Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting motor neurons. The etiology of the majority of cases remains unknown. Recent findings from several laboratories suggest a role for neurofilaments in the development of motor neuron disorders. The C-terminal region of the human neurofilament heavy subunit (NEFH) contains a unique functional domain consisting of 43 repeat motifs of the amino acids Lys-Ser-Pro (KSP). This C-terminal region of NEFH forms the sidearm projections which cross-link the neurofilaments. Previously, we have demonstrated polymorphism in the C-terminal region of the human NEFH: an allelic variant of a slightly larger molecular size, containing an additional KSP phosphorylation motif. Novel mutations in this region were found in five ALS patients. We propose that changes in the KSP-repeat domain may affect the cross-linking properties of the heavy neurofilament subunit and perhaps contribute to the development of neurofilamentous swellings in motor neurons, a hallmark of ALS.

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Elderly subjects diagnosed with mild cognitive impairment (MCI) are becoming the target of intervention trials. The criteria used for MCI are principally issued from prospective clinical studies, although longitudinal population-based studies having identified several cognitive predictors of dementia can be of great contribution in the definition of these criteria. This study was conducted to explore the external validity of MCI criteria issued from a longitudinal population-based study, and subsequently to identify the best predictors of the short-term conversion to Alzheimer’s disease 2 years after the MCI diagnosis. Ninety elderly volunteers with memory complaint diagnosed with MCI on the basis of their functional and neuropsychological performances were followed up within 2 years. The potential predictors of the conversion to dementia collected at baseline included age, gender, educational level, size of temporal lobe, apolipoprotein E genotype and a series of neuropsychological measures (Mac Nair Scale, Mini-Mental State Examination, Benton Visual Retention Test, Isaacs Set Test, Digit Symbol Substitution Task, Letter Cancellation Task, digit span tasks and finger-tapping test). Within the 2 years, 29 subjects (32.2%) presented a conversion to dementia. The risk of conversion to dementia was associated with age and size of temporal lobe but not with gender, education, or apolipoprotein E4 genotype. Several neuropsychological measures were associated with the risk of conversion to dementia, but in a logistic regression performed with the significant variables found in the univariate analysis, only the Letter Cancellation Test was shown to be an independent predictor. In conclusion, the quite elevated conversion rates obtained show the usefulness, when defining MCI criteria, of considering not only memory impairment but also impairment in other cognitive areas, as well as mild impairment on higher-order activities of daily living. Among the variables considered, the Letter Cancellation Test proved to be a major predictor of short-term conversion to dementia.

No neuroprotective or beneficial symptomatic effects of riluzole in Huntington's disease were demonstrated.

Although alpha-tocopherol did not appear to affect the survival and motor function in ALS, patients receiving riluzole plus alpha-tocopherol remained longer in the milder states of the ALS Health State scale and showed, after 3 months, changes in biochemical markers of oxidative stress. Further studies are required to confirm the greater sensitivity of the ALS Health State scale over other clinical endpoints.