Clinical, pathological and genetic characteristics of Perry disease-new cases and literature review.

BACKGROUND AND PURPOSE: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease. METHODS: Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed. RESULTS: Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play. CONCLUSIONS: Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.

L-Dopa response, choreic dyskinesia, and dystonia in Perry syndrome.

INTRODUCTION: A marked response to L-Dopa and L-Dopa-induced dyskinesia (LID) make the diagnosis of Parkinson's disease (PD) highly likely. This paper evaluates response to L-Dopa in Perry syndrome (PS), parkinsonism with distinct molecular and neuropathologic characteristics. METHODS: Six patients with PS with a mean follow-up of 5 years (0.5-12) were assessed by movement disorder specialists and video recorded in states off and on. Additionally, DATSCAN-SPECT was performed in 3 subjects. RESULTS: Four patients displayed a marked and sustained response to L-Dopa and LID. Additionally, we observed a distinct pattern of off-state predominant craniocervical dystonia responsive to L-Dopa in 4 patients, truncal dystonia in one, and dystonic head tremor in another. DATSCAN-SPECT was abnormal in 3 patients. CONCLUSIONS: Patients with PS may present PD-like parkinsonism with a marked and sustained response to L-Dopa and LID. The characteristic pattern of craniocervical dystonia may be a helpful clue to the diagnosis of PS.