The First Case of Huntington's Disease like 2 in Mali, West Africa.

Background: Huntington's disease like 2 (HDL2) has been reported exclusively in patients with African ancestry, mostly originating from South Africa. Case report: We report three patients in Mali including a proband and his two children who have been examined by neurologists and psychiatrists after giving consent. They were aged between 28 and 56 years old. Psychiatric symptoms were predominant in the two younger patients while the father presented mainly with motor symptoms. Genetic testing identified a heterozygous 40 CTG repeat expansion in the Junctophilin-3 (JPH3) gene in all three patients. Discussion: This study supports the hypothesis that HDL2 may be widely spread across Africa. Highlights: We report here the first case of HDL2 in West Africa, suggesting that HDL2 is widely spread across African continent, and increasing access to genetic testing could uncover other cases.

Hereditary spastic paraplegia in Mali: epidemiological and clinical features.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases divided into pure and complex forms, with spasticity in lower limbs only, or associated with other neurologic and non-neurologic manifestations, respectively. Although widely reported in other populations, very little data exist in sub-Saharan Africa. METHODS: Patients with neurodegenerative features were evaluated over a 19-month period at the Department of Neurology, Teaching Hospital of Point "G", Bamako, Mali. The diagnosis of HSP was considered based on family history and the absence of other known non-genetic causes. Genetic analysis including candidate gene and whole exome sequencing was performed and variant pathogenicity was tested using prediction tools and ACMG guidelines. RESULTS: Of the 170 families with hereditary neurological disorders enrolled, 16 had features consistent with HSP, a frequency of 9%. The average age of onset was 14.7 years with 46% starting before age 6. The male/female ratio was 2.6:1. Complex forms were seen in 75% of cases, and pure forms in 25%. Pyramidal findings were present in all patients. Associated features included mental retardation, peripheral neuropathy, epilepsy, oculomotor impairment and urinary urgency. Most patients were treated with a muscle relaxant and physical therapy, and restorative surgery was done in one. Genetic testing identified novel variants in three families (19%). CONCLUSION: This study confirms the clinical variability of HSPs and adds African data to the current literature.

Severe meningo-radiculo-neuritis associated with ipilimumab.

PURPOSE: Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) to promote antitumoural immunity. In phase III trials, ipilimumab was shown to be the first agent to improve survival in advanced melanoma patients, regardless of previous treatment. We report a case of severe neurologic disease after ipilimumab treatment. PATIENT AND METHODS: Neurologic symptoms including facial diplegia, tetraplegia, areflexia progressed with time a few days after the fourth monthly ipilimumab infusion. Analysis of the cerebro-spinal fluid showed elevated proteinorachy and lymphocytic meningitis. Despite high doses of steroids and symptomatic treatment, the symptoms worsened. RESULTS: Veinoglobulins were then infused and the patient began to improve and recovered almost normal activity two years later. CONCLUSION: The adverse event profile associated with ipilimumab was primarily immune-related. This is the first case in which such a severe event has been reported.

Clinical and Genetic Aspects of Huntington's Disease in the Malian Population.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by mutation in the HTT gene and characterized by involuntary movements as well as cognitive and behavioral impairment. Since its first description 150 years ago, studies have been reported worldwide. However, genetically confirmed cases have been scarce in Africa. OBJECTIVE: To describe the clinical and genetic aspects of HD in the Malian population. METHODS: Patients with HD phenotype and their relatives were enrolled after obtaining consent. Symptoms were assessed using the Total Motor Scale (TMS) of the United Huntington's Disease Rating Scale (UHDRS) and the Mini-Mental State Examination (MMSE). Brain imaging and blood tests were performed to exclude other causes. DNA was extracted for HTT sequencing. RESULTS: Eighteen patients (13 families) with a HD phenotype were evaluated. A familial history of the disease was found in 84.6% with 55.5% of maternal transmission. The average length of the HTT CAG repeat was 43.6±11.5 (39-56) CAGs. The mean age at onset was 43.1±9.7years. Choreic movements were the predominant symptoms (100% of the cases) with an average TMS of 49.4±30.8, followed by cognitive impairment (average MMSE score: 23.0±12.0) and psychiatric symptoms with 22.2% and 44.4%, respectively. CONCLUSION: This is one of the largest HD cohorts reported in Africa. Increasing access to genetic testing could uncover many other HD cases and disease-modifying genetic variants. Future haplotype and psychosocial studies may inform the origin of the Malian mutation and the impact of the disease on patients and their relatives.

[Tremor/ataxia syndrome related to Fragile X premutation]. / Syndrome tremblement-ataxie lié à une prémutation de l'X fragile.

The FXTAS syndrome (Fragile X-associated tremor/ataxia syndrome) is a specific neurodegenerative syndrome affecting subjects carrying a premutation of the FMR1 (fragile X mental retardation 1) gene. It affects mainly men with the premutation and aged more than 50 years. This syndrome is separate and distinct from the fragile X syndrome. The FXTAS syndrome remains underestimated today. It should be considered in patients older than 50 years with tremors and cerebellar ataxia, especially when Parkinson disease or cognitive disorders are present or when there is a family history of infertility, early menopause, or mental retardation. In these patients, hyperintense signals of mid-cerebellar peduncle images on T2 and FLAIR MRI justify genetic testing for the FMR1 premutation.