Ultrastructural immunocytochemical abnormalities of peripheral myelin proteins in hereditary sensory-motor neuropathies: 12 cases.

Hereditary sensorimotor neuropathies form a heterogeneous group of genetically determined diseases, of which Charcot-Marie-Tooth (CMT) disease is the most common. In order to establish relations between genotype and the expression of peripheral myelin proteins, we carried out a quantitative study by ultrastructural immunocytochemistry of several myelin proteins (PMP22, P0, MBP) on sural nerve biopsy samples from 12 unrelated CMT patients. The diagnosis of CMT was based on the clinical, electrophysiological, and histological findings along with those of molecular biological studies. CMT X diagnoses were not included in this study. The expression of myelin proteins was well correlated with the molecular biological findings in these patients. The results also provided evidence for interference between different myelin proteins. Our findings are in line with the results from animal studies (trembler and knock-out mice), which may provide insights into the pathogenesis of these human conditions.

[The involvement of myelin proteins in hereditary neuropathies]. / Implications des protéines myéliniques dans les neuropathies héréditaires.

Hereditary sensoro-motor neuropathies such as Charcot-Marie-Tooth disease (CMT) form a heterogeneous group including some genetic conditions whose clinical manifestations differ in severity within a group or even within a sub-group. Diagnosis is based on the clinical, electrophysiological and pathological findings along with a genetic analysis. The current classification of CMT encompasses the clinical signs, mode of transmission, genomic localization and identification of the proteins actually involved. Several authors have identified the mutations on genes coding for proteins of peripheral myelin in CMT patients. Recent advances in molecular genetics have thrown more light on the differences between phenotypes within a sub-group, and have established genotype-phenotype relationships. It has been shown recently that the severity of the clinical signs depends on the nature and site of various mutations affecting the genes coding for certain myelin proteins. These mutations give rise to "dominant negative effects" or "mutations with loss of function of the allele". These observations may be extended to other proteins as many of them belong to the super family of immunoglobulins and have similar structures. In this study, we present a review of the literature focussing on the principal myelin proteins and the genomic modifications observed in patients with CMT.

[Prevalence of HTLV-1 virus infection in Togo (Kozah prefecture and the University Hospital Center of Lomé]. / Prévalence de l'infection par le virus HTLV-1 au Togo (préfecture de la Kozah et CHU de Lomé).

The aim of this study was to determine the prevalence of Human T cell Leukaemia Virus Type 1 (HTLV1) in a representative population sample, in neurological and non-neurological patients hospitalised in the Lomé teaching hospital in order to study the clinical manifestations of this retrovirus. There was no statistical difference among the three groups concerning the prevalence of HTLV1 respectively (1.2%: 21/1717, 1.8%: 15/828 and 1.6%: 4/244). Spastic paraparesis was the only disease significantly linked to HTLV1 (15.5%: 9/58).

Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients.

BACKGROUND: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. OBJECTIVE: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. METHODS: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. RESULTS: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. CONCLUSION: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.

Peripheral facial paralysis (PFP) and HIV infection in Togo.

OBJECTIVES: The purpose of this study was to determine the seroprevalence of HIV in a group of 150 patients with PFP and to study the semiological and evolutive aspect of PFP in patients with or without HIV. MATERIAL AND METHODS: This semilongitudinal study was conducted during 6 years (1990-1995) at the Lomé teaching hospital. Patients consulting for PFP had the HIV test and regular controls. RESULTS: The HIV seroprevalence was 52%. The average age was 31.4+/-8.81 years There was no difference on clinical features between patients with or without HIV infection. Cerebrospinal fluid was normal in patients without HIV infection, but it showed pleiocytosis in patients with HIV infection (87.88%). Of the HIV carriers 14% presented a recurrence. A total of 26.32% of the patients screened in 1990 developed AIDS when followed up. CONCLUSION: Peripheral facial paralysis is frequently associated to HIV infection. An HIV test must be proposed to all patients with PFP in Africa.

Expression of myelin proteins in the adult heterozygous Trembler mouse.

The Trembler mouse (Tr) suffers from a dominantly inherited autosomal mutation (glycine to aspartic acid. G150D) affecting the PMP22 gene, which results in an abnormal myelination of the peripheral nervous system. The Tr mouse represents an animal model for the human hereditary neuropathy, Charcot-Marie-Tooth disease. We compared the expression of PMP22, P0, myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) in nerve biopsies from a 1-year-old heterozygous Tr mouse (Tr/+) with that of a control mouse of the same age. Quantitative and qualitative ultrastructural immunocytochemical analysis showed a significant decrease in PMP22, P0 and MBP and an abnormal location of the MAG in the sciatic nerve of the Tr/+ mouse. We also noted a marked reduction in number of myelinated fibers associated with the presence of two types of myelinated axons: a population of abnormally thin myelin sheaths with lower PMP22 labeling than that observed in myelinated fibers from the control mouse, and some others fibers with normal sheaths for axons of comparable diameter to those of normal mouse with no difference in the PMP22 immunolabeling. This pointed to an involvement of PMP22 in the structure of myelin sheaths.

Ultrastructural protein zero expression in Charcot-Marie-Tooth type 1B disease.

Charcot-Marie-Tooth type 1B (CMT 1B) disease, an inherited demyelinating peripheral neuropathy, results from different point mutations located in the P0 gene on chromosome 1 q21-23. We have quantified, at the ultrastructural level, the immunocytochemical expression of the P0 protein in two unrelated CMT 1B patients with mutations (Ser 78 to Leu and Asn 122 to Ser) located in two different exons in the extracellular domain of the protein. A twofold decrease in P0 expression was observed in compact myelin in each case, compared with age-matched controls. The severity of the phenotypes showed no direct relationship to the levels of P0 protein expression in these 2 patients.