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Diagnosing Carpal Tunnel Syndrome

Sensitivity of ultrasonography versus nerve conduction study and their necessity

A.W.F. Grift s1973428 10 March 2016 Plastic Surgery, Isala Zwolle Supervisor: Dr. P. Houpt, Plastic Surgeon

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Contents List of abbreviations ......................................................................................................................... 5

Abstract ............................................................................................................................................ 6

Samenvatting .................................................................................................................................... 7

1. Introduction .................................................................................................................................. 8

1.1 Carpal Tunnel Syndrome ........................................................................................................ 8

1.2 Pathophysiology ...................................................................................................................... 8

1.3 Etiology ................................................................................................................................... 8

1.4 Prevalence ............................................................................................................................... 9

1.5 Anatomy .................................................................................................................................. 9

1.6 Clinical Symptoms & Signs .................................................................................................. 10

1.7 Treatment .............................................................................................................................. 11

1.7.1 Conservative treatment ................................................................................................... 11

1.7.2 Surgery ........................................................................................................................... 11

1.8 Diagnosing CTS .................................................................................................................... 11

1.9 Electrodiagnostic studies ...................................................................................................... 12

1.9.1 Nerve conduction studies ............................................................................................... 12

1.9.2 Electromyography .......................................................................................................... 16

1.9.3 Electrodiagnostic studies values and limitations ......................................................... 16

1.9.4 Costs of electrodiagnostic studies .................................................................................. 16

1.10 Ultrasonography .................................................................................................................. 16

1.10.1 Ultrasonography values and limitations .................................................................... 17

1.10.2 Costs of ultrasonography .............................................................................................. 17

1.11 Aim of this study ................................................................................................................. 17

1.12 Hypothesis ........................................................................................................................... 17

2. Materials & Method ................................................................................................................... 18

2.1 Study design .......................................................................................................................... 18

2.2 Inclusion criteria ................................................................................................................... 18

2.3 Exclusion criteria .................................................................................................................. 18

2.4 Further analysis ..................................................................................................................... 18

2.5 Interventions ......................................................................................................................... 20

2.5.1 Ultrasonography ............................................................................................................. 20

2.5.2 Nerve Conduction Study ................................................................................................ 20

2.5.3 Surgery: Carpal Tunnel Release ..................................................................................... 21

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2.6 Cut-off points measurements ................................................................................................ 21

2.7 Analysis of data ..................................................................................................................... 22

2.8 Typical or atypical CTS ........................................................................................................ 22

2.9 Surgery outcome ................................................................................................................... 22

2.10 Study outcomes ................................................................................................................... 22

3. Results ........................................................................................................................................ 23

3.1 Patient characteristics in the overall CTS group ................................................................... 23

3.2 Patient characteristics in the typical and atypical CTS group ............................................... 23

3.3 Incidence of symptoms and signs in the overall CTS group................................................. 24

3.4 Incidence of symptoms and signs in the typical and atypical CTS group ............................ 24

3.5 Primary study outcome ......................................................................................................... 24

3.5.1 Ultrasonography ............................................................................................................. 24

3.5.2 Nerve conduction study .24

3.5.3 Ultrasonography and nerve conduction study outcomes combined ............................... 25

3.5.4 Ultrasonography and nerve conduction study, differences in outcomes ........................ 25

3.6 Secondary study outcome ..................................................................................................... 26

3.7 Surgery outcome ................................................................................................................... 26

4. Discussion .................................................................................................................................. 27

4.1 Mean results .......................................................................................................................... 27

4.1.1 Hypothesis ...................................................................................................................... 27

4.2 Other results .......................................................................................................................... 27

4.2.1 Differences between groups ........................................................................................... 27

4.2.2 Combined outcome US and NCS ................................................................................... 27

4.2.3 Surgery outcome ............................................................................................................ 27

4.2.4 Costs ............................................................................................................................... 28

4.4 Strengths of this study ........................................................................................................... 29

4.5 Limitations of this study ....................................................................................................... 29

4.6 Recommended future study design ....................................................................................... 30

4.7 Further recommendations ..................................................................................................... 31

5. Conclusion .................................................................................................................................. 32

6. Bibliography ............................................................................................................................... 33

7. Appendix .................................................................................................................................... 38

7.1 CTS-6 (Six-item CTS symptom scale) form......................................................................... 38

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List of abbreviations

AAEM = American Association of Electrodiagnostic Medicine

AAN = American Academy of Neurology

AAOS = American Academy of Orthopedic Surgeons

AAPM&R = American Academy of Physical Medicine and Rehabilitation

CSA = cross-sectional area

CTR = carpal tunnel release

CTS = carpal tunnel syndrome

CTS-6 = Six-item Carpal Tunnel Syndrome Symptom Scale

ECTR = endoscopic carpal tunnel release

EMG = electromyography

MNCV = motor nerve conduction velocity

NCS = nerve conduction study

NIH = National Institute of Health

OCTR = open carpal tunnel release

SNCV = sensory nerve conduction velocity

SSCT = subsynovial connective tissue

US = ultrasonography

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Abstract

Introduction. Carpal Tunnel Syndrome (CTS) is the most common nerve entrapment of the

upper extremity and results from an entrapment of the median nerve beneath the flexor

retinaculum at the wrist. The prevalence of CTS is high (5% to 15%) among the general

population, with women five times more affected than men. Symptoms of CTS are pain, tingling

in the median nerve distribution area of the hand, numbness, weakness, nocturnal paresthesia,

hypotrophy and/or paresis of the thenar musculature, dropping items due to loss of sensory and/or

motor function, and/or decreased sweat function. There is no golden standard for diagnosing

CTS. Nerve conduction study (NCS) and ultrasonography (US) are the most used examinations

for confirming clinical CTS. Although NCS is frequently used to diagnose CTS, the rate of false-

negatives can be as high as 10% to 34%. Also, NCS is time consuming and uncomfortable for

patients. In order to determine whether the diagnosis CTS could be made by US only so NCS

would be unnecessary, the aim of this study is to examine the sensitivity of US and NCS of the

median nerve related to the clinical symptoms in diagnosing CTS.

Methods. In this retrospective study, a database with patients with clinical CTS was used.

Clinical symptoms, US outcomes and NCS outcomes were retrieved from medical records. The

outcomes of US and NCS were analyzed in three groups: an overall CTS group, a typical CTS

group and an atypical CTS group. The primary study outcomes were the outcomes of US and

NCS in these groups. The secondary study outcome was the sensitivity of US and NCS in

patients with clinical CTS.

Results. A total of 92 wrists from 57 patients were analyzed (67 (72,8%) wrists of women): 54

(57,7%) wrists in the typical CTS group and 38 (42,3%) wrists in the atypical CTS group. US

was positive in 73,9%, 72,2% and 76,3% of the overall group, the typical CTS group and the

atypical CTS group, respectively. NCS was positive in 81,5%, 79,6% and 84,2% in the overall

group, the typical CTS group and the atypical CTS group, respectively. The sensitivity of US and

NCS in the overall group was 73,9% and 81,5%, respectively (p 0,204). In the typical CTS group,

the sensitivity for US and NCS was 72,2% and 79,6%, respectively (p 0,289). In the atypical CTS

group, the sensitivity for US and NCS was 76,3% and 84,2%, respectively (p 0,238).

Conclusion. This study showed that the sensitivity of US is comparable with the sensitivity of

NCS in the overall CTS group, the typical CTS group and atypical CTS group. Although there

was no significant difference between US and NCS, US could be preferred as first examination to

confirm the diagnosis CTS, because this examination is less uncomfortable for patients in

comparison with NCS. Further prospective and blinded studies are needed to confirm these

outcomes.

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Samenvatting

Introductie. Het Carpale Tunnel Syndroom (CTS) is de meest voorkomende zenuwbeklemming

van de bovenste extremiteit en ontstaat door een beklemming van de nervus medianus onder het

flexor retinaculum in de pols. De prevalentie van CTS is hoog onder de algemene bevolking (5-

15%), waarbij vrouwen vijf keer vaker zijn aangedaan dan mannen. Symptomen van CTS zijn

pijn, tintelingen in het gebied van de nervus medianus, doofheid, zwakte, nachtelijke pijn,

hypotrofie en/of parese van de thenar musculatuur, het laten vallen van objecten door verlies van

sensorische en/of motore functie, en/of verminderde zweet productie. Er is geen Gouden

Standaard voor het diagnosticeren van CTS. Zenuwgeleidingsonderzoek en echografie zijn de

meest gebruikte onderzoeken om klinisch CTS te bevestigen. Hoewel zenuwgeleidingsonderzoek

vaak gebruikt wordt om CTS te diagnosticeren, is het percentage vals-negatieven 10-34%.

Daarnaast kost het zenuwgeleidingsonderzoek veel tijd en is het oncomfortabel voor patinten.

Om vast te stellen of de diagnose CTS gesteld kan worden met alleen echografie en om vast te

stellen of zenuwgeleidingsonderzoek overbodig zou zijn, is het doel van deze studie om de

sensitiviteit van echografie en zenuwgeleidingsonderzoek van de nervus medianus te bepalen ten

opzichte van de klinische diagnose CTS.

Methode. In deze retrospectieve studie werd gebruik gemaakt van een database met patinten

met klinisch gediagnosticeerd CTS. De klinische symptomen, echografie uitslagen en

zenuwgeleidingsonderzoek uitslagen werden verzameld uit de medische dossiers. De uitkomsten

van de onderzoeken werden geanalyseerd in drie groepen: een totale groep, de groep met typisch

CTS en de groep met atypisch CTS. De primaire studie uitkomsten waren de uitkomsten van

echografie en zenuwgeleidingsonderzoek in deze drie groepen. De secundaire studie uitkomst

was de sensitiviteit van echografie en zenuwgeleidingsonderzoek.

Resultaten. In totaal werden 92 polsen van 57 patinten geanalyseerd (67 (72,8%) polsen van

vrouwen): 54 (57,7%) polsen behoorden in de typisch CTS groep en 38 (42,3%) polsen in de

atypische groep. Echografie was positief in respectievelijk 73,9%, 72,2% and 76,3% van de totale

groep, de typisch CTS groep en de atypisch CTS groep. Het zenuwgeleidingsonderzoek was

positief in respectievelijk 81,5%, 79,6% en 84,2% van de totale groep, de typisch CTS groep en

de atypisch CTS groep. De sensitiviteit van echografie en zenuwgeleidingsonderzoek in de totale

groep was respectievelijk 73,9% en 81,5% (p 0,204). In de typisch CTS groep was dit

respectievelijk 72,2% en 79,6% (p 0,289) en in de atypisch CTS groep was dit 76,3% en 84,2%

(p 0,238).

Conclusie. Deze studie toont aan dat de sensitiviteit van echografie vergelijkbaar is met die van

het zenuwgeleidingsonderzoek in zowel de totale, de typische, als de atypische CTS groep.

Hoewel er geen significant verschil is in de sensitiviteit van echografie en het

zenuwgeleidingsonderzoek, zou echografie het onderzoek van eerste keus kunnen zijn om de

diagnose te bevestigen bij patienten met klinische CTS, omdat echografie minder oncomfortabel

en belastend is voor patienten ten opzichte van het zenwgeleidingsonderzoek. Verder prospectief

en geblindeerd onderzoek is nodig om deze uitkomsten te bevestigen.

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1. Introduction

1.1 Carpal Tunnel Syndrome

Carpal Tunnel Syndrome (CTS) is the most common nerve entrapment of the upper extremity

and results from an entrapment of the median nerve beneath the flexor retinaculum at the

wrist(1). The American Academy of Orthopedic Surgeons (AAOS) defines CTS as a

symptomatic compression neuropathy of the median nerve at the level of the wrist(2).

A similar description of CTS was first given by Paget (1814-1899). Paget described the

compression of the median nerve after a fracture of the distal radius(3). Marie and Foix reported a

lesion of the median nerve with a neuroma, next to the flexor retinaculum, in 1913(4). Finally,

Phalen was the first to describe the current principles of CTS in 1950: numbness and tingling in

the first, second, third, and fourth finger, which is worse at night and after using the hand(s)(5).

Phalen also found that most of the time a positive Tinel sign (see section 1.6) over the median

nerve at the wrist and flexion of the wrists worsens the symptoms(5). The latter is now called

Phalens sign.

1.2 Pathophysiology The exact pathophysiology of CTS is unknown, but the cause of idiopathic CTS is suggested to

be due to compression of the median nerve(6). This compression may lead to alterations of the

morphological structure of the nerve and demyelination, which is due to mechanical stress

deforming the myelin sheath(7). Paresthesia experienced by patients during the night could be the

cause of a decreased blood flow in the microcirculation and, due to the decreased circulation, the

ischemia that occurs(4,7). Additionally, it is suggested that fibrosis, thickening of the synovium,

new axonal growth, endoneurial edema and remyelination contributes to compression(8). The

edema could result from the increase of pressure in the carpal tunnel(4). When the pressure

increases more than 40-50 mmHg, the intraneural microcirculation is diminished, which causes

venous stasis with edema. Furthermore the axonal transport decreases, which could contribute to

the development of CTS, since the lack of nutrients could degrade the median nerve(4).

Microtear hypothesis

The microtear hypothesis, described by Werthel et al.(9) in 2014, suggests that CTS starts with a

tear in the surrounding Subsynovial Connective Tissue (SSCT). Repetitive movements of the

wrist, the hand or the fingers can lead to idiopathic CTS, probably due to the alterations of the

SSCT. With flexion, the pressure in de carpal tunnel increases and the forces on the SSCT

increase. A tiny tear could originate in the SSCT. With this tear the cascade of the woundhealing

process starts, causing inflammation and fibrosis, which provides thickening of the structures in

the carpal tunnel and in that way an increase in pressure in the carpal tunnel. This causes the

entrapment of the median nerve, which can lead to problems like ischemia, edema and

remyelination. Werthels hypothesis is that these problems cause CTS.

1.3 Etiology

Many factors may contribute to the development of CTS, including rheumatological diseases,

acromegaly, myxedema, bursal fibrotic alterations or pregnancy. Other contributing factors

mentioned in literature are abnormalities of the carpal tunnel, such as dislocation or subluxation

of the carpal bones, fractures of the distal radius and arthritis. Also inflammatory alterations,

tenosynovitis, lipomas, neuromas, cysts and hematomas may contribute(4,7,8). Furthermore,

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manual activities may contribute to the development of CTS(7), but the major part (65-80%) of

CTS is idiopathic(4).

1.4 Prevalence

The prevalence of CTS is high, ranging from 5% to 15% among the general population with

women five times more affected than man. In The Netherlands the prevalence is 9% among

women and only 0,6% among men(10). The majority of patients (80%) is older than 40

years(7,11). The National Institute of Health (NIH) suggests that the carpal tunnel in women may

be smaller than in men, which could be the cause of the higher amount of woman that is

affected(12).

1.5 Anatomy

The carpal tunnel has a complicated anatomy with many different structures. On the dorsal,

medial and lateral sides it is limited by the carpal bones. On the palmar side the flexor

retinaculum (transverse carpal ligament) limits the carpal tunnel. The carpal tunnel contains nine

flexor tendons (four flexor digitorum profundus tendons, four flexor digitorum superficialis

tendons and the flexor pollicis longus tendon) and the median nerve, all of which are surrounded

by subsynovial connective tissue(9)(fig. 1).

Fig. 1. Anatomy of the carpal tunnel with the nine tendons, the median nerve and the flexor

retinaculum.

The median nerve passes the carpal tunnel beneath the flexor retinaculum and then continues into

two branches. The first branch, the palmar digital nerve, is responsible for the sensory innervation

of the palmar skin of the first, second, third and the lateral side of the fourth digit. The palmar

digital nerve is also responsible for the sensory innervation of the dorsal nail beds of these digits

(fig. 2). Besides the sensory innervation, this branch also provides the motor innervation to the

lateral two lumbrical muscles. These muscles are responsible for the flexion of the

metacarpophalangeal joints of the second and third digit. The second branch of the median nerve

is the so-called recurrent branch. This branch innervates two of the four the thenar muscles: the

abductor pollicis brevis muscle and the opponens pollicis muscle, which are associated with

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abduction and opposition of the thumb. The third thenar muscle, the flexor pollicis brevis muscle,

is partly innervated by the median nerve, but also by the ulnar nerve. The fourth thenar muscle,

the adductor pollicis muscle, is innervated by a branch of the ulnar nerve only.

Fig. 2. Median nerve distribution area of the hand. Left: palmar side of the hand. Right: dorsal

side of the hand. In blue, the area in which the median nerve supplies the sensory innervations

(13).

1.6 Clinical Symptoms & Signs

Patients with CTS can experience pain, tingling in the median nerve distribution of the hand,

numbness and weakness. Also nocturnal paresthesia, hypotrophy of the thenar musculature,

dropping items due to loss of sensory and/or motor function, and/or decreased sweat function

have been described(8,14,15). When patients with suspicion of CTS are examined, several signs

suggest the diagnosis CTS. One of these is a positive Tinels test. This test is positive when

tapping on the palmar side of the wrist gives paresthesia in the median nerve distribution of the

hand (fig. 3). The sensitivity of Tinels test is 26% to 79% and its specificity is 40% to 100%(4).

Another examination is Phalens test, which is positive when flexion of the wrists gives

paresthesia in the median nerve distribution of the hand (fig. 4). The sensitivity and specificity of

this test are 67% to 83% and 47% to 100%, respectively(4).

Fig. 3. Tinels test is positive when

tapping on the palmar site of the wrist

gives paresthesia in the median nerve

distribution area of the hand.

Fig. 4. Phalens test is positive when

flexion of the wrists gives paresthesia

in the median nerve distribution area

of the hand.

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1.7 Treatment The treatments of CTS can be divided in two groups: conservative treatment and surgical

treatment.

1.7.1 Conservative treatment

The conservative treatment of CTS consists for example of rest, exercise, splinting of the wrist in

neutral position, injection with corticosteroids, medication (e.g. NSAIDs or vitamin B6), or

education about e.g. positioning the wrists(16-18). In general, conservative treatments have a

worse outcome(17,19): more than 50% of the patients who received a conservative treatment,

eventually received surgery(17).

1.7.2 Surgery

Carpal Tunnel Release (CTR) is a surgery in which the flexor retinaculum (transverse carpal

ligament) is released(19). Recent studies have found no difference in outcome when performing

an Open Carpal Tunnel Release (OCTR) or an Endoscopic Carpal Tunnel Release (ECTR)(20-

22). The symptom improvement within three months (short term) and after three months (long

term) is not significantly different between both surgeries(20,21). One of the advantages of

OCTR is that the anatomical structures can be seen properly(20). Furthermore, ECTR seems to

give more nerve problems, but only temporary (e.g. numbness, neurapraxia, parasthesia)(20). On

the other hand, OCTR seems to give more wound problems (e.g. infection, scar tenderness or

hypertrophic scarring)(21). Overall, Gerritsen et al.(20) recommend to perform an OCTR.

Although the outcome of OCTR is equal to ECTR, OCTR is technically less hard to perform,

which lowers the risks of complications(20). After CTR, 88% had a significant improvement of

the symptoms and 79% of the patients had improvement of function(23).

1.8 Diagnosing CTS

Finding the best way to diagnose CTS has been subject of many studies, but there is no consensus

in these studies. Some studies suggest to diagnose CTS based on the clinical symptoms with an

electrodiagnostic study alone(7,11,24,25). Some studies suggest to diagnose CTS based on the

clinical symptoms in combination with ultrasonography(1,26-29). Other studies suggest to

diagnose CTS based on clinical symptoms with a combination of an electrodiagnostic study and

ultrasonography(14,30-32). Beside this, some studies suggest to diagnose CTS based on clinical

symptoms alone(33). Furthermore, it is described that the diagnosis CTS could be made only

post-operative, when the patient experience no more symptoms.

In the hospital this research is conducted, Isala in Zwolle, The Netherlands, the diagnosis for CTS

is made by clinical symptoms in combination with an electrodiagnostic study: Nerve Conduction

Study (NCS). When the NCS is negative for CTS, additionally ultrasonography (US) is carried

out.

1.8.1 Gold standard There is no gold standard for diagnosing CTS. However, the electrodiagnostic studies have a

sensitivity of 49% to 84% and a specificity of at least 94%(7,8). Because of this high sensitivity

and specificity percentages, these examinations in combination with clinical symptoms and signs

(section 1.6) are considered to be the best for CTS diagnosis in most hospitals(6,8,14,34). The

CBO-guideline, a guideline from the Dutch institute of healthcare quality, advises to confirm the

clinical diagnosis of CTS with NCS(35). This guideline states that US should be carried out only

if desired, in order to determine structural abnormalities.

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1.9 Electrodiagnostic studies

Electrodiagnostic studies are techniques that can trace abnormalities of the median nerve fibers

within the carpal tunnel(36). By comparing the median nerve responses with other healthy

nerves, abnormalities of the median nerve are documented. Several studies proved that

comparison of sensory nerve responses are more useful than the absolute median nerve latency

time(36,37). The reason for this is the larger proportion of large myelinated fibers in the sensory

fibers. These large fibers require more energy and thus are more prone to ischemic damage(38).

Damage of the myelin and ischemia could result from the compression of the median nerve

which is present in CTS. This results in a reduced conduction velocity, because damaged myelin

causes a decrease in axonal conduction.

The greatest accuracy to confirm the clinical diagnosis of CTS with electrodiagnostic studies is

by comparing the median nerve sensory latency to the radial and/or ulnar nerve sensory latency.

The comparison with a segment of the median nerve outside the carpal tunnel can also contribute

to diagnosing CTS(36).

The electrodiagnostic study used most for diagnosing CTS is the nerve conduction study, but

when this examination does not confirm CTS, an electromyography may be carried out as

well(2,37,39).

1.9.1 Nerve conduction studies Nerve Conduction Studies (NCS) are performed with electrodes, which are placed on the skin.

With electrical signals the nerves are stimulated and the electrical activity is measured. The

electrodes measure the nerve conduction latency time. The value of the nerve conduction latency

time is compared with the cut-off point, which is defined differently at each hospital. If the nerve

conduction latency time is lower than the cut-off point, the diagnosis CTS is set.

There are several options to measure the nerve conduction latency time. The American

Association of Electrodiagnostic Medicine (AAEM), the American Academy of Neurology

(AAN) and the American Academy of Physical Medicine and Rehabilitation (AAPM&R) have

formulated recommendations to confirm a clinical diagnosis of CTS with the assistance of

electrodiagnostic studies(39) (table 1).

With NCS the sensory latency time, the Sensory Nerve Conduction Velocity (SNCV) and the

motor latency time are measured. These variables can say something about the rate of conduction

of the sensory or motor nerve. The diagnosis CTS is suggested when the latency time of the

median nerve is decreased compared with other, healthy, nerves. The decreased latency time

suggests that the conduction is decreased and this could be caused by CTS.

The recommendations from the American institutions in table 1, are comparable with the Dutch

guideline for diagnosing CTS(35). The Dutch guideline recommends measuring the latency time

of the sensory action potential of the median nerve, the latency time of the sensory action

potential of the median nerve compared with the ulnar nerve and the SNCV of the median nerve

across the wrist/palm segment. These three measurements are comparable with the measurements

mentioned in table 1; number 1, 2a, 2b and 2c.

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Fig. 5. The sensory latency time of the median

nerve can be measured across the wrist and a

digit, with a conduction distance of 13-14 cm.

The electrode is usually placed on the second or

third finger. If the sensory latency time is

abnormal, it should be compared with another

nerve at the same limb, for example the ulnar

nerve(37).

SNCV: sensory nerve conduction velocity; MNCV: motor nerve conduction velocity; EMG:

electromyography. Further explanation: see next pages.

Firstly, the sensory latency time of the median nerve can be measured across the wrist and a digit,

with a conduction distance of 13-14 cm (fig. 5). If the sensory latency time is abnormal, it should

be compared with the ulnar or radial nerve in the same limb (fig. 5). This comparison is needed

because a difference has to be proved.

If the initial median nerve sensory latency time is normal, three options are left to examine to

determine if the median nerve is abnormal compared to other nerves.

Table 1. Recommendations of the AAEM, AAN and AAPM&R to diagnose CTS

with assistance of electrodiagnostic studies

1. Median nerve sensory latency time across the wrist and a digit with a long distance

of 13-14cm;

2. If the measurement mentioned at number 1) is normal:

a. Median nerve sensory latency time across the wrist and the palm with a short

distance of 7-8 cm, compared with the ulnar sensory latency time;

b. Median nerve sensory latency time across the wrist, compared with the ulnar

sensory latency time (at fourth digit) and/or the radial sensory latency time (at the

first digit);

c. Median nerve SNCV across the wrist/palm segment compared with the

segment of the forearm/digit;

3. Motor latency time of the median nerve, innervating the thenar muscle;

4. Motor latency time of the median nerve, innervating the lumbrical muscles, and the

ulnar nerve, innervating the interossei muscles;

5. EMG, including thenar muscle innervated by the median nerve.

14

Firstly, the median nerve sensory latency time

across the wrist over a short conduction distance

(7-8 cm) can be compared with the ulnar

sensory latency time(fig. 6). If the median nerve

latency time is decreased compared to the ulnar

nerve, this measurement is abnormal.

Secondly, the median nerve sensory latency time across the wrist can be compared with the radial

sensory latency time (segment between the wrist and the thumb) (fig. 7) or with the ulnar sensory

latency time (segment between the wrist and the fourth digit) (fig. 8). This measurement of the

ulnar sensory latency time differs from the first option, because it is the latency time over a

longer segment.

Again, if the latency time of the median nerve is decreased compared to the latency time of the

radial and/or ulnar nerve, this measurement is abnormal.

Fig.7. The median nerve sensory latency time

across the wrist can be compared with the radial

sensory latency time at the segment between the

wrist and the thumb(37).

Fig. 8. The median nerve sensory latency time

across the wrist can be compared with the

ulnar sensory latency time at the segment

between the wrist and the fourth digit(37).

Fig. 6. The median nerve sensory latency time can

be compared with the ulnar nerve sensory latency

time across the wrist over a short conduction

distance of 7-8 cm(37).

15

Fig. 11. The motor latency time of the median nerve, innervating the second lumbrical mucles, and the

motor latency time of the ulnar nerve, innervating the

second interossei can be measured (37).

Thirdly, the median nerve SNCV of the wrist and palm segments can be compared with the

segments of the forearm and a digit (fig. 9). The wrist segment goes through the carpal tunnel and

the palm segment does not. In this way the two segments can be compared to determine the

difference between passing and not passing the carpal tunnel.

Also, the motor latency time of the median nerve can be measured at the thenar muscle (fig. 10).

The median nerve partly innervates the thenar muscles, so a decrease in motor latency time

indicates an abnormality of the median nerve. The ulnar nerve innervates the other parts of the

thenar muscles, so the latency times can be compared. Also now, the measurement is abnormal if

the latency time of the median nerve is decreased compared to the latency time of the ulnar nerve.

Furthermore, the motor latency time of the median

nerve, innervating the second lumbrical muscles, and

the motor latency time of the ulnar nerve,

innervating the second interossei can be measured

(fig. 11). A difference between these two

measurements indicates a difference between the

median and ulnar nerve.

At last, if the diagnosis CTS is unclear after these

measurements, a needle electromyography can be

done of the thenar muscle which is innervated by the

median nerve.

Fig. 9. The median nerve SNCV of the wrist

and palm segments can be compared with the

segments of the forearm and a digit(37).

Fig. 10. The MNCV of the median nerve can be

measured at the thenar muscle(37).

16

1.9.2 Electromyography

Electromyography (EMG) can be used in combination with NCS, when NCS does not confirm

the diagnosis CTS(39). With EMG, the electrical activity in the muscles is measured. Needles are

placed into the muscles and register the electrical activity of the muscles in relaxed or tensed

position(40). A healthy muscle in relaxed position does not show electrical activity. When the

patient tenses the muscles, electrical activity will occur. In severe CTS, the innervation of the

muscles can be decreased, causing a decrease of electrical activity during attempts to activate the

muscle. In the resting state there will be abnormal electrical activity.

This examination is carried out rarely in the hospital this study is conducted, because it is an

invasive examination.

1.9.3 Electrodiagnostic studies values and limitations

Electrodiagnostic studies have a sensitivity of 56-85% and a specificity of 94% or higher(31).

Becker et al.(41) suggest that electrodiagnostic studies could contribute to the decision to operate,

because they could determine the severity of CTS. In case of patients with more severe CTS, the

decision to operate could be made earlier.

Although electrodiagnostic studies are frequently used to diagnose CTS, the rate of false-

negatives can be as high as 10% to 34%(6,8,14,42). Also, electrodiagnostic studies are time

consuming, uncomfortable for patients and it is sometimes an invasive procedure, when using

EMG(14,26,42). Furthermore, electrodiagnostic studies cannot assess the anatomy of the carpal

tunnel with the median nerve in it, so abnormal anatomy cannot be seen(26). One of the factors

that can affect the outcome of electrodiagnostic studies is skin temperature(4). When the skin

temperature is below 30 degrees Celsius, the nerve conduction velocity can decrease, which can

be interpreted as a false positive outcome(15).

1.9.4 Costs of electrodiagnostic studies The costs of all electrodiagnostic studies differ at each centre. In Isala in Zwolle, the Netherlands,

where this study is conducted, the costs of NCS are 340,- in the year 2015(43). The price

depends on the extent of the examination.

1.10 Ultrasonography

Several recent studies have described ultrasonography (US) as a useful tool in diagnosing

CTS(7,14,26). It has a sensitivity of 44% to 95% and a specificity of 57% to 100%(8). US is used

to measure the Cross-Sectional Area (CSA) of the median nerve in the wrist. Several studies

suggest that an increase of the CSA of the median nerve can diagnose CTS(1,15,26-29,44-46).

The hypothesis is that in CTS, the CSA of the median nerve increases because of e.g. the edema,

as mentioned in section 1.2.

There is no consensus about the cut-off point above which the diagnosis CTS could be made. The

values differ between 6,0 mm2 to 16,0mm

2(11). The most used cut-off point is around 10,0

mm2(11).

Also the location where to measure in the wrist to determine the CSA is unclear. Some studies

suggest that the carpal-inlet (at the level of the pisiform) is the best location

(6,8,14,28,29,32,42,46). Another study suggests that the carpal-outlet is the best location to

measure(1).

17

1.10.1 Ultrasonography values and limitations US at the wrist provides more insight into the cause of the symptoms as it can assess structural

abnormalities(7,26), such as space-occupying lesions, malalignment of the carpal bones,

tenosynovitis, ganglia, tumors or changes in the vascularization(8,32). Furthermore, it is simple,

pain-free, quickly and non-invasive(7,8,15). Beside this, recent studies suggest that also US could

determine the severity of CTS(31,47).

The biggest limitation of US is that this examination is observer-dependent(7,8).

1.10.2 Costs of ultrasonography The costs of all US examinations differ at each centre. In Isala in Zwolle, the Netherlands, where

this study is conducted, the costs of US are 412,- in the year 2015(43). The price depends on the

extent and duration of the examination.

1.11 Aim of this study

Because no consensus exists about the best way to diagnose CTS, probably a lot of unnecessary

examinations are conducted. This could be unpleasant and aggravating for patients and is not

cost-effective. In order to ascertain that the diagnosis CTS could be made by one test, the aim of

this study is to examine the sensitivity of US and NCS of the median nerve related to the clinical

symptoms in diagnosing CTS. Secondly, this study attempts to determine whether US alone can

be enough to diagnose CTS in patients with typical CTS symptoms.

1.12 Hypothesis

The first hypothesis is that US and NCS have a comparable sensitivity. The second hypothesis is

that in patients with clinical CTS, US could be enough to diagnose CTS and NCS would be

unnecessary.

18

2. Materials & Method

To determine whether US has a higher sensitivity than NCS and to determine whether US alone

can be enough to confirm the diagnosis in patients with clinical CTS, we studied 92 wrists in a

retrospective study.

2.1 Study design

For this study we used a database that was recorded in the period of December 2012 until

November 2015 in Isala in Zwolle, the Netherlands. The database consisted of 607 patients with

clinical CTS who are planned for CTR. Patients could be added twice to the database, if they

were planned for CTR on both hands. They were identified by patient number and left of

right. The patient characteristics were added to the database. All patients were seen before

surgery by a nurse who inquired about all the clinical symptoms.

2.2 Inclusion criteria

The inclusion criteria were: 1) 18 years of age; 2) underwent both US and NCS of the median

nerve; 3) both US and NCS outcome of the median nerve were known; 4) symptoms were noted.

2.3 Exclusion criteria

The exclusion criteria were: 1) previous CTS surgery on the same side; 2) wrist fracture/trauma

in history; 3) polyneuropathy; 4) diabetes mellitus; 5) cervical neuropathy; 6) pregnancy.

These exclusion criteria were used because of the probable influence of these disorders on the

development of CTS, as mentioned in section 1.3, or because the disorder could cause the same

symptoms, as in cervical neuropathy.

2.4 Further analysis

A total of 126 wrists met the inclusion criteria, however, 34 wrists were excluded; 16 because of

previous CTS surgery, 2 because of wrist fracture or trauma in history, 1 because of

polyneuropathy and 15 because of diabetes mellitus. A total of 92 wrists from 57 patients

remained (fig. 12). For these wrists, the outcomes of the US and NCS were retrieved from the

medical record and added to the database. Also the surgery outcome was added to the database.

The following variables were added:

Ultrasonography:

Cross-sectional area (CSA) of the median nerve in the carpal tunnel (in mm2). Nerve conduction study:

Sensory latency time: latency difference between the median nerve and the ulnar nerve and between the median nerve and the radial nerve (in milliseconds);

The speed difference between the sensory conduction of the median nerve in the palm of the hand and the conduction of the median nerve in the wrist (SNCV) (in meter/second);

Motor latency time: latency difference between the median nerve and the ulnar nerve (in milliseconds).

Surgery outcome:

Positive (patient was satisfied and experienced no more symptoms post-operative) or negative (patient was dissatisfied and experienced still symptoms post-operative).

After completing the database, the database was exported to SPSS for analysis.

19

Fig. 12: Flow diagram

Power analysis

A prior power analysis was made with a power of 80%, an alfa-error of 5% and a clinical relevant

difference of 10%. In literature the sensitivity of NCS variables from 50 to 80%(7,8), so the mean

sensitivity was set on 65%. With a clinical relevant difference of 10%, the sensitivity of US

should be 75%.

The following formula for calculating a sample size with percentages(48) was used to calculate

the number of patients that is needed:

n1 = n2 = ((z+z)2 x (1 p) x 2) / (p1-p2)

2

z = alfa error (5%)

z = power (0,84 in case of a power of 80%)

p = mean sensitivity of NCS from literature (65%)(7,8)

p1 = percentage of sensitivity of NCS (75%)

p2 = percentage of sensitivity of US (65%)

This formula shows that the number of patients needed in each group was 367 patients, thus 714

patients for this study.

Because the expectation is that including so many patients in this study will not be realistic, the

intention is to include at least 90 patients from the database. With that amount of patients, a

significant difference between the sensitivity of NCS and US could not be determined, but

probably a trend could be seen in the outcomes of this study.

Wrists diagnosed with clinical CTS,

planned for CTR, dec. 2012-oct. 2015

(n=607)

Wrists that met inclusion criteria

(n=126)

Total amount of wrists analyzed

(n=92)

Excluded because of

exclusion criteria

(n=34)

- Previous CTR (n=16)

- Wrist fracture/trauma (n=2)

- Polyneuropathy (n=1)

- Diabetes Mellitus (n=15)

- Cervical Neuropathy (n=0)

- Pregnancy (n=0)

20

2.5 Interventions

All patients included in this study have had ultrasonography, nerve conduction study and a carpal

tunnel release.

2.5.1 Ultrasonography

Ultrasonography was executed at the neurology department of the hospital by technicians of the

clinical neurophysiology department. The equipment used was the Philips iU22, NZE 934 with

the L16-4 nerve transducer for superficial measurement, at a frequency of 4,8MHz. The patient

was seated in front of the researcher with the forearm supinated. The wrist was positioned in

neutral position, with the fingers in normal resting position, which means in mild flexion at the

metacarpophalangeal joints and the proximal interphalangeal joints. The transducer was held

perpendicular to the median nerve and the median nerve was followed from proximal to distal,

from the forearm to the palm of the hand. At the level of the carpal tunnel, the biggest cross-

sectional area (CSA) of the median nerve was measured by using a continuous tracing method.

To measure the CSA of the median nerve properly, the area within the hyperechoic epineurium

was measured. The cut-off point for diagnosing CTS was 11,0 mm2. In order to not deform the

nerve, the researcher gave just enough pressure to bring the median nerve into vision.

2.5.2 Nerve Conduction Study

Nerve Conduction Study (NCS) was also performed at the neurology department of the hospital

by technicians of the clinical neurophysiology department. The equipment used was the Medelec

Synergy. The patient was seated in front of the researcher with the forearm supinated. The wrist

was positioned in neutral position. Patients were asked to try to keep their hands warm, for

example to wear gloves when they came to the hospital. The temperature of the hands was not

monitored, but when the hands felt cold they were warmed and all the tests were done at room

temperature. This was because it is suggested that when the skin temperature is below 30 degrees

Celsius, the conduction velocity decreases (see also section 1.9.3). The hands were degreased

before starting the procedure.

First the sensory latency time was measured. Two electrodes were placed on the fourth digit with

some gel between the skin and the electrodes for better conduction. The median nerve was

stimulated just proximal of the wrist and the sensory action potential is monitored on the

computer with special Medelec Synergy software. Then the ulnar nerve was stimulated just

proximal of the wrist and the latency time of this nerve was also monitored on the computer. The

software calculated the difference between the two nerve sensory latencies. A difference in

latencies larger than 0,4 milliseconds was abnormal.

The second measurement was the sensory latency difference between the median nerve and the

radial nerve. The two electrodes with some gel were placed on the first digit. The median nerve

and radial nerve were stimulated just proximal of the wrist. Again the latency times were

monitored on the computer and the software calculated the difference. A difference in latencies

larger than 0,4 milliseconds was abnormal.

The third measurement was the motor latency time. Two electrodes were placed; one on the distal

phalanx of the second digit and one in the palm of the hand. The median nerve was stimulated

proximal of the wrist. The amperage was increased until the monitored amplitude was at the

maximum. At that point, the motor latency time was monitored. Then the radial nerve was

stimulated proximal of the wrist till the monitored amplitude was at the maximum and the motor

latency time of the radial nerve was monitored. The difference between the two latencies was

calculated by the software. A difference in latencies larger than 0,4 milliseconds was abnormal.

21

The fourth measurement was not a standard measurement, but could be an additional

confirmation of the diagnosis. This measurement was the SNCV. It measured differences

between the proximal SNCV and the distal SNCV (proximal-distal ratio). Two electrodes were

placed on the third digit. Seven centimeter proximal of the most proximal electrode, the median

nerve was stimulated and the SNCV is monitored. Then fourteen centimeter proximal to the most

proximal electrode, the median nerve was stimulated and the SNCV was monitored. The

difference was again calculated by the software. The difference in SNCVs was abnormal when

the velocity difference was more than 10,0 meter/second in the distal segment compared to the

proximal segment.

When two of the first three measurements were abnormal, the diagnosis CTS was set. So, if two

of the following three measurements were abnormal, the diagnosis CTS was set: the sensory

latency time difference between the median and ulnar nerve, the sensory latency time difference

between the median and radial nerve and/or the motor latency time difference between the

median and radial nerve. The SNCV of the proximal and distal ratio was an additional

measurement to confirm the diagnosis.

2.5.3 Surgery: Carpal Tunnel Release

The carpal tunnel releases (CTR) in the hospital where this study was conducted, was an open

CTR. The surgery took place as an outpatient surgery procedure and under local anaesthesia, with

lidocaine 1% with adrenaline. A pneumatic tourniquet was placed on the upper arm to control

bleeding. The hand and forearm were disinfected and were covered with sterile surgical drapes.

The incision was marked at the palmar side of the wrist, just distal to the wrist flexion crease,

with a length of three centimeters. The incision was located slightly ulnar to the midline of the

wrist, in line with the third web space. With a 15-scalpel the incision was made and the cutis and

subcutis were opened with use of a blunt scissor or mayo scissor and a tissue forceps. After that,

the wound was held open with a spreader and with a blunt hook. The flexor retinaculum was cut

to the distal and proximal side. The cutis was closed with 3.0 ethilon. In order to compress the

wound, it was bandaged with cotton wool and a swaddle for two days. Patients were advised to

start active movement of the fingers as soon as possible and to keep their hand high. The stitches

were removed after fourteen days.

At all the surgeries, an experienced plastic surgeon performed the surgery or was present at the

surgery, to make sure the procedure was well done, with a complete release of the flexor

retinaculum.

2.6 Cut-off points measurements

The cut-off points for the examinations are tabulated in table 2.

Table 2: Cut-off points examinations

Examination Cut-off point

Ultrasonography CSA at carpal tunnel 11,0 mm2

NCS Sensory latency time median-ulnar nerve Difference -0,4 ms

NCS Sensory latency time median-radial nerve Difference -0,4 ms

NCS Motor latency time 2nd

digit-palm Difference -0,4 ms

NCS SNCV prox-dist ratio Difference 10,0 m/s

CSA: cross-sectional area; NCS: nerve conduction study; prox: proximal; dist: distal; SNCV: sensory

nerve conduction velocity; ms: milliseconds; m/s: meter/second.

22

2.7 Analysis of data

For the statistical analysis, IBM SPSS Statistics for Windows, version 23.0.0.0 (IBM Corp,

Armonk, NY) was used. To compare groups and to calculate the significance, the Student T-test,

Spearman test, Pearson test and Chi-square test were used.

In case of results with a normal distribution, the mean and standard deviation were mentioned.

When results were non-normally distributed, the median and interquartile range were mentioned.

Differences between normally distributed scale variables were analyzed with the independent

Student T-test. The Mann-Whitney U-test was used to analyze differences between non-normally

distributed scale variables or categorical variables. Correlation between scale and categorical

variables were analyzed with the Spearman test and correlations between categorical variables

were analyzed with the Pearson test. The Chi-square test was used to analyze correlations

between nominal variables or between nominal and categorical variables.

A p-value

23

3. Results

3.1 Patient characteristics in the overall CTS group (table 3)

A total of 92 wrists from 57 patients were analyzed (67 (72,8%) wrists of women), with an

average age of 51,4 years (14,13 years, range 19 to 87 years). The age of men and women had

an average of 57,92 and 51,39 years, respectively (significant difference, p 0,041). Of all the

wrists, in 91,3% the right hand was dominant and in 51,1% the right hand was operated. The

duration of symptoms had a median of 16 months (interquartile range (IQR): 6-24 months).

Sixteen percent of the wrists had a conservative treatment before surgery, against 84% of the

wrists that underwent surgery. Fifteen patients in this study had co-morbidities: two patients had

rheumatoid arthritis, two patients osteoporosis, one patient thyroid gland disease, three patients

fibromyalgia, one patient gout, two patients breast cancer, two patients colon cancer and two

patients had osteoarthritis. The other 42 patients did not have co-morbidities. Of the 92 wrists, 56

(60,9%) wrists were from patients with a paid job. Of these wrists from patients with a paid job,

19 (33,9%) did light physical work like a office job, 35 (62,5%) did an intermediate physical job

like working in a store and 2 (3,6%) did heavy physical work like construction work. Except for

the age, there were no differences in patients characteristics between men and women (p > 0,05).

3.2 Patient characteristics in the typical and atypical CTS group (table 3)

Sixty wrists did met the criteria of typical CTS. In 6 wrists another diagnosis was likely, so 54

(57,7%) wrists remained in the typical CTS group and 38 (42,3%) wrists were added to the

atypical CTS group. There were no significant differences found in patient characteristics

between the typical and atypical CTS group.

Table 3: Patient characteristics

Variable All CTS (n=92)

Typical CTS

(n=54) Atypical CTS

(n=38) Sign (p)

Women, No. (%) 67 (72,8) 42 (77,8) 25 (65,8) 0,203

Age, mean (SD), y 53,16 (14,05) 53,37 (14,42) 52,87 (13,68) 0,867

Dominant right hand, No. (%) 84 (91,3) 47 (87,0) 37 (97,4) 0,083

Operated hand right, No. (%) 47 (51,1) 26 (48,1) 21 (55,3) 0,501

Duration of symptoms, median (IQR),

months 12 (6-24) 12 (6-24) 12 (5,75-24) 0,506

Conservative treatment, No. (%) 13 (14,1) 6 (11,1) 7 (18,4) 0,322

Paid job, No. (%) 56 (60,9) 34 (63,0) 22 (57,9) 0,624

Work, No. (%)

Light 19 (33,9) 12 (22,2) 6 (15,8) 0,444

Intermediate 35 (62,5) 21 (38,9) 14 (36,8) 0,842

Heavy 2 (3,6) 1 (1,9) 2 (5,3) 0,364

Sign : significance (significant difference when p

24

3.3 Incidence of symptoms and signs in the overall CTS group (table 4)

Symptoms in the distribution area of the median nerve were present in 66,3% of all the wrists. In

25% of the wrists patients had continuous pain. Furthermore, in 95,7% of the wrists patients

experienced tingling, 71,7% had a diminished sensibility in one or more digits in the distribution

are of the median nerve, 51,1% of the patients experienced diminished strength in the affected

hand and 80,4% experienced symptoms at night. In 71,7% of the wrists the Tinel test was

positive and in 66,3% the Phalen test was positive. There were no differences in symptoms

between men and women (p > 0,05).

3.4 Incidence of symptoms and signs in the typical and atypical CTS group (table 4)

When analyzing the symptoms and signs in the typical and atypical CTS group, there was a

significant higher incidence of symptoms in the median area in the typical CTS group than in the

atypical CTS group (p 0,000). Also the incidence of experiencing diminished sensibility had a

significant higher incidence in the typical CTS group than in the atypical CTS group (p 0,001).

No significant differences in the other symptoms and signs were found between the typical and

atypical CTS group.

3.5 Primary study outcome

3.5.1 Ultrasonography The mean CSA of the median nerve in the carpal tunnel was 12,83mm

2 (3,95). There was no

significant difference between men and women (p 0,502). When the typical and atypical CTS

groups were analyzed, the mean CSA was slightly different: 12,74mm2 (4,30) and 12,94mm

2

(3,44) respectively, but no significant difference was found (p 0,908)(table 5).

3.5.2 Nerve conduction study

The mean difference between the median nerve sensory latency time and the ulnar nerve sensory

latency time in the overall CTS group was 1,16 ms ( 1,06). The mean difference between the

median nerve sensory latency time and the radial nerve sensory latency time was 1,05 ms (

0,76). The mean difference between the median nerve motor latency time and the ulnar nerve

motor latency time was 1,13 ms ( 1,09).

In the typical CTS group, the mean differences between the median and ulnar nerve sensory

Table 4: Symptoms and signs in the overall, typical and atypical CTS group

Symptom/sign All CTS (n=92)

Typical CTS

(n=54) Atypical CTS

(n=38) Sign (p)

Median nerve area, No. (%) 61 (66,3) 54 (100,0) 10 (26,3) 0,000*

Continuous pain, No. (%) 23 (25,0) 14 (25,9) 9 (23,7) 0,688

Tingling, No. (%) 88 (95,7) 54 (100,0) 37 (97,4) 0,244

Diminished sensibility, No. (%) 66 (71,7) 45 (83,3) 21 (55,3) 0,001*

Diminished strength, No. (%) 47 (51,1) 23 (42,6) 24 (63,2) 0,058

Symptoms at night, No. (%) 74 (80,4) 44 (81,5) 30 (78,9) 0,149

Tinels test positive, No. (%) 66 (71,7) 38 (70,4) 28 (73,7) 0,980

Phalens test positive, No. (%) 61 (66,3) 36 (66,7) 25 (65,8) 0,752

Sign: significance (significant difference when p

25

latency time, the median and radial nerve sensory latency time and the median and ulnar nerve

motor latency time were 1,21 ms ( 1,17), 1,11 ms ( 0,81) and 1,38 ms ( 1,18), respectively.

In the atypical group these mean differences were 1,11 ms ( 0,94), 0,97 ms ( 0,68) and 1,14 ms

( 0,94), respectively. There were no significant differences found between the typical and

atypical CTS groups (table 5).

Sign : significance (significant difference between typical and atypical CTS group when p < 0,05). CSA:

cross sectional area (mm2). SD: standard deviation. Sens lat time med-uln: Sensory latency time

(milliseconds), difference between median and ulnar nerve. Sens lat time med-rad: sensory latency time

(milliseconds), difference between median and radial nerve. Mot lat time med-uln: motor latency velocity

time (milliseconds).

3.5.3 Ultrasonography and nerve conduction study outcomes combined (table 6)

US was positive in 68 of the 92 cases (73,9%) in the overall group. In the typical CTS group, US

was positive in 72,2% and in the atypical CTS group in 76,3%. NCS was positive in 81,5% in the

overall group. In the typical CTS group, NCS was positive in 79,6% and in the atypical CTS

group in 84,2%.

Table 6: Outcome measurements US and NCS

Outcome NCS, US All cases with CTS (n=92)

Typical CTS

(n=54) Atypical CTS

(n=38) Sign (p)

US +, No. (%) 68 (73,9) 39 (72,2) 29 (76,3) 0,660

US -, No. (%) 24 (26,9) 15 (27,8) 9 (23,7) 0,660

NCS +, No. (%) 75 (81,5) 43 (79,6) 32 (84,2) 0,549

NCS -, No. (%) 17 (18,5) 11 (20,4) 6 (15,8) 0,549

US+, NCS+, No. (%) 53 (57,6) 29 (53,7) 24 (63,2) 0,412

US+, NCS-, No. (%) 15 (16,3) 10 (18,5) 5 (13,2) 0,497

US-, NCS+, No. (%) 22 (23,9) 14 (25,9) 8 (21,1) 0,596

US-, NCS-, No. (%) 2 (2,2) 1 (1,9) 1 (2,6)

26

CTS group or between the outcomes of NCS in the two groups.

Of all negative NCS outcomes, in the overall group US was positive in 15 of the 17 wrists

(88,2%). In the typical CTS group, this was 10 of the 11 wrists (90,9%) and in the atypical CTS

group 5 of the 6 wrists (83,3%). This shows that in 88,2% to 90,9% of all the cases with clinically

definite CTS and with normal NCS, US is positive.

On the other hand, of all negative US outcomes, NCS was positive in 22 of the 24 wrists (91,2%)

of the overall CTS group. In the typical CTS group this was in 14 of the 15 wrists (93,3%) and in

the atypical group in 8 of the 9 wrists (88,9%). This shows that in 88,9% to 93,3% of all cases

with clinically definite CTS and with normal US, NCS is positive.

3.6 Secondary study outcome 3.6.1 Sensitivity US, NCS or both (table 7)

The sensitivity of US found in this study is 73,9% and the sensitivity of NCS is 81,5% (no

significant difference, p 0,204). In the typical CTS group, the sensitivity of US and NCS is 72,2%

and 79,6%, respectively (no significant difference, p 0,289). In the atypical CTS group, the

sensitivity of US and NCS is 76,3% and 84,2%, respectively (no significant difference, p 0,238).

Table 7: Sensitivity US and NCS

CTS group US sensitivity (%) NCS sensitivity (%) Sign (p)

All CTS 73,9 81,5 0,204

Typical CTS 72,2 79,6 0,289

Atypical CTS 76,3 84,2 0,238

Sign: significance (significant difference when p 0,05).

Positive: patient was satisfied, no more symptoms post-operative; Negative: patient was dissatisfied, still

symptoms post-operative; Sign: significance (significant difference when p

27

4. Discussion

4.1 Mean results

4.1.1 Hypothesis

The first hypothesis in this study was that US and NCS have a comparable sensitivity. This study

showed that the sensitivity of US and NCS is not significant different in both the typical and

atypical CTS group, as well as the overall group, what means that the hypothesis is confirmed.

The second hypothesis was that in patients with clinical CTS, US is enough to diagnose CTS so

that NCS is unnecessary. As mentioned before, the sensitivity of US and NCS is comparable in

all three groups (typical CTS, atypical CTS and the overall group). Despite this comparability,

US could be preferred as first examination in diagnosing CTS, because this examination is less

time-consuming and less uncomfortable for patients in comparison with NCS.

4.2 Other results

4.2.1 Differences between groups

This study showed a significant higher incidence of symptoms in the median nerve area and

diminished sensibility in the typical CTS group than in the atypical CTS group. No significant

differences were found in other signs and symptoms between the typical and atypical CTS group.

The significant higher incidence of symptoms in the median nerve area and diminished sensibility

in the typical CTS group, could be explained by the small sample size or the criteria that were set

for the diagnosis typical CTS in this study. The remained 33,7% of patients that were not labeled

with experiencing symptoms in the median nerve area, experienced for example symptoms in all

fingers and not only in the median nerve area. This could also be the cause of the difference

between the typical and atypical CTS group.

4.2.2 Combined outcome US and NCS

This study showed no significant differences in the outcome of US and NCS between the typical

and atypical CTS group. The only significant difference found in the combined outcomes of US

and NCS was a significant difference between the typical and atypical group in the variable US

and NCS outcome negative (p < 0,001) (table 6). The small numbers in this variable (only 1

wrist in each group) may be the cause of this significant difference. This outcome does not have

clinical relevance.

4.2.3 Surgery outcome

In this study, in 76,1% of the wrists, patients had no post-operative symptoms. Unfortunately, in

20,7% the surgery outcome could not be retrieved from the medical record. This could bias the

analysis of this variable. The reason for the unknown outcome was because in some cases

patients decided to cancel the surgery, for example when they had other illnesses, e.g. cancer.

Also in some cases the follow-up of the patients after surgery could not be found in the medical

record or patients were not yet operated. It seems that in a majority of the patients the surgery

relieved the symptoms, because only in 3,3% patients were not satisfied about the surgery

outcome.

It is notable that in the 3 cases the patients were not satisfied about the surgery outcome, in 2 of

these cases the NCS was positive and in all three US was positive. This suggests that US and

NCS could not predict the outcome of surgery, but the numbers in this study are too limited to

state this.

28

As mentioned before, some literature uses a post-operative diagnosis of CTS. In this study, this

means that in 76,1% the diagnosis CTS could be made, but in 20,7% the diagnosis could not be

made due to unknown surgery outcome. Therefore, this study could not be used to diagnose CTS

post-operative.

It should also be noticed that when the post-operative diagnosis is used, it could occur that patient

would undergone surgery unnecessarily. Because of this, the present study does not recommend

to use these criteria to diagnose CTS.

4.2.4 Costs

The outcome of this study suggests that NCS could be unnecessary as first examination to

confirm the diagnosis of CTS when the clinical diagnosis is set. This means that initially only US

could be performed instead of both NCS and US. Performing US only could lead to a decrease in

costs of 340,- for each patient that could be examined with US only. In this study, in 68 cases

US was positive. This suggests that in these 68 cases NCS should not have been performed to

confirm the clinical diagnose of CTS, what means a total of 23.120,- could have been saved. In

literature, only one study was found that describes the costs of US and NCS(34). In that study the

costs of NCS was $400,30 what is about 365,-. Although this is a comparable amount of money,

it is difficult to compare these costs because of changes in valuta value, inflation and differences

in costs between institutions.

Beside this, an ethical dilemma raises from this outcome. NCS costs less than US, but US is less

uncomfortable for patients. The question is what is more important: the costs of examinations or

the patients well-being. Another question could be: What is the maximum of costs that is

accepted for examinations? This study prefers to perform US, because in our opinion the small

difference in costs counts for little compared to the patients well-being.

4.3 Outcome of other studies about ultrasonography and nerve conduction study in

diagnosing CTS.

The present study showed that the sensitivity of US and NCS was comparable in both the typical

and atypical CTS group, as well as the overall group. This suggests that in patients with clinical

symptoms of CTS, US could be preferred as first examination for confirming the diagnosis CTS,

because this is less time-consuming and less uncomfortable for patients in comparison with NCS.

A recent study in The Netherlands from Kasius et al.(49), suggests that in patients with typical

CTS symptoms, such as tingling in the median nerve area, US can be used as first diagnostic tool.

When US outcome is negative, NCS can be used as second diagnostic tool. Kasius suggests that

in patients with typical CTS, which is 60% of the patients in her study, NCS does not need to be

performed to confirm the diagnosis of CTS. These findings are partly comparable with the

findings in the present study. Also other literature describes US as the preferred first examination

in diagnosing CTS(50-53).

The sensitivity of NCS found in this study was 79,6-84,2%. This is higher than found in literature

(56-85%, see section 1.9.3). The cause of this difference could be that in this study no difference

was made in the severity of CTS. It could be possible that in other studies a lot of patients were

included with mild CTS and in this study patients were included with more severe CTS. In

patients with mild CTS, the symptoms they experience could be due to damage to the small fibers

only and not (yet) the large fibers. These small fibers cannot be measured with NCS, only the

large fibers can be measured. This could lead to a normal NCS, although patients do experience

symptoms(54). This lowers the percentage of abnormal NCS outcomes and thus the sensitivity.

Furthermore, in this study in 88,2% of the 17 wrists in the overall CTS group with a negative

29

NCS outcome, US is positive. This is higher than described in other literature(55). El-Hashel

found that in patients with clinical definite CTS and with normal NCS, US was positive in

49%(55). This difference possibly could be explained by small sample sizes, differences in the

origin of patients or differences in the equipment that was used. The meaning of this outcome is

that US is recommended when NCS is negative, because in 88,2% to 90,9% the diagnosis CTS

can still be made.

Although US and NCS has a comparable sensitivity, US cannot be the only diagnostic tool for

CTS. In this study, in 2 cases US was negative and NCS was positive. In order not to miss the

diagnosis CTS in these patients, NCS should be performed as second examination when US is

negative.

4.4 Strengths of this study

A strength of this study is the comparison of NCS and US and the aim to say something about the

necessity of both examinations. In recent literature, a lot of studies are conducted about the use of

NCS and/or US, but fewer studies were conducted about the necessity of NCS in diagnosing

CTS.

4.5 Limitations of this study One limitation of this study was the small sample size. This could lead to a statistical bias with

less precise outcomes. It could occur that the sensitivity of US and NCS changes, when the

sample size is big enough. Further studies are needed to determine this.

Also the retrospective design was a limitation. Because of this retrospective design, the

information was searched from medical records. In some cases information about symptoms

missed in the medical record and this information could not always be retrieved.

Beside this, there was no control group to compare with the study group. All patients in this

database were diagnosed with clinical definite CTS, no healthy people were added to the

database. Because there was no control group, no specificity could be calculated. The specificity

in combination with the sensitivity, could say more about the accuracy of examinations. That is

because the specificity is the proportion of negative results of a test in patients who does not have

the disease. So it would be the proportion of healthy people who have a negative US and/or NCS.

To determine the specificity of US and NCS could be helpful in diagnosing CTS.

Furthermore, in this study different technicians performed the US and NCS examinations.

Although all the technicians have had the same education, differences in measurements could

occur. Beside this, the inter-rater reliability is not tested, because of the retrospective design.

Also only patients with an email address were added to the database. The reason for this was that

they were asked by mail to fill in questionnaires about their symptoms. Unfortunately these

questionnaires could not be used in this study, because of the lack of enough completed

questionnaires. People without an email address were not added to the database, which could lead

to a bias in the study population.

Another limitation is that only patients seen by a nurse were added to the database. Patients who

were seen directly by the plastic surgeon were not added. The reason for this was because of the

limited time plastic surgeons had to see a patient. This time was not enough to conduct all the

needed proceedings to add the patient to the database.

In order to collect a sample size that was as big as possible, patients with bilateral symptoms

were added with both wrists to the database, which is a limitation too. This could lead to a

statistical bias.

30

Also the fact that in this study typical CTS was defined as tingling in the median nerve

distribution area is a limitation. Because no clear criteria for typical CTS were described in

literature, the definition this study used was chosen after asking plastic surgeon what they thought

was typical CTS. The outcomes of this study, for example the sensitivity of US and NCS in

patients with typical CTS, could be different when using other criteria for typical CTS.

Finally, only patients with primary CTS were included in this study, so the value of US and NCS

in patients with recurrent CTS is not sure.

4.6 Recommended future study design Because the limitations of this study, further research is recommended. This future study should

be a prospective study with a large sample size and with a control group. Patients with clinical

CTS and healthy patients should be examined with US and NCS. There should be a limited

amount of technicians to conduct these examinations. In order to make sure the technicians

measure the same outcomes, the interrater reliability should be analyzed. All technicians should

perform the examinations blinded for the outcome of earlier (clinical) examinations in order not

to influence their outcome.

Furthermore, not only patients with an email address or patients seen by a nurse should be

selected, but all patients who have clinical diagnosis of CTS seen in the clinic. In order to collect

a large sample size, the study could be conducted in different hospitals.

Beside this, there should be a guideline about how to perform US. This guideline should give

exact indications about, for example, the location of measuring the CSA and the cut-off point of

the CSA.

The exact location for measuring the CSA of the median nerve should be determined. In literature

there is a lot of controversy about this (50-53). The most used location for measuring the CSA is

the pissiform, also named the carpal tunnel inlet(6,8,14,28,29,32,42,46). The reason for this is

that when the CSA is measured at other locations in the wrist the values were too heterogeneous

to determine one cut-off point(32). Also, the low inter-reader reliability of measuring the CSA of

the carpal tunnel outlet (the hook of the hamatum(56)) is described in literature(57), what could

be a reason for not choosing the carpal tunnel outlet as location for measuring the CSA of the

median nerve. Furthermore, it is difficult to measure the exactly CSA of the median nerve at the

location of the carpal tunnel outlet, because of the distance between the skin and the median

nerve. At the level of the carpal tunnel inlet, the median nerve is located relative superficial, what

makes it easier to determine the CSA. In contrast with this, at the carpal tunnel outlet, the median

nerve is located deeper underneath other structures such as fat and muscles. Because of this, the

CSA is difficult to measure at the carpal tunnel outlet and the measurement is less reliable.

The cut-off point of the CSA of the median nerve in the carpal tunnel is also a point of

controversy in the literature. This varies from 6,0mm2 to 16,0mm

2(11,52). The most recent study

(2014) suggests that the best cut-off point for the CSA of the median nerve, located at the carpal

tunnel inlet, is 10,5mm2(52). Further studies are needed to determine the best cut-off point. In

these studies the differences in CSA between races should be taken into account, because it is

known there is a difference in normal CSA between races(58).

Furthermore, there should be an international guideline for performing NCS. Although there are

just little differences between, for example, the American and Dutch guideline(35), these small

differences could lead to other outcomes of the examination. This aggravates the comparison of

different international studies.

Also, there are no clear criteria for diagnosing CTS. These criteria should be international the

same. When all studies use the same criteria, this could contribute to the knowledge about, for

31

example, US and NCS, because all these studies could be compared. Nowadays, a lot of different

criteria are used and this hinders the comparison of different international studies. Clear criteria

for diagnosing CTS with clinical symptoms should be made, but also the difference between

typical and atypical CTS or the use of post-operative diagnosis should be studied.

Finally, because in this study only patients with primary CTS were included, no conclusions

could be made about the values of US and NCS in patients with recurrent CTS. The value of NCS

and US for diagnosing recurrent CTS should be determined in future studies.

4.7 Further recommendations

A point of interest is the use of a questionnaire to determine whether or not a patient has clinical

definite CTS or typical CTS, before executing any examinations. By making an inventory of

the symptoms that patients experience, the diagnosis of clinical CTS could be made. This could

be helpful in deciding to execute first US alone, in order not to load patients unnecessary. An

example of this is the Six-item Carpal Tunnel Syndrome symptom scale (CTS-6)(59)(see also:

appendix). This validated questionnaire is developed by Brent Graham(59). It combines data

from the history and data from the physical examination in order to predict the outcome of

electrodiagnostic testing(45). Graham suggested that, in patients with a positive CTS-6, the pre-

test probability of having CTS is that high, that it makes electrodiagnostic testing

unnecessary(59). Fowler confirmed this with his study(45). Fowler found in his study also that

most physician consider patients with a positive CTS-6 as typical CTS, so this indicates that

this questionnaire could be helpful in differentiate between typical or atypical CTS. This

questionnaire could be used to set the clinical diagnose of CTS and this could help in making the

decision to perform only US. Although the outcome of Grahams study was promising, there is a

lot of controversy about the value of provocative tests in literature(60-63). Two provocative tests

are used in the CTS-6: Phalens test and Tinels test. Further studies are thus needed to confirm

the functioning of this questionnaire and to examine the value of the provocative tests.

32

5. Conclusion In conclusion, this present study showed that the sensitivity of US and NCS is not significant

different in both the typical and atypical CTS group, as well as the overall group. Although there

was not a significant difference between US and NCS, US could be preferred as first examination

to confirm the diagnosis CTS, because this examination is less uncomfortable for patients and

less time-consuming in comparison with NCS. Further prospective and blinded studies are

needed to confirm these outcomes.

33

6. Bibliography

(1) Paliwal PR, Therimadasamy AK, Chan YC, Wilder-Smith EP. Does measuring the median

nerve at the carpal tunnel outlet improve ultrasound CTS diagnosis? J Neurol Sci 2014 Apr

15;339(1-2):47-51.

(2) American Academy of Orthopedic Surgeons. Clinical practice guidelines on diagnosis of

carpal tunnel syndrome. 1st ed. Rosemont: American Academy of Orthopedic Surgeons. 2007.

(3) Paget J. The first description of carpal tunnel syndrome. J Hand Surg Eur Vol 2007

Apr;32(2):195-197.

(4) Chammas M, Boretto J, Burmann LM, Ramos RM, Dos Santos Neto FC, Silva JB. Carpal

tunnel syndrome - Part I (anatomy, physiology, etiology and diagnosis). Rev Bras Ortop 2014

Aug 20;49(5):429-436.

(5) Phalen GS. The carpal-tunnel syndrome. Seventeen years' experience in diagnosis and

treatment of six hundred fifty-four hands. J Bone Joint Surg Am 1966 Mar;48(2):211-228.

(6) Roll SC, Case-Smith J, Evans KD. Diagnostic accuracy of ultrasonography vs.

electromyography in carpal tunnel syndrome: a systematic review of literature. Ultrasound Med

Biol 2011 Oct;37(10):1539-1553.

(7) de Jesus Filho AG, do Nascimento BF, Amorim Mde C, Naus RA, Loures Ede A, Moratelli

L. Comparative study between physical examination, electroneuromyography and

ultrasonography in diagnosing carpal tunnel syndrome. Rev Bras Ortop 2014 Sep 16;49(5):446-

451.

(8) Ghasemi-Rad M, Nosair E, Vegh A, Mohammadi A, Akkad A, Lesha E, et al. A handy

review of carpal tunnel syndrome: From anatomy to diagnosis and treatment. World J Radiol

2014 Jun 28;6(6):284-300.

(9) Werthel JD, Zhao C, An KN, Amadio PC. Carpal tunnel syndrome pathophysiology: role of

subsynovial connective tissue. J Wrist Surg 2014 Nov;3(4):220-226.

(10) de Krom MC, Knipschild PG, Kester AD, Thijs CT, Boekkooi PF, Spaans F. Carpal tunnel

syndrome: prevalence in the general population. J Clin Epidemiol 1992 Apr;45(4):373-376.

(11) Descatha A, Huard L, Aubert F, Barbato B, Gorand O, Chastang JF. Meta-analysis on the

performance of sonography for the diagnosis of carpal tunnel syndrome. Semin Arthritis Rheum

2012 Jun;41(6):914-922.

(12) National Institute of Neurological Disorders and Stroke. Carpal Tunnel Syndrome Fact

Sheet. NIH Publication No. 12-4898. 2015.

(13) Jones O. The Carpal Tunnel. 2015; Available at: www.teachmeanatomy.info.

34

(14) Tajika T, Kobayashi T, Yamamoto A, Kaneko T, Takagishi K. Diagnostic utility of

sonography and correlation between sonographic and clinical findings in patients with carpal

tunnel syndrome. J Ultrasound Med 2013 Nov;32(11):1987-1993.

(15) Roll SC, Evans KD, Li X, Freimer M, Sommerich CM. Screening for carpal tunnel

syndrome using sonography. J Ultrasound Med 2011 Dec;30(12):1657-1667.

(16) Jordan R, Carter T, Cummins C. A systematic review of the utility of electrodiagnostic

testing in carpal tunnel syndrome. Br J Gen Pract 2002 Aug;52(481):670-673.

(17) Baker NA, Livengood HM. Symptom severity and conservative treatment for carpal tunnel

syndrome in association with eventual carpal tunnel release. J Hand Surg Am 2014

Sep;39(9):1792-1798.

(18) Viera AJ. Management of carpal tunnel syndrome. Am Fam Physician 2003 Jul

15;68(2):265-272.

(19) Gerritsen AA, de Vet HC, Scholten RJ, Bertelsmann FW, de Krom MC, Bouter LM.

Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial.

JAMA 2002 Sep 11;288(10):1245-1251.

(20) Gerritsen AA, Uitdehaag BM, van Geldere D, Scholten RJ, de Vet HC, Bouter LM.

Systematic review of randomized clinical trials of surgical treatment for carpal tunnel syndrome.

Br J Surg 2001 Oct;88(10):1285-1295.

(21) Vasiliadis HS, Georgoulas P, Shrier I, Salanti G, Scholten RJ. Endoscopic release for carpal

tunnel syndrome. Cochrane Database Syst Rev 2014 Jan 31;1:CD008265.

(22) Atroshi I, Hofer M, Larsson GU, Ranstam J. Extended Follow-up of a Randomized Clinical

Trial of Open vs Endoscopic Release Surgery for Carpal Tunnel Syndrome. JAMA 2015 Oct

6;314(13):1399-1401.

(23) Badger SA, O'Donnell ME, Sherigar JM, Connolly P, Spence RA. Open carpal tunnel

release--still a safe and effective operation. Ulster Med J 2008 Jan;77(1):22-24.

(24) Dudley Porras AF, Rojo Alaminos P, Vinuales JI, Ruiz Villamanan MA. Value of

electrodiagnostic tests in carpal tunnel syndrome. J Hand Surg Br 2000 Aug;25(4):361-365.