Mechanism of acute ischemic stroke in patients with severe middle cerebral artery atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke worldwide. Although the pathogenesis of cerebral infarct in ICAD has been reported from autopsy series, the mechanism of stroke is not well known. This study used baseline perfusion imaging and diffusion-weighted imaging (DWI) or computerized tomography (CT) imaging to help identify the mechanism of stroke in ICAD involving the middle cerebral artery (MCA). METHODS: We retrospectively reviewed baseline CT or magnetic resonance (MR) perfusion studies and diffusion-weighted MR imaging or CT scans in patients with severe symptomatic MCA stenosis. Perfusion scans were classified according to stage of perfusion deficit, and the acute stroke patterns were categorized as borderzone, cortical, or perforating artery infarcts according to DWI or noncontrast CT. RESULTS: Fifteen patients were included in this analysis. All 15 patients had some type of borderzone infarct. Six had borderzone infarct only, 4 had borderzone and cortical infarcts, and 5 had borderzone, cortical, and perforating artery infarcts. Thirteen of the 15 patients had baseline perfusion deficits. CONCLUSIONS: In patients with severe MCA ICAD, the mechanism of stroke is multifactorial, but hemodynamic insufficiency plays a significant role. This finding is important in selecting a subgroup of patients who may benefit from revascularization.

Ecopipam for Tourette Syndrome: A Randomized Trial.

BACKGROUND AND OBJECTIVES: All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit. RESULTS: Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences -3.44, 95% confidence interval -6.09 to -0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events. CONCLUSIONS: Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.

Acute dystonic reaction associated with foscarnet administration.

Drug-induced movement disorders are commonly seen in the inpatient setting and outpatient movement disorders centers. The most common acute reactions are dystonia, parkinsonism, and akathisia. Drug-induced movement disorders are classically associated with dopamine receptor blocking agents, most notably typical and atypical antipsychotic medications. However, extrapyramidal side effects can also be seen with antiemetics, promotility drugs, serotonergic agents, and opioid agonists. We describe a patient who developed an acute dystonic reaction shortly after the administration of intravenous foscarnet, an antiviral agent. Her work-up for secondary causes of dystonia was otherwise negative, and her symptoms resolved after receiving intravenous anticholinergic treatment.

Status epilepticus due to tiagabine ingestion.

Tiagabine, in excess dosing scenarios, has been rarely documented to cause status epilepticus. We describe such a case that was not responsive to benzodiazepines, but only to propofol infusion.

Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy.

OBJECTIVE: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD). METHODS: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5-15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d, or placebo for 12 weeks. In phase 2, placebo participants were randomly assigned to 1 of the 3 active treatment groups. Participants originally assigned to an active treatment continued that treatment for an additional 40 weeks. The primary efficacy endpoint was average change in muscle strength from baseline to week 12 compared with placebo. The study was completed in 1995. RESULTS: All treatment groups (DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, and PRED 0.75 mg/kg/d) demonstrated significant improvement in muscle strength compared with placebo at 12 weeks. Participants taking PRED had significantly more weight gain than placebo or both doses of DFZ at 12 weeks; at 52 weeks, participants taking PRED had significantly more weight gain than both DFZ doses. The most frequent adverse events in all 3 active treatment arms were Cushingoid appearance, erythema, hirsutism, increased weight, headache, and nasopharyngitis. CONCLUSIONS: After 12 weeks of treatment, PRED and both doses of DFZ improved muscle strength compared with placebo. Deflazacort was associated with less weight gain than PRED. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for boys with DMD, daily use of either DFZ and PRED is effective in preserving muscle strength over a 12-week period.

Initiation and dose optimization for levodopa-carbidopa intestinal gel: Insights from phase 3 clinical trials.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) provides continuous infusion and reduces "off" time in advanced Parkinson's disease (PD) patients with motor fluctuations despite optimized pharmacotherapy. METHODS: Clinical experience with 2 LCIG dosing paradigms from phase 3 studies was examined. In an open-label, 54-week study, LCIG was initiated as daytime monotherapy via nasojejunal (NJ) tube then switched to percutaneous endoscopic gastrojejunostomy (PEG-J) tube; adjunctive therapy was permitted 28 days postPEG-J. In a 12-week, double-blind, placebo-controlled, double-dummy trial, patients continued stable doses of existing anti-PD medications, but LCIG replaced daytime oral levodopa-carbidopa and was initiated directly via PEG-J. RESULTS: In the open-label study, 92% of 354 patients received monotherapy at post-PEG-J week 4; mean titration duration was 7.6 days; dosing remained stable post-titration (mean total daily dose [TDD] was 1572 mg at last visit). In the double-blind trial, 84% received polypharmacy; mean titration took 7.1 days for the LCIG arm (TDD post-titration: 1181 mg; n = 37). At post-PEG-J week 4, mean "off" time with LCIG was reduced by 3.9 h (open-label/monotherapy study) and 3.7 h (double-blind/polypharmacy trial). NJ treatment (open-label study only) required an additional procedure with related adverse events (AEs) and withdrawals. The most common AEs during PEG-J weeks 1-4 in the open-label/monotherapy and double-blind/polypharmacy trials, respectively, were complication of device insertion (35%, 57%) and abdominal pain (26%, 51%). Discontinuations due to nonprocedure/nondevice AEs were low (2.2%, 2.7%). CONCLUSION: These results support the option of initiating LCIG with or without NJ and as either monotherapy or polypharmacy.

Epilepsy in sports and recreation.

In the US, millions of people participate in physical activity on a regular basis. However, among the many people with epilepsy, few incorporate exercise into their daily routine. Whether it is because of parental or physician restriction, the fact remains that people with epilepsy are less fit and are not getting the exercise they need. For many years, patients with seizure disorders have been discouraged from participating in physical fitness and team sports due to the fear that it will exacerbate their seizure disorder. However, this overprotective attitude has been slowly changing in light of more recent data on this subject. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without adversely affecting seizure frequency. This article reviews the effects of exercise on seizure control among patients with epilepsy. It examines the morbidity and mortality associated with exercise, as well as its psychological and physiological effects. Various topics concerning antiepileptic drugs and exercise are also discussed.

Acute chorea associated with metoclopramide use.

Metoclopramide is a dopamine receptor antagonist that is used to treat diabetic gastroparesis, chemotherapy-induced nausea, and migraines. It is known to cause extrapyramidal side effects such as tardive dyskinesia, parkinsonism, dystonia, and akithisia, but not chorea. We describe a patient who presented with choreiform movements shortly after the administration of intravenous metoclopramide. Her work-up for secondary causes of chorea was otherwise negative and her symptoms abated with the administration of oral quetiapine and intravenous diazepam.