Dados do Trabalho

Título

ACUTE ENCEPHALOPATHY AND BRAIN ABNORMALITIES ON MAGNETIC RESONANCE IMAGING DURING COMBINATION THERAPY WITH ADRENOCORTICOTROPIC HORMONE AND VIGABATRIN FOR INFANTILE SPASMS

Apresentação do caso

A 11-month-old female patient with Trisomy 21 (Down Syndrome) who developed infantile spasms at 6-months-old. She was diagnosed with West Syndrome and firstly treated with Vigabatrin (VGB). A positive response was observed, with control of the spams and regression of hypsarrhythmia at the electroencephalogram register. She was well controlled until 10-months-old, when the spasms returned with developmental regression. A treatment with synthetic adrenocorticotropic hormone (ACTH) was started in a low-dose, but with partial control of the spasms. It was decided to increase the dose of the ACTH and we observed regression of spasms and recovery of developmental milestones. An oral corticosteroid withdrawal was maintained.
She evolved drowsiness, diarrhea, tachycardia, hypotension and abnormal movements, characterized by sudden limb movements (ballismus) and chorea on the face. A treatment for sepsis was initiated, with improvement in laboratory parameters and hypotension, but she persisted with encephalopathy, abnormal movements, paroxysmal tachycardia and diarrhea. A cranial tomography (CT) was performed, showing a symmetrical and bilateral image of hypoattenuation in the basal nuclei. All the clinical abnormalities stopped after withdrawing the VGB. Magnetic Resonance Imaging (MRI) findings showed T2/FLAIR hypersignal in basal nuclei with diffusion restriction.

Discussão

VGB, ACTH and prednisone are first-line treatments for IS. Benefits from the use of combination VGB and hormonal therapy are already established. Acute encephalopathy with extrapyramidal symptoms, dysautonomic features and vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) has been reported after the use of combination-therapy for IS.
Asymptomatic VABAM is common and appears to be associated with the use of higher doses of VGB. Main locations for MRI abnormalities included globi pallidi, brainstem, followed by thalami and dentate nuclei. MRI abnormalities usually to be resolved following VGB discontinuation, in a mean interval of 3 months.
A literature review supports increased risk of fulminant, symptomatic VABAM in patients receiving VGB in association with hormonal therapy. Patients with Trisomy 21 seem to be particularly sensible to evolve it.

Comentários finais

This report and review raise concerns regarding the safety of combination therapy with adrenocorticotropic hormone and Vigabatrin for Infantile Spasms, mainly in Trisomy 21 patients.

Referências (se houver)

Bhalla S, Skjei K. Fulminant vigabatrin toxicity during combination therapy with adrenocorticotropic hormone for infantile spasms: Three cases and review of the literature. Epilepsia. 2020 Oct;61(10):e159-e164. doi: 10.1111/epi.16663. Epub 2020 Sep 17. PMID: 32944947.

Reyes Valenzuela G, Crespo A, Princich J, Fassulo L, Semprino M, Gallo A, Rugilo C, Pociecha J, Calvo A, Caraballo RH. Vigabatrin-associated brain abnormalities on MRI and other neurological symptoms in patients with West syndrome. Epilepsy Behav. 2022 Apr;129:108606. doi: 10.1016/j.yebeh.2022.108606. Epub 2022 Feb 15. PMID: 35180571.

Hussain SA, Tsao J, Li M, Schwarz MD, Zhou R, Wu JY, Salamon N, Sankar R. Risk of vigabatrin-associated brain abnormalities on MRI in the treatment of infantile spasms is dose-dependent. Epilepsia. 2017 Apr;58(4):674-682. doi: 10.1111/epi.13712. Epub 2017 Feb 23. PMID: 28230253.

Lotan E, Bluvstein J, Zan E. Vigabatrin Toxicity in a Patient with Infantile Spasms Treated with Concomitant Hormonal Therapy. Isr Med Assoc J. 2020 Jul;22(7):461-462. PMID: 33236576.

Hernández Vega Y, Kaliakatsos M, U-King-Im JM, Lascelles K, Lim M. Reversible vigabatrin-induced life-threatening encephalopathy. JAMA Neurol. 2014 Jan;71(1):108-9. doi: 10.1001/jamaneurol.2013.1858. PMID: 24247994.

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