Behavioral & Cognitive Disorders
Nov. 14, 2023
At vero eos et accusamus et iusto odio dignissimos ducimus qui blanditiis praesentium voluptatum deleniti atque corrupti quos dolores et quas.
The author explains the clinical presentation, etiology, differential diagnosis, and diagnostic workup of progressive subcortical gliosis, a chromosome-17-linked dementia with unique pathologic features. Microscopically, the major pathologic change is a marked fibrillary astrocytosis, particularly in the area of the short cortical association tracts at the junction of cortical lamina VI and the subcortical white matter and in the subpial cerebral cortex. Overall, the survival of patients with progressive subcortical gliosis averages about 10 years and is similar to that of other types of frontotemporal dementia.
• Progressive subcortical gliosis is a rare dementing disorder resembling Pick disease but with distinctive neuropathologic features. The clinical manifestations are those of a frontotemporal dementia and overlap with those of other frontotemporal dementias.
• Progressive subcortical gliosis has an insidious onset, generally in the fifth or sixth decade. The course is progressive, generally over 5 to 15 years, but both fulminant and protracted courses occur.
• Common initial manifestations include personality and emotional changes, lack of judgment and insight, deterioration in social behavior, delusions, paranoia, auditory and visual hallucinations, and depression.
• Microscopically, the major pathologic change is a marked fibrillary astrocytosis, particularly in the area of the short cortical association tracts at the junction of cortical lamina VI and the subcortical white matter and in the subpial cerebral cortex.
• Most cases have been sporadic, but some hereditary forms are recognized, with linkage demonstrated in one kindred to a region on the long arm of chromosome 17 (17q21-22).
• Overall, the survival of patients with progressive subcortical gliosis averages about 10 years and is similar to that of other types of frontotemporal dementia.
Progressive subcortical gliosis is a rare dementing disorder clinically and pathologically resembling Pick disease but with distinctive neuropathologic features. In 1949, Neumann described three cases under the appellation of "Pick disease, type II" (47). In 1967, Neumann and Cohn reported four additional cases and suggested the designations "primary subcortical gliosis" and "progressive subcortical gliosis" (48); although neither of these terms is ideal, the latter has become established in the literature (10).
Although rare reports of familial cases were reported beginning in the 1940s, it was not until the late 1980s and 1990s that it was recognized that progressive subcortical gliosis could be transmitted as an autosomal dominant trait (16; 36). Progressive subcortical gliosis was linked to a tau mutation in the microtubule-associated protein tau (MAPT) gene on the long arm of chromosome 17 (54; 24) and, thus, it was included in the group of "frontotemporal dementias and Parkinsonism linked to chromosome 17" group (FTDP-17) (21; 10). More than 60 MAPT mutations have since been identified, usually causing behavioral variant frontotemporal dementia (FTD) or parkinsonism clinically (59).
MAPT-related frontotemporal dementia (MAPT-FTD) is a progressive neurodegenerative disorder characterized by frontotemporal dementia, often with parkinsonian manifestations. Most affected individuals have behavioral changes consistent with a diagnosis of behavioral variant FTD (bvFTD) or a parkinsonian syndrome, but there is considerable phenotypic heterogeneity, even between and within families with the same MAPT variant (56). End-stage disease is characterized by severe dementia often with muteness and profound functional motor impairment (often becoming chairbound or bedbound) (56). Mean disease duration is about 9 years but can be more than 30 years (56).
The concept of "frontotemporal dementias and Parkinsonism linked to chromosome 17" has since been challenged (19). Review of known cases suggested that distinct MAPT mutations result in particular tau subtypes linked to frontotemporal lobar degeneration (FTLD). As such, Forrest and colleagues argued FTLD-tau cases with MAPT mutations should be considered familial forms of FTLD-tau subtypes rather than a separate FTDP-17 category.
Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.