Clinical predictors of intractable childhood epilepsy.

OBJECTIVE: This study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable seizures in children in the Al Ain Medical District in the United Arab Emirates. METHODS: This work used a prospective case-control study of children referred to pediatric neurology and neurodevelopmental clinics at Tawam and Al Ain University Hospitals. RESULTS: There were 55 children with intractable epilepsy; their data were compared with 50 children who responded well to antiepileptic drugs and who were seizure-free for at least 2 years. Onset <1 year of age, a high seizure frequency at onset, positive history of neonatal seizures, developmental delay and status epilepticus, neurological deficits, and abnormal brain imaging results were found to be significantly more common in the study group. Symptomatic localization-related epilepsy was more common in children in this group than in the control group. CONCLUSION: Our study suggests that children who present with idiopathic localization-related and generalized epilepsy syndromes with few seizures at onset and with no neurological deficits tend to have a relatively good prognosis.

Prevalence and psychosocial correlates of global developmental delay in 3-year-old children in the United Arab Emirates.

OBJECTIVE: Developmental disabilities are lifelong conditions with considerable public health impact, incurring substantial financial and societal costs. Data on prevalence and associated factors can provide the basis for setting priorities and designing interventions. METHODS: A representative random sample of 694 United Arab Emirates national children aged 3 years were evaluated in a two-stage epidemiological study. RESULTS: Stage 1 screening using the Denver Developmental Screening Test found that 8.4% [confidence interval (CI): 6.4-10.7] had global developmental delay (GDD). Using clinical diagnostic interview in Stage 2, the weighted prevalence for clinically significant developmental disability was estimated to be 2.44% (CI: 1.28-3.56). GDD was associated with pregnancy and birth complications, poor maternal education, family history of developmental problems, and major traumatic life events, as well as behavioral problems in children. CONCLUSION: Our findings suggest the need for comprehensive and early screening programs for developmental problems, and the importance of training medical and child care professionals accordingly.

Hippocampal dysgenesis associated with temporal lobe hypoplasia and arachnoid cyst of the middle cranial fossa.

We describe two children with left hippocampal dysgenesis in association with temporal lobe hypoplasia and arachnoid cyst of the middle cranial fossa. The hippocampus showed an abnormal globular shape and blurred internal structure in both patients. One of the patients had juvenile myoclonic epilepsy without evidence of seizure onset in the abnormal temporal region. The other patient did not have epilepsy; however, he showed developmental language disorder with a probable relationship to the left temporal abnormalities.

Electroencephalography, Doppler vascular scanning, and single photon emission computed tomography in a child with hydranencephaly and intractable seizures.

In a child with hydranencephaly and refractory seizures, the electroencephalogram showed a flat isoelectric pattern with no significant slow waves or epileptiform activity; cranial computed tomography, magnetic resonance imaging, Doppler vascular scanning, and single photon emission computed tomography (SPECT) were done to define the pathogenesis of the seizures. The investigations were suggestive of a lack of significant cortical, subcortical, or thalamic structures with hypoplasia of the vermis and cerebellum. SPECT showed little activity in the base of the brain and cerebellum. The cause of the seizures remained unclear in spite of the investigations.

Magnetic resonance imaging findings and novel mutations in GM1 gangliosidosis.

Two unrelated children and their siblings of Arab origin were diagnosed as having GM1 gangliosidosis on the basis of clinical features and markedly low levels of beta-galactosidase. The T2-weighted magnetic resonance images of the brain revealed certain characteristic features, including delayed myelination and abnormal appearance of the subcortical white matter, internal capsule, and basal ganglia. Their mutation analysis showed two novel mutations, which have not been described in an Arabic population.

L-2-hydroxyglutaric aciduria in two siblings.

Two Pakistani siblings with L-2-hydroxyglutaric aciduria are reported herein. A 6-year-old male and a 2-year-old female, born to consanguineous parents, had chronic slowly progressive neurodegenerative disorder with insidious onset after infancy. Mental regression and seizures were evident in both patients, whereas cerebellar dysfunction was the main motor handicap in the male and pyramidal symptoms were prominent in the female. Magnetic resonance imaging revealed bilateral symmetrical abnormal signal in the subcortical white matter, internal and external capsules, basal ganglia, and dentate nuclei. The underlying metabolic defect, which is likely inherited in an autosomal recessive mode, remains unknown in this disorder.

Temporal lobe epilepsy in children: etiology in a cohort with new-onset seizures.

PURPOSE: The aim of this study was to characterize the incidence and etiology of temporal lobe epilepsy (TLE) in a community-based cohort of children with new-onset disease. METHODS: A community-based cohort of 30 children with TLE was studied. The patients had new-onset disease before age 14 years between 1995 and 1999. They underwent clinical, EEG, and magnetic resonance imaging investigations. RESULTS: The patients could be divided in three main groups according to likely etiology, as suggested by Harvey et al. (Neurology 1997;49:960-8). Group 1 consisted of eight (26.7%) children with malformations or long-standing, nonprogressive tumors (developmental TLE). Arachnoid cysts were found in three, dual pathology [cortical dysplasia and hippocampal sclerosis (HS)] in one, and focal cortical dysplasia with glioproliferative changes in one patient. Dysembryoplastic neuroepithelial tumor was responsible for the epilepsy in one, and ganglioglioma, in two children. Group 2 consisted of seven (23.3%) children with a significant antecedent and/or HS. Five children had a significant illness or event before the onset of TLE, including perinatal hypoxic-ischemic encephalopathy in one, encephalitis in one, traumatic brain injury in two, and complex febrile seizures in one. HS was found in the patients with traumatic brain injury and complex febrile seizures in the history in addition to two children without known antecedents. Group 3 comprised 15 (50%) children with no abnormality on neuroimaging and no significant antecedents (cryptogenic TLE). CONCLUSIONS: Etiologic differences between children with new-onset TLE may have prognostic implications: children with TLE and significant antecedents/HS are expected to have the greatest risk of continued seizures and psychological problems.

Linkage analysis in families with Joubert syndrome plus oculo-renal involvement identifies the CORS2 locus on chromosome 11p12-q13.3.

Joubert syndrome (JS) is an autosomal recessive developmental brain condition characterized by hypoplasia/dysplasia of the cerebellar vermis and by ataxia, hypotonia, oculomotor apraxia, and neonatal breathing dysregulation. A form of JS that includes retinal dysplasia and cystic dysplastic kidneys has been differentiated from other forms of JS, called either "JS type B" or "cerebello-oculo-renal syndrome" (CORS), but the genetic basis of this condition is unknown. Here, we describe three consanguineous families that display CORS. Linkage analysis defines a novel locus on chromosome 11p12-q13.3, with a maximum two-point LOD score of Z=5.2 at the marker D11S1915. Therefore, the cerebello-oculo-renal form of JS is a distinct genetic entity from the Joubert syndrome 1 (JBTS1) locus described elsewhere, in which there is minimal involvement of retina or kidney. We suggest the term "CORS2" for this new locus.

Mutations in the AHI1 gene, encoding jouberin, cause Joubert syndrome with cortical polymicrogyria.

Joubert syndrome (JS) is an autosomal recessive disorder marked by agenesis of the cerebellar vermis, ataxia, hypotonia, oculomotor apraxia, neonatal breathing abnormalities, and mental retardation. Despite the fact that this condition was described >30 years ago, the molecular basis has remained poorly understood. Here, we identify two frameshift mutations and one missense mutation in the AHI1 gene in three consanguineous families with JS, some with cortical polymicrogyria. AHI1, encoding the Jouberin protein, is an alternatively spliced signaling molecule that contains seven Trp-Asp (WD) repeats, an SH3 domain, and numerous SH3-binding sites. The gene is expressed strongly in embryonic hindbrain and forebrain, and our data suggest that AHI1 is required for both cerebellar and cortical development in humans. The recently described mutations in NPHP1, encoding a protein containing an SH3 domain, in a subset of patients with JS plus nephronophthisis, suggest a shared pathway.