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560

J Neurol Neurosurg Psychiatry 2001;70:560562

SHORT REPORT

Indicators of rapid clinical recovery in

Guillain-Barr syndrome
S Kuwabara, M Mori, K Ogawara, T Hattori, N Yuki

Department of
Neurology, Chiba
University School of
Medicine, 181
Inohana, Chuo-ku,
Chiba, 2608670, Japan
S Kuwabara
M Mori
K Ogawara
T Hattori
Department of
Neurology, Dokkyo
University School of
Medicine, Tochigi,
Japan
N Yuki
Correspondence to:
Dr S Kuwabara
kuwabara@
med.m.chiba.u.ac.jp
Received 14 August 2000
and in revised form
2 November 2000
Accepted 11 December 2000

Abstract
To elucidate the features of patients with
Guillain-Barr syndrome who show
markedly rapid clinical recovery, clinical,
serological, and electrophysiological data
of 80 consecutive patients were reviewed.
Antigangliosides, and Campylobacter jejuni and Haemophilus influenzae antibodies were measured by enzyme linked
immunosorbent assays. Nine (11%) patients showed rapid recovery (improvement by two or more Hughes grades
within 2 weeks). They often had electrodiagnosis of acute motor axonal neuropathy
(AMAN; 67%), preserved tendon reflexes
(44%), anti-GM1 antibodies (89%), preceding H influenzae infection (44%), and
received
immunoglobulin
treatment
(44%). On the other hand six patients with
poor prognosis often had AMAN (100%)
and anti-GM1 antibody (83%), but a
higher incidence of preceding C jejuni
infection (83%). It is concluded that
patients with Guillain-Barr syndrome
with AMAN and anti-GM1 antibodies
have either faster or slower recoveries.
Among the axonal subgroup of patients
with Guillain-Barr syndrome, preserved
tendon reflexes, H influenzae infection,
and the patient having received immunoglobulin treatment may be indicators of
rapid recovery.
(J Neurol Neurosurg Psychiatry 2001;70:560562)
Keywords: Guillain-Barr syndrome; acute motor
axonal neuropathy; tendon reflex; Haemophilus influenzae; anti-GM1 antibody

Guillain-Barr syndrome is a monophasic disease with spontaneous or treatment induced

recovery. Several factors have been suggested
as prognostic indicators in Guillain-Barr syndrome. These include age of patient, speed of
progression, respiratory muscle paralysis, amplitude of distally evoked compound muscle
action potential (CMAPs), the presence of
anti-GM1 antibody and Campylobactor jejuni
infection.1 2
Guillain-Barr syndrome is now classified
into demyelinating and axonal categories according to clinical, serological, electrodiagnostic, and pathological criteria.3 4 The axonal
subtype of Guillain-Barr syndrome, termed

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acute motor axonal neuropathy (AMAN),5 is

characterised by primary axonal damage.4
Patients with AMAN invariably have low distal
CMAPs, which, according to previous studies,
usually indicate a poor prognosis or slow
recovery. Some patients with AMAN actually
experience poor outcomes,6 but a considerable
number recover quickly and some of them can
have an even more rapid improvement than
patients with demyelinating Guillain-Barr
syndrome.7 8
Whereas almost all previous studies have
focused on factors associated with poor
prognoses,1 2 we aimed to elucidate the clinical,
serological, and electrophysiological features of
patients with Guillain-Barr syndrome with
rapid recovery. The data suggest that certain
factors could be indicators of rapid recovery in
Guillain-Barr syndrome.
Patients and methods
Eighty patients with Guillain-Barr syndrome,
who attended Chiba University Hospital or its
aYliated hospitals between 1993 and 1999,
were studied. They fulfilled the clinical criteria
for the disease9 except for that of areflexia.
Their median age was 42 years (range 3 to 80
years). Patient disability was evaluated with the
Hughes functional grading scale (grade 1,
minimal symptoms and signs, able to run;
grade 2, able to walk 5 m independently; grade
3, able to walk 5 m with the use of aids; grade
4, chair or bed bound; grade 5, requires
assisted ventilation), and was followed for up to
6 months after the onset of disease. Rapid
clinical recovery was defined as improvement
by 2 or more Hughes grades within 2 weeks
from the peak of the illness, whereas slow
recovery was defined as inability to walk independently 6 months after onset.
Patients serum samples taken during the
first 3 weeks after onset, before immune treatment, were frozen at 80C and stored until
use. The serum samples were tested to detect
recent infection by C jejuni, Haemophilus
influenzae, Mycoplasma pneumoniae, cytomegalovirus, or Epstein-Barr virus. C jejuni and H
influenzae antibodies were measured by an
enzyme linked immunosorbent assay (ELISA),
as described elsewhere.10 11 The same serum
samples were tested for the presence of IgM
and IgG antibodies against gangliosides GM1,
GM1b, GD1a, GalNAc-GD1a, GD1b, GT1b,

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561

Indicators of rapid clinical recovery in Guillain-Barr syndrome

Table 1 Features of patients with Guillain-Barre syndrome (GBS)

Age: mean ((range))

Preceding episode:
Upper respiratory
Gastrointestinal
Preserved tendon reflexes
Highest grade (mean (range)):
Peak
Week 4
Treatment:
Plasmapheresis
Immunoglobulin
Preceding infection:
Campylobacter jejuni
Haemophilus influenzae
IgG anti-GM1 antibody
Electrodiagnosis:
AMAN
AIDP

GBS with rapid

recovery (n=9)

All GBS (n=80)

p Value*

40 (1880)

44 (580)

NS

4 (44%)
4 (44%)
4 (44%)

34 (43%)
21 (26%)
7 (9%)

NS
NS
0.01

3.4 (24)
1.1 (02)

3.4 (25)
2.6 (25)

NS
0.001

5 (56%)
4 (44%)

43 (54%)
16 (20%)

NS
NS

2 (22%)
4 (44%)
8 (89%)

17 (21%)
9 (11%)
34 (43%)

NS
0.01
0.01

6 (67%)
1 (11%)

36 (45%)
34 (43%)

NS
0.04

*2 or Fishers exact test unless indicated; Mann-Whitney test; AMAN=acute motor axonal neuropathy; AIDP=acute inflammatory demyelinating polyneuropathy.

and GQ1b by an ELISA, as described

elsewhere.10
Nerve conduction studies were done using
conventional procedures within 16 days of the
onset of Guillain-Barr syndrome. Patients
were classified as having acute inflammatory
demyelinating polyneuropathy (AIDP) or
AMAN according to the electrodiagnostic criteria of Ho et al.12
Results
Nine (11%) of the 80 patients with GuillainBarr syndrome had a rapid recovery. At the
peak of the disease, their clinical disability was
not significantly diVerent from that of all
patients with Guillain-Barr syndrome (table):
Hughes grade was 4 in five of them, 3 in three,
and 2 in one. These nine patients were treated
with plasmapheresis (n=5) or intravenous
immunoglobulin (n=4). Their condition began
to improve 2 to 6 days after the initiation of the
treatment, and within 14 days, they had
improved by 2 or more Hughes grades. On the
other hand, six (8%) patients were unable to
walk independently by the end of the study and
were classified as having a slow recovery. At the
peak of the disease, all six of these patients had
Hughes grade 4, and 6 months after the onset
of the disease, the Hughes grade remained 4 in
five of them.
Table 1 shows clinical features of the
subgroups of patients with Guillain-Barr syndrome with rapid recovery. The age of a patient
did not increase his or her likelihood of a rapid
recovery. Patients with rapid recovery often had
preserved tendon reflexes (44%). Intravenous
immunoglobulin (IVIg) therapy tended to be
associated with rapid clinical recovery: four
(44%) of the nine patients with rapid recovery
were treated with IVIg. The intervals between
the neurological onset and the initiation of
treatment did not significantly diVer between
patients with rapid recovery and all patients
with Guillain-Barr syndrome. Patients with
slow recovery often had antecedent gastroenteritis (83%).
Table 1 also shows the relation of rapid
recovery with preceding infection, anti-GM1
antibody, and electrodiagnosis. Patients with

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rapid recovery often had preceding H influenzae infection: nine (11%) of 80 patients had
positive serology for H influenzae, and they
often had anti-GM1 antibody (89%), the
AMAN pattern (67%), and good recovery
(four patients had rapid recovery and the
remaining five were able to walk 4 weeks after
onset). Infections by C jejuni were not frequent
(22%) in patients with rapid recovery and were
significantly more frequent in patients with
slow recovery (83%). Preceding infections by
cytomegalovirus, M pneumoniae, and EpsteinBarr virus had no significant correlation with
the patterns of recovery. Among antiganglioside antibodies, anti-GM1 IgG antibody correlated with both rapid and slow
recoveries. The AMAN pattern was often
found for both patient groups, with rapid
(67%) and slow (67%) recovery.
Discussion
Our results showed that factors such as
preserved tendon reflexes, preceding H influenzae infection, and IVIg treatment, are associated with markedly rapid recovery in GuillainBarr syndrome. Whereas patients with rapid
recovery often had anti-GM1 IgG antibodies
and an AMAN electrodiagnosis, these features
were also frequent in patients with slow recovery. Our findings, therefore, confirmed that the
axonal subtype of Guillain-Barr syndrome has
diVerent patterns of recovery from those of the
classic demyelinating form of Guillain-Barr
syndrome (AIDP): patients with axonal
Guillain-Barr syndrome can show both rapid
and slow recoveries.8
Tendon reflexes tend to be preserved in
patients with acute motor axonal neuropathy
and anti-GM1 antibody.13 It has been reported
that some Chinese5 and Japanese13 patients
with Guillain-Barr syndrome have even had
exaggerated tendon reflexes in the early recovery phase, and most of these have had good
recoveries. Furthermore, anti-GM1 antibodies
and AMAN are occasionally associated with
evidence of increased motor neuron excitability.13 In the present study, patients who, at the
peak of the disease, had relatively preserved
reflexes often showed rapid improvement. It is
reasonable to think that patients with preserved
tendon reflexes recover quickly because at least
some of the motor units need to function to
elicit visible reflexes: van der Mech et al14
found that, in patients with pure motor
Guillain-Barr syndrome, tendon reflexes were
preserved up to MRC grade 3 paresis.
In this study, nine (11%) of 80 patients with
Guillain-Barr syndrome had serological evidence of recent H influenzae infection. Four of
the nine patients with rapid recovery had
preceding H influenzae infection, and the
remaining five patients with H influenzae infection did not have slow recovery. H influenzae is
a gram negative bacillus with an outer membrane containing lipopolysaccharide. This bacteria has recently been recognised as a
pathogen that can elicit axonal Guillain-Barr
syndrome,11 15 and its incidence in a study of 46
patients in Japan has been reported to be
13%.11 The good recovery rate in H influenzae

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562

Kuwabara, Mori, Ogawara, et al

related disease was by contrast with poor

outcomes in C jejuni related disease. Rees et al2
showed that preceding C jejuni infection is a
marker of a poor prognosis. The reason for the
diVerent speeds of recovery in H influenzae and
C jejuni related Guillain-Barr syndrome is
unknown, but it is clinically relevant that
recovery depends on the micro-organisms of
the preceding infection.
This study showed that patients with rapid
recovery were treated with IVIg more often
than other patients with Guillain-Barr syndrome. Jacobs et al16 reported that, among their
31 anti-GM1 positive patients, the recovery in
21 patients treated with IVIg was significantly
faster than in 10 patients treated with plasmapheresis. Our findings are consistent with
the results of this study because almost all of
our patients with rapid recovery contained
anti-GM1 antibodies.
The very rapid clinical recovery seen in our
patients suggests that, as speculated in previous
studies,4 7 8 17 instead of axonal degeneration or
demyelination, reversible eVects such as impaired physiological nerve conduction occur
on the axonal membrane. These findings
further suggest that the pathophysiology in the
axonal subtype of Guillain-Barr syndrome is
potentially reversible, especially in the early
stages, and eVective treatment could result in
very rapid improvements. It is concluded that
axonal subtype, preserved tendon reflexes, preceding H influenzae infection, and the patient
having received IVIg treatment could be
indicators of rapid recovery in Guillain-Barr
syndrome.

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Indicators of rapid clinical recovery in

Guillain-Barr syndrome
S Kuwabara, M Mori, K Ogawara, et al.
J Neurol Neurosurg Psychiatry 2001 70: 560-562

doi: 10.1136/jnnp.70.4.560

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