Dados do Trabalho

Título

BOTULINUM TOXIN TYPE A AS A TREATMENT OPTION OF CERVICAL DYSTONIA IN CACNA1A DISORDER: A SAFE CHOICE

Introdução

10-year-old girl presents with global developmental delay, beginning at 4 months of age with episodes of upward tonic eye deviation, which were later associated with intermittent dystonia in the hands and cephalic region after 1 year of age, initially confused with epileptic events and treated unsucessfully. After 2.5 year-old, she experienced focal motor seizures with impaired awareness and a prior event of focal status epilepticus treated in the ICU, with no new seizures since the age of 7. At the admission in our service, she presented with choreoathetosis, orolingual dyskinesia and head version to the left in a dystonic pattern. Brain MRI was normal. An epilepsy panel revealed a pathogenic heterozygous variant in the CACNA1A gene. In follow-up, medications for extrapyramidal symptoms were optimized, though with poor response. Later, botulinum toxin type A (BTX-A) was administered for cervical dystonia, with the family choosing to continue the treatment due to the excellent response.

Objetivo

Demonstrate that the application of BTX-A should be included in the therapeutic arsenal for childhood-onset dystonias as a safe and effective option, even for those of genetic origin

Método

Case report and literature review

Resultados

Clinical spectrum disorders related with the CACNA1A gene have expanded in the last years. Pathogenic variants of this gene have been associated with developmental delay, epilepsy, paroxysmal dystonia, neuropsychiatric disorders and other disorders. Seizures usually beginning in the first year of life, although our patient had her first seizure after that and the first clinical findings were confused with epileptic events. CACNA1A disorders may also feature dystonic symptoms, with some typical age-specific patterns. We can observe the occurrence of transient episodes of cervical dystonia and the paroxysmal tonic upward gaze, but both are rare and the attacks usually remit spontaneously within 3–5 years of age. Our patient, however, continued to present both after this limit age, specially the cervical dystonic episodes. The administration of BTX-A is a well established therapeutic option for dystonia and in this case represented a dramatic change in symptoms control. The positive effect noticed in controling dystonia lasted around 5 months, with a sporadic recurrence between applications.

Conclusão

This case shows that botulinum toxin is a good therapeutic option in segmental dystonias, even if it is a genetically determined one.

Referências

1. Indelicato E, Boesch S. From Genotype to Phenotype: Expanding the Clinical Spectrum of CACNA1A Variants in the Era of Next Generation Sequencing. Front Neurol. 2021 Mar 2;12:639994. doi: 10.3389/fneur.2021.639994. PMID: 33737904; PMCID: PMC7960780.
2. Lipman AR, Fan X, Shen Y, Chung WK. Clinical and genetic characterization of CACNA1A-related disease. Clin Genet. 2022 Oct;102(4):288-295. doi: 10.1111/cge.14180. Epub 2022 Jun 26. PMID: 35722745; PMCID: PMC9458680.
3. Kessi M, Chen B, Pang N, Yang L, Peng J, He F, Yin F. The genotype-phenotype correlations of the CACNA1A-related neurodevelopmental disorders: a small case series and literature reviews. Front Mol Neurosci. 2023 Jul 24;16:1222321. doi: 10.3389/fnmol.2023.1222321. PMID: 37555011; PMCID: PMC10406136.
4. Erro R, Picillo M, Pellecchia MT, Barone P. Improving the Efficacy of Botulinum Toxin for Cervical Dystonia: A Scoping Review. Toxins (Basel). 2023 Jun 9;15(6):391. doi: 10.3390/toxins15060391. PMID: 37368692; PMCID: PMC10302246.

Palavras Chave

BOTULINUM TOXIN TYPE A; CERVICAL DYSTONIA; CACNA1A