ABSTRACT
OBJECTIVE: PCDH19-related epilepsy occurs predominantly in girls and is caused by pathogenic variant of the protocadherin-19 gene. The initial seizures usually develop in association with fever, begin on average at 15 months of age, and often occur in clusters. Autistic symptoms, intellectual disability, and sleep disturbance are often associated. METHODS: In our retrospective, multicenter study, we reviewed clinical data of nine children with epilepsy genetically confirmed to be associated with PCDH19. RESULTS: In the Hungarian patient population aged 0-18 years, the prevalence of PCDH19-related epilepsy was found to be lower (1/100000 live births in females) than the reported international data (4-5/100000 live births in females). Four of our nine patients had positive family history of epilepsy (cousins, sister, and mother). We assessed brain anomalies in three patients (in one patient focal cortical dysplasia and left anterior cingulate dysgenesis, and in two children right or left hippocampal sclerosis) and in another three cases incidentally identified benign alterations on brain MRI were found. The first seizure presented as a cluster in seven out of nine children. In seven out of nine cases occurred status epilepticus. Six out of nine children had autistic symptoms and only one child had normal intellectual development. Seven of our patients were seizure free with combined antiseizure medication (ASM). The most effective ASMs were levetiracetam, valproate, and clobazam. SIGNIFICANCE: The prevalence of PCDH19-related epilepsy is presumably underestimated because of the lack of widely performed molecular genetic evaluations. Molecular genetic testing including PCDH19 pathogenic variants is recommended for female patients with an onset of seizures before the age of 3 years.
ABSTRACT
In our review we discuss the group of approved antiepileptic drugs for children in Hungary. We cite the results of the review conducted by the International League Against Epilepsy on antiepileptic drug efficacy and effectiveness as initial monotherapy for newly diagnosed epileptic seizures and syndromes in pediatric age group. 25% of pediatric epilepsy is therapy resistant, so we further need new drugs, which must be investigated according to the rules of the European Medicine Agency. The ethical dilemmas of childhood drug studies lead to the situation that the new antiepileptic drugs, approved as monotherapy in adult epilepsies, are in the majority just in add-on regimen tested in pediatric patients. As clinicians we appreciate open label extension safety studies. An old-new antiepileptic drug in Europe is zonisamide. Though it was approved for first line monotherapy in pediatric and adult patients with partial and generalised epilepsy in 1989 in Japan, the European Medicine Agency licensed its use as adjunctive therapy in children aged 6 years or older with partial seizures (with or without secondary generalisation) just in 2013. The results of the openlabel extension study appeared in 2014. The mean dose received was 7.5 mg/kg/day. During the open label phase 11% of the patients achieved seizure freedom and it was maintained throughout the study. The drug was generally well tolerated. The most frequently reported treatment-related adverse events were decreased weight (6%), decreased appetite (4%), and headache (2%). No new or unexpected side effects emerged. In conclusion oral zonisamide as adjunctive therapy in pediatric patients aged 6-17 years with partial seizures demonstrated an acceptable safety and tolerability profile and efficacy over a period at least 1 year. So it is a good treatment option in this population.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsies, Partial/drug therapy , Isoxazoles/therapeutic use , Adolescent , Child , Female , Humans , Male , ZonisamideABSTRACT
OBJECTIVES: Otogenic lateral sinus thrombosis is a rare complication of acute otitis media whose clinical presentation has changed with the early use of antibiotics. The aim of this study was to analyze the changing clinical signs, vaccination status, therapeutic management and outcome of these patients. METHODS: Retrospective chart review of 10 children treated with otogenic lateral sinus thrombosis in a tertiary level teaching hospital in Budapest, Hungary, from January 1998 till August 2013. RESULTS: Patients were divided into Early and Late presenting groups. In the Early presenting group, sepsis developed within one week after the onset of acute otitis media. At admission otological symptoms were predominant. The Late presenting group experienced acute otitis media several weeks prior to presentation and in this group neurologic symptoms dominated the clinical picture at admission. All patients received antibiotics. Eight of them were also treated with low molecular weight heparin. All children underwent cortical mastoidectomy. After surgery, the clinical signs of elevated intracranial pressure transiently worsened. This manifested as progression of papilledema in seven children, causing severe visual disturbance in two cases. After medical treatment and serial lumbar punctures all patients except one recovered. This child has permanent visual acuity failure of 0.5D unilaterally. At one year follow up complete and partial recanalization were noted in five and two patients, respectively. CONCLUSIONS: After mastoidectomy the signs of elevated intracranial pressure can transiently worsen, papilledema can progress. Daily bedside monitoring of visual acuity and regular ophthalmoscopy with neurologic examination is recommended during hospitalization. Close follow up is advised up to one year. When the dominant sinus is occluded, the clinical scenario is more protracted and severe.
