A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor

Background: We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb. Methods: We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3–6 weeks after baseline. Results: Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6–6 weeks), four of them rated themselves as “improved” and two as “much improved.” Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4–6) to 3 (2–5) (p = 0.01). Discussion: This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebo-controlled studies evaluating larger samples of patients are warranted to confirm these findings

Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology

The British Association for Psychopharmacology developed an evidence-based consensus guideline on the management of catatonia. A group of international experts from a wide range of disciplines was assembled. Evidence was gathered from existing systematic reviews and the primary literature. Recommendations were made on the basis of this evidence and were graded in terms of their strength. The guideline initially covers the diagnosis, aetiology, clinical features and descriptive epidemiology of catatonia. Clinical assessments, including history, physical examination and investigations are then considered. Treatment with benzodiazepines, electroconvulsive therapy and other pharmacological and neuromodulatory therapies is covered. Special regard is given to periodic catatonia, malignant catatonia, neuroleptic malignant syndrome and antipsychotic-induced catatonia. There is attention to the needs of particular groups, namely children and adolescents, older adults, women in the perinatal period, people with autism spectrum disorder and those with certain medical conditions. Clinical trials were uncommon, and the recommendations in this guideline are mainly informed by small observational studies, case series and case reports, which highlights the need for randomised controlled trials and prospective cohort studies in this area

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Estimation of the phase response curve from Parkinsonian tremor

Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period

Pallidal stimulation for cervical dystonia does not correct abnormal temporal discrimination

Background: We investigated whether clinical improvement observed after deep brain stimulation (DBS) of the globus pallidus internus (GPi) in cervical dystonia (CD) is paralleled by the normalisation of temporal discrimination thresholds (TDTs), a marker of abnormal sensory processing in CD. Methods: TDT was tested in 11 patients with CD after they received DBS and was compared with TDT scores from 24 patients with CD and a group of 61 controls. Results: A clear clinical response to GPi-DBS was demonstrated (total Toronto Western Spasmodic Torticollis Rating Scale scores fell from 50 to 18; P<0.001). In contrast, TDT remained abnormal in the CD-DBS group (P<0.001) and was not significantly different from the abnormal TDT range observed in CD. Conclusions: Underlying sensory abnormalities in temporal discrimination observed in dystonia do not seem to be corrected by successful GPi-DBS. This adds further data to the ongoing debate regarding which pathophysiological abnormalities observed in dystonia are likely to be causal in the genesis of the disease rather than epiphenomena observed secondary to abnormal motor activity. © 2013 Movement Disorder Society