Moutvic, Margaret A.

ABSTRACTBackgroundTreating functional movement disorder (FMD) with motor retraining is effective but resource intensive.ObjectivesIdentify patient, disease, and program variables associated with favorable treatment outcomes.MethodsRetrospective review of the 1 week intensive outpatient FMD program at Mayo Clinic in Minnesota from February 2019 to August 2021. Outcomes included patient‐reported measures (Canadian Occupational Performance Measure‐Performance and Satisfaction subscales [COPM‐P and COPM‐S, range 0–10] and Global Rating of Change [GROC, −7 to +7]) and a retrospective investigator‐rated scale (0–3, worse/not improved to significantly improved/resolved). Linear regression models identified variables predicting favorable outcomes.ResultsParticipants (n = 201, 74% female, mean age = 46) had median FMD duration of 24 months. The commonest FMD subtypes were gait disorder (65%), tremor (41%) and weakness (17%); 53% had ≥2 subtypes. Most patients (88%) completed a therapeutic screening process before program entry. Patient‐reported outcomes at the end of the week improved substantially (COPM‐P average change 3.8 ± 1.9; GROC post‐program average 5.5 ± 1.7). Available investigator‐rated outcomes from short‐term follow‐up were also positive (102/122 [84%] moderately to significantly improved/resolved). Factors predicting greater improvement in COPM‐P were completing therapeutic screening, higher number of non‐motor symptoms, shorter FMD duration, earlier program entry, lower baseline COPM scores, and (among screened patients) higher GROC between therapeutic screening and program start.ConclusionPatients with diverse FMD subtypes improved substantially over a 1 week period. Utilization of therapeutic screening and greater improvement between therapeutic screening and program start were novel predictors of favorable outcomes. Non‐motor symptoms did not preclude positive responses, although patients with predominant non‐motor burden were excluded.

Abstract Background (+)‐Epicatechin (EPI) induces mitochondrial biogenesis and antioxidant metabolism in muscle fibers and neurons. We aimed to evaluate safety and efficacy of (+)‐EPI in pediatric subjects with Friedreich's ataxia (FRDA). Methods This was a phase II, open‐label, baseline‐controlled single‐center trial including 10 participants ages 10 to 22 with confirmed FA diagnosis. (+)‐EPI was administered orally at 75 mg/d for 24 weeks, with escalation to 150 mg/d at 12 weeks for subjects not showing improvement of neuromuscular, neurological or cardiac endpoints. Neurological endpoints were change from baseline in Friedreich's Ataxia Rating Scale (FARS) and 8‐m timed walk. Cardiac endpoints were changes from baseline in left ventricular (LV) structure and function by cardiac magnetic resonance imaging (MRI) and echocardiogram, changes in cardiac electrophysiology, and changes in biomarkers for heart failure and hypertrophy. Results Mean FARS/modified (m)FARS scores showed nonstatistically significant improvement by both group and individual analysis. FARS/mFARS scores improved in 5/9 subjects (56%), 8‐m walk in 3/9 (33%), 9‐peg hole test in 6/10 (60%). LV mass index by cardiac MRI was significantly reduced at 12 weeks ( P = .045), and was improved in 7/10 (70%) subjects at 24 weeks. Mean LV ejection fraction was increased at 24 weeks ( P = .008) compared to baseline. Mean maximal septal thickness by echocardiography was increased at 24 weeks ( P = .031). There were no serious adverse events. Conclusion (+)‐EPI was well tolerated over 24 weeks at up to 150 mg/d. Improvement was observed in cardiac structure and function in subset of subjects with FRDA without statistically significant improvement in primary neurological outcomes. Synopsis A (+)‐epicatechin showed improvement of cardiac function, nonsignificant reduction of FARS/mFARS scores, and sustained significant upregulation of muscle‐regeneration biomarker follistatin.