Search

To determine the clinical features of a Guillain-Barré syndrome variant with prominent facial diplegia, we retrospectively reviewed approximately 8,600 cases referred to our neuroimmunological laboratory for serological tests during the past seven years. Patients' histories, neurological signs, and laboratory and electrophysiological data were clarified based on their clinical records. Sera obtained during the acute phase were tested for prior infectious serology and anti-ganglioside antibodies. In 22 patients, clinical signs such as acute progressive bifacial weakness, paresthesias in the distal dominant limbs, and hypo- or areflexia, were compatible with a Guillain-Barré syndrome variant, facial diplegia and paresthesias. Other cranial nerve involvements, limb weakness, and ataxia were absent or minimal. Clinical courses were monophasic, the nadir being reached within four weeks. Eighteen patients (86%) had had infectious symptoms within the four weeks preceding the onset of neurological illness. In the infection serology tests, anti-cytomegalovirus IgM antibodies were the most frequent (35%). All the patients had cerebrospinal fluid albuminocytologic dissociation. In nerve conduction studies, 14 (64%) showed demyelination in their limbs. Anti-GM2 IgM antibodies were detected in four patients who had anti-cytomegalovirus IgM antibodies. Patients with conditions similar to facial diplegia and paresthesias, but lacking either distal paresthesias or hyporeflexia, were regarded as having marginal facial diplegia and paresthesias, because they also frequently had features of Guillain-Barré syndrome, such as an antecedent infection or cerebrospinal fluid albuminocytologic dissociation. Our findings are further evidence of a facial variant of Guillain-Barré syndrome and provide important information essential for its diagnosis.

Complement-mediated disruption of voltage-gated sodium channels at the nodes of Ranvier acts in the development of acute motor axonal neuropathy. Nafamostat mesilate, a synthetic serine protease inhibitor, used in clinical practice for more than 20 years, has anti-complement activity. Acute motor axonal neuropathy rabbits obtained by GM1 ganglioside sensitization were or were not given nafamostat mesilate intravenously. Complement deposition and sodium channel disruption in the spinal anterior roots were significantly less frequent in the treated rabbits than in the controls. Nafamostat mesilate inhibited complement deposition and prevented sodium channel disruption. This provided the rationale for a clinical trial.

Guillain-Barré syndrome is divided into two subtypes: acute inflammatory demyelinating polyneuropathy, and acute motor axonal neuropathy. Autoantibodies to gangliosides GM1, GM1b, GD1a, or GalNAc-GD1a were proposed as serologic markers of acute motor axonal neuropathy in adults. In a previous study of Japanese children with Guillain-Barré syndrome, acute motor axonal neuropathy was associated with anti-GM1 immunoglobulin G antibodies. Larger, comprehensive studies are required to confirm this finding. The present study revealed that immunoglobulin G antibodies were against GM1 (34%), GM1b (22%), GD1a (25%), GalNAc-GD1a (13%), and any of these (44%) in 32 Japanese children with Guillain-Barré syndrome. Patients who had the autoantibodies more often manifested previous diarrhea (71% vs 11%, P = 0.001), acute motor axonal neuropathy (64% vs 11%, P = 0.003), and slower recovery (healthy at final follow-up: 29% vs 78%, P = 0.011; able to run with minor signs, 64% vs 11%, P = 0.003) than patients who did not. The clinical features were consistent with those in adults carrying anti-ganglioside antibodies. Anti-ganglioside antibody testing may help predict outcomes in pediatric patients with Guillain-Barré syndrome who prefer not to undergo repeated nerve-conduction studies.

The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain-Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity. Ganglioside-specific IgG antibodies generally induced leukocyte activation, irrespective of specificity. The magnitude of leukocyte degranulation correlated with GM1- and GQ1b-specific IgG titers, but not with disease severity. Finally, GM1-specific IgA activated leukocytes through the IgA receptor, FcalphaRI (CD89). Therefore, both ganglioside-specific IgG and IgA can recruit leukocyte effector functions, which may be relevant in the pathogenesis of GBS and MFS.

This report describes a male, age 8 years 10 months, with severe Guillain-Barré syndrome after Campylobacter jejuni infection. The patient developed fulminant muscle weakness, external ophthalmoplegia, bulbar palsy, and respiratory distress. A high level of serum monospecific anti-GT1a immunoglobulin G antibody was detected. He was treated with intravenous immunoglobulins and artificial ventilation. Two years after the onset, the patient still suffered from residual leg weakness and foot drop. After 3 years and clinical recovery, the antibody was no longer detectable. This report presents the first case in childhood suggesting an association between a severe Guillain-Barré syndrome after C. jejuni enteritis with monospecific anti-GT1a immunoglobulin G antibody.

We report a patient with acute oropharyngeal palsy following enteritis. A 19-year-old woman developed increasing nasal voice over a few days. Neurological examination on day 7 of her course showed paretic dysarthria and mild weakness of neck flexion and quadriceps femoris muscle (Medical Research Council grade, 4+). Her palatal movement was diminished, whereas both palatal and pharyngeal reflex was normal. She could swallow water, although she had a slight amount of liquid reflux to her nose on swallowing. High titers of serum anti-Campylobacter jejuni, anti-GQ1b and anti-GT1a IgG antibodies were detected. Her symptoms improved gradually without any treatment, and disappeared by 40 days from neurological onset. Nasal voice with slight swallowing impairment as initial symptom has been rarely reported, but can occur in acute oropharyngeal palsy. Therefore, neurologists should take into account the possibility of Guillain-Barré syndrome and the regional variants in patients who show nasal voice during the initial stage.

A 14-year-old boy presented with progressive ascending muscle weakness, urinary retention and disturbed consciousness. Initially his cerebrospinal fluid showed pleocytosis, and protein-cellular dissociation developed later. Campylobacter jejuni was isolated from his stool and serum anti-ganglioside antibodies were positive. Our case suggests that coexistence of meningoencephalitis at an early stage of illness does not necessarily exclude the diagnosis of Guillain-Barre syndrome.

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1-2 wk after various infections, in particular, Campylobacter jejuni enteritis. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] between the bacterial lipooligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in Guillain-Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1 IgG from patients with Guillain-Barré syndrome did not induce paralysis but blocked muscle action potentials in a muscle-spinal cord coculture, indicating that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.

A patient with Facial diplegia and paresthesias, a rare regional variant of Guillain-Barré syndrome (GBS), is described. A 37-year-old woman developed paresthesias in the distal limbs and subsequently bifacial weakness. She had had a preceding episode of laryngitis. Neurological examination showed severe facial diplegia with loss of taste sensation on the tip of the tongue. Limb muscle power was preserved. Deep tendon reflexes were generally absent. She complained of paresthesias in the distal limbs, but sensory examination was normal. Cerebrospinal fluid showed albuminocytological dissociation. Electrophysiological studies revealed severe facial nerve involvements and demyelinative findings in her limbs. Intravenous immunoglobulin rapidly improved the abnormal sensation in her limbs. Although facial diplegia gradually lessened after the therapy, mild residual weakness was noted 6 months after the neurological onset. To diagnose facial diplegia and paresthesias, it is important to clarify the findings common to typical GBS such as the antecedent illness, acute and monophasic course, distal paresthesias, areflexia, cerebrospinal fluid albuminocytological dissociation, and demyelinative conduction abnormalities in the limbs.

Background: Patients with Guillain-Barré syndrome (GBS) after Mycoplasma pneumoniae infection often have antibodies to galactocerebroside (GalC). Electrodiagnosis may show acute inflammatory demyelinating polyneuropathy (AIDP)., Methods: The authors report a patient with acute motor axonal neuropathy (AMAN) after Mycoplasma infection and review seven cases of Mycoplasma-associated GBS. They investigated anti-GalC serology under various conditions associated with Mycoplasma infection., Results: The patient had immunoglobulin (Ig)G and IgM antibodies against GM1 and GalC, which cross-reacted. During the acute phase, IgM selectively immunostained axons. The cholera toxin B-subunit and rabbit anti-GM1 IgG stained a band in the lipid extract from M pneumoniae, indicative of the presence of a GM1 epitope. Six Mycoplasma-associated GBS patients with anti-GalC antibodies had non-AIDP electrodiagnoses, whereas one with Mycoplasma-associated AIDP had no anti-GalC antibodies. Anti-GalC antibodies were positive in two of five patients who had neurologic diseases other than GBS after Mycoplasma infection and in one of 12 who had acute respiratory disease caused by M pneumoniae not followed by a neurologic disease., Conclusions: Anti-GalC antibodies in Mycoplasma-associated GBS may be an epiphenomenon. In certain cases, anti-GM1 antibodies induced by molecular mimicry with M pneumoniae may cause acute motor axonal neuropathy.

Two patients with acute facial diplegia and hyperreflexia are described. Both patients had serologic evidence of preceding Campylobacter jejuni infection and antiganglioside IgG antibodies as well as other laboratory and electrophysiologic findings suggesting Guillain-Barré syndrome (GBS). IV immunoglobulin produced recovery. Hyperreflexia does not necessarily exclude the diagnosis of a GBS variant. Antiganglioside antibodies can help with diagnosis in difficult cases.

We described a patient with ataxic Guillain-Barré syndrome who subsequently developed facial diplegia. A 38-year-old man developed ataxia, distal limb paresthesias, mild dysphagia, urinary retention and orthostatic hypotension a week after an episode of laryngitis. He had high titers of serum anti-GQ1b, anti-GD1b, anti-GM1b, anti-GT1a, and anti-GD1a IgG antibodies during the acute phase. Although the initial symptoms markedly improved by intravenous immunoglobulin therapy, asymmetric facial diplegia subsequently occurred and remained longer than ataxia. Similar course of facial nerve palsy has been reported in patients with Fisher syndrome. Common pathophysiological mechanism may function in the development of delayed facial diplegia in Fisher syndrome and ataxic Guillain-Barre syndrome.

We report two cases of pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré syndrome (GBS). The patients developed dysphagia and weakness of the neck and arms subsequent to Campylobacter jejuni infection. Oropharyngeal palsy recovered poorly. Electrophysiological findings demonstrated axonal conduction failure. Anti-GD1a immunoglobulin G (IgG) antibody was detected in one case, and anti-GM1b IgG antibody in another. Anti-GT1a IgG and immunoglobulin M (IgM) antibodies were negative in both cases. The current cases suggest that the PCB and axonal variants of GBS form a continuous spectrum from the viewpoint of electrophysiological studies as well as antiganglioside serology.

A 37-year-old man developed an acute encephalitic condition after respiratory infection. His condition rapidly deteriorated, and he experienced ophthalmoplegia, tetraplegia, loss of brainstem reflexes and deep tendon reflexes, and deep coma. Electrophysiological evaluations indicated involvement of the peripheral nerve as well as the brainstem. Follow-up studies found acute progression of peripheral nerve damage. Serum anti-GQ1b IgG antibody was present. The initial condition was diagnosed as Bickerstaff's brainstem encephalitis, and subsequent overlapping of Guillain-Barré syndrome probably was responsible for the clinical deterioration. When unusual worsening is observed in clinically suspected encephalitis, neurologists must take into account the possibility of associated Guillain-Barré syndrome and related disorders.

Anti-ganglioside antibodies frequently are present in sera from patients with Guillain-Barré syndrome (GBS) during the acute phase, but no patients in whom anti-ganglioside antibodies were tested before the onset of the syndrome have been reported. We describe the first case of GBS subsequent to Campylobacter jejuni infection, in which longitudinal changes in anti-ganglioside antibody titers were measured before and after the onset of limb weakness. Serum antibody titers against GM1 (IgM/IgG), GM1b (IgM/IgG), GalNAc-GD1a (IgM/IgG), and GD1b (IgG) were highest on the day of onset, but negative before onset. Anti-C. jejuni IgG and IgA antibody titers paralleled those of the anti-ganglioside antibodies, indicative that C. jejuni infection triggered anti-ganglioside antibody production. Press et al. [J. Neurol. Sci. 190 (2001) 41] reported that anti-ganglioside antibody titers peaked during the recovery phase, but our findings are counter to theirs. We speculate that anti-ganglioside antibodies are the primary effectors of nerve damage in GBS.

We investigated the prevalence of anti-LM1 IgG antibody and its fine specificity in Guillain-Barré syndrome (GBS). Anti-LM1 IgG and IgM antibodies from sera of 47 patients with GBS--19 with acute inflammatory demyelinating polyneuropathy (AIDP), 27 with acute motor axonal neuropathy (AMAN), and 1 with acute motor-sensory axonal neuropathy (AMSAN)--were tested. Anti-LM1 IgG antibody was detected in only one patient with AIDP, whereas it was present in seven with AMAN and in one with AMSAN. Sera from the eight IgG anti-LM1-positive patients with AMAN/AMSAN also had IgG activity against the gangliosides GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, or GQ1b. Anti-LM1 IgG antibodies from the AMAN/AMSAN patients cross-reacted with other gangliosides, whereas IgG antibody from the AIDP patient was monospecific against LM1. Anti-LM1 IgG antibody therefore, cannot be a marker of AIDP. In addition, whether monospecific anti-LM1 IgG antibody is associated with AIDP remains to be concluded. Larger studies are needed to verify whether monospecific anti-LM1 IgG antibody could be a marker of AIDP.

A 28-year-old man was admitted after developing acute onset unstable gait following acute enteritis. Neurological examination revealed mild weakness in four limbs, areflexia and ataxia. Serum obtained from the patient during the acute stage contained a high titer of anti-GD1b IgG antibody. Because the patient showed obvious cerebellar ataxia unrelated to muscle weakness, without ophthalmoplegia or proprioceptive sensory disturbance, we concluded that he had ataxic form of Guillain-Barré syndrome (GBS) (Richter, 1962). Although ataxic GBS is not an established conception, one should pay attention to the possible existence of such a rare GBS variant. It is necessary to accumulate additional case reports to clarify the association between ataxic GBS and anti-ganglioside antibodies.

Herpes simplex virus (HSV) is a rare, antecedent infectious agent in Guillain-Barré syndrome (GBS). We report a patient with overlapping GBS and Bickerstaff's brainstem encephalitis (BBE). The patient had a vesicular lesion on her nose. Antecedent HSV type 1 (HSV-1) infection was confirmed by isolation of the virus and detection of the presence of serum anti-HSV-1 IgM antibody during the acute phase. Her serum IgG had high anti-GQ1b antibody titer. External ophthalmoplegia has been noted in 2 of 4 reported cases of HSV-associated GBS. Herpetic brainstem encephalitis cases of poor prognosis are known, but only 2 cases of benign brainstem encephalitis secondary to HSV infection, in which there was acute ophthalmoplegia and clinical features consistent with those of BBE have been reported.

Some humans develop the axonal form of Guillain-Barré syndrome after receiving bovine brain ganglioside. On sensitization with the ganglioside mixture, all of a group of rabbits injected developed high anti-GM1 IgG antibody titers, flaccid limb weakness of acute onset, and a monophasic illness course. Pathological findings for the peripheral nerves showed predominant Wallerian-like degeneration, with neither lymphocytic infiltration nor demyelination. IgG was deposited on the axons of the anterior roots, and GM1 was proved to be present on the axons of peripheral nerves. Sensitization with purified GM1 also induced axonal neuropathy, indicating that GM1 was the immunogen in the mixture. A model of human axonal Guillain-Barré syndrome has been established that uses inoculation with a bovine brain ganglioside mixture or isolated GM1. This model may help to clarify the molecular pathogenesis of the syndrome and to develop new treatments for it.

The authors reviewed the medical records of seven patients with anti-GQ1b immunoglobulin G (IgG) who had no or minimal external ophthalmoplegia but showed ataxia. The clinical features of the patients were consistent with the ataxic form of Guillain-Barré syndrome (GBS). Anti-GQ1b IgG antibodies from the patients, as well as from those with Miller Fisher syndrome (MFS), were absorbed by GT1a. The finding that ataxic GBS and MFS have in common an autoantibody with the same fine specificity suggests that they form a continuous spectrum.

A letter to the editor about rhinolalia after diarrhea is presented.

Presents a letter to the editor regarding post-infectious acute ataxia and facial diplegia associated with anti-GD1a lgG antibody published in the 2004 issue of the "European Journal of Neurology."