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Nerve conduction studies in patients with ankylosing spondylitis

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o r i g i n a l c o m m
Nerve Conduction Studies in Patients
With Ankylosing Spondylitis
Osman Hakan Gündüz, MD; Mehmet Zeki Kıralp, MD; Levent Özçakar, MD; Engin Çakar, MD;
Pelin Yıldırım, MD; Gulseren Akyuz, MD
Objectives: The objective of this study was to investigate any
relationship between peripheral neuropathy and ankylos-
ing spondylitis (AS), and to evaluate the peripheral nervous
system of AS patients and disclose any relationship between
neuropathy and disease-related parameters.
Patients and Methods: Thirty-two AS patients without any
symptoms of neuropathy were prospectively recruited in
2 centers. They were substantially evaluated both for AS
and evidence of peripheral neuropathy. Motor and sen-
sory nerve conduction studies with regard to median, ulnar,
common peroneal, tibial, and sural nerves were performed.
Nerve conduction study results of AS patients were com-
pared with those of 30 healthy subjects.
Results: Six patients (18.8%) were diagnosed to have involve-
ment of the peripheral nervous system (5 sensory and 1 sen-
sorimotor), and 7 patients (21.9%) had focal nerve involve-
ments (6 had prolonged median distal sensory latency and
1 patient had slowing of the right ulnar nerve motor conduc-
tion velocity at the cubital tunnel). Tibial nerve motor con-
duction velocity was positively correlated with Schober (r =
0.48, p = .03) and chest expansion tests (r = 0.44, p = .05).
Sural nerve sensory action potential amplitude was found to
be negatively correlated with age (r = –0.53, p = .02) and
disease duration (r = –0.55, p = .02). Ulnar nerve motor con-
duction velocity at the forearm was positively correlated
only with Schober values (r = 0.48, p = .03).
Conclusions: We imply that the peripheral nervous system
can as well be involved as the central nervous system in
asymptomatic AS patients. Further studies with larger sam-
ples and with longer disease duration are awaited to con-
firm our results and to unravel its clinical relevance. Other
types of neuropathies or the burden of several drugs on
peripheral neuropathy also remains to be deciphered.
Keywords: inflammation n neuropathy
J Natl Med Assoc. 2010;102:243-246
Author Affiliations: Department of Physical Medicine and Rehabilitation,
Marmara University Medical School, Istanbul, Turkey (Drs Gündüz, Yıldırım,
and Akyuz); Department of Physical Medicine and Rehabilitation, Gül-
hane Military Medical Academy, Istanbul, Turkey (Drs Kıralp, Özçakar, and
Çakar); Department of Physical Medicine and Rehabilitation, Hacettepe
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
u n i c a t i o n
University Medical School, Ankara, Turkey (Dr Özçakar).
Correspondence: Osman Hakan Gündüz, MD, Louisiana School of
Medicine, Department of Medicine, Section of Physical Medicine and
Rehabilitation, 2020 Gravier St, 7th Floor, Rm 734, New Orleans, LA 70112
(drhakang@hotmail.com).
Introduction
P
eripheral nerve involvement has been reported in
several rheumatic diseases,1-6 and there are mainly
3 mechanisms underlying the neuropathy: direct
involvement of the nerve(s), mechanical entrapment due
to adjacent arthritis or tenosynovitis, and medications.
The former has been mentioned to ensue in association
with immune-mediated processes, small-vessel vascu-
litis, amyloidosis, and inflammation.2 Entrapment syn-
dromes at the carpal tunnel and tarsal tunnel have been
described in patients with various inflammatory disor-
ders. Further, concerning the potential neurotoxic effects
of several drugs, the number of which seems to mount
continuously, neuropathy remains to be an important
issue during the management of these disorders.
Objectives
Nervous system involvement, more of the central ner-
vous system (multiple sclerosis, cauda equina syndrome,
focal epilepsy, vertebrobasilar insufficiency) and less of
the peripheral nerves, is known in ankylosing spondylitis
(AS).7-11 On the other hand, although studies have been
performed regarding the electrophysiologic evaluations
of the peripheral nervous system in rheumatoid arthri-
tis1,3,6 and Behçet’s disease,4,5 to the best of our knowledge,
a similar study has not been carried out in AS. Therefore,
the purpose of our study was to investigate any possible
relationship between peripheral nervous system involve-
ment and disease-related parameters in AS.
Patients and Methods
Patients
Thirty-two AS patients (29 males and 3 females),
admitted consecutively, fulfilling the modified New York
criteria—without any symptoms with respect to periph-
eral nerves—were prospectively recruited in 2 centers.
VOL. 102, NO. 3, MARCH 2010 243
Peripheral Nerve Involvement in Ankylosing Spondylitis
All patients were under a combination of nonsteroidal
anti-inflammatory drug and sulphasalazine treatment.
Subjects with diabetes mellitus, hypothyroidism, chronic
renal failure, alcoholism, cervical/lumbar root compres-
sion, with contraindication for electrophysiological test-
ing, or those using drugs that can cause neuropathy were
excluded.
Clinical Assessment
All patients were substantially evaluated both for AS
and evidence of peripheral neuropathy. The former com-
prised duration of morning stiffness; lumbar Schober;
occiput-wall, chin-chest, finger-floor distances; Bath
Ankylosing Spondylitis Disease Activity Index
(BASDAI) and Bath Ankylosing Spondylitis Functional
Index (BASFI). The latter included questions including
the presence of motor (loss of or decreased strength),
sensory symptoms (decreased or abnormal sensation),
ataxia and physical/neurological examination, namely
motor (muscle strength testing), sensory (pinprick, light
touch, temperature, position and vibration senses) and
reflex testing (muscle stretch reflexes and pathological
reflexes) in all extremities.
Electrophysiological Testing
All the electrophysiological examinations were per-
formed by the same experienced electrophysiologist.
Motor and sensory nerve conduction studies with regard
to median, ulnar, common peroneal, tibial, and sural
nerves were performed in the right upper and lower limbs
of each and every patient in accordance with Oh’s proto-
col, using the same distances for each nerve, in all the
patients and the controls.12 Electrophysiological testing
was carried out at 25ºC room temperature by using
Medelec (Sapphire, England). If an abnormal finding was
detected during these initial evaluations, the protocol was
extended to all extremities. The electrophysiologist was
not blind to the patients’ diagnosis but had no information
Table 1. Clinical Features of the Patients
Mean ± SD
Age at disease onset, y 20.30 ± 7.97
Disease duration, y 9.09 ± 6.78
Duration of morning stiffness, h 1.07 ± 1.10
Erythrocyte sedimentation rate, mm/h 28.96 ± 23.68
C-reactive protein, mg/dl 16.17 ± 12.07
Visual analogue scale, cm 5.76 ± 2.00
BASFI 4.10 ± 1.61
BASDAI 3.41 ± 1.27
Schober, cm 2.85 ± 1.40
Chest expansion, cm 3.70 ± 1.78
Finger-floor distance, cm 21.43 ± 14.48
Chin-chest distance, cm 1.13 ± 1.58
Occiput-wall distance, cm 2.17 ± 3.60
Abbreviations: BASDAI, Bath Ankylosing Spondylitis Disease
Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index.
244 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
about their clinical evaluation parameters. Demyelination
was described as the slowing of nerve conduction veloci-
ties, and axonal involvement was described as diminished
motor or sensory action potentials. Nerve conduction
study results of AS patients were compared with those of
30 healthy subjects who were recruited from hospital staff
and their relatives (27 males, 3 females).
The study was approved by the local ethics commit-
tee, and the subjects signed an informed consent form
prior to entering the study.
Statistical Analysis
Statistical analysis was done by using SPSS version
15.0 (SPSS Inc, Chicago, Illinois). Student t test was
used for group comparisons, and correlation analysis
was defined by Pearson coefficients. Statistical signifi-
cance was set at p < .05.
Results
Mean age values of the patients and controls were 31.23
± 11.27 and 31.40 ± 10.17 years, respectively (p > .05).
Clinical features of the patients are given in Table 1. The AS
group included patients with a mean disease duration of
9.09 ± 6.78 years, and fairly active disease, as seen from the
BASDAI scores, erythrocyte sedimentation rate, and
C-reactive protein levels. Regarding neurological examina-
tions, 5 patients had hypoesthesia, 1 had distal hypoesthesia
in all of the extremities, 1 had hypoesthesia in both lower
extremities (these 2 patients were later diagnosed to have
sensory polyneuropathy), and 2 had hypoesthesia in the
median nerve distribution (these patients had electrophysi-
ological diagnosis of carpal tunnel syndrome). None of the
patients had motor and reflex abnormalities upon neurolog-
ical examination. Electro-physiological parameters of AS
patients and control subjects are given in Table 2. Overall,
6 patients (18.8%) were diagnosed to have involvement of
the peripheral nervous system (5 sensory and 1 sensorimo-
tor), and 7 patients (21.9%) had focal nerve involvements
(6 of which had prolonged median distal sensory latency—5
right-sided and 1 left-sided carpal tunnel syndrome—and 1
patient had slowing of the right ulnar nerve motor conduc-
tion velocity at the cubital tunnel) (Table 3). Mean disease
duration of AS patients was 9.14 years in those with a focal
and 14.17 years in patients with a generalized peripheral
nerve involvement (Table 3).
Tibial nerve motor conduction velocity was posi-
tively correlated with Schober (r = 0.48, p = .03) and
chest expansion (r = 0.44, p = .05). Sural nerve sensory
action potential amplitude was found to be negatively
correlated with age (r = –0.53, p = .02) and disease dura-
tion (r = –0.55, p = .02). Ulnar nerve motor conduction
velocity at the forearm was positively correlated only
with Schober values (r = 0.48, p = .03).
One patient in the control group had electrophysio-
logical evidence of mild right-sided carpal tunnel syn-
drome. All others were found to be normal.
VOL. 102, NO. 3, MARCH 2010
 Peripheral Nerve Involvement in Ankylosing Spondylitis

Discussion include nerve entrapment, drug toxicity, vasculitis, amy-

In this study, we evaluated the peripheral nervous
system in a group of AS patients and observed that a sig-
nificant number of patients (40.6%) had electrophysio-
logically proven peripheral nerve involvement. Previous
studies have reported peripheral nerve involvement in
rheumatic disorders with controversial results: 23%6 and
57.4%3 in rheumatoid arthritis, and 14.2% in Behçet’s
disease.4 Although few, neurological complications in
AS have classically been reported due to the involve-
ment of the central nervous system. Generally proposed
mechanisms encompass instability (atlantoaxial sublux-
ation, fracture, dislocation), inflammation (cauda equina
syndrome, single root lesions), and compression of the
neural structures (by ossified intraspinal ligaments,
granulation tissue, or foraminal stenosis).13 To the best
of our knowledge, involvement of the peripheral ner-
vous system has not been studied by nerve conduction
studies in the hitherto literature concerning AS. Whether
related with amplitude, latency, or conduction velocity
values, in our study group, median, ulnar, common pero-
neal, tibial, and sural nerves were found to be affected to
different extents when compared with the normal indi-
viduals (Table 2). Further, some parameters of those
nerves (tibial and sural nerves), in which polyneuro-
pathic involvement generally outweighs that of entrap-
ment syndromes, also correlated with some disease-
related measures (age, disease duration, chest expansion,
and Schober). As the AS patients had more limitations
of axial motions (ie, decreased chest expansion and
Schober measurements), tibial and ulnar nerve motor
conduction velocities were found to be decreased.
Various causes of neuropathy in rheumatic diseases
loidosis, and autoimmunity.2,3 Far from explaining the
exact mechanisms, according to our results, we may
imply that the character of peripheral nervous system
involvement in AS seems to be both axonal (decreased
amplitude) and demyelinating (prolonged distal latency
and decreased conduction velocity). Herewith, needle
electromyography examination is also necessary to con-
firm such a conclusion. Although sensory and motor
involvements were present, the sensory component was
overwhelming (Table 3). Moreover, when compared
with the neuropathy of rheumatoid arthritis as reported
by Agarwal et al3 (12 cases of neuropathy within the first
year of disease), the clinical scenario seems to be slower
in AS. Yet, mean disease duration of AS was 9.14 years
in patients with focal neural involvement and 14.17
years in those likely to have generalized involvement.
This finding is also in accordance with the central ner-
vous system involvement of AS being worse in patients
with long-standing disease course.
The peripheral nerve involvement in some of our
patients might also be due to sulphasalasine use.
However, sulphasalasine-related peripheral neuropathy
is rare and has been reported anecdotally in the litera-
ture, either in patients with slow acetylator phenotype or
due to prolonged use of the drug.14-16
Conclusions
To conclude, in light of our first and preliminary
results, we imply that the peripheral nervous system can be
involved as the central nervous system in asymptomatic
AS patients. Further studies with larger samples and with
longer disease duration are awaited to first confirm our

Table 2. Comparative Electrophysiological Measurements of the Subjectsa

AS Patients Control Group

(Mean ± SD) (Mean ± SD) P
Median nerve motor distal latency 3.2 ± 0.4 2.9 ± 0.4 .00
Median nerve motor amplitude 6.8 ± 2.7 10.1 ± 3.1 .00
Median nerve motor conduction velocity 59.8 ± 5.4 57.5 ± 4.8 .09
Ulnar nerve motor amplitude 5.6 ± 2.1 7.4 ± 1.2 .00
Ulnar nerve motor conduction velocity 62.6 ± 6.2 65.6 ± 6.1 .06
Median nerve sensory amplitude 36.9 ± 14.7 53.6 ± 20.4 .00
Median nerve sensory conduction velocity 52.1 ± 5.9 53.9 ± 3.1 .14
Ulnar nerve sensory amplitude 38.4 ± 16.5 41.5 ± 12.4 .42
Ulnar nerve sensory conduction velocity 51.3 ± 5.5 54.2 ± 3.3 .02
Common peroneal nerve distal motor latency 3.9 ± 0.6 3.6 ± 0.7 .05
Common peroneal nerve motor amplitude 3.2 ± 1.7 4.6 ± 1.2 .00
Common peroneal nerve motor conduction velocity 51.1 ± 3.9 50.2 ± 4.1 .40
Tibial nerve distal motor latency 5.5 ± 1.0 4.3 ± 0.6 .00
Tibial nerve motor amplitude 4.8 ± 2.2 6.4 ± 1.8 .00
Tibial nerve motor conduction velocity 47.6 ± 4.7 46.3 ± 3.4 .25
Sural nerve sensory amplitude 15.1 ± 7.7 19.7 ± 6.6 .02
Sural nerve sensory conduction velocity 48.5 ± 5.7 50.4 ± 5.7 .24
a
Latency (ms), motor amplitude (mV), sensory amplitude (µV), conduction velocity (m/s).

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION VOL. 102, NO. 3, MARCH 2010 245
 Peripheral Nerve Involvement in Ankylosing Spondylitis

Table 3. Description of Patients With a Peripheral Nervous System Involvement

Disease Schober, Chest ESR,
Patient Duration, y cm Expansion, cm BASFI BASDAI mm/h Diagnosis
29 y, male 8 4.5 5.5 5.1 0.9 18 Left CTS
23 y, male 5 1.3 2.5 6.1 4.8 55 Right CTS
22 y, male 8 3.5 6.5 5.3 4.2 11 Sensory PNP
46 y, male 25 2.5 3.5 3.5 3.5 28 Right CTS
48 y, male 27 2.5 2.0 3.5 3.5 78 Sensory PNP
30 y, male 7 2.0 3.7 2.3 2.7 25 Right CTS
34 y, male 11 1.2 2.0 5.6 2.9 21 Sensory PNP
25 y, male 7 4.5 5.0 3.9 3.5 5 Right CTS
42 y, female 7 3.0 2.0 2.3 4.5 33 Right CuTS
30 y, male 11 3.0 4.5 4.3 3.4 35 Sensory PNP
59 y, male 19 2.5 1.0 1.5 1.5 61 Sensory PNP
22 y, male 9 3.0 4.0 7.4 4.9 7 Sensorimotor PNP
39 y, male 5 4.1 4.3 5.2 4.5 32 Right CTS

Abbreviations: BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; CTS:
carpal tunnel syndrome; CuTS: cubital tunnel syndrome; ESR: erythrocyte sedimentation rate; PNP: polyneuropathy.

results and to unravel its clinical relevance. Last but not
least, other types of neuropathies or the burden of several
drugs, including tumor necrosis factor-a antagonists,17 on
peripheral neuropathy also remains to be deciphered.
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