Autosomal dominant dystonia-plus with cerebral calcifications.

OBJECTIVE: To report genealogic, clinical, imaging, neuropathologic, and genetic data from a Canadian kindred with dystonia and brain calcinosis originally described in 1985. METHODS: The authors performed clinical examinations and CT and PET studies of the head and analyzed blood samples. One autopsy was performed. RESULTS: The family tree was expanded to 166 individuals. No individuals were newly affected with dystonia, but postural tremor developed in two. The mean age at symptom onset was 19 years. Eight individuals had dystonia: three focal, one segmental, one multifocal, and three generalized. Seven displayed additional signs: chorea, intellectual decline, postural tremor, and dysarthria. CT studies were performed on five affected and 10 at-risk family members. All affected individuals and eight at-risk individuals had brain calcinosis. PET scans in two individuals showed reduced D(1)- and D(2)-receptor binding and reduced uptake of 6-[(18)F]fluoro-l-dopa. Autopsy of one affected individual showed extensive depositions of calcium in the basal ganglia, thalamus, cerebral white matter, and cerebellum. No specific immunohistochemistry abnormalities were seen. Genome search data showed no evidence of linkage to the previously described loci IBGC1, DYT1, and DYT12. CONCLUSIONS: The phenotype of this family consists of dystonia-plus syndrome. Brain calcium deposits vary in severity and distribution, suggesting that calcifications alone are not entirely responsible for the observed clinical signs. Further studies are needed to elucidate the etiology of this heterogeneous group of disorders.

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers.

BACKGROUND: The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. OBJECTIVES: To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. METHODS: A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. RESULTS: Eighty-four percent of patients were 'poor sleepers' with global sleep scores (GLSc) > 5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc > or = 10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc > 5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. CONCLUSIONS: PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.

Familial and sporadic Parkinson's disease usually display the same clinical features.

We examined the clinical features of familial (n = 26) and sporadic (n = 52) Parkinson's disease (PD) in patients presenting over the age of 40 years. Familial PD cases were tested for alpha-synuclein or parkin mutations as appropriate. No mutations were found in any of the families investigated. We found no between-group differences in the age at onset of PD, the pattern or severity of parkinsonian features, the dose of antiparkinsonian medications or treatment related complications. Cases of familial and sporadic PD in our cohort of patients display similar clinical features. This may suggest similar etiologies for both familial and sporadic PD.

Positron emission tomography of dopamine pathways in familial Parkinsonian syndromes.

Positron emission tomography (PET) scan is considered to be the most useful tool with which to assess the integrity of nigrostriatal function in the living brain. Recently, different genetic defects have been associated with a variety of familial parkinsonian syndromes, the clinical phenotypes of which have varying degrees of similarities to idiopathic parkinsonism (IP), (sporadic Parkinson's disease). This review summarizes: (1) the PET scan findings (fluorodopa uptake and raclopride binding) in both familial parkinsonian syndromes and IP; and (2) the similarities and differences of the clinical and PET features between familial parkinsonian syndromes and IP. This analysis demonstrates that more similarities than differences exist in PET scan findings in the different familial parkinsonian syndromes with the exception of pallido-ponto-nigral degeneration (PPND), that is perhaps best considered as multisystem degeneration. As a result of this analysis, we believe that while different genetic defects may underlie different mechanisms of nigrostriatal degeneration, the final pattern of nigrostriatal dysfunction is essentially similar to that of IP. 'Parkinson's disease', therefore, may not represent a single disease entity, but rather the final manifestation of different pathogenetic mechanisms-mediated by genetic or environmental factors, or an interaction of genetic and environmental factors.

Daytime somnolence in patients with Parkinson's disease.

We studied daytime sleepiness in 160 patients with Parkinson's disease and 40 normal subjects. We compared the prevalence of daytime sleepiness in patients who were taking levodopa alone, levodopa with bromocriptine, levodopa with ropinirole, and levodopa with pramipexole. We found that (1) all these anti-Parkinson drugs can cause daytime sleepiness; (2) 'dozing off' correlated highly with 'falling asleep without warning'; (3) after statistical adjustment for confounding variables there was no significant difference among the risks for any of these anti-Parkinson drugs causing daytime somnolence.