Efficacy of parent-delivered behavioral therapy for primary complex motor stereotypies.

AIM: Primary complex motor stereotypies (CMS) are persistent, patterned, repetitive, rhythmic movements in young people with typical development. This study evaluated the efficacy of an instructional DVD as a home-based, parent-administered, behavioral therapy for primary CMS. METHOD: Eighty-one children with primary CMS were enrolled. Primary outcome measures included the Stereotypy Severity Scale (SSS) - Motor and Impairment scores, and Stereotypy Linear Analog Scale (SLAS). Mean CMS onset was 13.4 months (SD 13.1). Eligibility required observed CMS. Psychiatric disorders were not exclusionary and a stable medication regimen was required. Intellectual disability, neurological disorder, autism spectrum disorder, and tics were exclusionary. Initial assessments were completed via REDCap before receipt of the DVD. Fifty-four of the 81 children (34 male, 20 female; mean age 8y 2mo, SD 1.42, range 7-14y) completed assessments at 1, 2, or 3 months after receiving the DVD. RESULTS: Reductions (baseline to last assessment) in SSS Motor, SSS Impairment, and SLAS scores (all p<0.001) represented change ratios of -15%, -24%, and a -20% respectively. Greatest relative treatment benefit was observed by younger children (ages 7-8y), and by 1 month after receipt of DVD, while a parent global assessment scale showed progressive improvement throughout the study. INTERPRETATION: An instructional DVD for parent-delivered behavioral therapy was a safe, effective intervention for primary CMS.

Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene.

Motor stereotypies are common in children with autism spectrum disorder (ASD), intellectual disability, or sensory deprivation, as well as in typically developing children ("primary" stereotypies, pCMS). The precise pathophysiological mechanism for motor stereotypies is unknown, although genetic etiologies have been suggested. In this study, we perform whole-exome DNA sequencing in 129 parent-child trios with pCMS and 853 control trios (118 cases and 750 controls after quality control). We report an increased rate of de novo predicted-damaging DNA coding variants in pCMS versus controls, identifying KDM5B as a high-confidence risk gene and estimating 184 genes conferring risk. Genes harboring de novo damaging variants in pCMS probands show significant overlap with those in Tourette syndrome, ASD, and those in ASD probands with high versus low stereotypy scores. An exploratory analysis of these pCMS gene expression patterns finds clustering within the cortex and striatum during early mid-fetal development. Exploratory gene ontology and network analyses highlight functional convergence in calcium ion transport, demethylation, cell signaling, cell cycle and development. Continued sequencing of pCMS trios will identify additional risk genes and provide greater insights into biological mechanisms of stereotypies across diagnostic boundaries.

Monday-focused tailored rapid interactive mobile messaging for weight management 2 (MTRIMM2): results from a randomized controlled trial.

BACKGROUND: Text-messaging interventions can reach many individuals across a range of socioeconomic groups, at a low cost. Few randomized controlled trials (RCTs) of text-messaging weight loss interventions have been conducted in United States. METHODS: From September of 2016 to September of 2018, we conducted a two-parallel group, superiority, RCT of a 16-week text-messaging, weight loss intervention in Baltimore, Maryland, in overweight and obese adults younger than 71, who were able to receive text-messages. Our objective was to assess the effect of receiving the message content only (in printed documents distributed at baseline and week 8), versus receiving messages via short messaging service (SMS) on weight loss (primary outcome), body mass index, perceived exercise benefits and barriers, self-efficacy, and physical activity (PA). The random allocation sequence was equally balanced intervention groups by gender and age groups. Participants were randomized after the baseline assessment. Then, participants and most study staff were unblinded. Follow-up assessments were conducted at 8-, 16-, and 42-week post randomization. We performed intention-to-treat analysis using mixed linear regression models. RESULTS: Of the 155 adults randomized (printed messages =77, SMS =78), 87.1% were women, 53.5% were African Americans, and 93.5% non-Hispanic. Participants who completed at least one follow-up assessment were included in regression analyses (n=145, printed messages =74, SMS =71). Compared to baseline, at the 42-week assessment, the average percent weight loss was 1.23 for the SMS group (P=0.006) and 0.86 for the printed messages group (P=0.047). Both groups experienced small reductions in weight (printed messages: -0.96 kg, P=0.022; SMS: -1.19 kg, P=0.006), BMI (printed messages: -0.32, P=0.035; SMS: -0.52, P=0.002), and percent energy from fat consumption (printed messages: -1.43, P=0.021; SMS: -2.14, P≤0.001). No statistically significant between groups differences were detected for any of the study outcomes. SMS response rates were not statistically significantly associated with study outcomes. No adverse events were reported. CONCLUSIONS: A semi-tailored SMS weight loss intervention among overweight and obese adults was not statistically superior in efficacy to paper-based messaging. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04506996.

Anomalous Putamen Volume in Children With Complex Motor Stereotypies.

BACKGROUND: Complex motor stereotypies in children are repetitive rhythmic movements that have a predictable pattern and location, seem purposeful, but serve no obvious function, tend to be prolonged, and stop with distraction, e.g., arm or hand flapping, waving. They occur in both "primary" (otherwise typically developing) and secondary conditions. These movements are best defined as habitual behaviors and therefore pathophysiologically hypothesized to reside in premotor to posterior putamen circuits. This study sought to clarify the underlying neurobiologic abnormality in children with primary complex motor stereotypies using structural neuroimaging, emphasizing brain regions hypothesized to underlie these atypical behaviors. METHODS: High-resolution anatomic magnetic resonance images, acquired at 3.0 T, were analyzed in children aged eight to twelve years (20 with primary complex motor stereotypies and 20 typically developing). Frontal lobe subregions and striatal structures were delineated for analysis. RESULTS: Significant reductions (P = 0.045) in the stereotypies group were identified in total putamen volume but not in caudate, nucleus accumbens, or frontal subregions. There were no group differences in total cerebral volume. CONCLUSIONS: Findings of a smaller putamen provide preliminary evidence suggesting the potential involvement of the habitual pathway as the underlying anatomic site in primary complex motor stereotypies.

Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome.

BACKGROUND: It has been hypothesized that glutamatergic transmission may be altered in Tourette syndrome. In this study, we explored the efficacy of a glutamate agonist (D-serine) and antagonist (riluzole) as tic-suppressing agents in children with Tourette syndrome. METHODS: We performed a parallel three-arm, 8-week, double-blind, randomized placebo-controlled treatment study in children with Tourette syndrome. Each child received 6 weeks of treatment with D-serine (maximum dose 30 mg/kg/day), riluzole (maximum dose 200 mg/day), or placebo, followed by a 2-week taper. The primary outcome measure was effective tic suppression as determined by the differences in the Yale Global Tic Severity Scale score; specifically, the total tic score and the combined score (total tic score + global impairment) between treatment arms after 6 weeks of treatment. Mann-Whitney U tests were performed to analyze differences between each group and the placebo group. RESULTS: Twenty-four patients (males = 21, ages 9-18) enrolled in the study; one patient dropped out before completion. Combined Yale Global Tic Severity Scale score and total tic scores improved in all groups. The 6-week mean percent improvement of the riluzole (n = 10), D-serine (n = 9), and placebo (n = 5) groups in the combined Yale Global Tic Severity Scale score were 43.7, 39.5, and 30.2 and for total tic scores were 38.0, 25.0, and 34.0, respectively. There were no significant differences in Yale Global Tic Severity Scale score or total tic score, respectively, between the riluzole and placebo (P = 0.35, 0.85) or D-serine and placebo (P = 0.50, 0.69) groups. CONCLUSION: Tics diminished by comparable percentages in the riluzole, D-serine, and placebo groups. These preliminary data suggest that D-serine and riluzole are not effective in tic suppression.

Primary complex motor stereotypies in older children and adolescents: clinical features and longitudinal follow-up.

BACKGROUND: Complex motor stereotypies are rhythmic, repetitive, fixed, and purposeless movements that stop with distraction. Once believed to occur only in children with autism spectrum or other developmental disorders, their presence in otherwise typically developing children (primary) has been well-established. In primary complex motor stereotypies, little information is available about the long-term outcome of these movements or existing comorbidities. METHODS: Forty-nine healthy participants (31 boys), ages 9 to 20 years with primary complex motor stereotypies who were previously diagnosed at a pediatric movements disorder clinic, were identified from medical records. Parents or the young adult (if older than age 18), completed a telephone interview evaluating family history, outcome, and comorbidities including attention-deficit hyperactivity disorder, obsessive compulsive disorder, anxiety, and tics/Tourette syndrome. Standardized questionnaires assessing attention-deficit hyperactivity, obsessive compulsive disorder, and anxiety were used to validate parent report of comorbidities. RESULTS: Stereotypy onset occurred before age 3 years in 98%. In all but one individual, stereotypies persisted at the time of phone follow-up (follow-up range: 6.8-20.3 years). Positive family history of complex motor stereotypies was identified in 39%. Most participants (92%) had concern for at least one comorbid disorder, including parent-/patient-reported clinically elevated levels of anxiety (73%), attention-deficit hyperactivity (63%), obsessive compulsive disorder (35%), and tics/Tourette syndrome (22%). CONCLUSION: Primary motor stereotypies typically begin in early childhood and, although reduced in frequency and duration, persist at least through the teenage years. Repetitive movements are associated with a variety of comorbidities that often have a greater functional impact than the stereotypic behavior.