Aithala Gururaj

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.

Epilepsy in children with cerebral palsy

OBJECTIVES To study the occurrence, associated factors, nature and prognosis of seizures in children with cerebral palsy (CP). DESIGN A prospective, descriptive, hospital-based, case-control study. SETTING Tertiary level University Teaching Hospitals in the Al Ain Medical District, United Arab Emirates. PATIENTS Fifty-six children with CP and seizures seen in the neurodevelopmental clinics at Al Ain and Tawam University Hospitals during the period of 1997-1999 were studied (group 1). Two control groups of 35 children with CP without seizures (group 2) and 50 children with seizures but no CP (group 3) were also studied. RESULTS Spastic tetraplegia was the commonest type of CP associated with seizures whereas spastic diplegia was the commonest variety of CP in group 2. Most children with CP had an early onset of seizures within the first year of life as against those without CP. The children in group 1 had a higher incidence of neonatal seizures (42.9% vs. 29.4% in group 2 and 0% in group 3), presence of significant developmental delay (98.2% vs. 20.0% in group 3), occurrence of significant abnormalities on brain imaging (94.6% vs. 19.6% in group 3) and a need for use of more than 1 antiepileptic drug (66.1% vs. 30.0% in group 3). Over half of children in the study group presented with generalized tonic clonic seizures; the electroencephalogram (EEG) showed focal epileptic discharges with or without secondary generalization in 39.3%. The overall outcome of seizures in children with CP was poor needing prolonged course of anticonvulsant medications, polytherapy and higher incidence of refractory seizures and admissions for status epilepticus compared to the control group. CONCLUSIONS Cerebral palsy is associated with a higher incidence of seizure disorders, which, in a majority, has its onset in the neonatal period; brain imaging showed abnormal pathology in most affected children, which possibly accounts for the tendency to more refractory seizures in these children.

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

Summary:  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.

Are the strokes in moyamoya syndrome associated with Down syndrome due to protein C deficiency

Moyamoya syndrome has occasionally been seen in association with Down syndrome. We report a child with moyamoya syndrome and Down syndrome who was admitted with repeated episodes of strokes; his magnetic resonance imaging and magnetic resonance angiography findings confirmed the presence of occlusive cerebrovascular disease with basal collateral vessels. His protein C levels were significantly decreased during the stroke. Complete clinical recovery was seen during follow-up. This raises the possibility of a link between protein C deficiency and Down syndrome with moyamoya syndrome.

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 β-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. (J Child Neurol 2005;20:57—60).

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.

Predictors of Febrile Seizure: A Matched Case‐control Study

In a prospective matched case-control study carried out to determine risk factors of febrile seizures among children in the United Arab Emirates, 84 patients with febrile seizure were identified and were matched with 84 control febrile patients without seizure in the same age range, who attended the same hospital during the same period of time. Logistic regression analysis showed that the age at first seizure, family history of febrile seizure, duration of fever, and height of temperature were the only significant predictors for febrile seizures.

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. (J Child Neurol 2005;20:926—930).

CT and MR Patterns of Hypoxic Ischemic Brain Damage Following Perinatal Asphyxia

The objectives were to study the clinical and neurological abnormalities in children with cerebral palsy and to attempt to correlate the signs with radiological abnormalities detected by CT scan and/or MRI of the brain. In a prospective, hospital-based study, 65 children with cerebral palsy were examined neurologically and their perinatal history was reviewed. Their cranial CT scan, and/or magnetic resonance images were studied. The association between the gestational ages, perinatal history, neurological deficits, and the radiological appearances were studied. Of the 24 preterm-born and 41 term-born children, 23 had spastic diplegia; 57 per cent of these children has significant periventricular leucomalacia, which was more common among preterm-born children. Of the 13 children with hemiplegia, 12 had unilateral lesions on neuroimaging. Spastic tetraplegia was associated with extensive, bilateral, diffuse brain damage. Extrapyramidal cerebral palsy was far more common among term-born infants and 80 per cent of these showed significant abnormalities in the basal ganglia region. Ataxic cerebral palsy was an uncommon variety and there was no significant correlation between neurological signs and abnormalities on brain imaging. In conclusion, the radiological findings were closely related to the type of cerebral palsy and the neurological deficit except in the ataxic type. We believe that CT and MRI imaging are helpful in understanding the pathology and the timing of the lesion in cerebral palsy.

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. (J Child Neurol 2005;20:446—449).