Profiling deutetrabenazine extended-release tablets for tardive dyskinesia and chorea associated with Huntington's disease.

INTRODUCTION: Tardive dyskinesia (TD) and Huntington's disease (HD)-associated chorea are persistent and disabling hyperkinetic disorders that can be treated with vesicular monoamine transporter type 2 (VMAT2) inhibitors, including the recently approved once-daily (QD) formulation of deutetrabenazine (DTBZ ER). While its efficacy and safety profile have not been directly investigated, currently available data confirms bioequivalence and similar bioavailability to the twice-daily formulation (DTBZ BID). AREAS COVERED: The authors briefly review the pivotal trials establishing efficacy of DTBZ for TD and HD-associated chorea, the pharmacokinetic data for bioequivalence between QD and BID dosing of DTBZ, as well as dose proportionality evidence, titration recommendations, and safety profile for DTBZ ER. EXPERT OPINION: Long-term data show that DTBZ is efficacious and well tolerated for the treatment of TD and HD-associated chorea. DTBZ ER likely demonstrates therapeutic equivalence with no new safety signals. Due to the lack of comparative clinical trial data, no evidence-based recommendation about choice of VMAT2 inhibitor or switching between VMAT2 inhibitors can be made about best practice. Ultimately, QD dosing may offer the chance of improved medication adherence, an important consideration in patients with complex treatment regimens and/or patients with cognitive decline.

An overview of the pharmacotherapeutics for dystonia: advances over the past decade.

INTRODUCTION: Dystonia is the third most common movement disorder, impacting quality of life and work productivity. Its pathogenesis is heterogeneous, and many pharmacotherapeutics have been suggested for its treatment. The mainstay of management for focal dystonia is botulinum toxin. Oral pharmacotherapeutics usually are nonspecific and associated with risk of unwanted side effects such as drowsiness and lethargy. There is tremendous need for robust clinical trials for new pharmacotherapeutics as we deepen our understanding of dystonia. AREAS COVERED: This review will focus on the advances and research in the pharmacologic treatment of dystonia from January 2012 to April 2022. We performed a systematic database search on PubMed for the period mentioned. EXPERT OPINION: Botulinum toxins remain the mainstay of focal dystonia treatment but may be insufficient for treatment of patients with more widespread dystonia manifestations. The most novel emerging therapies include daxibotulinumtoxinA, dipraglurant, and sodium oxybate. There is a strong clinical need for more effective therapeutic options in dystonia, which may involve the development of individualized treatment options based on dystonia subtype, etiology, or novel mechanisms of action that target specific underlying contributing features.

The global pandemic has permanently changed the state of practice for pre-DBS neuropsychological evaluations.

The evaluation and management of patients with movement disorders has evolved considerably due to the COVID-19 pandemic, including the assessment of candidates for deep brain stimulation (DBS) therapy. Members of the Neuropsychology Focus Group from the Parkinson Study Group Functional Neurosurgical Working Group met virtually to discuss current practices and solutions, build consensus, and to inform the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19. It is our viewpoint that the practice of neuropsychology has adapted successfully to provide tele-neuropsychological pre-DBS evaluations during the global pandemic, thus permanently changing the landscape of neuropsychological services.

A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome.

OBJECTIVE: To investigate the effects of topiramate on Tourette syndrome (TS). BACKGROUND: Dopamine-receptor-blocking drugs have been traditionally used to control tics in patients with TS, but these neuroleptics are associated with potentially limiting side effects. METHODS: This is a randomised, double-blind, placebo-controlled, parallel group study. To be included in the study, subjects required a DSM-IV diagnosis of TS, were 7-65 years of age, had moderate to severe symptoms (Yale Global Tic Severity Scale (YGTSS) > or =19), were markedly impaired as determined by the Clinical Global Impression (CGI) scale severity score of > or =4 and were taking no more than one drug each for tics or TS comorbidities. RESULTS: There were 29 patients (26 males), mean age 16.5 (SD 9.89) years, randomised, and 20 (69%) completed the double-blind phase of the study. The primary endpoint was Total Tic Score, which improved by 14.29 (10.47) points from baseline to visit 5 (day 70) with topiramate (mean dose 118 mg) compared with a 5.00 (9.88) point change in the placebo group (p = 0.0259). There were statistically significant improvements also in the other components of the YGTSS as well as improvements in various secondary measures, including the CGI and premonitory urge CGI. No differences were observed in the frequency of adverse events between the two treatment groups. CONCLUSION: This double-blind, placebo-controlled trial provides evidence that topiramate may have utility in the treatment of moderately severe TS.

Re-emergence of childhood stuttering in Parkinson's disease: a hypothesis.

OBJECTIVE: To characterize speech patterns in patients with Parkinson's disease (PD) who have a history of childhood stuttering. BACKGROUND: Childhood stuttering usually resolves, but it re-emerges in some patients after stroke or other brain disorders. This phenomenon of recurrent stuttering has not been characterized in childhood stutterers who later develop PD. METHODS/PATIENTS: Twelve patients with a history of childhood stuttering that remitted and subsequently recurred were included in the study. A structured interview was administered to seven patients, and six were able to answer questions about childhood stuttering. The Johnson Severity Scale (JSS) (range 0-7) and a Situation Avoidance Scale (SAS) were used to rate stuttering severity (range 0-15) and avoidance (range 0-15). RESULTS: The mean age at onset of childhood stuttering was 6.2 years (range 5-10); the mean latency from the onset of childhood stuttering to adult stuttering was 46.1 years; and the stuttering recurred on average 5.9 years (range 0-21) after the onset of PD. The stuttering characteristics in childhood and adulthood included repetitions of sounds and syllables at the beginnings of words, blocks and interjections, physical tension, and a worsening of symptoms with stress. The patients rated themselves as having mild-to-moderate childhood stuttering by the JSS (mean 3.0, range 2-4) and mild-to-moderate stuttering and avoidance by the SAS (mean stuttering score 5.3, range 3-7; mean avoidance score 4.2, range 3-6). There was no apparent association between the severity of childhood stuttering and the severity of PD, but those patients who had higher Unified Parkinson's Disease Rating Scale scores tended to have more and worse symptoms of stuttering. CONCLUSION: Our patients provide evidence for the hypothesis that childhood stuttering may re-emerge in adulthood with the onset of PD.