Treatment This has proved to be difficult, both in managing motor symptoms as mentioned above and more so, in treating psychosis. If orthostatic hypotension or wide swings in blood pressure supervene, the picture becomes even more complicated. For the blood pressure changes, midodrine is often prescribed; we have had less success with mineralocorticoids. At least one randomized trial has described benefit from the anticholinesterase inhibitor, rivastigmine, in reducing delusions, hallucinations, and anxiety (McKeith and colleagues, 2000). Pimavanserin, a selective serotonin 5-HT2A inverse agonist used to treat psychosis in Parkinson disease, has shown some modest benefit for psychosis and hallucinations in a trial in Lewy body dementia without worsening motor symptoms (see Cummings et al). Antipsychotic drugs such as quetiapine and clozapine are also used but are limited by their risks and side effects.
This obscure entity has been connected with a late-life dementia in which behavioral disturbances precede memory difficulty. Whether the finding of argyrophilic grains in the medical temporal lobe, different from tau-laden neurofibrillary tangles and from the glial inclusions (putatively a defining feature of multiple system atrophy), constitutes a specific entity is not clear to the authors. The finding overlaps with the deposition of other materials that are more closely associated with dementing diseases such as phosphorylated tau and Lewy bodies. Probst and Tolnay remarked that these small argyrophilic inclusions are not found in nondemented individuals. It is unlikely that the condition can be identified in life; if it is a genuine entity, it must be rare. The interested reader may consult the review by Ferrer.
There have been infrequent case reports of dominantly inherited, adult-onset dementia with a fulminant evolution suggestive of encephalopathy and the special feature of seizures. The distinctive feature has been the presence at autopsy of large eosinophilic, PAS-positive intraneuronal inclusions that contain aggregates of neuroserpin, thus the initial description of “familial encephalopathy with neuronal inclusion bodies.” The serpins are a family of protease inhibitors that include neuroserpin, a protein expressed exclusively in neurons, and α1-antitrypsin. The neuronal inclusions are densest in the deep layers of the cortex and in the substantia nigra. Missense mutations in the gene encoding neuroserpin have been identified as the cause. This entity is reviewed by Lomas and Carrell.
This disease, distinguished by the triad of dominant inheritance, choreoathetosis, and dementia, commemorates the name of George Huntington, a medical practitioner of Pomeroy, Ohio. In 1872, his paper, read before the Meigs and Mason Academy of Medicine and published later that year in the Medical and Surgical Reporter of Philadelphia, gave a succinct and graphic account of the disease that was based on observations of patients that his father and grandfather had made in the course of their practice in East Hampton, Long Island. Reports of this disease had appeared previously (see DeJong for historical background) but they lacked the completeness of
Huntington’s description. In 1915, Davenport was able to show that practically all the patients with this disease in the eastern United States could be traced to about 6 individuals who had emigrated in 1630 from the tiny East Anglian village of Bures, in Suffolk, England. One remarkable family was traced for 300 years through 12 generations, in each of which the disease had expressed itself.