T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: It has been suggested that autoimmunity to peripheral myelin proteins is involved in the pathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We aimed to compare reactivity of peripheral blood mononuclear cells (PBMC) to antigens of peripheral myelin proteins in patients with GBS and patients with CIDP with that of healthy controls and patients with other non-immune mediated neuropathies (ON). METHODS: We prepared PBMC from blood from 83 healthy controls and from 64 patients with GBS, 54 with CIDP, and 62 with ON. PBMC were tested in antigen specific proliferation assays against peptides from myelin proteins P0, P2, PMP22, and myelin basic protein (MBP), which is identical to myelin P1, and against whole human MBP. Interferon-gamma (IFN-gamma) and interleukin (IL)-5 enzyme linked immunospot (ELISPOT) assays were also performed in some subjects to assess spontaneous and peripheral myelin antigen specific PBMC cytokine secretion. RESULTS: Antigen specific PBMC proliferation assays showed no significant elevation of peptide specific T cell responsiveness in patients with GBS or CIDP compared with healthy controls or patients with ON. Levels of spontaneous ELISPOT IFN-gamma secretion were increased in patients with GBS and significantly increased in those with CIDP compared with healthy controls and patients with ON. No convincing differences in antigen specific ELISPOT IFN-gamma secretion levels to individual peptides were detectable in patients with GBS. The proportion of patients with CIDP with an increased number of PBMC producing IFN-gamma in response to peptide PMP-22(51-64) was significantly increased compared with healthy controls and patients with ON. No significant differences in antigen specific ELISPOT IL-5 secretion levels were detectable in patients with GBS or CIDP compared with controls, but levels of spontaneous IL-5 secretion were significantly higher in patients with CIDP than in healthy controls or patients with ON. CONCLUSIONS: Although the lack of significantly increased antigen specific PBMC proliferation in GBS and CIDP does not support a role for T cells, the more sensitive ELISPOT technique detected increased numbers of PBMC secreting IFN-gamma spontaneously in 25% of patients with GBS, providing further evidence for a role of T cells in the immunopathology of GBS. Increased numbers of spontaneous IFN-gamma and IL-5 secreting cells, and increased IFN-gamma secretion in response to PMP-22(51-64), in patients with CIDP provide further evidence for a role of myelin specific T cells in CIDP.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy): an Australian perspective.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients.

Parkinsonism after correction of hyponatremia with radiological central pontine myelinolysis and changes in the basal ganglia.

Parkinsonism has been rarely described following central pontine and extrapontine myelinolysis. We report a case of parkinsonism developing following rapid correction of hyponatremia with radiological evidence of central pontine myelinolysis and changes in the basal ganglia. A 56-year-old man developed drooling and bilateral hand tremors 3 weeks after correction of hyponatremia from 103 to 125 mmol/L over 14 h. He had a prominent 6 Hz resting tremor which worsened with action and mild cogwheel rigidity. Magnetic resonance imaging (MRI) showed changes consistent with central pontine myelinolysis and increased signal on T1-weighted images in the putamen bilaterally. His tremor responded well to L-dopa therapy. There have been several other cases of parkinsonism developing after central pontine/extrapontine myelinolysis. Increased signal in the basal ganglia on T1-weighted images has been described in another case of central pontine myelinolysis imaged about the same time after sodium correction as our case.

Cerebral histoplasmosis in an Australian patient with systemic lupus erythematosus.

A 39-year-old woman with systemic lupus erythematosus suffered a prolonged neurological illness associated with very low levels of glucose in her cerebrospinal fluid (CSF). Six months later, and after numerous CSF investigations, Histoplasma capsulatum was cultured. To our knowledge, this is the first report of cerebral histoplasmosis in Australia in a patient who is not HIV positive.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a recently described genetic disease characterized by recurrent subcortical infarcts and dementia. Based on linkage analysis its gene has been assigned to chromosome 19p13. We report an Australian kindred with typical clinical features of CADASIL, the diagnosis being supported by linkage analysis. No expansion was detected on repeat expansion detection (RED) testing.

Oculopharyngeal muscular dystrophy (OPMD)--report and genetic studies of an Australian kindred.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant disease. Due to a founder effect, it is most commonly found in the French Canadian population. The gene has recently been mapped to chromosome 14q11.2-q13 in some of these families. Here we report an Australian kindred of German descent with OPMD. Linkage analysis supports its locus to chromosome 14q. Repeat expansion studies were also carried out, but a CAG trinucleotide repeat expansion detected did not cosegregate with the disease. We conclude that there is no evidence of genetic heterogeneity or involvement of repeat expansion in OPMD.