Cobblestone Malformation in LAMA2 Congenital Muscular Dystrophy (MDC1A).

Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin α2 (LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.

Fatal outcome in hemiconvulsion-hemiplegia syndrome.

Hemiplegia-hemiconvulsion-epilepsy syndrome is characterized by prolonged unilateral clonic seizures in a child followed by the development of hemiplegia. Focal status epilepticus results in unilateral cerebral edema of the epileptic hemisphere in the acute phase followed by cerebral hemiatrophy. Literature in the last 5 years does not describe malignant cerebral edema or resultant death. We report a case of a 3-year-old girl with hemiplegia-hemiconvulsion-epilepsy syndrome who died due to malignant cerebral edema and temporal lobe herniation. The first indication of worsening of clinical status after being seizure free was voltage suppression on continuous electroencephalography (EEG). We describe neuroimaging, EEG findings, and neuropathologic findings at autopsy and review pertinent literature. We also evaluate the evolving role of continuous EEG monitoring in the pediatric intensive care unit.

Pediatric optic neuritis: does a prolonged course of steroids reduce relapses? A preliminary study.

BACKGROUND: Optic neuritis is an important pediatric disorder causing visual impairment. Because of the absence of pediatric-specific studies, data extrapolated from the adult-based optic neuritis treatment trial are used to guide management of pediatric patients. Recent literature promotes a prolonged course of oral steroids to prevent relapses. However, there are no published data to support this view. Patients who were recently treated in our hospital received a longer course of steroids, relative to those treated several years ago. We hypothesized that a longer course of steroids results in fewer relapses and better final visual acuity. METHODS: A retrospective analysis of 26 consecutive patients (age 4.5-19 years) treated for optic neuritis within the past 10 years was conducted. Patients received either a short course (2 weeks) or a prolonged course (more than 2 weeks) of steroids. Some patients were not treated. Mean follow-up was 70 weeks (3 weeks-10 years). Comparisons were made among the groups receiving 2 weeks of steroid treatment (16 of 26 patients) and greater than 2 weeks of steroid treatment (seven of 26 patients) to evaluate relapse rate, eventual visual acuity, and reported side effects. RESULTS: There were no significant differences in the relapse rates, reported side effects, and final visual acuity in the two treatment groups. CONCLUSIONS: In this cohort, a prolonged course of steroids was not associated with reduced relapse rate, increased side effects, or improved visual outcome. This cohort was small, but the results do not identify any reason to deviate from the common approach of optic neuritis treatment, which is 2 weeks of steroids.