Mild Dementia Associated with Joseph Disease in a Japanese Family

Abstract

We clinically studied 4 patients with Joseph disease in a Japanese family, who developed mild dementia, and neuropathologically examined one autopsied case among them. Neurological findings included cerebellar ataxia, progressive external ophthalmoplegia, peripheral amyotrophy, and pyramidal signs. Mental state examination revealed mild impairment of intelligence. The dementia was characterized by mild memory disturbance with preservation of orientation, slowing of thought processes, affective changes including apathy and depression, impaired ability to manipulate acquired knowledge, and the absence of aphasia, apraxia and agnosia. CT demonstrated severe atrophy of the brain stem and severe dilatation of the fourth ventricle with mild atrophy of the cerebral and cerebellar hemispheres. EEG showed slowing of background activity. The autopsied case showed atrophy of the tegmentum of the brain stem in addition to the common pathological findings of Joseph disease. The features of dementia in the 4 patients were similar to those seen in ‘subcortical dementia’, suggesting that its pathological basis may be involvement of the tegmentum of the brain stem.

Striatonigral Degeneration Combined with Olivopontocerebellar Atrophy with Subcortical Dementia and Hallucinatory State

“…No aphasia, apraxia, or agnosia, which are suggestive of cerebral cortical pathology, was observed. These symp toms were consistent with those seen in subcortical de mentia [II, [13][14][15][16][17].…”

Delirium associated with Joseph disease.

“…The two necropsy cases revealed degeneration of the reticular formation, raphe nuclei and locus ceruleus, all of which are located in the brainstem tegmentum. The slowing of background activity on the EEGs of the patients supports a dysfunction of the reticular formation, by the absence of obvious cerebral pathology.25 Atrophy of the brainstem tegmentum in Joseph disease has been noted in several papers 18-20 24 25 30 but has attracted little attention. A few reports also neuropathologically described brainstem tegmental atrophy associated with degeneration of the reticular formation, 20 24 raphe nuclei20 24 and locus ceruleus,'7 2024 although they72024 did not discuss its pathological significance.…”

“…In Japan, the initial necropsy report was by Sakai Many reports of clinical and necropsy cases with Joseph disease have detailed neurological and neuropathological findings, but they lack any detailed description of the psychiatric features. 25 We present three Japanese Joseph disease patients from different families associated with delirium, which is presumed to be rare, and discuss the relationship between delirium and its pathological basis.…”

Sporadic Olivopontocerebellar Atrophy with 'Subcortical Dementia' and Hallucinatory Paranoid State: Report of an Autopsy

“…Shiraki [17] investigated 8 cases of progressive supranuclear palsy and 9 cases of dyssynergia cerebellaris myoclonica and sug gested that the psychotic features including dementia in both progressive supranuclear palsy and dyssynergia cere bellaris myoclonica are due to involvement of the tegmen tum of the brain stem. We [18] previously reported 4 patients with Joseph disease associated with subcortical dementia, to which the pontine tegmental atrophy may have contributed.…”