Treatment Approaches for Altered Facial Expression: A Systematic Review in Facioscapulohumeral Muscular Dystrophy and Other Neurological Diseases.

Background: Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities. Objective: We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD. Methods: A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning. Results: Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures. Conclusions: Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.

Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson's disease: a double-blind, randomised controlled trial.

BACKGROUND: High-intensity aerobic exercise might attenuate the symptoms of Parkinson's disease, but high-quality evidence is scarce. Moreover, long-term adherence remains challenging. We aimed to evaluate the effectiveness of aerobic exercise-gamified and delivered at home, to promote adherence-on relieving motor symptoms in patients with Parkinson's disease with mild disease severity who were on common treatment regimes. METHODS: In this single-centre, double-blind, randomised controlled trial (Park-in-Shape), we recruited sedentary patients with Parkinson's disease from the outpatient clinic at Radboudumc, Nijmegen, Netherlands. Patients were made aware of the study either by their treating neurologist or via information in the waiting room. Patients could also contact the study team via social media. We included patients aged 30-75 years with a Hoehn and Yahr stage of 2 or lower, who were on stable dopaminergic medication. Patients were randomly assigned (in a 1:1 ratio) to either aerobic exercise done on a stationary home-trainer (aerobic intervention group) or stretching (active control group) by means of a web-based system with minimisation for sex and medication status (treated or untreated) and permuted blocks of varying sizes of more than two (unknown to study personnel). Patients were only aware of the content of their assigned programme. Assessors were unaware of group assignments. Both interventions were home based, requiring 30-45 min training three times per week for 6 months. Both groups received a motivational app and remote supervision. Home trainers were enhanced with virtual reality software and real-life videos providing a so-called exergaming experience (ie, exercise enhanced by gamified elements). The primary outcome was the between-group difference in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor section at 6 months, tested during the off state (≥12 h after last dopaminergic medication). The analysis was done on an intention-to-treat basis in patients who completed the follow-up assessment, regardless of whether they completed the assigned intervention. Patients reported adverse events directly to their coach and also after the 6-month visit retrospectively. A between-group difference of 3·5 points or more was deemed a-priori clinically relevant. The study is concluded and registered with the Dutch Trial Registry, NTR4743. FINDINGS: Between Feb 2, 2015, and Oct 27, 2017, 139 patients were assessed for eligibility in person, of whom 130 were randomly assigned to either the aerobic intervention group (n=65) or the active control group (n=65). Data from 125 (96%) patients were available for the primary analysis; five patients were lost to follow-up (four in the intervention group; one in the control group). 20 patients (ten in each group) did not complete their assigned programme. The off-state MDS-UPDRS motor score revealed a between-group difference of 4·2 points (95% CI 1·6-6·9, p=0·0020) in favour of aerobic exercise (mean 1·3 points [SE 1·8] in the intervention group and 5·6 points [SE 1·9] for the control group). 11 patients had potentially related adverse events (seven [11%] in the intervention group, four [6%] in the control group) and seven had unrelated serious adverse events (three in the intervention group [vestibilar disorder, vasovagal collapse, knee injury during gardening that required surgery; 6%], four in the control group [supraventricular tachycardia, hip fracture, fall related injury, severe dyskinesias after suprathreshold dose levodopa in a patient with deep brain stimulation; 7%]). INTERPRETATION: Aerobic exercise can be done at home by patients with Parkinson's disease with mild disease severity and it attenuates off-state motor signs. Future studies should establish long-term effectiveness and possible disease-modifying effects. FUNDING: Netherlands Organization for Health Research and Development.

What predicts falls in Parkinson disease?: Observations from the Parkinson's Foundation registry.

BACKGROUND: We undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit. METHODS: We analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no or rare falls at the baseline visit will report at least monthly falls at the annual follow-up visit. Multivariable models were constructed using logistic regression. Variables were introduced in 4 blocks: in the 1st block, variables present at or before the baseline visit were entered; in the 2nd, baseline visit assessments; in the 3rd, interventions implemented during baseline visit; and, in the 4th block, changes in comorbidities, living situation, and treatment between visits. RESULTS: Of 3,795 eligible participants, 3,276 (86.3%) reported no or rare falls at baseline visit, and of them, 382 (11.7%) reported at least monthly falls at follow-up visit. Predictors included female sex, <90% diagnostic certainty, motor fluctuations, levodopa treatment, antidepressant treatment, prior deep brain stimulation (DBS), worse quality of life, Hoehn & Yahr stage 2 or 3, worse semantic fluency, and, between visits, addition of amantadine, referral to occupational therapy, social services, or DBS, new diagnoses of cancer or osteoarthritis, and increased emergency visits. CONCLUSIONS: This large-scale analysis identified several predictors of progression to falling in PD. Such identifiers may help target patient subgroups for falls prevention intervention. Some factors are modifiable, offering opportunities for developing such interventions.

Rare inborn errors of metabolism with movement disorders: a case study to evaluate the impact upon quality of life and adaptive functioning.

BACKGROUND: Inborn errors of metabolism (IEM) form an important cause of movement disorders in children. The impact of metabolic diseases and concordant movement disorders upon children's health-related quality of life (HRQOL) and its physical and psychosocial domains of functioning has never been investigated. We therefore conducted a case study on the HRQOL and development of adaptive functioning in children with an IEM and a movement disorder. METHODS: Children with co-existent IEM and movement disorders were recruited from paediatric outpatient clinics. We systematically collected clinical data and videotaped examinations. The movement disorders were diagnosed by a panel of specialists. The Pediatric Quality of Life Inventory 4.0 and the Vineland Adaptive Behavior Scale were used to assess the HRQOL and adaptive functioning, respectively. RESULTS: We recruited 24 children (10 boys, mean age 7y 5 m). Six types of movement disorders were recognised by the expert panel, most frequently dystonia (16/24), myoclonus (7/24) and ataxia (6/24). Mean HRQOL (49.63, SD 21.78) was significantly lower than for other chronic disorders in childhood (e.g. malignancy, diabetes mellitus, rheumatic disease, psychiatric disorders; p <0.001) and tended to diminish with the severity of the movement disorder. The majority of participants had delayed adaptive functioning, most evident in their activities of daily living (51.92%, SD 27.34). Delay in adaptive functioning had a significant impact upon HRQOL (p = 0.018). CONCLUSIONS: A broad spectrum of movement disorders was seen in patients with IEM, although only five were receiving treatment. The overall HRQOL in this population is significantly reduced. Delay in adaptive functioning, most frequently seen in relation to activities of daily living, and the severity of the movement disorder contribute to this lower HRQOL. We plead for a greater awareness of movement disorders and that specialists should be asked to diagnose and treat these wherever possible.

Task force report: scales for screening and evaluating tremor: critique and recommendations.

The Movement Disorder Society established a task force to review rating scales for the assessment of tremor. Screening instruments used in identifying patients with tremor were also reviewed. Seven tremor severity scales, six activities of daily living (ADL)/disability scales, four quality-of-life scales, and five screening instruments were identified by searching PubMed.gov. The availability, use, acceptability, reliability, validity, and sensitivity to change were reviewed for each scale; and each scale was classified as recommended, suggested or listed based on whether 3, 2, or 1 of the following criteria were met: (1) used in the assessment of tremor (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no). Five tremor severity scales (the Fahn-Tolosa-Marin Tremor Rating Scale, the Bain and Findley Clinical Tremor Rating Scale, the Bain and Findley Spirography Scale, the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale, and the Tremor Research Group Essential Tremor Rating Assessment Scale), one ADL/disability scale (the Bain and Findley Tremor ADL Scale), one quality-of-life scale (the Quality of Life in Essential Tremor Questionnaire), and one screening instrument (the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale, version 1) are recommended using these criteria. However, all scales need a more comprehensive analysis of sensitivity to change in order to judge their utility in clinical trials and individual patient assessments. The task force recommends that further work with existing recommended scales be performed as opposed to the development of new tremor scales.

[Nocturnal stridor in multiple system atrophy]. / Nachtelijke stridor bij multipele systeematrofie.

BACKGROUND: Multiple system atrophy is a neurodegenerative disorder with parkinsonism, cerebellar ataxia and autonomic dysfunction. The occurrence of nocturnal stridor in patients with multiple system atrophy is associated with a decreased life expectancy. This is what makes adequate treatment so important. Nevertheless, stridor goes often unrecognized and there is frequent uncertainty about the therapeutic options. CASE: We present a 58-year-old woman with multiple system atrophy and nocturnal stridor. Direct laryngoscopy showed bilateral paresis of the vocal cords and glottic stenosis. Since the outcome of treatment with continuous positive airway pressure (CPAP) was unsatisfactory, a tracheotomy was performed after which the stridor disappeared. CONCLUSION: Polysomnography and laryngoscopy are the important diagnostic tools for this condition, after the clinical interview. Tracheotomy used to be the only therapeutic option for stridor. However, recent studies show a comparable effectiveness of non-invasive treatment with CPAP, provided there is a correct indication. The choice of therapy is a multidisciplinary process in which the neurologist, the sleep medicine specialist, the otolaryngologist, and the patient are involved.

Genome-wide association study confirms extant PD risk loci among the Dutch.

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).