Faculty Bibliography

Myoclonus is a hyperkinetic movement disorder characterized by quick, involuntary jerks. It encompasses a vast range of etiologies and widespread anatomic locations. Treatment frequently requires multiple agents and is often only partially beneficial. These patients pose a considerable challenge for the clinician, further complicated by the fact that many of the treatment choices lack evidence-based support. In the past few years, publications regarding therapy have been largely observational case reports or series. Although the literature on treatment of cortical myoclonus appears to be growing, evidence regarding myoclonus of noncortical origin is less well established. Investigation of more satisfactory treatments is needed, as this condition can be disturbing, debilitating, and sometimes harmful for patients. Continuing investigations are using various animal models (mostly of posthypoxic myoclonus), electrophysiologic studies, new imaging techniques such as diffusion tensor imaging, and genetic studies. Meanwhile, the clinical approach to diagnosing and classifying myoclonus remains largely unchanged. This review updates readers on current investigations and suggests guidelines for diagnosing and treating myoclonus.

Spatial covariance analysis has been used with (18)F-fluorodeoxyglucose (FDG) PET to detect and quantify specific metabolic patterns associated with Parkinson's disease (PD). However, PD-related patterns cannot necessarily serve as biomarkers of the processes that underlie the atypical parkinsonian syndromes. In this FDG PET study, we used strictly defined statistical criteria to identify disease-related metabolic patterns in the imaging data from patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the two most common of these atypical conditions. We found that MSA and PSP were each associated with a specific, highly stable metabolic brain network (P < 0.0001, bootstrap estimation). The MSA-related pattern was characterized by decreased metabolism in the putamen and cerebellum. The PSP-related pattern was characterized by metabolic decreases in the brainstem and medial frontal cortex. For both conditions, pattern expression was significantly elevated in patients relative to age-matched healthy control subjects (P < 0.001). For each condition, we validated the associated disease-related metabolic pattern by computing its expression on an individual scan basis in two independent patient cohorts, and in one subsequent healthy volunteer cohort. We found that for both MSA and PSP, prospective assessments of pattern expression accurately discriminated patients from controls (P < 0.001). These findings suggest that the major atypical parkinsonian syndromes are associated with distinct patterns of abnormal regional metabolic activity. These disease-related networks can potentially be used in conjunction with functional brain imaging as quantifiable biomarkers for the assessment of these pathological conditions

OBJECTIVE: To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene. DESIGN: We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset < or =50 years) and 104 control probands enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband. SETTING: Tertiary care movement disorders center. Patients Cases, controls, and their first-degree relatives were enrolled in the GEPD study. MAIN OUTCOME MEASURES: Estimated age-specific penetrance in first-degree relatives. RESULTS: Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes. One Parkin homozygote was reported in 2 siblings with PD. The cumulative incidence of PD to age 65 years in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% confidence interval, 0.4%-71.9%), compared with 1.7% (95% confidence interval, 0.8%-3.4%) in noncarrier relatives of the cases (P = .59) and 1.1% (95% confidence interval, 0.3%-3.4%) in relatives of the controls (compared with noncarrier relatives, P = .52). CONCLUSIONS: The cumulative risk of PD to age 65 years in a noncarrier relative of a case with an age at onset of 50 years or younger is not significantly greater than the general population risk among controls. Age-specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study.

Myoclonus-dystonia (M-D) due to SGCE mutations is characterized by early onset myoclonic jerks, often associated with dystonia. Penetrance is influenced by parental sex, but other sex effects have not been established. In 42 affected individuals from 11 families with identified mutations, we found that sex was highly associated with age at onset regardless of mutation type; the median age onset for girls was 5 years versus 8 years for boys (P < 0.0097). We found no association between mutation type and phenotype.