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Surgical Science, 2011, 2, 8-12
doi:10.4236/ss.2011.21003 Published Online January 2011 (http://www.SciRP.org/journal/ss)
Copyright © 2011 SciRes. SS
Comparison of Histopathology of Transverse Carpal
Ligament in Patients with Idiopathic Carpal Tunnel
Syndrome and Hemodialysis Patients with Carpal
Erdinc Civelek1, Tufan Cansever1, Serdar Kabatas1, Ebru Demiralay2,
Emre Demircay3, Cem Comunoglu2, Cem Yilmaz4, Nur Altınors4
1Department of Neurosurgery, Baskent University Istanbul Hospital, Istanbul, Turkey
2Department of Pathology, Baskent University Istanbul Hospital, Istanbul, Turkey
3Department of Orthopedics, Baskent University Istanbul Hospital, Istanbul, Turkey
4Department of Neurosurgery, Baskent University, Ankara, Turkey
Received August 14, 2010; revised September 15, 2010; accepted September 25, 2010
The aim of this paper is to point out the growing clinical importance of Carpal tunnel syndrome in patients
on hemodialysis especially in aspect of the diagnosis, treatment and possible cause of the syndrome. Sixty
patients with clinical diagnosis of Carpal Tunnel Syndrome was defined as the presence of two subjective
symptoms (numbness, tingling in the median nerve distribution). The diagnosis was confirmed by electro-
myography. The patients with rheumatoid arthritis, thalasemia and thyroid dysfunction and the patients hav-
ing pain due to arthritis or tenosynovitis were excluded. Fifty patients with clinical diagnosis of idiopathic
CTS and seven hemodialysis patients having CTS were analyzed. Of 50 patients (47 female, 3 male) with
clinical diagnosis of idiopathic CTS, 11 patients (22%) were involved bilaterally, 25 patients (50%) were
affected only on the right and 14 patients (28%) were symptomatic only on the left. Of 7 hemodialysis pa-
tients (2 female, 5 male) with CTS, 1 patient (14%) was involved bilaterally (having two-sided A-V fistula),
4 patients (57%) were affected only on the right and 2 patients (28%) were symptomatic only on the left.
There was significant correlation between the arteriovenous fistula and subsequent development of CTS. The
all patients had fistulas in the affected side (5 of them were patent and 2 were occluded). In the relation be-
tween the duration of hemodialysis and development of CTS, 4 patients were over 10 years of hemodialysis,
2 patients were between 5 to 9 years and only 1 patient was below 4 years of duration. Amyloid deposit was
demonstrated in 4 of 7 operated hands in the hemodialysis group. When we compared the presence of amy-
loid deposits in these groups, the difference between these two groups were found as statistically significant
(p < 0.009). Although hemodialysis has no significant effect on development of fibrosis, the incidence of
fibrosis was found as statistically significant in idiopathic carpal tunnel syndrome (p < 0.048). It is likely that
there are numerous factors that may act either independently or in concert to potentiate the risk for develop-
ing CTS in patients on long-term hemodialysis.
Keywords: Carpal Tunnel Syndrome, Hemodialysis, Chronic Renal Failure
Neurological complications in patients with renal failure
and hemodialysis are well-known. Among them periph-
eral nerve involvement has been considered as a toxic
polyneuropathy affecting mainly distal parts of the four
extremities. Entrapment neuropathy such as Carpal tun-
nel syndrome (CTS) could be completely curable with
defined diagnosis and proper treatment [1,2].
CTS is divided into two large groups; idiopathic CTS
and symptomatic CTS. Symptomatic CTS may range
from due to traumas, anomalies, inflammation, neo-
E CIVELEK ET AL.
Copyright © 2011 SciRes. SS
plasms, rheumatism, metabolic disorders and etc. Among
them we list a hemodialysis as a one of crucial causes of
symptomatic CTS. A raised intracarpal canal pressure
results in median nerve compression and impaired nerve
perfusion that leads to discomfort and paresthesias in the
one or both hands. In early stages, patients usually com-
plain of symptoms due to the involvement of the sensory
component of the median nerve and only later report
symptoms from involvement of motor fibers. Patients
may also complain of pain radiating to the forearm, el-
bow or even the shoulder.
The exact pathogenesis of CTS is not clear. Several
theories are present to explain the symptoms and im-
paired nerve conduction studies. The most popular ones
are mechanical compression, micro-vascular insuffi-
ciency, and vibration theories [3,4].
The patient with mild symptoms of CTS can be man-
aged with conservative treatment, particularly local in-
jection of steroids. However, in moderate to severe cases,
surgery is the only treatment that provides cure. The ba-
sic principle of surgery is to increase the volume of the
carpal tunnel by dividing transverse carpal ligament to
release the pressure on the median nerve.
The aim of this paper is to point out the growing clin-
ical importance of CTS in patients on hemodialysis es-
pecially in aspect of the diagnosis, treatment and possible
cause of the syndrome.
All patients (the number of 60) in the study had a clinical
diagnosis of Carpal Tunnel Syndrome (CTS), which was
defined as the presence of two subjective symptoms
(numbness, tingling in the median nerve distribution).
Electromyography was examined in the abductor pollicis
brevis, first dorsal interosseous and flexor carpi radialis
muscles with concentric needle electrodes. The CTS di-
agnosis was confirmed by electromyography. A total of
10 patients had one or more associated predisposing fac-
tors or conditions (renal failure = 7; rheumatoid arthritis
= 1; thalasemia = 1; thyroid dysfunction = 1). The pa-
tients with rheumatoid arthritis, thalasemia and thyroid
dysfunction and the patients having pain due to arthritis
or tenosynovitis were excluded. Fifty patients with clini-
cal diagnosis of idiopathic CTS and seven hemodialysis
patients having CTS were analyzed.
The median age was 65 years (range 42 – 83 years),
with a mean follow-up period of 14 months (range 12 to
26 months). Decompression of the carpal tunnel was
performed using a standard open technique, which in-
volved a 3-4 cm curvilinear incision. The palmar fascia
and flexor retinaculum was then divided under direct
vision, taking care to protect the recurrent motor branch.
Sectioned specimens of the transverse carpal ligament
of operated cases were stained with Hematoxylene (H)
and eosin (E) and crystal violet and examined with light
and polarized-light microscopes (Figures 1,2 and 3). The
specimens from transverse carpal ligament were pathol-
ogically evaluated according to parameters of presence
of amyloid deposits, fibrosis, edema, lipomatosis, vascu-
lar proliferation, and perivascular lenfositic infiltration.
Semi-quantatively, edema, fibrosis and vascular prolif-
eration were classified as none (0), mild (1), moderate
(2), lipomatosis, perivascular lymphocyte infiltration and
amyloid deposition were classified as none(0) and pre-
sent (1) (Table 1). The pathological results were com-
pared statistically by using linear regression test. P value
less than 0.01 and 0.05 was accepted as significant.
Figure 1. Hematoxylene and eosin staining of specimen of
transverse carpal ligament showing vascular proliferation
(arrows) and lipomatosis (asterisks) (H&E x 100).
Figure 2. Hematoxylene and eosin staining of specimen of
transverse carpal ligament showing perivascular lympho-
cyte infiltration (arrows) (H&E x 100).
E CIVELEK ET AL.
Copyright © 2011 SciRes. SS
Figure 3. Crystal violet staining of specimen of transverse
carpal ligament showing amyloid deposits (Crystal violet x
Table 1. Semi-quantities measurement criteria of edema,
vascular proliferation and fibrosis.
Grade Edema Vascular prolifera-
0 none none none
1 Minimal dissocia-
tion of collagen
Minimal increase in
in number of fibro-
tion of collagen
bands and fluid
between the bands
Intense clustering of
vascular structures Extensive fibrosis
Of 50 patients (47 female, 3 male) with clinical diagnosis
of idiopathic CTS, 11 patients (22%) were involved bi-
laterally, 25 patients (50%) were affected only on the
right and 14 patients (28%) were symptomatic only on
the left. Of 7 hemodialysis patients (2 female, 5 male)
with CTS, 1 patient (14%) was involved bilaterally
(having two-sided A-V fistula), 4 patients (57%) were
affected only on the right and 2 patients (28%) were
symptomatic only on the left. There was significant cor-
relation between the arteriovenous fistula and subsequent
development of CTS. The all patients had fistulas in the
affected side (5 of them were patent and 2 were oc-
cluded). In the relation between the duration of hemodi-
alysis and development of CTS, 4 patients were over 10
years of hemodialysis, 2 patients were between 5 to 9
years and only 1 patient was below 4 years of duration.
Amyloid deposit was demonstrated in 4 of 7 operated
hands in the hemodialysis group. When we compared the
presence of amyloid deposits in these groups, the differ-
ence between these two groups were found as statisti-
cally significant (p < 0.009).
Fibrosis was not observed in the hemodialysis group,
but it was demonstrated in 19 of 50 operated hands in the
idiopathic group. Although hemodialysis has no signifi-
cant effect on development of fibrosis, the incidence of
fibrosis was found as statistically significant in idiopathic
carpal tunnel syndrome (p < 0.048). This may be due to
slow progression of the pathology of the idiopathic car-
pal tunnel syndrome.
When we compared these two groups according to
parameters of presence of edema, lipomatosis, vascular
proliferation, and perivascular lenfositic infiltration,
there was no significant difference (Table 2).
Paresthesia such as sensation of swelling, numbness or
tingling of the first three radial digits and radial volar
aspect of the palm were noted in 100% of the hands. Pain
in the first radial digits and wrist were particularly severe
at night and sometimes during hemodialysis. Motor
weakness and muscle atrophy were found only in the
thenar muscles of the advanced cases. Tinel’s and Pha-
len’s signs were demonstrated in 45% and 36% of the
symptomatic hands, respectively.
No patients developed minor wound infection post-
operatively. Following the operation, all symptoms were
disappeared in a month except slight numbness in the
small area of the second and third finger tips.
4. Results and Discussion
Carpal tunnel syndrome is the most common form of
peripheral neuropathy, affecting around 0.1 to 1% of the
Normal 09839,288,2 62,715,7
Choronic Renal Failure14,313,7085,757,114,3
proliferation lipomatosis l ymphocyte
Table 2. Comparison of the hemodialysis (chronic renal
failure) and the idiopathic group according to parameters
of presence of amyl oid deposits, fibrosis, edema, lipomatosis,
vascular proliferation, and perivascular lenfositic infiltra-
E CIVELEK ET AL.
Copyright © 2011 SciRes. SS
population with an estimated lifetime risk of 10%. In
hemodialysis patients, the incidence of Carpal tunnel
syndrome is 4-15%. The carpal tunnel syndrome is
commonly seen in patients who have received hemodi-
alysis for a long time [5,6]. The prevalence of the syn-
drome increases with the duration of dialysis, and nearly
all patients treated for more than 18 years require a de-
compression operation [5,6]. In an other study, the per-
centage of patients requiring surgery was none before 8
years, 50% of those on hemodialysis for 14 years and
100% of patients on hemodialysis for 20 years . In the
relation between the duration of hemodialysis and de-
velopment of CTS, 4 patients were over 10 years of he-
modialysis, 2 patients were between 5 to 9 years and
only 1 patient was below 4 years of duration in our
Pathogenesis of CTS in hemodialysis patients has not
been fully explained. It may differ somewhat from that
of idiopathic CTS. The incidence of CTS appears to be
higher in hemodialysis patients than commonly esti-
mated rate in general population. A relatively high inci-
dence of male patients (71% in our series) is another
characteristic point in CTS in hemodialysis patients. In
idiopathic CTS, a predominance of female patients
(60-80%) has been generally described [8,9,10]. It was
94 % in our study.
Dialysis-induced amyloidosis is a well-known com-
plication involving deposition of amyloid fibrils that
consists of β2-microglobulin. It has been suggested that
the deposition of this new form of amyloid is related to
chronic immunologic stimulation during hemodialysis
with the use of poorly biocompatible membranes .
But, the other reports have shown that β2-microglobulin
precipitates in vitro to form amyloid. Because the circu-
lating levels of β2-microglobulin are elevated in cases of
renal failure, an accumulation of β2-microglobulin and
subsequent formation of amyloid deposits in tissue is
possible [12,13]. In hemodialysis patients, Kachel et al.
investigated other tissue sites and demonstrated amyloid
deposits in the peripheral tissue, skins and rectum . In
the present study, it is possible to confirm the relation-
ship between the development of CTS in hemodialysis
patients and deposits of amyloid in the carpal tunnel.
Miyasaka et al. detected several macrophage-like cells
around local blood vessels as well as invading the syno-
vial tissues of CTS, and discovered that these cells were
positive for IL-1 and IL-6 .
In the literature, one possible explanation for the de-
velopment of CTS during hemodialysis could be an in-
creased pressure in the carpal tunnel due to periodic in-
crease of total body water and venostasis . The in-
creased pressure then leads to impaired microcirculation
around the carpal tunnel. This circulatory hypothesis
may explain a transient relief of the symptoms following
hemodialysis and an exacerbation at night. The high in-
cidence of CTS in patients with generalized edema due
to myxoedema and pregnancy may also support this hy-
A close relationship between CTS and presence of an
arteriovenous fistula has been postulated . High rates
of blood flow through the fistula may lead to nerve en-
trapment. High rates of blood flow through the fistula
may lead to nerve entrapment. High rates of blood flow
may cause an increased venous pressure and engorge-
ment of the structures within the carpal tunnel. An alter-
native possibility is that high rates of blood flow may
lead to ischemia within the carpal tunnel and may pre-
dispose the nerve to injury . In our study, the all pa-
tients had fistulas in the affected side (5 of them were
patent and 2 were occluded). Anatomic changes in the
wrist area due to the fistula are probably important in the
development of this syndrome.
It is likely that there are numerous factors that may act
either independently or in concert to potentiate the risk
for developing CTS in patients on long-term hemodialy-
sis. Further investigations are necessary to substantiate
the pathogenesis of CTS.
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