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Current therapies and therapeutic decision making for childhood-onset movement disorders
Shekeeb S Mohammad1,2, Simon P Paget3, Russell C Dale1,2
1Kids Neuroscience Centre, The Kids Research Institute at the Children's Hospital at Westmead, Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.
Insights
Childhood movement disorders, including tics and stereotypies, are increasingly understood through genetics. Precision medicine and targeted therapies, including gene and cellular options, offer new treatment avenues for pediatric movement disorders.
Area of Science:
- Pediatric Neurology
- Neurogenetics
- Movement Disorders
Background:
- Childhood movement disorders differ from adult presentations, with neurodevelopmental conditions like tics and stereotypies being more common.
- Genomic advancements are crucial for understanding early-onset dystonic syndromes in children.
- Co-occurring psychiatric and cognitive issues significantly impact disability in pediatric movement disorders.
Purpose of the Study:
- To outline a systematic approach for evaluating children with movement disorders.
- To highlight the role of precision medicine and novel therapeutic strategies.
- To provide a contemporary overview of treatment options for childhood-onset movement disorders.
Main Methods:
- Phenomenological definition of movement abnormalities.
- Assessment of functional impairment.
- Screening for comorbid psychiatric and cognitive conditions.
- Review of current and emerging therapeutic interventions.
Main Results:
- Genomic insights are revolutionizing the diagnosis of early-onset dystonic syndromes.
- Precision medicine approaches target specific treatable conditions and modifiable disease processes.
- Disease-modifying therapies include metabolic, neurotransmitter, inflammatory, autoimmune, gene, and cellular treatments.
- Symptomatic therapies target specific neurochemical pathways, and neuromodulation techniques like DBS are gaining importance.
Conclusions:
- A comprehensive approach to pediatric movement disorders involves detailed assessment and consideration of comorbidities.
- Genomic findings are driving personalized and individualized treatment strategies.
- A combination of disease-modifying, symptomatic, neuromodulatory, and rehabilitative interventions is essential for optimal management.
Abstract:
Movement disorders differ in children to adults. First, neurodevelopmental movement disorders such as tics and stereotypies are more prevalent than parkinsonism, and second, there is a genomic revolution which is now explaining many early-onset dystonic syndromes. We outline an approach to children with movement disorders starting with defining the movement phenomenology, determining the level of functional impairment due to abnormal movements, and screening for comorbid psychiatric conditions and cognitive impairments which often contribute more to disability than the movements themselves. The rapid improvement in our understanding of the etiology of movement disorders has resulted in an increasing focus on precision medicine, targeting treatable conditions and defining modifiable disease processes. We profile some of the key disease-modifying therapies in metabolic, neurotransmitter, inflammatory, and autoimmune conditions and the increasing focus on gene or cellular therapies. When no disease-modifying therapies are possible, symptomatic therapies are often all that is available. These classically target dopaminergic, cholinergic, alpha-adrenergic, or GABAergic neurochemistry. Increasing interest in neuromodulation has highlighted that some clinical syndromes respond better to DBS, and further highlights the importance of "disease-specific" therapies with a future focus on individualized therapies according to the genomic findings or disease pathways that are disrupted. We summarize some pragmatic applications of symptomatic therapies, neuromodulation techniques, and some rehabilitative interventions and provide a contemporary overview of treatment in childhood-onset movement disorders. © 2019 International Parkinson and Movement Disorder Society.
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