RESUMEN
BACKGROUND: Mutations in the ATP1A3 gene are known to be the cause of three distinct neurological syndromes including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP) and cerebellar ataxia, arefexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS). Recent studies have suggested the broader diversity of ATP1A3-related disorders. This study aimed to investigate the clinical spectrum in patients carrying causative mutations within the ATP1A3 gene. METHOD: The medical histories of nine unrelated patients with diverse phenotypes harboring variants in ATP1A3 were retrospectively analyzed after they were referred to a tertiary epilepsy center in one of the two different health care systems (Germany or Thailand). Clinical features, neurophysiological data, imaging results, genetic characteristics and treatments were reviewed. RESULTS: Three patients harbor novel mutations in the ATP1A3 gene. Atypical clinical features and imaging findings were observed in two cases, one with hemiplegia-hemiconvulsion-epilepsy syndrome, and the other with neurodegeneration with brain iron accumulation. All nine patients presented with intellectual impairment. Alternating hemiplegia of childhood (AHC) was the most common phenotype (67%). Flunarizine and topiramate led to symptom reduction in 83% and 25% of AHC cases administered, respectively. CONCLUSION: The present case series expands the clinical and genetic spectrum of ATP1A3-related disorders.
Asunto(s)
Mutación , Enfermedades del Sistema Nervioso/genética , Fenotipo , ATPasa Intercambiadora de Sodio-Potasio/genética , Adolescente , Niño , Trastornos Distónicos/diagnóstico , Trastornos Distónicos/genética , Electroencefalografía , Femenino , Hemiplejía/diagnóstico , Hemiplejía/genética , Humanos , Masculino , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Neuroimagen , Adulto JovenRESUMEN
ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients' anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.
Asunto(s)
Epilepsia/genética , Hemiplejía/genética , ATPasa Intercambiadora de Sodio-Potasio , Adulto , Anticonvulsivantes/uso terapéutico , Ataxia Cerebelosa/genética , Niño , Trastornos Distónicos , Epilepsia/dietoterapia , Epilepsia/tratamiento farmacológico , Femenino , Pérdida Auditiva Sensorineural , Hemiplejía/dietoterapia , Hemiplejía/tratamiento farmacológico , Humanos , Levetiracetam , Masculino , Mutación , Atrofia Óptica/genética , Reflejo Anormal , Estudios Retrospectivos , Convulsiones/genética , Topiramato , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: Anti-NMDAR encephalitis is an acute autoimmune neurological disorder that is increasingly recognized in pediatric populations. Several studies of the disorder have been conducted worldwide but there are few publications in Thailand. Here, we describe the clinical manifestations, treatment outcomes, and prognostic factors in children with anti-NMDAR encephalitis. METHODS: Between January 2007 and September 2017, we conducted a retrospective/prospective cohort study of children diagnosed with anti-NMDAR encephalitis from three tertiary care hospitals in Thailand: King Chulalongkorn Memorial Hospital, Chonburi Hospital, and Prapokklao Hospital. We assessed the Modified Rankin Score (mRS) score for each participant to measure severity of disease and treatment outcome at baseline, 12, and 24â¯months. RESULTS: We recruited 14 participants (1-13â¯years with median age 8.4â¯years). Participants were followed up for a median of 20.5â¯months. Clinical manifestations included behavioral dysfunction (100%), movement disorder (93%), speech disorder (79%), sleep disorder (79%), and seizures (79%). All patients received first-line immunotherapy (corticosteroids: 100%, intravenous immunoglobulin: 79%, plasma exchange: 21%). Second-line immunotherapy (cyclophosphamide) was administered to 57% of patients. During the first 12â¯months, 8 patients (62%) achieved a good outcome (mRSâ¯≤â¯2). At 24â¯months, 9 patients (81%) had achieved a good outcome. Altered consciousness and central hypoventilation were predictors of poor outcome. (pâ¯<â¯0.05). CONCLUSIONS: We observed similar clinical manifestation of anti-NMDAR encephalitis in Thai children to those reported in other countries. Furthermore, the percentage of patients with good outcomes in our study was comparable with previous studies. Further studies are required to investigate other populations in other regions of Thailand.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/fisiopatología , Inmunoterapia/métodos , Resultado del Tratamiento , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Centros de Atención Terciaria , TailandiaRESUMEN
Phenytoin is one of the most well established and most effective antiepileptic medications for the treatment of focal seizures. In our clinical practice, it has proven difficult to maintain therapeutic phenytoin levels in infants less than three months of age. Incidence of phenytoin toxicity in infants is very rare. The cytochrome P450 super family plays an important role in phenytoin metabolism, especially CYP2C9 and CYP2C19. In this case report, we profiled a two-month-old Thai infant who developed phenytoin toxicity resulting from CYP2C9 gene polymorphism.