1

DECLARATION

I, Dr. Sai Satish Kandraju, hereby declare that this project was undertaken by me

under the supervision of the faculty, Department of Neurology, Sree Chitra

Tirunal Institute for Medical Sciences and Technology.

Thiruvananthapuram Dr. Sai Satish.Kandraju

Date:

2

Forwarded

The candidate, Dr Sai Satish.Kandraju, has completed the project under my guidance.

He has carried out the minimum required project.

Thiruvananthapuram Dr.Muralidharan Nair,

Date: Professor and Head,

Department of Neurology

SCTIMST.

3

ACKNOWLEDGEMENT

I take this opportunity to express my sincere gratitude to Dr Dr.Muralidharan Nair, Professor of

Neurology and Head, Department of Neurology, SCTIMST, my guide for the study, for his expert

guidance, constant review, kind help and keen interest at each and every step of the study

I am thankful to Mr Anees & Mr.Kenaz, Neurotechnologists for helping me with the technical

guidance while performing the study.

I express my sincere thanks to Dr. Sankara Sarma, Professor, AchuthaMenon Centre for Health

Science Studies for helping me with the statistical analysis of this study.

I am extremely thankful to the nursing staff, technicians and my colleagues in the Department

of Neurology for their valuable input and assistance to the study.

Last but not the least, I extend my gratitude to all my patients and their primary caregivers who

willingly participated in this study.

Dr Sai Satish Kandraju

Senior Resident

Department of Neurology

SCTIMST, Trivandrum, Kerala

4

INDEX

i. Introduction 1

ii. Review of Literature 3

iii. Hypothesis and objectives of the study 23

iv. Subjects and Methods 24

v. Results 27

vi. Discussion 56

vii. Conclusions and summary 63

viii. Limitations 65

ix. References 66

x. Annexure 76

5

INTRODUCTION:

Standard diagnostic nerve conduction tests evaluate integrity of large nerve fibers which

explain numbness and tingling, but not pain and dysesthesias which are common in Carpal

tunnel syndrome (CTS). Cutaneous silent period (Cu.SP) is an electrodiagnostic method to

evaluate small nerve fibers1.This study looks at the variables of Cu.SP in CTS as compared to

normal individuals.

6

REVIEW OF LITERATURE

Electrophysiology is an integral part of the physician’s diagnostic armamentarium. It is

considered as an extension of the physical examination to determine the neuro-anatomical

localization and underlying pathophysiology. Nerve conduction studies and electromyography

are widely used to evaluate the integrity and various disorders affecting the peripheral nervous

system.

Classification of Peripheral Nerves: A brief note.

Peripheral nerve fibers were classified by Erlanger and Gasser into A (α,ß,γ,δ),B and C

fibers based on their diameter and conduction velocities2.While the thickly myelinated Aα, Aß

fibers designated as “large fibers”, sub serve motor efferents to extrafusal fibers in addition to

touch, vibration and joint position sense, thinly myelinated Aδ and unmyelinated C fibers are

segregated as “small fibers” which sub serve pain and temperature sensation in addition to

autonomic functions. Figure 1 shows a Classification of peripheral nerve fibers3.

7

1

Routine nerve conduction studies do not evaluate small nerve fibers: Simple tool to evaluate

function of small nerve fibers-Unmet need.

Most of the parameters in various nerve conduction tests done routinely, like distal

latency, compound muscle action potential and conduction velocity in the motor conduction

studies evaluate the functioning of large nerve fibers, and similarly peak latency of sensory

nerve action potential in the sensory conduction studies also evaluate large nerve fiber’s

integrity. Thus, these parameters are unperturbed in disorders affecting small nerve fibers

selectively. In another view, the above modalities of investigations are also insensitive to

Figure 1:-Classification of peripheral nerve fibers3

8

implicate the involvement of small nerve fibers in patients complaining of pain in disorders such

as in Carpal tunnel syndrome.

There are few semi quantitative electrophysiological methods by which small nerve

fibers are evaluated. These include Quantitative cold, warm and pain threshold tests. However,

these tests need sophisticated equipment like neodymium Laser (Nd: YAP) stimulator to elicit

pinprick (pain) sensation and Thermal Sensory Analyzer for determining warm and cold sensory

threshold4. In addition, these tests rely on response of the individual, thereby hindered because

of subjective bias. Quantitative sudomotor axon reflex test (QSART) and Thermoregulatory

sweat tests evaluates autonomic nervous system.5 The definitive diagnostic test for small fiber

neuropathy is Intraepidermal nerve fiber density estimation, which needs minimally invasive

skin biopsy and immunostaining with protein gene product of 9.5 which is available, mainly in

research or referral lab settings6. In this context, there is a need for a simple, readily available,

cost effective and technically feasible test for evaluating small nerve fibers.

Cutaneous silent period (Cu.SP) is a brief period of cessation of muscle contraction that

occurs after stimulation of the cutaneous nerves close to or distant from the muscle that is

contracting.1 Stimulation of small nerve fibers, especially Aδ fibers, is needed to elicit this

response, which can be done with standard electromyography equipment using simple settings.

Hence, Cu.SP is a simple non invasive approach to study small nerve fibers, which needs

standardization of method.

9

Cutaneous Silent Period for evaluation of small nerve fiber’s dysfunction. What is it?

The Cu.SP is protective painful withdrawal reflex as it is obtained by electrical stimuli

that are felt as painful1. It is a spinal inhibitory reflex sub served essentially primarily by small-

diameter Aδ fibers, which enter the spinal cord’s dorsal horn and inhibits activity in spinal

motor nuclei in neighboring myotomes. This motor neuron inhibition may be mediated by

Renshaw cells which are presumed to be directly activated by high threshold cutaneous

afferents i.e small fibers14.

Thinly myelinated afferents fibers are the important component of the afferent arc of

the Cu.SP in limb muscles. Even though the electrical stimulus needed to elicit the Cu.SP

stimulates both large- as well as small-diameter fibers, the long latency of the CSP, seen in

muscles of distal upper extremity, 50 –80 ms after stimulation of the finger, is more consistent

with a spinal reflex mediated by afferent fibers with slow conduction velocities.Conduction

velocity of the afferents fibers were derived by stimulating two points of a cutaneous nerve,

which yielded approximate values of 9 –18 m/s, within the range of conduction velocities of A-

delta fibers7.The high intensity of stimuli required to elicit the Cu.SP are beyond that required

for eliciting a maximal Sensory Nerve Action Potential8. In addition, when afferents with large

diameter blocked are blocked by ischemia Cu.SP was still elicitable 9. Above observations

support the hypothesis that the afferent pathway of the Cu.SP is composed by fibers which are

small and have thin myelination. Moreover, preserved Cu.SPs were observed in patients with

peripheral neuropathy affecting large diameter sensory fibers, who had unelicitable Sensory

Nerve Action Potentials or somato sensory evoked potentials (SSEPs), which strengthens the

10

argument against an important role for fibers with large diameter in the CSP10. However, large-

diameter afferent fibers contributed for Cu.SP, albeit this contribution may not be important11.

Figure 2 depicts Cutaneous silent period elicited in hand and leg in a normal subject.

Different variables in Cutaneous Silent Period:

As depicted in Figure 2 (red colored lines), different variables of Cu.SP can be

determined from the averaged surface electromyography traces. The beginning and endpoint

latencies of Cu.SPs can be identified through visual inspection at the start of a sudden cessation

and at the time of return of surface electromyographic activity, respectively. The “latency” of

the Cu.SP can be derived by measuring the time between the stimulation and the sudden

beginning of the silent period. The latency of the Cu.SP increases with height of the subject. The

“duration” of the CuSP can be derived by measuring the time from the beginning to endpoint of

the silent period, which denotes intensity of suppression. In contrast to averaged EMG traces,

rectified EMG traces allows to calculate Cu.SP area which can also be used to express the

intensity of suppression11.

Cutaneous silent period: from bench to bedside.

The clinical significance of this inhibition might be to ‘‘prime’’ the extremity (Eg. upper

extremity) for a prompt withdrawal away from a noxious stimulus, by selectively inhibiting

muscles that are responsible for approaching and grasping (triceps and intrinsic hand

muscles).At the same time, allowing the activation of the muscles that sub serve withdrawal

(biceps & deltoid muscles). From a practical viewpoint, it is pertinent that reflex inhibition of

continuing motor activity might be a part of reflex withdrawal. For instance, in case of a hand

11

unknowingly approaching and grasping a hot object, it is safe and beneficial to drop the object

before withdrawing the extremity12.If he doesn’t leave, he will burn himself.

12

13

Sites where Cutaneous silent period can be elicited:

In upper limbs, Cu.SP elicited by stimulation of the fingers is marked in the intrinsic

muscles of hand. In one study, stimulation of the finger elicited Cu.SPs lasting from 50 - 100 ms

in the abductor pollicis brevis muscle13. In another study which looked at the distribution of the

Cu.SP elicited after stimulating the index finger, revealed incrementally longer latency of Cu.SP

in distal muscles and the greater magnitude of inhibition in thenar and hypothenar hand

muscles. Finger stimulation elicited relatively briefer periods of Cu.SP in muscles of the forearm

and masseter, while Cu.SP was unelicitable in the orbicularis oculi muscles14. It is also observed

that the same stimulus facilitated the ongoing contraction the biceps and deltoid muscles15.

In lower limbs, Cu.SPs is elicited in soleus and tibialis anterior muscles after stimulating

either plantar or sural nerves innervating the foot13. Latency and duration of Cu.SP was 80–100

ms and 40-80ms respectively in both muscles after stimulating sural nerve. Plantar stimulation

elicited Cu.SPs with a latency about 20 ms longer relatively.

In cranial musculature (Masseter and Temporalis) stimulating Trigeminal stimulation

over face, gums or teeth elicits Silent Periods16. The Masseter Inhibitory Reflex is elicited after

stimulating the mental nerve during maximal steady bite by the subject. In contrast to Cu.SPs

elicited in upper limbs, Silent periods elicited in cranial musculature has two discrete periods of

silence analogous to oligosynaptic and polysynaptic components of the blink reflex (R1 & R2

components respectively).

14

Though silent period can be elicited from cranial, upper and lower limb musculature,

major advantage in utilizing the upper limb depends on the fact that particularly strong reflex

changes can be evoked by stimulating fingers and thumb17.

Cutaneous silent period in various disorders:

Central nervous system disorders:

Parkinson’s Disease & Dystonia:

While CuSP duration was prolonged in Parkinson’s disease18 and dystonia19, its latency,

magnitude of suppression and intensity of post inhibition facilitation was not different from

controls. Dopa replacement rectified prolonged CuSP in Parkinson’s disease but not in atypical

Parkinsonism.

Syringomyelia:

CuSP abnormalities range from shortened duration to unelicitable CuSP depending on

the severity of the cavitation involving the posterior horn of spinal cord20,21.

Peripheral nervous system disorders:

Radiculopathies:

As stimulated impulse needs to traverse the proximal sensory radicles to reach the

spinal cord, one of the suggested uses of Cu.SP was to assess the integrity of the sensory

radicles especially following traumatic brachial plexopathy22. The muscle selected for recording

must be innervated from different radicle as compared to the sensory level being assessed. By

15

this approach, the absence of the CSP could point the discontinuity of the sensory root at the

level corresponding to the stimulated finger.

Peripheral neuropathies:

The application of Cu.SPs to diagnose generalized neuropathy has been overall

ineffective.

Cu.SPs were normal in neuropathies with large fiber involvement like in idiopathic

sensory neuronopathy10, abetalipoproteinemia23 Friedreich’s ataxia14.

Considerable interest has been directed at determining whether the Cu.SP can be

utilized for evaluating small-fiber neuropathies, as small diameter fibers are not well evaluated

by standard nerve conduction tests. Even though all evidence suggest an important

contribution from small myelinated fibers to the Cu.SP, unequivocal abnormalities in the Cu.SP

have been identified only in subjects with severe small-fiber dysfunction as in Fabry disease and

Hereditary sensory and autonomic neuropathy. Cu.SP in patients with Fabry disease was of

shorter duration and intensity of suppression was also abnormal as compared to controls.24

Cu.SP in patient with Hereditary sensory and autonomic neuropathy was unelicitable upon

stimulation of one digit, while it was delayed and shorter upon stimulating 2 digits25.

Carpal tunnel syndrome:

Yong Seo Koo et al reported longer mean Cu.SP latencies in CTS when compared to

control group, although there was no difference in duration of Cu.SP. The duration and latency

of Cu.SP correlated with the severity of CTS.26

16

M.J. Pablo et al reported no responses in a small percentage of severe CTS. In the rest of

the severe CTS, and the moderate/severe cases, the latency was increased and the duration

was decreased. No alterations were found in the Cu.SP in mild and moderate cases.27

S.K. Aurora et al reported absent Cu.SP in severe cases and prolonged duration in mild to

moderately severe CTS cases.28

Although there have been studies on variables of Cutaneous silent period in patients

with Carpal tunnel syndrome, results were variable. Hence we attempted to systematically

examine Cu.SP in CTS of variable severity which would help us to validate changes of Cu.SP in

CTS.

Carpal tunnel syndrome:

Carpal tunnel syndrome is defined as “a constellation of clinical symptoms and signs

resulting as a consequence of compression of median nerve at the level of wrist and ensuing

slowed conduction.”29

There are no epidemiological data from India. Studies from western population report

an incidence of 1-3 cases per 1000 persons per year30,31,32.Study from Sweden reports

prevalence of clinical and electrophysiologically proven carpal tunnel syndrome to at 2.7%

(CI,2.1%-3.4%)33.Females are 3-10 times more commonly diagnosed with CTS as compared to

males30.The peak age range susceptible for CTS is 45-60yrs.Only 10% of CTS patients are

younger than 31 years30.

17

The features that highly suggest CTS are (1) Pain or paresthesias during driving, holding

a phone,book or news paper. (2)Above symptoms involving 1st, 2nd, 3rd along with radial aspect

of 4th digit. (3)Nocturnal arousal from sleep due to sensory symptoms. (4)Shaking or wringing

the hand to relieve the symptoms. (5)Weakness or wasting of thenar group of muscles.

(6)Phalen’s maneuver precipitating the symptoms34.

Boston Carpal Tunnel Questionnaire (BQ)35:

Also known as Levine scale, BQ is a patient- derived outcome measure that was

structured particularly for patients with CTS.

It includes 2 discrete scales, the Symptom Severity Scale (SSS) which consists 11

questions with a 5 point rating scale and the Functional Status Scale (FSS) with 8 items which

needs to be rated for extent of difficulty on a 5 point scale. Each scale gives an ultimate score

calculated as sum of individual scores divided by number of items. The final score ranges from 1

to 5, with an increasing score score signifying increasing disability 35. The BQ has been adopted

as an outcome measure in several studies, and also withstood considerable testing in terms of

validity, reliability and responsiveness. The evidence indicates that the BQ is a valid, reliable,

responsive and satisfactory tool that should be considered as a primary outcome variable in CTS

trials36.

Diagnosis of clinically suspected CTS is confirmed electrophysiologically by

demonstrating focal conduction slowing of median nerve at the level of the carpal tunnel.

When the standard motor as well as sensory median nerve conduction tests are normal, CTS is

diagnosed based on internal comparison studies between median and ulnar or radial nerves.

18

Sensitivity and specificity of these internal comparison test are depicted in the Table 137,38.

Accordingly, severity of CTS can be graded based on electrophysiological data according to

Canterbury neurophysiological grading as described in Table 239.

Table .1.Characteristics of internal comparison studies in CTS37,37.

Test Sensitivity(%) Specificity (%) Distance Significant

difference

Median – Ulnar digit IV

sensory latency

74 97 12-14cm >0.5 msec

Median-Radial digit I

sensory latency

76 97 8-10cm >0.5msec

Median-Ulnar palm-

wrist latency study

70 97 8cm >0.4msec

19

Table.2.Canterbury Neurophysiological grading of CTS39.

Severity

grade

Sensory

conduction

velocity

SNAP Motor

conduction

velocity

Motor

potential

amplitude

0 Normal No neurophysiological abnormality

1 Very mild Above tests are normal

Detected by sensitive tests (Internal comparision studies)

2 Mild Slowing Preserved Normal Preserved

3 Moderate Slowing Preserved >4.5 - <6.5ms Preserved

4 Severe Absent >4.5 - <6.5ms Preserved

5 Very severe Absent >6.5ms Preserved

6 Extremely

severe

Sensory and motor potentials effectively unrecordable (surface

motor potential from APB <0.2mV amplitude)

20

HYPOTHESIS AND OBJECTIVES OF THE STUDY

HYPOTHESIS:

There is involvement of small sensory fibers causing pain in Carpal Tunnel Syndrome,

which is responsible for abnormal Cu.SP. Depending on the severity of small sensory fibers

involvement there will be corresponding changes in CuSP.

We propose following pathophysiological mechanisms underlying the abnormalities of

Cu.SP in CTS.

In CTS, pain carrying fibers in the median nerve gets compressed as they traverse the

carpal tunnel and become dysfunctional, there by delaying their conduction velocity, which

should reasonably prolong the latency of Cu.SP.

Normal pain carrying fibers decrease in number as disease progress, thereby decreasing

the magnitude of inhibition of motor neurons, which can be conceivably reflected in NCS as

decrease in duration of Cu.SP.

In case of severe CTS where all pain fibers are dysfunctional and there is no conduction

possible and motor fibers are not inhibited, it is plausible that Cu.SP will be absent.

OBJECTIVES OF THE STUDY:

1. To systematically study the characteristics of Cu.SP in the sample.

2. To attempt a correlation between clinical and electrophysiological severity of the CTS and the

characteristics of Cu.SP.

21

SUBJECTS AND METHODS

Study design and setting:

This study was a hospital based cross-sectional descriptive study. The subjects were

selected among the patients attending the Electromyography lab of Department of Neurology,

Sree Chitra Tirunal Institute of Medical Sciences and Technology, Thiruvananthapuram.

Study period:

The study was conducted over a period of 18 months from 4th March 2014 to September

2015.

Methodology:

Consecutive patients attending the Electromyography lab in the Sree Chitra Tirunal

Institute of Medical Sciences and Technology were screened for eligibility for the study.

Those fulfilling the inclusion criteria were explained the procedure and those willing to give

informed consent were recruited into the study. The subjects were interviewed using a detailed

questionnaire to note the demographic data, duration of symptoms, symptom severity and

functional severity score. The subjects were then evaluated by nerve conduction studies and

surface electromyography.

22

Ethical considerations:

The study was approved by the Institute Ethical Committee. Written informed consent

was obtained from all the subjects participating in the study. The informed consent procedure

was done according to the guidelines provided in the Declaration of Helsinki and the ICH E6

Guideline for Good Clinical Practice.

Inclusion criteria:

1. Consecutive patients evaluated in EMG laboratory for CTS and those consenting for the

study.

2. Patients referred to EMG laboratory for evaluation of their primary condition, but with

normal conduction studies and consenting for the study were included as Controls.

3. Patients referred to EMG laboratory for diagnosis other than CTS with abnormal nerve

conduction studies and those consenting for the study were included as Disease controls.

Exclusion criteria:

1. Subjects not tolerating the discomfort and not co-operating for the study.

2. Patients with history of surgery for cervical spondylosis or herniated intervertebral discs

(nucleus pulposus) were excluded.

Symptom Evaluation:

Details of symptoms regarding the duration, severity of the symptomps and consequent

functional disability were noted based on Boston Questionnaire (See Appendix i). The

questionnaire consists of 11 questions on the severity of symptoms i.e Symptom Severity Scale

23

(SSS) and 8 on functional disability i.e Functional Severity Scale (FSS). SSS and FSS scores were

obtained after calculating the means of responses to the individual questions. Answers to the

first 5 questions of the SSS were used to assess pain severity [Pain Severity Score (PSS)].

Neurophysiological evaluation:

I. Diagnosis and electrophysiological grading of CTS

CTS: Diagnosed based on nerve conduction studies, and the severity graded according to

the Canterbury neurophysiological grading of CTS (See Table 2).

II. Method to elicit CuSP

• Surface electromyographic activity was recorded from the abductor pollicis brevis (APB ).

• During a maximal voluntary contraction, a single painful stimulus was given to ipsilateral 2nd

finger until a complete silent period of reproducible latency and duration was acquired.

• To obtain a maximum and steady contraction, the subject was asked to contract against

resistance, and muscle contraction was monitored with help of auditory output from EMG

machine.

• A stimulus of 0.2 ms duration was given and gradually intensity of stimulus was increased

up to values above 40 mA, until a constant response was obtained. The latency, duration

and end point of CuSP was determined.

• 5 recordings showing Cutaneous silent period with shorter latency in addition to longer

duration were selected for analysis. The average of latencies, durations and endpoints of

Cu.SPs (the average values of the 5 recordings) were used in the final analysis.

24

Statistics:

Data analysis was performed using SPSS ver.22.0.Quantitative variables were described

by mean and standard deviation. Qualitative variables were described by frequency

distribution.

Comparison of Quantitative variables between two groups was done by independent

sample t-test. Comparison of averages among more than two groups was analyzed by ANOVA,

while multiple comparisons among the group were analyzed by post hoc test.

Variables which were found to be significant during univariate analysis were subjected

to multivariate analysis of binary logistic regression.

A p value of <0.05 was taken as level of significance.

25

Results:

50 patients satisfyied the inclusion criteria for CTS cases and lab controls. However, 6

patients, each from CTS group and control group did not co-operate to elicit Cu.SP because of

discomfort associated with stimulus. Hence, they were not included in the analysis. Among

remaining 44 patients in each group, 3 patients from CTS group and 6 patients from control

group co-operated to elicit Cu.SP in one hand only. Hence, data of 85 hands from 44 CTS cases

and 82 hands from control cases were available for analysis. As Cu.SP was absent in 4 out of 85

CTS hands, finally 81 CTS hands were considered for analyzing the Cu.SP variables and various

clinical and electrophysiological characteristics.

50 CTS patients

44 CTS patients (88

hands)

3 CTS patients allowed

examination of only one hand

85 hands were

analyzed

6 didn't tolerate

procedure

50 lab controls

44 CTS lab controls (88

hands)

6 subjects allowed only

one hand examination

82 hands were

analyzed

6 didn't tolerate

procedure

26

Demographic characteristics:

CTS group was significantly elder than the control group. Mean age of CTS group being

49.1 +11.04 yrs as compared to mean age of control group (35.2+13.71yrs) which was

statistically significant (p<0.001). The gender distribution and height were not statistically

different between the two groups (p 0.647 and 0.106 respectively). 29.5% (n=13) of CTS group

and 34.1% (n=15) of control group were males. 70.5% (n=31) among CTS group and 65.9%

(n=29) among control group were females. Mean height of CTS group was 159.0 +9.4 cm as

compared to 162+8.3 cm in control group.

49.1

35.2

0

10

20

30

40

50

60

70

CTS Control

Age in years(p<0.001)

27

159 162.1

0

20

40

60

80

100

120

140

160

180

CTS Controls

Height in cm(p =0.106 )

29.5 34.1

70.5 65.9

0%

20%

40%

60%

80%

100%

CTS Controls

Gender distribution(p =0.647 )

Male Female

28

Characteristics of CTS group:

Among the CTS group, mean Symptom Severity Score (SSS) was 1.95 + 0.67, mean Pain

Severity Score (PSS) was 1.94 + 0.97 and Functional Severity Score (FSS) was 2.03 + 0.89. All the

severity scores were positively correlated with each other, which was statistically significant as

depicted in the table.

Correlation between scores of Boston Questionnaire

Symptom Score

Severity

Pain Severity

Score

Pain Severity Score .840** 1

Functional Severity

Score

.694** .662**

** Correlation is significant at .001 level

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

0 1 2 3 4 5

Sym

pto

m a

nd

Pai

n s

eve

rity

sco

re

Functional severity score

Correlation between FSS,SSS & PSS

Pain severity score

Symptom severity score

Linear (Pain severity score)

Linear (Symptom severity score)

29

Duration of symptoms ranged from 0.5 months to 84 months with median duration of

12 months (IQR 6-24 months).Duration of symptoms was significantly positively correlated with

SSS (r 0.22,p 0.01) and FSS (r 0.27,p 0.01), but not with PSS (r 0.11,p >0.05).

Based on the Canterbury scale, among 85 hands with CTS, 4 hands were grade1, 26

were grade2, 39 were grade 3, 6 were grade 4, 9 were grade 5 and one hand was grade 6.

Subgroups based on Canterbury scale were not different in terms of age, gender

distribution and height (p=0.93, p=0.57 & p=0.39 respectively). Similarly, duration of symptoms,

symptom severity score, pain severity score and functional severity scores were not different

among the subgroups divided by Canterbury scale (p=0.17, p=0.07, p=0.46 & p=0.32

respectively).

5%

31%

46%

7%

10%

1%

Percentage of hands in each Grade of CTS (n=85)

Grade 1 (very mild, n=4)

Grade 2 (mild,n=26)

Grade 3 (moderate,n=39)

Grade 4 (severe,n=6)

Grade 5 (very severe,n=9)

Grade 6 (extremely severe,n=1)

30

Comparison of mean age between CTS subgroups

Neurophysiological

grading

N Age in years F p

Mean sd

1.0 4 52.25 14.77

.273

.927

2.0 26 49.19 12.56

3.0 39 49.13 10.70

4.0 6 48.60 13.59

5.0 9 45.90 7.77

6.0 1 55.00

Total 85 48.95 11.13

Comparison of mean height between CTS subgroups

Neurophysiological

grading

N Height in cm F p

Mean sd

1.0 4 150.75 6.65

1.062

.388

2.0 26 159.35 9.40

3.0 39 158.73 8.37

4.0 6 160.00 8.03

5.0 9 163.15 12.90

6.0 1 160.00

Total 85 159.15 9.27

31

Comparison of Gender distribution between CTS subgroups

Neurophysiological

grading

Male Female

N % N %

1.0 2 8.0 2 3.3

2.0 9 36.0 17 28.3

3.0 8 32.0 31 51.7

4.0 2 8.0 4 5.0

5.0 4 16.0 5 10.0

6.0 0 0.0 1 1.7

Total 25 100.0 60 100.0

χ2 =3.870 df =4 p=0.568

Comparison of Mean Symptom severity score between CTS subgroups

Neurophysiological

grading

N symptom severity F p

Mean sd

1.0 4 1.40 0.33

2.153

.068

2.0 26 1.88 0.69

3.0 39 1.94 0.66

4.0 6 1.82 0.16

5.0 9 2.35 0.71

6.0 1 3.18

Total 85 1.95 0.67

Comparison of Mean Pain severity score between CTS subgroups

Neurophysiological

grading

N Pain severity score F p

Mean sd

1.0 4 1.20 0.40

2.0 26 1.99 1.02

32

3.0 39 1.94 0.91

.941

.459

4.0 6 1.72 0.82

5.0 9 2.12 1.23

6.0 1 3.20

Total 85 1.94 0.97

Comparison of Mean Functional severity score between CTS subgroups

Neurophysiological

grading

N Functional severity

score

F p

Mean sd

1.0 4 1.97 1.13

1.194

.320

2.0 26 1.94 1.00

3.0 39 1.93 0.72

4.0 6 2.13 0.85

5.0 9 2.56 1.11

6.0 1 3.13

Total 85 2.03 0.90

Comparison of Mean duration of symptoms between CTS subgroups

Neurophysiological

grading

N Duration of symptom in

months

F p

Mean sd

1.0 4 19.88 27.96

1.616

.166

2.0 26 18.23 14.89

3.0 39 15.48 18.88

4.0 6 9.00 2.83

5.0 9 31.26 24.48

6.0 1 36.00

Total 85 18.24 18.77

33

Characteristics of Cu.SP.

Considering both CTS and control groups together (n=177), among the demographic

factors, Age had significant positive correlation with latency (r 0.29, p<0.001) and endpoint (r

0.37,p <0.001).Height had significant correlation with latency alone (r 0.32 p <0.001).On linear

regression analysis both age and height predicted Cu.SP latency and endpoint.

Correlation of Latency

Pearson

correlation - r

p

Age .293** <0.001

height .324** <0.001

Correlation of End point

Pearson

correlation - r

p

Age .373** .000

height .132 .094

Correlation of Duration

Pearson

correlation - r

p

Age .153 .052

height -.111 .157

34

Linear regression analysis was performed on all hands (n=177)

Dependent Variable: latency

Predictors: (Constant), height, Age

Unstandardized

Coefficients

t p

B Std. Error

(Constant) -8.614 13.324 -.646 .519

Age .221 .048 4.564 .000

height .459 .081 5.673 .000

Linear regression analysis was performed on all hands (n=177)

Dependent Variable: Duration

Predictors: (Constant), height, Age

Unstandardized

Coefficients

t p

B Std. Error

(Constant) 76.065 27.097 2.807 .006

Age .184 .099 1.865 .064

height -.208 .165 -1.263 .208

Linear regression analysis was performed on all hands (n=177)

Dependent Variable: Endpoint

Predictors: (Constant), height, Age

Unstandardized

Coefficients

t p

B Std. Error

(Constant) 38.893 24.579 1.582 .115

Age .470 .089 5.258 .000

height .404 .149 2.708 .007

35

When latency, duration and endpoint of Cu.SP were analyzed, latency had significant

negative correlation with duration (r -0.341,p 0.01) as depicted in scatter diagram below and

positive correlation with endpoint (r 0.271, p=0.01). Endpoint had significant positive

correlation with duration (r 0.741, p=0.01).

Correlation between Cu.SP variables

Latency Duration End point

Latency 1.000 -.341** .271**

Duration -.341** 1.000 .741**

**. Correlation is significant at the 0.01 level (2-tailed).

0

20

40

60

80

100

120

140

0 20 40 60 80 100 120

Latency

Duration

Correlation of latency & duration

36

0

50

100

150

200

250

0 20 40 60 80 100 120

Endpoint

Latency

Correlation between latency & endpoint

0

20

40

60

80

100

120

140

160

180

0 20 40 60 80 100 120

E

n

d

p

o

i

n

t

Duration

end point in ms

37

Cu.SP in CARPAL TUNNEL SYNDROME Group:

Of all CTS hands (n=85), Cu.SP could be elicited in 81 hands (95.3%) and Cu.SP was

absent in 4 hands (4.7%).Cu.SP was absent in very severe (n=3) and extremely severe (n=1) CTS

hands and none in less severe grades of CTS.

Mean latency, duration and endpoint of Cu.SP among CTS hands were 78.07 + 12.35ms,

50.56 + 20.36 ms and 127.61 +15.0ms respectively.

When variables of Cu.SP and severity scores were analyzed, only functional severity

score had significant positive correlation with duration (r=0.28, p 0.01) and endpoint (r=0.29, p

0.001) of Cu.SP. Latency of Cu.SP didn’t have any significant correlation with any of the clinical

severity scores (SSS, PSS or FSS).

Correlation between Cu.SP variables and score on Boston Questionnaire

Latency Duration End point

Symptom severity score -.100 .163 .129

Pain severity score -.138 .090 .018

Functional severity

score

-.113 .281* .289**

**. Correlation is significant at the 0.001 level.

*. Correlation is significant at the 0.01 level.

38

In addition, among the Cu.SP variables, endpoint (r 0.25, p=0.01) alone was positively

correlated with duration of symptoms.

Cu.SP latency increased as neurophysiological grade of CTS increased. Mean Cu.SP

latency in very severe CTS (grade 5) was longest (86.12+3.16ms), followed by severe (grade 4,

82.57+16.83ms), moderate (grade 3, 78.35+12.49ms, p=0.067), mild (grade 2, 76.83+11.1ms,

p0.034) and very mild CTS (grade 1, 64.65+11.89ms, p=0.001).Mean Cu.SP latency of all severe

CTS hands (severe + very severe hands, 84.34+11.69 ms) was significantly greater than that of

very mild CTS (p=0.005) but not significantly longer than that of mild and moderate CTS (p=0.75

& p=0.13, respectively)

64.6576.83 78.35 82.57 86.12

0

20

40

60

80

100

120

1 2 3 4 5

Late

ncy

in m

s

Neurophysiological grade

Cu.SP latency in different grades of CTS

39

Mean Cu.SP duration was not significantly different among different grades of CTS.

Similar to Cu.SP latency, endpoint also increased as neurophysiological grade of CTS

increased. Mean Cu.SP endpoint of Very Severe CTS (grade 5, 142 +11.83ms) was longest

followed by severe (grade 4, 136.1 + 14.88ms), moderate (grade 3,124.15 + 14.66ms), mild

(grade 2, 127.9 + 13ms) and very mild (grade 1,124 + 22ms). Mean Cu.SP endpoint of very

severe CTS was statistically longer than that of very mild, mild and moderate CTS (p=0.048,

p=0.03, p=0.004 respectively), but was not statistically longer than severe CTS (p=0.43).

59.3551.127 47.879

53.55 56.617

0

10

20

30

40

50

60

70

1 2 3 4 5

Duration in ms

Neurophysiological grade

Cu.SP Duration in different grades of CTS

40

When variables of Cu.SP and nerve conduction parameters (distal latency of CMAP and

SNAP latency) were analyzed, Cu.SP latency and endpoint but not duration, were positively

correlated with CMAP latency and SNAP latency which was statistically significant.

Correlation between Cu.SP variables and distal motor latency and sensory latency

CMAP_latency SNAP_latency

latency_in_ms .372** .312**

duration_in_ms .097 .026

end_point_in_ms .272** .181*

**. Correlation is significant at the 0.01 level (2-tailed).

*. Correlation is significant at the 0.05 level (2-tailed).

124 127.93 124.15 136.12 142.65

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5

End point in ms

Neurophysiological Grade

Cu.SP Endpoint in different grades of CTS

41

Samples of Cu.SP traces elicited from a moderately severe CTS case. Individual traces (above)

and superimposed traces.

42

CONTROL group:

Mean Cu.SP latency among controls was 70.10 ms +6.61 ms, which was significantly

shorter as compared to CTS group (p <0.001).Age adjusted mean Cu.SP latency of controls was

also significantly shorter (p <0.001). As compared with control group, Mean Cu.SP latency was

significantly prolonged in all grades of CTS except for very mild CTS (grade 1).

Mean Cu.SP duration among controls was 50.05 +20.15ms, which was slightly shorter

than that of CTS group (50.6+20.36ms, p=0.87), but was not statistically significant.

Mean Cu.SP endpoint among controls was 118.80 +22.06ms, which was significantly

shorter as compared to that of CTS hands (P=0.003).However, this significance was lost when

age adjusted mean Cu.SP endpoints were compared (p=0.65).

43

78.0770.1

0

10

20

30

40

50

60

70

80

90

100

CTS Controls

Late

ncy

in m

s

64.6576.83 78.35 82.57 86.12

70.1

0

20

40

60

80

100

120

1 2 3 4 5 Control

Late

ncy

in m

s

Neurophysiological Grade

Cu.SP latency in different grades of CTS & controls

44

50.56 50.05

0

10

20

30

40

50

60

70

80

CTS Control I

Du

rati

on

in m

s

59.3551.13 47.88 53.55 56.62

50.05

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 Control

Du

rati

on

in m

s

Neurophysiological Grade

Cu.SP Duration in different grades of CTS & controls

45

127.61 118.8

0

20

40

60

80

100

120

140

160

CTS Control I

End

po

int

in m

s

124 127.93 124.15 136.12 142.65118.8

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5 Control

End

po

int

in m

s

Neurophysiological Grade

Cu.SP Endpoint in different grades of CTS & controls

46

Cu.SP traces elicited from a control. Individual traces (above) and superimposed traces.

47

Disease control group (Peripheral Neuropathy)

1 4 hands from 7 patients of peripheral neuropathy were analyzed. Mean Cu.SP latency

was 82.65 ms + 8.52ms which was significantly prolonged as compared to controls but not

significantly prolonged as compared to CTS group.

Category N Latency

p mean sd

CTS 81 78.07 12.34 <0.001

Controls 82 70.10 6.61

Disease

Controls 14 82.65 8.52

78.0770.1

82.65

0

10

20

30

40

50

60

70

80

90

100

CTS Controls Disease controls

Latency in ms

Comparison of mean Cu.SP latencies of different groups

Comparison Mean

difrerene se p

CTS and Disease Controls -4.5759 2.8329 .108

Controls and Disease Controls -12.5537* 2.8304 <0.001

48

Mean Cu.SP duration in the disease control group (49.69+7.09ms) was neither different from

that of the control nor the CTS group.

Category N Duration in ms

p mean sd

CTS 81 50.56 20.36 .980

Controls 82 50.05 20.15

Disease Controls 14 49.69 7.09

Comparison Mean

difference se p

CTS and Disease Controls .8698 5.6661 .878

Controls and Disease Controls .3606 5.6611 .949

50.56 50.05 49.69

0

10

20

30

40

50

60

70

80

CTS Controls Disease controls

Duration in ms

Comparison of mean Cu.SP Duration of different groups

49

Mean Cu.SP endpoint in the disease control group (132.11+12.25ms) was significantly

delayed as compared to Control group but was not statistically different from CTS group.

Category N End point in ms

p mean sd

CTS 81 127.61 15.00 .003

Control I 82 118.80 22.06

Control II 14 132.11 12.25

Comparison Mean difrerene se p

CTS and Control I 8.8148* 2.8943 .003

CTS and Control II -4.5007 5.3475 .401

Control I and Control II -13.3155* 5.3427 .014

127.61 118.8132.11

0

20

40

60

80

100

120

140

160

CTS Control Disease controls

End point in ms

Comparison of mean Cu.SP Endpoint of different groups

50

Discussion

The Cu.SP mean latency of patients with CTS was significantly prolonged in patients with

CTS as compared to that of controls. In addition, the prolonged mean latencies correlated with

the neurophysiological severity grading of CTS according to the Canterbury scale. There was

significant direct correlation between CuSP latencies and nerve conduction (CMAP distal

latency and SNAP latency) data. There was no correlation between latency and scores from

Boston questionnaire (SSS, PSS or FSS). Based on the proposed hypothesis that the Cu.SP

reflects the function of Aδ fibers, the prolongation of mean Cu.SP latencies might be related to

slowed conduction and dysfunction of the fastest-conducting fibers among the Aδ fibers40. This

observation is similar to those from previous studies26,40. Svilpauskaite et al40 in their study

involving forty CTS patients reported prolonged Cu.SP latencies in clinically severe CTS.

Similarly, Yong Seo Koo et al26 also reported prolonged distal latency in severe CTS group.

However, Aurora et al28, had observed that mean latency of CuSP in CTS group did not differ

significantly as compared to that of control group. Disparity in the results of this study might

have emerged because of methodological differences in eliciting the CuSP or incomplete

control of factors that plausibly affect CuSP, such as age, gender and height, as well as a fewer

number of subjects (n=19).This is important because age and gender has complex influence on

Cu.SP41, with age changes being more pronounced in males but not in females, especially when

younger than 35 years of age. In addition in our study and previous study by Yong Seo Koo et al

observed that age and height predicted Cu.SP latency.

51

We observed that Cu.SP latency of very mild group was prolonged than that of control

group, though it was not statistically significant. However, rest of all the severe grades of CTS

had Cu.SP latency which was significantly greater than the control group. Hence, Cu.SP latency

may not be sensitive enough to delineate very mild CTS grade from normal hands.

In our study, duration of Cu.SP was little longer in CTS group than that of control group,

though it was not statistically significant. However, duration in severe CTS was shorter as

compared to very mild CTS. The above finding indicate that as the number of normally

functional Aδ fibers decreases, the intensity of motor neuron inhibition decreases, thereby

decreasing the duration of Cu.SP. Shorter duration of Cu.SP in CTS group was also reported by

Yong Seo Koo et al26. On the contrary, Aurora et al28 reported increased Cu.SP duration in CTS

group and proposed that oversensitization of remaining polymodal C fibers as the mechanism

to explain their observation. Similar to the finding in study by Svilpauskaite et al40 , we observed

prolonged duration of Cu.SP in very mild and mild cases as compared to controls. This may be

secondary to following factors: (1) In order to attain maximal contraction of APB, thumb is

contracted against a resistance. In mild CTS groups, voluntary contraction of APB can be slightly

decreased because of decreased perception of the resistance applied to the thumb caused by

the dysfunctional sensory fibers. This might increase duration of Cu.SP. Two studies have shown

that CuSP duration increases as strength of contraction decreases.42,9 (2) Partial dysfunction of

median motor fibers compressed within the carpal tunnel (caused by axonotmesis or

neurapraxia) can also lead to reduction in the voluntary activity, and thereby increasing Cu.SP

duration.

52

The Endpoint of Cu.SP was found to be significantly delayed in CTS hands as compared

to that of controls. Given the positive correlation we found between endpoint and latency

(which is prolonged in CTS) and duration being similar in both the study groups, it is plausible

that endpoint may be prolonged as a function of latency in CTS cases. Leis AA et al7, studied

silent period produced by electrical stimulation of mixed peripheral nerves and reported that

endpoint of Cu.SP was determined by Cutaneous afferents. On the contrary, Yong Seo Koo et al

reported no difference in Cu.SP endpoints between study groups and suggested that endpoint

was not influenced by peripheral nerve lesions but a function of supraspinal control. This

discrepancy needs to be sorted out in future studies.

In addition as Cu.SP Endpoint increased, Cu.SP duration was expected to increase, as

both showed a positive correlation. However, though CuSP endpoint was significantly

prolonged in the CTS group as that of control group, duration was not significantly increased

nor decreased as we hypothesised. This finding would suggest that, after spinal motor neurons

gets inhibited by afferent volley of impulses from small nerve fibers, duration after which they

recover may depend on other influences on motor neurons like supraspinal mechanisms. This

was exemplified in a study by Serrao et al18 where Cu.SP duration was prolonged in Parkinson’s

disease patients in “off” state that decreased in “on” state following L-dopa treatment,

implicating supraspinal dopaminergic pathways influencing duration of Cu.SP. In another study

by Logigian et al43, reported decreased intensity of spinal motor inhibition in complete cervical

spinal cord injury patients as compared to normal suggesting the influence of supraspinal

mechanisms on Cu.SP.

53

Following table gives an overview of studies on Cu.SP in CTS.

Overview of studies of Cutaneous Silent Period in Carpal tunnel syndrome

Study

(CTS=n)

(controls=n)

Latency in ms

Duration in ms

Endpoint in ms

/

CTS

Control

P value

CTS

Control

P

value

CTS

Control

P

value

Aurora et.al28

1996 (CTS = 19)

(Controls=20)

NA

NA

NS

51.8

36.9

0.001

127.3

113.4

0.005

Svilpauskait et

al40

2006 (CTS = 40)

(Controls=40)

Mild

77.91+4.34

75.47+5.81

NS

Mild

55.1+8.4

43.19

<0.01

NA

NA

NA

Moderate

81.66+6.56

<0.01

Moderate

57.11+10.28

<0.01

NA

Severe

85.02+6.45

<0.01

Severe

39.74+8.68

NS

NA

Y. S. Koo et al26

2010 (CTS = 114)

(Controls=30)

72.4+16.1

64.6+13.4

0.014

58.9+21.4

65.1+15

0.133

129.7+16.2

131.3+17.6

0.519

Current study

2015 (CTS = 44)

(Controls=44)

78.07+12.35

70.1+6.61

<0.001

50.56+20.36

50.05+20.15

0.87

127.61+

118.8+22

0.003

NA – Not available, NS-Not significant

54

Cu.SP was absent in 4.71% of CTS hands (n=4/85) and none in the control group. All the

hands in which Cu.SP was absent were of very severe (n=3) or extremely severe (n=1) grade of

CTS, but none of the CTS hands with lower severity Cu.SP was absent. This in agreement with

our hypothesis that when all pain carrying fibers become dysfunctional as in hands of severe of

CTS, there will be no motor neuron inhibition and as a result Cu.SP will be absent. Similarly,

Cu.SP was absent in few of severe CTS hands in previous two studies28,40.

When we looked at the utility of the Cu.SP in assessing the severity of pain, we found

that there was no statistically significant correlation between Cu.SP parameters and clinical

questionnaires quantifying symptom and pain severity.Only functional severity score were

positively correlated with prolonged endpoint. Conceivably, more impaired the Cutaneous

sensations, more difficult it would be to fine tune the skilled hand movements, hence more

functional disability.In a previous study by Inghilleri et al who investigated changes in the Cu.SP

in healthy subjects following administration of opioids, observed that there were no changes in

Cu.SP parameters following administration of opiods, even though there was significant

decrease in painful sensation with electrical stimulation. These findings convey that the Cu.SP,

which reflects Aδ fiber function, may be not a dependable tool for assessing severity of pain.

One explanation may be because painful sensations from periphery are carried by both C fibres

and Aδ fibres and, C fibers being unmyelinated and smallest in diameter are least susceptible to

compression effects or are affected last44.

55

As a sub test, we looked at variables of Cu.SP in 7 cases (14 hands) of peripheral

neuropathy and observed that only latency was significantly prolonged as compared to

controls. This was similar to observations made by Yaman et al in diabetic peripheral

neuropathy, wherein Cu.SP latency was longer as compared to controls45. When compared to

CTS group none of the variables were significantly different.

To conclude, Cutaneous Silent Period is a simple, less cumbersome and easily performed

electrophysiological tool to evaluate patients with carpal tunnel syndrome especially of mild or

greater severity. This was similar to studies done in other painful conditions like Fabry’s disease,

where in there was no significant change in variables of Cu.SP in mild to moderate

cases24.There is a need to improve the methodology to improve the sensitivity of Cu.SP to

pickup even the subtle small fiber dysfunction.

56

CONCLUSION

1. Cutaneous silent period is a simple, non cumbersome and easily available test that can be

done with standard electromyography equipment.

2. Cu.SP latency was prolonged in Carpal tunnel syndrome especially of mild or greater

severity.

3. Cu.SP duration and endpoint changes are variable in CTS as they are also influenced not

only by peripheral but also by supraspinal mechanisms, which are yet to be clearly

delineated.

4. Cu.SP variables were not affected by symptom severity or duration of symptoms.

5. Age and height of the individuals affect variables of Cu.SP.

6. The utility of Cu.SP is to assess the integrity of peripheral nerves in severe peripheral

neuropathies, where Cu.SP can be elicited in spite of unexcitable peripheral nerves during

standard conduction studies.

57

SUMMARY

Cutaneous silent period is a temporary cessation of voluntary muscle activity following a

painful stimulus. It evaluates small nerve fibers which form the afferent arc of this nociceptive

reflex. Cutaneous silent period is abnormal in Carpal tunnel syndrome, which is characterized

by pain, in addition to paresthesias. It should be included in protocols evaluating the peripheral

nervous system disorders as a complimentary to standard nerve conduction studies which

reflect large fiber dysfunction.

Based on the observations in previous studies18,40,43 and current study the beginning of

the Cu.SP may be mostly influenced by small fibers in the peripheral nerves, while its duration

and endpoint may be regulated by both peripheral mechanisms and supraspinal mechanisms in

the central nervous system.

Cutaneous silent period needs to be studied in greater detail in other peripheral and

central nervous system disorders to understand the anatomic elements and physiological

principles sub serving it and various pathologies affecting it. Further studies are needed to see

how well it fares in comparison with skin biopsy in diagnosing small nerve fiber neuropathy. If

validated and standardized it will be an invaluable tool to alleviate the ‘pain’ in diagnosing

conditions with small fiber dysfunction.

58

LIMITATIONS OF THE STUDY

1. Small number of subjects in each subgroup of CTS segregated based on Canterbury

neurophysiological grading.

2. Intensity of APB contraction was gauged by auditory output from EMG machine, which

can have subjective bias.

59

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63

ANNEXURE i

Proforma of Thesis

1. Identification information

1.1 Serial number -------------------------

1.2 Hospital number -------------------------

1.3 Age --------------------------

1.4. Gender -------------------------

1.5.Height (in cm.) --------------------------

2. Details of Carpal tunnel syndrome

2.1.Right or Left hand.

2.2.Duration of symptoms

2.3.Boston Questionnaire

2.3.1. Symptom severity scale

The following questions refer to your symptoms for a typical 24 hour period during the past

two weeks (circle one answer to each question)

i. How severe is the hand or wrist pain that you have at night?

1. I do not have hand or wrist pain that you have at night

2. Mild pain

64

3. Moderate pain

4. Severe pain

5. Very severe pain

ii. How often did hand or wrist pain wake you up during a typical night in the past two

weeks?

1. Never

2. Once

3. Two or three times

4. Four or five times

5. More than five times.

iii. Do you typically have pain in your hand or wrist during daytime?

1. I never had pain during the day.

2. I have mild pain during the day.

3. I have moderate pain during the day.

4. I have severe pain during the day.

5. I have very severe pain during the day.

iv. How often do you have hand or wrist pain during the daytime?

1. Never

2. Once or twice a day

3. Three to five times a day

4. More than five times a day.

5. The pain is constant

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v. How long on average, does as episode of pain last during the daytime?

1. I never get pain during the day.

2. Less than 10 minutes

3. 10 to 60 minutes

4. Greater than 60 minutes

5. The pain is constant throughout the day.

vi. Do you have numbness (loss of sensation) in your hand?

1. No

2. I have mild numbness.

3. I have moderate numbness.

4. I have severe numbness.

5. I have very severe numbness.

vii. Do you have weakness in your hand or wrist?

1. No weakness

2. Mild weakness

3. Moderate weakness

4. Severe weakness

5. Very severe weakness

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viii. Do you have tingling sensations in your hand?

1. No tingling

2. Mild tingling

3. Moderate tingling

4. Severe tingling

5. Very severe tingling

ix. How severe is numbness (loss of sensation) or tingling at night?

1. I have no numbness or tingling at night.

2. Mild

3. Moderate

4. Severe

5. Very severe

x. How often did numbness or tingling sensation wake you up during a

typical night during the last two weeks?

1- Never

2- Once

3- Twice to three times

4- Four to five times

5- More than five times

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xi. Do you have difficulty with the grasping and use of small objects such as keys or pens?

1- No difficulty

2- Mild difficulty

3- Moderately difficulty

4- Severe difficulty

5- Very severe difficulty

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2.3.2..Functional status scale

On a typical day during the past two weeks have hand and wrist symptoms caused you to have

any difficulty doing the activities listed below? Please encircle one number that best describes

your ability to do the activity.

Activity No

difficulty

Mild

difficulty

Moderate

difficulty

Severe

difficulty

Cannot do at all due to hand or

wrist symptoms

Writing 1 2 3 4 5

Buttoning

of clothes

1 2 3 4 5

Holding a

book

while

reading

1

2

3

4

5

Gripping a

telephone

handle

1

2

3

4

5

Opening

of jars

1 2 3 4 5

Household

chores

1 2 3 4 5

Carrying

of grocery

bags

1

2

3

4

5

Bathing

and

dressing

1

2

3

4

5

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3.1.Neurophysiological grading of Carpal tunnel syndrome.

Severity

grade

Sensory

conduction

velocity

SNAP Motor

conduction

velocity

Motor

potential

amplitude

0 Normal No neurophysiological abnormality

1 Very mild Above tests are normal

Detected by sensitive tests (Internal comparision studies)

2 Mild Slowing Preserved Normal Preserved

3 Moderate Slowing Preserved >4.5 - <6.5ms Preserved

4 Severe Absent >4.5 - <6.5ms Preserved

5 Very severe Absent >6.5ms Preserved

6 Extremely

severe

Sensory and motor potentials effectively unrecordable (surface

motor potential from APB <0.2mV amplitude)

3.2.Cutaneous silent period

1. Elicitable

a. Yes

b. No

2. If Yes

a. Latency

b. Duration

c. Endpoint

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