Distal median- and ulnar nerve compression syndromes Education & Training

Transcription

Distal median- and ulnar nerve compression syndromes Education & Training
Education & Training
Distal median- and ulnar
nerve compression syndromes
Jens Haase
Introduction
Best understood in this context are the median- and ulnar nerve
compression syndromes.3-5,11-13,15-17,21,23,26-28,31,35,36,47 (p38-45)
Most common among these is the median nerve compression in the carpal tunnel = carpal tunnel syndrome (CTS).
Compression syndromes may be treated conservatively e.g.
by a splint or by steroid injections.14,17 Similarly they may
be treated surgically.3,5,12,17,47
Most important and relevant to all kinds of surgery is the
question ‘‘Will the actual procedure relieve symptoms caused
by the disease and are the complication rates low and/or
insignificant?’’. In Denmark with 5.4 million inhabitants a
total of 5,000 hands with CTS are operated upon each year,
and equivalent figures are found in Sweden and US. These
high numbers make it therefore relevant to discuss involved
surgical technique, as complications are possible with all
surgical interventions.
discussion elsewhere.15,17
The median nerve may most often be compressed at the
carpal tunnel distal to the wrist and the position of the
median nerve under the TCL and can clearly be seen with
ultrasound imaging (Fig. 1).
Hook of
hamate
Pisiform
Transverse carpal ligament
Figure 1 - Ultrasound image of the carpal tunnel.
Most common surgical procedure since 1854, has been the
open surgical release (OCTR) of the median nerve by cutting
the transverse carpal ligament (TCL).17 The first endoscope
procedure (ECTR) for transecting the TCL was introduced
in 1987 and many modifications have been described since
then.1,8,22,32,40,49 A combination of open surgery and endoscope
surgery has been introduced recently.24 Surgical treatment
of ulnar nerves has been performed since the19th century.5
Despite the fact that this procedure seems to be a rather
trivial and simple operation, the problems of learning to
perform these operations requires thorough training.11,18,25
Median nerve compression - CTS
For diagnosing CTS the reader is referred to a more detailed
Faculties of Engineering, Science & Medicine
Department of Health Science & Technology
Aalborg University
Denmark
Correspondence:
Prof. Jens Haase
Faculties of Engineering, Science & Medicine
Department of Health Science & Technology
Aalborg University
Fredrik Bajers Vej 7, E-4
9220 Aalborg
Denmark
38
For a compressed median nerve an increase of the carpal
tunnel space can be obtained by cutting the TCL by two
different surgical methods e.g. 1) OCTR or 2) ECTR.17
The major difference between an OCTR and an ECTR
procedure is the way the TCL is cut. With the OCTR the
surgeon cuts the TCL from outside the carpal tunnel thereby
viewing all structures in - for the surgeon - a normal 3D
fashion. This is in contrast to the ECTR where the TCL is
cut from inside the carpal tunnel viewing it in a - for the
surgeon - new, and only 2D fashion.17 This endoscopic
procedure is for many reasons much more difficult and
must be learned thoroughly through training and regular
practice.18
Through literature validation, both surgical methods seem
to lead to the same results but the complications of the
methods are different, apparently being more severe among
the endoscope method.1,9,11,17,34,39, 46, 49,50
To carry out carpal tunnel release surgery the surgeon needs
anaesthesia, and anaesthetic complications must be added to
the surgical failures.6,17
Anaesthesia for CTS treatment comprise of:
1. Local infiltration anaesthesia (LA)
PAN ARAB JOURNAL OF NEUROSURGERY
DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
2.
3.
4.
Local infiltration anaesthesia with use of tourniquet
Intravenous anaesthesia with use of tourniquet and
General anaesthesia.
The author prefers the first simple method (LA) where the
skin is infiltrated in the hand by injection of lidocain 1%
with adrenaline. Hand surgeons in many countries traditionally use LA combined with extremity exsanguinations
to obtain a bloodless field. Whereas a bloodless field is
absolutely mandatory for dissecting tendons and synovial
tissue, it is not the case for nerve dissection. The entrapment (CTS) cause cyanotic colour changes of the nerve
and/or distended vessels on the nerves, which cannot be
visualized in a bloodless field.19,30 Postoperative venous
haemorrhages in the operative field are also more common
following use of tourniquet. However, if one compares
blood oozing by the use of tourniquet and simple local
lidocain + adrenaline, the simple infiltration of skin with
adrenalin is superior to tourniquet.6
Intravenous anaesthesia combined with tourniquet is a
standard for many hand surgical procedures, but is more
complicated than LA.
carpal tunnel from the proximal wrist crease. After 4 - 5
minutes the quality of sensation is tested with small pin
pricks at the anaesthetic area and outside. Thereby the
patient will relax, learning the difference between normal
painful areas and the operative analgesic area. The hand is
then placed on a well-bolstered separate arm table. If it is
the right hand, the right-handed surgeon places himself at
the ulnar side of the hand to be operated upon. Visa versa if
the surgeon is left-handed. The reason being that the
surgeon then, in all cases, will cut and dissect from proximal
towards distal, whereby the risk of injuring nerve branches
that diverse from proximal to distal is reduced.
Before the operation, the surgeon prepares the microscope.
The surgeon must set the oculars and interpupillary distance
correctly and the microscope may be draped. He must also
determine if his own glasses shall be used or not. The
operative field is, with this type of surgery, rather stationary
so draping can be excluded as the hand can be moved to
maintain focus. The operative microscope is now brought
to its place (Fig. 2).
General anaesthesia may be indicated in cases of reoperations with significant scarring or if the patients are
very nervous.
Surgical techniques
Open carpal tunnel release
Open surgical section of the TCL has been the gold
standard surgical treatment for patients with CTS since
1854.12,17,21,23 Cutting the TCL with a scalpel under direct
vision produces reliable symptom relief in the vast majority
of cases.17 However, despite this high clinical success rate,
transient postoperative symptoms such as ‘‘pillar pain’’,
scar tenderness, or hand weaknesses are known to occur.22,
Figure 2 - Operative microscope.
37,44
Preoperatively the patient is carefully informed about how
the operation is carried out. It is thus described how local
anaesthesia is used and that he/she can feel “something”,
but no pain during the operation. During the operation
additional local anaesthetics can be applied, if necessary.
Instruments needed are simple: a surgical knife with a 15blade, a small retractor, that is used to hold the skin edges
apart, and an operative microscope for better viewing and
light. Magnifying loupes may be used in case a microscope
is not available. The author always advocates use of some
kind of magnification.
The hand/arm is carefully prepped with hexidine alcohol or
similar disinfection material. With a thin needle 4 - 5 cc
lidocain 1% with adrenaline is infiltrating the skin over the
VOLUME 14, NO. 2, OCTOBER 2010
The author uses two separate pairs of gloves for the surgery
for prevention of infection from skin flora.45 A 3 - 4 cm
long incision is made with a 15-blade from the distal crease
of the hand towards the interdigital space 3/4. All bleeding
vessels must be carefully occluded with bipolar coagulation,
with a low setting.29 Thereby postoperative blood oozing
in the wound is very seldom experienced. The small
retractor is placed to hold the skin edges. With aid of the
microscope the palmar aponeurosis is now visualized and
cut longitudinally. Eventual cutaneous nerve structures or
vessels are avoided. It is at this time exchange of the first
pair of gloves that are always contaminated with skin
bacterial flora is done. The TCL with its white transverse
fibres is now visualized and is opened by cutting with a 15blade in the middle, slightly ulnar to the midline. When the
carpal tunnel contents are encountered, the incision is
39
DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
carried further distally to the rim of the TCL until the
normal yellow fat is visualized. Then the proximal part of
the ligament is cut and eventually part of the antebrachial
fascia, again keeping ulnar (Fig. 3).
above systolic pressure are often necessary to obtain a
bloodless field. The introduction of the endoscope into the
carpal tunnel may increase pressure on the median nerve
and cause unpleasant sensations for the patient if carried out
in LA.17 Even with perfectly planned endoscope surgery
the surgeon must be prepared to change to an open type of
surgery if anatomical landmark identification is not possible.
Single-portal techniques are those in which a single
skin incision is made in the proximal wrist crease.1,22 Dualportal techniques are those in which a second supplementary small incision is made in the palm when the
endoscope/obturator has reached this area.8,40 Both methods
require some degree of hyperextension and fixation of the
hand during surgery. This hyperextension decreases the
volume of the carpal tunnel, as does the introduction of the
endoscope equipment.
Figure 3 - Median nerve inside the carpal tunnel.
The palmar motor branch of the median nerve is usually
never seen with this approach. The median nerve is
visualized in the tunnel and hourglass shape and eventual
cyanosis indicating the compression site is seen (Fig. 4).17
Figure 4 - Hourglass shape of compressed median nerve.
Movements of the tendons and the median nerve are
obtained by pulling the fingers and secures that the contents
in the canal is free. The TCL edges are coagulated with
bipolar coagulation and the skin closed in one layer with
single 5 - 0 sutures. The wound is covered with a band-aid
and the hand bolstered leaving the fingers free for active
movements immediately after surgery. The hand is kept
high for the first day and skin sutures removed after 12 - 14
days. Decreased wrist movements are common after two
weeks (relative immobilization) and should be treated by
active movements after the skin sutures have been removed.
Endoscopic carpal tunnel release techniques
Visualization of anatomical structure is of course of paramount importance when performing endoscope procedures.20
Blood obscures vision and extremity exsanguinations with
an Esmarch bandage followed by inflation of tourniquet
40
1) ECTR single-port technique: A small incision is
made in the distal hand crease on the ulnar side of the long
palmar muscle tendon. Through this an obturator is introduced blindly into the carpal tunnel developing a channel
for the endoscope. The endoscope sheet is then inserted
directly in the carpal tunnel through this channel followed
by introduction of the endoscope. A window near the tip of
the system angled upwards makes it possible to continuously view the undersurface of the TCL through the
endoscope. A hook knife cutting blade is then inserted via
the endoscope and cutting of the TCL takes place often
from distal to proximal viewing the ligament, but not the
median nerve.1,17
2) ECTR dual-port technique: With the two portal
techniques the introducer/obturator is also passed blindly
through the carpal tunnel through a similar small transverse
cut in the distal skin crease. When the obturator reaches the
palm a supplementary contra incision is made here and the
tip of this introducer is thereafter pushed out through the
skin (Fig. 5).
Loop around median nerve
Long
flexors
tendons
TCL - cut edges
Figure 5 - Two-portal endoscope technique.
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DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
The endoscope is then passed into the introducer from the
proximal end of the carpal tunnel and the channel is
inspected for contents. The custom designed instrumentation protects the median nerve and flexor tendons, and
positioning of the slotted cannula through the two portals
ensures a stable surgical environment.8,40 The surgeon
inserts a hook knife via the proximal port and advances it
behind the distal end of the TCL. The TCL is caught by the
knife and the ligament is cut with a backwards pull.
Complications due to operative treatments:
Nowadays, complications range from 0 - 24%.17 This huge
variation documents the influence of the surgical learning
curve/ and or surgical competence. According to recent
studies, the overall complication rate should be in the range
of 1 - 2% in experienced hands for both ECTR and OCTR
surgery.2,10,13,34,41,42,44,49-51
The most common complication due to OCTR and ECTR
is inadequate cutting of the distal part of the TCL.17 These
patients will not experience the immediate normal relief of
the painful hand paraesthesia after the operation. So, if the
patient still complains of painful paraesthesia after 2 - 3
days the surgeon must consider this complication.
Other complications are direct surgical lesion of the median
nerve including its motor branch and compression neuropathy due to pressure by the endoscope. A lesion of the
palmar cutaneous branch of median nerve may often lead to
a complex regional pain syndrome.17 Hypertrophic
hypersensitive skin scar is only seen if the skin incision has
been carried proximal to the distal wrist crease, whereas
slight pillar pain is common in the first weeks after OCTR
surgery. Injury to the superficial vascular arch distal in the
hand and wound infection are rarely encountered. Decreased grip strength is common with both methods for the
first 2 - 3 postoperative months, but will normally gradually
disappear. Erroneous decompression of the ulnar nerve in
Guyon´s canal instead of the median nerve may be the
result of lack of experience, both in OCTR and in
ECTR.17,30
incisions must take aim of visualization of the ligament and
then the contents of the carpal tunnel. Lack of magnification and light both disturb the possibilities of viewing the
carpal ligament sufficiently. Many open cases are rather
closed as a “Mickey”-probe is introduced into the canal and
the TCL thereafter cut on this probe that is supposed to
prevent lesions of the median nerve. Similarly, some
surgeons use a pair of scissors to cut the ligament with e.g.
introducing one branch blindly into the canal. They cannot
see the distal cut of the TCL. “To see” for the author, is the
first and most important factor for reducing complications
in OCTR.17 With the technique described here, the median
nerve is clearly viewed due to magnification and excellent
light in the operative field provided by the operative
microscope. Performing the skin incision the larger cutaneous nerves may be seen and protected. The white
transverse fibres of the TCL are also easily visualized with
the microscope. Another important point is that the author
never uses a tourniquet, thereby all degrees of nerve
compression including colour changes and vessels stasis are
clearly shown. The motor branch of the median nerve is
never found during this dissection and thus never sectioned
because you see all necessary details of the procedure nothing is blind. For teaching / learning activities it is also
possible to preserve the whole operation on a DVD or as
slides in a PowerPoint presentation for validation (MöllerWedelc).
Most series published are "personal" and thus not suited for
generalization - which is still done. The surgical learning
curve is important and because one great endoscope surgeon
or micro-neurosurgeon can carry out CTS operations with
minimal complications this does not invariably indicate that
all surgeons will accomplish the same.17 Endoscope techniques has many proponents who cite the potential benefits
of faster patient recovery time, less incision pain and
improved grip strength recuperation.1,10,11,22,31,32,34,40-43 No
controlled randomized series exist to prove these statements. Application of endoscopy techniques has not
decreased operative expenses, nor increased operative efficiency, or improved intraoperative visualization (compared
with conventional OCTR).42
Results of surgical treatment of CTS
Carpal tunnel syndrome must be graded in different
stages.17,39 In the early stages of CTS, total relief of pain
and nightly paraesthesia is obtained in close to 96% of all
cases within 24 - 48 hours. In later stages of CTS, full
return of sensation and muscle power cannot be anticipated,
as regeneration of the axonal injured nerve fibres will take
up to several years. The influence of postoperative training
- or “remodeling the brain” - is very important.38
Evans stated in an editorial in Journal of Handsurgery: “The
serious complications (… to CTS operations) must be
regarded as the result of: careless or inexperienced surgery
and the established principle of surgery under direct vision
has provided reliable protection against disaster".11
One of the main causes for surgical mistakes in OCTR is
improperly placed incisions.12,21 Hands are different and
Ulnar nerve entrapments
VOLUME 14, NO. 2, OCTOBER 2010
Proper formal training in both open and endoscope techniques must be obtained. 18
Ulnar nerve anatomy: Many variations in the ulnar
41
DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
nerve anatomy exist. The ulnar nerve follows the medial
head of the triceps muscle and enters the retrocondylar
groove behind the olecranon heavily protected in a fibroosseous tunnel. Distally the nerve gives off sensory
branches to the elbow joint and skin at the olecranon and
motor branches to the ulnar carpal flexor- and the medial
half of the deep flexor muscles.2,5,23,24,35,36 The space just
outside and distal to the groove created by an arcuate
aponeurosis (“Osborne ligament”) and the two heads of the
ulnar carpal flexor muscle is also called the Osborne
compartment.33 The ulnar nerve digs down and continues
into the forearm, lying between the ulnar carpal flexor
muscle and the deep long flexor muscle closely joined with
the ulnar artery. Distal at the wrist it enters Guyon´s canal
where it divides into sensory branches to the volar ulnar
part of the hand and 4th and 5th fingers, and superficial and
deep motor branches to the small hand muscles.19 Nerve
anastomosis between the ulnar- and median nerves exists in
the forearm and distally in the palm in many patients. A
gliding movement of up to 4.7 cm of the only 2 - 4 fascicles
of the ulnar nerve is taking place during flexion/extension
of the elbow in the average person.47 The fibro-osseous
canal size decreases during flexion and increases during
extension. In contrast, the Osborne compartment space
decreases with elbow extension. Therefore, we may anticipate two different types of entrapment and subsequently
two different operative treatments. The strain at elbow
flexion is maximal directly behind the medial epicondyle
with pressures that increases up to 3 times by elbow flexion.
The ulnar nerve may very rarely be compressed proximal to
the sulcus. Most common it is found in younger patients
compressed at the level of medial epicondyle due to recent
elbow fractures. If the fibro-osseous tunnel size is reduced
by trauma, the ulnar nerve may easily be entrapped here. In
the cubital compartment an elbow flexion causes stretching
of the ligament and the compartment flattens leading to
pressure on the ulnar nerve.27,33,36
Conservative treatment: Involves prevention of bending the elbow or compressing the nerve by sitting with the
elbow on the table, which is the most common treatment.17
Surgical treatment must be reserved for long-lasting
symptoms and thorough documentation. For indications to
surgery, the readers are kindly asked to read the more
detailed discussion.5,7,27,48 For the simple “Osborne” decompression LA is sufficient. Additional anaesthetics can be
applied if necessary and no tourniquet is needed.2,17,33 With
transposition procedures general anaesthesia is preferred.2,36
The minimal invasive technique by endo/ micro-surgery
may have an advantage, but needs long-term validation.24
Simple decompression techniques
1) “Osborne” operation: The skin distal to the ole-
42
cranon is infiltrated with 5 cc of local anaesthetics. The
skin is then opened from the middle of the line between the
olecranon and the epicondyle distal to the groove. The
muscle aponeurosis over the cubital tunnel is opened but the
retrocondylar groove is left untouched. After cutting the
muscle-aponeurosis the Osborne compartment is opened
and the ulnar nerve is located and dissected beneath the two
heads of the ulnar carpal flexor muscle. The author always
uses operative microscope at this stage. When the fascia
has been opened, the arm is moved to see how the nerve is
sliding. The author, does not open the fibro-osseous tunnel
(retrocondylar groove) unless compression here is suspected by inspection. If opened, it is only the distal half of
the fibro-osseous tunnel that is cut to allow release of the
ulnar nerve. Other authors do open the whole fibro-osseous
tunnel routinely releasing the nerve and leaving it to lie
freely only covered by connective tissue. The patient needs
to have a deep condylar groove in these cases. The risk of a
new postoperative chronic nerve irritation may easily
develop if the released nerve slides over the epicondyle
with elbow flexion. The skin is closed in two layers. The
patient is urged to move the elbow freely immediately after
surgery. At night an elbow bandage is used to prevent
maximum elbow flexion for the next 2 - 3 weeks. Skin
sutures are removed after 14 days.16,33
Open surgery is still the standard but cubital tunnel release
with endoscope assistance has been advocated with a new
micro/endo version in 2006.24 The author has no personal
experience with this method.
2) Epicondylectomy: Medial epicondylectomy is another
hypothetical way to release pressure on the ulnar nerve at
the elbow. This operation demands general anaesthesia.
Excision of the proper amount of bone is critical to the
success of this procedure. If too much bone is excised
damage to the medial collateral ligament of the elbow, deep
in the groove, may lead to a valgus position of the elbow
joint and painful instability of the medial elbow. Osteomyelitis is another severe complication to this operation.
Heterotope ossification may be the result of osteotomy and
thereby continuous minor trauma to the nerve may occur as
it is now unprotected.23,36,37 The author has also never
carried out this operation.
3) Ulnar nerve decompression with transpositions
of the nerve: Surgical decompression of the ulnar nerve
with subsequent anterior transposition to the medial
epicondyle is often suggested. Hereby the position of the
ulnar nerve should be shorter and tension of the nerve thus
be relieved. Interfascicular gliding should similarly be
improved. The ulnar nerve may be positioned subcutaneously above the muscle fascia or submuscular either under
or inside the pronator teres muscle.2,5,23,24,27 Lesions of
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DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
cutaneous branches to the olecranon/ elbow joint may result
from transposition techniques and long dissection of muscular and cutaneous branches may also be needed.
technique exist. Postoperatively, the elbow is immobilized
in 45 degrees of flexion in a post mould or cast for 3 - 4
weeks.2,23
A) The subcutaneous technique: An incision starts
some 8 cm proximal to the medial epicondyle and continues in front of this to 6 cm distal over the flexor carpi
ulnaris muscle. Branches of the medial antebrachial
cutaneous nerve are carefully protected to prevent lesions
and neuroma development. The ulnar nerve is found proximally and then dissected distally. It is freed from all septa,
Osborne ligament and flexor carpi ulnar fascia. The distal
medial intermuscular septum should also be cut protecting
major vessels. The ulnar nerve is mobilized in front of the
medial epicondyle preserving the motor branches to the
flexor muscles. If necessary, the articular branch to elbow
joint should be preserved too. The nerve now lies on the
fascia and the subcutaneous fat is sutured to the tip of the
medial epicondyle with non-absorbable sutures, thereby a
subcutaneous tunnel is created. It is ensured that the nerve
lies and moves freely (Fig. 6).
4) Guyon´s canal - wrist - decompression: A surgical
decompression is carried out most often from the volar side
of the wrist with a straight incision with a Z- at the wrist
creases. Another approach is from the ulnar side of the
hand via a Z-shaped incision lateral along the hypothenar.
Hereafter the pisiform bone is removed whereby the deep
motor branch is decompressed. Minor postoperative problems are the result of this latter procedure.2,19
Ulnar nerve transposed
Osborne compartment
opened
Sulcus
Olecranon
Cutaneous branch
for olecranon
Figure 6 - Ulnar nerve transposed subcutaneously.
Then the skin is sutured in two layers. Postoperatively, the
elbow is immobilized in a post mould or cast at 45 degrees
of flexion for 2 weeks. Active mobilization can start after
two weeks. This is the simplest transposition technique but
must be carried out meticulously to prevent later kinking of
the nerve both proximally and distally.2,7,27
B) Submuscular techniques: In submuscular transposition the initial dissection is as with the subcutaneous
technique. The idea is to position the ulnar nerve deeper
inside the muscle tissue. Therefore the origin of the flexorpronator muscle group is released and the nerve positioned
under these lying on the brachial muscle. Then the flexorpronator muscle is reattached securely. Variations of this
VOLUME 14, NO. 2, OCTOBER 2010
Results of surgical treatment of ulnar nerve
compression
The ulnar neuropathy is manifested by multiple pathogenesis factors. This manifests in different clinical situations
with similar symptoms. The acute ulnar nerve neuritis is a
completely different entity then that of an ulnar nerve
neuropathy or a median nerve neuritis. We have no
controlled and validated information with regard to which
surgical treatment to offer.2,7 We must accept this and be
cautious in our suggestions of what type of treatment the
patients should receive. Prevention seems better than any
surgical cure in the first stadium of the ulnar nerve diseases.
It seems more than relevant to carry out a careful
electrophysiological examination before surgery is decided
upon.17,19
Conservative treatment is based primarily on prevention of compression. Keep the elbow as straight as possible
if elbow flexions provoke symptoms. Use headsets instead
of mobile telephone, adjust workspace if necessary and use
elbow protectors if compression seems to be leading to
symptoms. This will, in most cases lead to reduced symptoms. Only if these treatments fail, surgery can be considered.2
Basically, the operative treatments consist of the "simple"
decompression with a minimum of complications. Simple
decompression will, in the majority of cases, be the best
choice of surgery.7 The technically, much more complicated
nerve-transposition procedures of the ulnar nerve, leads to
many complications.2,7,27,33 Transposition is carried out in
cases where medial dislocation of the nerve is a prominent
feature and the choice of subcutaneous and submuscular
transposition is not clear - the author favours the simplest
choice.
Complications
A kinking of the ulnar nerve can easily occur against the
medial intermuscular septum and under the aponeurosis
arch between the two heads of the ulnar flexor carpi muscle.
This happens if sufficient decompression is not carried
43
DISTAL MEDIAN– AND ULNAR NERVE COMPRESSION SYNDROME • Haase
out.2,7 Most common complications to operative treatment
are injury to the nerve while decompressing it or transposing it and neuromata of the medial antebrachial cutaneous
nerve.36
Endoscope decompression has been described, but only
lately with the combined endo-micro technique and it
seems to be a tool to be taken seriously in the future.24
Conclusion
Surgical treatment of median- and ulnar nerve compression
syndromes are very rewarding. The operations demands
similar micro techniques as with aneurysm surgery. All
techniques must be properly learned before being applied to
our patients.
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