Gbs hyperreflexia

Hyper reflexia in Guillain-Barré
syndrome: relation with acute motor
axonal neuropathy and anti-GM1
antibody
 JNNP-1999;67;180-184(august)
 Satoshi Kuwabaraa, Kazue Ogawaraa, Michiaki
Kogab, Masahiro Moria, Takamichi Hattoria,
Nobuhiro Yukib
 a Department of Neurology, Chiba University School
of Medicine, Chiba, Japan, b Department of
Neurology, Dokkyo University School of Medicine,
Tochigi, Japan

objectives:
 Guillain-Barré syndrome (GBS) is an immune mediated polyneuropathy
clinically characterised by acute symmetric muscle weakness and
areflexia. Whereas most GBS is demyelinating neuropathy (acute
inflammatory demyelinating polyneuropathy, AIDP) in western
countries, an axonal form of GBS, termed acute motor axonal
neuropathy (AMAN), has been recognised in northern China and in
other countries. It is suggested that AMAN is associated with pure motor
axonal involvement, antiganglioside GM1 antibodies, or preceding
Campylobacter jejuni infection.
 Chinese patients with AMAN are reported to often develop hyperreflexia
during the early phase of recovery, and other studies described patients
with acute motor neuropathy with preserved tendon reflexes.Preserved
or exaggerated tendon reflexes do not usually occur in patients with
AIDP and in patients with other peripheral neuropathies.
 We, therefore, investigated the incidence of hyperreflexia and its
relation with electrophysiological subtypes (AMAN or AIDP), anti-GM1
antibodies, or C jejuni infection in consecutive patients with GBS in
Japan

Patients and methods:
 Fifty four patients with GBS who were seen at Chiba University Hospital
and its affiliated hospitals between January 1992 and April 1998 were
studied. The mean age was 40.1 years (range 3 to 78 years). Their first
neurological examination and electrodiagnostic study were done within
2 weeks of onset. They fulfilled the clinical criteria for GBS, except for
two patients who had normal or brisk tendon reflexes in the first
examination. The two patients were diagnosed as having AMAN
because of electrophysiological evidence of motor axonal loss. Clinical
disability was evaluated with the Hughes functional grading scale and
patients were followed up for 3 months after onset.
 Hyperreflexia was regarded as present when there were increased
amplitudes of tendon reflexes, abnormal reflex spread (finger jerks after
tendon tapping of the biceps brachii or brachioradialis muscle, or thigh
adduction after patella tendon tapping), and decreased reflex threshold
(biceps contraction after tendon tapping of the brachioradialis, or
quadriceps contraction after tapping of the midportion of the patella).
Hoffmann's and Babinski's signs were also examined.

electrophysiology
 Nerve conduction and H-reflex studies were done sequentially using the
conventional procedures. AMAN or AIDP was diagnosed based on the
electrodiagnostic criteria described by Ho et al. When, besides the
AMAN pattern, amplitude reduction of sensory nerve action potentials
was present, the patients were classified as having acute motor-sensory
axonal neuropathy (AMSAN). When nerve conduction studies were
done more than once within 2 weeks of onset, the results of the last
study were used for the electrodiagnostic classification.
 The H-reflex in the soleus muscle was recorded after submaximum
stimulation delivered to the tibial nerve at the knee. Stimulus duration
was 1.0 ms and the rate was 0.5 Hz. Patients lay in the prone position
with the ankle joint maintained at approximately 120°. The ratio of the
peak to peak maximum H-reflex to the maximum compound muscle
action potential (H/M ratio) was measured. Whether the H-reflex was
elicited in the abductor pollicis brevis or abductor hallucis muscle, was
also examined after stimulation at the wrist or ankle respectively. The
H/M ratio control data were obtained from 15 normal volunteers aged
21 to 52 years (mean 38.6 years).

 ANTI-GM1 ANTIBODY ASSAY
Serum samples obtained in the first 4 weeks after onset were frozen at
80°C until used. The serum samples were tested for the presence of
IgG and IgM antibodies to GM1 by the enzyme linked immunosorbent
assay . Well characterised human serum with high IgG anti-GM1
antibody titre was the internal control. Antibody titre was the highest
serum dilution at which the optical density at 492 nm was 0.1 or more.
Serum was considered positive when the titre was 1:500 or more.
 ANTI-CAMPYLOBACTER JEJUNI ANTIBODY ASSAY
IgG anti-C jejuni antibody was measured by the enzyme linked
immunosorbent assay . Serum was considered positive when the titre
was 1:2000 or more. The IgG anti-C jejuni antibody assay is sufficiently
sensitive and specific for serological evidence of C jejuni infection, even
if IgM and IgA antibodies are not determined. All anti-GM1 and anti-C
jejuni antibody assays were done by one investigator (MK) who was
blinded to the clinical and electrophysiological data.

STATISTICAL ANALYSIS
Differences in percentages
were tested
with X2 or Fisher's exact test, and in
medians with the Mann-Whitney U test
using Stat View 4.5 software


results
 TENDON REFLEX AND H-REFLEX
In the first examination (3 to 14 days after onset,
mean 7.9 days), 52 of the 54 patients had areflexia
(n=44) or hyporeflexia (n=8). Of the remaining two
patients, one had normal reflexes, and the other,
hyperreflexia (patient 6 in tables 1 and 2). During
weeks 3 to 4, seven patients (13%), including
patient 6, developed hyperreflexia (table 1).
Hyperreflexia was associated with abnormal reflex
spread and decreased reflex threshold. Hoffmann's
sign were present in four patients, but none had
Babinski's sign

Copyright ©1999 BMJ Publishing Group Ltd.
Kuwabara, S. et al. J Neurol Neurosurg Psychiatry 1999;67:180-184
No Caption Found

 Figure 1 Ratio of the maximum H reflex to the
maximum compound muscle action potential (H/M
ratio) in patients with GBS and normal subjects. In
the acute phase (A), the ratios did not differ
significantly between patients with GBS who later
developed hyperreflexia and normal subjects,
whereas patients with GBS without hyperreflexia
had significantly low ratios. In the recovery phase
(B), the ratios were significantly increased in the
patients with GBS with hyperreflexia (p<0.01) but
decreased in the other patients with GBS without
hyperreflexia (p<0.01), compared with those of the
normal subjects

 Figure 2 Soleus H-reflexes in patient 4 recorded on day 8 (left)
when achilles tendon reflexes were absent and on day 40 (right)
when the reflexes were hyperactive. Left traces: peak to peak
amplitude of compound muscle action potential
(CMAP) = 0.742 mV; H-reflex amplitude = 0.571 mV; H/M
ratio = 0.77. Right traces: CMAP amplitude=1.724 mV; H reflex
amplitude=0.785 mV; H/M ratio=0.46. Note the increased H/M
ratio despite the marked reduction in the CMAP in the left traces
(normal mean (SD) of H/M ratio, 0.17 (SD 0.08)). Lowest traces:
superimposed responses.

 Figure 3 H-reflexes in the abductor pollicis
brevis muscle of patient 3 (day 55). Lowest
traces: superimposed responses.

Electro diagnosis
 Patients were classified as having AMAN (n=23), AIDP (n=18), or
AMSAN (n=2), or were unclassified (n=11). Of the seven patients
with hyperreflexia, six had AMAN and one AIDP (table 1).
Sequential findings of patella tendon reflexes in AMAN and
patients with AIDP are shown in fig 4. In the acute phase (week
1 or 2), 65% of AMAN, and 100% of patients with AIDP showed
absence of patella tendon reflexes. During the early recovery
phase (weeks 4 to 6), 34% of patients with AMAN and 12% of
patients with AIDP had normal or brisk patella tendon reflexes.
Most patients (88%) with AIDP still had areflexia 3 months after
the onset. Two patients with AMSAN had areflexia up to
3 months after the onset. Hyperreflexia was significantly more
frequent in AMAN (table 2).

 Figure 4 Sequential findings of patella
tendon reflexes in patients with acute motor
axonal neuropathy (AMAN) or acute
inflammatory demyelinating polyneuropathy
(AIDP).

 ANTI-GM1 ANTIBODY
Positive anti-GM1 antibodies were found in 28 (52%) patients; 21 had IgG alone,
four IgM alone, and three had both classes. All the seven patients with
hyperreflexia had anti-GM1 antibodies, most of which were of IgG class (table 1
). Hyperreflexia was significantly more frequent in patients with than without anti-
GM1 antibodies .
 ANTI-C JEJUNI ANTIBODY
Positive anti-C jejuni antibodies were found in 13 (24%) patients. Hyperreflexia
was present in two (15%) of the 13 patients with anti-C jejuni antibodies, and in
five (14%) of 36 patients without anti-C jejuni antibody. C jejuni infection,
therefore, had no relevant association with hyperreflexia.
 CLINICAL FEATURES OF PATIENTS WITH HYPERREFLEXIA
The clinical manifestations of the patients with hyperreflexia were similar to
those of the other patients with AMAN; less frequent cranial and sensory nerve
involvement . They had, however, significantly less peak disabilities than the
other patients with GBS. On the Hughes functional grading scale, the median
(range) in patients with hyperreflexia was 2.5 (2.0-3.0), whereas it was 3.5 (2.0-
5.0) in patients without hyperreflexia (p=0.03). Of the hyperreflexic patients,
three were able to walk with aids (Hughes grade 3), and the other four were able
to walk independently (Hughes grade 2). The three patients were treated with
intravenous immunoglobulin infusion (2 and 4) or plasmapheresis (1). All seven
patients recovered well, six being able to run 3 months after onset. Two patients
(3 and 5) had moderate atrophy of the small hand muscles 3 months after onset.

 Our study showed that some patients with GBS showed obvious
hyperreflexia when they had the AMAN pattern, anti-GM1
antibody, and milder muscle weakness. The incidence of
hyperreflexia in AMAN was 33%, whereas McKahnn et al. found
that 12 (48%) of 25 Chinese patients with AMAN showed
hyperreflexia. Most of the Chinese patients were children, but our
findings showed a similar incidence of hyperreflexia in AMAN
that occurs in adults.
 Because sensory nerve involvement in AIDP or AMAN should
contribute to the areflexia, the selective involvement of motor
axons in AMAN could account for the relative preservation or
earlier appearance of reflexes; but it does not account for
hyperreflexia and reflex spread to other segments. Some of our
patients with AMAN had electrophysiological evidence of
increased motor neuron excitability shown by the increased
soleus H/M ratios and the abnormal appearance of H-reflexes in
the small muscles of the hands or feet. Our hyperreflexic patients
had less peak disability than the other patients with GBS. We
consider that hyperreflexia could be evident when motor axonal
loss is less severe and sensory nerves are intact. Van der Meché
et al found that, in patients with pure motor GBS, tendon reflexes
were preserved up to MRC grade 3 paresis.

 The mechanism that causes hyperreflexia in GBS is unknown.
The abnormal reflex spread to other segments suggests a
central mechanism; possibly due to the dysfunction of spinal
inhibitory interneurons, or of the upper motor neurons. Because
hyperreflexia was found only in patients with anti-GM1
antibodies, we speculate a possible role of this antibody.
Hyperreflexia is occasionally seen in chronic motor neuropathy
associated with high titre anti-GM1 antibody,and anti-GM1 serum
injected in the subarachnoid space was reported to cause
damage to the central axons in the spinal cord as well as nerve
roots.
 In addition, the spinal nerve roots, where the blood-nerve barrier
is anatomically deficient, are preferentially affected in
GBS.Inflammation in the spinal roots may lead to local
dysfunction of the blood-CNS barrier and allow anti-GM1
antibodies to bind with the neural structures in the spinal cord.
Further study is required to clarify the mechanism of increase in
motor neuron excitability in GBS.

 In AMAN or anti-GM1 positive GBS, excitability of the motor neuron
could increase even in the acute progressive phase. In most of our
patients, hyperreflexia developed in the early recovery phase, but a few
patients with AMAN had brisk reflexes in the acute phase. Moreover,
patient 4 had an increased soleus H/M ratio despite the markedly low
compound muscle action potential at the time when achilles tendon
reflexes were absent (fig 2, on day 8), suggestive of hyperexcitability of
the residual motor neurons. Several studies described patients who had
acute pure motor neuropathy with preserved tendon reflexes throughout
the course,and in some cases, the disorder was not diagnosed as GBS
because of preserved reflexes.
 Yuki and Hirata described four patients with AMAN with preserved
tendon reflexes (two of them had even brisk reflexes), and proposed
that these patients should be treated as having GBS. Our results
confirm that hyperreflexia is not a finding inconsistent with the diagnosis
of GBS.
 In conclusion, hyperreflexia often occurs in patients with GBS with
AMAN, anti-GM1 antibody, and less severe disease. Increased motor
neuron excitability further characterises the subgroup of patients with
GBS with the AMAN pattern and anti-GM1 antibodies.

references
 1. Asbury AK, Cornblath DR. Assessment of current diagnostic criteria for Guillain-Barré
syndrome. Ann Neurol 1990;27(suppl):S21-S24.
 2. Vriesendorp FJ, Mishu B, Blaser MJ, et al. Serum antibodies to GM1, GDlb, peripheral
myelin, Campylobacter jejuni and in patients with Guillan-Barré syndrome and controls:
correlation and prognosis. Ann Neurol 1993;34:130-135[Medline].
 3. Rees JH, Gregson NA, Hughes RAC. Anti-GM1 antibodies in Guillain-Barré syndrome
and their relationship to Campylobacter jejuni infection. Ann Neurol 1995;38:809-816
[Medline].
 4. McKhann GM, Cornblath DR, Ho TW, et al. Clinical and electrophysiological aspects of
acute paralytic disease of children and young adults in northern China. Lancet
1991;338:593-597[Medline].
 5. McKahnn GM, Cornblath DR, Griffin JW, et al. Acute motor axonal neuropathy: a
frequent cause of acute flaccid paralysis in China. Ann Neurol 1993;33:333-342[Medline].
6. Visser LH, van der Meché FGA, van Doorn PA, et al. Guillan-Barré syndrome without
sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic
and laboratory features. Brain 1995;118:841-847[Abstract/Free Full Text].
 7. Kuwabara S, Yuki N, Koga M, et al. IgG anti-GM1 antibody is associated with reversible
conduction failure and axonal degeneration in Guillan-Barré syndrome. Ann Neurol
1998;44:202-208[Medline].
 8. Kornberg AJ, Pestronk A, Bieser K, et al. The clinical correlates of high-titer IgG anti-
GM1 antibodies. Ann Neurol 1994;35:234-237[Medline].
 9. Jacobs BC, van Doorn PA, Schmitz PIM, et al. Campylobacter jejuni infections and anti-
GM1 antibodies in Guillain-Barré syndrome. Ann Neurol 1996;40:181-187[Medline].
 10. Pryor WM, Freiman JS. Guillain-Barré syndrome associated with Campylobacter
infection. Aust N Z J Med 1984;14:687-688[Medline].

 11. Jackson CE, Barohn RJ, Mendell JR. Acute paralytic syndrome in three American men. Comparison
with Chinese cases. Arch Neurol 1993;50:732-735[Abstract].
 12. Yuki N, Hirata K. Preserved tendon reflexes in Campylobacter neuropathy [letter]. Ann Neurol
1998;43:546-547[Medline].
 13. Guillain-Barré syndrome steroid trial group. Double blind trial of intravevous methylprednisolone in
Guillan-Barré syndrome. Lancet 1993;341:586-590[Medline].
 14. Ho TW, Mishu B, Li CY, et al. Guillain-Barré syndrome in northern China. Relationship to
Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 1995;118:597-605
[Abstract/Free Full Text].
 15. Fisher MA. AAEM minimonograph No 13: H reflexes and F waves: physiological and clinical
indications. Muscle Nerve 1992;15:1223-1233[Medline].
 16. Yuki N. Acute paresis of extraocular muscles associated with IgG anti-GQ1b antibody. Ann Neurol
1996;39:668-672[Medline].
 17. Koga M, Yuki N, Takahashi M, et al. Close association of IgA anti-ganglioside GM1 antibodies with
antecedent Campylobacter jejuni infection in Guillain-Barré and Fisher's syndromes. J Neuroimmunol
1998;81:138-143[Medline].
 18. Asbury AK, Cornblath DR. Preserved tendon reflexes in Campylobacter neuropathy [reply to letter].
Ann Neurol 1998;43:547.
 19. van der Meché FGA, Meulstee J, Vermeulen M, et al. Patterns of conduction failure in the Guillain-
Barré syndrome. Brain 1988;111:405-416[Abstract/Free Full Text].
 20. Pestronk A, Cornblath DR, Ilyas AA, et al. A treatable multifocal motor neuropathy with antibodies to
GM1 ganglioside. Ann Neurol 1988;24:73-78[Medline].
 21. Kinsella LJ, Lange DJ, Trojaborg W, et al. Clinical and electrophysiologic correlates of elevated anti-
GM1 antibody titers. Neurology 1994;44:1278-1282[Abstract/Free Full Text].
 22. Schwerer B, Lassmann H, Kitz K, et al. Ganglioside GM1, a molecular target for immunological and
toxic attacks: similarity of neuropathological lesions induced by ganglioside-antiserum and cholera toxin.
Acta Neuropathol 1986;72:55-61[Medline].
 23. Olsson Y. Topographical difference in the vascular permeability of the peripheral nervous system.
Acta Neuropathol 1968;10:26-33[Medline]
 . 24. Brown WF, Snow R. Patterns and severity of conduction abnormalities in Guillain-Barré syndrome. J
Neurol Neurosurg Psychiatry 1991;54:768-774[Abstract/Free Full Text].
 © 1999 by Journal of Neurology, Neurosurgery, and Psychiatry

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