Combined central and peripheral demyelination in two siblings, immune mediated or genetic?

We report unusual cases of combined central and peripheral demyelination in two siblings related to pregnancy, each presenting with progressive tetraparesis and cranial nerve palsies. The elder sister had a relapsing-remitting course with optic nerve dysfunction and died during a relapse from respiratory insufficiency. The younger sister presented with disorientation and acute-onset limb and facial weakness. She responded well to corticosteroid therapy. Their clinical presentation, response to immunomodulatory therapy, nerve conduction studies, cerebrospinal fluid and histology supported an acquired demyelinating cause. Whole-exome sequencing identified variants in two genes not previously linked to this clinical phenotype. Serological tests for antibody-mediated demyelination were negative. Despite the undefined pathogenesis, these cases provide a platform to explore the confluence of genetic, immune and environmental factors in the context of acquired demyelination. We discuss the differential diagnosis and a diagnostic approach to such cases from the perspectives of neuroimmunology and neurogenetics.

A Comparison of Clinical, Electro-Diagnostic, Laboratory, and Treatment Outcome Differences in a Cohort of HIV-Infected and HIV-Uninfected Patients With Myasthenia Gravis.

There is limited literature comparing the clinical parameters and treatment outcomes in HIV-infected and HIV-uninfected myasthenia gravis (MG) patients. The aim of the study was to investigate the clinical differences and treatment outcomes in the two categories of patients, particularly the safe use of immunosuppressive therapy in immunocompromised patients. The study was a retrospective analysis of medical records of MG patients from the neuromuscular unit at Inkosi Albert Luthuli Central Hospital in Kwa-Zulu Natal between 2003 and 2019. One hundred and seventy-eight (178) patients fulfilled the clinical criteria for MG. Twenty-four (13.4%) were HIV-infected and 154 (86.5%) were HIV-uninfected. There were 116 (65%) females, median 45 years, (IQR 40-62), 90 (50.5%) black African, 66 (37%) Indian, 20 (11.2%) white, and 2 (1.1%) of mixed ancestry. In the HIV-infected cohort, 20 (87%) had generalized MG, 12 (50%) bulbar, and 14 (60.9%) respiratory onset MG, 12 (50%) presented with MG Foundation of America (MGFA) class five diseases at diagnosis, six (25%) presented with MG crisis during the 5-year follow-up. Thirteen (54%) of the HIV-infected group required rescue therapy using (plasma exchange or IV immunoglobulin) combined with pulse cyclophosphamide compared with 17 (11%) in the HIV-uninfected cohort, respectively. At 5 years, 8 (33%) of the HIV-infected group remained refractory to treatment compared with 10 (6.5%) HIV-uninfected cohort, respectively. No adverse events were documented in HIV-infected patients receiving combination rescue therapy (PLEX or IVIG combined with IV cyclophosphamide). In conclusion HIV-infected MG patients are more likely to require combination rescue therapy with PE/IVIG and IV cyclophosphamide compared with those who were HIV-uninfected. No side effects were documented in the HIV-infected group receiving the above therapy.

Motor lumbosacral radiculopathy in HIV-infected patients.

BACKGROUND: This study is a review of the clinical findings and treatment outcome of 11 HIV-infected patients with motor lumbosacral radiculopathy. OBJECTIVES: To describe the clinical, laboratory, electrophysiological features and treatment outcome in HIV-infected motor lumbosacral radiculopathy which is a rare manifestation of HIV. METHOD: A retrospective review of HIV-infected patients with motor lumbosacral radiculopathy was performed at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa between 2010 and 2015. RESULTS: Eleven black African patients met the inclusion criteria. There were six women. The median age was 29 years, the interquartile range (IQR) was 23-41 years, the median duration of symptom progression was 6.5 months (IQR 3-7.5 months). The median CD4 count was 327 cells/µL (IQR 146-457). The cerebrospinal fluid (CSF) median polymorphocyte count was 0 cells/µL (IQR 0 cells/µL - 2 cells/µL), lymphocyte count was 16 cells/µL (IQR 1 cells/µL - 18 cells/µL), glucose level was 3.1 mmol/L (IQR 2.8 mmol/L - 3.4 mmol/L) and protein level was 1.02 g/dL (IQR 0.98 g/dL - 3.4 g/dL). All patients were treated with corticosteroid therapy. Ninety-one per cent recovered fully within 6 months of treatment, the median time for recovery was 3.4 months (IQR 1.8-5.6 months). There were no relapses during the 18-month follow-up. CONCLUSION: HIV-infected patients with motor lumbosacral radiculopathy responded to corticosteroids, with no relapses during the 18-month follow-up period.

A comparative study of motor neuron disease in HIV-infected and HIV-uninfected patients.

BACKGROUND: This study is a descriptive review of the clinical and treatment outcome differences in HIV-infected patients with motor neuron syndrome (MNS) and HIV-uninfected patients with motor neuron disease (MND). METHODS: A retrospective analysis of patients with MND/S was performed at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa between 2003 and 2017. RESULTS: One hundred and thirty six patients were included in the study, 101 (76%) were HIV-uninfected and 35 (26%) were HIV-infected. Ninety four percent of the HIV-infected cohort were <50 years, median 41, IQR (33-45), p < 0.001, had median ALS functional rating scale revised (ALSFRS-R) score of 28, IQR [24-30] and 40% of these patients on anti-retroviral therapy (ART) survived longer than 10 years. Ninety one percent of the HIV-uninfected cohort were >50 years, median 66, IQR(57-74), P < 0.001, had median ALSFRS-R score of 44 (IQR 42-45) and 93% died within 5 years of their illness. CONCLUSION: HIV-infected MNS patients were younger, had more severe disease at presentation and survived longer if treated with ART with possible reversal of the disease process, compared to patients with MND.

A comparative study of CIDP in a cohort of HIV-infected and HIV-uninfected patients.

OBJECTIVE: To investigate differences in clinical presentation, electrodiagnostic measures, CSF changes, and treatment outcome measures in HIV-infected and HIV-uninfected patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: A retrospective analysis of medical records of all patients meeting the European Federation of Neurology diagnostic criteria for idiopathic CIDP was performed in 2 neuromuscular units in Kwa-Zulu Natal between 2003 and 2015. RESULTS: Eighty-four patients were included in the study; 39 were HIV-infected and 45 were HIV-uninfected. Among the HIV-infected patients, the majority were younger, were female, and had a monophasic progressive illness. Eighty-six percent (86%) were corticosteroid-responsive and 76% were in remission within 6-12 months requiring no further treatment. Among the HIV- uninfected patients, the majority were older, were male, and had a relapsing-remitting course. Twenty-seven percent (27%) were corticosteroid-responsive, 95% required combination therapy, and 33% were not in remission by 18 months on therapy. CONCLUSION: This study shows that HIV-infected patients with CIDP were younger, were more often female, displayed a monophasic progressive course, were highly steroid-responsive, and went into remission within 12 months of corticosteroid initiation.

The hereditary adult-onset ataxias in South Africa.

There is little data on the spectrum and frequencies of the autosomal dominant spinocerebellar ataxias (SCAs) from the African continent. We undertook a large prospective population-based study over a 10-year period in South Africa (SA). Affected persons were clinically evaluated, and the molecular analysis for the SCA1, 2, 3, 6 and 7 expansions was undertaken. Of the 54 SA families with dominant ataxia, SCA1 accounted for 40.7%, SCA2 for 13%, SCA3 for 3.7%, SCA6 for 1.9%, SCA7 for 22.2% and 18.5% were negative for all these mutations. The frequency of the SCA1 and SCA7 expansions in SA represents one of the highest frequencies for these expansions reported in any country. In this study, the SCA7 mutations have only been found in SA families of Black ethnic origin.