Yukihiro Nishimoto

Acute motor axonal neuropathy rabbit model: immune attack on nerve root axons.

Macrophages in the periaxonal space and surrounding intact myelin sheath are the most prominent pathological feature of acute motor axonal neuropathy (AMAN). We describe this characteristic in nerve roots from paralyzed rabbits immunized with bovine brain ganglioside or GM1. IgG was deposited on nerve root axons. Distal nerve conduction was preserved, and late F wave components were absent during the acute phase. Initial lesions were located mainly on nerve root axons, as in human AMAN. This study thus provides supportive evidence that the rabbits constitute a model of AMAN. Ann Neurol 2003;54:000–000

Usefulness of anti-GQ1b IgG antibody testing in fisher syndrome compared with cerebrospinal fluid examination

Fisher syndrome (FS), a variant of Guillain-Barré syndrome (GBS), is a rare disorder, and there are few reported studies of a large number of patients with FS. Cerebrospinal fluid (CSF) albuminocytological dissociation was found in 59% of 123 FS patients during the first 3 weeks of illness, while serum anti-GQ1b IgG antibody was positive in 85%. Whereas the incidence of CSF albuminocytological dissociation increased from the first to second weeks in FS, anti-GQ1b IgG antibody peaked in the first week, but there was no CSF albuminocytological dissociation. Statistically, anti-GQ1b antibody testing was superior to a CSF examination in supporting a diagnosis of FS during the first 3 weeks of illness, especially in the first week.

Various immunization protocols for an acute motor axonal neuropathy rabbit model compared

Various ganglioside immunization protocols were examined to refine the procedure for establishing an animal model of acute motor axonal neuropathy. The most effective was subcutaneous injection of an emulsion of 2.5mg of bovine brain ganglioside mixtures, keyhole lympet hemocyanin, and complete Freunds adjuvant to Japanese white rabbits, repeated at 3-week intervals. Under that protocol, all the rabbits developed marked flaccid paralysis associated with plasma anti-GM1 IgG antibody. This acute motor axonal neuropathy rabbit model also could be reproduced by the use of incomplete Freunds adjuvant, methylated bovine serum albumin, and New Zealand white rabbits. These results provide useful information for the confirmation of and further research on the model.

Immunoglobulin improves a model of acute motor axonal neuropathy by preventing axonal degeneration.

Background: The action mechanism of IV immunoglobulin (IVIg) for Guillain-Barré syndrome has yet to be clarified. Objective: To evaluate clinical, histologic, and immunologic effects in a disease model of acute motor axonal neuropathy (AMAN) treated by IVIg. Methods: Rabbits were sensitized with gangliosides including GM1 and divided randomly into two groups at disease onset. One group received IV homologous γ-globulin (400 mg/kg/day) for 5 days (n = 15), and the other received saline (n = 15). Disease severity was scored (0 to 13 points) daily. Sixty days after onset, anti-GM1 antibodies were tested by ELISA, and the number of degenerative axons was counted in spinal anterior roots. Results: Between both groups at onset, there was no difference in any characteristics including clinical score. The IVIg group had faster recovery than the saline group (p = 0.03). The percentage of rabbits that improved by a score of ≤4 was higher in the IVIg (53%) than in the saline (13%) group 60 days after onset (p = 0.03). Anti-GM1 IgG titers 60 days after onset did not differ between the groups. The anterior roots of rabbits surviving 60 days after onset showed lower frequency of axonal degeneration in the IVIg-treated (n = 11; mean 4.5%) than in the saline-treated (n = 8; mean 11.1%) rabbits (p = 0.01). Conclusions: The therapeutic efficacy of IVIg in an AMAN model was confirmed. IVIg may not affect the production or catabolism of anti-GM1 IgG, but it may prevent axonal degeneration of motor nerves.

Guillain–Barré syndrome presenting with loss of taste

Taste loss is a rare sign in Guillain–Barre syndrome (GBS). Two of 100 patients reported subjective alteration of taste in one study,1 whereas none of 169 experienced taste loss in another.2 We have investigated the frequency of patients with GBS who present with taste loss as the initial symptom. We conducted retrospective examinations of 457 patients with GBS who had been referred to our neuroimmunologic laboratory between 1997 and 2001 for serum antiganglioside antibody tests. Five patients had accompanying subjective alteration of taste during the illness. As the initial symptom, only three patients had taste loss. An illustrative case is described here. A 45-year-old man had a respiratory infectious illness, which was resolved within 2 days. Three days after resolution (day 1), he could not identify the flavor of a nutrition drink. On day 4, he experienced numbness in the perioral region and his four limbs. He had deficiencies for salty, bitter, sour, and …

Paediatric brainstem encephalitis associated with glial and neuronal autoantibodies

Central nervous system (CNS) autoantibodies have been reported in a range of neuroimmune diseases, but there has not been a systematic evaluation of autoantibodies in paediatric patients with brainstem encephalitis.

Neck stiffness in two children with Guillain-Barré syndrome after Campylobacter jejuni infection

Sirs: The association of meningismus with enteric infections caused by Salmonella or Shigella is well recognized, and we can find two reports of an association between meningismus and Campylobacter jejuni enteritis [4, 5]. We here describe two children with GuillainBarre syndrome (GBS) after C. jejuni infection, who had meningismus. Patient 1. Four days after a 3day bout of watery diarrhea, a 15year-old boy developed ascending muscle weakness, paresthesias, and urinary retention (day 1). On day 4, he was alert, and his cranial nerve function was intact. Generalized areflexia and tetraparesis of Medical Research Council (MRC) grades 3–4 were found in his arms and 0–1 in his legs. He complained of severe pain from the buttocks to the legs, but sensory disturbance was absent. Neck stiffness was moderate, and the Kernig sign was elicited. No autonomic disturbance was found. Serum had a high antiGM1 IgG antibody titer of 1:4000 (normal, less than 1:500). CSF analysis showed 2 cells/μl and 57 mg/dl protein on day 3, and 12 cells/μl with 153 mg/dl protein on day 16. C. jejuni was isolated from a stool specimen taken on admission. Neck stiffness had disappeared by day 8. From day 8, he was treated with intravenous immunoglobulin (IVIg: 0.4 g/kg/day for 5 consecutive days). A nerve conduction study on day 9 showed inexcitable motor responses. Left facial palsy and incomplete limitation of left eye movement respectively appeared on days 14 and 16, after which both gradually disappeared. Leg pains were resolved by day 19. He had MRC grades of 2–3 in the arms and 2–4 in the legs on day 44. Ten months after onset, he could walk independently and had MRC grades of 4–5 in the arms and legs. Patient 2. A 6-year-old boy developed vomiting with fever. Six days later, he had pain in the popliteal fossa (day 1), and fever reappeared. Because of limb weakness he could not walk the next day. On admission (day 3) he was alert, and cranial nerve function was intact. He had tetraparesis of MRC grades 1–2 in the arms and the legs. Deep tendon reflexes were absent in the lower limbs, but preserved in the upper ones. He complained of severe leg pains, especially at the patellar fossae, but there were no sensory disturbances. Neck stiffness was obvious. The Kernig and Brudzinski signs were elicited. Passive neck flexion led to worsening leg pain. The nerve conduction study showed a low compound muscle action potential (4.0 mV) with normal distal motor latency (3.4 ms) and normal motor nerve conduction velocity (60 m/s) in the median nerve. No motor responses were evoked in the peroneal nerves. Serum had a high anti-GM1 IgG antibody titer of 1:16000. CSF analysis showed 3 cells/μl and a normal protein level on day 3, and 8 cells/μl with elevated protein (123 mg/dl) on day 11. He had no history of diarrhea, but C. jejuni was isolated from a stool specimen taken on admission. From day 4, IVIg was initiated, after which his neck stiffness and severe leg pain decreased and respectively had disappeared by days 10 and 20. There was temporary urinary retention and bowel dysfunction from admission to the end of IVIg therapy. From day 149, he was again treated with IVIg because of residual neurological deficits. He always used a wheelchair and still needed assistance to walk on day 169. Ten months after onset, he was able to run although his hands remained weak. To our knowledge this is the first report of meningismus on patients with GBS from whom C. jejuni was actually isolated. McKhann and coworkers [2], however, had already described patients with GBS of children and young adults in northern China who occasionally showed the resistance to passive flexion of the neck. The resistance to neck flexion disappeared within days of onset. The patients with GBS in northern China frequently had serological evidence of recent C. jejuni infection [1]. In one series of childhood GBS, moreover, onethird of the cases had meningismus [3]. These give us warning that some patients with GBS, especially of children, after C. jejuni infection, or both, can have a stiff neck in the early phase of the illness. Because the combination of neck stiffness and preceding C. jejuni enteritis is expected to occur occasionally, a large prospective study is needed to determine the causal relationship between them.

Serologic Marker of Acute Motor Axonal Neuropathy in Childhood

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.

Cytoalbuminologic dissociation in Asian patients with Guillain-Barré and Miller Fisher syndromes

Cerebrospinal fluid (CSF) protein level, cell count, and its relationship to the timing of lumbar puncture were collected from patients with Guillain‐Barré syndrome (GBS) and Miller Fisher syndrome (MFS) from various Asian centers. A total of 507 patients with GBS were studied. Overall, 56% had elevated CSF protein level. This was significantly lower than that reported in a recent Dutch study (56% vs 64%). Cytoalbuminologic dissociation was also lower in the Asian cohort (55% vs 64%), with a significantly higher proportion of patients with mild pleocytosis (26% vs 15%). A lower proportion of the 164 patients with MFS had elevated CSF protein level (38% vs 56%), mild pleocytosis (11% vs 26%), and cytoalbuminologic dissociation (41% vs 55%) compared to patients with GBS. In both conditions, cytoalbuminologic dissociation was linked to the timing of lumbar puncture. Cytoalbuminologic dissociation was only observed in half of the Asian patients with GBS and MFS, and it is strongly dependent on the timing of the lumbar puncture.