Michael Nork

Joubert's syndrome: new cases and review of clinicopathologic correlation.

The authors report on seven patients, six males and one female, with Jouberts syndrome who underwent developmental evaluation, neurologic and ophthalmologic examinations, and magnetic resonance imaging of the brain. All patients had severe developmental delay, hypotonia, impairment of smooth visual pursuit, and saccadic eye movements. Six had jerky eye movements and ptosis was observed in two patients and retinal dystrophy in one. The posterior lobe of the vermis was absent in all patients and the small rudimentary anterior lobe lacked fusion in the midline, with cleft formation in five patients. Malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa, was observed in all patients. Abnormal cerebellar-brainstem and cerebellocortical connections because of the lack of the posterior vermis and dysplasia of the deep cerebellar nuclei might be responsible for the abnormal eye movements and retarded development in Jouberts syndrome. Correlation between radiologic findings and clinical symptoms and the possible role of abnormal patterning of the midbrain-hindbrain by homeotic genes during embryonic development are reviewed.

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.

Bilateral frontoparietal polymicrogyria and epilepsy

Two patients with bilateral frontoparietal polymicrogyria are reported. Severe developmental delay, mental retardation, spastic tetraplegia, and seizures were the main clinical features. Magnetic resonance imaging revealed a bilateral thick cortex with irregular gyri and a festoonlike gray-white matter junction. Bilateral frontoparietal polymicrogyria may represent a further form of the bilateral polymicrogyria syndromes in addition to perisylvian and parasagittal parieto-occipital polymicrogyria.

Novel missense mutation in the L1 gene in a child with corpus callosum agenesis, retardation, adducted thumbs, spastic paraparesis, and hydrocephalus.

Corpus callosum agenesis, retardation, adducted thumbs, spastic paraparesis, and hydrocephalus (CRASH syndrome) is an X-linked recessive disorder caused by mutations in the neuronal cell adhesion molecule L1 (L1 CAM) gene. L1 plays a key role in axon outgrowth and pathfinding during the development of the nervous system. We describe the case of a boy from the United Arab Emirates who presented with CRASH syndrome. Scanning the L1 gene of the patient resulted in the discovery of a novel missense mutation: transition of a G (guanine) to T (thymine) at position 604 (G604→T), which results in conversion of aspartic acid to tyrosine at position 202 (D202Y) of the L1 protein. It is very likely that the cerebral dysgenesis is due to the abnormal structure and function of L1. (J Child Neurol 2000;15:239-243).

Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency).

The case of a Yemeni girl with isolated peroxisomal acyl‐CoA:dihydroxyacetonephosphateacyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very‐long‐chain fatty acid profile, phytanic acid concentration, alkyl‐dihydroxyacetonephosphate synthase (alkyl‐DHAP synthase) activity, and peroxisomal 3‐ketoacyl‐CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl‐DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girls abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity.

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.

Abnormal myelination in peroxisomal isolated dihydroxyacetone-phosphate acyltransferase deficiency☆

The cranial magnetic resonance imaging findings in three siblings with nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency are reported. Areas of high signal intensity in a patchy distribution on the T2-weighted images were detected in the centrum semiovale in the eldest patient (a 6-year-old girl). The white matter of the second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2-year-old boy) manifested very severe white matter abnormalities. DHAP-AT catalyzes the first step in the synthesis of plasmalogens, which are major constituents of myelin. Defective plasmalogen synthesis may have contributed to abnormal myelin formation in 2 patients. Because the clinical presentation of the child without detectable defect in myelination was similar to that of his siblings, the neurologic signs observed in isolated DHAP-AT deficiency cannot be attributed solely to the disturbances in the myelin formation.

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.

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).