Browsing by Subject "Cerebrum"

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    Enlarging the Nosological Spectrum of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids (HDLS)
    (Wiley, 2014-09) Hoffmann, Sarah; Murrell, Jill; Harms, Lutz; Miller, Kelly; Meisel, Andreas; Brosch, Thomas; Scheel, Michael; Ghetti, Bernardino; Goebel, Hans-Hilmar; Stenzel, Werner; Pathology and Laboratory Medicine, School of Medicine
    Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant disease clinically characterized by cognitive decline, personality changes, motor impairment, parkinsonism and seizures. Recently, mutations in the colony-stimulating factor-1 receptor (CSF1R) gene have been shown to be associated with HDLS. We report clinical, neuropathological and molecular genetic findings of patients from a new family with a mutation in the CSF1R gene. Disease onset was earlier and disease progression was more rapid compared with previously reported patients. Psychiatric symptoms including personality changes, alcohol abuse and severe depression were the first symptoms in male patients. In the index, female patient, the initial symptom was cognitive decline. Magnetic resonance imaging (MRI) showed bilateral, confluent white matter lesions in the cerebrum. Stereotactic biopsy revealed loss of myelin and microglial activation as well as macrophage infiltration of the parenchyma. Numerous axonal swellings and spheroids were present. Ultrastructural analysis revealed pigment-containing macrophages. Axonal swellings were detected by electron microscopy not only in the central nervous system (CNS) but also in skin nerves. We identified a heterozygous mutation (c.2330G>A, p.R777Q) in the CSF1R gene. Through this report, we aim to enlarge the nosological spectrum of HDLS, providing new clinical descriptions as well as novel neuropathological findings from the peripheral nervous system.
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    The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study
    (Wolters Kluwer, 2013) Cash, David M.; Ridgway, Gerard R.; Liang, Yuying; Ryan, Natalie S.; Kinnunen, Kirsi M.; Yeatman, Thomas; Malone, Ian B.; Benzinger, Tammie L. S.; Jack, Clifford R., Jr.; Thompson, Paul M.; Ghetti, Bernardino F.; Saykin, Andrew J.; Masters, Colin L.; Ringman, John M.; Salloway, Stephen P.; Schofield, Peter R.; Sperling, Reisa A.; Cairns, Nigel J.; Marcus, Daniel S.; Xiong, Chengjie; Bateman, Randall J.; Morris, John C.; Rossor, Martin N.; Ourselin, Sébastien; Fox, Nick C.; Dominantly Inherited Alzheimer Network (DIAN); Radiology and Imaging Sciences, School of Medicine
    Objective: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. Methods: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxel-based morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. Results: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. Conclusions: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.