Faculty Bibliography

Movement disorder emergencies occur in both hypokinetic and hyperkinetic patients. Prompt recognition of these emergencies is crucial, and diagnosis is based on history and phenomenology. Supportive and temporizing measures must be implemented immediately before disease-specific therapy is begun. For neuroleptic malignant syndrome and related conditions, we recommend a three-tier approach depending on severity, starting with benzodiazepines, dopamine agonists or levodopa, and dantrolene or electroconvulsive therapy. Methylprednisolone pulse therapy also is beneficial for neuroleptic malignant syndrome due to abrupt medication withdrawal in patients with Parkinson's disease. In treatment of other acute antidopaminergic-induced emergencies, anticholinergics usually suffice. To manage airway obstruction related to movement disorders, we rely on laryngoscopic evaluation to determine whether noninvasive or invasive interventions are needed. Hyperkinetic emergencies are treated individually based on the type of abnormal movements. If an antidopaminergic is needed, we prefer a dopamine depletor to a dopamine receptor blocker because of the risk of tardive syndromes with the latter. When focal hyperkinetic movements dominate the picture, botulinum toxin injection is a useful adjunct to medications.

Although myoclonus and dystonia are the hallmarks of myoclonus-dystonia (M-D), psychiatric features, particularly obsessive-compulsive disorder and alcohol dependence, have been reported in three families linked to chromosome 7q21. As the epsilon sarcoglycan (SGCE) gene for M-D was subsequently identified, we evaluated the relationship between psychiatric features and SGCE mutations in these original and two additional families and confirm that OCD and alcohol dependence are associated with manifesting mutated SGCE.

Dopaminergic imaging has been found to be normal in approximately 15% of parkinsonian patients enrolled in neuroprotective trials. We used (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) to determine the metabolic basis for this finding. We reviewed scans from 185 patients with clinical signs of Parkinson's disease (PD) who underwent (18)F-fluorodopa PET imaging for diagnostic confirmation. Of this group, 27 patients (14.6%) had quantitatively normal scans; 8 of these patients were additionally scanned with FDG PET. Pattern analysis was performed on an individual scan basis to determine whether the metabolic changes were consistent with classic PD. Computer-assisted single-case assessments of the FDG PET scans of these 8 patients did not disclose patterns of regional metabolic change compatible with classical PD or an atypical parkinsonian variant. Similarly, network quantification revealed that PD-related pattern expression was not elevated in these patients as it was in an age- and duration-matched cohort with classical PD (P < 0.0001). None of these patients developed clinical signs of classical PD or of an atypical parkinsonian syndrome at a follow-up visit conducted 3 years after imaging. The results suggest that parkinsonian subjects with normal dopaminergic imaging do not have evidence of classical PD or an atypical parkinsonian syndrome

OBJECTIVE: To evaluate the frequency of leucine-rich repeat kinase gene (LRRK2) mutations and single nucleotide polymorphisms (SNPs) in early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD). METHODS: We genotyped five previously reported LRRK2 mutations (G2019S, L1114L, I1122V, R1441C, and Y1699C) and 17 coding SNPs for haplotype analysis in 504 cases with PD and 314 controls enrolled in the Genetic Epidemiology of PD Study. Cases and controls were recruited without knowledge of family history of PD and cases were oversampled in the < or =50 age at onset (AAO) category. RESULTS: The LRRK2 G2019S mutation was present in 28 cases with PD (5.6%) and two controls (0.6%) (chi(2) = 13.25; p < 0.01; odds ratio 9.18, 95% CI: 2.17 to 38.8). The mutations L1114L, I1122V, R1441C, and Y1699C were not identified. The frequency of the LRRK2 G2019S mutation was 4.9% in 245 cases with AAO < or =50 years vs 6.2% in 259 cases with AAO >50 (p = 0.56). All cases with PD with the G2019S mutation shared the same disease-associated haplotype. The frequency of the LRRK2 G2019S mutation was higher in the subset of 181 cases reporting four Jewish grandparents (9.9%) than in other cases (3.1%) (p < 0.01). Age-specific penetrance to age 80 was 24% and was similar in Jewish and non-Jewish cases. CONCLUSIONS: The G2019S mutation is a risk factor in both early- and late-onset Parkinson disease and confirms the previous report of a greater frequency of the G2019S mutation in Jewish than in non-Jewish cases with Parkinson disease.

Tetrabenazine (TBZ), a presynaptic dopamine depletor and postsynaptic dopamine receptor blocker, is widely used for the treatment of hyperkinetic movement disorders in adults. However, reports of its use in children are limited. We review the efficacy and tolerability of TBZ therapy in 31 children with hyperkinetic movement disorders refractory to other medications. TBZ was effective in reducing the severity of movement disorders resistant to treatment with other medicines. When compared to adult patients, pediatric patients required higher doses. Side effects were similar to the adult population; however, children had a lower incidence of drug-induced Parkinsonism.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a classic clinical triad of symptoms, including dementia, urinary incontinence, and gait disturbance. Recent work has demonstrated that the maximal midbrain anteroposterior (AP) diameter is significantly smaller in patients with INPH than in healthy, age-matched controls. The current study was undertaken to determine the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH patients. METHODS: Twelve consecutive INPH patients undergoing ventriculoperitoneal shunt placement with pre- and postoperative computed tomographic scans at the Columbia University Medical Center were enrolled. Each patient's pre- and postoperative maximum AP and left-to-right diameters of the midbrain at the pontomesencephalic junction were independently measured in a blinded fashion by two of the authors. The average value of each dimension was computed by calculating the mean values of the measurements of the two observers. RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm; postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter (preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029) increased from pre- to postoperative imaging. The approximate cross-sectional area determined as the product of AP and left-to-right diameters also increased from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm; postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study provides supportive evidence that midbrain cytoarchitecture may play a role in the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH patients