We find the report by Bromley et al.1 of an increased incidence of autism spectrum disorders in the offspring of mothers taking antiepileptic drugs (AEDs) during pregnancy intriguing and suggest low vitamin D as a possible mechanism deserving further investigation. Several AEDs are known to bind to the pregnane X receptor to increase the catabolism of vitamin D by upregulating the mitochondrial enzyme CYP24. AEDs, including valproic acid, are known to decrease 25-hydroxyvitamin D levels.2 It has been reported that babies born to women taking AEDs during pregnancy had significantly lower 25-hydroxyvitamin D concentrations compared to healthy control newborns.3 Vitamin …

BACKGROUNDThe preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance.OBJECTIVETo describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET.DESIGNCase report.PATIENTA 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor.INTERVENTIONSLeft pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS.MAIN OUTCOME MEASURESControl of symptoms of PD and ET.RESULTSThe left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS.CONCLUSIONPlacement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.

Psychosis is common among patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Limited data exist on the most effective therapies.Retrospective cohort study comparing patients with PD or DLB initiated on quetiapine or pimavanserin for psychosis. Primary outcome was time to discontinuation of pimavanserin or quetiapine using Kaplan-Meier survival analysis. We hypothesized the rate of antipsychotic discontinuation would be lower in the pimavanserin group. Subjects were included if the indication for treatment was psychosis and excluded if there was a history of major mental illness or no follow up data were available.Forty-seven patients were included in the quetiapine cohort and 45 in the pimavanserin cohort. Patients in the pimavanserin cohort were more likely to have a diagnosis of DLB (33% vs. 11%, P = 0.01) and to have been prescribed an antipsychotic previously (62% vs. 6%, P < 0.01); otherwise, the groups were similar. Time to discontinuation analysis, which accounts for efficacy, safety and tolerability, revealed a lower early pimavanserin discontinuation rate and a higher late pimavanserin discontinuation rate (HR < 1 before day 43, HR > 1 after day 43; P = 0.04). There was no difference in mortality in the pimavanserin group compared to the quetiapine group (HR 0.37, 95% CI 0.06 to 2.45; P = 0.88). More individuals had a documented secondary indication for taking quetiapine than pimavanserin (38% vs. 4%; P = 0.001).Accounting for efficacy, safety and tolerability, pimavanserin may be more clinically useful for promptly managing psychosis, while quetiapine may confer additional secondary benefits long-term.

Treating psychosis in patients with Parkinson's disease (PD) is extremely challenging because conventional antipsychotics commonly worsen motor dysfunction, while atypical antipsychotics, such as clozapine, risperidone, and olanzapine, may be associated with anticholinergic, extrapyramidal (EPS), or hematologic side effects. Quetiapine ('SEROQUEL') has been shown to be effective and well tolerated in patients with PD and psychosis. A single-center, long-term (24 week), open-label trial evaluated the safety, tolerability, and efficacy of quetiapine for treating psychosis in patients with parkinsonism who failed treatment with clozapine, risperidone or olanzapine. Failure could be due to lack of efficacy, intolerable side effects, or lack of compliance with blood monitoring. Twenty-nine patients (mean age 73 years) with parkinsonian and psychotic symptoms received up to 400 mg/day of quetiapine, dosed according to clinical response and tolerability. Assessments included the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI) Severity of Illness, Neuropsychiatric Inventory (NPI), and Unified Parkinson's Disease Rating Scale (UPDRS). The mean BPRS total score improved by >30% and remained significantly improved throughout the 24-week trial (p = 0.004). The mean NPI psychosis subscale (delusions, hallucinations and agitation/aggression) score had 50% improvement (p = 0.028). The mean UPDRS total and motor subscale scores did not worsen indicating that the motor symptoms did not deteriorate. There were no clinically important effects on mean vital signs, weights, clinical laboratory tests and electrocardiograms. The results provide further evidence that quetiapine is effective and well tolerated in patients with PD, and extends previous findings to include patients who may have failed treatment with other atypical antipsychotics.

Modulation of the human spinal stretch reflex (SSR) may be important in treating hyperactive reflexes or may be a tool to enhance normal performance. Eight of 9 subjects given feedback of biceps brachii SSR amplitude and instructed to increase (uptrain) or decrease (downtrain) this response were able to do so in the appropriate direction. These results imply that, as in non-human primates, SSR amplitude can be modified.