A Brazilian SCN8A-related Epilepsy Cohort
Abstract number :
2.14
Submission category :
4. Clinical Epilepsy / 4B. Clinical Diagnosis
Year :
2023
Submission ID :
759
Source :
www.aesnet.org
Presentation date :
12/3/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Cristine Cukiert, MD MsC – Clinica Cukiert
Vanessa Cristina Lessa, MD – Clinica Cukiert; Julia Vieira, MD – Clinica Cukiert; João Palo Oliveira, MD – Clinica Cukiert; José Burattini, MD – Clinica Cukiert; Rafael Guimaraes, MD – Clinica Cukiert; Arthur Cukiert, PhD MsC MD – Clinica Cukiert
Rationale: SCN8A-related epilepsy or neurodevelopmental disorder is an autosomal dominant disease with a spectrum of phenotypes that includes a wide range of developmental delays, including epileptic encephalopathy (DEE) and pharmacoresistant epilepsy. Other clinical features such as motor, movement, and language abnormalities can occur. The diagnosis is made by genetic testing, being related to a heterozygous pathogenic variant (or likely pathogenic) in SCN8A. Individuals with more severe phenotypes are more likely to have a de novo mutation. Brain MRI is usually normal and EEG may be normal or exhibit focal or multifocal epileptiform activity. Treatment differs from similar disorders having a more favorable response to sodium channel blockers. Our goal was to evaluate the characteristics and management of this disease in Brazil.
Methods: Affected individuals were recruited through a network of collaborating parents. Based on the available information, we analyzed epidemiological, clinical, and therapeutic data.
Results: We recruited twenty four patients. The average age at seizure onset was two to three months and at genetic testing was 33 and 2 months. The most predominant phenotype was DEE with severe developmental delay and pharmacoresistance (50%), followed by DEE with mild to moderate developmental delay and partial response to medical treatment (29,1%) and neurodevelopmental delay with generalized epilepsy (20,8%). The main clinical findings were hypotonia (71%) and ataxia (52,9%). One third of the cohort developed status epilepticus (37,5%) at some point. All patients had bilateral generalized tonic-clonic seizures and tried at least five distinct antiseizure medications (ASM), including at least one sodium channel blocker. The average dosage (mg/kg) of sodium channel blockers which showed a good response regarding seizures was 40,7 for oxcarbazepine, 41,7 for carbamazepine, 11 for lacosamide, 9,6 for phenytoin and 7 for lamotrigine. Two patients became seizure free (8,3%). A total of 13 patients had worsening of seizures during medical treatment under levetiracetam (76,9%) or topiramate(30,7%). Five patients have VNS (20,8%) and seventeen used cannabidiol (70,8%). All of them reported some improvement in seizure control.
Conclusions: SCN8A mutation is a rare cause of epilepsy. Its unique therapeutic management makes it crucial to identify it as early as possible. It would be relevant to recognize its clinical profile to adequately address the need for genetic testing and try to bridge the treatment gap for the disease.
Funding: None
Clinical Epilepsy