Dataset Information

Emerging Monogenic Complex Hyperkinetic Disorders.

ABSTRACT: PURPOSE OF REVIEW:Hyperkinetic movement disorders can manifest alone or as part of complex phenotypes. In the era of next-generation sequencing (NGS), the list of monogenic complex movement disorders is rapidly growing. This review will explore the main features of these newly identified conditions. RECENT FINDINGS:Mutations in ADCY5 and PDE10A have been identified as important causes of childhood-onset dyskinesias and KMT2B mutations as one of the most frequent causes of complex dystonia in children. The delineation of the phenotypic spectrum associated with mutations in ATP1A3, FOXG1, GNAO1, GRIN1, FRRS1L, and TBC1D24 is revealing an expanding genetic overlap between epileptic encephalopathies, developmental delay/intellectual disability, and hyperkinetic movement disorders,. Thanks to NGS, the etiology of several complex hyperkinetic movement disorders has been elucidated. Importantly, NGS is changing the way clinicians diagnose these complex conditions. Shared molecular pathways, involved in early stages of brain development and normal synaptic transmission, underlie basal ganglia dysfunction, epilepsy, and other neurodevelopmental disorders.

SUBMITTER: Carecchio M

PROVIDER: S-EPMC5662693 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Emerging Monogenic Complex Hyperkinetic Disorders.

Carecchio Miryam M Mencacci Niccolò E NE

Current neurology and neuroscience reports 20171030 12

<h4>Purpose of review</h4>Hyperkinetic movement disorders can manifest alone or as part of complex phenotypes. In the era of next-generation sequencing (NGS), the list of monogenic complex movement disorders is rapidly growing. This review will explore the main features of these newly identified conditions.<h4>Recent findings</h4>Mutations in ADCY5 and PDE10A have been identified as important causes of childhood-onset dyskinesias and KMT2B mutations as one of the most frequent causes of complex ...[more]

PMID: 29086067

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Project description:ObjectiveThis proof-of-concept feasibility trial examined the potential of the Cognitive Orientation to daily Occupational Performance Approach (CO-OP) to augment deep brain stimulation (DBS) outcomes in childhood-onset hyperkinetic movement disorders (HMD) including dystonia and dyskinetic cerebral palsy.MethodsThis is a single case experimental design using multiple baseline as n-of-1 trial comprising 10 intervention sessions, with replications across participants (n = 10). Treatment focused on 3 participant-selected goals. Transfer was assessed on 2 additional untreated goals. Individuals enrolled were 6-21 years of age and had DBS in situ and sufficient manual ability. Primary outcome was functional performance change on the Performance Quality Rating Scale-Individualized (PQRS-i) measured before, during, and posttreatment, and at 3-month follow-up. Assessors of outcome were blinded to time of assessment, number of intervention session, and treatment allocation. To measure effect size, a nonoverlapping index, Tau-U, was used. Feasibility measures were captured.ResultsOne participant withdrew before baseline assessment. Effect sizes of at least 0.66 were seen at both posttreatment and follow-up with all participants showing improvements in at least one trained goal in PQRS-i. Six participants improved on all 3 goals and 2 improved on 2 trained goals. Two children showed deterioration in one trained goal each. Transfer to untrained goals was observed in 3 participants for a total of 5 goals. CO-OP was feasible and acceptable to all participants.ConclusionA cognitive-based, task-oriented approach to support performance of personally relevant functional skills enabling participation is acceptable in childhood-onset HMD post-DBS. Further, preliminary efficacy to improve outcomes and proof of concept with CO-OP has been established in this population.Classification of evidenceThis study provides Class IV evidence that for children with HMD who had undergone DBS, CO-OP improves performance of personally relevant functional skills.

Project description:BackgroundHyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive.ObjectivesProviding a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures.MethodsA systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes.ResultsMost articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described.ConclusionKey brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes.

Dataset Information

Emerging Monogenic Complex Hyperkinetic Disorders.

Publications

Emerging Monogenic Complex Hyperkinetic Disorders.

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