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Movement disorders in children with congenital Zika virus syndrome

      Abstract

      Background

      Congenital Zika Virus Syndrome (CZVS) denotes the neurologic and developmental sequelae of congenital infection of the Zika virus. While prior studies have detailed the associated clinical phenotypes, new findings continue to be identified. Abnormal postures and movements have been previously described in children with CZVS, but not in detail.

      Objective

      To examine a cohort of infants with CZVS and characterize the spectrum of motor abnormalities, especially movement disorders.

      Design

      Cross-sectional prospective study of 21 infants with confirmed CZVS.

      Setting

      Single-center cohort of 32 patients with serologically confirmed CZVS cared for in a referral center in Brazil.

      Participants

      21 children (67% female), evaluated by two child neurologists and one movement disorders specialist, with clinical and laboratory diagnosis of CZVS aged between 16 and 30 months, with a mean age of 16 months at the time of the last examination.

      Main outcome(s) and measure(s)

      Prospective neurologic examination by a team of three neurologists, including one movement disorders specialist. Sixteen (76.2%) children had a longitudinal evaluation with a six-month interval. The same team of experts analyzed recorded videos of all patients to characterize motor abnormalities and movement disorders. Neuroimaging findings were also analyzed to correlate with clinical findings.

      Results

      Twenty (95.2%) patients presented with dystonic postures, including “125” posture of the fingers in 17 (80.1%), “swan neck” posture of the fingers in three (18.8%), oromandibular dystonia in nine (42.9%), extensor axial hypertonia in eight (38.1%) and internal rotation of the shoulder posture in two (9.5%). Four (19%) patients had tremor. All children had malformations of cortical development, and in 13 (61.9%), the pattern was consistent with a severe and diffuse gyral simplification. Seventeen children (81%) had calcification in the transition of grey and white matter, whereas 11 (52.4%) patients had basal ganglia calcifications.

      Conclusion and relevance

      In our series, dystonic postures and other extrapyramidal signs were frequent and potentially disabling. Although children with CZVS are assessed and treated for spasticity, dystonia and other movement disorders remain neglected. This study emphasizes that extrapyramidal findings may potentially influence optimal strategies for rehabilitation and management.

      Keywords

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      References

      1. Boletim Microcefalia: Ministério da Saúde investiga 4291 casos suspeitos no país (in Portuguese). Ministério da Saúde [cited 2013 Mar 30]. Available from: https://cidadeverde.com/noticias/216428/microcefalia-ministerio-da-saude-investiga-4291-casos-suspeitos-no-pais.

      2. de Fatima Vasco Aragao M, van der Linden V, Brainer-Lima AM, Coeli RR, Rocha MA, Sobral da Silva P, et al. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. BMJ 2016;353:i1901.

      3. Boletim Epidemiológico 08 (in Portuguese). Ministério da Saúde do Brasil [cited 2019 Mar 15]. Available from: https://www.saude.gov.br/images/pdf/2019/marco/22/2019-001.pdf.

      4. van der Linden V, Filho OL, Lins OG, van der Linden A, de Fatima Vasco Aragao M, Brainer-Lima AM, et al. Congenital Zika syndrome with arthrogryposis: retrospective case series study. BMJ 2016;354:i3899.

        • van der Linden V.
        • Pessoa A.
        • Dolbyns W.
        • Barkovich A.J.
        • van der Linden Junior H.
        • Rolim Filho E.L.
        • et al.
        Description of 13 infants born during October 2015-January 2016 with congenital Zika virus infection without microcephaly at birth—Brazil.
        MMWR Morb Mortal Wkly Report. 2016; 65: 1343-1348
        • del Campo M.
        • Feitosa I.M.L.
        • Ribeiro E.M.
        • Pessoa A.L.
        • França G.V.
        • García-Alix A.
        • et al.
        The phenotypic spectrum of congenital Zika syndrome.
        Am J Med Gen Part A. 2017; 173A: 841-857
        • Sanger T.D.
        • Ferman D.
        Similarity of involuntary posture between different children with dystonia.
        Mov Disord Clin Pract. 2017; 14: 870-874
        • Luc Q.N.
        • Querubin J.
        Clinical management of dystonia in childhood.
        Ped Drugs. 2017; 19: 447-461
        • Pereira H.V.F.S.
        • Santos S.P.
        • Amâncio A.P.R.L.
        • Oliveira-Szejnfeld P.S.
        • Flor E.O.
        • Tavares J.S.
        • et al.
        Neurological outcomes of congenital Zika syndrome in toddlers and preschoolers: a case series.
        Lancet Child Adolesc Health. 2020; 4: 378-387
        • Defazio G.
        • Albanese A.
        • Pellicciari R.
        • Scaglione S.L.
        • Esposito M.
        • Morgante F.
        • et al.
        Expert recommendations for diagnosis of cervical, oromandibular and limb dystonia.
        Neurol Sci. 2019; 40: 89-95
        • van der Linden V.
        • de Lima Petribu N.C.
        • Pessoa A.
        • Faquini I.
        • Paciorkowski A.R.
        • van der Linden H.
        • et al.
        Association of severe hydrocephalus with congenital Zika syndrome.
        JAMA Neurol. 2016; 76: 203-210
        • Sanger T.D.
        • Delgado M.R.
        • Gaebler-Spira D.
        • Hallet M.
        • Mink J.W.
        and Task force on childhood movement disorders. Classification and definition of disorders causing hypertonia in childhood.
        Pediatrics. 2003; 111: e89-e97
        • Albanese A.
        • Bhatia K.
        • Bressman S.
        • Delong M.R.
        • Fahn S.
        • Fung V.S.
        • et al.
        Phenomenology and classification of dystonia.
        Mov Disord. 2013; 28: 863-873
        • Moura da Silva A.A.
        • Gans J.S.
        • Souza P.D.
        • Doriqui M.J.
        • Ribeiro M.R.
        • Branco M.D.
        • et al.
        growth and neurological outcomes in infants with probable congenital Zika virus infection.
        Em Inf Diseases. 2016; 22: 1953-1956
        • Yearglin-Alsoop M.
        • Van Naarden K.B.
        • Doernberg N.S.
        • Benedict R.E.
        • Kirby R.S.
        • Durkin M.S.
        Prevalence of cerebral palsy in 8-year-old children in three areas of United States in 2002: a multisite collaboration.
        Pediatrics. 2008; 121: 547-554
        • Aragao M.F.
        • Brainer-Lima A.M.
        • Holanda A.C.
        • van der Linden V.
        • Aragao L.V.
        • Silva Junior M.L.
        • et al.
        Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.
        Am J Neuroradiol. 2017; 38: 1045-1053
        • Neymotin S.A.
        • Dura-Bernal S.
        • Lakatos P.
        • Sanger T.D.
        • Lytton W.W.
        Multitarget multiscale simulation for pharmacological treatment of dystonia in motor cortex.
        Front Pharmacol. 2016; 7: 157https://doi.org/10.3389/fphar.2016.00157
        • Jinnah H.A.
        • Hess E.J.
        A new twist on the anatomy of dystonia: the basal ganglia and the cerebellum?.
        Neurology. 2006; 67: 1740-1741
        • Neychev V.K.
        • Fan X.
        • Mitev V.
        • Hess E.J.
        • Jinnah H.A.
        The basal ganglia and cerebellum in the expression of dystonic movement.
        Brain. 2008; 131: 2499-2509
        • Rasmussen S.A.
        • Jamieson D.J.
        • Honein M.A.
        • Etersen L.R.
        Zika virus and birth defects. Reviewing the evidence for causality.
        N Engl J Med. 2016; 374: 1981-1987
        • Dang J.
        • Tiwari S.K.
        • Lichinchi G.
        • Qyn Y.
        • Patil V.S.
        • Eroshkin A.M.
        • et al.
        Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3.
        Cell Stem Cell. 2016; 19: 258-265
        • Franki I.
        • Mailleux L.
        • Emsell L.
        • Peedima M.J.
        • Fehrenbach A.
        • Feys H.
        • et al.
        The relationship between neuroimaging and motor outcome in children with cerebral palsy: a systematic review – Part A. Structure imaging.
        Res Rev Disabil. 2020; 16103606
        • Cameron N.
        • Gormley Jr, M.
        • Deshpande S.
        Severity of disability in patients with cerebral palsy secondary to symptomatic congenital cytomegalovirus encephalopathy.
        J Ped Rehab Med. 2013; 6: 241-244
        • van der Linden Jr H.
        • Carvalho M.
        • van der Linden V.
        • Lacerda K.M.
        • Pessoa A.
        • Carneiro M.L.
        • et al.
        Epilepsy profile in children with congenital Zika virus infection.
        N Eng J Med. 2018; 379: 891-892
        • Nahm N.J.
        • Graham H.K.
        • Gormley Jr, M.E.
        • Georgiadis A.G.
        Management of hypertonia in cerebral palsy.
        Curr Opin Pediatr. 2018; 30: 57-64
        • Stewart K.
        • Harvey A.
        • Johnston L.
        A systematic review of scales to measure dystonia and choreoathetosis in children with dyskinetic cerebral palsy.
        Dev Med Child Neurol. 2017; 59: 786-795