Language function in childhood idiopathic epilepsy syndromes.

PURPOSE: To examine the impact of diverse syndromes of focal and generalized epilepsy on language function in children with new and recent onset epilepsy. Of special interest was the degree of shared language abnormality across epilepsy syndromes and the unique effects associated with specific epilepsy syndromes. METHODS: Participants were 136 youth with new or recent-onset (diagnosis within past 12 months) epilepsy and 107 healthy first-degree cousin controls. The participants with epilepsy included 20 with Temporal Lobe Epilepsy (TLE; M age = 12.99  years, SD = 3.11), 41 with Benign Epilepsy with Centrotemporal Spikes (BECTS; M age = 10.32, SD = 1.67), 42 with Juvenile Myoclonic Epilepsy (JME; M age = 14.85, SD = 2.75) and 33 with absence epilepsy (M age = 10.55, SD = 2.76). All children were administered a comprehensive test battery which included multiple measures of language and language-dependent abilities (i.e., verbal intelligence, vocabulary, verbal reasoning, object naming, reception word recognition, word reading, spelling, lexical and semantic fluency, verbal list learning and delayed verbal memory). Test scores were adjusted for age and gender and analyzed via MANCOVA. RESULTS: Language abnormalities were found in all epilepsy patient groups. The most broadly affected children were those with TLE and absence epilepsy, whose performance differed significantly from controls on 8 of 11 and 9 of 11 tests respectively. Although children with JME and BECTS were less affected, significant differences from controls were found on 4 of 11 tests each. While each group had a unique profile of language deficits, commonalities were apparent across both idiopathic generalized and localization-related diagnostic categories. DISCUSSION: The localization related and generalized idiopathic childhood epilepsies examined here were associated with impact on diverse language abilities early in the course of the disorder.

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy.

BACKGROUND: Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. OBJECTIVE: We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). METHODS: We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. RESULTS: The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. CONCLUSIONS: Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Violent recurrent ballism associated with infections in two children with static encephalopathy.

A variety of cerebral insults can result in static encephalopathy with developmental delays and relatively fixed motor and cognitive deficits. We describe two boys with static encephalopathy who experienced recurrent episodes of generalized, violent ballism seemingly provoked by relatively minor infectious illnesses or surgical procedures. These episodes first began at ages 14 and 9 years, respectively. The baseline clinical states included relatively mild choreoathetosis plus cognitive impairment, as well as spasticity and/or ataxia. These episodes of ballism developed over hours, remained for weeks, and ultimately returned to baseline. Neuroleptics, anticonvulsants, and benzodiazepines were only partially beneficial; responses corresponded to the degree of sedation. Potential for self-injury or rhabdomyolysis/myoglobinuria led to the use of general anesthetics or neuromuscular blocking agents during selected episodes. Blood, urine, and cerebrospinal fluid studies, magnetic resonance imaging head scans, and electroencephalography revealed no diagnostic clues as to the precise causative factor precipitating these episodes.

Unusual presentation and MRI findings in Rasmussen's syndrome.

Rasmussen's syndrome is a chronic disorder characterized by uncontrollable focal seizures and eventually epilepsia partialis continua, ipsilateral hemiparesis, developmental arrest, and cerebral inflammation. Viral and autoimmune etiologies have been postulated. A patient is presented who illustrates the wide variability of clinical and radiographic presentations in this disorder. The patient is an 8-year-old female who developed intermittent facial twitching at 2 years of age that eventually progressed to epilepsia partialis continua. Electroencephalography demonstrated clinical seizures that emanated from the right parasagittal area. Cranial magnetic resonance imaging revealed pronounced atrophy of the right caudate nucleus, globus pallidus, and putamen, with mild increased T2-weighted signal in the right striatum, without accompanying cortical atrophy. Ictal single-photon emission computed tomography revealed markedly reduced uptake in the right hemisphere that was maximum in the right basal ganglia. Cerebrospinal fluid, blood, and urine collected for metabolic and immunologic screening and DNA testing for a wide variety of disorders were all unremarkable. Neuropsychologic testing demonstrated difficulties in memory, attention, and calculation. Brain biopsy revealed mild microglial activation, rare glial nodules, and collections of lymphocytes and histiocytes, consistent with the clinical diagnosis of Rasmussen's syndrome. After a modified hemispherectomy, she demonstrated marked clinical improvement.

Molecular analysis of odd-skipped, a zinc finger encoding segmentation gene with a novel pair-rule expression pattern.

odd-skipped (odd) is one of eight known pair-rule genes that establish portions of alternating segments during Drosophila embryogenesis; odd mutant embryos exhibit pattern defects in anterior regions of odd-numbered segments. P element transposon tagging was used to clone 25 kb of DNA from the odd genomic region. Molecular analysis of phenotypic revertants confirmed that the P element used to tag the locus was responsible for the corresponding odd mutation, and significant structural changes were identified in two additional odd mutants. Several cDNA clones derived from a 2.2 kb embryonic transcript were isolated and the longest was sequenced. The predicted odd protein of 392 amino acids is highly basic and contains four tandem Cys-Cys/His-His zinc finger repeats, consistent with a presumed function for odd as a DNA binding protein and transcriptional regulator. In situ hybridization analysis indicated that odd transcripts accumulate in a dynamic pattern during early embryogenesis, with two temporally distinct modes of expression. The first mode results in a 'pair-rule' pattern of seven stripes at the blastoderm stage, representing the expected double segment periodicity. During gastrulation, the seven primary stripes are supplemented by secondary stripes which appear in alternate segments, resulting in the equivalent labeling of every segment in the extended germ band. Similar double to single segment transitions have now been reported for four of the six pair-rule genes analyzed.