In a neurologically healthy cohort, the associations of PVS differ according to their topography. PVS distribution may be useful for the early detection and classification of small vessel disease.

Background and Purpose-Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. Methods-A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores Ͻ27 or Ͼ1.5 SDs below the age-related mean were regarded as subnormal. Results-MBs were found in 35 subjects (6.8%). MMSE score Ͻ27 was found in 25 subjects (4.8%), with MMSE score Ͼ1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores.

Objective: The fukutin gene (FKTN) is the causative gene for Fukuyama-type congenital muscular dystrophy, characterized by rather homogeneous clinical features of severe muscle wasting and hypotonia from early infancy with mental retardation. In contrast with the severe dystrophic involvement of skeletal muscle, cardiac insufficiency is quite rare. Fukuyama-type congenital muscular dystrophy is one of the disorders associated with glycosylation defects of ␣-dystroglycan, an indispensable molecule for intra-extra cell membrane linkage. Methods: Protein and functional analyses of ␣-dystroglycan and mutation screening of FKTN and other associated genes were performed. Results: Surprisingly, we identified six patients in four families showing dilated cardiomyopathy with no or minimal limb girdle muscle involvement and normal intelligence, associated with a compound heterozygous FKTN mutation. One patient died by rapid progressive dilated cardiomyopathy at 12 years old, and the other patient received cardiac implantation at 18 years old. Skeletal muscles from the patients showed minimal dystrophic features but have altered glycosylation of ␣-dystroglycan and reduced laminin binding ability. One cardiac muscle that underwent biopsy showed altered glycosylation of ␣-dystroglycan similar to that observed in a Fukuyama-type congenital muscular dystrophy patient. Interpretation: FKTN mutations could cause much wider spectrum of clinical features than previously perceived, including familial dilated cardiomyopathy and mildest limb girdle muscular dystrophy.

Background and Purpose-Brain microbleeds (MBs) are considered to be associated with cognitive decline and can be pathologically and topographically classified as cerebral amyloid angiopathy-related (located in lobar regions) and hypertensive microangiopathy-related (located in deep regions). We examined whether different effects on global cognitive function might be seen with different distributions of MBs. Methods-A total of 1279 adults without neurological disorders were studied prospectively. Subjects were divided into 4 groups: without-MBs group; lobar group; deep group; and with in both areas (diffuse group). The Mini-Mental State Examination was administered to determine global cognitive functions, with scores Ͻ27 regarded as subnormal. Results-MBs were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48 subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal scores were found in 76 subjects (5.9%), associated with age, education, hypertension, severe white matter hyperintensities, and distribution and number of MBs. In the final model of logistic regression analysis, the deep group (OR, 2.79; 95% CI, 1.14 -6.79) was associated with subnormal scores, whereas the lobar group (OR, 0.77; 95% CI, 0.17-3.44) was not. Trend for the diffuse group did not reach the level of significance (OR, 5.01; 95% CI,). These trends were also seen in analysis using another cut-off point for subnormal score. Scores for total Mini-Mental State Examination and attention and calculation were significantly lower in the deep group and the diffuse groups compared with the without-MBs group. Conclusions-ThisJapanese cross-sectional study demonstrated that MB-related global cognitive dysfunction seems to occur based on hypertensive pathogenesis rather than on cerebral amyloid angiopathy. (Stroke. 2012;43:1800-1805.)Key Words: microbleeds Ⅲ cognitive impairment Ⅲ hypertension Ⅲ cerebral amyloid angiopathy B rain microbleeds (MBs) on gradient-echo T2*-weighted magnetic resonance imaging (MRI), which are characterized histologically by the presence of hemosiderin around small vessels, are now accepted as a manifestation of cerebral small vessel pathologies, including hypertensive small vessel disease and cerebral amyloid angiopathy (CAA). 1,2 MBs are often detected in patients with stroke, 2,3 and are also reportedly associated with dementia disorders such as Alzheimer's disease, 4 and vascular dementia, 5 or memory loss, 6 as well as cognitive decline. 7-11 However, their pathological impacts on cognitive function remain uncertain.The pathological differences in MBs according to distribution is now well-known, with MBs in deep regions (deep MBs) considered to be associated with hypertensive microangiopathy, whereas strictly lobar MBs (lobar MBs) share risk factors with CAA. 12,13 According to this pathological and distributional concept, we assessed whether different effects on global cognitive function might be seen with different topographical distributions of MBs in a sample of independen...

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS.