Voice and swallowing dysfunction in X-linked dystonia parkinsonism.

OBJECTIVES: To systematically characterize and describe voice and swallowing manifestations in patients with X-linked dystonia parkinsonism (XDP) and correlate with quality-of-life (QOL) measures. METHODS: Thirty-four patients with XDP with communication and swallowing difficulties underwent neurological examination, head and neck examination, nasopharyngoscopy, QOL surveys (Swallowing Quality of Life questionnaire [SWAL-QOL] and Voice Handicap Index [VHI]), and functional endoscopic evaluation of swallowing (FEES) to assess the extent of dysfunction. RESULTS: All patients showed high rates of lingual, oromandibular, and laryngeal dysfunction, as well as severe QOL changes in swallowing and communication ability. The most common head and neck manifestations of dystonic symptoms were difficulty coordinating the mouth and tongue (79%), uncontrollable tongue thrusting (53%), and jaw opening (35%). Laryngeal symptoms including vocal strain (adductor voice breaks) or stridor (32%), as well as velopharyngeal insufficiency (20%), were also identified. Of the patients with laryngeal symptoms, 18% had respiratory dystonia. Swallowing assessments showed significant abnormalities in oral bolus control and oropharyngeal dysphagia. FEES examinations showed that 87.5% of the study group had penetration or aspiration. QOL scores showed an average VHI of 94.4 (severe dysfunction), and SWAL-QOL showed an average of 37.7 (severe dysfunction). CONCLUSION: Swallowing and voice impairment in XDP is not well characterized and presents a more distinctive phenomenology than other neurological disorders, with a unique set of challenges for treatment. This is the first study to systematically evaluate laryngeal and pharyngeal dysfunction in XDP patients and correlate with QOL measures. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:171-177, 2020.

Hand stereotypies: Lessons from the Rett Syndrome Natural History Study.

OBJECTIVE: To characterize hand stereotypies (HS) in a large cohort of participants with Rett syndrome (RTT). METHODS: Data from 1,123 girls and women enrolled in the RTT Natural History Study were gathered. Standard tests for continuous and categorical variables were used at baseline. For longitudinal data, we used repeated-measures linear and logistic regression models and nonparametric tests. RESULTS: HS were reported in 922 participants with classic RTT (100%), 73 with atypical severe RTT (97.3%), 74 with atypical mild RTT (96.1%), and 17 females with MECP2 mutations without RTT (34.7%). Individuals with RTT who had classic presentation or severe MECP2 mutations had higher frequency and earlier onset of HS. Heterogeneity of HS types was confirmed, but variety decreased over time. At baseline, almost half of the participants with RTT had hand mouthing, which like clapping/tapping, decreased over time. These 2 HS types were more frequently reported than wringing/washing. Increased HS severity (prevalence and frequency) was associated with worsened measures of hand function. Number and type of HS were not related to hand function. Overall clinical severity was worse with decreased hand function but only weakly related to any HS characteristic. While hand function decreased over time, prevalence and frequency of HS remained relatively unchanged and high. CONCLUSIONS: Nearly all individuals with RTT have severe and multiple types of HS, with mouthing and clapping/tapping decreasing over time. Interaction between HS frequency and hand function is complex. Understanding the natural history of HS in RTT could assist in clinical care and evaluation of new interventions.

Defining Hand Stereotypies in Rett Syndrome: A Movement Disorders Perspective.

INTRODUCTION: Hand stereotypies (HS) are a primary diagnostic criterion for Rett syndrome (RTT) but are difficult to characterize and quantify systematically. METHODS: We collected video on 27 girls (2-12 years of age) with classic RTT who participated in a mecasermin trial. The present study focused exclusively on video analyses, by reviewing two five-minute windows per subject to identify the two most common HS. Three raters with expertise in movement disorders independently rated the five-minute windows using standardized terminology to determine the level of agreement. We iteratively refined the protocol in three stages to improve descriptive accuracy, categorizing HS as "central" or "peripheral," "simple" or "complex," scoring each hand separately. Inter-rater agreement was analyzed using Kappa statistics. RESULTS: In the initial protocol evaluating HS by video, inter-rater agreement was 20.7%. In the final protocol, inter-rater agreement for the two most frequent HS was higher than the initial protocol at 50%. CONCLUSION: Phenotypic variability makes standardized evaluation of HS in RTT a challenge; we achieved only 50% level of agreement and only for the most frequent HS. Therefore, objective measures are needed to evaluate HS.

Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.

ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation.