Effect of istradefylline on postural abnormalities in patients with Parkinson's disease: An association study of baseline postural angle measurements with changes in Unified Dystonia Rating Scale total score.

In our previous study, istradefylline treatment in patients with Parkinson's disease (PD) improved postural abnormalities (PAs), as seen from a decrease in the mean Unified Dystonia Rating Scale (UDRS) total score from week 0 to week 24. A subgroup analysis based on baseline clinical characteristics investigated the association between improvement in the UDRS total score and istradefylline treatment. However, the association between an objective assessment of PAs and improvement in the UDRS total score is unclear. This ad hoc analysis investigated the association between improvement in the UDRS total score after istradefylline treatment and baseline trunk and neck angles, objective assessments of PAs, measured from patients' photographs taken in the previous study. The patients (n = 31) were stratified into groups based on the trunk forward flexion angle (TFFA), trunk lateral flexion angle (TLFA), and neck flexion angle (NFA) values at baseline. From week 0 to week 24, significant improvements in the UDRS total score were found in median percent change (-8.33% [interquartile range: -43.97, 0.00], P = 0.039) in patients with equal to or above the median TFFA values, and in median change (-|1.50 [-9.25, 0.00], P = 0.015) and median percent change (-13.33% [-50.47, 0.00], P = 0.009) in patients with equal to or above the median TLFA values. Patients with more advanced PAs showed more consistent improvements in the UDRS total score with istradefylline. Baseline TFFA and TLFA values, which are objective values, may be useful to assess the istradefylline effectiveness in patients with PD and PAs.

Efficacy and safety of istradefylline in patients with Parkinson's disease presenting with postural abnormalities: Results from a multicenter, prospective, and open-label exploratory study in Japan.

Postural abnormalities in Parkinson's disease (PD) can devastatingly impair the quality of life, especially in patients with advanced disease, and are generally refractory to dopaminergic agents. The objective of this exploratory study was to investigate the efficacy and safety of istradefylline for the treatment of postural abnormalities in PD. In this open-label, 24-week, single-arm prospective trial, PD patients with postural abnormalities experiencing the wearing-off phenomenon on levodopa-containing therapies were enrolled and received a starting dose of 20 mg/day istradefylline orally for 4 weeks, which was then increased to 40 mg/day. The primary endpoint was the change from baseline to week 24 in the 14-item Unified Dystonia Rating Scale (UDRS) total score. Pivotal secondary endpoints were changes in the sub-items of UDRS, Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, and adverse drug reactions (ADRs). Overall, 24/31 enrolled patients completed the study; mean (standard deviation) age and duration of motor complications were 73.3 (7.7) years and 3.2 (4.4) years, respectively. Mean (95% confidence interval [CI]) change in the UDRS total score was 4.84 (1.97, 7.71; P = 0.002), with significant improvements in the neck, right distal arm and hand, and trunk severity scores. Mean (95% CI) change in the MDS-UPDRS part III score was 7.84 (4.34, 11.34; P < 0.001). The most common ADRs were malaise, dyskinesia exacerbation, and visual hallucinations in 2 (6.5%) patients each. This exploratory study demonstrated that istradefylline could be efficacious for postural abnormalities and was generally well tolerated in patients with PD experiencing the wearing-off phenomenon with levodopa-containing therapies.

Intrathecal baclofen therapy for Lesch-Nyhan disease: illustrative case.

BACKGROUND: Lesch-Nyhan disease (LND) is a very rare metabolic disorder involving the purine salvage pathway. LND manifests hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia, whose control is difficult pharmaceutically. OBSERVATIONS: Intrathecal baclofen (ITB) therapy was received by a 22-year-old male for generalized dystonia. His paroxysmal abnormal dystonic posturing reduced after surgery, making the task of caregivers easier despite the unchanged assignment on the dystonia scale during a follow-up period of 4 years. LESSONS: ITB may be a safe and feasible option for dystonic symptoms and difficulty with nursing care in patients with LND.

Oromandibular dystonia in yemeni patients with khat chewing: a response to botulinum toxin treatment.

Khat-(Catha edulis)related oromandibular dystonia is a difficult-to-treat subset of movement disorders that involve masticatory muscles with diverse and incapacitating manifestations. The aim of this study was to evaluate the efficacy of Botulinum toxin-type A therapy in khat chewer Yemeni patients with oromandibular dystonia. This prospective study included 18 khat-chewers Yemeni patients with refractory oromandibular dystonia, who were subjected to Botulinum toxin-A injection and followed up for 3 months thereafter. Primary efficacy outcome was the global impression scale, and secondary outcome measure was the Unified Dystonia Rating Scale. Patients showed improvement of both efficacy measures, maximum satisfactory responses were detected at the forth week after injection. No major adverse events were detected. Botulinum toxin-A is considered an effective and safe treatment option for refractory oromandibular dystonia in khat-chewers.