Doença de Unverricht-Lundborg: Enfrentando os Desafios de um Quadro Clínico Complexo
DOI:
https://doi.org/10.46531/sinapse/CC/220078/2023Palavras-chave:
Criança, Síndrome Unverricht-LundborgResumo
A doença de Unverricht-Lundborg, também chamada de epilepsia mioclónica progressiva tipo 1, é caracterizada por mioclonias induzidas por estímulo e crises epiléticas sem défice cognitivo progressivo importante, geralmente apresentando-se no final da infância e início da adolescência. É uma doença de hereditariedade autossómica recessiva e, até ao momento, foram descritas variantes patogénicas causadoras da doença apenas no gene que codifica a cistatina B (CSTB). Descrevemos o caso de um menino de 9 anos que começou por apresentar crises tónico-clónicas generalizadas e desenvolveu eventos mioclónicos paroxísticos progressivamente, ao longo de vários anos. Foi submetido a tratamento com fármacos anti-crise epilética, mas a progressão da doença ao longo do tempo resultou em várias mudanças no esquema terapêutico, com respostas clínicas altamente variáveis. O estudo genético identificou a variante patogénica c.67-1G>C p.(?) em heterozigotia no gene CSTB, após se ter identificado a típica expansão dodecamérica no outro alelo, confirmando o diagnóstico de ULD.Downloads
Referências
Knupp K, Wirrell E. Progressive myoclonic epilepsies – It takes a village to make a diagnosis. Neurology. 2014;82:378379. doi: 10.1212/WNL.0000000000000091
Hosny H, El Tamawy M, Gouider R, Lesca G, Abdel Naseer M, Kishk N, et al. Clinical and molecular characterization of Unverricht-Lundborg disease among Egyptian patients. Epilepsy Res. 2021;176:106746. doi: 10.1016/j.eplepsyres.2021.106746.
de Haan GJ, Halley DJ, Doelman JC, Geesink HH, Augustijn PB, Jager-Jongkind AD, et al. Univerricht-Lundborg disease: underdiagnosed in the Netherlands. Epilepsia. 2004;45:1061-3. doi: 10.1111/j.0013-9580.2004.43703.x.
Kälviäinen R, Khyuppenen J, Koskenkorva P, Eriksson K, Vanninen R, Mervaala E. Clinical picture of EPM1-Unverricht-Lundborg disease. Epilepsia. 2008;49:549-56. doi:10.1111/j.1528-1167.2008.01546.x.
Lasek-Bal A, Lukasik M, Zak A, Sulek A, Bosak M. Unverricht-Lundborg disease: Clinical course and seizure management based on the experience of polish centers. Seizure. 2019;69:87-91. doi: 10.1016/j.seizure.2019.04.008.
Holmes GL. Drug Treatment of Progressive Myoclonic Epilepsy. Paediatr Drugs. 2020;22:149-64. doi: 10.1007/s40272-019-00378-y.
Hyppönen J, Äikiä M, Joensuu T, Julkunen P, Danner N, Koskenkorva P, et al. Refining the phenotype of Unverricht-Lundborg disease (EPM1): a population-wide Finnish study. Neurology. 2015;84:1529-36. doi: 10.1212/WNL.0000000000001466.
Magaudda A, Ferlazzo E, Nguyen VH, Genton P. UnverrichtLundborg disease, a condition with self-limited progression: long-term follow-up of 20 patients. Epilepsia. 2006;47:8606. doi: 10.1111/j.1528-1167.2006.00553.x.
Lalioti MD, Scott HS, Genton P, Grid D, Ouazzani R, M’Rabet A, et al. A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset. Am J Hum Genet. 1998;62:842-7. doi: 10.1086/301798.
Kyllerman M, Sommerfelt K, Hedström A, Wennergren G, Holmgren D. Clinical and neurophysiological development of Unverricht-Lundborg disease in four Swedish siblings. Epilepsia. 1991;32:900-9. doi: 10.1111/j.1528-1157.1991.tb05549.x.
Mohamadpour M, Gabriel G, Grant AC. A Native Haitian Woman with Unverricht-Lundborg Disease. Case Rep Neurol. 2017;9:284-8. doi: 10.1159/000484136.
Genton P, Delgado Escueta A, Serratosa JM, Michelucci R, Bureau M. Progressive myoclonus epilepsies. In: Bureau M, Genton P, Delgado Escueta A, Dravet C, Tassinari CA, Thomas , et al, editors. Epileptic Syndromes in Infancy, Childhood and Adolescence. 5th ed. London: John Libbey Eurotext Ltd; 2012. p.575-606.
Segal E, Vendrame M, Gregas M, Loddenkemper T, Kothare SV. Effect of treatment of obstructive sleep apnea on seizure outcomes in children with epilepsy. Pediatr Neurol. 2012;46:359-62. doi: 10.1016/j.pediatrneurol.2012.03.005.
Lanzone J, Ricci L, Tombini M, Boscarino M, Mecarelli O, Pulitano P, et al. The effect of Perampanel on EEG spectral power and connectivity in patients with focal epilepsy. Clin Neurophysiol. 2021;132:2176-83. doi: 10.1016/j.clinph.2021.05.026.
Crespel A, Ferlazzo E, Franceschetti S, Genton P, Gouider R, Kälviäinen R, et al. Unverricht-Lundborg disease. Epileptic Disord. 2016;18:28-37. doi: 10.1684/epd.2016.0841.
Edwards MJ, Hargreaves IP, Heales SJR, Jones SJ, Ramachandran V, Bhatia KP, et al. N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects. Neurology. 2002;59:1447-9. doi: 10.1212/wnl.59.9.1447.
Tallarico M, Leo A, Guarnieri L, Zito MC, De Caro C, Nicoletti F, et al. N-acetylcysteine aggravates seizures while improving depressive-like and cognitive impairment comorbidities in the WAG/Rij rat model of absence epilepsy. Mol Neurobiol. 2022;59:2702-14. doi: 10.1007/s12035-02102720-3.
Smith B, Shatz R, Elisevich K, Bespalova IN, Burmeister M. Effects of vagus nerve stimulation on progressive myoclonus epilepsy of Unverricht-Lundborg type. Epilepsia. 2000;41:1046-8. doi: 10.1111/j.1528-1157.2000.tb00293.x.
Khiari HM, Franceschetti S, Jovic N, Mrabet A, Genton P. Death in Unverricht-Lundborg disease. Neurol Sci. 2009;30:315-8. doi: 10.1007/s10072-009-0102-2.
Franceschetti S, Michelucci R, Canafoglia L, Striano P, Gambardella A, Magaudda A, et al. Progressive myoclonic epilepsies: definitive and still undetermined causes. Neurology. 2014;82:405-11. doi: 10.1212/WNL.0000000000000077.
