Kuroki S

Antibodies to gangliosides and galactocerebroside in patients with Guillain–Barré syndrome with preceding Campylobacter jejuni and other identical infections

The relationship between preceding infections and antibodies to glycolipids was investigated in 205 Japanese patients with Guillain-Barré syndrome (GBS). Serological evidence of recent Campylobacter jejuni (C. jejuni) infection was found in 45% of the patients, compared with 1% in healthy controls. In contrast, recent infection of cytomegalovirus (CMV), Mycoplasma pneumoniae (M. pneumoniae) and Epstein-Barr virus (EBV) was detected in only 5%, 2% and none of the patients, respectively. C. jejuni-associated GBS was more frequent in early spring than in other seasons. All stool specimens positive for C. jejuni isolation were obtained within 10 days after the onset of GBS symptoms. Of 13 C. jejuni isolates from GBS patients, 10 (77%) belonged to Penner serotype 19 (heat-stable, HS-19). Elevated titers of anti-GM1 antibody were found in 8 (80%) of 10 GBS patients whose C. jejuni isolates belonged to HS-19 and in none of those infected with non-HS-19 C. jejuni (P = 0.04), and in 49% of 92 patients with C. jejuni infection and 25% of patients without infection of C. jejuni, CMV, EBV, or M. pneumoniae (P = 0.0007). The frequencies of elevated antibody titers to GD1a, GD1b and GQ1b were also significantly higher in GBS patients associated with C. jejuni than those not associated with C. jejuni, CMV, EBV, and M. pneumoniae. GBS in Japan seems to be associated more frequently with C. jejuni and less frequently with CMV than in Europe and North America.

Post-infectious encephalitis with anti-galactocerebroside antibody subsequent to Mycoplasma pneumoniae infection

Galactocerebroside (Gc) is a major component of myelin in both the peripheral and central nervous systems. Although it is regarded as an important glycolipid hapten of myelin in rabbit experimental allergic neuritis (EAN), its role in human demyelinating diseases is not known. We studied three post-infectious encephalitis (PIE) patients related to Mycoplasma pneumoniae infection. All three of three patients with encephalitis and M. pneumoniae infection were positive for Gc antibodies (100%), while 25% of 32 M. pneumoniae-infected patients without neurological disease were positive, and 3.8% of 52 healthy controls. This indicates anti-Gc antibody is induced by M. pneumoniae infection. One of the PIE patients, who had extraordinary high titer antibody to Gc, showed an extensive, diffuse white matter demyelination and poor recovery. Since circulating anti-Gc antibody induces central nervous system demyelination in animals with elevated antibody titers and disruption of the blood-brain barrier, anti-Gc antibody may have an important function in the increased demyelination in PIE patients after M. pneumoniae infection.

Anti-GalNAc-GD1a antibody–associated Guillain-Barré syndrome with a predominantly distal weakness without cranial nerve impairment and sensory disturbance

The serum antibodies to N‐acetylgalactosaminyl GD1a (GalNAc‐GD1a) and other gangliosides as well as to Campylobacter jejuni were determined in 147 patients with Guillain‐Barré syndrome (GBS). We found a distinctive clinical pattern in patients with anti‐GalNAc‐GD1a antibodies compared with those without the antibodies, that is, lack of cranial nerve involvement (87% versus 38%), distal‐dominant weakness (80% versus 25%), and no sensory disturbance (73% versus 22%). The frequency of distal‐dominant weakness was significantly higher in patients with both C jejuni infection and anti‐GalNAc‐GD1a positivity (100%) than in C jejuni–negative/anti‐GalNAc‐GD1a–positive (25%), C jejuni–positive/anti‐GalNAc‐GD1a–negative (32%) and C jejuni–negative/anti‐GalNAc‐GD1a–negative patients (20%). Lack of cranial nerve involvement and sensory disturbance were found in most C jejuni–positive/anti‐GalNAc‐GD1a–positive and C jejuni–negative/anti‐GalNAc‐GD1a–positive patients, but not in C jejuni–positive/anti‐GalNAc‐GD1a–negative and C jejuni–negative/anti‐GalNAc‐GD1a–negative patients. Although the anti‐GM1–positive/anti‐GalNAc‐GD1a–negative patients mostly (75%) lacked cranial nerve involvement, distal‐dominant weakness (38%) and lack of sensory disturbance (13%) were infrequent. These results may indicate that (1) the combination of C jejuni infection and anti‐GalNAc‐GD1a antibodies, but not anti‐GalNAc‐GD1a, anti‐GM1, or C jejuni infection alone, is associated with a predominantly distal weakness, (2) the presence of anti‐GalNAc‐GD1a, rather than C jejuni infection or anti‐GM1 antibody, is associated with a lack of sensory disturbance, (3) both anti‐GalNAc‐GD1a and anti‐GM1 antibodies are independently associated with a lack of cranial nerve impairment. Ann Neurol 1999;45:758–768

Characterization of Campylobacter jejuni isolates from patients with Guillain-Barré syndrome

Campylobacter jejuni is a major pathogen preceding Guillain-Barré syndrome (GBS), and most C. jejuni isolates from GBS patients belong to Penner serotype 19 (heat-stable; HS-19). We analyzed sixteen independent clinical isolates from GBS patients, twelve of which belonged to HS-19, three to HS-2, and one to HS-4, using PCR-based RFLP analysis of a flagellin-A (flaA) gene. Two isolates from patients with Miller Fisher syndrome (MFS), and 27 from patients with uncomplicated enteritis were also examined. All HS-19 isolates, regardless of GBS, showed an identical pattern (Cj-1) by RFLP typing and were distinguishable from those of the other Penner serogroups. In contrast, HS-2 and HS-4 isolates were divided into several different RFLP groups, suggesting HS-19 strains are genetically distinctive among C. jejuni isolates. A DNA fingerprinting method also failed to detect any specific band pattern for GBS-related C. jejuni isolates. We examined relationships among anti-GM1 antibody titres in the sera of GBS patients, clinical forms of GBS, serotype of C. jejuni, and the presence of GM1-like structures in lipopolysaccharide (LPS) components from C. jejuni isolates by immunoblotting. HS-19 related GBS was significantly associated with elevated anti-GM1 antibody titers in the sera of the patients, but not associated with any clinical pattern of GBS. No significant correlations were found between anti-GM1 antibody and the pattern of disease, or between GBS-related C. jejuni strains and the presence of GM1-like structures. HS-19 strains seem to be unique among C. jejuni isolates, and HS-19-related GBS may provide an excellent model for clarification of the pathogenesis of GBS.

Congenital muscular dystrophy of non-Fukuyama type with characteristic CT images.

A 9-year-old Japanese boy with congenital muscular dystrophy (CMD) with normal intelligence was presented. He was extremely floppy and had joint contractures since birth. Motor milestones were delayed and he did not learn to walk alone. Intellectual development was normal and no convulsions were observed. On physical examination at 9 years old, he had diffuse muscle weakness and atrophy and flexion contractures of joints. Creatine kinase was normal and IQ was 95. Biopsied muscle showed myopathic changes consistent with muscular dystrophy. CT scans of the head revealed diffuse low density area in the white matter of the cerebrum. These findings suggest central nervous system involvement in CMD is not confined to Fukuyama-type CMD.

Ocular manifestations in fukuyama type congenital muscular dystrophy

We describe a child with Fukuyama type congenital muscular dystrophy (FCMD) who had several ocular manifestations since birth. These included high myopia, strabismus, nystagmus and optic atrophy of both eyes. Later he developed retinal detachment of both eyes. Our survey of 33 cases with FCMD revealed that high myopia and optic atrophy are common in FCMD. Retinal detachment was reported in two cases in addition to the present one and was considered to be of developmental origin. The association of congenital muscular dystrophy with brain changes and ocular anomalies were found in FCMD, muscle, eye and brain disease (MEB) and Walker-Warburg syndrome (WWS). Ocular manifestations in FCMD were, in general, less severe than those in WWS or MEB. Our study suggests that FCMD, MEB and WWS are developmental abnormalities with a continual spectrum of disease severity.

Clinical and Electroencephalographic Studies of Postencephalitic Epilepsy

We retrospectively reviewed the clinical features and results of investigation of 62 patients with acute encephalitis or encephalopathy in the acute phase to identify the prognostic factors in the development of postencephalitic epilepsy. Patients who later developed epilepsy showed more marked disturbance of consciousness, convulsions, and seizure activities on EEG during the acute phase than those who did not. There was no relation between CSF abnormalities and postencephalitic epilepsy. Control of convulsions during the acute phase, especially of status epilepticus, seem to be important to improve the prognosis.

Plasmapheresis in the treatment of the Guillain-Barré syndrome in childhood

Four patients (two boys and two girls, 6 to 13 years of age) with the Guillain-Barré syndrome (GBS) exhibiting such pronounced symptoms as dyspnea and dysphagia were treated with plasmapheresis using an intermittent flow system or double filtration plasmapheresis. The duration of the disease before plasmapheresis varied between 4 and 11 days. Three of the four patients experienced marked improvement during the course of plasmapheresis, but one patient had only partial improvement. No serious complications occurred. Good clinical and electrophysiologic recovery enjoyed by most patients treated with plasmapheresis appears to confirm the efficacy of plasmapheresis in children with severe GBS.

Leigh syndrome associated with West syndrome

Leigh syndrome (LS) (sub-acute necrotizing encephalomyelopathy) is characterized by symmetric brain lesions occurring mainly in the basal ganglia and associated with variable clinical manifestations such as hypotonia, psychomotor retardation, and feeding difficulties. Patients with LS may develop seizures. Only three patients with LS have been identified in the literature as having West syndrome (WS). We have seen 12 children with LS in the past 20 years, and noticed that as many as five of them developed WS. This report discusses five LS children with WS, comparing them with seven LS children without WS. In all five patients, infantile spasms developed after LS had become evident, in addition to other type(s) of seizures. The onset of LS in all the patients with WS was before 10 months of age. Although not statistically proven, early onset of LS, spasticity, nystagmus, apnea, poor feeding, and cardiac problems seemed to be associated with the development of WS. We were not able to conclude that certain types of symptoms or examination results of patients with LS indicated the development of WS. The association of LS with WS did not markedly influence the prognoses of the children. WS may not be a rare complication of LS, especially in infants under 12 months of age. This report is the first review of LS associated with WS.

The effect of intraventricular interferon on subacute sclerosing panencephalitis

Two patients with subacute sclerosing panencephalitis (SSPE) were treated with intraventricular alpha interferon (IFN-alpha) via an Ommaya reservoir for 20-57 months. The clinical course of the disease was followed for 20-67 months. Clinical improvement was observed after daily intraventricular administration of IFN in one case. There were no serious complications or side effects during interferon therapy except for the fever. Intraventricular administration of IFN appears superior to intrathecal administration for long-term treatment in several respects and is considered to be a potential therapeutic modality for SSPE.