Brainstem pathology in DYT1 primary torsion dystonia

Kevin St P. McNaught, Alexander Kapustin, Tehone Jackson, Toni Ann Jengelley, Ruth JnoBaptiste, Pullanipally Shashidharan, Daniel P. Perl, Pedro Pasik, C. Warren Olanow

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


DYT dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem other involved bramstem structures in mediating motor activity and muscle tone also suggest that alterations in these structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia.

Original languageEnglish
Pages (from-to)540-547
Number of pages8
JournalAnnals of Neurology
Issue number4
StatePublished - Oct 2004


Dive into the research topics of 'Brainstem pathology in DYT1 primary torsion dystonia'. Together they form a unique fingerprint.

Cite this