Current therapies and therapeutic decision making for childhood‐onset movement disorders

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

Pro‐inflammatory dopamine‐2 receptor‐specific T cells in paediatric movement and psychiatric disorders

“…19 Additionally, D2R antibodies can be useful in identifying patients who can be amenable to immunotherapy. 17,[21][22][23][24][25] The field has focused predominantly on aberrant antibody responses and less is known about the autoreactive T-cell response against D2R in movement and psychiatric disorders. Cellular immunity is a major compartment of the adaptive immune response, and in particular, CD4 + T helper cells are key in orchestrating the effects of other immune cells and molecules.…”

“…The precise mechanisms underlying autoimmunity in these disorders remain unclear, but it has been postulated that D2R antibodies may alter dopaminergic signalling by stimulating excess dopamine secretion, 20 inducing inhibitory D2R signalling 16 and triggering receptor internalisation 19 . Additionally, D2R antibodies can be useful in identifying patients who can be amenable to immunotherapy 17,21–25 …”

A special issue on childhood‐onset movement disorders

“…In the fourth and final article, “Current Therapies And Therapeutic Decision Making for Childhood‐Onset Movement Disorders,” Mohammad, Paget, and Dale cover existing and emerging treatments including pharmacologic, surgical, and gene therapy approaches . Faced with a broad task, the authors start out by outlining guiding principles for the treatment of movement disorders in children.…”

“…In the fourth and final article, "Current Therapies And Therapeutic Decision Making for Childhood-Onset Movement Disorders," Mohammad, Paget, and Dale cover existing and emerging treatments including pharmacologic, surgical, and gene therapy approaches. 11 Faced with a broad task, the authors start out by outlining guiding principles for the treatment of movement disorders in children. From these principles that apply to all movement disorders the authors venture to discuss specific medications, physical therapies, invasive therapies, neuromodulation, and emerging targeted therapies.…”

Table_4.DOCX

“…The risk of a given treatment should always be considered before starting, since the adverse effects of the treatment may be worse than the MD itself. Providentially, side effects are transient and reversible for most treatments (149).…”