Essential tremor with ubiquitinated intranuclear inclusions and cerebellar degeneration.

BACKGROUND: Essential tremor (ET), a progressive, age-associated disease, is one of the most common neurological disorders. Yet until recently, there had been few postmortem examinations so that the full range of pathological changes associated with this disease has not been catalogued. OBJECTIVES: We report a patient with ET who had a pattern of pathological change which to our knowledge has not previously been reported in ET or another neurological disease. METHODS: Clinical-pathological case report. RESULTS: The patient had adult-onset, non-familial, kinetic arm tremor that gradually worsened. Voice and head tremors were also present. The clinical diagnosis was ET. She died at age 102. On postmortem examination, there was severe segmental loss of Purkinje cells, Bergmann gliosis and numerous torpedoes in the cerebellum. The other outstanding change was the presence of neurons in the cerebral cortex and hippocampus that contained an ubiquitinated, nuclear inclusion. These inclusions were not detected in Luxol fast blue/hematoxylin and eosin-stained sections. CONCLUSIONS: This ET patient had a pattern of pathological change that has not been reported previously. This case further reinforces the view that ET is likely to be a heterogeneous family of degenerative diseases whose underlying pathological anatomy involves the cerebellum.

Torpedoes in the cerebellar vermis in essential tremor cases vs. controls.

The study of the postmortem changes in essential tremor (ET) is in its infancy, although recent evidence points to a central role of the cerebellum, where Purkinje cell axonal swellings ("torpedoes") are significantly more common in ET than control brains. Yet, all existing studies have been confined to the cerebellar hemispheres, and whether there is a more widely distributed cerebellar problem is presently unknown. Our aims were to address whether: (1) ET cases have greater numbers of torpedoes in the vermis than controls, (2) there a correlation between the extent of vermal torpedo pathology and hemispheric torpedo pathology, and (3) vermal torpedo pathology is correlated with clinical features of the disease. A parasagittal neocerebellar block and a vermal block were harvested from 24 ET and 10 control brains. Paraffin sections (7 µm) were stained with Luxol fast blue/hematoxylin and eosin, and torpedoes were quantified. All torpedo counts were corrected for Purkinje cell layer length. Vermal corrected torpedo count (VermTc) was higher in ET cases than controls (7.1±6.8 [median, 4.3] vs. 2.6±2.5 [median, 2]), p=0.002). The VermTc and the hemispheric corrected torpedo count (HemTc) were correlated with one another (Spearman's r=0.54, p=0.002). ET cases with neck, voice, and jaw tremors had the highest VermTc (p=0.046). The abundance of torpedoes in the ET brain is not confined to the ponto- or neocerebellum but is more broadly distributed, also involving the spino- or paleocerebellum. These data further confirm the central role of the cerebellum in the underlying pathophysiology of this common neurological disorder.