Faculty Bibliography

The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.

PURPOSE OF REVIEW: Myoclonus, one of the most common involuntary movement disorders, poses particular challenges for the treating physician. The evaluation of a patient with myoclonus depends completely on the clinical history and examination, supported when necessary by electrophysiology, neuroimaging and selected genetic and laboratory testing. The sudden, shock-like jerks which define myoclonus may be highly disabling, and when they persist, often require treatment. RECENT FINDINGS: In a paper published in this journal, we reviewed the published trials of antimyoclonic agents, and formulated a treatment algorithm based on the available evidence. In the current paper, we present our approach for evaluating patients with myoclonus, and suggest practical guidelines for treating patients based on the pre-2000 literature and on studies published in the last 2 years. The newer medications which are being used in management of myoclonus are levetiracetam and gamma-hydroxybutyric acid. Levetiracetam is especially useful for posthypoxic myoclonus and gamma-hydroxybutyric acid for alcohol-sensitive myoclonus. A combination of medications is often needed to obtain adequate control of symptoms. Botulinum toxin is also being introduced for focal myoclonus with encouraging results. SUMMARY: There are no approved medications for myoclonus, and most therapies are borrowed from the antiepileptic and psychiatric armamentarium. Nonetheless, there is a logic to the choice and dosing of antimyoclonic drugs, and we hope that by applying a few simple principles, neurologists will approach the care of these patients with confidence.

BACKGROUND: Genetic studies of PD frequently rely on family history interviews (FHI), yet the accuracy of data obtained in this way is unclear. OBJECTIVE: To assess the interinformant reliability and validity of family history information on PD in first-degree relatives of PD cases and controls. METHODS: A structured FHI was administered to nondemented PD cases and controls and to a second informant (self-report, sibling or child of the subject) for each relative. Interinformant agreement was assessed on four algorithm-derived diagnostic categories of PD: definite, definite or probable, definite, probable or possible ("conservative diagnosis"); or definite, probable, possible, or uncertain ("liberal diagnosis"). The sensitivity and specificity of each diagnostic category were assessed, using as the gold standard diagnoses based on either in-person examination or medical record review. RESULTS: Five hundred thirty-six families containing 2,225 first-degree relatives were included in the interinformant reliability study. Agreement between informants was excellent for definite or probable PD for all three pairwise comparisons: proband vs self-report (kappa = 0.92), proband vs sibling of subject (kappa = 0.80), and proband vs child of subject (kappa = 0.87). Agreement was also good to excellent for the conservative diagnosis (kappa = 0.66, 0.49, and 0.79). In the validity analysis (141 individuals in 96 families), the conservative diagnosis provided the best combination of sensitivity (95.5%) and specificity (96.2%) for the proband's family history report. No difference was apparent across categories defined by case or control status, relationship to the proband, or gender or age at onset of the proband. However, specificity was lower for deceased relatives than for living relatives. CONCLUSION: The FHI can be used to obtain reliable and valid family history information on PD in first-degree relatives when a conservative diagnostic algorithm is applied.

Tetrabenazine (TBZ) is widely used to treat adults with hyperkinetic movement disorders; however, published experience with the drug in pediatric patients is limited. We report on 5 children with severe chorea who were treated with TBZ. TBZ effectively controlled chorea in 4 patients, and despite the need for relatively high doses, it was well tolerated.

Head tremor is one of the major expressions of essential tremor (ET). It is not well understood why some patients develop head tremor, whereas others do not. A study of the characteristics of patients with head tremor has not been undertaken. Our goal was to estimate the prevalence of head tremor and to identify demographic and clinical characteristics associated with an increased risk of head tremor in ET. Cases were ascertained from a community-based study of ET in northern Manhattan, New York. Arm tremor severity was rated with a total tremor score. Logistic regression analyses resulted in odds ratios (OR). Head tremor was present in 37 (34.9%) of 106 ET cases. Female gender was associated with a fourfold increased risk of head tremor (OR = 3.73; P = 0.005). Total tremor score was divided into quartiles; individuals in the lowest or highest quartile were four times more likely to have head tremor (OR = 4.16; P = 0.001). Individuals with both risk factors (female gender and lowest or highest total tremor score quartile) were 16 times more likely to have head tremor (OR = 15.88; P = 0.0006). Being related to a proband with head tremor marginally increased the risk of head tremor (OR = 11.30; P = 0.08). Age and tremor duration did not influence the risk of head tremor. We identified several factors that were associated with an increased risk of head tremor in ET; female gender, coexisting arm tremor that was either very mild or extremely severe, and relation to an ET case with head tremor. These disease associations require further exploration, and might provide insight into the mechanisms underlying head tremor.

Parkinsonism is a rare neurological complication of cancer treatment. Although individual case reports of this syndrome have been reported, the clinical features and prevalence of this syndrome are unknown. We present 3 patients, encountered over 6 months at one institution, who developed parkinsonism after treatment with various chemotherapeutic agents. Parkinsonism was severe in 2 patients, affecting postural reflexes, speech, and swallowing. All 3 patients responded dramatically to treatment with levodopa, and parkinsonism spontaneously improved or remitted over months. This unusual complication of cancer therapy is treatable and may be underappreciated.