Localising movement disorders in childhood

Bamford, Nigel S.; McVicar, Kathryn

doi:10.1016/s2352-4642(19)30330-x

Cited by 6 publications

(3 citation statements)

References 75 publications

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“…Monoamine action plays an essential role in striatal physiology and motor control [11,22]. Although research has often focused on DA, adrenergic receptors also contribute to striatal regulation [25,26,54].…”

Section: Discussionmentioning

confidence: 99%

Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice

et al. 2020

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Background: Parkinsonism is caused by dopamine (DA) insufficiency and results in a hypokinetic movement disorder. Treatment with L-Dopa can restore DA availability and improve motor function, but patients can develop L-Dopa-induced dyskinesia (LID), a secondary hyperkinetic movement disorder. The mechanism underlying LID remains unknown, and new treatments are needed. Experiments in mice have shown that DA deficiency promotes an imbalance between striatal acetylcholine (ACh) and DA that contributes to motor dysfunction. While treatment with L-Dopa improves DA availability, it promotes a paradoxical rise in striatal ACh and a further increase in the ACh to DA ratio may promote LID. Methods: We used conditional Slc6a3DTR/+ mice to model progressive DA deficiency and the β-adrenergic receptor (β-AR) antagonist propranolol to limit the activity of striatal cholinergic interneurons (ChIs). DA-deficient mice were treated with L-Dopa and the dopa decarboxylase inhibitor benserazide. LID and motor performance were assessed by rotarod, balance beam, and open field testing. Electrophysiological experiments characterized the effects of β-AR ligands on striatal ChIs. Results: LID was observed in a subset of DA-deficient mice. Treatment with propranolol relieved LID and motor hyperactivity. Electrophysiological experiments showed that β-ARs can effectively modulate ChI firing. Conclusions: The work suggests that pharmacological modulation of ChIs by β-ARs might provide a therapeutic option for managing LID.

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Section: Discussionmentioning

confidence: 99%

Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice

et al. 2020

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“…Pediatric movement disorders, and especially hyperkinetic involuntary movements, were traditionally viewed as disorders involving mainly the basal ganglia circuitry. [ 93 ] Nevertheless, one of the converging themes in PKD and MDS (as reviewed in Sections 2.2 and 3.1 ) is the fundamental role of cerebellar circuits in the genesis of abnormal motor patterns. Indeed, both the cerebellum and the basal ganglia are phylogenetically old brain regions, and their reciprocal connections have been increasingly recognized to play important roles in motor control.…”

Section: Common Themes and Prospectsmentioning

confidence: 99%

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders

Lin

2022

Advanced Genetics

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The era of next‐generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease‐causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood‐onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus‐dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease‐causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control—a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi‐omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.

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“…Many antiseizure medications exert their effect on GABAergic spiny projection neurons of the striatum as well as cholinergic and GABAergic interneurons. 2,3 These, in addition to dopaminergic and cholinergic neurons, regulate the basal ganglia, 3,4 and this connection may explain the mechanism of antiseizure medications treating and causing movement disorders.…”

mentioning

confidence: 99%

Movement Disorders Secondary to Novel Antiseizure Medications in Pediatric Populations: A Systematic Review and Meta-analysis of Risk

et al. 2022

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Novel antiseizure medications are thought to be safer than their conventional counterparts, though no dedicated analysis of movement disorder risk among pediatric populations using novel antiseizure medications has been completed. We report a systematic review with meta-analysis describing the relationship between novel antiseizure medications and movement disorders in pediatrics. MEDLINE, EMBASE, and the World Health Organization’s International Clinical Trials Registry Platform were searched up to October 2020 for randomized controlled trials investigating novel antiseizure medications in pediatric populations. Antiseizure medications included lacosamide, perampanel, eslicarbazepine, rufinamide, fenfluramine, cannabidiol, and brivaracetam. Outcomes were pooled using random effects models; risk difference (RD) and 95% confidence intervals (CIs) were calculated. Twenty-three studies were selected from 1690 nonredundant manuscripts (n = 1912 total). There was a significantly increased risk of movement disorders associated with perampanel (RD 0.07, 95% CI 0.01-0.13; n = 133), though only 1 relevant trial was found. No increased risk of movement disorders was found with other antiseizure medications. Our findings indicate most novel antiseizure medications are safe to use in pediatric populations with respect to movement disorders. However, findings were limited by quality of adverse event reporting.

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Localising movement disorders in childhood

Cited by 6 publications

References 75 publications

Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice

Propranolol Relieves L-Dopa-Induced Dyskinesia in Parkinsonian Mice

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders

Movement Disorders Secondary to Novel Antiseizure Medications in Pediatric Populations: A Systematic Review and Meta-analysis of Risk

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