Our clinical experience with zonisamide in resistant generalized epilepsy syndromes.

PURPOSE: Zonisamide is licensed in the European Union for adjunctive therapy for partial epilepsy, but its efficacy in generalized epilepsy was less explored. METHODS: This prospective observational study included 47 patients (mean age 29 years, range 3-50) with different resistant generalized epilepsy syndromes: idiopathic generalized syndromes (IGE) 15 patients, (juvenile myoclonic epilepsy four, absence epilepsy four, myoclonic absence two, unclassified IGE five), progressive myoclonic epilepsy type 1 (PME1) four, severe myoclonic epilepsy of infancy (SMEI) three, borderline SMEI three, Lennox-Gastaut syndrome/secondary generalized epileptic encephalopties 23 patients. All patients were followed up for at least six months. The mean dose given was 367 mg/day (range 100-600 mg/day), the patients received at least one and no more than two concomitant AE. Response was defined as more than 50% seizure reduction or seizure freedom. RESULTS: The best effect was achieved in PME one, all the patients were responders. Myoclonic seizures were reduced 80%, none of the patients had generalized tonic clonic (GTC) seizures. In two of the four patients all other antiepileptics were tapered of (including piracetam), so they were GTC seizure and almost myoclonia free on zonisamide only. Responder rates were in GEFS +/- SME 62.5%, in resistant IGE 62.5%, and in epileptic encephalopathies 33.3% patients. Tolerance after initial efficacy developed in six patients. Adverse effects were mild: weight loss, somnolence and confusion were repeatedly reported. Three patients reported cognitive improvement. CONCLUSION: Clinical benefit of a broad spectrum antiepileptic zonisamide extends across seizure types, ages and epilepsy syndromes. The efficacy in PME proved to be excellent.

[Surgical treatment of resistant epilepsy, caused by hemispherical dysgenesis--case report]. / Hemisphaerialis dysgenesis okozta rezisztens epilepszia mûtéti kezelése--esetismertetés.

A part of patients with the therapy resistant epilepsy can be cured by surgical interventions. The more concordant the presurgical evaluation data, the better prognosis the patient has postoperatively. In case of discordant examination data, multimodal evaluation or case-specific decision might be successful. We report on a five-year-old boy with bilateral (left-dominated) cortical dysplasia and therapy resistant epilepsy. The ictal EEG did not help to localize the seizure onset zone, semiology had little lateralization value; however, FDG-PET showed left hemispheric hypermetabolism. The child became almost seizure-free and showed improved development after left-sided hemispherotomy.

[Devastating epileptic encephalopathy-pseudoencephalitis: the new type of catastrophe epilepsy in our department]. / Pusztító epilepsziás encephalopathia- pseudoencephalitis a katasztrófaepilepsziák uj alcsoportjának elofordulása osztályunk betegei között.

PURPOSE: Analysis of history of our five patients with intractable epilepsy whose illness have begun with prolonged status epilepticus (SE) and high-grade fever of unknown cause. METHODS: Retrospective study analysis of selected five intractable epileptic patients at a median age of 11.5 (8-14) years. RESULTS: All children had normal development before epilepsy begun. Intractable SE lasted 3-10 (median seven) days by four patients and three months by one patient. The cause of illness was unknown at the beginning and the MRI were normal. Intractable epilepsy followed the SE in all cases without any latent period. Follow-up of the children was 3-15 (median 9.5) years. The seizures came continually with few-day-long breaks, antiepileptic drugs were ineffective. Semiology of seizures, EEG, and functional imaging examinations (PET, SPECT) referred to temporal and frontal lobe damages. Later on, the MR images showed hippocampal sclerosis in one patient and mild generalized brain atrophy in the others. During the years, cognitive deterioration and behavioral problems have been realized. The most severe patient developed tetraparesis, fell in vigil coma and died after five years. CONCLUSIONS: The symptoms of our patients fulfilled the criteria of devastating epileptic encephalopathy in school-aged children.

[Clinical and genetic diagnosis of Dravet syndrome: report of 20 cases]. / A dravet-szindróma klinikai es genetikai diagnosztikájáról husz esetünk kapcsán.

OBJECTIVE AND BACKGROUND: Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by prolonged febrile hemiconvulsions or generalized seizures starting in the first year of life. Later on myoclonic, atypical absence, and complex partial seizures appear. When one of these seizure forms is lacking the syndrome of borderline SMEI (SMEB) is defined. Psychomotor delay resulting in mental retardation is observed during the second year of life. In most patients a de novo sodium channel alpha-1 subunit (SCN1A) mutation can be identified. By reviewing the clinical, laboratory, and neuroimaging data of our SMEI patients diagnosed between 2000 and 2008, we would like to share our experiences in this rare but challenging syndrome. Our results will facilitate the earlier and better diagnosis of Hungarian children with SMEI. PATIENTS AND METHODS: Clinical, EEG, MRI and DNA mutation data of 20 SMEI patients treated in the Bethesda Children's Hospital (Budapest) were reviewed. RESULTS: The first seizure appeared at age 6.3+/-3.0 months. At least one of the first two seizures were complex febrile seizures in 19/20 and unilateral seizures in 12/20 children. All children except for one showed hemiconvulsions at least once; all children had seizures lasting longer than 15 minutes. Eight of twenty patients had SMEB. DNA diagnostics identified an SCN1A mutation in 17 patients (6 missense, 4 nonsense, 4 frameshift, 2 splice site, 1 deletion) while 3 children had no mutation. CONCLUSION: Early diagnosis of SMEI is important for the avoiding unnecessary examinations and false therapies as well as for genetic counselling. Typical symptoms of SMEI are early and prolonged febrile hemiconvulsions with neurological symptoms, mental retardation and secondary seizure types later on. The presence of an SCN1A mutation supports the diagnosis. We propose the availability of molecular diagnostics and stiripentol therapy for SMEI children in Hungary

[Congenital cataracts facial dysmorphism neuropathy syndrome--first Hungarian case report]. / Congenitalis cataracta facialis dysmorphismus neuropathia szindróma--elso magyarországi közlés.

The congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is a recently described autosomal recessive developmental disorder. It is almost completely restricted to an endogamous group of the European Vlax Roma population, called the Rudari. The CCFDN syndrome is a complex phenotype involving multiple systems, characterized by facial dysmorphism, congenital cataracts, microcorneae, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, and serious complications related to general anaesthesia. This disorder is caused by a homozygous mutation of the carboxy-terminal domain phosphatase 1 (CTDP1) gene, localized to the 18q23 region. Authors present one genetically identified case in a large Roma family. The case documents that the CCFDN mutation is present also in the Hungarian Roma population. Underlie of antropomorphological data the authors presume that the CCFDN mutation reached Hungary as a result of emigration of Vlax Gypsies in the 18th century. The paper calls attention to the fact that molecular genetic diagnostics can replace invasive methods and makes possible the identification of heterozygotes without clinical symptoms. The introduction of the genetic screening enables us to perform genetic counselling and prevention in this high-risk population.

[Experience with levetiracetam in childhood epilepsy]. / Tapasztalatok a levetiracetamkezeléssel gyermekkori epilepsziákban.

OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam in children with drug resistant epilepsy from a retrospective study. METHODS: We report the result of a study of 85 pediatric patients (mean 10.5 years, range: 1-24) with refractory generalized and focal epilepsy, who received levetiracetam as add-on treatment. The average duration of epilepsy was eight years, and the patient were treated with mean of 6.0 antiepileptic drugs before levetiracetam was introduced. RESULTS: Ten patients (12%) became seizure-free, three (3%) responded with seizure reduction of more than 90%, 32 (38%) responded with seizure reduction of more than 50% following introduction of levetiracetam. No response to levetiracetam was reported in 34% (n: 29). Positive psychotropic effect was observed in 26 patient (30%). Mild to moderate side effects were reported in 11 patients (13%), consisting most frequently general behavioral changes, aggression, sleep disturbances, but they ceased after decreasing the dose of levetiracetam. Mental retardation was associated with poor response and associated with more side effects. CONCLUSION: Levetiracetam is a well tolerated new antiepileptic drug that may effectively improve seizures control as an add-on drug in resistant epilepsy in childhood with good tolerability.

Hippocampal sclerosis in severe myoclonic epilepsy in infancy: a retrospective MRI study.

PURPOSE: Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by early prolonged febrile convulsions (PFCs) with secondary psychomotor delay and a variety of therapy-resistant seizures. Although the initial symptoms are repeated PFCs, the MRI performed at the onset of disease shows no hippocampal structural abnormalities. We aimed to assess clinical and serial MRI data of patients with SMEI with a special attention to the temporomedial structures. To our knowledge, this is the first systematic MRI study in this disease. METHODS: Clinical and MRI data of all SMEI patients treated in our hospitals between 1996 and 2004 were reviewed. RESULTS: Twenty-eight MRIs from 14 children (one to four images/patient) were included. Age at disease onset was between 3 and 9 months; age at initial MRI was 5 months to 13 years. Ten of 14 patients showed hippocampal sclerosis (HS) during the course of the disease (nine unilateral, one bilateral). Six of these 10 had a normal initial MRI. Age at the first verified HS was between 14 months and 13 years. Neither complex partial seizures nor anterior temporal irritative zone was recorded in these children. CONCLUSIONS: After initially normal structures, in most patients with SMEI, HS develops several months or years after the first PFC. These data support the hypothesis that PFC might be responsible for HS, but other factors and individual sensitivity should play a role in this process.

Comparative evaluation of concomitant structural and functional neuroimages in Rasmussen's encephalitis.

BACKGROUND AND PURPOSE: Rasmussen's encephalitis (RE) is a rare condition of unknown cause characterized by intractable seizures, progressive hemiparesis, mental impairment, and inflammatory histological findings in the cortex. The primary diagnosis is based on biopsy to confirm the typical clinical, electroencephalography, and brain imaging findings. The main objective of this study was to compare simultaneous structural and functional neuroimages in RE. METHODS: Concomitant magnetic resonance imaging and 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography data from the authors' series of 5 children and 8 patients described in the literature were analyzed and compared. RESULTS: Typical early findings of RE include metabolic abnormalities (hypermetabolism and hypometabolism) starting in the frontal or temporal regions or, occasionally, involving the whole hemisphere. Focal abnormalities of cerebral glucose metabolism indicate lesions sooner and depict their extent better than concomitant magnetic resonance images. The major structural abnormality remains unilateral; however, contralateral frontal lobe hypometabolism or crossed cerebellar diaschisis can be a finding of this disease. Basal ganglia involvement and whole hemispheric metabolic abnormality appear typically only after several months of disease onset. CONCLUSION: Concomitant structural and functional neuroimaging provide possibly complementary information in the early noninvasive workup of RE and may facilitate the early diagnosis of this rare disorder.

[Epilepsy surgery in childhood: theory and practice]. / Epilepsziasebészet gyermekkorban: elmélet és gyakorlat.

1-1.5% of the Hungarian child population has epilepsy, and around 20% of them produces seizures in spite of modern antiepileptic drugs. A part of the pharmaco-resistant children may benefit from surgical removal of the epileptogenic focus. Presurgical evaluation has been developed a lot since the progress of neuroimaging, video-EEG monitoring, neuropsychology, and neurosurgical techniques in the 1990s. Authors summarize the important steps of presurgical evaluation in epileptic children emphasizing the role of history taking, physical examination, neuroimaging, standard EEG, long term monitoring, and neuropsychology. They describe the surgical treatment of the most important epilepsy syndromes in childhood analyzing the data of 58 epileptic children examined in the Bethesda Children's Hospital and operated in the National Institute of Neurosurgery (Budapest, Hungary). Age of children at surgery was between 16 months and 18 years, dysplasia and benign tumors covered etiology in 59% of the cases. The most frequent intervention was resection; however also some callosotomies and hemispherotomies were completed. Authors emphasize the importance of early surgical intervention of therapy resistant children in order to prevent the deteriorating effects of epilepsy on childhood psychomotor development.

[The role of PET scan in the investigation of epileptic functional disorders]. / A PET helye az epilepsziás agyi múködészavar meghatározásában.

Systematic research is needed to evaluate the exact role of pathological factors in the determination of the extension of the hypometabolic area in partial epileptic patients. Together with structural damage, previous seizures, deafferentation and inhibitory mechanisms may contribute to the functional disorders. Benzodiazepine receptor studies showed that the density and binding ability of these receptors decreased in the area of epileptic functional disorder. Circumscribed hypermetabolism may appear during epileptic seizures or even more electrical discharges. The authors' PET studies aimed at presurgical evaluation showed that bilateral temporal hypometabolism occurred more frequently with right-sided seizure start. FDG-PET supported the localization of the pacemaker area both in temporal lobe epilepsies and in extratemporal epilepsies. This method proved instrumental in delineating the extension of the background pathology, too. The authors also demonstrated the strength of PET brain activation in mapping the hemispheric distribution of speech functions required in the planning of surgical interventions. The role of hippocampal sclerosis in temporal lobe hypometabolism was investigated and a short account is given of the observations relating to the relationship of hypermetabolism due to subclinical epileptic discharges and cognitive deficit symptoms.