|Gearing, M., Juncos, J. L.,
Procaccio, V., Gutekunst, C. A., Marino, E. M., Gyure, K. A., Ono, S.,
Santoianni, R., Krawiecki, N. S., Wallace, D. C. & Wainer, B. H.
(2002) Aggregation of actin and cofilin in identical twins with
juvenile-onset dystonia. Ann. Neurol. 52, (in press).
neuropathology of the primary dystonia is not well understood. We
examined brains from identical twins with DYT1-negative, dopa-unresponsive
dystonia. The twins exhibited mild developmental delays until age 12
years when they began developing rapidly progressive generalized
dystonia. Genetic, metabolic, and imaging studies ruled out known causes
of dystonia. Cognition was subnormal but stable until the last few
years. Death occured at ages 21 and 22 years. The brains were
macroscopically unremarkable. Microscopic examination showed unusual
glial fibrillary acidic protein-immunoreactive astrocytes in multiple
regions and iron accumulations in pallidal and nigral neurons. However,
the most striking findings were 1) eosinophilic, rod-like cytoplasmic
inclusion in neocortical and thalamic that were actin depolymerizing
factor/cofilin-immunoreactive but only rarely actin-positive; and 2)
abundant eosinophilic spherical structures in the striatum that were
strongly actin- and actin depolymerizing factor/cofilin-positive.
Electron microscopy suggests that these structures represent
degenerating neurons and processes; the accumulating filaments had the
same dimensions as actin microfilaments. To our knowledge, aggregation
of actin has not been reported previously as the predominant feature in
any neurodegenerative disease. Thus, our findings may shed light on a
novel neuropathological change associated with dystonia that may
represent a new degenerative mechanism involving actin, a ubiquitous
constituent of the cytskeletal system.