Megalencephalic leukoencephalopathy with cysts without MLC1 defect.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disease characterized by early infantile macrocephaly and delayed motor and cognitive deterioration. Magnetic resonance imaging (MRI) shows diffusely abnormal and swollen cerebral white matter and subcortical cysts. On follow-up, atrophy ensues. Approximately 80% of MLC patients have mutations in MLC1. We report 16 MLC patients without MLC1 mutations. Eight retained the classical clinical and MRI phenotype. The other 8 showed major MRI improvement. They lacked motor decline. Five had normal intelligence; 3 displayed cognitive deficiency. In conclusion, 2 phenotypes can be distinguished among the non-MLC1 mutated MLC patients: a classical and a benign phenotype.

Prevalence of antiphospholipid and antinuclear antibodies in children with epilepsy.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous thrombosis or arterial occlusive events and fetal losses associated with elevated levels of antiphospholipid antibodies (aPLs). MATERIAL/METHODS: The presence of antinuclear, anti-beta2-glycoprotein I, and anticardiolipin antibodies were investigated in 60 consecutive children with epilepsy who were followed up in a single Hungarian center. RESULTS: Almost 50% (28/60) of the patients were ANA positive. Twelve (20%) patients had moderate titer (1:160) of ANA. Anti-C1q antibody was positive in 4 cases, all of them symptom free considering renal manifestation of lupus. Interestingly, only 1 child had aCL antibody, while 6/43 patients were LAC positive. Five were also ANA positive among the LAC positive patients (4 children with moderate titer). Anti-beta2GPI antibody positivity was not detected in this cohort of patients. CONCLUSIONS: The clinical relevance of aPL tests in childhood are difficult to explain. In the present study, obviously lower total prevalence of aPLs (aCL and anti-beta2GPI) was observed in children with epilepsy than in previously reported investigations (20-30%). The higher amount of LAC-positive patients indicates that coagulation studies (LAC) should be included in the neuroimmunological assessment of suspected APS patients with epileptic disorders. The difference between the results of serological and LAC studies could be explained by the possible positivity of other, uninvestigated antibodies. The wide spectrum of detected immunological alterations highlight the importance of the participation of pediatric rheumatologists in the management of patients with idiopathic epilepsy or with secondary induced autoimmune disease due to antiepileptic medications.

[Adrenocorticotropic hormone therapy in acquired childhood epileptic aphasia]. / Szerzett gyermekkori epilepszias beszédzavar kezelése adrenokortikotrop hormonnal.

Although Landau-Kleffner syndrome, a childhood-acquired epileptic aphasia, is frequently studied either the underlying pathophysiology or the optimal therapy remained unknown. In our study we aimed to investigate the efficacy of ACTH therapy in Landau-Kleffner syndrome. We have analysed retrospectively the documentation of five children treated by ACTH, who suffered from Landau-Kleffner syndrome. We studied the longitudinal changes of the four most characteristic symptoms and signs of the syndrome: epileptiform EEG, speech and behaviour disorders, seizures together with the ACTH regimes. Besides, we analysed the relation between the starting date of the therapy and its efficacy. Before giving ACTH, epileptiform EEG and speech disorders were observed in all the five children, seizures in four of them, behaviour disorders in three of them. In two patients the speech disorder had been persisting for years before. Due to the starting ACTH stoss-therapy (20 E/day for one-two weeks) all the four examined signs disappeared or showed quick softening in all the five children in maximum two weeks. We adjusted long-term low dose maintenance therapy to avoid relapses in the long-term follow-up. Epileptiform EEGs have normalised in one case and have decreased in four cases. Speech disorders have disappeared in two and have softened in three children. Behaviour disorders have cured in 3/4 cases, softened in one case. Seizures have disappeared in all cases. One child is totally asymptomatic, four of them lives with softened symptoms. Analysing our data we found that the earlier the therapy starts, the more effective it is. On the basis of our data ACTH is an effective treatment for Landau-Kleffner syndrome. After giving it for only a short period, relapses often occur, to avoid relapses adjustment of long term low dose maintenance therapy is advisable.

Comprehensive mutation analysis of GLDC, AMT, and GCSH in nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. NKH is caused by deficiency of the glycine cleavage multi-enzyme system with three specific components encoded by GLDC, AMT, and GCSH. We undertook the first comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56, six, and seven families with neonatal, infantile, and late-onset type NKH, respectively). GLDC or AMT mutations were identified in 75% of neonatal and 83% of infantile families, but not in late-onset type NKH. No GCSH mutation was identified in this study. GLDC mutations were identified in 36 families, and AMT mutations were detected in 11 families. In 16 of the 36 families with GLDC mutations, mutations were identified in only one allele despite sequencing of the entire coding regions. The GLDC gene consists of 25 exons. Seven of the 32 GLDC missense mutations were clustered in exon 19, which encodes the cofactor-binding site Lys754. A large deletion involving exon 1 of the GLDC gene was found in Caucasian, Oriental, and black families. Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms. This study provides a comprehensive picture of the genetic background of NKH as it is known to date.

Converging evidences on language impairment in Landau-Kleffner Syndrome revealed by behavioral and brain activity measures: a case study.

OBJECTIVE: To assess the linguistic abilities of a boy having Landau-Kleffner Syndrome, and relate the focal disturbance of brain activity due to epilepsy to the cognitive and linguistic deficits. METHODS: Several kinds of assessments were carried out, including epileptic source analysis using electronic source localization methods and PET, neuropsychological assessment of cognitive functions, and assessment of speech perception skills (discrimination of phonetic and stress cues) using ERPs. RESULTS: The source of epileptic activity was localized in the left superior temporal lobe. The neuropsychological assessment showed dissociation between verbal and nonverbal functions, and the performance in former was bellow the normal range. ERPs obtained to the processing of phonetic and stress speech cues indicated that the two cues were processed asymmetrically: the mismatch negativity component (MMN) was obtained for the phoneme difference, but not for the stress pattern difference. CONCLUSIONS: Our data converged as it showed that the patient presented a selective impairment of the language system, and the verbal working memory system appeared to be especially defective. It is suggested that the language deficit is at least partly due to the focal disturbance of those neural networks that underlie the functioning of the working memory system. SIGNIFICANCE: LKS is a childhood language disorder that might serve as a model in studying what happens to the language system if, in the course of development, the essential neural circuits are severely disturbed.

Heterozygous GLDC and GCSH gene mutations in transient neonatal hyperglycinemia.

Transient neonatal hyperglycinemia is clinically or biochemically indistinguishable from nonketotic hyperglycinemia at onset. In the case of transient neonatal hyperglycinemia, the elevated plasma and cerebrospinal fluid glycine levels are normalized within 2 to 8 weeks. To elucidate the pathogenesis of transient neonatal hyperglycinemia, we studied three patients by screening mutations in the genes that encode three components of the glycine cleavage system. Heterozygous mutations were identified in all of the three patients, suggesting that transient neonatal hyperglycinemia develops in some heterozygous carriers for nonketotic hyperglycinemia.