Polymorphisms in the presenilin 1 and presenilin 2 genes and risk for sporadic Alzheimer's disease

We examined the possible involvement of polymorphisms of the presenilin 1 (PS1) and presenilin 2 (PS2) genes in the risk for sporadic Alzheimer's disease (AD), either through an independent effect or through interaction with the existing apolipoprotein E (ApoE) risk, in 211 AD cases and 188 age-matched control subjects. No significant differences were obtained in any of the comparisons relating the effect of the PS1 and PS2 polymorphisms; thus, these polymorphisms do not appear to be sufficient risk factors by themselves for sporadic AD. Although the ApoE varepsilon4 genotype is the only definite predictor of risk, homozygosity for either the 1 allele of the PS1 or the C allele of the PS2 genes may increase the risk conferred by the presence of an ApoE epsilon4 allele. Additionally, combination of PS1/11 and PS2/CC genotypes might have a small synergistic effect on the risk for AD.     

Creutzfeldt-Jakob disease with severe involvement of cerebral white matter and cerebellum

Summary We describe a patient with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Postmortem examination revealed the characteristic lesions of CJD in the grey matter and profound white matter involvement was seen with immunocytochemical techniques. Ultrastructural white matter lesions were identical to those described in experimentally transmitted CJD. There was marked loss of cerebellar granule cells with virtual disappearance of parallel fibres, but Purkinje cells were only slightly reduced. Electron microscopic studies revealed extensive degenerative changes including cytoplasmic vacuoles in both cell types. Silver methods disclosed massive impregnation of white matter and striking abnormalities of Purkinje cells consisting of hypertrophy and flattening of thick dendritic branches, reduction in the number of terminal branchlets, segmentary loss of spines and polymorphic spines. These findings show the extensive involvement of all three cerebellar cortical layers and the reactive plasticity of Purkinje cells to deafferentiation. They favour the hypothesis that demyelination represents a primary lesion of the white matter.     

Muscle MRI in severe Guillain–Barré syndrome with motor nerve inexcitability

We report on the clinical, electrophysiological, and lower-limb musculature MRI findings in a severe demyelinating Guillain–Barré syndrome (GBS) patient with follow-up over 6 months. After 3 weeks of tetraplegia and mechanical ventilation, there was progressive improvement until almost complete recovery. On day 4 after onset, electrophysiological study revealed absent F waves and widespread conduction block. On four further electrophysiological studies on days 12, 19, 45, and 150, there was marked and reversible slow down of motor conduction velocities in upper-limb nerves, and persistent inexcitability of lower-limb nerves. Mild signs of active denervation were recorded in calf and foot muscles as of day 45. On day 39, MRI T2-weighted fat-suppressed images showed patchy hypersignal of variable intensity involving pelvic, thigh, and calf muscles, which disappeared in a second imaging study on day 190; in this study T1-weighted images did not disclose muscle fatty atrophy. We conclude that in severe demyelinating GBS prolonged motor nerve inexcitability should not necessarily be taken as a predictor of poor prognosis, and that MRI is useful in assessing the topography and evolution of muscle denervation.