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.

Treatment of status epilepticus.

Status epilepticus (SE) is a common pediatric emergency, which warrants prompt and aggressive treatment. This report presents a brief description and classification of SE. Therapy should be directed towards rapid termination of the SE, prevention of seizure recurrence and treatment of any underlying cause. A review of drugs commonly used in the treatment of SE is presented. The morbidity and mortality of SE is significant and directly dependant upon prompt and appropriate medical therapy. The treatment of refractory SE requires labour intensive hemodynamic support and suppression of seizures using either barbiturates or anesthetic agent. Formulation and adherence to standard treatment protocols provides the best results.

MRI signal changes in the white matter after corpus callosotomy.

Magnetic resonance imaging (MRI) changes reported after corpus callosotomy include hyperintensity in the corpus callosum, perifalcine hyperintensity caused by surgical retraction, and acute changes associated with surgical complications. The authors have observed MRI signal changes in the cerebral white matter of corpus callosotomy patients that are separate from the sectioned callosum and not clearly related to surgical manipulation or injury. Brain MRI scans were retrospectively reviewed in 25 of 38 patients who underwent anterior, posterior, or total callosotomy for refractory seizures between 1988 and 1995. Nine patients had signal changes in the cerebral white matter on postoperative MRI. Six of these patients had preoperative MRI studies available for comparison, and none of the white matter signal abnormalities were evident preoperatively. T2 prolongation or hyperintensity on proton-density images was observed in areas including the centrum semiovale, forceps major, and forceps minor. Three patients had signal changes that had distinct borders extending only to the posterior limit of the callosotomy. MRI signal changes in the cerebral white matter after corpus callosotomy have not been previously reported and may represent distant effects of callosal section. Wallerian degeneration occurring in the neuronal processes cut during surgery could account for the signal changes.

Vitamin E deficiency and associated neurological deficits in children with protein-energy malnutrition.

Vitamin E is important in maintaining normal neurological structure and function. In this study, 100 children with protein-energy malnutrition (PEM) were studied and compared to a suitably age-matched control group. Posterior column deficits, cerebellar deficits, and problems with fine motor coordination were present to a significant degree in the PEM subjects. The presence of neurological signs was correlated with various parameters of vitamin E deficiency, including low serum alpha-tocopherol levels and a low tocopherol/total lipid ratio which was present in 92 per cent of subjects. There was good concordance between vitamin E levels and vitamin E to serum lipid ratio in assessing vitamin E deficiency. We conclude that vitamin E deficiency is prevalent, to a hitherto unsuspected degree, in children with PEM and that these malnourished children have significant neurological deficits attributable to low vitamin E levels. This observation is of clinical significance as the neurological deficits are potentially reversible with vitamin E supplementation.

Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability.

Twenty-six children with intellectual disability and six normal children, all suffering from refractory partial seizures, received open-label gabapentin (range = 10-50 mg kg(-1) day(-1); mean = 26.7 mg kg(-1) day(-1) as an add-on medication to their antiepileptic drug regimen. Mean seizure frequency during baseline was 9.5 seizures per week. Both groups had a significant reduction in seizure frequency. Response scores and response ratios did not differ between the intellectually disabled and normal groups (1.67+/-0.67 and 1.25+/-0.69, P = 0.697, and -0.400+/-0.089 and -0.283+/-0.159, P = 0.961, respectively). Behavioural side-effects were more likely to occur in patients with intellectual disability in comparison with the mentally normal group (P = 0.0107). In the present patient population, patients younger than 10 years of age, all of whom had intellectual disability, were more likely to have side-effects than those older than 10 years of age. Observed adverse effects, which were generally mild, occurred in patients with baseline intellectual disability, attention deficit disorder and behavioural problems. Behavioural adverse effects warranted discontinuation of the medication in only three patients. The severity of intellectual disability (mild versus moderate or severe) did not affect the extent of the response or the occurrence of side-effects. It is concluded that gabapentin is equally effective as an add-on medication against partial seizures in patients with or without intellectual disability. However, children with intellectual disability who also are less than 10 years of age with baseline attention deficit appear to be at a higher risk of behavioural side-effects.

Efficacy of gabapentin therapy in children with refractory partial seizures.

Thirty-two children with refractory partial epilepsy received open-label gabapentin as an additional medication to their antiepileptic drug regimen. Gabapentin was given in a dose ranging from 10 to 50 mg/kg per day (mean dose, 26.7 mg/kg daily). All patients had partial seizures with or without secondary generalization. Compared with baseline, 11 patients (34.4%) had a greater than 50% decrease in seizure frequency, and 4 (12.5%) had a 25% to 50% decrease in seizure frequency. Of the seven children who received the medication for 6 months or longer, two were seizure free and four were almost seizure free (having one seizure every few months). Mean gabapentin concentration was 4.8 micrograms/ml, and mean apparent clearance was 372 ml/kg per hour. The major reported side effects were behavioral. These consisted of hyperactivity, irritability, and agitation that occurred in patients with baseline mental retardation with attention deficit. We conclude that gabapentin can be a useful adjunctive medication in the treatment of refractory partial epilepsy in children.

Vertebral artery dissection: issues in diagnosis and management.

Vertebral artery dissection is an uncommon cause of stroke in children. Accuracy of diagnosis by magnetic resonance angiography (MRA) instead of invasive transfemoral angiography (TFA) has been controversial. The need for anticoagulation and duration of such therapy is also arguable. We report 2 boys with vertebral artery dissection: one, aged 7 years, presented with hemiparesis and seizures and the other, aged 4 years, presented with ataxia. Each boy's initial MRA was not interpreted as delineating occlusive lesions to explain the posterior circulation infarcts visualized on computed tomography and magnetic resonance imaging scans. However, subsequent MRAs were suspicious for vertebral artery dissection, which was confirmed by TFA. Both children were treated with anticoagulation therapy. The first patient continued to manifest evidence of new infarcts despite treatment (initially with aspirin alone, followed by anticoagulation with heparin and warfarin), and is now maintained on a combination of high dose warfarin and aspirin. The second patient is now maintained on aspirin alone after initial anticoagulation for 6 months with heparin followed by warfarin. A high index of suspicion for vertebral artery dissection may allow diagnosis on the basis of MRA alone. Previous reports have indicated good outcomes of vertebral artery dissection in children and adults irrespective of anticoagulation treatment. Our experience suggests that anticoagulation may be beneficial in preventing further strokes caused by the dissection.