MRI (Williams and Park, 2003). Myelography is improved by the use of postmyelography CT scanning in this setting, as well as in evaluating spinal stenosis. Bell et al. found myelography more accurate than CT scanning for identifying herniated nucleus pulposus and only slightly more accurate than CT scanning in the detection of spinal stenosis (Bell et al., 1984). 1.11.3: Plain Radiography 1. Lumbosacral radiculopathy The changes found in plain x-rays are mostly scoliosis, loss of lumbar lordotic curve (These are mostly due to chronic spasm of the low back muscle due to chronic irritation of nerve roots by the disc or osteophytes). Other changes found in plain x-ray lumbosacral spines are: sacralisation, reduction of intervertebral space, spina bi-fida (congenital), osteophytes causing narrowing of

intervertebral

foramina.

Ossified 31

posterior

longitudinal

ligament,

Chapter 1 Introduction and Literature Review Hypertrophied or thickened ligamentum flava may cause canal stenosis causing neurogenic claudication. Hypertrophy of the facet joint causes compression on nerve roots which causes radiculopathy. These bony abnormalities act as predictor for future possibility of prolapsed lumbar intervertebral disc (PLID) (Ansary et al., 2010). 2. Cervical radiculopathy The first test that is typically done is plain x-ray. Antero-posterior and lateral views are useful for demonstrating the overall alignment of the spine as well as the presence of any obvious spondolytic changes. Lateral flexion and extension views are helpful to diagnose any instability that may be present and not seen on a static radiograph. On the lateral view, there may be disk-space narrowing. Typically, the cervical disk spaces get larger from C2-C6, with C5-C6 being the widest disk space in normal necks, and C6-C7 slightly narrower. Besides narrowing, there may be subchondral sclerosis and osteophyte formation. On oblique views, there may be foraminal stenosis at the level of the suspected radiculopathy, comparing it with the opposite foramina, if uninvolved (Regan et al. 2011, Kaiser and Holland, 1998). The atlantodens interval is the distance from the posterior aspect of the anterior C1 arch and the odontoid process. This interval should be less than 3 mm in adults and less than 4 mm in children. An increase in the atlantodens interval suggests atlanto-axial instability, such as in cases of trauma or rheumatoid arthritis. Flexion and extension views can be helpful in assessing spinal mobility and stability in these patients (Kaiser and Holland, 1998, Yue et al., 2001). Plain radiographs of the cervical spine may show a loss of normal cervical lordosis, suggesting muscle spasm, but most other features of degenerative disease are found in asymptomatic people and correlate poorly with clinical symptoms (Canadian Chiropractic Association, 2005). Other studies also outlined the limitations of conventional radiographs of the cervical spine. This is due to the low sensitivity of radiography for the 32

Chapter 1 Introduction and Literature Review detection of tumors or infections, as well as its inability to detect disk herniation and the limited value of the finding of cervical intervertebral narrowing in predicting nerve-root or cord compression (Mink et al., 2003, Pyhtinen and Laitinen, 1993). 1.11.4: Computed tomography (CT) Scanning 1. CT in lumbosacral radiculopathy Although CT has made substantial advances and the diagnostic accuracy has substantially improved to the level of MRI, the vast majority of surgeons today prefer MRI. The application is therefore mostly limited to patients with contraindications for MRI such as pacemakers and metal implants. However, in these cases CT is often combined with myelography for better depiction of the nerve roots. Compared with the surgical findings, the accuracy of MRI was 90.3% and of CT myelography 77.4% (Herzog, 1996). 2. CT in cervical radiculopathy CT scanning provides good visualization of bony elements and can be helpful in the assessment of acute fractures. It can also be helpful when C6 and C7 cannot be clearly seen on traditional lateral radiographic views. The accuracy of CT imaging of the cervical spine ranges from 72% to 91% in the diagnosis of disk herniation. The accuracy has approached 96% when combining CT scanning with myelography. The addition of contrast material allows for the visualization of the subarachnoid space and assessment of the spinal cord and nerve roots (Stafira et al., 2003). CT scanning with myelography is thought to best assess and localize spinal cord compression and any underlying atrophy. This study can also determine the functional reserve of the spinal canal in evaluating patients with possible cervical stenosis. Because of the improved soft-tissue visualization provided by magnetic resonance imaging (MRI), CT scanning is being replaced by MRI for most cervical spine disorders (Kaiser and Holland, 1998, Stafira et al., 2003) but it can be useful in distinguishing the extent of bony spurs, foraminal encroachment, or the presence of ossification of the posterior 33

Chapter 1 longitudinal ligament.

The

Introduction and Literature Review combination of CT with the intrathecal

administration of contrast material (CT myelography) provides accuracy similar to and possibly superior to that of MRI, but its invasive nature makes MRI preferable in most cases. 1.11.5: MRI in radiculopathy: 1. Lumbosacral radiculopathy: MRI is the imaging modality of choice for evaluation of suspected lumbar disc herniation and is frequently used in the diagnostic evaluation of spinal disorders. Although MRI provides excellent anatomic detail, the relationship between pathoanatomy and clinical symptoms is controversial. It can be difficult to know which details of the anatomic picture are important, and what findings are more likely than others to manifest clinically (Lurie et al., 2009).  Intervertebral disc prolapse and degeneration Extrusion of the softer material from within an intervertebral disc into or through a posterior or posterolateral radial tear in the annular fibrosis is a common cause of neural involvement. This takes the form of a focal broadbased bulge in the margin of the annulus, or a focal mass extending upwards or downward in the anterior epidural space. Far lateral protrusions or extruded fragments involve the intervertebral foramina, not the spinal canal. They are commonest in the lumbar spine. On MRI, extruded fragments often are brighter than disc substance in T2-weighted images, and may enhance after intravenous gadolinium (Sutton, 2003).  Degenerative changes Loss of normal tension or volume in the nucleus pulposus tends to cause a circumfrential bulging of the annulus fibrosus and tension on the periosteum resulting in osteophytosis and marginal sclerosis. Reactive changes occur in the adjacent vertebral bodies and are well shown by MRI. Degeneration in ligaments can lead to fibrocartilagenous metaplasia, calcification, ossification and myxomatous degeneration, all of which can lead to diffuse thickening or a 34

Chapter 1 Introduction and Literature Review focal mass which may compress neural tissue. This process can involve the posterior longitudinal ligament, the cruciform ligament at the craniocervical junction, the ligament flava and the capsular ligaments of the facet joints with subsequent ossifications. With the exception of focal masses directly compressing spinal roots, clinic-radiological correlation generally is poor, even with MRI. MRI often presents direct evidence that compression is damaging cord substance, in the form of focal signal changes in the spinal cord at or minimally below the relevant intervertebral level (Sutton, 2003). The diagnostic utility of MRI in radiculopathy is influenced by both the timing of the study and the dynamic nature of the pathologic lesion. Modic and his collegues studied patients with lumbar radiculopathy using serial MRI scans and showed substantial decreases in the size of large disk herniations in 36% of patients at 6 weeks, and in more than 60% at 6 months (Modic et al. 1995). Additional studies of both lumbar and cervical disk herniations have shown significant regression in the size of these lesions at follow-up intervals ranging from 5 to 12 months; in many cases, herniations have disappeared (Komori et al, 1996, Bush et al, 1997, Westmark et al., 1997). 2. Cervical radiculopathy MRI is the method of choice in cervical radiculopathy and can demonstrate disc protrusions. MRI is more reliable than CT at demonstrating soft disc protrusions in the cervical spine where there is less epidural fat. MR, in contrast to CT myelography, is non-invasive and does not utilize ionizing radiation (Birchall et al., 2003). Also it demonstrates far lateral protrusions (Sutton, 2003). MR-myelography is reported to achieve higher sensitivity rates ( Birchall et al., 2003, Fortin et al., 2002, Kaiser et al., 1998). The imaging data should always be interpreted in the clinical context as particularly MRI often yields false positive results showing abnormalities in asymptomatic patients (Van et al., 2006, Van et al., 2005). 35

Chapter 1 Introduction and Literature Review MRI exhibits disc herniation in 20–35% and disc bulging in 56% of asymptomatic adults under 60 years of age. MRI frequently demonstrates endplate (Modic) changes which have been shown to be indicative of symptomatic disc degeneration in the lumbar spine (Weishaupt 2001). MRI also allows for an excellent assessment of the craniocervical junction (C0–C2). However, alterations of ligamentous structures and particularly rotational abnormalities are frequently seen in asymptomatic controls (Pfirrmann et al., 2001, Pfirrmann et al., 2000).  Spinal stenosis The term spinal stenosis should be used with caution, because it has a tendency to become a diagnosis when it may be inappropriate. Clinical correlation only becomes good when the lumbar spinal canal is very narrow: cross-sectional area even less than 110 mm2 on CT, or narrow enough to eliminate CSF signal on T2-weighted MRI. The lateral part of the spinal canal (lateral recess) often is the most affected, usually mainly due to hypertrophy of the facet joints. However, with the exception of S1, the spinal roots are within the thecal sac as they cross the disc and simply are displaced medially rather than entrapped (Sutton, 2003).

1.12: Electrodiagnosis (EDX) in radiculopathy In patients with radiculopathy, nerve conduction studies in most cases are normal and electrodiagnosis is usually established on Needle EMG. Although some motor abnormalities are occasionally seen in radiculopathy, the more important reason to perform nerve conduction studies is to exclude other conditions that may mimic radiculopathy as carpal tunnel syndrome and ulnar neuropathy at elbow in case of upper limb and peroneal neuropathy at fibular neck in case of lower limb (Preston and Shapiro, 2005). Clinically

EMGs

are

commonly

performed

to

demonstrate

radiculopathy, particularly in the following situations (Barr, 2013):

36

a

Chapter 1 Introduction and Literature Review 1. To determine if the structural changes seen on MRI are the common finding of an asymptomatic abnormality or are actually causing physiologic abnormalities in the nerve root. 2. To determine the most likely affected level if clinical symptoms and imaging levels do not match. 3. To look for physiologic evidence if noncompressive radiculopathies are suspected. 4. To determine prognosis related to axonal loss. 5. To search for other causes of neurologic symptoms. 1.12.1: Nerve conduction studies in radiculopathy.  Lumbosacral radiculopathy 1. Sensory nerve conduction studies Sensory nerve conduction studies are normal in radiculopathy, even if the physical examination reveals significant sensory loss, because the lesion occurs proximal to the dorsal root ganglion. Sensory NCS may be abnormal only if farlateral osteophytes reach far enough to impinge on the dorsal root ganglia (Dumitru, 1995). Forty to sixty-five percent of DRG at the L5 and S1 levels may be proximal to the intervertebral foramen (Hamanishi and Tanaka, 1993; Kikuchi et al., 1994) and as such subject to compression with radiculopathies. Abnormal superficial peroneal and sural SNAPs have been reported with L5 and S1 root injury (Levin, 1998). The usual sparing of SNAPs may be due to the type of fibers affected and not only absence of DRG injury. SNAP amplitudes (and conductions) are dependent on discharge in large afferent fibers that would be unaffected by injury to the small fibers which convey pain (Morris, 2002). 2. Motor nerve conduction studies: Compound motor action potentials are usually normal unless severe damage has occurred, or if multiple root levels are involved, in which case there may be some diminished amplitude (Barr, 2013). Decreased compound muscle 37

Chapter 1 Introduction and Literature Review action potential amplitudes elicited from the extensor digitorum brevis with peroneal motor studies may help diagnose axonal degeneration of an L5 radiculopathy (Kraft, 1998), and also low CMAP amplitudes are seen when severe axonal loss has occurred, such as with cauda equina lesions or penetrating trauma that severely injures a nerve root. The distal motor latencies and conduction velocities usually are preserved because they reflect the fastest conducting nerve fibers (Wilbourn and Aminoff, 1998). CMAP abnormalities in radiculopathies are limited by the overlapping root innervations and the usually incomplete nature of the root injury. For similar reasons, slowing of motor conduction velocities between proximal and distal stimulation sites is uncommon and, if present, limited in degree. Decrease in motor conduction would be restricted to the mild slowing seen with loss of the largest, fastest conducting motor fibers (Morris, 2002). 3. F-waves F-waves (first recorded from foot muscles) are late responses involving the motor axons and axonal pool at the spinal cord level. They can be assessed and classified by using the minimal latency, mean latency, and chronodispersion (Wilbourn and Aminoff, 1998). F-wave responses assess nerve conduction both distally and proximally. Abnormal F-wave responses with normal distal conduction studies suggest a proximal lesion, either in the plexus or roots. However, F-waves will be abnormal if the recorded muscle is innervated by the affected nerve roots (Preston and Shapiro, 2005). F waves can be recorded following stimulation of every motor nerve; however, they are commonly recorded in distal muscles. In these muscles, F waves are easily seen, because the long latency of the F wave relative to the shorter M latency is such that there is no overlap between the potentials. In more proximal muscles, this difference lessens and the F wave overlaps the M wave, making it difficult to detect the smaller F wave (Rivner, 1998) 38

Chapter 1 Introduction and Literature Review F-waves demonstrate low sensitivities and are not specific for radiculopathy; rather, they are a better screen for polyneuropathy. Published sensitivities range from 13% to 69%; however, these studies lacked a control group and because they are mediated over such a long physiologic pathway, they can be abnormal owing to polyneuropathy, sciatic neuropathy (Kuruoglu et al., 1994, Scelsa et al., 1995). 4. H-reflexes The H-reflex is a useful electrophysiological procedure for diagnosing radiculopathy at the lumbosacral spinal level (Dhand et al., 1991, White, 1991, Troni, 1983). The recommended H-reflex diagnostic criteria are side-to-side latency differences (Han et al., 1997), prolonged latency, absence of the Hreflex on the affected side (Fisher, 1992, Troni, 1983, Aiello, 1981), or H-reflex amplitude reduction on the affected side (Han et al., 1997, White, 1991). Other criteria include the threshold level of evoked potential and changes in the shape and number of phases of the H-reflex action potential (Alrowayeh and Sabbahi, 2011). H-reflexes have been used commonly to determine whether a radiculopathy demonstrates S1 involvement (Wilbourn and Aminoff, 1998). It is a monosynaptic reflex that is an S1-mediated response and can differentiate, to some extent, L5 from S1 radiculopathy. H-reflexes may be useful to identify subtle S1 radiculopathy, yet there are a number of shortcomings related to these responses. They can be normal with radiculopathies (Marin et al., 1995), and because they are mediated over such a long physiologic pathway, they can be abnormal owing to polyneuropathy, sciatic neuropathy, or plexopathy (Wilbourn and Aminoff, 1998). They are most useful in the assessment for polyneuropathy. Many researchers also have evaluated their sensitivity and specificity with respect to lumbosacral radiculopathies and generally found a range of sensitivities from 32% to 88% (Wilbourn and Aminoff, 1998, Kuruoglu and Thompson, 1994, Linden and Berlit, 1995, Marin et al., 1995), however many of 39

Chapter 1 Introduction and Literature Review these studies lacked a control group, used imprecise inclusion criteria, or had small sample sizes. Abnormal S1-root H-reflexes (Soleus H-reflex elicited with high-voltage electrical stimulation of the S1 nerve root at the S1 foramen) reveal lesions at the S1 root in patients with normal tibial H-reflexes; therefore, enhancing diagnostic sensitivity. The appearance of the H-reflex to L4/L5-level stimulation in patient with absent H-reflex to S1-foramen stimulation further localizes the site of S1 nerve root lesion to the L5/S1 spine level. However, the limitation of S1 nerve-root stimulation is the discomfort that is experienced using highvoltage electrical stimulation which is more painful than that of magnetic nerveroot stimulation (Xiang et al., 2010). 1.12.2: Needle EMG:  Needle EMG in lumbosacral radiculopathy: Lumbosacral radiculopathy (LSR) is a common disorder whose diagnosis relies heavily on needle-EMG (nEMG), and, as a consequence, the latter is extensively discussed in the literatures (Fisher, 2002, Katirji, 2002, Levin, 2002) and in textbooks (Dumitru et al., 2002, Geiringer and Davidson, 1999) where many suggestions on how to perform the nEMG are prescribed. In needle EMG, distal, proximal and paraspinal muscles in the symptomatic extremity are sampled looking for abnormalities in a myotomal pattern that are beyond the distribution of any one nerve. It is important to exclude a mononeuropathy, polyneuropathy, or a more diffuse process that might account for the signs and symptoms. Muscles innervated by the same myotomes but by different peripheral nerves and muscles innervated by myotomes above and below the suspected lesion with paraspinal muscles must be sampled (Preston and Shapiro, 2005) (Table 1.6). Table 1.6: Electromyography in lower extremity radiculopathy: Most useful muscles to sample (Wilbourn, 1993).

41

Chapter 1

Introduction and Literature Review L

L

L

S

Superior gluteal nerve L3 L4 L5 S1 S2 Gluteus maximus Inferior gluteal nerve Gluteus medius Tensor fascia latae Obturator nerve Adductor longus Femoral nerve Iliopsoas Rectus femoris Vastus medialis/lateralis Sciatic nerve Medial hamstring Lateral hamstring Deep perineal nerve Tibialis anterior Extensor hallucis longus Superficial perineal nerve Peroneus longus Tibial nerve Medial gastrocnemius Soleus Flexor digitorum longus Tibialis posterior Abductor hallucis brevis Solid rectangles indicate "marker" muscles that are most often abnormal for that root in isolated radiculopathy. Shaded rectangles indicate muscles that may be involved but are abnormal less frequently. The sensitivity of electromyography (EMG) has been reported to range from 49% to 86% (Khatri et al., 1984, Kuruoglu et al., 1994, Nardin et al., 1999, Schoedinger, 1987, Tonzola et al., 1981) in subjects with possible to definite radiculopathy, based upon history and physical examination as the gold standard. 41

S

Chapter 1 Introduction and Literature Review The presence of positive sharp waves and fibrillations in a myotomal distribution is a reliable evidence of radiculopathy. They most likely first appear in the paraspinal muscles by about 7 days, but may not be seen in distal muscles for 5 or 6 weeks. Total myotomal involvement is rare and many muscles within myotomes never show damage. Other spontaneous activity, such as fasciculation potentials and complex repetitive discharges, are sometimes present and may help make the diagnosis. Abnormal motor unit action potential recruitment in a neurogenic pattern may be seen. Chronic neurogenic motor unit action potential changes are frequent in chronic radiculopathies (Barr, 2013).  Cervical radiculopathy: In cervical radiculopathy, same principles are applied regarding sensory and motor nerve conduction studies and late responses (F-waves). Electrodiagnostic (EDX) testing might appear to be the most suitable reference standard. A comprehensive review determined that needle EMG has a sensitivity of 50–71% for subjects with neurological or radiological signs of a cervical radiculopathy, although the lack of a standardized gold standard may have resulted in an underestimation of this figure (American Association of Electrodiagnostic Medicine, 1999). Most useful muscles to sample for cervical radiculopathy are illustrated in table 1.7. Table 1.7: Electromyography in upper extremity radiculopathy: Most useful muscles to sample (Wilbourn, 1993). C5

Dorsal scapular nerve Rhomboid major/minor Suprascapular nerve Supraspinatus Infraspinatus Axillary nerve Deltoid Musculocutaneous nerve 42

C6

C7

C8

T1

Chapter 1

Introduction and Literature Review Biceps brachii

Median nerve Pronator teres Flexor carpi radialis Flexor pollicis longus Abductor pollicis brevis Ulnar nerve Flexor carpi ulnaris Flexor digitorum profundus Abductor digiti minimi First dorsal interosseous Radial nerve Triceps Brachioradialis Extensor carpi radialis Extensor digitorum communis Extensor indicis proprius Solid rectangles indicate "marker" muscles that are most often abnormal for that root in isolated radiculopathy. Shaded squares indicate muscles that may be involved but are abnormal less frequently.

1.13: Utility of electrodiagnostic parameters with MRI in radiculopathy Electrophysiologic studies are frequently used in conjunction with imaging modalities in the evaluation of lower back and neck pain, primarily for the purpose of establishing the presence or absence of radiculopathy. Magnetic resonance imaging (MRI) has largely replaced computed tomography (CT) as the primary diagnostic imaging modality in the evaluation of suspected radiculopathy, while needle electromyography (EMG) remains the mainstay of the electrodiagnostic evaluation. The EMG provides a measure of the physiologic integrity of the nerve roots, while MRI provides structural details of 43

Chapter 1 Introduction and Literature Review the nerve roots and surrounding structures. Studies examining the specific utility of EMG and MRI in the evaluation of clinical radiculopathy have shown that both are useful diagnostic tools (Albeck et al., 1995). However, both procedures have inherent limitations (Rachel, 1999). MRI and EMG often are discordant in the diagnosis of radiculopathy. The simple concept behind diagnosing radiculopathy using MRI is that a disk bulges or protrudes and presses on the nerve root; this mechanical compression causes pain. However, the story is more complex than that. First, in the case of disk disease, simple compression does not explain all the pathophysiology. Saal and colleagues have demonstrated that a ruptured disk releases phospholipase A2, an enzyme that plays a central role in the inflammatory response and the arachidonic acid cascade. This local inflammation seems to play a very significant role in the symptomatology of radiculopathy. Imaging studies do not demonstrate whether inflammation accompanies the disk bulge or protrusion and thus may not be able to distinguish between symptomatic and asymptomatic disks. Moreover, not all radiculopathies are caused by mechanical compression and disk disease (Saal et al., 1990). There are nonstructural causes of radiculopathy (e.g., metabolic or inflammatory) which can result in symptoms and EMG changes without MRI changes. The high prevalence of incidental findings (bulges and protrusions) in asymptomatic individuals, however, has brought into question the value of MRI in therapeutic decision making (Buirski and Silberstein, 1993, Boos et al., 1995, Stadnik et al., 1998, Jarvik et al., 2001, Dora et al., 2002, Modic and Ross, 2007,). In particular, 22% to 51% of asymptomatic individuals have been shown to demonstrate MRI irregularities in their lumbar spines, with this number increasing to between 57% and 80% for those older than 60 years of age. Even in symptomatic patients, the presence of different types of abnormalities on MRI demonstrates little correlation with self-reported pain and appears to have a negligible effect on patient care or outcome (Jensen et al., 1996, Modic and Ross, 2007). 44

Chapter 1 Introduction and Literature Review Of course, needle EMG has its diagnostic limitations as well. First, it primarily detects recent motor axon loss and does not detect sensory axon loss, demyelination, or conduction block. While using evidence of reinnervation as a diagnostic criterion may increase yield, it also probably increases the false positive rate. (Nardin et al., 1999).

45

Chapter 2 2:Subjects, materials and methods

Subjects and Study Design

2.1: Subjects and study design: This is a cross sectional study conducted at the EMG unit of Shaheed Dr. Aso's hospital in Sulaimani city from February 2012 to January 2013. The subjects included in the present study were divided into 3 groups; the first group comprised 70 patients with symptoms suggestive of lumbosacral radiculopathy who referred for electrodiagnostic evaluation. The second group consisted of 50 patients with symptoms suggestive of cervical radiculopathy who also referred for electrodiagnostic evaluation. Both patient groups were recruited at the outpatient’s clinic at Dr. Aso's neurosurgical hospital. The third group is the control group which is comprised of 40 apparently healthy subjects selected from the same hospital staff and their relatives. All the patients and controls gave their informed consent. The study was approved by the research ethics committee of school of medicine. The first group comprised of (25) males and (45) females (LSR group) whose ages ranged from 24 to 60 years (mean ± SE 43.53 ± 1.09 years). The second group comprised of (8) males and (42) females (CR group) with their age ranged from 25 to 60 years (mean ± SE 42.86 ± 1.3 years). The control group included (22) males and (18) females whose age ranged from 20 to 55 years (mean ± SE 40.82±1.6 years). All the members of this group underwent clinical assessment by the researchers and supervisors to confirm that they are free from obvious symptoms and signs of lumbosacral and cervical radiculopathy, peripheral nerve disorders, inflammation and infection.

2.2: Patient selection: 2.2.1: Inclusion criteria Patients enrolled in the study according to the following clinical diagnostic criteria: 64

Chapter 2 1. Age ranges from 20 to 60 years

Subjects and Study Design

2. History of back pain with or without lower limb pain, tingling, numbness or neurological finding indicating one or more of the following: 

Symptoms more than three weeks



Decreased or absent muscle stretch reflex



Impaired bowel and bladder function suspected cauda

equina involvement 

Foot drop, weakness of foot dorsiflexor muscles.

3. History of neck pain with or without upper limb pain, tingling, numbness or neurological finding indicating one or more of the following: 

Symptoms more than three weeks



Decreased or absent muscle stretch reflex



Wrist drop or weakness of hand dorsiflexor muscles.

2.2.2: Exclusion criteria. 1. Patients with local nerve injuries/lesions that may interfere with the electrophysiological study 2. History of alcohol consumption, pregnancy, thyroid disorders, diabetes mellitus, rheumatoid arthritis and renal failure. 3. History or clinical signs suggesting myopathy, polyneuropathy and neuromuscular junction disorders like myasthenia gravis. 4. Signs or symptoms of inflammation or infection.

2.3: Study protocol Data acquired at study entry included age, sex, duration of symptoms, history of other conditions associated with peripheral nerves involvement such as diabetes mellitus and rheumatoid arthritis. Information of physical and neurological examination was also included (Appendix 1).

64

Chapter 2

Subjects and Study Design

2.4: Blood samples After clinical assessment of patients and controls were completed, 8 ml of venous blood was obtained from each subject. 3 ml was put in EDTAcontaining tube and sent for total WBC count and erythrocyte sedimentation rate (ESR). Another 5 ml of blood was put in plain plastic tube without anticoagulant and centrifuged at 3000 rpm for 30 min. One part of the obtained serum was stored at -65 C° till time of analysis for high sensitivity C-reactive protein. The remained serum was used for measurement of serum glucose , serum glutamate oxaloacetic transaminase (AST), glutamic pyruvate transaminase (ALT) and creatine phosphokinase (CPK). After blood sampling, the electrodiagnostic protocol recommended by Preston and Shapiro was used for nerve conduction study and needle electromyography examination (Preston and Shapiro, 2005). Two subjects were examined each day. For ethical reasons, it was not appropriate to do needle EMG for apparently healthy controls.

2.5: Clinical assessment All patients were assessed for stretch reflex, foot or wrist drop (weak ankle dorsiflexion or wrist extension) and vibration and position sensation. The biceps reflex is elicited by placing examiner's thumb on the biceps tendon and striking the thumb with the reflex hammer and observing the arm movement. The triceps reflex is measured by striking the triceps tendon directly with the hammer while holding the patient's arm with the other hand (New York University, 2006).

With the lower leg hanging freely off the edge of the bench, the knee jerk is tested by striking the quadriceps tendon directly with the reflex 64

Chapter 2 Subjects and Study Design hammer. The ankle reflex is elicited by holding the relaxed foot with one hand and striking the achilles tendon with the hammer and noting plantar flexion. The plantar reflex (Babinski) is tested by coarsely running a key or the end of the reflex hammer up the lateral aspect of the foot from heel to big toe (New York University, 2006) Regarding the reflexes, the patients are divided into two groups: (1) those with normal reflex and (2) those with diminished or absent reflex. The deep tendon reflexes were graded as follows: 0 = no response; always abnormal 1+ = a slight but definitely present response; may or may not be normal 2+ = a brisk response; normal 3+ = a very brisk response; may or may not be normal 4+ = a tap elicits a repeating reflex (clonus); always abnormal The reflexes were compared to the asymptomatic side. Hyporeflexia is an absent or diminished response to tapping. Hyperreflexia refers to hyperactive or repeating (clonic) reflexes (Walker, 1990). Position sense of lower limb is assessed by lightly grasping the great toe on its medial and lateral surfaces between first finger and thumb and asking the patient with eyes closed to indicate whether the toe has been moved up or down. The joint is moved slowly, over one to two seconds, as the sensitivity of the test is inversely related to the velocity of the displacement. Vibration sense is assessed by applying the base of a vibrating 128 cycle per second tuning fork to the great toe and asking the patient to describe the sensation. The patients were tested with their eyes closed. Position and vibration senses were assessed in accordance with Gilman, 2002 (Gilman, 2002).

64

Chapter 2 2.5.1 Diabetes mellitus

Subjects and Study Design

Diabetes was defined by self report of diabetes diagnosis, use of drug or if fasting plasma glucose >126 mg/dl (Larsson et al., 1998). 2.5.2. Thyroid disease The presence of thyroid disorders was defined by self report of thyroid disease or use of drugs (Lanzillo et al., 1998). 2.5.3 Rheumatoid arthritis Rheumatoid arthritis is assessed by self report of RA or use of drugs or abnormalities including joint swelling, tenderness, and range of motion, limited motion and joint deformity. Joint tenderness defined as pain induced by pressure or motion on joint examination (Sokka and Pekka, 2000). 2.5.4 Drug history and Alcohol consumption Subjects with positive history of alcohol abuse and patients receiving Infliximab as possible causes of peripheral neuropathy were excluded (Lanzillo et al., 1998; Maria et al., 2007). 2.5.5 Body Mass Index Measurement (BMI): The height and weight for each patient were measured and used for calculation of body mass index (BMI) as follows (Wikipedia, 2013): BMI = weight (kg) / height (m2).

2.6: Interpretation of results of MRI Patients have performed MRI at multiple imaging centers in Sulaimani province. The MRI findings were reviewed by specialist radiologist who was not aware about clinical and neurophysiologic findings.

05

The MRI was

Chapter 2 Subjects and Study Design evaluated for any signs of root compression due to one or more of the following: 1. Disc bulging, herniation, prolapse or extrusions. 2. Signs of degenerative disc disease 3. Spinal canal stenosis (congenital and acquired). 4. More than one cause.

2.7: Assessment of biochemical parameters 2.7.1: Serum High Sensitivity C - reactive protein (Hs-CRP) Biocheck high sensitivity C-reactive protein (Hs-CRP) ELISA kit was used for quantitative determination of high sensitivity C-reactive protein in human serum (Catalog number: BC-1119, Biocheck, Inc, CA 94404). Expected normal serum CRP in healthy adults ranged between 0.068 – 8.2 mg/l as suggested by the manufacturer. Principle and method The principle of Hs-CRP ELISA test is based on a solid phase enzyme-linked immunosorbent assay. The assay system utilizes a unique monoclonal antibody directed against a distinct antigenic determination on the CRP molecules. This mouse monoclonal anti-CRP antibody was used for solid phase immobilization (on the micro titer wells). A goat anti-CRP antibody in the antibody-enzyme (horseradish peroxidase) conjugate solution was used. The test sample was allowed reacting simultaneously with the two antibodies, resulting in the CRP molecule being sandwiched between the solid phase and enzyme-linked antibodies. After 45 minutes incubation at room temperature, the wells were washed with distilled water to remove unbound labeled antibodies.

05

Chapter 2

Subjects and Study Design A solution of Tetra-methyl-benzidine (TMB) reagent was added and

incubated for 20 minutes, resulting in the development of a blue color. The color development was stopped with the addition of 1N hydrochloric acid (HCl) changing the color to yellow. The concentration of CRP was directly proportional to the color intensity of the test sample. Absorbance was measured spectrophotometrically at 450 nm. The concentration of each sample was determined from the standard curve (Fig. 2.1)

Figure 2.1: Calibration curve for Hs-CRP standards against absorbance at 450nm.

2.7.2: Serum Creatine phosphokinase (CPK) ACCENT-200 CK (version ADI) kit was used for quantitative measurement of serum CPK (ACCENT-200, PZ -CORMAY S.A., ul.Wiosenns 22, 05-092 Lomianki, POLAND). Expected normal serum CPK in healthy adults are < 167 U/L for females and < 190 U/L for males. Principle: Enzymatic method used for measuring serum CPK in the present study as described by international federation of clinical chemistry (IFCC). CK

Creatine phosphate + ADP

Creatine +ATP

HK

D-Glucose + ATP

ADP + G-6-Phosphate G6-PDH

G-6-Phosphate + NADP

+

6-Phosphogluconate + NADPH+ + H+ 05

Chapter 2 Subjects and Study Design Preparation of reagents, standards and samples were done according to the instructions provided by the manufactured company. Then procedure, measurment of absorbance and calculation done. The increase in absorbance which was proportional to CK activity in the serum was measured at 340 nm. 2.7.3: Serum glutamate oxaloacetic transaminase (GOT-AST) AST/GOT BIOLAB SA (version: AT 80025 18 09 2008) kit was used as reagent for quantitative determination of aminotransferase activity in human serum (BIOLAB SA,02160,Maizy,France.). Expected normal value for adult is 8-20 IU/L. Principle: The method used for measuring serum GOT (AST) level in the present study is developed by Karmen and Al and optimized by Henry and Al (Henry and Al, 1960). Reaction scheme is as follow: AST L-Aspartate + 2-Oxogluterate Oxaloacetate + L-Glutamate MDH Oxaloacetate + NADH + H+

L-Malate + NAD +

Steps of preparation of sample, procedure and calculation done according to instructions provided by the manufacturer. The decrease in absorbance due to the conversion of NADH into NAD +, which was proportional to AST activity in the specimen, was measured at 340 nm. 2.7.4: Serum glutamic pyruvate transaminase (GPT-ALT) ALT/GPT BIOLAB SA (Version: AT 80027 22 09 2008) kit was used for quantitative determination of alanin aminotransferase activity in human serum (BIOLAB SA, 02160, Maizy, France). Expected normal adult value for women is 5-25 IU/l and for men 7-28 IU/L. 05

Chapter 2 Principle:

Subjects and Study Design

The method used for measuring serum GPT level was developed by Wrobleski and LaDue, optimized by Henry and Bergmeyer (Henry and Al, 1960, Bergmyer and Al, 1978).Reaction scheme is as follow:

ALT L-Alanin + 2-Oxogluterate

Pyruvate + NADH + H

+

Pyruvate + L-Glutamate

LDH

L-Lactate + NAD+

The methodology provided by the manufacturer was used as a guide for preparation, procedure and calculation process. The decrease in absorbance due to the conversion of NADH into NAD +, which was proportional to ALT activity in the specimen was measured at 340 nm.

2.8: Nerve Conduction Study Protocol The following nerves were examined in control and patient groups: 1. Lower limb a. Motor nerve conduction study of posterior tibial and common peroneal nerves. b. Sural sensory nerve conduction study c. F-wave minimum latency (F-min) of posterior tibial and peroneal nerves. d. H-reflex latency of posterior tibial nerve 2. Upper limb a. Motor nerve conduction study of median and ulnar nerves. b. Sensory nerve conduction study of median and ulnar nerves. c. F-wave minimum latency (F-min) of median and ulnar nerves. 06

Chapter 2 Subjects and Study Design Patients and control subjects were kept in supine position at suitable room temperature (22-25°C) during nerve conduction study procedures. The NCSs were carried out using NIHON KOHDEN EMG/EP measuring machine (neuropack version - software) (Fig. 2:2) and the following settings were used to get clear waveforms as much as possible (Table 2:1). Table 2.1: EMG measuring machine settings for NCS (Kimura, 2001) EMG Machine setting Sensory nerve conduction Motor nerve conduction Sensitivity 10-20 µv/div 5 m v/div High-cut filter 20 Hz 5Hz Low-cut filter 3-10 Hz 3-10 Hz Analysis time 2 ms/division 2 ms/division Frequency rate 1Hz 1Hz Duration of 0.2ms 0.2ms stimulation

Figure 2.2: Photograph of NIHON KOHDEN EMG/EP machine used in the present study 00

Chapter 2 2.8.1: Sensory Nerve Conduction Study

Subjects and Study Design

The sensory nerve action potential (SNAP) was recorded through surface and ring electrodes and placed longitudinally on the skin that’s located above the nerve and nerve stimulated anti-dromically (a method that measures an action potential propagation from center towards the periphery opposite to natural condition of sensory action potential transmition) (Kimura, 2001). The following parameters were recorded from SNAP: Latency: The time from the stimulus to the initial SNAP deflection from baseline. Amplitude: Measured from baseline to the negative peak (baseline-topeak amplitude). If two recording electrodes are placed on the surface of the nerve, there is no potential (voltage) difference between them at rest. When the nerve is stimulated and an impulse is conducted past through the two electrodes, a characteristic sequence of potential changes results. As the wave of depolarization reaches the electrode nearest the stimulator, this electrode becomes negative relative to the other electrode. It is conventional to connect the electrodes in such a way that when the first electrode becomes negative relative to the second, an upward deflection is recorded. Sensory Nerve Conduction Velocity (SCV): Calculated by dividing the distance between the stimulation point and recording electrode by the sensory latency (distance /latency) (Fig. 2.3).

04

Chapter 2

Subjects and Study Design

Figure 2.3: Sensory nerve action potential parameters recorded in this study D=distance between stimulation and recording electrode, SCV=sensory conduction velocity (Kimura and Kohara, 2003). 2.8.2: Motor Nerve Conduction Study The motor compound muscle action potential (CMAP) was recorded through surface electrodes as active electrode placed over belly of the muscle and reference over tendon of the muscle or distally (Preston and shapiro, 2005 and Kimura, 2001). The following parameters were recorded from CMAP: Latency: The time from the stimulus to the initial CMAP deflection from baseline. Amplitude: Measured as the voltage difference between the rising point and the peak of the first negative deflection.

04

Chapter 2 Subjects and Study Design Motor Nerve Conduction Velocity (MCV); Calculated by dividing the distance between the distal and proximal stimulation points by the latency difference between the distal and proximal waveforms (Fig. 2.4).

Figure 2.4: Compound muscle action potential parameters measured in our study, L1=distal latency, L2=proximal latency, D=distance between distal and proximal stimulation point, MCV=motor conduction velocity (Kimura and Kohara, 2003).

2.9: Recording Methods Standardized nerve conduction study procedures were used in this study according to Kimura and Kohara (2003), Delisa et al. (2005) and Buschbacher and Prahlow (2006) protocols as follows: 2.9.1: Sensory Nerve Conduction Study Procedure 1. Median nerve A pair of ring electrodes (active and reference) were placed on the proximal interphalyngeal joint of

the index finger (2cm apart) and the

stimulating electrode was applied anti- dromically at the wrist between the palmaris longus and the flexor carpi ulnaris tendons and the grounding electrode placed in between the recording and stimulating electrodes. The distance between recording and stimulation was kept at 14 cm (Fig 2.5). Then 04

Chapter 2 Subjects and Study Design the intensity of stimulation was gradually increased until a clear sensory nerve action potential obtained and the required parameters (sensory latency, sensory nerve action potential amplitude and sensory nerve conduction velocity) were calculated.

Reference Stimulator Ground

Active

Figure 2.5: Median sensory nerve conduction study in the present study. GND=Ground electrode. 2. Ulnar nerve A pair of ring electrodes(active and reference) were placed on the PIP joint of the 5th finger (2 cm apart) and the stimulation was applied at the wrist 14 cm proximal to the active electrode and just lateral to the flexor carpi ulnaris (Fig 2.6). The grounding electrode was placed in between the stimulating and recording electrodes. In the same way as done for median nerve sensory study, the intensity of stimulation was gradually increased and the required parameters were obtained.

04

Chapter 2

Subjects and Study Design

Ground Stimulator

Active Reference

Figure 2.6: Ulnar sensory nerve conduction study in the present study 3. Sural nerve The patient was laid in prone position and the ankle placed on a pillow. Active electrode was placed posterior to the lateral malleolus one third to the lateral malleolus along the line drawn between the heel and the lateral malleolus. Reference electrode was placed 2 cm distal to the active electrode. The stimulation was applied 14 cm proximal to the active electrode and 1 to 2 cm lateral to the Achilles tendon (Fig. 2.7). Then the sensory parameter for sural nerve was obtained after gradual increase of stimulation intensity and obvious sensory nerve action potential was recorded.

45

Chapter 2

Subjects and Study Design

Figure 2.7: Sural nerve conduction study. 2.9.2: Motor Nerve Conduction Study Procedure 1. Median nerve The active recording electrode was placed over the belly of the abductor pollicis brevis muscle (APB) and the reference electrode was placed on its tendon. The first stimulation was applied at the wrist 8cm proximal to the active electrode (to record distal latency) (Fig. 2.8) and the second stimulation was applied at the medial side of the biceps muscle tendon and just lateral to the brachial artery (to record proximal latency). The intensity of stimulus gradually increased until a clear compound muscle action potential obtained, then distal and proximal motor latencies, compound muscle action potential amplitude and motor nerve conduction velocity were calculated.

45

Chapter 2

Subjects and Study Design

Ground Stimulator

Active

Reference Figure 2.8: Median motor nerve conduction study 2. Ulnar nerve The active recording electrode was placed on the belly of abductor digiti minimi muscle (ADM) and the reference electrode was placed on its tendon 3cm apart. The stimulation was applied at the ulnar side of wrist 8cm proximal to the recording electrode (to record distal latency). The second stimulus was applied above elbow (5 cm proximal to the ulnar groove in order to record above elbow proximal latency). The intensity of stimulus gradually increased until a clear compound muscle action potential obtained, then distal and above elbow motor latencies, compound muscle action potential amplitude, motor nerve conduction velocity were calculated. 3. Peroneal nerve The active recording electrode was placed on the extensor digitorum brevis (EDB) muscle and the reference electrode was placed distal to it on the tendon at base of fifth toe, while the stimulation was applied at ankle 8 cm proximal to the active electrode just lateral to the tibialis anterior muscle tendon (to obtain distal latency). The second stimulus was applied below the fibular head and the third stimulus was applied 10 cm proximal to the fibular 45

Chapter 2 Subjects and Study Design head just medial to the end of the biceps femoris muscle (to obtain above fibular head proximal latency) (Fig. 2.9). The intensity of stimulus gradually increased until a clear compound muscle action potential obtained, then distal at anterior ankle, below fibular head and above fibular head motor latencies, compound muscle action potential amplitude, motor nerve conduction were calculated.

Reference

Active Stimulator

Figure 2.9: Peroneal motor nerve conduction study 5. Tibial nerve The active recording electrode was placed over the belly of abducter hallucis brevis muscle (AHB) and the reference electrode was applied distal to it on the tendon at base of big toe. The stimulation was applied at the ankle 10 cm proximal to the active electrode and on the middle portion of the medial malleolus (to record distal latency) and the second stimulus at the central portion of the popliteal fossa (to record proximal latency). The grounding electrode was placed in between the active and stimulating electrodes. The intensity of stimulus gradually increased until a clear compound muscle action potential obtained, then distal and proximal motor latencies, compound muscle 45

Chapter 2 Subjects and Study Design action potential amplitude and motor nerve conduction velocity were calculated. 2.9.3: Late responses 1. F-wave The F response is a late motor response that occurs after the compound muscle action potential (CMAP) or M-wave. It is first recorded from the foot muscles. Among the parameters of F-wave, the minimal F-wave latency is the most reliable and useful measurement. To record the minimum F-wave, the setup is essentially the same as that of a routine motor conduction study using distal stimulation. Several adjustments must be made; the gain should be increased to 200 µV and sweep speed should be increased to 5-10 ms. Around 10 stimuli is applied. Supramaximal stimulation must always be used (Fig. 2.10) and

(Preston

Shapiro, 2005).

M-wave latency (5.1 ms)

F-wave minimal latency (48.2 ms) 46

Chapter 2 Subjects and Study Design Figure 2.10: Normal minimal F-wave latency of tibial nerve in one control subject. 2. H-reflex latency The H reflex is elicited by stimulating tibial nerve in the popliteal fossa, recording the gastroc-soleus muscle. The recording montage consists of G1 placed over the soleus and G2, the reference electrode, placed over the Achilles tendon (Fig. 2.11). The gain is set at 200-500 µV. The stimulus duration is increased to 1 ms in order to selectively stimulate the Ia fibers. The optimal location that yields the largest H reflex is done by drawing a line from popliteal fossa posteriorly to the Achilles tendon where the medial malleolus flares out and then divides that line in to eight equal parts, the optimal location is at the fifth or sixth segment distally over the soleus (Fig. 2.12).

Figure 2.11: H-reflex recorded from soleus muscle. G2: Reference electrode, G1: Active electrode, GND: Ground electrode, CATH, cathode pole of the stimulator (Preston and Shapiro, 2005).

40

Chapter 2

Subjects and Study Design

H-reflex latency

A

B

Figure 2.12 A: optimal location for G1 placement (double arrows). B: H-reflex response

2.10: Needle Electromyography Needle EMG examination was done for all patients. Disposable bipolar concentric needle electrodes (Spes-medica, Italy, 0.35 (28G) × 30 mm) were used. 1.

Lumbosacral radiculopathy 44

Chapter 2 Subjects and Study Design The following muscles were examined according to the lumbosacral roots representing common myotomes involved in radiculopathy (Dillingham et al., 2000):

2.

1.

Medial gastrocnemius (S1)

2.

Biceps femoris-short head(S1)

3.

Peroneous longus (L5)

4.

Tibialis Anterior (L4,L5)

5.

Vastus medialis(L3,L4)

6.

Lumbar paraspinals

Cervical radiculopathy

The following muscles were examined according to the cervical roots representing common myotomes involved in radiculopathy (Dillingham et al., 2000): 1.

First dorsal interosseous (C8-T1)

2.

Pronator teres (C6-C7)

3.

Triceps(mainly C7)

4.

Bicesps brachii(C5-C6)

5.

Deltoid(C5-C6)

6.

Cervical paraspinals

The site of EMG needle insertion into each muscle was selected according to standard available techniques (David and Barbara, 2005). For needle EMG of the PSM, this is done by inserting the needle at an angle of 45° and 2.5 cm lateral and 1 cm cranial to the spinous process (Morris, 2002, Haig, 1997). The following settings were used during EMG procedures: 44

Chapter 2 Subjects and Study Design Low-cut filter=10Hz, high-cut filter=10 kHz, sweep speed=10 ms/division, sensitivity 50µv-1mv (Kimura, 2001). During needle EMG every muscle mentioned in the list was observed for the following (Delisa, 2005, Kimura, 2001 and Preston and Shapiro, 2005): 1. Observation of insertion activity of muscle (in normal case it is about <100 ms) after insertion of needle into a specific muscle. 2. Observation of spontaneously discharging potentials at rest after inserting needle electrode into a specific muscle and waiting for about 5-10 sec (normally muscle is silent at rest ). 3. Identification of individual motor unit potential (MUP) after the patient produced mild contraction of the muscle and following

MUP

parameters were measured (Fig. 2.11-A): 

Amplitude: Measured from negative peak to positive peak of the

wave (0.5-1 mV), 

Area: Surrounded by waveform and baseline.



Duration: Time length from beginning of waveform to the end of

waveform, 

Phases: Number of zero –crossing by waveform.



Turn: A point of change in the direction of the waveform.

4. Recruitment and interference pattern. After motor unit potential was evaluated, the patient increased the strength of muscle contraction to observe the recruitment and interference pattern. Recruitment: Firing of motor unit started from thinner motor unit, successive action of the same motor and additional ones increased the strength of voluntary muscle contraction by asking the patient to contract the muscle forcefully (Fig. 2.11-B). 44

Chapter 2 Subjects and Study Design Interference pattern: Electric activity was recorded from a muscle during maximal voluntary effort with a needle electrode. A full interference pattern implies that no individual motor unit action potentials can be clearly identified (the waveforms that appear at the maximum contraction). A reduced interference pattern (intermediate pattern) is one in which some of the individual motor unit action potentials may be identified while others cannot due to superimposition of waveforms (Kimura, 2001, Preston and Shapiro, 2005). This procedure was done by asking the patient to either flex or extend the limb against resistance (Kimura, 2001).

A

B

Figure 2.13: Muscle fiber motor unit potential parameters (A), Recruitment and interference pattern (B) (Kimura, 2001). A positive EMG study is relied predominantly on the presence of signs of denervation (abnormal spontaneous activity) including fibrillation potentials and positive sharp waves and/or neuropathic MUAPs (long-duration, largeamplitude motor unit potentials), decreased recruitment and interference pattern (American Association of Electrodiagnostic Medicine, 1999).

44

Chapter 2

Subjects and Study Design

2.11: Statistical analysis Data were translated into a computerized database structure. An expert statistical advice was sought for. Statistical analyses were computer assisted using SPSS version 16 (Statistical Package for Social Sciences). Frequency distribution for selected variables was done first. Variables were conveniently described by mean, SE (standard error).

Unpaired -t test was used to further explore the significance of

difference in mean between the studied groups. A value of p<0.05 was reported as statistically significant (Sorlie, 1995). 2.11.1. Test Performance Characteristics The performance characteristics (validity) of a test or criteria include among others: sensitivity, specificity, positive predictive value and negative predictive value. Sensitivity is the conditional probability showing that a diseased person has a positive result. Its value can be changed by changing the cutoff point for positive test results. Specificity is the conditional probability showing that a disease-free person has a negative test result (Sorlie, 1995). Positive Predictive Value (PPV) is the conditional probability showing that a person with a positive test result is truly diseased. Its value depends on the cutoff point for positive test result and the prevalence of the disease in the screened population. Negative predictive value (NPV) is the conditional probability showing that a person with a negative test result is truly free of the disease. Accuracy (percent agreement) is the proportion of true results among all test results (positive and negative) (Sorlie, 1995).

45

Chapter 2

Subjects and Study Design

Formulas used in calculation Sensitivity =Number of true positives/ Number of diseased people Specificity =Number of true negatives/ Number of non-diseased people PPV =Number of true positives/Number of positive test results NPV =Number of true negatives/Number of negative test results Accuracy=Number of true results (both negative and positive) / Number of negative test results

Depending on the sensitivity and specificity for each possible cut off value and the pretest probability of the outcome, one can calculate the predictive value of both positive and negative results according to the following formulas.

PPV =

[Sensitivity × Prevalence] [Sensitivity × Prevalence] + [(1-Prevalence) × (1-Specificity)]

NPV =

[Specificity × (1-Prevalence)] [(1-Sensitivity) × Prevalence] + [(1-Prevalence) × Specificity]

2.11.2. Limitations for the use of ROC results The ROC method is used to evaluate the performance of a quantitative test in differentiating between a disease status or an outcome and a second comparison group. The interpretation of validity measures derived will therefore depend on following: 1. The selection of the comparison group If the test is intended for use as a screening tool, to detect possible cases in a general population context, one needs a sample of general population controls, which by definition include a certain proportion of people with 45

Chapter 2 Subjects and Study Design different diseases. In the same context, a general population sample is also needed if the test was intended for use in diagnosis to establish the presence of a certain disease with certainty in a clinical situation where the person in charge of diagnosis is not a physician (with no clinical training) and has no prior knowledge about the pretest probability of having the disease. Using a general population, the control has an important drawback of being impractical, since one needs a very large sample of controls involving all possible diseases that might affect the performance of the test. One solution to this dilemma is to use a healthy control group and ascertain the pretest probability of having the disease (depending on clinical criteria in combination with other laboratory tests). In this context, the validity parameters may add to the already available information about the probability of having the disease and might not substitute the clinical assessment.

2. The biological relevance of the test To use the term diagnostic in its absolute sense, the test needs to be biologically specific for the disease, i.e. the test is only abnormal in association with the disease (or condition) studied and always normal in nondiseased people, a requirement which is rarely found in clinical laboratory tests. The terms positive and negative predictive values should therefore be used in their specific context.

45

Chapter 3

Results

3. Results 3.1 Demographic parameters The age and body mass index of the study groups are shown in table 3.1. There is no significant difference in the mean age among studied groups. The body mass index in both patient groups was significantly higher than that of the control group. Table 3.1: Demographic parameters of the study groups Demographic parameters

Age in years

BMI (Kg/m2)

N

Mean±SE

Healthy control

40

40.82±1.5

LSR

70

43.53±1.0

CR

50

42.86±1.3

Healthy control

40

25.985±0.5

LSR

70

29.281±0.5

CR

50

29.246±0.7

P(ANOVA)

0.34

0.001

3.2 Blood test parameters for patients with suspected lumbosacral radiculopathy (LSR) and cervical radiculopathy (CR) compared with control group These results are shown in the table 3.2. Patients with suspected LSR and CR showed significant increase in serum level of Hs-CRP compared with control group (mean ± SE 5.81 ±0.49 and 5.83±0.53 mg/L respectively compared to mean ± SE 4.07±0.68 mg/ L for control group). However other measured blood parameters showed no statistically significant difference between LSR and CR with control group.

37

Chapter 3

Results

Table 3.2: Comparison of blood parameters between LSR and CR patients with control group Group Blood parameters LSR

Group n= 70

Control

Mean± SE

n=40

CR n= 50

Mean ±SE

Control n=40

LSR

6.9 ±0.20

CR

6.8± 0.21

Healthy control

7.5 ±0.42

Healthy Control

7.5±0.42

LSR

15.7 ±1.45

CR

15.6± 1.2

Healthy control

17.0 ±2.1

Healthy Control

17.0±2.1

Fasting blood sugar LSR

93.83 ±1.6

CR

93.3±2.5

FBS (mg/dl)

98.3 ±2.2

Healthy Control

98.3±2.2

CR

28.5±1.0

Healthy Control

28.7±1.3

CR

29.0±2.8

Healthy Control

24.7±2.1

CR

132.4±9.9

Total WBC 3

(cell/mm ) ESR (mm/hr)

Healthy control LSR

29 ±1.1

SGOT (U/L) Healthy control

28.7 ±1.3

LSR

27 ±1.2

SGPT (U/L) Healthy control Creatine

24.7 ±2.1

LSR

164.2 ±38.78

Healthy control

127.5 ±13.03

LSR

5.81 ±0.49*

CR

5.83±0.53*

Healthy control

4.07 ±0.68

Healthy Control

4.07±0.68

phosphokinase CPK (U/L)

Healthy Control

127.5±13.03

Hs-CRP (mg/L)

* P<0.05 3.3: Nerve conduction parameters in patients suspected of LSR and CR compared with the control group Tibial CMAP amplitude was significantly lower in patients with LSR compared with the control group (7.4 Vs 10.9 mV, P=0.001) respectively (table 3.3). Other NCS parameters in patients with suspected LSR and CR were not statistically different compared with control group. Table 3.3: NCS parameters of LSR and CR patients compared with control groups NCS parameters

Group LSR n=70 Control n=40 LSR

Peroneal latency (ms)

Healthy Control

NCS parameters

4.6 ± 0.08

Mean ±SE

CR

3.4 ±0.09

Control

3.6 ±0.09

CR

7.6 ±0.39

Control

7.0 ±0.45

Median motor latency(ms)

Healthy Controls 4.9 ± 0.11 LSR

Peroneal CMAP (mV)

Mean ±SE

Group CR n=50 Control n=40

3.3 ± 0.18 Median CMAP(mV)

3.9 ± 0.47

37

Chapter 3

Results LSR

Peroneal NCV (m/s) Peroneal F-wave latency (ms) Tibial latency (ms)

Tibial CMAP (mV)

Tibial NCV (m/s) Tibial F-wave latency (ms) Sural latency (ms)

Sural SNAP (µV)

Sural NCV (m/s) H reflex latency (ms)

49.8 ± 0.81

Healthy Control

50.2 ±1.19

LSR

47.6 ± 0.59

Median sensory latency

Healthy Control

48.1 ± 0.94

(ms)

LSR

5.1 ± 0.10

Healthy Control

5.4 ± 0.12

LSR

7.4 ± 0.47* 10.9 ± 0.81*

LSR

48.1 ± 1.02 46.7 ± 1.6

LSR

49.2 ± 0.52

Healthy Control

49.5 ± 0.80

LSR

3.2 ± 0.04

Healthy Control

3.1 ± 0.09

LSR

11.5 ± 0.39

Healthy Control

10.4 ± 0.39

LSR

47.4 ± 0.77

Healthy Control

49.1 ± 1.2

LSR

30.8 ± 0.27

Healthy Control

29.7 ± 0.50

54.7 ±1.04

Control

55.2 ±1.25

CR

2.4 ±0.07

Control

2.2 ±0.08

CR

27.4 ±0.26

Control

26.8 ±0.45

CR

2.5 ±0.06

Control

2.6 ±0.09

CR

8.1 ±0.26

Control

8.4 ±0.40

CR

56.1 ±1.07

Control

56.0 ±1.08

CR

2.1 ±0.03

Control

2.0 ±0.04

CR

27.3 ±0.18

Control

27.3 ±0.38

Median F wave (ms)

Healthy Control

Healthy Control

CR Median NCV(m/s)

Ulnar Motor latency(ms)

Ulnar CMAP(mV)

Ulnar NCV(m/s)

Ulnar sensory latency (ms)

Ulnar F-wave (ms)

*p <0.05

A

B

Figure 3.1: Tibial distal and proximal motor responses recorded from abductor hallucis brevis muscle. A: Normal tibial CMAP amplitude recorded from a control subject. B: Decreased tibial CMAP amplitude recorded from a patient with chronic S1 radiculopathy. 37

Chapter 3 Results 3.4 Correlation between selected parameters (NCS and blood parameters) in the control group These correlations are shown in table 3.4. Both WBC and ESR are significantly positively correlated with serum Hs-CRP (r=0.522, P=0.018 and r=0.849, P=0.001 respectively). There was also significant positive correlation of age with each of peroneal and tibial F wave latencies (r=0.786, P=0.001, r=0.521, P=0.019). Table 3.4: Significant correlations between selected parameters in control groups A-Pearson correlation between parameters

r value

P value

WBC (cell/mm3) with Hs-CRP

0.522

0.018

ESR (mm/Hr) with Hs-CRP

0.849

0.001

Age with peroneal F-wave latency (ms)

0.786

0.001

Age with tibial F-wave latency (ms)

0.521

0.019

among control group

3.5 Correlation between selected parameters (Blood and NCS parameters) in LSR and CR patients. In both LSR and CR groups, there was significant positive correlations between Hs-CRP and CPK levels (r=0.356*, p=0.003 and r=0.333*, p=0.018 respectively) (table 3.5). Tibial H-reflex latency was significantly positively correlated with tibial F-wave latency (r=0.439, p=0.001). Table 3.5: Significant correlations between selected parameters in LSR and CR group r value

P value

Hs-CRP (mg/L) with CPK

0.356

0.003

H-reflex (ms) with tibial F-wave

0.439

0.001

r value

P value

0.333

0.018

Pearson correlation between parameters for LSR

Pearson correlation between parameters for CR

Hs-CRP (mg/L) with CPK

37

Chapter 3 Results 3.6: Receiver operating characteristic (ROC) curve analysis for NCS parameters of upper limb to predict cervical radiculopathy These results are shown in table 3.6 and figures 3.2 and 3.3. It is clear that none of the selected parameters is valid to predict cervical radiculopathy as far as the areas under the curves (AUC) were < 0.7 Table 3.6: ROC area for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls NCS parameters Median CMAP mV Median sensory latency ms Median F-wave latency ms Ulnar sensory latency ms Ulnar F-wave latency ms Median motor latency ms Median NCV m/s Ulnar Motor latency ms Ulnar CMAP mV Ulnar NCV m/s

AUC 0.559 0.616 0.592 0.584 0.520 0.613 0.539 0.497 0.698 0.522

P NS NS NS NS NS NS NS NS NS NS

Figure 3.2: ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls.

33

Chapter 3

Results

Figure 3.3: ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for selected nerve conduction study parameters when used as test to predict cases with cervical radiculopathy differentiating them from healthy controls. 3.7: Receiver operating characteristic (ROC) curve analysis for NCS parameters of lower limb to predict lumbosacral radiculopathy Table 3.7 shows that tibial CMAP amplitude is of high validity to predict LSR with an area under the curve of 0.782, p <0.001 (figure 3.4). However, all other selected parameters were not valid (AUC <0.7 and p=NS). Table 3.7: ROC area for selected nerve conduction study parameters when used as test to predict cases with lower limb radiculopathy differentiating them from healthy controls AUC 0.536 0.568 0.571 0.615 0.569

Tibial nerve conduction velocity m/s Sural latency ms Sural CMAP mV Peroneal motor latency ms Peroneal CMAP amplitude mV 37

P NS NS NS NS NS

Chapter 3

Results

Peroneal NCV m/s Peroneal F wave ms Tibial motor latency millisecond Tibial CMAP amplitude mV Tibial F wave ms Sural NCV m/s H-reflex (ms) NS= Not significant

0.533 0.575 0.684 0.782 0.553 0.630 0.609

NS NS NS <0.001 NS NS NS

Figure 1.4: ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for selected nerve conduction study parameters when used as test to predict cases with lumbosacral radiculopathy differentiating them from healthy controls. 3.8: Validity parameters for tibial CMAP amplitude when used to predict LSR Typical cut off value (optimum cut off value) for tibial CMAP amplitude is 8.8 mV which is associated with a sensitivity76.5%, specificity 75% and accuracy 37

Chapter 3 Results 76.1%. Testing positive at this cut off value may establish the diagnosis of LSR in clinically suspected cases with75.4% confidence. In the same context, testing negative will exclude the diagnosis of LSR with 96.6% confidence (table 3.8). Table 1.8: Validity indices for selected nerve conduction study parameters when used as test to predict cases with lumbosacral radiculopathy differentiating them from healthy controls.

Positive if < cut-off value

Tibial CMAP amplitude mV 8.8

Sensitivity

76.5

Specificity Accuracy

37

76.1

PPV at pretest probability = 50% 90%

75.4

96.5

NPV at pretest probability = 10%

96.6

3.9 ROC area for BMI and Hs-CRP when used to predict radiculopathy (cervical or lumbosacral radiculopathy) These results are illustrated in table 3.9. BMI and Hs-CRP were of high validity to predict cervical or lumbosacral radiculopathy with AUC (0.709 and 0.738 respectively, p<0.001) (figures 3.5 and 3.6). Table 3.9: ROC area for BMI and Hs-CRP when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls.

AUC 0.709 0.738

Body mass index (Kg/m2) High sensitivity CRP mg/L

78

P value <0.001 <0.001

Chapter 3

Results

Figure 3.5: ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for BMI when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls.

78

Chapter 3

Results

Figure 3.6: ROC curve showing the trade-off between sensitivity (rate of true positive) and 1-specificity (rate of false positive) for Hs-CRP when used as test to predict cases with radiculopathy (cervical and LSR) differentiating them from healthy controls.

3.10. Validity parameters of BMI and Hs-CRP when used as test to predict radiculopathy. A typical cut off value of BMI was equal or greater than 29.45 kg/m2. Testing positive at this cut-off value may establish the diagnosis of radiculopathy with 79.2% confidence. However, testing negative may exclude the diagnosis of radiculopathy with 93.8% confidence. On the other hand, the typical cut-off value of serum Hs-CRP was equal to or greater than 3.05 mg/L. Testing positive at this cut off value may establish the diagnosis of radiculopathy in clinically suspected cases with 76.3% confidence. Meanwhile, testing negative at this cut off value will exclude the diagnosis of radiculopathy with 98.2% confidence (table 3.10).

78

Chapter 3

Results

Table 3.10: Validity indices for BMI and Hs-CRP when used as test to predict cases with radiculopathy (both cervical and lumbosacral radiculopathy) differentiating them from healthy controls.

Positive if ≥ cut-off value

Body mass index (Kg/m2) 29.45 Hs-CRP (mg/L) 3.05

PPV at pretest probability = Sensitivity Specificity Accuracy

50%

90%

NPV at pretest probability = 10%

47.5

87.5

57.5

79.2

97.2

93.8

88.3

72.5

84.4

76.3

96.7

98.2

3.11 Electrodiagnostic results according to duration of symptoms (DOS) Out of 70 patients with suspected LSR, 57 (81.4%) had abnormal needle EMG results, 19 patients (27.1%) had abnormal NCS, 9 (12.9%) had abnormal F-wave response and 15 patients (21.4%) had abnormal H-reflex. Higher percentage of needle EMG abnormality (n=27, 87.1%) were observed in patients with DOS of more than 1 year compared to those with DOS of 3 weeks-6month and 6 month-1 year (n=15 and n=15 respectively) but it was statistically not significant. Regarding other EDX results (NCS, F-wave and H-reflex), the percentage of abnormality of each of these parameters also showed no statistically significant differences according to DOS (table 3.11- A). Among 50 patients with suspected CR, 37 (74%) patients had abnormal needle EMG results. Higher percentage of this abnormality was observed in patients with DOS between 6 months and more than 1 year (p=0.77) but like patients with suspected LSR it was statistically not significant. Other electrodiagnostic test results also showed no significance differences according to DOS (table 3.11- B).

77

Chapter 3

Results

Table 3.11- A: Different Electrodiagnostic results according to duration of symptoms in LSR DOS Pearson Chi-

EDX results

3 week to 6 6 month to 1 More than 1

Needle

Normal

Count

EMG

N=13 (18.6%)

% within DOS

Abnormal

Count

N=57 (81.4%)

% within DOS

Normal

Count

N=51(72.9%)

% within DOS

Abnormal

Count

N=19(27.1%)

% within DOS

F wave

Normal

Count

N=70

N=61(87.1%)

% within DOS

Abnormal

Count

N=70

NCS N=70

month

year

year

6

3

4

28.6%

16.7%

12.9%

15

15

27

71.4%

83.3%

87.1%

13

15

23

61.9%

83.3%

74.2%

8

3

8

38.1%

16.7%

25.8%

19

14

28

90.5%

77.8%

90.3%

2

4

3

9.5%

22.2%

9.7%

17

14

24

81.0%

77.8%

77.4%

4

4

7

19.0%

22.2%

22.6%

square

0.352 (NS)

0.317(NS)

N=9(12.9)

0.387(NS) % within DOS

H reflex

Normal

Count

N=70

N=55(78.6%)

% within DOS

Abnormal

Count

N=15(21.4%)

0.950(NS) % within DOS

NS= not significant Table 3.11-B: Different Electrodiagnostic results according to duration of symptoms in CR EDX results

DOS 3 Week to 6

Needle

Normal

Count

EMG

N=13 (26%)

% within DOS

Abnormal

Count

N=37 (74%)

% within DOS

NCS

Normal

Count

N=50

N=46 (92%)

% within DOS

Abnormal N=4 (8%)

Count

N=50

more than 1

Pearson Chi-square

month

6 M to 1 year

year

6

3

4

31.6%

23.1%

22.2%

13

10

14

68.4%

76.9%

77.8%

18

12

16

94.7%

92.3%

88.9%

1

1

2

5.3%

7.7%

11.1%

19

12

18

100.0%

92.3%

100.0%

0

1

0

0.77(NS)

0.80(NS) % within DOS

F wave

Normal

Count

N=50

N=49 (98%)

% within DOS

Abnormal

Count

77

0.23(NS)

Chapter 3

Results

N=1 (2%)

% within DOS

.0%

7.7%

.0%

3.12: Electrodiagnostic results and foot drop/weak dorsiflexion As shown in table 3.12, all patients with foot drop (n=17, 100%) showed abnormal needle EMG study. However 75.5% of patients with negative foot drop showed abnormal needle EMG study and this difference was turned out to be statistically significant (p=0.02). Abnormal NCS parameters (29.4% vs. 26.4%), abnormal F-wave latency (11.8% vs. 13.2%) and abnormal H-reflex latency (23.5% vs. 20.8%) were not significantly different between patients with positive and negative foot drop/weak dorsiflexion. Table 3.12: Electrodiagnostic results and foot drop EDX

Foot drop/weak dorsiflexion Negative N=53 (75.7%)

Needle EMG Normal N=13 Abnormal N=57 NCS parameters

Normal N=51 Abnormal N=19

F-wave latency

Normal N=61 Abnormal N=9

H-reflex latency

Normal N=55

Count % within Foot drop Count % within Foot drop Count % within Foot drop Count % within Foot drop Count % within Foot drop Count % within Foot drop Count % within Foot drop

77

Pearson Chi-square Positive N=17(24.3%) (P-value)

13

0

24.5%

.0%

40

17

75.5%

100.0%

39

12

73.6%

70.6%

14

5

26.4%

29.4%

46

15

86.8%

88.2%

7

2

13.2%

11.8%

42

13

79.2%

76.5%

0.02

0.80(NS)

0.87(NS)

0.80(NS)

Chapter 3

Results Abnormal N=15

Count % within Foot drop

11

4

20.8%

23.5%

3.13: Electrodiagnostic results and straight leg raising test (SLRT) in LSR group Table 3.13 presents the number and percentage of patients with abnormal and normal electrodiagnostic test results according to SLRT. The difference regarding abnormal needle EMG between patients with positive SLRT (86.8%) and patients with negative SLRT (75%) was turned out to be statistically not significant. In the same manner, results of abnormal NCS parameter (23.7% vs. 31.2%) and F-wave latency (15.8% vs. 8.9%) between patients with positive and negative SLRT were not statistically different. Interestingly, the number and percentage of patients with positive SLRT having abnormal H-reflex latency (n=13, 34.2%) was statistically significantly higher than patients with negative SLRT having abnormal H-reflex latency (n=2, 6.2%) (p=0.001) Table 3.13: Electrodiagnostic test results according to straight leg raising test (SLRT) SLRT EDX results

Count

Negative

Positive

N=32 (45.7)

N=38 (54.3)

8

5

25.0%

13.2%

24

33

75.0%

86.8%

22

29

68.8%

76.3%

10

9

31.2%

23.7%

29

32

90.6%

84.2%

Pearson chi-square

Normal Needle EMG

% within SLRT

N=70

Count

0.20 (NS) Abnormal % within SLRT Count Normal % within SLRT

NCS N=70

0.47(NS) Count Abnormal % within SLRT

F-wave N=70

Count Normal

0.42(NS) % within SLRT

77

Chapter 3

Results Count

3

6

9.4%

15.8%

30

25

93.8%

65.8%

2

13

6.2%

34.2%

Abnormal % within SLRT Count Normal % within SLRT

H-reflex N=70

0.001 Count Abnormal % within SLRT

3.14: Electrodiagnostic results and vibration and position senses These results are shown in table 3.14-A and 3.14-B. In both groups of patients (LSR and CR) abnormal results of needle EMG and other electrodiagnostic tests were statistically not different between patients with normal and abnormal vibration and position senses. Table 3.14-A.

Electrodiagnostic test results according to abnormal

vibration and position sense in LSR group EDX results

Vibration and position senses Normal

Abnormal

Pearson chi-

N=54(77.1%) N=16(22.9%) Needle EMG

Normal

Count

N=13

% within V and P

Abnormal

Count

N=57

% within V and P

Normal

Count

N=51

% within V and P

Abnormal

Count

N=19

% within V and P

Normal

Count

N=61

% within V and P

Abnormal

Count

N=9

% within V and P

Normal

Count

N=55

% within V and P

Abnormal

Count

N=15

% within V and P

12

1

22.2%

6.2%

42

15

77.8%

93.8%

38

13

70.4%

81.2%

16

3

29.6%

18.8%

46

15

85.2%

93.8%

8

1

14.8%

6.2%

44

11

81.5%

68.8%

10

5

18.5%

31.2%

square

0.14(NS)

NCS

0.39(NS)

F-wave

0.36(NS)

H-reflex

0.27(NS)

73

Chapter 3 Results Table 3.14: B. Electrodiagnostic results and vibration and position senses in CR group Vibration and Position sense Pearson chi-

EDX results

Needle EMG

Normal

Count

N=50

N=13

% within V and P

Abnormal

Count

N=37

% within V and P

NCS

Normal

Count

N=50

N=46

% within V and P

Abnormal N=4

Count

Negative

Positive

N=46(92%)

N=4(8%)

square

12

1

26.1%

25.0%

34

3

73.9%

75.0%

43

3

93.5%

75.0%

3

1

6.5%

25.0%

45

4

97.8%

100.0%

1

0

2.2%

.0%

0.96(NS)

0.19(NS) % within V and P

F wave

Normal

Count

N=50

N=49

% within V and P

Abnormal N=1

Count

0.76(NS) % within V and P

3.15. Different electrodiagnostic results according to dermatomal distribution. These results are shown in table 3.15-A and 3.15-B. According to dermatomal distribution, patients with positive dermatomal distribution showed no statistically significant differences regarding results of abnormal needle EMG, NCS and F-wave latency compared to those with negative dermatomal distribution having abnormal EMG, NCS and F-wave latency for both patient groups (LSR and CR). Also regarding patients with suspected LSR, those with positive dermatomal distribution and abnormal H-reflex (n=13, 27.7%) was appreciably different but statistically not significant when compared to those with negative dermatomal distribution having abnormal H-reflex (n=2, 8.7%).

77

Chapter 3

Results

Table 3.15- A. Electrodiagnostic results according to dermatomal distribution in LSR Dermatomal distribution EDX results

Negative

Positive

Pearson Chi-square

N=23 (32.9%) N=47(67.1%)

Normal Needle EMG

N=13

N=70

Abnormal

Count % within dermatome

6

30.4%

12.8%

16

41

69.6%

87.2%

18

33

78.3%

70.2%

5

14

21.7%

29.8%

20

41

87.0%

87.2%

3

6

13.0%

12.8%

21

34

91.3%

72.3%

2

13

8.7%

27.7%

0.07(NS) N=57

Count % within dermatome Count

NCS

7

Normal n=51 % within dermatome

N=70

0.47(NS) Abnormal N=19 Normal

F-wave N=70

N=61

Normal

N=70

% within dermatome Count % within dermatome

0.97(NS) Abnormal N=9

H-reflex

Count

N=55

Count % within dermatome Count % within dermatome

0.06(NS) Abnormal N=15

Count % within dermatome

Table 3.15- B. Electrodiagnostic results according to dermatomal distribution in CR EDX results

Needle EMG

Dermatomal distribution

Normal

Negative

Positive

Pearson Chi-

N=32(64%)

N=18(36%)

square

Count

10

3

% within dermatome

31.2%

16.7%

Count

22

15

% within dermatome

68.8%

83.3%

Count

29

17

% within dermatome

90.6%

94.4%

Count

3

1

% within dermatome

9.4%

5.6%

Count

32

17

0.25(NS) Abnormal

NCS

Normal

Abnormal

F wave

Normal

0.63(NS)

77

0.17(NS)

Chapter 3

Results Abnormal

% within dermatome

100.0%

94.4%

Count

0

1

% within dermatome

.0%

5.6%

3.16. Electrodiagnostic results and stretch reflex Number of patients with suspected LSR with decreased/absent stretch reflex and abnormal H-reflex latency (n=10, 40%) was significantly different from number of patient with normal stretch reflex but having abnormal H-reflex latency (n=5, 11.1%, p=0.001). However, in both groups of patients number and percentage of abnormal needle EMG, NCS and F-wave latency between patients with decreased or absent stretch reflex and normal stretch reflex were turned out to be statistically not significant (table 3.16-A and 3.16-B) Table 3.16: A. Electrodiagnostic results and stretch reflex in LSR group Stretch reflex Pearson Chi-

EDX results

Count

Normal

Decreased/Absent

N=45(64.3%)

N=25(35.7%)

10

3

22.2%

12.0%

35

22

77.8%

88.0%

32

19

71.1%

76.0%

13

6

28.9%

24.0%

41

20

91.1%

80.0%

4

5

8.9%

20.0%

40

15

88.9%

60.0%

5

10

11.1%

40.0%

square

Normal % within S reflex

0.29(NS)

Needle EMG Count Abnormal % within S reflex Count Normal % within S reflex

0.65(NS)

NCS Abnormal

Count % within S reflex Count

Normal % within S reflex

0.18(NS)

F wave Abnormal

Count % within S reflex Count

Normal % within S reflex

0.001

H reflex Abnormal

Count % within S reflex

78

Chapter 3

Results

Table 3.16: B. Electrodiagnostic results according to stretch reflex in CR group Stretch Reflex Reduced

Pearson Chi-

Normal

/Absent

square

N=32(64%)

N=18(36%)

9

4

28.1%

22.2%

23

14

71.9%

77.8%

30

16

93.8%

88.9%

2

2

6.2%

11.1%

31

18

96.9%

100.0%

1

0

3.1%

.0%

EDX results

Needle EMG

Normal

Count

N=50

N=13

% within Stretch reflex

Abnormal

Count

N=37

% within Stretch reflex

NCS

Normal

Count

N=50

N=46

% within Stretch reflex

Abnormal N=4

Count

0.64(NS)

0.54(NS) % within Stretch reflex

F wave

Normal

Count

N=50

N=49

% within Stretch reflex

Abnormal N=1

Count

0.44(NS) % within Stretch reflex

3.17. Association between types of EMG abnormality with types of MRI abnormality According to the types of MRI abnormality, patients with suspected LSR or CR were divided into subgroups (table 3.17-A and 3.17-B). According to these subdivisions, the types of needle EMG abnormality were turned out to be statistically not significant. It is worthy to mention that in both patient groups bulging on MRI was the most frequent finding (n=36 out of 55 for LSR and n=31 out of 33 for CR). Also in both groups of patients, neuropathic MUAPs with reduced recruitment and spontaneous activity was more frequent than neuropathic MUAPs with normal recruitment (n=54 out of 55 and n=27 out of 33 versus n=1 out of 55 and n=6 out of 33) (figure 3.7)

78

Chapter 3 Results Table 3.17- A. Types of EMG abnormality with types of MRI abnormality in LSR group Pearson Total chiEMG types for LSR group square Prolapse* Bulging Stenosis Extrusion MRI type

Neuropathic MUAP, normal recruitment

Count

1

% within 6.7% MRI type

Neuropathic MUAP, Count 14 reduced recruitment and % within Spontaneous activity MRI type 93.3%

Total

Count

15

% within 100.0% MRI type

0

0

0

1

.0%

.0%

.0%

1.8%

36

2

2

54

100%

100.0% 100.0%

98.2%

36

2

55

2

100.0% 100.0% 100.0%

0.20 (NS)

100.0%

* protrusion in some references

Figure 3.7: Neuropathic motor unit potentials and its parameters recorded from medial gastrocnemius muscle in a patient with chronic S1 sacral radiculopathy.

78

Chapter 3 Results Table 3.17-B. Types of EMG abnormality with types of MRI abnormality in cervical radiculopathy group MRI type

EMG types for CR Prolapse Neuropathic MUAP, normal recruitment Neuropathic MUAP, reduced recruitment and Spontaneous activity Total

Count

1

Bulging

Total

5

6

% within MRI type 50.0%

16.1%

18.2%

Count

1

26

27

50.0%

83.9%

81.8%

2

31

33

100.0%

100.0%

0.22 (NS)

% within MRI type

Count

Pearson chisquare

% within MRI type 100.0%

3.18. Association between Needle EMG, NCS, late responses and root/thecal compression in MRI. As shown in table 3.18-A, among 65 patients with abnormal MRI 54 patient exhibited thecal and root compression on their MRI and 11 patients showed no root or thecal compression. The results of abnormal needle EMG (n=47, 87%), NCS (n=17, 31.5%) and F-wave latency (n=8,14.8%) were statistically not significant when comparing between those with thecal and root compression with those with no root or thecal compression on their MRI. The interesting finding was that all patients with abnormal H-reflex showed thecal and root compression on MRI. However, none of patients with no root or thecal compression showed abnormal H-reflex latency and this difference was turned out to be statistically significant (n=15, 27.8% vs n=0, 0%) (p=0.04). Among patients with suspected CR, 33 patients with abnormal MRI had thecal and root compression and 10 showed no root or thecal compression. Results of abnormal needle EMG (n=26, 78.8% vs n=7, 70%), NCS (n=4, 12.1% vs n=0.0%) and F-wave (n=1, 3% vs n=0, 0%) between the two groups were statistically not significant (table 3.18-B). 77

Chapter 3 Results Table 3.18- A. Association of different Electrodiagnostic result and root/thecal compression in MRI MRI Comp EDX results for LSR group

Needle EMG

Normal N=10

Count

3

7

% within MRI Compression

27.3%

13.0%

8

47

72.7%

87.0%

Count

10

37

% within MRI Compression

90.9%

68.5%

1

17

9.1%

31.5%

Count

10

46

% within MRI Compression

90.9%

85.2%

1

8

9.1%

14.8%

Count

11

39

% within MRI Compression

100.0%

72.2%

0

15

.0%

27.8%

Abnormal Count N=55 % within MRI Compression NCS

Normal N=47

Abnormal Count N=18 % within MRI Compression F wave

Normal N=56

Abnormal Count N=9 % within MRI Compression H reflex

Normal N=50

Thecal and No root, no thecal root compression compression N=11 N=54

Abnormal Count N=15 % within MRI Compression

NS: Not significant.

77

Pearson Chi-square

0.23 (NS)

0.13(NS)

0.61(NS)

0.04

Chapter 3

Results

Table 3.18- B. Association of different Electrodiagnostic result and root/thecal compression in MRI MRI compression No root, no thecal compression n=10

Thecal and root compression n=33

Count

3

7

% within MRI compression

30.0%

21.2%

7

26

70.0%

78.8%

Count

10

29

% within MRI compression

100.0%

87.9%

0

4

.0%

12.1%

Count

10

32

% within MRI compression

100.0%

97.0%

0

1

.0%

3.0%

EDX results for CR group

Needle EMG

Normal N=10

Abnormal Count N=33 % within MRI compression

NCS

Normal N=39

Abnormal Count N=4 % within MRI compression

F wave

Normal N=42

Abnormal Count N=1 % within MRI compression

77

Pearson chisquare

0.56(NS)

0.24(NS)

0.57(NS)

Chapter 3 3.19. Electrodiagnostic results according to MRI root level

Results

Patients with suspected LSR were subdivided into 6 groups according to the root involved on MRI (levels of MRI abnormality). Out of 65 patients with abnormal MRI finding, L4,L5/L5,S1 levels were the commonest level of root involvement (n=21) (table 3.19-A). Statistical analysis of abnormal EDX test results including abnormal needle EMG, NCS, F-wave latency and H-reflex latency showed none significant differences. Patients with suspected cervical radiculopathy were divided to into 8 subgroups according to the level of root involved on MRI (level of MRI abnormality) (3.19-B). C5,C6 level was the commonest involved root level seen on MRI (n=12 out of 43). As observed in patients with suspected LSR, statistical analysis for patients with suspected CR with abnormal electrodiagnostic test results including abnormal needle EMG, NCS and F-wave latency showed no significance differences.

77

73

H-reflex

F-wave

NCS

Needle EMG

EDX test results

1 (100%

4 (40%)

Abnormal

2(12.5%)

0 (0%)

6 (60%)

14 (87.5%)

Normal

1 (10%)

2 (12.5%)

Abnormal

0 (0%)

1 (100%

9 (90%)

0 (0%)

1 (100%

14 (87.5%)

9 (90%)

13 (81.2%)

1 (100%

Normal

10 (100%)

12 (75%)

0 (0%)

N =1

1 (5.6%)

0 (0%)

4 (25%)

N =10

N =16

S1,S2

3 (16.7%)

Abnormal

Normal

Abnormal

Normal

L5,S1

L4,L5

N=65

3 (14.3%)

18 (85.7%)

3 (14.3%)

18 (85.7%)

7 (38.9%)

14 (66.7%)

16 (76.3%)

5 (23.8%)

N =21

L4,L5/L5,S1

Levels of MRI abnormality

3 (42.9%)

4 (57.1%)

2 (28.6%)

5 (71.4%)

3 (16.7%)

4 (57.1%)

7 (100%)

0 (0%)

N =7

L3,L4/L4,L5

Table 3.19-A. Different EDX results according to level of MRI abnormality in LSR group

2 (20%)

8 (80%)

1 (10%)

9 (90%)

4 (22.2%)

6 (60%)

9 (90%)

1 (10%)

N =10

Multi-level

Chapter 3 Results

77

F-wave

NCS

EMG

Needle

results

EDX test

2(100%)

0(0%)

Abnormal

1(50%)

Abnormal

Normal

1(50%)

2(100%)

0(0.0%)

0(0%)

12(100%)

1(8.3%)

11(97.1%)

7(58.3%)

5(41.7%

N=12

N=2

Normal

Abnormal

Normal

C5,C6

C4,C5

0(0%)

7(100%)

0(0%)

7(100)

4(57.1%)

3(42.9%)

N=7

C6,C7

0(0%)

5(100%)

0(0%)

5(100%)

4(80%)

1(20%)

N=5

C4,C5/C5,C6

N=43

1(12.5%)

7(87.5%)

1(12.5%)

7(87.5%)

7(87.5%)

1(12.5%)

N=8

C5,C6/C6,C7

0(0%)

1(100%0

0(0%)

1(100%)

1(100%)

0(0%)

N=1

C6,C7/C7,C8

0(0%)

2(100%)

0(0%0

2(100%)

2(100%)

0(0%)

N=2

C3,C4/C4,C5

Table 3.19-B. Different EDX results according to level of MRI abnormality in CR group Level s of MRI abnormality

0(0%)

6(100%)

1(16.7%)

5(83.3%)

6(100%)

0(0%)

N=6

level

Multiple

Chapter 3 Results

Chapter 3 Results 3.20. Consistency of abnormal needle EMG with abnormal MRI findings regardless the root level Among 65 patients with abnormal MRI findings, 55 patients (84.6%) had also an abnormal needle EMG finding that was consistent with MRI abnormality and it was turned to be statistically highly significant (p=0.01) (table 3.20- A). In contrary to LSR, among 43 patients of CR group who have abnormal MRI, 33 patients (76.7%) were consistent with needle EMG abnormality that was statistically not significant (p= 0.270 (table 3.20-B). Table 3.20: Consistency of abnormal needle EMG findings with abnormal MRI findings regardless the root level in LSR and CR groups A. EDX result for LSR Needle EMG

Normal

Count % within MRI Abnormal Count % within MRI B. EDX result for CR Needle EMG Normal Count % within MRI Abnormal Count % within MRI

MRI Normal Abnormal 3 10 60.0% 15.4% 2 55 40.0% 84.6% 3 42.9% 4 57.1%

10 23.3% 33 76.7%

P-value

0.01

0.27

3.21. Consistency of abnormal needle EMG with abnormal MRI regarding the root level Regarding the root level of MRI in LSR group, out of 56 patients who had abnormal needle EMG, 47 patients (83.9%) had needle EMG abnormality which was consistent with the root level of MRI abnormality and it was turned to be statistically highly significant (p=0.001) (table 3.21-A). Also in patients with CR, out of 37 patients who had abnormal needle EMG, 30 patients (81.1%) had needle EMG abnormality which was consistent

77

Chapter 3 Results with the root level of MRI abnormality and it was also statistically highly significant (p=0.001) (table 3.21- B). Table 3.21: Consistency of abnormal needle EMG with abnormal MRI regarding the root level A. Needle EMG result for LSR Needle EMG Normal

Count % within MRI with Level

Abnormal

Count % within MRI with Level

Consistency Regarding Pearson chiRoot Level square No Yes (P-value) 11

0

55.0%

.0%

9

47

45.0% (16.1%)*

100.0% (83.9%)*

13

0

65.0%

.0%

7

30

35.0% (18.9%)*

100.0% (81.1%)*

0.001

B. Needle EMG result for CR Needle EMG Normal

Count % within MRI with Level

Abnormal

Count % within MRI with Level

0.001

* % within needle EMG 3.22. Comparison of rate of positive (Abnormal) electrodiagnostic tests, MRI findings and clinical findings between patients with cervical and lumbosacral radiculopathy Needle EMG was abnormal in 74% of cases with suspected cervical radiculopathy and in 81.4 % of patients with suspected lumbosacral radiculopathy. The difference between rate of positive (abnormal) needle EMG was turned to be statistically not significant (table 3.22). NCS and F-waves were abnormal in patients with suspected cervical radiculopathy with a frequency of 8% and 2% compared with 27.1% and 12.9% respectively in patients with suspected LSR and both were statistically significantly different when used to compare the rate of positive test findings between CR and LSR.

888

Chapter 3 Results Regarding MRI, 76.7% of patients with cervical radiculopathy showed abnormal results compared to 83.1% patients with suspected LSR and the difference was statistically not significant. Comparing the rate of positive clinical findings; dermatomal involvement, abnormal vibration and position sense and foot drop in patients with suspected LSR were 67%, 22.9% and 24.3% respectively compared to 36%, 8% and 0.0% (wrist drop) respectively in patients with suspected cervical radiculopathy. The rate of positive tests of these clinical findings were statistically significantly higher in patients with LSR compared to those with suspected cervical radiculopathy (p<0.001, p=0.22 and p<0.001 respectively). The rate of other positive clinical findings were statistically not significant between patients with suspected cervical and lumbosacral radiculopathy. Table

3.22:

The

difference

between

cervical

and

lumbosacral

radiculopathy in rate of positive tests findings Cervical radiculopathy (n=50) N % Positive clinical findings (signs and symptoms) History of neck pain / backache Upper / lower limb Parasthesia/pain Dermatomal involvement Positive Stretch reflex (absent, decreased) Vibration and position sense abnormality Wrist / foot drop or weak dorsiflexion Straight leg raising test Positive test findings Needle EMG NCS F wave H reflex MRI finding

* Not considered for CR group

888

Lumbosacral radiculopathy P value (n=70) N %

50 48 18 18 4 0 *

100.0 96.0 36.0 36.0 8.0 0.0 *

67 67 47 25 16 17 38

95.7 95.7 67.1 35.7 22.9 24.3 54.3

NS NS <0.001 NS 0.022 <0.001 *

37 4 1 * 43

74.0 8.0 2.0 * 76.7

57 19 9 15 65

81.4 27.1 12.9 21.4 83.1

NS 0.009 0.034 * NS

Chapter 3 Results 3.23. Case-control comparison in positivity rate of selected tests for cervical and lumbosacral radiculopathy These results are shown in table 3.23. The positivity rate for selected tests in patients with suspected CR regarding abnormal NCS and abnormal F-wave latency between patients and control group was turned out to be statistically not significant. However, in patients with suspected LSR, the positivity rate for selected tests regarding abnormal H-reflex latency and abnormal NCS were statistically different compared to control group (p=0.02 and p=0.005 respectively). At the same time the positivity rate for abnormal F-wave latency in patients with LSR was statistically not significant compared with control group (p=0.2). Table 3.23: Case-control comparison in positivity rate of selected tests for LSR and CR groups

EDX test result for LSR group

Healthy controls N %

Cases with lumbosacral radiculopathy N %

p (Fisher's exact)

Abnormal (positive) H reflex

0 / 40

0.0

15 / 70

21.4

0.02

Abnormal (positive) NCS alone

0 / 40

0.0

19 / 70

27.1

0.005

Abnormal (positive) F wave

0 / 40

0.0

9 / 70 12.9 Cases with cervical radiculopathy N %

EDX test results for CR group Healthy controls N %

0.20[NS] p (Fisher's exact)

Abnormal (positive) NCS alone

0 / 40

0.0

4 / 50

8.0

0.32[NS]

Abnormal (positive) F wave

0 / 40

0.0

1 / 50

2.0

1 [NS]

888

Chapter 4

Discussion

4. Discussion 4.1 Blood test parameters in patients with suspected lumbosacral radiculopathy (LSR) and cervical radiculopathy (CR) compared with control group In the present study there was significant increase in serum level of Hs-CRP in both patient groups in comparison to control group. Inflammation plays a major role in radiculopathy. Once inflammation has been established, the nerves become exquisitely sensitive to pressure, producing prolonged and pain-generating discharge with either gentle manipulation or pressure (Refshauge and Maher, 2006). The results of high levels of Hs-CRP in patients with radiculopathy in current study support previous finding of an association between pain/inflammation and HsCRP levels. Thus Hs-CRP might be a marker of severity of pain in patients with specific musculoskeletal disorders. Stümer et al. observed a strong association between pain severity and Hs-CRP levels in patients with acute sciatic pain but not in those with chronic low back pain. The higher Hs-CRP levels were associated with higher pain Levels (Stürmer et al., 2005). 4.2. Nerve conduction parameters in patients suspected of LSR and CR compared with the control groups In this study routine nerve conduction studies (NCS) were found to be abnormal in fairly low percentage of patients with suspected LSR (n=19, 27.1%) but normal in other study groups (CR and control groups). This finding is consistent with results commonly reported in the literature (Dumitru et al, 2002, Dillingham, 2002, Ghugare et al., 2009). Motor NCS typically are normal in patients who have radiculopathy, because only a portion of nerve fascicles within a nerve root trunk is injured (Dumitru et al, 2002). CMAP abnormalities in radiculopathies are limited by the overlapping root innervations and the usually incomplete nature of the root injury. For similar reasons, slowing of motor conduction velocities between proximal and distal stimulation sites is uncommon and, if present, limited in degree. Decrease in motor conduction would 301

Chapter 4 Discussion be restricted to the mild slowing seen with loss of the largest, fastest conducting motor fibers (Morris, 2002). If the radiculopathy results in sufficient motor axon loss (up to 50% of motor axons within a nerve trunk) the compound motor action potential (CMAP) amplitude may be reduced significantly. Even in the presence of severe axon loss, however, routine motor NCS may appear normal unless the CMAP is generated from a muscle that receives innervation from the injured nerve root. In addition, the pathophysiology of radiculopathy at the root level infrequently is a focal, purely demyelinating conduction block. If this occurs, routine motor NCS remain normal even if weakness is present in corresponding myotomes (Bryan, 2007). In the current study, F-wave latency is found to be of little value in the diagnosis of radiculopathy. In LSR group, out of 70 patients, only 9 (12.9%) patients had abnormal F-wave latency and all patients with suspected CR showed normal Fwave latency except one patient who had also carpal tunnel syndrome. Furthermore, unlike H-reflex latency, no significant relation was observed between F-wave latency and any one of the different abnormal clinical test findings. In spite of articles suggesting the possible contribution of F-waves in the diagnosis of radiculopathy (Eisen, 1985, Berger et al., 1999, Olmed et al., 2009 ) most authorities agree that the overall diagnostic yield of F-wave latency is low (10%–20%) for several reasons (Berger et al., 1999). The theoretic advantage that F waves evaluate the proximal segment of the motor nerve is offset by the fact that focal slowing within a short segment is diluted by normal conduction along the rest of the motor nerve pathway. Moreover the F-wave latencies are limited in that they assess only the fastest conducting fibers. Thus, a lesion that produces focal slowing has to affect all fibers equally to increase the minimal F latency, whereas most cases of radiculopathy cause partial axon loss and only rarely focal demyelination (Tsao, 2007). Consequently, it has been concluded that F waves often are normal in patients who have suspected radiculopathy, and ‘‘even when they are abnormal, their findings are inconsequential because the (needle electrode examination) findings are also abnormal and help to establish the diagnosis more definitively (Aminoff, 2002).’’ 301

Chapter 4 Discussion Although the specifics of the studies varies, reports using F wave parameters other than minimal latencies support the idea that F waves can be abnormal in at least L5/S1 radiculopathies. F waves by themselves cannot be used as evidence for a radiculopathy since any proximal nerve injury may disturb F wave parameters. At the same time, F waves could be useful in the electrophysiological evaluation of radiculopathies where such evidence of involvement of the anterior rami could be helpful (Morris, 2002). In 96 patients with L5/S1 radiculopathies, over 40% of these patients had clinically relevant absent or prolonged latency F waves and 76% had abnormal chronodispersion (Berger et al., 1999). Some researchers have found that if multiple features of the F wave are taken into account (for example, considering the minimum latency, the maximum latency, and the number of repeaters), they can be helpful in making the diagnosis. Overall, they appear less sensitive than the needle study and when F-waves are abnormal in patients with LSR, all of these patients also have abnormal needle EMG studies (Olmed et al., 2009). In a systematic review of evidence published through mid-2006, the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM, 2006) assessed the utility of electrodiagnostic testing for patients with lumbosacral radiculopathy. The AANEM observed that the available evidence suggests a low sensitivity for peroneal and tibial F waves (Cho et al., 2010). 4.3. Correlation between selected parameters (NCS, late responses and blood parameters) in the control group Both WBC and ESR were significantly positively correlated with serum HsCRP. Prior studies have also delineated the positive correlation of WBC and probably ESR with serum Hs-CRP particularly in relation to oxidative stress and aging process in asymptomatic subjects (Kotani and Sakane, 2012). In the present study, both peroneal and tibial minimum F-wave latency were positively correlated with age, a finding consistent with that reported by others (Hatamian and Imamhadi, 2005, Thakur et al., 2010). Decreased nerve fibers, 301

Chapter 4 Discussion reduction in nerve diameter, change in fiber membrane and loss of myelinated and unmyelinated nerve fibers are attributable factors of age (Stetson et al., 1992). 4.4 Correlation between selected parameters (Blood and NCS parameters) in LSR and CR patients. In both LSR and CR groups, there was significant positive correlations between Hs-CRP and CPK levels. The presence of such a correlation in patients with radiculopathy is not clear, however studies found an elevation of CPK level in patients with S1 radiculopathy who developed focal myositis with unilateral hypertrophy of the calf muscle (Gobbele et al., 1999, Gross et al., 2008). Determining factors for the localization of a focal myositis are not known, but S-1 radiculopathy might be a possible predisposing factor for the localization of the focal myositis in the calf muscle. This could be a consequence of increased vulnerability of muscle tissue to inflammatory processes as a result of the electromyographically proven chronic denervation (Gobbele et al., 1999). There is a strong support to the notion that denervated muscles can develop an inflammatory reaction (Streichenberger et al., 2004, Khan et al., 2005) 4.5: Validity parameters for tibial CMAP amplitude when used to predict LSR This study showed significant decrease of tibial CMAP in patients with suspected lumbosacral radiculopathy compared to control group (7.4 vs 10.9 mV, p<0.05) respectively. Tibial CMAP amplitude was the only NCS test result being valid to predict lumbosacral radiculopathy (AUC=0.782, p<0.05) which was significantly lower in LSR group in comparison to control group. Typical cut off value (optimum cut off value) for tibial CMAP amplitude was 8.8 mV which is associated with a sensitivity76.5%, specificity 75% and accuracy 76.1%. Data regarding this particular finding are little, to our opinion it is reasonably related to the fact that tibial motor response (CMAP amplitude) is recorded from abductor hallucis brevis muscle which receives motor fibers from both L5 and S1 roots and we found that the commonest root(s) level with abnormal needle EMG examination were L5 and S1 roots (n=15(26.3%), n=8(14%) respectively. In addition to that, 12(21.1%) of patients had combined L5-S1 root abnormality. 301

Chapter 4

Discussion

4.6 Validity parameters of BMI and Hs-CRP when used as test to predict radiculopathy. BMI and Hs-CRP were of high validity to predict cervical and lumbosacral radiculopathy with AUC of > 0.7 and p <0.001. A typical cut off value of BMI was equal or greater than 29.45 kg/m2 and for serum Hs-CRP was equal to or greater than 3.05 mg/L. Body weight is consistently associated with elevated Hs-CRP, and weight loss is associated with reduction in Hs-CRP levels, with some authors suggesting that HsCRP is merely a marker for obesity.

This association of Hs-CRP with these

conditions is poorly defined from a mechanism standpoint, and is possibly due to coassociation with prevalent vascular disease (Lemieux et al., 2001, Ziccardi et al., 2002, McLaughlin et al., 2002). Prior reviews also suggest that overweight or obesity is associated with clinically defined sciatica. Overweight can increase the risk of sciatic pain by increasing the mechanical load on the intervertebral discs. Weight-related factors associated more consistently with clinically defined sciatica than with mere selfreported pain. Overweight may also cause sciatica via inflammatory processes. Obesity is accompanied with a low-grade systemic inflammation and most obese people have elevated levels of inflammatory markers, including C-reactive protein (Shiri et al., 2007). In this study, body mass index and Hs-CRP were also associated with cervical radiculopathy. Similar results were obtained in a Finnish normal population study in which clinically defined “chronic neck syndrome” and radiating neck pain was associated with body mass index. Biomechanical factors may explain the result to some extent. Metabolic factors might also be involved, as obesity has been associated with general osteoarthrosis (Felson, 1988, Makela et al., 1991, Viikari et al., 2001). 4.7 Electrodiagnostic results according to duration of symptoms (DOS) In the present study, although higher percentage of needle abnormality in both LSR and CR groups of patients were found in those with longer DOS (from 6 months to a year and more), but this was turned out to be statistically not significant. Once 301

Chapter 4 Discussion first few months of a nerve root injury has past, it is difficult electrophysiologically to date whether or not the injury occurred three months ago or thirty years ago (On call medical, 2010, AANEM, 2002). Duration of symptoms appear to have little impact on probability of having abnormal electrodiagnostic results. Membrane abnormalities lead to appearance of spontaneous activity (fibrillation potentials and positive sharp waves) may persist for a year or more. Fibrillation potentials have been observed 5-6 years after laminectomy in patients with radiculopathy. Reinnervation (i.e. adopting of denervated muscle fibers by neighboring viable axons) does occur resulting in large amplitude polyphasic MUAPs (Johnson, 1993). The probability of spontaneous activity in a muscle is most likely related to which axons are involved at the root level, the rate and extent of denervation, whether needle EMG sampling of a muscle includes an area of the muscle showing denervation and the rate and extent of Reinnervation by remaining axons. The study of Dillingham et al. did not support the hypothesis of a statistically significant relationship between the probability of spontaneous activity in paraspinal muscles and other limb muscles and symptoms duration (Dillingham, 1998, Dillingham, 2013). Fibrillation potentials decrease in amplitude and therefore prominence with time after injury, possibly due to atrophy. Fibrillations and positive sharp waves will disappear with time because of recovery with reinnervation or due to loss of muscle reactivity. Even with injury to motor fibers, abnormal spontaneous activity may never be present. Abnormal spontaneous activity will not occur with demyelination since there is functional but not structural injury to axons. Abnormal spontaneous activity will also not occur if the pathological effects are slow such that reinnervation can compensate for axonal loss (Dumitru et al., 2001). 4.8 Electrodiagnostic test results according to different clinical test findings: The clinical symptoms associated with radiculopathy (dermatomal sensory loss, reflex change, motor weakness) are not straight forward. Clinical symptoms may be present to a varying degree and also may be quite variable. Sensory loss may not be 301

Chapter 4 Discussion present or difficult to define. Because of sclerotomal pain referral, symptoms may be present in a non-dermatomal distribution. Deep tendon reflexes may be diminished or lost depending on a specific root injury. The biceps reflex is commonly used to monitor lesions of the C5 root, the brachioradialis C6, the triceps C7, the patella L4, and the Achilles’ S1. However, all muscles in a myotome may not be affected, and multiple roots supply an individual muscle. Because of overlapping findings, clinical differentiation between even commonly injured roots such as C6 and C7 can be difficult (Morris, 2002). In the current study, the percentage of abnormal clinical examinations was as follow; Sensory abnormalities (loss or diminished sensation and positive dermatomal distribution) were found in 67.1% of LSR group Vs 36% of CR group. SLRT was positive in 54.3% of LSR group and abnormal stretch reflex was found in 35.7% of LSR Vs 36% of CR group. Foot drop/weak dorsiflexion was seen in 24.3% of LSR group and abnormal vibration and position sensations identified in 22.9% for LSR Vs 8% for CR group. Similarly, a study conducted on patients with LSR found that SLRT was positive in 62.5% of patients. Abnormal muscle stretch reflexes, sensory abnormalities, and strength deficits were present in a smaller percentage of patients (Foley et al., 2006). In the systematic review of Al Nezari et al. which compared and analyzed the neurological test results with surgical and/or radiological reference testing for disc herniation and uniquely evaluated the relationship between neurological findings and specific levels of disc herniation in radiculopathy, they reported that the overall findings revealed limited diagnostic accuracy of all components of the neurological examination to detect a disc herniation in patients with suspected radiculopathy, which was independent of either the testing procedure used to detect disc herniation or the level of herniation (Al Nezari et al., 2013). Strikingly, in one study, subjective muscle weakness and sensory loss actually diminished the likelihood of nerve root compression. These findings are at variance with current opinion. The selection bias in previous studies may have affected the understanding of the true relation of these complaints to nerve root compression. It is 301

Chapter 4 Discussion possible that subjective weakness and sensory loss have no neurological basis in most patients (Vroomen et al., 2002). Among the different EDX test results, needle EMG was significantly abnormal in patients with positive foot drop or weak dorsiflexion compared to other abnormal clinical findings. This means that whenever there is motor abnormality, evidenced by foot drop or weak dorsiflexion, the probability of abnormal needle EMG exam significantly rises. Rachel et al., found that EMG was abnormal in 76% of patients with demonstrable weakness compared with 40% of patients without weakness (Nardin et al., 1999). Foot drop or weak dorsiflexion in LSR mainly occurs in L5 lumbar involvement. L5 root was the most frequent root involvement on needle EMG (n= 15, 26.3%) in isolation and (n=13, 22.8%) in combination with L4 radiculopathy. Studies focusing on this entity are scarce, although there is an agreement that EMG abnormality is higher in those with motor weakness. EMG, which tests only the anterior nerve root function, may be normal in root injuries that affect the dorsal root fibers predominantly (Wilbourn and Aminoff, 1998). This likely explains our finding that EMG was only significantly abnormal in patients with foot drop or weak dorsiflexion compared to other abnormal clinical tests. NCS and EMG have a high diagnostic utility for radiculopathy when neurologic weakness is present for at least three weeks that is why these studies are most often considered for those with persistent unexplained symptoms. The yield is lower in patients with only pain or sensory loss as manifestations of radiculopathy. For patients with nonspecific spine pain, EMG can help to distinguish pain-related reduced muscular effort from true neurogenic weakness. In patients with weakness due to radiculopathy, NCS and EMG together can localize the specific spinal nerve root that is damaged, distinguish between old and new axon loss nerve damage, and provide indirect support for the presence of demyelinating conduction block at the root level (Levin, 2000, Tsao et al., 2003). H-reflex of tibial nerve was also found to be significantly associated with some abnormal clinical findings than other. We found that the number and percentage of patients with positive SLRT and abnormal H-reflex latency was statistically 330

Chapter 4 Discussion significantly higher than patients with negative SLRT having abnormal H-reflex latency (p=0.001). Furthermore, number of patients with suspected LSR with decreased/absent stretch reflex and abnormal H-reflex latency was significantly different from number of patient with normal stretch reflex but having abnormal Hreflex latency (p=0.001). H reflex abnormalities have been found to have a high predictive value in S1 radiculopathies in a series of 25 patients with lumbosacral radiculopathies, 20 of whom had surgical confirmation of their root lesion (Albeck et al., 2000). In this study, S1 root was the next most common root involved by needle EMG (n=8, 14%) in isolation and ( n=12, 21.1%) in combination with L5 radiculopathy. Hreflex appears to be promising in the diagnosis of S1 radiculopathy. H-reflexes have several strengths, including the ability to detect injury to sensory fibers, and they become abnormal as soon as a compression occurs and the deficit can last indefinitely (Barr, 2013). Other studies have investigated the tibial nerve H-reflex in the diagnosis of lumbosacral radiculopathy. The diagnostic sensitivity and specificity varied widely. One study (Haig et al., 2005) noted 100% sensitivity and specificity, whereas others (Albeck et al., 2000, Marin et al., 1995) reported sensitivity of 51 and specificity of 91% in S1 radiculopathy group. 4.9 Association between types of EMG abnormality with types of MRI abnormality In both LSR and CR groups, bulging on MRI was the most frequent finding. Also in both groups of patients, neuropathic MUAPs with reduced recruitment and spontaneous activity were more frequent. The term (herniation) can be used to describe a wide spectrum of abnormalities involving disk extension beyond the interspace, from a bulge to a frank extrusion; therefore, the reported data on the prevalence of herniation can be misleading. We avoided using "herniation" and we chose only the following terms; bulging, prolapse (protrusion), extrusion and stenosis. In the present study, bulging was the commonest type of MRI abnormality followed by protrusion and extrusion. This is also 333

Chapter 4 Discussion documented in other studies (Jensen et al., 1994, Jarvik et al., 2001, Dora et al., 2002). In the current study, we relied on the presence of neuropathic MUAPs, reduced recruitment with spontaneous activity and it was observed that these are the most frequent needle EMG abnormality in patients with suspected LSR and CR and the overall percentage of abnormal needle EMG was high in patients who had also abnormal MRI (whether bulging, protrusion, extrusion or stenosis). With injury to motor axons and disruption of the normal interactions between nerve and muscle, abnormal spontaneous activity occurs due to resultant membrane instability in muscle fibers. The most prevalent of these changes are fibrillations and positive sharp waves. With chronic neurogenic injury and reinnervation, motor units increase in size and therefore motor unit duration since this correlates with the area occupied by a single motor unit. Motor unit amplitudes may also be increased. Increase in motor unit amplitude in a myotomal distribution can be helpful in establishing a radicular process as well as its chronicity (Morris, 2002). Dillingham and colleagues performed a prospective study on patients referred for electrodiagnostic testing for suspected radiculopathy. For all patients, a standardized electrodiagnostic screen was performed that consisted of 11 muscles. Muscles were considered abnormal if they had abnormal spontaneous activity, abnormal motor unit morphology consistent with nerve injury, or a neuropathic recruitment pattern (reduced recruitment) (Dillingham et al., 2000). 4.10 Electrodiagnostic (EDX) results according to MRI root level In the current study, out of 65 patients suspected of LSR with abnormal MRI finding, L4,L5/L5,S1 levels were the commonest level of root involvement. And in CR group, C5,C6 level was the commonest involved root seen on MRI (n=12 out of 43). This finding is also commonly seen in previous studies (Tarulli et al., 2007, Roth et al., 2009) In patients with suspected LSR, L5 root was the most frequent root involvement on needle EMG (n= 15, 26.3%) in isolation and (n=13, 22.8%) in 331

Chapter 4 Discussion combination with L4 radiculopathy followed by S1 root. Other level roots were not frequent. This finding is established in other studies (Wilbourn and Aminoff, 1998,) Most radiculopathies – 60–90% – occur at the lumbosacral level. Cervical radiculopathies may account for only 5–10% of root disorders (Wilbourn and Aminoff, 1998, Dillingham et al., 2000, Dumitru, 2002). Seventy to eighty percent of lumbosacral radiculopathies involve the L5 or S1 roots while about 10% affect the L2, L 3, or L4 roots (Dumitru, 2002). In the study of Dillingham

on

patients

with

electrodiagnostically

confirmed

lumbosacral

radiculopathies, the most frequent level on needle EMG was L5 (n=29), 9 involved only the L3–4 levels, 12 the L4–5 levels, 21 the L5–S1 levels, 19 at the S1 level, 4 involved multiple (>2) levels, and 8 were indeterminate, with only the paraspinal muscles demonstrating abnormalities (Dillingham et al., 2000). L2, 3, 4 radiculopathies need to be considered together because of the myotomal overlap of the thigh muscles innervated by these roots. The tibialis anterior receives L4 innervation, but the absence of neurogenic injury on needle EMG cannot be used to exclude an L4 radiculopathy. L2–4 radiculopathies can be difficult to differentiate from femoral mononeuropathies or lumbar plexopathies. With Neurogenic injury in the tibialis anterior due to root injury, absence of paraspinal abnormalities occurs frequently enough such that absence of such findings cannot be used to exclude a radiculopathy (Morris, 2002). The most frequent root level found on needle EMG in patients with suspected CR in the present study was C7 root (n=11, 29.7%). This is in agreement with the study of Levin et al. In their report comparing electrodiagnostic findings with surgically observed solitary root lesions in 50 patients, Levin et al. found that C7 root injury was present in 56% with C5, C6, and C8 root lesions comprising 14, 18, and 12%, respectively. Defining isolated C6 lesions by needle EMG alone may be difficult due to overlapping innervation of muscles supplied by the C5 and C7 roots (Levin et al., 1996). A possible explanation is that intervertebral foramina are largest in the upper cervical region and progressively decrease in size in the middle and 331

Chapter 4 Discussion lower cervical areas. Thus, the middle and lower cervical regions are most susceptible for mobility and stress (Tanaka, 2000). 4.11 Consistency of abnormal needle EMG with abnormal MRI findings regardless/regarding the root level The primary root innervation of many muscles remains unclear. Besides a lack of consensus in this area, there is considerable individual variation in the innervation of individual muscles. Because of this, if needle EMG changes are found in a muscle, the examining physician cannot say with 100% certainty what root level innervates that muscle; the examiner can only state what is thought to be the usual level for a typical patient (Barr, 2013). In the current study, in the LSR group, among 65 patients with abnormal MRI findings, 55 patients (84.6%) had also an abnormal needle EMG finding that was consistent with MRI abnormality and it was turned to be statistically significant (p=0.01). Regarding the root level of MRI in LSR group, 47 patients (83.9%) had needle EMG abnormality which is consistent with the root level of MRI abnormality and it was turned to be statistically highly significant (p=0.001). In a study done by Foley et al., a retrospective study was conducted to compare MRI and EMG in patients with lumbosacral radiculopathy. MRI and EMG were highly correlative in 74.1% of patients (Foley et al., 2006). Similar agreements were estimated by the American Association of Electrodiagnostic Medicine (AAEM) which stated that good agreement is found between needle EMG and imaging studies (about 65%-85%)(AAEM, 1999). Because of the anatomy of lumbar and sacral region, there are many locations where the nerve root may be injured by a ruptured disk or other compressive force. For example, a disk herniation between the L4 and L5 vertebral bodies (which is the most common level) can affect the L4 root if it is a far lateral herniation, the L5 root if it is a posterior lateral herniation, and the S1–S4 roots if it is a central herniation. Within the cauda equina, roots are packed closely together so it is common for bilateral, multiroot lesions to be found in lumbar central stenosis (Wilbourn and Aminoff, 1998). 331

Chapter 4 Discussion Among 43 patients of CR group who had abnormal MRI, 33 patients (76.7%) were consistent with needle EMG abnormality that was statistically not significant. But, regarding the root level on MRI, out of 37 patients who had abnormal needle EMG, 30 patients (81.1%) had needle EMG abnormality which is consistent with the root level of MRI abnormality and was statistically highly significant (p=0.001). In the study of Kwast and Libelius, abnormal EMG of C5 and C6 myotomes correlated significantly with intraforaminal narrowing on MRI at C5–6 (p < 0.001) and EMG of C7 myotome correlated with the MRI abnormality at C6-7 level (p < 0.001) (Kwast and Libelius, 2006). If the specificities and sensitivities of specific electrophysiological techniques for evaluating

radiculopathies are to be established, then accepted criteria for

diagnosing radiculopathies using other information need to be present. Neither clinical nor imaging information provides such a ‘gold standard’ (Morris, 2002). 4.12 Comparison of positive (Abnormal) electrodiagnostic tests, MRI findings and clinical findings between patients with cervical and lumbosacral radiculopathy In the current study, the difference between rates of positive (abnormal) needle EMG between LSR and CR groups was turned to be statistically not significant (81.4% vs 74%). Regarding MRI, 76.7% of patients with cervical radiculopathy showed abnormal results compared to 83.1% patients with suspected LSR and the difference was also statistically not significant indicating that both MRI and EMG are of same value for diagnosis of lumbosacral and cervical radiculopathy. These findings are consistent with the study of Nardin et al. who concluded that EMG and MRI findings agree in a majority of patients with a clinical history compatible with cervical or lumbosacral radiculopathy (Nardin et al., 1999). The chance of having at least one abnormal study is greater in patients with objective neurologic examination abnormalities consistent with radiculopathy. Overall this study suggests that EMG and MRI remain complementary modalities in the evaluation of lumbosacral and cervical radiculopathy. 331

Chapter 4 Discussion On the other hand the results of NCS and F-waves in patients with LSR compared with CR were statistically significant when used to compare the rate of positive test findings between cervical and LSR. Also the rate of positive tests of dermatomal involvement, abnormal vibration and position sense and foot drop were statistically significantly higher in patients with LSR compared to those with suspected cervical radiculopathy. These interesting results suggest that NCS studies should be performed in all patients with suspected LSR and rate of abnormal NCS findings is much higher than in patients with suspected CR. These findings are in agreement with what is commonly reported (Preston and Shapiro, 2005). In patients with radiculopathy, NCS are normal and the diagnosis is established on needle EMG. However, depending on the underlying pathophysiology and the level of the lesion, abnormality may be seen on motor NCS and F-waves. If the pathophysiology also involves axonal loss, motor NCS abnormality may be seen. Here again, abnormalities were seen only in the recorded muscle innervated by the affected root. Axonal loss results in decreased CMAP amplitude with some slowing of conduction velocity and distal latency (Preston and Shapiro, 2005). In the present study, abnormalities were observed in peroneal and tibial CMAP amplitudes (particularly abnormal tibial CMAP amplitude). These nerves innervate extensor digitorum brevis (peroneal innervated) and abductor hallucis muscles (tibial innervated) in the lower limb and these muscles are mainly innervated by L5-S1 roots respectively. L5-S1 roots were found to be most frequently affected in the current study. In this study, F-wave latency was abnormal almost in patients with suspected LSR (n=9, 12.9% of patients with suspected LSR versus n=1, 2% in patients with suspected CR). The only patient who had prolonged F-wave latency in the CR group was found to have carpal tunnel syndrome (CTS). F-waves will be abnormal only if the recorded muscle is innervated by the affected roots. In cervical radiculopathy, Fwaves are routinely recorded only for the median and ulnar nerves, which are C8-T1 innervated. Thus, median and ulnar F-wave abnormalities may be seen in C8-T1 radiculopathy; however, these roots are infrequently affected by disc or bone 331

Chapter 4 Discussion impingement. A radiculopathy at C5,C6 or C7, which are more common sites of root impingement, will not be reflected in the median and ulnar F-wave responses. The situation is different in the lower extremity. The distally recorded peroneal and tibial muscles (extensor digitorum brevis, abductor hallucis brevis) are innervated by the L5-S1 nerve roots, which often are affected by lumbosacral radiculopathy. Thus, in L5-S1 radiculopathies, tibial and peroneal F-wave responses may be prolonged (Preston and Shapiro, 2005). Moreover, strict and detailed clinical examination in assessment of patients with suspected LSR is more valuable than in patients with suspected CR as far as these patients showed higher abnormal rate of clinical tests. The possible explanation for this is that in lower limbs, presence of foot drop/weak dorsiflexion and abnormal vibration/position test results are mostly L5-S1 innervated which are commonly affected in radiculopathy. Regarding the dermatomal distribution, although in lumbosacral and cervical radiculopathy, a dermatomal distribution of pain is not a useful historical factor in the diagnosis of radicular pain, the possible exception to this is the S1 nerve root, in which the pain does commonly follow the S1 dermatome. The dermatome pattern for the S1 nerve root that is most commonly described in the literature involves the posterolateral thigh and leg and the lateral foot. This study found that this pattern of pain was seen in 65% of patients with S1 radicular pain. Thus, a dermatomal pain pattern may be useful diagnostically in patients with S1 nerve root pain. It is known that the lower extremity referred pain pattern of somatic structures innervated by the S1 segment also commonly follows the classic S1 dermatome (Murphy et al., 2009). 4.13 Case-control comparison in positivity rate of selected tests for cervical and lumbosacral radiculopathy In the present study, a statistically significant difference between healthy controls and patient groups in positivity rate of selected tests was only noted between healthy controls and LSR patient group. The positivity rate for selected tests regarding abnormal H-reflex latency and abnormal NCS were statistically different 331

Chapter 4 Discussion compared to control group. Meanwhile compared with control group, the positivity rate for abnormal F-wave latency in patients with LSR was statistically not significant. None of the selected tests were significantly different regarding the positivity rates between healthy controls and CR patient group. Regarding the F-wave latency, the present study disagrees with that reported in the study of Pastore et al. in 2009 which compared F-waves between patients with LSR and healthy subjects and concluded that the use of F waves might improve the electrodiagnosis of the LSR. The explanation for that includes; they have selected only patients with L5 or S1 lumbosacral radiculopathy; also parameters in addition to F-wave latency as persistence, chronodispersion, and absolute and relative F-wave amplitude were measured and compared between patients and healthy subjects (Olmed et al., 2009).

331

5.1: Conclusions 1. Inflammation plays an important role in pathophysiology of radiculopathy indicated by high levels of Hs-CRP in patients with radiculopathy and the current study confirms previous finding of an association between pain/inflammation and Hs-CRP levels. 2. Estimation of BMI found in this study supports that overweight is a predisposing factor for radiculopathy and overweight can increase the risk of radiculopathy by increasing the mechanical load on the intervertebral discs, especially lumbosacral radiculopathy. 3. ROC analysis showed that serum Hs-CRP level and BMI are of high validity for diagnosis of cases with suspected LSR and CR. 4. Positive correlations between serum CPK and Hs-CRP levels is most likely secondary to focal inflammatory myositis in patients with S1 radiculopathy. 5. The possible abnormal NCS parameters to be detected in patients with suspected LSR are decreased tibial CMAP amplitude and prolonged H-reflex latency. However, NCS parameters in patients with suspected CR are usually normal and not valuable for diagnosis of CR. 6. ROC analysis indicated that only tibial CMAP amplitude is valid for diagnosis of LSR in clinically suspected cases and none of other NCS parameters of lower and upper limbs were valid for diagnosis of LSR and CR. 7. Results of abnormal NCS (except H-reflex latency) and needle EMG examination are not influenced by abnormal results of SLRT, vibration and position senses, dermatomal distribution of sensory abnormality and stretch reflex evidenced by non-significant differences in NCS and needle EMG results between patients having either normal or abnormal above clinical parameters. 8. Results of abnormal H-reflex latency in patients with suspected LSR is significantly influenced by positive or abnormal results of SRLT and stretch reflex, indicated by significantly higher abnormal percentage of H-reflex latency in patients with positive or abnormal SLRT and stretch reflex. 111

9. Duration of symptoms has little impact on electrodiagnostic results evidenced by statistically non-significant difference in NCS and Needle EMG results according to duration of symptoms. 10. NCS and late responses were mainly useful in the diagnosis of LSR but not for CR as the results of NCS and F-waves in patients with LSR compared with CR were statistically significant when used to compare the rate of positive test findings between CR and LSR. 11. Needle EMG is imperative for diagnosis of radiculopathy as it was the electrodiagnostic part most abnormal in patients with suspected radiculopathy 12. The utility of needle EMG in diagnosis of radiculopathy improves by increasing the number of muscles being screened for radiculopathy as majority of patients with lumbosacral and cervical radiculopathy in this study had abnormal needle EMG examination when six muscle screening was used. 13. The probability of abnormal needle EMG exam rises whenever there is motor abnormality on clinical examination, evidenced by significantly higher percentage of abnormal needle EMG findings seen in the current study in patients with foot drop or weak dorsiflexion. 14. Both EMG and MRI are complementary tests and are significantly consistent in diagnosis of patients with suspected radiculopathy. 15. Both EMG and MRI are of the same value for diagnosis of lumbosacral versus cervical radiculopathy as the difference between rates of positive (abnormal) needle EMG and abnormal MRI results between LSR and CR groups turned out to be statistically not significant

121

5.2: Recommendations We recommend that: 1. Needle EMG should be performed on all patients with suspected radiculopathy while NCS should be performed to exclude other possible disorders that mimic radiculopathy. 2. Decreasing body weight should be introduced as a strategy in treating patients with suspected radiculopathy. 3. Anti-inflammatory drugs should be prescribed to decrease an inflammatory reaction at the root level especially when the serum samples show high level of Hs-CRP (> 3.05 mg/L).

121

Adams C. Cervical Spondylotic Radiculopathy and Myelopathy. Amsterdam: Elsevier Publishing Company, 1976.

Aiello I, Rosati G, Serra G, Maca M: The diagnostic value of H-index in S1 root compression. J Neurol Neurosurg Psychiatry 1981; 44:171-210.

Berger Alan R., Khema Sharma and Richard B. Lipton. Comparison of motor conduction abnormalities in lumbosacral radiculopathy and axonal polyneuropathy. Muscle Nerve 1999; 22: 1053–1057.

Albeck MJ, Hilden J, Kjaer L, Holtas S, Praestholm J, Henriksen O, Gjerris F: A controlled comparison of myelography, computed tomography, and magnetic resonance imaging in clinically suspected lumbar disc herniation. Spine 1995;20: 443–448. Albeck MJ, Taher G, Lauritzen M, Trojaborg W. Diagnostic value of electrophysiological tests in patients with sciatica. Acta Neurol Scand 2000; 101:249. American Association of Electrodiagnostic Medicine Guidelines in electrodiagnostic medicine, Chap 9. The electrodiagnostic evaluation of patients with suspected cervical radiculopathy: literature review on the usefulness of needle electromyography. Muscle Nerve,1999, 22(Suppl 8):S213– S221 American Association of Electrodiagnostic Medicine. Practice parameter for needle electromyogrphic evaluation of patients with suspected cervical radiculopathy: summary statement. Muscle Nerve, 1999, 22(Suppl 8):S209–S211 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Guidelines in Electrodiagnostic Medicine, 1999; AANEM 121

Recommended Policy for Electrodiagnostic Medicine, 2002; AANEM: 1995 Course D: Needle Electromyography – Fundamentals. Aminoff MJ. Electrophysiological evaluation of root and spinal cord disease. Semin Neurol 2002;22:197–9. Tarulli

Andrew

W.

and

Elizabeth

M.

Raynor.

Lumbosacral

Radiculopathy. Neurol Clin 25 (2007) 387–405

Ansary A, Mondle M S, Hossain M A. Abnormalities in Plain X-Ray Findings of Lumbosacral Spine in Prolapsed Lumbar Intervertebral Disc. MEDICINETODAY. 2010 Volume 22 Number 01

Bais R, Edwards JB. Creatine kinase. Crit Rev Clin Lab Sci, 1982;16:291–335. Ghugare Balaji, Piyali Das, Jayshri Ghate, Kisan Patond, Manisha Koranne and Ramji Singh. Assessment of nerve conduction in evaluation of Radiculopathy among chronic low back pain patients without clinical neurodeficit. Indian J Physiol Pharmacol 2010; 54 (1) : 63–68 Kuijper Barbara, Jos Th J Tans, Bas F van der Kallen, Frans Nollet, Geert J Lycklama a Nijeholt, Marianne de Visser. Root compression on MRI compared with clinical findings in patients with recent onset cervical radiculopathy. J Neurol Neurosurg Psychiatry , 2011; 82:5 561-563. Bartlett RJ, Hill CR, Gardiner E. A comparison of T2 and gadolinium enhanced MRI with CT myelography in cervical radiculopathy. Br J Radiol 1998;71:11e19. Bell GR, Rothman RH, Booth RE, et al: A study of computer-assisted tomography. II. Comparison of metrizamide myelography and computed tomography, Spine surgery: 1984 122

Benzel EC.: techniques, complication avoidance, and management. Spine surgery 2005.

Berger AR, Sharma K, Lipton RB. Comparison of motor conduction abnormalities in lumbosacral radiculopathy and axonal polyneuropathy. Muscle Nerve 1999;22:1053–1057.

Bergmyer HU., and al. Clin. Chem. (1978), 24, p.58-73

Bharadwaj D., Pastein M., VolzeM R, Mold C, and Du Clos Terry W. "The Major Receptor for C-Reactive Protein on Leukocytes Is Fc Receptor II." J Exp Med (1999).; 190(4): 585-590.

Birchall D, Connelly D, Walker L, et al. Evaluation of magnetic resonance myelography in the investigation of cervical spondylotic radiculopathy. Br J Radiol 2003;76:525e31. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW: Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects: a prospective investigation. J Bone Joint Surg [Am] 1990;72: 403–408.

Bogduk N. Low back pain. In: Bogduk N, editor. Clinical anatomy of the lumbar spine and sacrum. 3rd edition. NewYork: Churchill Livingstone; 1997. p. 187–214.

Boos N, Rieder R, Schade V, Spratt KF, Semmer N, Aebi M. The 1995 Volvo Award in clinical sciences. The diagnostic accuracy of magnetic resonance imaging, work perception, and psychosocial factors in identifying symptomatic disc herniations. Spine (Phila Pa 1976) 1995;20(24):2613-25. 121

Bovim G, Schrader H, Sand T. Neck pain in the general population. Spine 1994;19:1307-9. Tsao Bryan. The Electrodiagnosis of Cervical and Lumbosacral Radiculopathy. Neurol Clin 25 (2007) 473–494

Buirski G, Silberstein M. The symptomatic lumbar disc in patients with lowback pain. Magnetic resonance imaging appearances in both a symptomatic

and

control

population.

Spine

(Phila

Pa

1976)

1993;18(13):1808-11.

Buschbacher RM

and Prahlow ND. Manual of Nerve Conduction

Studies .Second Edition. Demos Medical Publishing, LLC (2006)..

Bush K, Chaudhuri R, Hillier S, Penny J: The pathomorphologic changes that accompany the resolution of cervical radiculopathy. A prospective study with repeat magnetic resonance imaging. Spine 1997;22:183–186.

Buttermann GR. Prospective nonrandomized comparison of an allograft with bone morphogenic protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. Spine J. May-Jun 2008;8(3):426–435.

Canadian

Chiropractic

Chiropractic

Regulatory

Association, Boards,

Canadian

Clinical

Federation

Practice

of

Guidelines

Development Initiative, Guidelines Development Committee (GDC). Chiropractic clinical practice guideline: evidence-based treatment of adult neck pain not due to whiplash. J Can Chiropr Assoc 2005;49:158209. 121

Carette S, Fehlings MG. Clinical practice. Cervical radiculopathy. N Engl J Med. Jul 28 2005;353(4):392–399

Park Chan Hong and Sang Ho Lee. Investigation of High-Sensitivity Creactive Protein and Erythrocyte Sedimentation Rate in Low Back Pain Patients. Korean J Pain 2010 June; Vol. 23, No. 2: 147-150

Cho Charles S., mark A. Ferrante, Kerry H. Levin, Robert I. Harmon, and yuen t. So. Utility of electrodiagnostic testing in evaluating patients with lumbosacral radiculopathy: an evidence-based review.Practice guidelines. Muscle & nerve. August 2010). Clark CR, Benzel EC, Currier BL, et al. The Cervical Spine, 4th ed. The Cervical Spine Research Society Editorial Committee. Philadelphia, PA: Lippincott Williams & Wilkins 2005.

Cohen MS, Wall ES, Olmarker K, et al. Anatomy of the spinal nerve roots in the lumbar and lower thoracic spine. In: Rothman RH, editor. The spine. 3rd edition. Philadelphia: W.B. Saunders; 1992.

Cote P, Cassidy J, Carroll L. The factors associated with neck pain and its related disability in the Saskatchewan population. Spine 2000;25:110917. Roth Daniel, Ai Mukai, Priya Thomas, Thomas H. Hudgins

and

Joseph T. Alleva. Cervical Radiculopathy. Dis Mon 2009;55:737-756

Preston David C. and Shapiro Barbara E. (2005). Chapter 29, Radiculopathy. Electromyography and Neuromuscular disorders, 2nd edition, ELSEVIER BTTURWORHT HEINEMANN.

121

Sutton David. Text book of radiology and imaging, section 6. Neuroradiology of the spine. 2003, Vol II, 1662-1664. Deleo TA, Hashizume H, Rutkowski MD, et al. Cyclooxygenase2inhibitor SC-236 attenuates mechanical allodynia following nerve injury in rats. J Orthop Res 2000;18:977–82.

Delisa , L Joel A, and Hang J (2005). Manual of Nerve Conduction Study and Surface Anatomy for Needle Electromyography. 4th edition. Lippincott Williams & Wilkins.

Devereaux MW. Anatomy and examination of the spine. Neurol Clin 2007; 25:331-51.

Deyo RA, Weinstein JN. Low back pain. N Engl J Med 2001; 344:363. Dhand UK, Das SK, Chopra JS: Pattern of H-reflex abnormality in patients with low back pain. Electromyogr Clin Neurophysiol 1991, 31:209-213.

Dillingham TR, Lauder TD, Andary M, Kumar S, Pezzin LE, Stephens RT, Shannon S: Identifying lumbosacral radiculopathies: an optimal electromyographic screen. Am J Phys Med Rehabil 2000;79:496–503.

Doita M, Kanatani T, Ozaki T, et al. Influence of macrophage infiltration of herniated disc tissue on the production of matrix metalloproteinases leading to disc resorption. Spine 2001;26:1522-7.

Murphy Donald R, Eric L Hurwitz, Jonathan K Gerrard and Ronald Clary. Pain patterns and descriptions in patients with radicular pain: Does

121

the pain necessarily follow a specific dermatome? Chiropractic & Osteopathy 2009, 17:9

Dora C, Walchli B, Elfering A, et al. The significance of spinal canal dimensions in discriminating symptomatic from asymptomatic disc herniations. Eur Spine J 2002;11:575–581.

Drake RL, Gray H. Gray’s atlas of anatomy. 1st ed. Philadelphia: Churchill Livingstone; 2008.

Dufour DR, Lott JA, Nolte FS, et al. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin Chem 2000;46:2027–49. Dumitru D, Diaz CA, King JC. Prevalence of denervation in paraspinal and foot intrinsic musculature. Am J Phys Med Rehabil 2001;80:482–490. Dumitru D, Zwarts MJ. Radiculopathies. In: Dumitru D, Amato AA, Zwarts M, editors. Electrodiagnostic medicine. 2nd edition. Philadelphia: Hanley & Belfus, Inc; 2002. p. 713–76.

Dumitru D. Electrodiagnostic medicine. Philadelphia: Hanley&Belfus, Inc; 1995. p. 564–66.

Dumitru D., Amato A.A., Zwarts M. Electrodiagnostic Medicine, second ed., Hanley & Belfus, Inc., Philadelphia, PA, 2002. Dvorak J. Epidemiology, physical examination, and neurodiagnostics. Spine 1998;23:2663-72.

121

Edgar MA, Nundy S. Innervation of the spinal dura mater. J Neurol Neurosurg Psychiat 1964;29:530–4.

Eisen A. Electrodiagnosis of radiculopathies. In: Aminoff MJ, editor. Neurologic

clinics:

symposium

on

electrodiagnosis,

vol.3,

no.3.

Philadelphia: W.B. Saunders; 1985. p 495–510.

Ellenberg MR, Honet JC, Treanor WJ. Cervical radiculopathy. Arch Phys Med Rehabil. Mar 1994;75(3):342–352. Johnson Ernest W. EMG in lumbosacral radiculopathy. J Thai Rehabil 1993;3(2).

Falco F, Hennessey WJ, Goldberg G, Braddom RI. H reflex latency in the healthy elderly. Muscle Nerve 1994;17:161–7.

Felson DT. Epidemiology of hip and knee osteoarthritis. Epidemiol Rev 1988;10:1–28.

Fisher M: AAEM Minimonograph #13: H reflexes and F waves: physiology and clinical indications. Muscle Nerve 1992, 15:1223-33. Foley B. , R. Buschbacher , J. Sorg , A. Peterson. Correlation of magnetic resonance imaging and electromyography in the diagnosis of radiculopathy. Clinical Neurophysiology 117 (2006) S49–S111

Fortin J, Riethmiller DW, Vilensky JA. No clear winner in differing imaging modalities for cervical radiculopathy. Pain Physician 2002; 5: 285–287. 121

Fouyas IP, Statham PF, Sandercock PA. Cochrane review on the role of surgery in cervical spondylotic radiculomyelopathy. Spine (Phila Pa 1976). Apr 1 2002;27(7):736–747 Frank Painter DC. Radiculopathy and Chiropractic. Chiro.org. Updated 2012. Franson RC, Saal JS, Saal JA. Human disc phospholipase A2is inflammatory. Spine 1992; 17S:129–32.

Furusawa N, Baba H, Miyoshi N, et al. Herniation of cervical intervertebral disc: immunohistochemical examination and measurement of nitric oxide production. Spine 2001; 26:1110-1116.

Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 34:448-54.

Gebhardt K, Brenner H, Sturmer T, et al. The course of high-sensitive Creactive protein in correlation with pain and clinical function in patients with acute lumbosciatic pain and chronic low back pain—A 6 months prospective longitudinal study. Eur J Pain 2006; 10:711–719. Geiringer S.R., S. Davidson, Anatomic Localization for Needle Electromyography, second ed., Hanley & Belfus, Inc., Philadelphia, PA, 1999.

Gilman S. Joint position sense and vibration sense: anatomical organisation

and

assessment.

Psychiatry 2002;73:473-477

121

J

Neurol

Neurosurg

Gobbele R., Schoen S.W., Schroder J.M., Vorwerk D. and M. Schwarz. S1 radiculopathy as a possible predisposing factor in focal myositis with unilateral hypertrophy of the calf muscles. Journal of the Neurological Sciences, 1999; 170 64–68

Goupille P, Jayson MI, Valat JP, et al. The role of inflammation in disk herniation associated radiculopathy. Semin Arthritis Rheum 1998;28:60– 71. Groen G, Baljet B, Drukker J. The nerves and nerve plexuses of the human vertebral column. Am J Anat 1990;188:282–96.

Gronblad M, Virri J, Seitsalo S, et al. Inflammatory cells, motor weakness, and straight leg raising in transligamentous disc herniations. Spine 2000;25:2803–7.

Habtemariam A, Virri J, Gronblad M, et al. The role of mast cells in disc herniation inflammation. Spine 1999;24:1516–20.

Haig AJ, Tong HC, Yamakawa KS, Quint DJ, Hoff JT, Chiodo A, et al. The sensitivity and specificity of electrodiagnostic testing for the clinical syndrome of lumbar spinal stenosis. Spine 2005;30: 2667–2676. Haig AJ. Clinical experience with paraspinal mapping. II: A simplified technique that eliminates three-fourths of needle insertions. Arch Phys Med Rehabil 1997a;78:1185–1190.

111

Haldeman

S,

Shouka

M,

Robboy

S.

Computed

tomography,

electrodiagnostic and clinical findings in chronic workers’ compensation patients with back and leg pain. Spine 1988; 13:345–350.

Hamanishi C, Tanaka S. Dorsal root ganglia in the lumbosacral region observed from the axial views of MRI. Spine 1993;18:1753–1756.

Han TR, Kim JH, Paik NJ: A study of new diagnostic criteria of Hreflex. Electromyogr Clin Neurophysiol 1997, 37:241-50.

Hatamian H. R. and Imamhadi M. R.. Determination of f-wave latency in individuals aged 20 years and older. Acta Medica Iranica, 2005, 43(3): 212-214.

Henry R.J and al. Am J Clin Path (1960), 34, 381-398.

Herzog RJ. The radiologic assessment for a lumbar disc herniation. Spine 1996 21:19S–38S

Alrowayeh Hesham N and Mohamed A Sabbahi. H-reflex amplitude asymmetry is an earlier sign of nerve root involvement than latency in patients with S1 radiculopathy. Alrowayeh and Sabbahi BMC Research Notes 2011, 4:102

Hogg-Johnson S, van der Velde G, Carroll LJ, et al. The burden and determinants of neck pain in the general population: Results of the bone and joint decade 2000-2010 task force on neck pain and its associated disorders. Spine 2008;33:S39-51 (suppl).

111

Holt EP Jr. The question of lumbar discography. J Bone Joint Surg Am. Jun 1968;50(4):720-6

Humphreys SC, Chase J, Patwardhan A, Shuster J, Lomasney L, Hodges SD. Flexion and traction effect on C5-C6 foraminal space. Arch Phys Med Rehabil. Sep 1998;79(9):1105–1109.

Igarashi T, Kikuchi S, Shubayev V, et al. Exogenous tumor necrosis factor-alpha mimics nucleus pulposus induced neuropathology: molecular, histologic, and behavioral comparisons in rats. Spine 2000;25:2975–80. Inman VT, Saunders JB. Referred pain from skeletal structures. J Nerv Ment Dis 1944; 99:660–7.

Janig W, Koltzenburg M. Receptive properties of pial afferents. Pain 1991;45:77–85.

Jarvik JJ, Hollingworth W, Heagerty P, et al. The longitudinal assessment of imaging and disability of the back (LAIDBack) study: baseline data. Spine 2001;26:1158–66. [PubMed: 11413431] Jensen M, Brant-Zawadzki M, Obuchowski N. Magnetic resonance imaging of the lumbar spine in people without back pain. N Engl J Med 1994;331:69–73. [PubMed: 8208267] Jensen MV, Tuchsen F, Orhede E. Prolapsed cervical intervertebral disc in male professional drivers in Denmark, 1981e1990. A longitudinal study of hospitalizations. Spine 1996;21:2352-2355. Regan John J., MD. Spondylosis or Spinal Osteoarthritis. Website: Spine Universe, 2012.

112

Caridi John M., Matthias Pumberger & Alexander P. Hughes. Cervical Radiculopathy: A Review. HSSJ (2011) 7:265–272

Lurie Jon D., David M. Doman, Kevin F. Spratt, Anna N. A. Tosteson, and James N. Weinstein. Magnetic Resonance Imaging Interpretation in Patients With asymptomatic low back pain. Spine, 2009 April 1; 34(7): 701–705

Kaiser J, Holland B. Imaging of the cervical spine. Spine 1998;15:270112.

Kamath PS. Clinical approach to the patient with abnormal liver test results. Mayo Clin Proc 1996;71:1089–95.

Kang JD, Georgescu HI, McIntyre-Larkin L, et al. Herniated cervical intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1995;20:2373–8.

Kang JD, Georgescu HI, McIntyre-Larkin L, et al. Herniated lumbar intervertebral discs spontaneously produce matrix metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2. Spine 1996;21:271-7. Kang JD, Stefanovic-Racic M, McIntyre LA, Georgescu HI, Evans CH. Toward a biochemical understanding of human intervertebral disc degeneration and herniation: contributions of nitric oxide, interleukins, prostaglandin E2, and matrix metalloproteinases. Spine 1997;22:1065-73.

Barr Karen. Electrodiagnosis of Lumbar Radiculopathy. Phys Med Rehabil Clin N Am 24 (2013) 79–91

111

Katirji B. The clinical electromyography examination. An overview, Neurol. Clin. N. Am. 20 (2002) 291–303.

Kawaguchi S, Yamashita T, Katahira G, et al. Chemokine profile of herniated intervertebral discs infiltrated with monocytes and macrophages. Spine 2002;27:1511-6.

Kawaguchi S, Yamashita T, Yokogushi K, et al. Immunophenotypic analysis of the inflammatory infiltrates in herniated intervertebral discs. Spine 2001;26:1209-14.

Kawakami M, Tamaki T, Matsumoto T, et al. Role of leukocytes in radicular pain secondary to herniated nucleus pulposus. Clin Orthop 2000;376:268–77.

Kayama S, Konno S, Olmarker K, et al. Incision of the anulus fibrosus induces nerve root morphologic, vascular, and function changes: an experimental study. Spine 1996;21: 2539–43.

Kotani Kazuhiko and Naoki Sakane. White Blood Cells, Neutrophils, and Reactive Oxygen Metabolites among Asymptomatic Subjects. International Journal of Preventive Medicine, Vol 3, No 6, June 2012, 428–431.

Williams Keith D., Ashley L. Park. Lower back pain and disorders of intervertebral discs.chapter 39, Elsevier science (USA) 2003.

111

Walker Kenneth H.. Deep Tendon Reflexes. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition, 1990.

Hakimi Kevin and

David Spanier. Electrodiagnosis of Cervical

Radiculopathy. Phys Med Rehabil Clin N Am 24 (2013) 1–12

Kew MC. Serum aminotransferase concentration as evidence of hepatocellular damage. Lancet 2000;355:591–2.

Khan SY, Hilton-Jones D, Rigby SP. A swollen calf. Lancet 2005; Vol 365; page 1662.

Khatri BO, Baruah J, McQuillen MP. Correlation of electromyography with computed tomography in evaluation of low back pain. Arch Neurol 1984;41:594 –597.

Kikuchi S, Sato K, Konno S, Hasue M. Anatomic and radiographic study of the dorsal root ganglia. Spine 1994;19:6–11.

Kimura J

and Kohara N Principles and Practice of Nerve Conduction

Studies and Electromyography. 1st edition. Igaku-Shoin Ltd (2003).

Kimura J. Electrodiagnosis in diseases of nerve and muscle: principles and practice .3rd edition. Oxford University Press, Inc. (2001).

Komori H, Shinomiya K, Nakai O, Yamaura I, Takeda S, Furuya K: The natural history of herniated nucleus pulposus with radiculopathy. Spine 1996;21:225–229.

111

Kraft G. A physiologic approach to the evaluation of lumbosacral spinal stenosis. Phys Med Rehabil Clin N Am 1998;9(2):381–9.

Kuruoglu R, Oh SJ, Thompson B. Clinical and electromyographic correlations of lumbosacral radiculopathy. Muscle Nerve 1994;17:250 – 251.

Kwast O. and Libelius R. Relations between electromyography and MRI in patients with symptomatic cervical spine disorders (CSD). Clinical Neurophysiology 2006; 117, Supplement 1, Pages 1-2.

Lanzillo B, Pappone N, Crisci C, Girolamo C, et al.. "Subclinical peripheral nerve involvement in patients with rheumatoid arthritis." Arthritis Rheum, 1998; 41(7): 1196-1202.

Larsson EM, Holtas S, Cronqvist S, Brandt L. Comparison of myelography, CT myelography and magnetic resonance imaging in cervical spondylosis and disk herniation: pre- and postoperative findings. Acta Radiol 1989;30:233-9.

Larsson H, Berglund G, Lindgard F, et al.. Comparison of ADA and WHO criteria for diagnosis of diabetes and glucose intolerance. Diabetologia (1998); 41: 1124-1125 Lauder TD. Musculoskeletal disorders and physical examination findings: implications for electrodiagnostic study. In: Course C, editor. Diagnosis and management of patients with cervical and lumbosacral radiculopathies. 1999 AAEM Course. Rochester (MN): American Association of Electrodiagnostic Medicine; 1999. p. 7–21.

111

Lawrence W. Mysliwiec, Jacek Cholewicki , Michael D. Winkelpleck • Greg P. Eis. MSU Classification for herniated lumbar discs on MRI: toward developing objective criteria for surgical selection. Eur Spine J (2010) 19:1087–1093

Le Gars L, Borderie D, Kaplan G, et al. Systemic inflammatory response with plasma Creactive protein elevation in disk-related lumbosciatic syndrome. Joint Bone Spine 2000;67:452–5.

Leblhuber F, Reisecker F, Boehm-Jurkovic H, Witzmann A, Deisenhammer E. Diagnostic value ofdifferen t electrophysiologic tests in cervical disk prolapse. Neurology 1988;38: 1879–81. Lee HM, Weinstein JN, Meller ST, et al. The role of steroids and their effects on phospolipase A2: an animal model of radiculopathy. Spine 1998;23:1191–6.

Leena Puksa, Erik Stalberg, Bjo¨rn Falck. Reference values of F wave parameters in healthy subjects.

Clinical Neurophysiology 114 (2003)

1079–1090

Lemieux I, Pascot A, Prud’homme D, et al. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol. 2001;21:961–967.

Lestini WF, Wiesel SW. The pathogenesis of cervical spondylosis. Clin Orthop Relat Res 1989;239:69-93.

Levin KH, Covington EC, Devereaux MW, et al. Neck and low back pain. New York, NY: Continuum, 2001 111

Levin KH, Maggiano HJ, Wilbourn AJ. Cervical radiculopathies: comparison of surgical and EMG localization of single-root lesions. Neurology 1996;46:1022–1025.

Levin, KH. Radiculopathy. In: Comprehensive Clinical Neurophysiology, Levin, KH, Lüders, HO (Eds), WB Saunders, New York 2000. p.627.

Levin K.H.. Electrodiagnostic approach to the patient with suspected radiculopathy. Neurol. Clin. 20 (2002) 397–421.

Linden D, Berlit P. Comparison of late responses, EMG studies, and motor evoked potentials (MEP’s) in acute lumbosacral radiculopathies. Muscle Nerve 1995;18:1205–7.

London SF, England JD. Dynamic F waves in neurogenic claudication. Muscle Nerve 1991;14:457–61. Lott JA, Wolf PL. Alanine and aspartate aminotransferase (ALT and AST) clinical enzymology: a case oriented approach. Chicago: Year Book Publishers; 1986. p. 111–38.

M.A. Fisher. Electrophysiology of radiculopathies. Clin. Neurophysiol. 113 (2002) 317–335.

Makela M, Heliovaara M, Sievers K, et al. Prevalence, determinants and consequences of chronic neck pain in Finland. Am J Epidemiol 1991;134:1356-67.

Maria GT, Serelis J, and Skopouli F N. "Peripheral neuropathy in two patients with rheumatoid arthritis receiving infliximab treatment." Clin 111

Rheumatol, 2007; 26: 258-260.

Marin R, Dillingham TR, Chang A, Belandres PV. Extensor digitorum brevis reflex in normals and patients with radiculopathies. Muscle Nerve 1995;18:52–9.

Marshall LL, Trethewie ER. Chemical irritation of nerve root in disc prolapse. Lancet 1973;2:320.

Matsumoto M, Chiba K, Ishikawa M, Maruiwa H, Fujimura Y, Toyama Y. Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations. Spine 2001;26:1592-8.

Maureen C. Jensen, Michael N. Brant-Zawadzki, Nancy Obuchowski, Michael T. Modic, Dennis Malkasian and Jeffrey S. Ross. MRI of the lumbar spine in people without backpain. The New England Journal of Medicine, 1994;Vol 331(2).

McLaughlin T, Abbasi F, Lamendola C, et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation. 2002;106:2908–2912.

Michael H. Rivner. F-Wave Studies: Limitations. Muscle & nerve, August 1998, 21 (8), 1101-1104.

Mink JH, Gordon RE, Deutsch AL. The cervical spine: radiologist’s perspective. Phys Med Rehabil Clin N Am 2003;14:493- 548. 111

Mixter WJ, Barr JS. Rupture of the intervertebral disc with involvement of the spinal canal. N Engl J Med 1934;211:210–214.

Miyamoto H, Saura R, Doita M, Kurosaka M, Mizuno K. The role of cyclooxygenase- 2 in lumbar disc herniation. Spine 2002; 27:2477-83.

Miyamoto H, Saura R, Harada T, et al. The role of cylooxygenase-2and inflammatory cytokines in pain induction of herniated lumbar intervertebral discs. Kobe J Med Sci 2000;46:13–28.

Mochida K, Komori H, Okawa A, Muneta T, Haro H, Shinomiya K. Regression of cervical disc herniation observed on magnetic resonance image. Spine 1998;23:9905.

Modic MT, Ross JS, Obuchowski NA, Browning KH, Cianflocco AJ, Mazanec

DJ: Contrast-enhanced MR

radiculopathy:

a

pilot

study of

the

imaging natural

in acute history.

lumbar

Radiology

1995;195:429–435.

Modic MT, Ross JS. Lumbar degenerative disk disease. Radiology 2007;245(1):43-61.

Montgomery DM, Brower RS. Cervical spondylotic myelopathy. Clinical syndrome and natural history. Orthop Clin North Am 1992;23:487-93. Morris

A.

Fisher

Electrophysiology

Neurophysiology 113 (2002) 317–335

111

of

radiculopathies.

Clinical

Mundt DJ, Kelsey JL, Golden AL, Pastides H, Berg AT, Sklar J, Hosea T, PanjabiMM. An epidemiologic study of non-occupational lifting as a risk factor for herniated lumbar intervertebral disc. Spine 1993;18:595–602

Nardin RA, Patel MR, Gudas TF, et al. Electromyography and magnetic resonance imaging in the evaluation of radiculopathy. Muscle Nerve 1999; 22:151.

New York University School of Medicine. Deep tendon reflexs. The precise neurological examination. 2006.

logical Exam Chahin Nizar, Eric J. Sorenson. Serum creatine kinase levels in spinobulbar Muscular atrophy and amyotrophic Lateral sclerosis. Muscle Nerve 40: 126–129, 2009

Al Nezari Nezar H., Anthony G. Schneiders, Paul A. Hendrick. Neurological examination of the peripheral nervous system to diagnose lumbar spinal disc herniation with suspected radiculopathy: a systematic review and meta-analysis. The Spine Journal 13 (2013) 657–674

Nordin M, Nystrom B, Wallin U, et al. Ectopic sensory discharge and parasthesiae in patients with disorders of peripheral nerves, dorsal roots, and dorsal columns. Pain 1984;20:231–45.

Nygaard OP, Mellgren SI, Osterud B. The inflammatory properties of contained and noncontained lumbar disc herniation. Spine 1997;22:2484-8.

111

Olmarker K, Rydevik B, Hansson T, et al. Compression induced changes to the nutrient supply to the porcine cauda equina. J Spinal Dis 1990;3:25– 29.

Olmarker K, Rydevik B, Holm S, et al. Effects of experimental, graded compression on blood flow in spinal nerve roots. J Orthop Res 1989;7:817–23.

Olmarker K, Ryedevik B, Nordborg C. Autologous nucleus pulposus induces neurophysiologic and histologic changes in porcine cauda equina nerve roots. Spine 1993; 18:1425–32. On call medical, Inc. Needle EMG Changes in Acute and Chronic Radiculopathy, 2010. [email protected]

Park ES, Park CI, Kim AY, Park MK. Relationship between electromyography and computed tomography in the evaluation of low back pain. Yonsei Med J 1993;34:84–89.)

Olmed Pastore C., O. Gonza´ lez and E. Geijo-Barrientos. A study of Fwaves in patients with unilateral lumbosacral Radiculopathy. European Journal of Neurology 2009, 16: 1233–1239

Petiot P, Bernard E. Diagnostic pitfalls in carpal tunnel syndrome. Rev Neurol (Paris). Jan 2011;167(1):64–71.

Pfirrmann CW, Binkert CA, Zanetti M, Boos N, Hodler J Functional MR imaging of the craniocervical junction. Correlation with alar ligaments

112

and occipito-atlantoaxial joint morphology: a study in 50 asymptomatic subjects. Schweiz Med Wochenschr (2000) 130:645–51

PfirrmannCW,

Binkert

CA,

Zanetti

M,

Boos

N,Hodler

J

MRmorphology of alar ligaments and occipitoatlantoaxial joints: study in 50 asymptomatic subjects. Radiology (2001)218:133–7

Hsu Philip S, Carmel Armon and Kerry Levin. Lumbosacral radiculopathy: Pathophysiology, clinical features, and diagnosis in Uptodate 2011. WWW.Uptodate.com

Philippe Goupille,

Malcolm I.V. Jayson, Jean-Pierre Valat and

Anthony J. Freemont. The role of inflammation in disc herniationassociated

radiculopathy.

Seminars

in

arthritis

and

rheumatism,

ScienceDirect, Volume 28, Issue 1, August 1998, Pages 60–71

Polston D. Cervical radiculopathy. Neurol Clin 2007;25:373-85.

Praemer A, Furner S, Rice DP. Musculoskeletal Conditions in the United States. Rosemont, IL: American Academy of Orthopedic Surgeons, 1999. p. 27-70.

Pyhtinen J, Laitinen J. Cervical intervertebral foramen narrowing and myelographic nerve root sleeve deformities. Neuroradiology 1993;35:5967. Nardin Rachel A., Aamy R. Zarrin, Gary L. Horowitz and Andrew W. Tarulli. Effect of newly proposed CK reference limits on neuromuscular diagnosis. Muscle Nerve 9: 494 – 497, 2009

111

Nardin Rachel A., Mahesh R. Patel, Thomas F. Gudas, Seward B. Rutkove, and Elizabeth M. Raynor. Electromyography and magnetic resonance imaging in the evaluation of radiculopathy. Muscle Nerve 22: 151–155, 1999 Radhakrishnan K, Litchy WJ, O’Fallon WM, et al. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990. Brain 1994;117:325-335.

Shiri

Rahman, Jaro Karppinen, Pa¨ivi Leino-Arjas, Svetlana

Solovieva, Helena Varonen, Eija Kalso, Olavi Ukkola, Eira ViikariJuntura. Cardiovascular and lifestyle risk factors in lumbar radicular pain or clinically defined sciatica: a systematic review. Eur Spine J (2007) 16:2043–2054

Rao R, Currier BL, Albert TJ, et al. Degenerative cervical spondylosis: Clinical syndromes, pathogenesis, and management. J Bone Joint Surg 2007;89: 1360-78.

Gross Raphaël, Céline Degive, Emmanuelle Dernis, Monique Plat, Odile Dubourg, and Xavier Puéchal. Focal Myositis of theCalf following S1 Radiculopathy. Semin Arthritis Rheum, 2008; 38:20-27

Refshauge KM, Maher CG. Low back pain investigations and prognosis: a review. Br J Sports Med 2006; 40: 494-8.

Rhee J, Yoon T, Riew K. Cervical radiculopathy. J Am Acad Orthop Surg 2007;15:486-94.

111

Kendall Richard and Robert A. Werner. Interrater reliability of the needle examination in lumbosacral radiculopathy. Muscle Nerve 2006 34: 238–241.

Windsor Robert E and Kevin P Sullivan. Lumbosacral Disc Injuries. eMedicine Specialties > Sports Medicine > Spine. Updated: Jun 23, 2008

Robinson JP, Brown PB, Fisk JD. Pathophysiology of lumbar radiculopathies and the pharmacology of epidural corticosteroids and local anesthetics. Phys Med Rehabil Clin North Am 1995;6:671–90.

Robinton J.E., Pearson J.M., Malloy M.J., Richards, R., Zamora, J. Diagnosis of Lumbar Radiculopathy by EMG, Nerve Conduction and Late Wave Testing, Muscle and Nerve, Oct., 2006; 34 (4): 387–544

Rothoerl R, Woertgen C, Holzschuh M, et al. Macrophage tissue infiltration, clinical symptoms, and signs in patients with lumbar disc herniation: a clinicopathological study on 179 patients. Acta Neurochir 1998;140:1245–1248.

Rydevik B, Holm S. Pathophysiology of the intervertebral disc and adjacent neural structures. In: Rothman RH, Sieone FA, editors. The spine. 3rd edition. Philadelphia: W.B. Saunders; 1990. p. 208–27.

Saal J, Franson R, Dobrow R, Saal JA, White AH, Goldthwaite N.: High level of inflammatory phospholipase A2 activity in lumbar disc herniations. Spine 1990;15:674–678.

111

Sabbahi MA, Khalil M. Segmental H-reflex studies in upper and lower limbs ofpatients with radiculopathy. Arch Phys Med Rehabil 1990;71:223– 7. Salemi G, Savettieri G, Meneghini F, et al. Prevalence of cervical spondylotic radiculopathy: a door-to-door survey in a Sicilian municipality. Acta Neurol Scand 1996;93: 184-8.

Scelsa SN, Herskovitz S, Berger AR. The diagnostic utility of F waves in L5/S1 radiculopathy. Muscle and Nerve 1995;18:1496–1497.

Schoedinger GR III. Correlation of standard diagnostic studies with surgically proven lumbar disc rupture. South Med J 1987;80:44–46.

Schwarzer AC, Aprill CN, Bogduk N. The sacroiliac joint in chronic low back pain. Spine 1995;20:31–33.

Schwarzer AC, Aprill CN, Derby R, Fortin J, Kine G, Bogduk N. Clinical features of patients with pain stemming from the lumbar zygapophysial joints. Is the lumbar facet syndrome a clinical entity? Spine 1994;19:1132–1137.

Semmes RE, Murphey MF. The syndrome of unilateral rupture of the sixth cervical intervertebral disk with compression of the seventh cervical nerve root: a report of four cases with symptoms simulating coronary disease. JAMA 1943;121:1209–14. Shelerud RA, Paynter KS. Rarer causes of radiculopathy: spinal tumors, infections, and other unusual causes. Phys Med Rehabi Clin N Am 2002;13:645-96.

111

Shigeru Kobayashi , Hidezo Yoshizawa , Shuuichi Yamada. Pathology of lumbar nerve root compression Part 1 : Intraradicular inflammatory changes induced by mechanical compression. Journal of Orthopaedic Research 22 (2004) 170-179

Simon Carette and Michael G. Fehlings. Cervical radiculopathy. N Engl J Med 2005;353:392-9.

Sokka T, Kankainen A and Pekka Hannonen. "Scores for functional disability in patients with rheumatoid arthritis are correlated at higher levels with pain scores than with radiographic scores." Arthritis Rheum (2000); 43(2): 386-389.

Song XJ, Hu SJ, Greenquist KW, Zhang JM, LaMotte RH. Mechanical and thermal hyperalgesia and ectopic neuronal discharge after chronic compression of dorsal root ganglia. J Neurophysiol 1999;82:3347-58.

Sorlie E D (1995). Medical Biostatistics and Epidemiology: examination & board review.87-98.A Simon and Schuster Company.

Stadnik TW, Lee RR, Coen HL, et al. Annular tears and disk herniation: prevalence and contrast enhancement on MR images in the absence of low back pain or sciatica. Radiology 1998;206:49–55.

Stafira J, Sonnad JR, Yuh WT, et al. Qualitative assessment of cervical spinal stenosis: Observer variability on CT and MR images. Am J Neuroradiol 2003;24:766-9.

111

Stemper BD, Yoganandan N, Pintar FA, et al. Anatomical gender differences in cervical vertebrae of size-matched volunteers. Spine 2008;33:E44-9.

Stetson DS, Albers JW, Silverstein BA, et al. Effects of age, sex, and anthropometric factors on nerve conduction measures. Muscle Nerve 1992;15:1095-104.

Streichenberger N, Meyronet D, Fiere V, Pellissier JF, Petiot P. Focal myositis associated with S-1 radiculopathy: report of two cases. Muscle and Nerve 2004;29:443-6.

Stürmer T, Raum E, Buchner M, Gebhardt K, Schiltenwolf M, Richter W, et al. Pain and high sensitivity C reactive protein in patients with chronic low back pain and acute sciatic pain. Ann Rheum Dis 2005; 64: 921-5.

Sugawara O, Atsuta Y, Iwahara T, Muramoto T, Watakabe M, Takemitsu Y. The effects of mechanical compression and hypoxia on nerve root and dorsal root ganglia: an analysis of ectopic firing using an in vitro model. Spine 1996;21:2089-94.

Sugimori K., Y. Kawaguchi, M. Morita, I. Kitajima, T. Kimura. Highsensitivity analysis of serum C-reactive protein in young patients with lumbar disc herniation. J Bone Joint Surg [Br] 2003;85-B:1151-4.

Takahashi H, Suguro T, Okazima Y, et al. Inflammatory cytokines in the herniated disc of the lumbar spine. Spine 1996;21:218-24. 111

Tanaka N, Fujimoto Y, An HS, et al. The anatomic relation among the nerve roots, intervertebral foramina, and intervertebral discs of the cervical spine. Spine 2000;25:286e91. Tarulli

AW

and

Raynor

EM.

Lumbosacral

radiculopathy;

pathophysiology, clinical features and diagnosis. Neurol Clin, 2007 May;25(2):387-405. Thakur D, B H Paudel, C B Jha. Nerve Conduction study in healthy individuals, a preliminary age based study. Kathmandu Univ Med J 2010;8(3):311-316

Thapa B.R and Anuj Walia. Liver Function Tests and their Interpretation. Indian Journal of Pediatrics, 2007; Volume 74,

Thomas PK, Ochoa JL. Clinical features and differential diagnosis. In: Dyck PJ, Thomas PK, editors. Peripheral neuropathy. 3rd edition. Philadelphia: W.B. Saunders; 1993.

Thompson D (2004). Oxford Textbook of Rheumatology, Acute phase response.3rd edition. Oxford University Press.

Dillingham Timothy R., Lilliana E. Pezzin and Tamara D. Lauder. Cervical paraspinal muscle abnormality and symptom duration; A multivariate analysis. Short reports. Muscle and nerve, 1998.

Dillingham Timothy R.. Electrodiagnostic approach to patients with suspected radiculopathy. Phys Med Rehabil Clin N Am 13 (2002) 567–588

111

Dillingham Timothy R.. Evaluating the Patient With Suspected Radiculopathy.

American

Academy

of

Physical

Medicine

and

Rehabilitation, 2013Vol. 5, Iss. 5S, Supplement 1.

Tonzola RF, Ackil AA, Shahani BT, Young RR. Usefulness of electrophysiological studies in the diagnosis of Lumbosacral root disease. Ann Neurol 1981;9:305–308.

Towne EB, Reichert FL. Compression of the lumbosacral roots of the spinal cord by thickened ligamenta flava. Ann Surg 1931;94:327–36.

Troni W: The value and limits of the H-reflex as a diagnostic tool in S1 root compression. Electromyogr Clin Neurophysiol 1983, 23:471-80.

Tsao BE, Levin KH, Bodner RA. Comparison of surgical and electrodiagnostic findings in single root lumbosacral radiculopathies. Muscle Nerve 2003; 27:60.

Van Rijn JC, Klemetso N, Reitsma JB, et al. Observer variation in the evaluation of lumbar herniated discs and root compression: spiral CT compared with MRI. The British Journal of Radiology 2006; 79: 372– 377.

Van Rijn JC, Klemetso N, Reitsma JB, et al. Observer variation in MRI evaluation of patients suspected of lumbar disk herniation. American Journal of Roentgenology 2005; 184: 299–303.

Verbiest H. A radicular syndrome from developmental narrowing of the lumbar intervertebral canal. J Bone Joint Surg Br 1954;36:230–7. 111

Viikari-Juntura E, R Martikainen, R Luukkonen, P Mutanen, E-P Takala, H Riihimäki. Longitudinal study on work related and individual risk factors affecting radiating neck pain. Occup Environ Med 2001;58:345–352

Virri J, Gronglad M, Seitsale S, et al. Comparison of the prevalence of inflammatory cells in subtypes of disc herniations and associations with straight leg raising. Spine 2001;26:2311-2315. Vroomen P C A J, M C T F M de Krom, J T Wilmink, A D M Kester, J A Knottnerus. Diagnostic value of history and physical examination in patients suspected of lumbosacral nerve root compression. Neurol Neurosurg Psychiatry 2002;72:630–634

Wainner R and Gill H. Diagnosis and nonoperative management of cervical radiculopathy. J Orthop Sports Phys Ther 2000;30:728-44.

Wainner RS, Fritz JM, Irrgang JJ, Boninger ML, Delitto A, Allison S. Reliability and diagnostic accuracy of the clinical examination and patient self-report measures for cervical radiculopathy. Spine 2003;28:52-62.

Walsh TR, Weinstein JN, Spratt KF, et al. Lumbar discography in normal subjects. A controlled, prospective study. J Bone Joint Surg Am. Aug 1990;72(7):1081-8.

Weber F, Albert U. Electrodiagnostic examination of Lumbosacral radiculopathies. Electromyogr Clin Neurophysiol 2000; 40:231–236.

111

Weber F. The diagnostic sensitivity of different F wave parameters. J Neurol Neurosurg Psychiatry 1998;65:535–40

Wehlig P, Bandara G, Evans CH. Synovial cytokines impair the function of the sciatic nerve in rats: a possible element in the pathophysiology of radicular syndromes. Neuroorthop 1990;7:55–9.

Weinstein JN. Neck and back pain. In: Physical Medicine and Rehabilitation State of Art Review. Philadelphia, PA: Hanley & Belfus, 1990. p. 201-14.

Weishaupt D, Zanetti M, Hodler J, Min K, Fuchs B, Pfirrmann CW, Boos N Painful lumbar disc derangement: relevance of endplate abnormalities at MR imaging. Radiology (2001) 218:420–7

Westmark RM, Westmark KD, Sonntag VKH: Disappearing cervical disc. J Neurosurg 1997;86:289–290.

White JC: The ubiquity of contraction enhanced H-reflexes: normative data and use in the diagnosis of radiculopathies. Electroencephalogr Clin Neurophysiol 1991, 81:433-42.

Wikipedia The free encyclopedia website. Body mass index calculation, 2013.

Wilbourn

AJ,

Aminoff

MJ.

AAEM

minimonograph

32:

the

electrodiagnostic examination in patients with radiculopathies. American Association of Electrodiagnostic Medicine. Muscle Nerve 1998; 21:161231. 112

Wilbourn AJ, Aminoff MJ: The electrophysiologic examination in patients with radiculopathies. Muscle Nerve 1988;11: 1099–1114.

Wilbourn AJ. Radiculopathies. In Brown WF, Bolton CF, eds. Clinical electromyography, 2nd ed. Boston: Butterworth-Heinmann, 1993

Woertgen C, Rothoerl RD, Brawanski A. Influence of macrophage infiltration of herniated lumbar disc tissue on outcome after lumbar disc surgery. Spine 2000;25:871-5.

Xiang Jin , Yu Zhu, Fei Zhou Lu , Xiao Dong Wu, Dong Qing Zhu , Robert Weber , Bernadette Dunn , Jian Yuan Jiang. H-reflex to S1root stimulation improves utility for diagnosing S1 radiculopathy. Clinical Neurophysiology 121 (2010) 1329–1335

Youdas JW, Carey JR, Garrett TR. Reliability of measurements of cervical spine range of motion–comparison of three methods. Phys Ther. Feb 1991;71(2):98–104.

Yue W, Tan SB, Tan MH, et al. The Torg-Pavlov ratio in cervical spondylotic myelopathy: A comparative study between patients with cervical spondylotic myelopathy and a nonsponylotic, nonmyelopathic population. Spine 2001;26: 1760-4.

Ziccardi P, Nappo F, Giugliano G, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation. 2002;105: 804–809.

111

Abstract Background: Referral for evaluation of suspected radiculopathy is a common request in electrodiagnostic laboratories. A combination of clinical signs/symptoms, imaging, and electrodiagnostic studies should be used to properly diagnose radiculopathy. Electromyography (EMG) continues to play an important role in the evaluation of radiculopoathy despite the wide use of imaging studies. Imaging studies are diagnostic in the more common radiculopathies caused by structural lesions whereas radiculopathies caused by non-structural lesions may be only revealed by electrodiagnostic studies. Consistency between the imaging and electrodiagnostic studies needs to be evaluated. Evidences indicate that inflammatory mediators — including matrix metalloproteinases, prostaglandin E2, interleukin-6, and nitric oxide are released at herniated intervertebral disks which lead to local inflammation and stimulate synthesis of acute phase reactants as high sensitivity C-reactive protein (Hs-CRP) in liver. Objectives: The aims of the study were; (1) to evaluate the diagnostic utility of different electrophysiologic tests and their consistentcy with MRI findings in patients with suspected radiculopathy; (2) to investigate the role of inflammation in pathophysiology of radiculopathy. Subjects and methods: The study involved one hundred sixty subjects who were divided into 3 groups; the first group comprised 70 patients with symptoms suggestive of lumbosacral radiculopathy (LSR). The second group consisted of 50 patients with symptoms suggestive of cervical radiculopathy (CR). The patients were enrolled in the study according to certain inclusion and exclusion criteria. The third group was the control group which was comprised of 40 apparently

III

healthy subjects. For each subject a pretested questionnaire was completed before blood sampling. Venous blood were obtained from each subject and sent for total white blood cell count (WBC) count and erythrocyte sedimentation rate (ESR). The obtained serum was used for measurement of serum glucose, glutamate oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and creatine phosphokinase (CPK). Moreover, serum Hs-CRP was measured using ELISA technique. After clinical assessment, electrodiagnostic (EDX) examination (nerve conduction study, late responses and needle electropmyography (nEMG)) were performed. The following nerves were examined in all subjects: For the lower limb; a) Motor nerve conduction study of posterior tibial and common peroneal nerves; b) Sural sensory nerve conduction study; c) F-wave minimum latency (F-min) of posterior tibial and peroneal nerves; d) H-reflex latency of posterior tibial nerve. For the upper limb; a) Motor nerve conduction study of median and ulnar nerves; b) Sensory nerve conduction study of median and ulnar nerves; c) F-wave minimum latency (F-min) of median and ulnar nerves. Needle EMG of 5 limb muscles and the paraspinal muscles were performed for each patient. The results of different electrodiagnostic examination were evaluated according to different clinical examination findings and MRI results. For ethical purposes, MRI and needle EMG were not performed for the control group. Results: The body mass index in both patient groups was significantly higher than that of the control group (p=0.001). Patients with suspected LSR and CR showed significant increase in serum level of Hs-CRP compared with control group (5.81 and 5.83 Vs 4.07, p<0.05). Patients with suspected lumbosacral radiculopathy showed significantly lower compound muscle potential (CMAP) amplitude of tibial nerve (7.4 Vs 10.9 mV, P=0.001, respectively) compared to IV

control group. There were no significant differences in the nerve conduction study parameters in both patient groups compared with controls. Serum Hs-CRP was significantly positively correlated with total WBC count and ESR in the control group (r=0.522, p=0.018 and r=0.849, p=0.001) respectively. Among patients groups, Hs-CRP was significantly positively correlated with serum CPK level (r=0.356, p=0.003 for LSR group and r=0.333, p=0.018 for CR group). In addition, tibial H-reflex latency was positively and significantly correlated with tibial F-wave latency (r=0.439, p=0.001) in patients with suspected LSR. Receiver operating characteristic (ROC) curve analysis for nerve conduction study (NCS) parameters of lower limb showed that tibial CMAP amplitude is of high validity to predict LSR with an area under the curve of 0.782, p <0.001. ROC area for body mass index (BMI) and Hs-CRP showed that both BMI and Hs-CRP were of high validity to predict cervical or lumbosacral radiculopathy with areas under the curves (AUC) 0.709 and 0.738 respectively, p<0.001. Electrodiagnostic results according to duration of symptoms showed none significant relations in both LSR and CR groups. Needle EMG was significantly abnormal in patients with foot drop/weak dorsiflexion (p=0.02) and H-reflex latency was significantly abnormal in patients with positive straight leg raising test (SLRT) in LSR group (p=0.001). Non significant relation between different EDX results according to vibration and position senses and dermatomal distribution were found in both patient groups. Percentage of abnormal H-reflex latency was significantly related with the number and percentage of abnormal stretch reflex (p=0.001). We also found that all patients with abnormal H-reflex showed thecal and root compression on MRI. However, none of patients with no root or thecal compression showed abnormal H-reflex latency and this difference was turned out to be statistically significant (p=0.04). V

The percentages and level of significance of abnormal electrodiagnostic tests and MRI conducted on both CR and LSR groups respectively were as follow: Needle EMG (74% vs. 81.4%, p=NS), NCS (8% vs. 27.1%, p=0.009), F wave (2% vs. 12.9%, p=0.034) and abnormal MRI findings (76.7% vs. 83.1%, p=NS). Both MRI and needle EMG were significantly consistent in LSR (83.9%) and CR groups (81.1%) regarding the root level (p=0.001). Both NCS and F-wave latency were statistically significantly different when used to compare the rate of positive test findings between CR and LSR. In patients with suspected LSR, the positivity rate for selected tests regarding abnormal H-reflex latency and abnormal NCS were statistically different compared to control group (p=0.02 and p=0.005 respectively).

Conclusion: Inflammation plays

an

important

role

in

pathophysiology of

radiculopathy evidenced by elevation of serum level of Hs-CRP. BMI is a predisposing factor for radiculopathy. Needle EMG is imperative for diagnosis of radiculopathy. The utility of needle EMG in diagnosis of radiculopathy improves by increasing the number of muscles being screened including the paraspinal muscles and the probability of abnormal needle EMG increases in patients who have motor weakness. Both EMG and MRI are significantly consistent in diagnosis of radiculopathy. NCS and late responses are often useful in diagnosis of LSR but not CR.

VI

‫تقييم المتغيرات الفسيولوجية العصبية مع فحص الرنين المغناطيسي في التشخيص المحتمل للضغط‬ ‫على الجذور العصبية‬ ‫خلفية الموضوع‪:‬‬ ‫تعد احالة المرضى الذين يعانون من الم أسفل الظهر‪/‬العنق نتيجة الضغط على الجذور العصبية من‬ ‫اسباب االحاال الشائعة الى مختبرا‬

‫الفسيولوجية العصبية‪ .‬لكي تتم عملية تشخيص هذه الحالة بشكل مناسب‪,‬‬

‫يجب الدمج بين كل من االعراض السريرية لدى المريض و فحص الرنين المغناطيسي و تخطيط االعصاب‬ ‫والعضال ‪ .‬ال زال الرنين المغناطيسي يلعب دورا مهما في تشخيص الضغط على الجذور العصبية اذا كان‬ ‫السبب بنيوي‪ ,‬بينما يمكن كشف االسباب يير بنيوية من خالل دراسة التخطيط العضال ‪ .‬لكن التناسق بين رنين‬ ‫المغناطيسب وتخطيط االعصاب والعضال‬

‫يحتاج الى دراسة‪ .‬البينا‬

‫السابقة تشير الى مسبا‬

‫االلتهاب‬

‫الموضعي الناتج من الضغط على الجذورالعصبية وهو من خالل افراز مواد كيماوية تسبب االلتهاب واأللم و‬ ‫كذلك ازدياد نسبة المواد المسببة لاللم الحادثة من (‪.)Hs-CRP‬‬ ‫الهدف‪:‬‬ ‫‪ .1‬تقيم االستخداما‬

‫التشخيصية لمختلف المتغيرا‬

‫الفسيولوجية العصبية وتناسقها مع الرنين‬

‫المغناطيسي في تشخيص حاال الضغط على الجذور العصبية للحبل الشوكي‪.‬‬ ‫‪ .2‬تقيم دور االلتهابا في عملية ضغط على جذور العصبية‬ ‫المواد وطريقة العمل‪:‬‬ ‫تم تصنيف اشخاص المشاركين في هذه الدراسة الى ‪ 3‬مجموعا ‪:‬‬ ‫‪ .1‬المرضى الذين لديهم اعراض الضغط على جذور عصبية ألسفل العمود الفقري (ع=‪.)07‬‬ ‫‪ .2‬المرضى الذين لديهم اعراض الضغط على الجذور العصبية لمنطقة العنقية للعمود الفقري‬ ‫(ع=‪)07‬‬ ‫‪ .3‬مجموعة اشخاص اصحاء كمجموعة ضابطة (ع=‪.)07‬‬ ‫تم أخذ عينة الدم الوريدي لكل مشارك لقياس سكر الدم‪ ,‬كرا الدم البيضاء و معدل الترسيب كرا الدم‬ ‫الحمراء‪ .‬وتم أيضا عزل مصل الدم لقياس كل من )‪ (Serum glucose, SGOT, SGPT, CPK‬وقياس‬ ‫تركيز ‪ Hs-CRP‬باستخدام تقنية (‪.)ELIZA‬‬ ‫بعد اجراء الفحص السريري‪ ,‬أجري فحص التغيرا‬ ‫مقارنتها بنتيجة فحص رنين المغناطيسي‪ .‬العتبارا‬

‫الفسيولوجية العصبية المختلفة لكل مريض مع‬

‫اخالقية الطبية‪ ,‬لم يتم اجراء فحص تخطيط العضال‬

‫ورنين مغناطيسي لمجموعة الضابطة‪.‬‬ ‫النتائج‪:‬‬ ‫وجد زيادة معنوية في قياس ‪ BMI‬وتركيز ‪ Hs-CRP‬في مصل الدم عند مرضى كال المجموعتين‬ ‫مقارنة باشخاص المجموعة الضابطة (‪ p<0.05, p=0.001‬على التوالي) ووجد نقص معنوي في مدى العصب‬

‫الظنبوبي ( ‪ )Tibial CMAP amplitude‬لدى المرضى المصابين بضغط على جذور االعصاب اسفل العمود‬ ‫الفقري مقارنة باشخاص المجموعة الضابطة (‪ .(7.4 vs 10.9 mV, P=0.001‬وجد ايضا ارتباط ايجابي‬ ‫ومعنوي بين كل من كريا‬

‫الدم البيضاء و معدل الترسيب لكريا‬

‫الدم الحمراء (‪ )ESR‬مع ‪Hs-CRP‬‬

‫(‪P=0.018‬و‪ P=0.001‬على التوالي) كما وجد ارتباط ايجابي معنوي بين ‪ Hs-CRP‬و‪.(p<0.05) CPK‬‬ ‫باستخدام تحليل منحنى (‪ )ROC‬لتغيرا التخطيط االعصاب لالطراف السفلي ظهر بان مدى العصب الظنبوبي‬ ‫و كل من ‪BMI‬و‪ Hs-CRP‬ذو صالحية عالية في التنبؤ بوجود ضغوط على جذور العصبية السفل العمود‬ ‫الفقري و الفقرا‬

‫العنقية بداللة نتيجة منطقة تحت المنحنى (‪0.709 ,0.782( )AUC‬و ‪ 0.738‬على التوالي‪,‬‬

‫‪ .)p<0.001‬وشوهد بان التخطيط العضلي األبري كان بشكل هام يير طبيعي لدى مرضى سقوط القدم‪.‬‬ ‫وجد ايضا الضغط على الغالف الشوكي اوالجذورالعصبية في رنين المغناطيسي عند جميع المرضى الذين كان‬ ‫لديهم منعكس ‪ H‬يير طبيعي )‪.(p=0.04‬‬ ‫ادناه النسبة المئوية واالهمية االحصائية لنتائج التغيرا الفسيولوجية العصبية المختلفة و الرنين المغناطيسي في‬ ‫المجموعتين االولى والثانية على التوالي كاآلتي‪:‬‬ ‫التخطيط العضلي األبري (‪ 81.4%‬مقابل ‪ , )74%‬بيانا‬

‫التخطيط العصبي ( ‪27.1%‬مقابل ‪ ,)8%‬موجة ‪F‬‬

‫( ‪12.9%‬مقابل ‪ ,)2%‬منعكس ‪ 21.4% ( H‬في مجموعة االولى فقط) و رنين مغناطيسي (‪ 83.1%‬مقابل‬ ‫‪.)76.7%‬‬ ‫عثرعلى تناسق احصائي هام بين نتائج كل من تخطيط العضال‬

‫والرنين المغناطيسي بخصوص الضغط على‬

‫الجذور العصبية لكال المنطقتين‪-‬اسفل العمودي الفقري (‪ )83.9%‬و المنطقة العنقية للعمود الفقري‬ ‫(‪ .)p=0.001()81.1%‬وكذلك لوحظ بان نتائج كل من تخطيط العصب وموجة ‪ F‬يختلف كثيرا بالداللة‬ ‫االحصائية اذا استخدم كفحص لمقارنة بين المرضى الذين يعانون من ضغط على الجذور العصبية السفل العمود‬ ‫الفقري والذين يعانون من ضغط على الجذور العصبي للمنطقة العنقية لعمود الفقري‪.‬‬ ‫النسبة االيجابية لمنعكس ‪ H‬وتخطيط االعصاب يير طبيعية كانا مختلف بداللة احصائية هامة مقارن بمجموعة‬ ‫االصحاء)‪p=0.02 and p=0.005‬على التوالي)‬ ‫األستنتاجات‪:‬‬ ‫أظهر‬

‫هذه الدراسة ان لاللتهاب دور هام في تطور االصابة الضغط على الجذور العصبية بناء على الزدياد‬

‫الحاصلة بتركيز ‪ Hs-CRP‬في مصل الدم اضافة الى ان زيادة الوزن عامل مؤهل الحداث الضغط على‬ ‫الجذور العصبية‪ .‬تبين ان اجراء تخطيط للعضال شيء الزامي للبحث عن وجود ضغط على الجذور العصبية‪.‬‬ ‫تزداد كفاءة تخطيط العضال‬ ‫يتم فحصها‪ .‬وكذلك اظهر‬

‫للكشف عن حالة الضغط على الجذور العصبية برفع عدد عينا‬ ‫الدراسة بان هناك تناسق مهم بين تخطيط االعصاب والعضال‬

‫المغناطيسي في تشخيص الضغوط على جذور العصبية للحبل الشوكي‪.‬‬

‫العضال التي‬ ‫و فحص الرنين‬

‫سوودى طؤرِانة كارئةندامزاني ية دةماريةكان و ثشكنينى تيشكى موطناتيسى لةو نةخؤشانةى كة ثةستان‬ ‫ضوةتة سةر رِةطى دةمارةكانى درِكة ثةتك‬ ‫ثيَشةكى‪:‬‬ ‫لة ناو هؤكارةكانى ناردنى نةخؤش بؤ هيلَكارى دةمارو ماسولكةكان‪ ,‬ئازارى بةشي خوارةوة و ناوضةى ملى برِبرةى ثشت بة‬ ‫هؤى فشار كةوتنة سةر رِةطى دةمارةكانى درِكة ثةتك بة باوترين هؤكار دادةنريَت‪ .‬بؤ ئةوةى ثرؤسةى دؤزينةوةى ئةم جؤرة‬ ‫نةخؤشية باش ئةجنام دريت‪ ,‬ثيَويستة ئةو زانياريةى كة لة حالَةتى كلينكى نةخؤشةكةوة وةردةطرييَت ليَك بدريَت لة طةلَ‬ ‫دةرئةجنامى ثشكنينى هيَلَكارى دةمارو ماسولكةكان و تيشكى موطناتيسى‪.‬هيَشتا ثشكنينى تيشكى موطناتيسى دةورى طرنط‬ ‫دةبينيت لة دؤزينةوةى ئةو هؤكارانةى كة ثيَكهاتةيني‪ ,‬بةلَام هؤكارة نا ثيكهاتةييةكان دةكريَت لة رِيطةى ثشكنينى‬ ‫هيَلَكارى دةمارو ماسولكةكانةوة بدؤزريَتةوة‪ .‬تويَذينةوةك ثيَويستة بؤ هةلَسةنطاندنى رِادةى طوجنان لة نيَواني ئةم دوو‬ ‫ثشكنينةدا ‪ .‬رِاثؤرتةكانى سالَانى ثيَشوو ئةوةيان نيشان داوة كة بة هؤى فشاركةوتنة سةر رِةطى دةمارةكان‪ ,‬هةنديَك‬ ‫ماددة دةرئةدرين كة ئةبنة هؤى هةوكردنى دةمارةكةو دروست كردنى ئازار و بةرزبوونةوةى رِيَذةى (‪.)Hs-CRP‬‬ ‫ئامانج‪:‬‬ ‫‪ -1‬هةلَسةنطاندنى رَؤلَى طؤرِانة كارئةندامزاني ية دةماريةكان لة طةلَ ثشكنينى موطناتيسى لة دؤزينةوةى‬ ‫ثةستان لة سةر رِةطى دةمارةكان لة ناوضةى مل وناوضةى خوارةوةى درِكة ثةتك‬ ‫‪ -2‬هةلَسةنطاندنى رِولَى هةوكردن لة دروست بوونى ثةستان لة سةر رِةطى دةمارةكان‪.‬‬ ‫ضؤنيةتى كاركردن و وةرطرتنى داتاكان‪:‬‬ ‫بةشداربووان لةم تويَذينةوةيةدا دابةشكراوون بؤ سيَ طروث‪:‬‬ ‫‪ -1‬ئةو نةخؤشانةى كة نيشانةى فشارى سةر رِةطة دةمارةكانى بةشى خوارةوةى درِكة ثةتك يان هةية (ذ=‪)07‬‬ ‫‪ -2‬ئةو نةخؤشانةى كة نيشانةى فشارى سةر رِةطة دةمارةكانى بةشى سةرةوةى درِكة ثةتك (مل) يان هةية (ذ=‪)07‬‬ ‫‪ -3‬طروثيَكى لةش ساغ وةك و طروثي كؤنرتؤلَ (ذ=‪)07‬‬

‫لة هةر بةشداربوويةك‪,‬برِيَك خويَن وةرطريا بة مةبةستى ثشكنينى شةكرى خويَن‪,‬خرِؤكة سثيةكان و رِادةى نيشتنى خرِؤكة‬ ‫سورةكان لة كاتذميَريَكدا‪.‬هةروةها رِيَذةى )‪ (Serum Creatinine, SGOT, SGPT,CPK‬ثيَورا‪ .‬دواييش رِيَذةى‬ ‫(‪ )Hs-CRP‬بة تةكنيكى (‪ )ELIZA‬ثيَورا‪.‬‬ ‫لة دواى هةلَسةنطاندنى حالَةتى كلينكى نةخؤش‪ ,‬ثشكنينى هيَلَكارى دةماروماسةلكة بؤ هةر نةخؤشيَك ئةجنام دراو‬ ‫بةراوورد كرا بة ثشكنينى تيشكى موطناتيسى نةخؤشةكة‪ .‬لة بةر رِةضاوكردنى اليةنى ئيتيكى ثزيشكى‪ ,‬هيلَكارى ماسولكة‬ ‫بة دةرزى لةكةلَ ثشكنينى موكناتيسى بؤ طروثي كؤنرتؤلَ ئةجنام نةدرا‪.‬‬ ‫ئةجنامةكان‪:‬‬ ‫زيادبوونييكى كرنط لة ثيَوةرى ‪BMI‬و رِيَذةى ‪ Hs-CRP‬بينرا لة نةخؤشةكانى هةردوو طرووثةكة بة بةراوورد بة‬ ‫طروثي كؤنرتؤل‪ p<0.05, p=0.001).‬بةدواى يةك)‪ .‬هةروةها كةمبوونيَكى بةرضاو بينرا لة بةرزى شةثؤىل تةلَةزمة‬ ‫دةمار (‪ )Tibial nerve‬لةو نةخؤشانةى كة تووشي فشاربوون لةسةر رِةطى دةمارةكانى خوارةوةى درِكة ثةتك بة‬ ‫بةراوورد لة طةلَ طرووثي كؤنرتِؤلَ (‪.(7.4 vs 10.9 mV, P=0.001‬‬ ‫لةم تويَذينةوةيةشدا‪ ,‬هاوزيادبوونيَكى ئةريَنى دةركةوت لة نيَوان هةريةك لة ‪ ESR ,WBC‬لةطةلَ ‪Hs-CRP‬‬ ‫(‪P=0.018‬و‪P=0.001‬بة دواى يةك)‪.‬هةروةها هاوزيادبوونيَكى تريش لة نيَوان‬

‫‪Hs-CRP‬و ‪CPK‬‬

‫دةركةوت()‪.(p<0.05‬‬ ‫لة رِيَطاى بةكارهيَنانى ضةماوةى (‪ )ROC‬بؤ طؤرِانكاري فسيؤلؤجية دةماريةكانى ثةلةكانى خوارةوة دةركةوت كى بةرزى‬ ‫شةثؤىل دةمارى (‪ )Tibial nerve‬و هةريةك لة ‪ (BMI( Body mass index‬و ‪ Hs-CRP‬توانايةكى بالَايان‬ ‫هةية لة برِياردان لةسةر هةبوونى فشار لةسةر رِةطى دةمارةكانى مل و خوارةوةى درِكة ثةتك بةوةى كة ناوضةى ذيَر‬ ‫ضةماوةكةيان (‪ )AUC‬بريتى بوو لة (‪0.709 ,0.782‬و ‪ 0.738‬بةدواى يةك‪ .)p<0.001 ,‬وةهةروةها بينرا كة‬ ‫هيَلَكارى دةرزى ماسولكةكان بةشيَوةيةكى بةرضاو نائاسايى ترة لةو نةخؤشانةى كة تووشي (كةوتنى ثيَ) بوون‪.‬‬ ‫ئةمةى خوارةوة بريتية لة رِيَذةى سةدى و طرنطى ئامارى ئةجنامةكانى هةريةك لة طؤرِانكارية فسيؤلؤجية دةماريةكان و‬ ‫ثشكنينى تيشكى موطناتيسى لة هةردوو نةخؤشةكانى طروثي يةكةم و دووةم بة دواى يةك‪:‬‬ ‫هيَلَكارى ماسولكةكان بةدةرزى (‪ %4110‬بةرامبةر ‪ ,)%00‬هيَلَكارى دةمارةكان (‪ 2011‬بةرامبةر ‪( ,)%4‬شةثؤىل ‪%1211( F‬‬ ‫بةرامبةر ‪ ,)%2‬ثةرضةكردارى ‪ %2110(H‬تةنها لة طروثي يةكةم) وة تيشكى موطناتيسى (‪ %4311‬بةرامبةر ‪.)%0.10‬‬

‫هةروةها دةركةوت كة هةماهةنطيةكى طرنط لة نيَوان ئةجنامةكانى هةر يةك لة هيَلَكارى ماسولكةكان و ثشكنينى تيشكى‬ ‫موطناتيسى هةية لة هةردوو ناوضةى فشار لةسةر رِةطى دةمارةكان(‪ 81.1% ,83.9%‬بة دواى يةك ‪ )p=0.001,‬وة‬ ‫ئةجنامةكانى هيَلَكارى دةمارو شةثؤىل ‪ F‬بة شيَوةيةكى ئامارى طرنط بةسوود ترة كاتيَك بةكاربهيَنريَ وةكو ثشكنني بؤ‬ ‫دؤزينةوةى فشار لة سةر رِةطى دةمارةكانى خوارةوةى درِكة ثةتك وةك لة دةمارةكانى ناوضةى ملى درِكة ثةتك‪.‬‬ ‫دةرئةجنام‪:‬‬ ‫ئةم تويَذينةوةية ئةوةى دةرخست كة هةوكردنى دةمارى رِؤلَيَكى طرنطى هةية لةرِوودانى فشارى سةر رِةطة دةمارةكانى درِكة‬ ‫ثةتك لة سةر بنةماى زيادبوونى رِيَذةى ‪Hs-CRP‬لة خويندا‪ ,‬سةرةرِاى ئةوةش زيادبوونى كيَش (‪ )BMI‬هؤكاريَكى‬ ‫مةترسي دارة بؤ رِوودانى فشار لة سةر رِةطى دةمارةكانى درِكة ثةتك‪.‬دةركةوت كة ئةجنامدانى هيَلَكارى ماسولكةكانةرزى بة‬ ‫شتيَكى ثيَويستة بؤ دؤزينةوةى فشار لةسةر رِةطى دةمارةكان وة ضوستى هيَلَكارى ماسولكةكان زياددةكات بة زيادكردنى‬ ‫ذمارةى ئةو ماسولكانةى كة هيَلَكاريان بؤ دةكريَت‪ .‬هةروةها هةمانهةنطيةكى طرنط بينرا لة نيوان ثشكنينى موطناتيسى و‬ ‫هيَلَكارى دةماروماسولكةكان لة دؤزينةوةى فشار لة سةر رِةطى دةمارةكان‪.‬‬