Histological appearance of a chronically stimulated vagus nerve in a pediatric patient.

Histological analysis of chronically stimulated human vagus nerves is lacking in the literature. In this study, we describe the first microscopic findings in a chronically stimulated left vagus nerve from a pediatric patient. Our results show many histological changes in and around the stimulated nerve with severe demyelination. Further long-term clinical and postmortem examinations of chronically stimulated vagus nerves in both children and adults are needed to ascertain whether prolonged exposure to electrical current can cause clinical dysfunction of this nerve.

The acute management of seizures.

There are a growing number of treatment options for children with acute seizures and SE. With continued new drug development and reformulation of existing antiepileptic drugs, better treatment protocols will be available. The primary goal continues to be minimizing the morbidity and mortality associated with acute seizures and SE. This is accomplished only if the pediatrician's aim is early seizure recognition and treatment with close monitoring for potential complications.

Congenital porencephaly: MR features and relationship to hippocampal sclerosis.

PURPOSE: We determined the frequency of amygdalar-hippocampal atrophy in patients with congenital porencephaly-related seizure disorders to ascertain whether specific MR features of the porencephaly correlate with amygdalar-hippocampal atrophy and epilepsy. METHODS: We studied brain MR images of 22 patients with congenital porencephaly and measured the volume of the amygdala, the hippocampal formation, and the porencephalic cyst. We then compared imaging features with seizure symptoms. RESULTS: Porencephaly was unilateral in 20 patients and bilateral in two. Eighteen patients had cortical or subcortical cavitation and four had encephaloclastic changes (noncircumscribed parenchymal destruction associated with cystic components). The porencephaly was located in the middle cerebral artery territory in 12 patients, in the posterior cerebral artery in four, in the internal carotid artery in two, and in multiple vessels in four. The volume of the porencephalic cyst ranged from 1% to 32% of total intracranial volume (mean, 11%). Volumetry detected atrophy of the hippocampal formation in 21 cases (11 unilateral, 10 bilateral) and atrophy of the amygdala in 12 (nine unilateral, three bilateral). No correlation was found between size or location of the porencephaly and degree of hippocampal atrophy. Seizure symptoms correlated with mesial temporal origin but not with cyst location. CONCLUSION: Amygdalar-hippocampal atrophy often coexists with congenital porencephaly (95%), and the atrophy may be bilateral despite unilateral cysts. Hippocampal structures should be carefully assessed in patients with porencephaly-related seizures.

Congenital porencephaly and hippocampal sclerosis. Clinical features and epileptic spectrum.

We studied clinical features and seizure localization in 14 patients with porencephaly and intractable seizures. Perinatal complications were present in nine patients, childhood febrile convulsions in two, congenital hemiparesis in 12, and intellectual impairment in seven. Ten patients had psychoparetic complex partial seizures (CPS), three had sensorimotor simple partial seizures, and one had generalized tonic-clonic seizures. Surface EEG showed temporal onset in nine patients (one bitemporal) and extratemporal onset in four. MRI showed porencephaly in the distribution of the middle cerebral artery in eight patients, posterior cerebral in three, internal carotid in one, and multiple vessels in two. MR-based volumetry revealed hippocampal formation atrophy in 13 patients (eight unilateral and five bilateral) and amygdalar atrophy in 10 patients (nine unilateral and one bilateral). Hippocampal formation atrophy was concordant with CPS semiology in 10 patients (71%) and with EEG temporal localization in nine patients. Two patients had pathologic confirmation of mesial temporal sclerosis and were seizure free after temporal lobectomy. We conclude that mesial temporal sclerosis often coexists with porencephaly and is the likely seizure focus in the presence of concordant electroclinical data. This recognition implies that effective surgical intervention can be offered to certain patients with porencephaly-related seizure disorders. The dual pathology and association with perinatal cerebral vascular occlusion suggest a common ischemic pathogenesis.

Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy.

Hypothalamic hamartomas and gelastic seizures are often associated with cognitive deterioration, behavioral problems, and poor response to anticonvulsant treatment or cortical resections. The origin and pathophysiology of the epileptic attacks are obscure. We investigated 3 patients with this syndrome and frequent gelastic seizures. Ictal single-photon emission computed tomography performed during typical gelastic seizures demonstrated hyperperfusion in the hamartomas, hypothalamic region, and thalamus without cortical or cerebellar hyperperfusion. Electroencephalographic recordings with depth electrodes implanted in the hamartoma demonstrated focal seizure origin from the hamartoma in 1 patient. Electrical stimulation studies reproduced the typical gelastic events. Stereotactic radiofrequency lesioning of the hamartoma resulted in seizure remission without complications 20 months after surgery. The functional imaging findings, electrophysiological data, and results of radiofrequency surgery indicate that epileptic seizures in this syndrome originate and propagate from the hypothalamic hamartoma and adjacent structures.

Supplementary sensorimotor area epilepsy. Seizure localization, cortical propagation and subcortical activation pathways using ictal SPECT.

We studied clinical signs, EEGs and ictal cerebral blood flow by single-photon emission computed tomography (SPECT) in eight patients with intractable supplementary sensorimotor area (SSMA) seizures. SPECT scans were performed after injection of the regional cerebral blood flow tracer [99mTc]HMPAO (hexametylpropylene amine oxime) early in the ictal phase (2-5 s after seizure onset). Ictal SPECT demonstrated unilateral predominance of hyper-perfusion of the SSMA in all patients, concordant with either lateralizing clinical signs, lateralization of ictal scalp EEG or with the site of ictal onset of seizures, obtained from intracranial electrodes. Two distinctive cortical blood-flow propagation patterns were identified in SSMA seizures. The type I pattern consisted of primary involvement of the ipsilateral SSMA and dorsal premotor and motor cortex. The type II pattern consisted of bilateral but asymmetric mesial frontal propagation. Ictal contraversive head and eye movements were associated with a type I propagation pattern (P < 0.03). Activation of subcortical structures led to variable hyper-perfusion of the basal ganglia and thalamus. Contralateral cerebellar hyperperfusion was observed in all cases. We conclude that ictal SPECT is a useful method for seizure localization in patients with SSMA epilepsy. The observed heterogeneity of clinical features in SSMA epilepsy correlates with propagation to, and activation of, specific cortical structures, and is consistent with known anatomical interconnections between the SSMA, ipsilateral cortical and transcallosal cortical structures.

Epilepsy surgery outcome: comprehensive assessment in children.

The effect of extratemporal and temporal lobe cortical resection on children with intractable epilepsy is not well understood. We evaluated a comprehensive array of outcome variables in 33 consecutive children who received epilepsy surgery at 12 years of age or younger. Twenty-two (67%) children were seizure-free, three (9%) had a greater than 90% reduction in seizures, and four had no improvement. Antiepileptic drugs (AEDs) were not required in 10 (30%) children and were reduced in number in another 10. Six (29%) of 21 tested children had an improvement of greater than 10 points in Verbal or Performance IQ after surgery, while one (4%) had a decrease greater than 10 points in Verbal IQ. One mild hemiparesis and one inferior quadrantanopsia occurred; both were anticipated. We used the Child Health Questionnaire (CHQ), a valid and reliable instrument for children, to assess health-related quality of life (HRQOL). Six of 12 subscale scores of the CHQ were significantly lower in the surgical group compared with 410 age-matched control subjects. Parents were satisfied with surgical results in 28 (85%) cases. Pathologic tissue diagnosis and site of resection were not associated significantly with any outcome measure. We conclude that surgery eliminates seizures and reduces AED requirements in most children with intractable epilepsy selected by currently available methods. Further investigation is needed to establish the nature and significance of inferior scores in the surgical group in the HRQOL domains of physical function, general health, and self-esteem.

New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol.

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.