Epilepsy and respiratory chain defects in children with mitochondrial encephalopathies.

OBJECTIVE: The purpose of this study was to determine the relationship between epilepsy and respiratory chain defects in children with mitochondrial encephalopathies (ME). STUDY DESIGN: We conducted a retrospective review of the medical records of children referred for evaluation of an ME. Only patients assigned a definite diagnosis of ME using modified Walker criteria and with a respiratory chain defect were included. Clinical data pertaining to the ME and epilepsy type were collected. Mitochondria were isolated by subcellular fractionation from a vastus lateralis muscle biopsy and studies were performed using polarographic and spectroscopic techniques for the quantitative determination of NADH and cytochrome components of the respiratory chain. RESULTS: A total of 38 children with ME were identified. Seizures were present in 61%. Sixteen of 23 children with epilepsy (70%) had refractory epilepsy associated with a progressive encephalopathy. Children with epilepsy had a significantly higher incidence of complex I defects than children without epilepsy (p<0.01). Complex III and IV defects were significantly higher in patients without epilepsy (p<0.01 and p<0.05, respectively) than in those with epilepsy. CONCLUSIONS: Epilepsy is an important component of ME. The higher incidence of complex I defects in patients with epilepsy suggests a possible relationship between mitochondrial oxidative stress dysfunction and epileptogenic process.

Mitochondrial activity in Pompe's disease.

Mitochondrial oxidative metabolism was examined in two infants with Pompe's disease. The clinical diagnosis was confirmed by the demonstration of intralysosomal glycogen accumulation and a deficiency of acid alpha-D-glucosidase in muscle biopsies. Light and electron microscopy studies demonstrated a normal number of mitochondria with normal ultrastructure. Spectrophotometric measurements revealed that the specific activities of citrate synthase and the partial reactions of electron transport were markedly elevated in the skeletal muscle homogenates prepared from both infants with Pompe's disease when calculated as micromoles per minute per gram wet weight of tissue. However, when respiratory chain enzyme activities were expressed relative to citrate synthase as a marker mitochondrial enzyme, a different pattern emerged, in which all Pompe muscle respiratory enzymes, except complex IV, were decreased relative to control subjects. These observations demonstrate that caution should be exercised when analyzing and interpreting data obtained from tissue homogenates in general and, in particular, in those prepared from tissues in which the wet weight of tissue may be altered, for example, by pathologic accumulation of carbohydrate or lipid.

Rasmussen encephalitis: complementary role of multitechnique neuroimaging.

Rasmussen encephalitis is a chronic, progressive inflammation of the brain of unknown origin. Early diagnosis and treatment with immunoactive agents and/or hemispherectomy are sought to prevent the progressive cognitive decline that accompanies this disease. Combined anatomic and functional neuroimaging may serve to focus the diagnostic workup and to hasten brain biopsy for definitive diagnosis. Two biopsy proved cases of Rasmussen encephalitis are presented. The importance of MR imaging, single-photon emission computed tomography, and proton MR spectroscopy in the workup of this disease is discussed.

Does the histamine skin prick test identify patients at risk for toxicity after the ingestion of astemizole?

Astemizole is a widely prescribed nonsedating antihistamine that suppresses wheal and flare reactions from histamine prick testing. We report a two-year-old girl with a serum concentration-proven overdose of astemizole who nonetheless exhibited a significant wheal and flare reaction after histamine skin prick testing for at least 22 hours after the ingestion. These findings suggest that histamine skin prick testing should not be used as a screening test to evaluate whether an ingestion of astemizole has occurred.