Morphological and functional changes of the median nerve after neurolysis for carpal tunnel syndrome

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. The
diagnosis can be made clinically but is usually confirmed by using nerve
conduction studies (NCS) or ultrasound (US). NCS provides functional
information by showing (a) slowing of the sensory or motor nerve conduction
over the wrist and (b) signs of possible axonal loss. US may reveal nerve
enlargement at the level of pisiform bone, as well as underlying causes for
CTS. In addition Doppler studies may detect increased vascularity of the median
nerve.

Surgery is the most effective treatment for CTS on the long term (1). Splinting
and local corticosteroid injections may also provide temporarily relief of
symptoms but a long term effect has not been proven (2). Repeated injections
are usually not recommended (3). A previous studies suggested that a local
steroid injection is less effective on the long term in patients with more
pronounced nerve thickening on US (4). In general nerve thickening diminishes
after surgery and injection for CTS and ulnar neuropathy at the elbow (5, 6).
There are also changes of vascularity of the median nerve after corticosteroid
injection (5). It is not known how the US changes develop over time in surgery.
Is there immediate decrease of nerve thickening? Does the shape of the nerve
change (e.g., become less flattened)? Is there a decrease or even increase of
vascularity? More knowledge of these changes may give insight in the
pathophysiological changes after neurolysis and aid in decision making in
patients in whom surgery was not successful. The Dutch guideline for CTS
(www.cbo.nl) recommends renewed surgery when clinical and NCS improvement is
insufficient three months after the initial operation. It is not clear what
role US can play in these cases although experts report incomplete release of
the transverse carpal ligament by means of US. Remaining abnormalities during
US and NCS should be interpreted with caution: e.g., the median nerve may
remain more or less thickened despite clinical improvement, the conduction
velocity may remain slowed after surgery because the internodal myelin segments
become shorter after remyelination.

The objectives of this study are twofold:
1. To describe morphological and functional changes of the median nerve after
neurolysis using US and NCS.
2. To correlate the morphological and functional changes to the clinical
symptoms and signs

Clinical assessment at baseline

A. Clinical assessment

History:
- duration of symptoms
- previous episodes of CTS
- contralateral CTS
- paresthesias digits 1-4
- numbness digits 1-4
- clumsiness
- muscle weakness
- number of nights that the patient awoke, due to the symptoms, during the past
week

Scales, questionnaires
- functional scales
- VAS pain
- VAS paresthesias

Examination
- thenar muscle wasting: no, mild, severe.
- muscle strenght using the MRC (0, 1, 2, 3, 4, 5), manually testing the
abductor pollicis brevis and opponens pollicis brevis muscles.
- pin prick sensation in the area of the median nerve (volair aspect of digit
1-4).


B. Nerve conduction studies

For sensory studies ring electrodes will be used and for motor studies surface
electrodes placed over the abductor pollicis brevis muscle in a belly-tendon
montage. Skin temperature must be held > 32 ºC. When necessary arms and hands
must be warmed by using hot tubs or packings. The following tests will be
performed:


1. Stimulating at the wrist, recording from digit 4: comparison of the sensory
conduction of the median and ulnar nerve over the wrist * digit 4 segment over
equal distances. A latency difference of > 0,4 ms is considered abnormal. Digit
5 will be recorded simultaneously to detect costimulation.
2. Stimulating at the wrist and palm, recording from digit 3: comparison of the
sensory conduction of the median nerve over the wrist * palm segment and the
palm * digit 3 segment over equal distances. A latency difference of > 0,4 ms
is considered abnormal.
3. Stimulating at the wrist, recording from digit 1: comparison of the sensory
conduction of the median and radial superficial nerve over the wrist * digit 1
segment over equal distances. A latency difference of > 0,4 ms is considered
abnormal.
4. Recording from the APB muscle at 6 cm from the wrist: a distal motor latency
of > 4 ms is considered abnormal.

When necessay the following test can be performed:

1. Stimulating at the wrist, recording from the lumbrical II and interosseous
II muscles over equal distances. A latency difference of > 0,5 ms is abnormal.


NCS is considered supportive for the diagnosis of CTS when:

1. Two or more of the above mentioned tests are abnormal. After two abnormal
tests the NCS exam will be stopped. The DML to the APB muscle should always be
measured.

or:

2. The combined sensory index (CSI) is >1,1 ms, CSI = sum of the latency
differences of tests 1, 2 and 3 (sensitivity 82%, specificity 100%).

The following classification will be used:

- mild sensory conduction abnormal, normal APB DML
- moderate sensory conduction abnormal, prolonged APB DML
- severe no median SNAP, prolonged APB DML
- very severe no median SNAP and no APB CMAP


C. Ultrasonography

Sonography of the median nerve will be performed using a 4-16 MHz probe.The
pisiform bone is easily identified during US and will be used as a reference
level. Measurements will be performed whithin the hyperechoic rim surrounding
the nerve. The scanning protocol will be as follows:

1. Transverse plane: from 10 cm proximal of the pisiform bone to the level of
the pisiform bone

Measurement of the CSA, AP diameter and transverse diameter:
- at the level of 10 cm proximal of the pisiform bone
- at the level of the pisiform bone
- at the level om maximal thickness at the wrist, noting the distance from the
pisiform bone

Images of these measurements should be stored and printed.

2. Longitudinal plane: including level of the pisiform bone and level of
maximum thickness

Measurement of the AP diameter:
- at the level of the pisiform bone
- at the level om maximal thickness at the wrist, noting the distance from the
pisiform bone

Images of these measurements should be stored and printed.

In case of a bifid median nerve the two parts of the nerve will be measured
separately as described above. Furthermore, the same measurements will be done
by assessing the entire circumference around the two parts.

In addition a swelling ratio will be calculated by dividing the CSA at the
level of maximum thickness at the wirst to the CSA at the level of proximal
forearm. A flattening ratio will be calculated by dividing the anteroposterior
and transverse diameter at the level of maximum thickness at the wrist and at
the level of the pisiform bone. Abnormal structures (e.g., persistant median
artery) will be noted.

A CSA at the level of the pisiform bone of > 10 mm2 is considered diagnostic
for CTS but this criterium will not be used for inclusion in this study.

3. Power flow signals

Screening for blood flow was done at the level of the pisiform bone.
Color doppler settings are chosen to optimize identification of weak signals
from vessels with slow velocity. The pulse repetition frequency (PRF) used is
0.5- 1 kHz and the band filter is set at 50 Hz. The presence of blood flow
signals in the epineurial plexus or endoneurial vessels indicates intraneural
vascularisation of the nerve during CD imaging. When bloodflow was seen, the
color gain and PRF were adjusted to optimize the imaging of bloodflow. We used
both CD and power doppler ultrasonography, and when in doubt about arterial
versus venous flow, spectral analysis was used.


Outcome measures

The following clinical, ultrasonograhic and neurophysiological data will we
obtained 7-10 days, 1, 3 and 6 months after surgery.

A. Clinical

History:
- paresthesias digits 1-4
- numbness digits 1-4
- clumsiness
- muscle weakness
- number of nights that the patient awoke, due to the symptoms, during the past
week

Scales, questionnaires
- functional scales
- VAS pain
- VAS paresthesias
- Level of satisfaction on a 11 point scale
- patient based improvement score + date of improvement on a 6 point scale: (1)
completely
recovered, (2) much improved, (3) slightly improved, (4) no change, (5)
slightly worse, (6) much worse.

Examination
- thenar muscle wasting: no, mild, severe.
- muscle strenght using the MRC (0, 1, 2, 3, 4, 5), manually testing the
abductor pollicis brevis and opponens pollicis brevis muscles.
- pin prick sensation in the area of the median nerve (volair aspect of digit
1-4).

B. Ultrasound

The measurements mentioned at baseline will be repeated. The follow-up
measurements must be done at the same levels as at baseline. New findings
should be noted.

C. Nerve conduction studies

The following tests will be repeated at follow up, only if performed at
baseline:
- Stimulating at the wrist, recording from digit 4: comparison of the sensory
conduction of the median and ulnar nerve over the wrist * digit 4 segment over
equal distances. Digit 5 will be recorded simultaneously to detect
costimulation.
- Stimulating at the wrist and palm, recording from digit 3: comparison of the
sensory conduction of the median nerve over the wrist * palm segment and the
palm * digit 3 segment over equal distances.
- Stimulating at the wrist, recording from digit 1: comparison of the sensory
conduction of the median and radial superficial nerve over the wrist * digit 4
segment over equal distances.
- Recording from the APB muscle at 6 cm from the wrist. Stimulating at the
wrist, recording from the lumbrical II and interosseous II muscles over equal
distances.

Follow-up

The following clinical, ultrasonograhic and neurophysiological data will we
obtained 7-10 days, 1, 3 and 6 months after surgery.

A. Clinical

History:
- paresthesias digits 1-4
- numbness digits 1-4
- clumsiness
- muscle weakness
- number of nights that the patient awoke, due to the symptoms, during the past
week

Scales, questionnaires
- functional scales
- VAS pain
- VAS paresthesias
- Level of satisfaction on a 11 point scale
- patient based improvement score + date of improvement on a 6 point scale: (1)
completely
recovered, (2) much improved, (3) slightly improved, (4) no change, (5)
slightly worse, (6) much worse.

Examination
- thenar muscle wasting: no, mild, severe.
- muscle strenght using the MRC (0, 1, 2, 3, 4, 5), manually testing the
abductor pollicis brevis and opponens pollicis brevis muscles.
- pin prick sensation in the area of the median nerve (volair aspect of digit
1-4).

B. Ultrasound

The measurements mentioned at baseline will be repeated. The follow-up
measurements must be done at the same levels as at baseline. New findings
should be noted.

C. Nerve conduction studies

The following tests will be repeated at follow up, only if performed at
baseline:
- Stimulating at the wrist, recording from digit 4: comparison of the sensory
conduction of the median and ulnar nerve over the wrist * digit 4 segment over
equal distances. Digit 5 will be recorded simultaneously to detect
costimulation.
- Stimulating at the wrist and palm, recording from digit 3: comparison of the
sensory conduction of the median nerve over the wrist * palm segment and the
palm * digit 3 segment over equal distances.
- Stimulating at the wrist, recording from digit 1: comparison of the sensory
conduction of the median and radial superficial nerve over the wrist * digit 4
segment over equal distances.
- Recording from the APB muscle at 6 cm from the wrist. Stimulating at the
wrist, recording from the lumbrical II and interosseous II muscles over equal
distances.

Clinical examination, NCS and US can be considered standard practice and are
safe. Surgery for CTS is a commonly and well accepted treatment modality, and
is not part of the study as such. Surgeons will inform the patients about the
operation (procedure, risks, advices) as usual. The four visits for clinical
exam, US and NCS after surgery are extra but without any important risks.