Behavior problems in children before first recognized seizures.

OBJECTIVE: It is not known when behavior problems begin in children with epilepsy. The purposes of this study were to: 1) describe the rates of behavior problems in children before their first recognized seizure, 2) determine the differences in behavior problems between children with a first recognized seizure and their healthy siblings, and 3) identify the seizure variables early in the course of the condition that are associated with behavior problems before the first recognized seizure. METHODS: The sample was 224 children (4-14 years old) with a first recognized seizure and their 135 healthy siblings. As part of a larger study, computer-assisted structured telephone interviews were conducted with mothers to measure child and sibling behavior problems. Behavior problems were measured using the Child Behavior Checklist. Frequencies, t tests, correlational analysis, and multiple regression were used to analyze data. RESULTS: Higher than expected rates of behavior problems in the 6 months before the first recognized seizure were found in the total seizure sample, with 32.1% being in the clinical or at-risk range. Rates were highest in children who had previous events that were probably seizures, with 39.5% in the clinical or at-risk range. Children with seizures had significantly higher Total, Internalizing, Attention, Thought, and Somatic Complaints problem scores than their nearest-in-age healthy siblings. Within the seizure sample, variables significantly associated with behavior problems after adjusting for research site, child sex, child age, and socioeconomic status (as represented by primary caregiver's education) were interactions of previously unrecognized seizures with gender and epilepsy syndrome/type of seizures. CONCLUSIONS: Children with previously unrecognized seizures are already at increased risk for behavior problems at the time of their first recognized seizure. These findings are consistent with the hypothesis that in some children, epilepsy is a pervasive condition that includes both seizures and behavioral problems.

Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus.

OBJECTIVE: To report the pharmacokinetics of intravenous valproate (VPA) in children with generalized convulsive status epilepticus (GCSE) or nonconvulsive status epilepticus (NCSE). To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsants. CASE SUMMARY: Two patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, phenytoin, and pentobarbital received intravenous VPA. Apparent volume of distribution (Vd) following a 20 mg/kg loading dose was 0.29 L/kg. Maintenance infusions of 4-6 mg/kg/h produced steady-state total concentrations of 66 mg/L and 92.4 mg/L (unbound concentration 44.6 mg/L). Clearance ranged from 63-66 mL/h/kg. An eight-year-old with NCSE received intravenous VPA (13.4 mg/kg load followed by 9 mg/kg every 8 h). Total and unbound steady-state VPA concentrations were 32.9 mg/L and 21.2 mg/L, respectively. Elimination half-life was eight hours. DISCUSSION: We constructed a pharmacokinetic simulation using VPA parameters from children receiving mono- or polyanticonvulsants. Our Vd and elimination half-life rates were comparable with published pediatric values. Patients on hepatic inducers had clearance rates 2.5 times those of children receiving oral anticonvulsant polytherapy. Unbound fractions (48.3% and 66%) were significantly higher than normal. CONCLUSIONS: A 20 mg/kg loading dose should produce a concentration after the bolus dose of approximately 75 mg/L. Initial infusion should consider hepatic induction (noninduced = 1 mg/kg/h, polyanticonvulsant therapy = 2 mg/kg/h, and high-dose pentobarbital = 4 mg/kg/h). Adjustments should be based on response and serum concentrations.

Moebius syndrome and central respiratory dysfunction.

Two infants, 18 months and 4 months of age, who were born with bilateral VI and VII nerve palsy (Moebius syndrome) experienced central respiratory failure requiring persistent ventilation. The computed tomography scan showed small brainstem tegmental calcifications. These findings suggest intrauterine brainstem necrosis including the respiratory center and poor prognosis for independent respiration.

Somatosensory evoked magnetic fields in patients with stroke.

We used magnetoencephalography to evaluate areas of sensory cortex in patients with ischemic strokes involving the somatomotor system. We measured somatosensory evoked magnetic fields using a 7-channel neuromagnetometer and estimated the location of cortical responses to median nerve stimulation in 5 patients with cortical or subcortical strokes involving the somatomotor system. All patients underwent quantitative neurological examinations and a high resolution volumetric magnetic resonance imaging. The estimated current dipoles were localized onto the patient's own MRI scan in all patients with measurable responses. The location of the estimated dipole was always in non-infarcted tissue in the anatomical region of the somatosensory cortex. In 1 patient the somatosensory dipole localized to a peninsula of cortex flanked by infarcted tissue. Single photon emission computed tomography found the localized area of cortex to have significant blood flow. The estimated current dipole strengths of somatosensory evoked fields from median nerve stimulation correlated significantly (r = 0.95, P < 0.02) with the patient's ability to recognize numbers written on the involved palm (graphesthesia). The combination of evoked magnetic field recording and magnetic resonance imaging is a promising non-invasive technology for studying brain function in patients with cerebrovascular disease.

Noninvasive preoperative cortical localization by magnetic source imaging.

The authors successfully used magnetoencephalography and MR data to localize the sensorimotor cortex in two patients prior to neurosurgery; preoperative localization influenced surgical management.

Comparison of CT- versus MRI-guided, computer-assisted depth electrode implantation.

Fourteen candidates for ablative seizure surgery underwent CT-guided, computer-assisted stereotactic depth electrode implantation and 21 underwent MRI-guided, computer-assisted implantation. A hand-held computer with no graphic capability was used for CT-guided procedures. A computer work station which included a high-resolution color graphics terminal with touchscreen interfacing and software capable of simulating targets and trajectories in single or multiple views was used for MRI-guided procedures. Previous phantom studies done with a 1.5-tesla MR scanner suggested acceptable localization error. Localizing information was obtained in 10 (71.4%) of 14 of the CT-guided implants and in 16 (76.2%) of 21 of MRI-guided cases. In the CT group, 7 (70%) were seizure-free and 8 (80%) were greater than 90% improved at 1 year follow-up. In the MRI group, 8 (80%) were seizure-free and 9 (90%) were greater than 90% improved at latest follow-up.

Magnetoencephalographic localization of subdural dipoles in a patient with temporal lobe epilepsy.

We report magnetoencephalographic localization of subdural electrode dipoles placed at the basal and mesial surfaces of the temporal lobe in a patient with temporal lobe epilepsy. The locations of the three dipoles were predicted from their magnetic fields with a computer model of the head as a conducting sphere. The predicted locations were within 1, 3, and 4 mm of the actual locations. These results, obtained in an area of the brain from which epileptiform discharges are frequently recorded, strongly support the capability of magnetoencephalography to accurately localize electrical events in this brain region.

Electroencephalographic studies of simple partial seizures with subdural electrode recordings.

We used subdural electrodes to study the EEG features of simple partial seizures in 7 patients. We detected epileptiform discharges in 61 of 68 subdurally recorded simple partial seizures compared with 6 of 55 simple partial seizures recorded with scalp electrodes (p less than 0.0001). The onset of 36 nonmotor simple partial seizures was detected only by the medial and basal temporal subdural electrodes, and the onset of 25 simple partial seizures with motor manifestations was recorded by subdural electrodes only from the lateral cortex of the posterior frontal lobe. There was a close correspondence between the area first involved in the epileptiform discharge during simple partial seizures and the area first involved during complex partial and secondary generalized tonic-clonic seizures. Subdural electrodes may be effective in localizing the onset and spread of simple partial seizures, including those that arise from the medial temporal lobe.

Subdural electrode as a dipole source for magnetoencephalography.

A subdural electrode was designed and constructed with 3 pairs of contacts to make 3 dipoles. The dipoles well approximate the expected magnetic behavior for a current dipole and can be used clinically to test localization capabilities of magnetoencephalography.

Improved accuracy of MEG localization in the temporal region with inclusion of volume current effects.

We studied the magnetic field maps generated by six dipoles in the temporal region of a plastic skull filled with conducting gel. The data were processed with two mathematical models. One, using Biot-Savart's law, considered only the magnetic field generated by a localized current dipole, and the other considered a dipole in a sphere and included volume current effects. The contribution of volume current effects to the MEG maps was significant. The localizing capability of MEG improved from an average distance of 2.9 cm to 0.9 cm when volume current effects were considered.

Magnetoencephalography and epilepsy research.

Magnetoencephalography is the detection of the magnetic field distribution across the surface of the head, which is generated by a neuronal discharge within the brain. Magnetoencephalography is used in clinical epilepsy to localize the epileptogenic region prior to its surgical removal. A discussion of the instrumentation based on the superconducting quantum interference device that is used for detecting the magnetic field distribution, the analytical techniques, current research, and future directions of magnetoencephalography in epilepsy research is presented.

Localization of magnetic interictal discharges in temporal lobe epilepsy.

Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.

Modelling the temporal region in patients with temporal lobe epilepsy.

EEG interictal epileptiform discharges in temporal lobe epilepsy are associated with magnetic fields. The maxima of magnetic spikes recorded over the spherical portions of the head appear fairly symmetric, whereas those over the lower temporal region often have irregular shapes. Furthermore, their magnitude is often unequal with the extremum over the lower temporal region usually of lower magnitude than the extremum over the upper temporal region. This lack of symmetry in shape and magnitude may be due to non-sphericity of the skull over the temporal region or to variations in conductivities of intervening tissues. We present our observation in two patients suggesting that the surface contours of the head contribute to the apparent asymmetries of the field pattern but that the head contours alone may not account for the asymmetries seen in the clinical data.

The electroencephalogram in the evaluation of the patient with epilepsy.

The authors describe the use of the electroencephalogram (EEG) in the diagnosis of patients with epilepsy, with specific reference to various seizures types and to commonly seen electrographic abnormalities. Also reviewed are normal variants that are sometimes erroneously thought to be epileptic in nature. The use of special studies, including invasive electrographic recording, is briefly discussed.

Verbal and cognitive sequelae following unilateral lesions acquired in early childhood.

Eight left-hemisphere lesioned children and eight right-hemisphere lesioned children between 18 months and 8 years of age were compared to control subjects on a battery of intelligence and language measures. Both left- and right-lesioned subjects had lower IQ scores than their controls, yet most functioned within the normal range or higher. Lexical comprehension and production were depressed in both subject groups and appeared to be depressed to a greater degree in right-lesioned subjects than in those with left lesions. In contrast, syntactic production in left-lesioned subjects was markedly deficient in comparison to controls as well as right-lesioned subjects. Although both subjects and controls included children with articulation errors, the number of misarticulating children and misarticulated sounds was greatest in the left-lesioned group. Finally, fluency disorders were observed in both right- and left-lesioned subjects but were not observed in controls. The study provides further evidence that the right and left hemispheres are not equipotential for language and that left-hemisphere lesions acquired early in childhood impair syntactic development to a greater degree than do right-hemisphere lesions.

Acquired capsular/striatal aphasia in childhood.

We studied a case of language loss caused by an acquired vascular lesion in the putamen, anterior limb of the internal capsule, and lateral aspect of the head of the caudate nucleus in a 7-year-old right-handed girl. Acute right-sided hemiplegia, mutism, oral apraxia, and disturbance in language comprehension but no dysarthria were present. During recovery, a nonfluent aphasia with anomia was evident. After six months, only mild hemiparesis and minor spelling difficulties persisted. We compared this patient with an 11-year-old right-handed girl with right-sided hemiparesis and dysarthria but no language loss following a lesion in the globus pallidus, a portion of the posterior limb of the internal capsule, and the body of the caudate. The presence of a language disturbance in the first but not the second patient was attributed to the difference in lesion location. The symptoms and lesions were similar to those in recent reports of adult patients. To our knowledge, this is the first report of these findings in a child with a left-hemisphere lesion.