The field of child movement disorders has faced unprecedented development over the last decade. This is largely due to advances in three key areas. The first is neuroimmunology, with the description of new antineuronal surface antibodies associated with specific clinical syndromes, including movement disorders, behavioural abnormalities and epilepsy, in particular anti–N-methyl-D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis. The second is neurogenetics, in which the mounting use of next-generation sequencing enabled prodigious discovery of new genes and an expansion of the phenotypic spectrum for many conditions. The last but equally important comes from advances in nonpharmacological treatment of movement. In this article, we review recent developments putting them into context with the purpose of enabling busy clinicians and researchers to better navigate the swelling literature in this field...
A UK-wide paediatric surveillance study detected 10 new cases of anti-NMDAR encephalitis over 13 months, giving an incidence of 0.85 per million children per year [95% confidence interval (95% CI) 0.64–1.06]. Previous series of encephalitis of an unknown origin suggest that it may represent up to 4% of these cases....
The presentation is age-dependent. Younger patients have more movement disorders and epilepsy at onset, and less commonly present underlying tumours. In a review of nine cases of infants and toddlers, none had a neoplasm despite investigations. Even adult patients usually present with movement disorders within the first month of presentation. Movement disorders include choreoathetosis, oro-facial dyskinesias and/or limb dyskinesias, varied severity of dystonias and Parkinsonian features. Atypical symptoms such as cerebellar ataxia or hemiparesis are rare but can be present in young children at onset. Most patients present with multiple symptoms....
In addition, herpes simplex virus (HSV) can trigger auto-immunity, which in turn can cause immune-mediated clinical relapses without viral activity on PCR testing or new lesions on MRI, and which often manifest with encephalopathy and treatment-resistant chorea associated with anti-NMDAR antibodies. The clinical implications of these recent findings require careful study. This evidence supports anti-NMDAR autoantibody testing is warranted in HSV relapses, that patients with HSV encephalitis could potentially benefit from concomitant testing and treating for auto-immunity during the early phases of disease to prevent clinical relapses and that prophylactic steroid use in the acute phase of the viral illness might hypothetically protect against future relapses...
Mutations in at least 10 different genes have been associated with neurodegeneration with brain iron accumulation (NBIA)...
AGS, which was described by Jean Aicardi and Françoise Goutières in 1984 as an infantile encephalopathy with basal ganglia calcification and mixed dystonia and spasticity, is now known to be an interferonopathy caused by mutations in at least seven genes associated with nucleic acid metabolism: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and the recently described mutations in IFIH1, a gene that codes for a receptor for viral RNA activating the interferon response...
Genetic heterogeneity, phenotypic pleiotropy and variable expressivity are not mutually exclusive and are in fact becoming the norm in genotype-phenotype correlations. TREX1, for example, which is one of seven genes causing AGS, also causes familial chilblain lupus, systemic lupus erythematosus and retinal vasculopathy with cerebral leucodystrophy due to its involvement with the immune response...
Many of the genes associated with paediatric movement disorders display significant variability in their expression...In 2012, proline-rich transmembrane protein 2 (PRRT2) was simultaneously described in association with paroxysmal kinesigenic dyskinesia (PKD, OMIM #128200), infantile convulsions and choreoathetosis (ICCA, OMIM #602066) and benign familial infantile seizures (BFIS, OMIM #605751), all dominantly inherited, except for a few autosomal recessive cases...
Genetic heterogeneity, phenotypic pleiotropy and variable expressivity are not mutually exclusive and are in fact becoming the norm in genotype-phenotype correlations. TREX1, for example, which is one of seven genes causing AGS, also causes familial chilblain lupus, systemic lupus erythematosus and retinal vasculopathy with cerebral leucodystrophy due to its involvement with the immune response...
For PRRT2, the most common mutation (a nucleotide insertion leading to a premature stop codon) has been associated with all the phenotypes described, and the only consistent genotype-phenotype correlation described so far is the difference between the milder autosomal dominant cases when compared with the more severe homozygous cases...
In addition to immunological and genetic factors, the role of socio-economic and psychodynamic elements as environmental determinants of paediatric movement disorders has received increased attention. A 13-year longitudinal population study from the UK showed a two-fold risk (odds ratio 2.09, 95% CI 1.38–3.47) of development of chronic tics and Tourette syndrome in children in the lowest tertile of socio-economic status when compared with the highest tertile...Current guidelines for clinical management of Tourette syndrome recommend behavioural therapy and encourage awareness promotion for voluntary management of the abnormal movements and the associated premonitory urges...
Dystonia, of any cause, including cerebral palsy (CP), has a severe impact on childhood; of a sample of 279 out of 294 cases referred for deep brain stimulation (DBS) or intrathecal baclofen (ITB), almost two-thirds referred worsening, one-third remaining as severe and few improving spontaneously...
Use of the Canadian Occupational Performance Measure (COPM) demonstrated meaningful performance and satisfaction in goal-attainment after DBS in all causes of dystonia, including CP and cases of NBIA/PANK2-disease and other disorders, for example glutaric aciduria type 1
http://journals.lww.com/co-neurology/Fulltext/2015/08000/A_field_guide_to_current_advances_in_paediatric.20.aspx?cid=MR-eJP-AdSales-Lundbeck-Neurology-WCO-NoPromo
Silveira-Moriyama L, Lin JP. A field guide to current advances in paediatric
movement disorders. Curr Opin Neurol. 2015 Aug;28(4):437-46.
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