Prolonged epileptic blindness in an infant associated with cortical dysplasia.

We report a female infant with status epilepticus amauroticus and intractable focal motor seizures associated with congenital cortical dysplasia. EEG demonstrated persistent epileptiform discharges over the right parieto-temporal regions extending to occipital areas. She required cortical resection of the epileptic zone at age 8 months given failure of very high dose antiepileptic combinations. Histological analysis of a sample of cortex resected from the right central parieto-temporal region, identified by electrocorticography as the focus of epileptic activity, showed cortical dysplasia. The seizures ceased and the infant gained full vision after 48 hours. During an 8-year follow-up period she has had a few short-lived seizures, currently controlled with carbamazepine and vigabatrin. Her cognition and speech are intact. This case demonstrates that: (1) resection of a central temporo-parietal focus, which may have spread to the occipital regions, may result in complete visual recovery and cessation of seizures; and (2) EEG should be considered in every infant with alleged delayed visual maturation, to rule out concealed epileptic activity.

Pediatric candidates for temporal lobe epilepsy surgery.

Temporal lobectomy is an under-valued and effective therapy for selected children with temporal lobe seizures. This article details three components of the identification and evaluation of such children. The ictal symptoms and signs remains an essential component. This includes an aura suggesting limbic system involvement, and the nature of automatisms and other motor phenomena which may have lateralising value. Electroencephalography continues to accurately identify a principally epileptogenic focus in children and adults. The value of high quality magnetic resonance imaging is emphasized. Invasive studies are required in only a minority of cases. Several studies have revealed that 73-100% of carefully selected children receive benefit from this procedure whereas significant neurosurgical complications rarely occur.

Free radical production correlates with cell death in an in vitro model of epilepsy.

Free radical (FR) production, a major step in calcium-dependent neurodegeneration, has been linked to the generation of epileptiform activity and seizure-induced cell death. However, direct evidence of FR production in neurons during seizures has never been presented. Using hippocampal cultured slices we demonstrate that FRs are produced in CA3 but not CA1 pyramidal neurons during the rhythmic synchronous activity induced by the GABAA receptor antagonist bicuculline. The production of FRs (measured as changes in the fluorescence emission of dihydrorhodamine 123) was correlated with an increase in the baseline levels of intracellular calcium ([Ca2+]i) estimated by fluo-3 injected into individual neurons via a patch pipette. [Ca2+]i increased during spike bursting and returned to baseline levels after the burst termination in CA1, but not in CA3, pyramidal neurons where 'interburst' calcium concentrations progressively increased. Measurement of cell death, performed with propidium iodide 48 h after a 30-min exposure to bicuculline, revealed most prominent degeneration of pyramidal neurons in the CA3 pyramidal layer. The FR scavengers vitamin E and glutathione significantly reduced the seizure-induced neurodegeneration without supressing spontaneous epileptiform activity. These observations indicate that FR overproduction is related to seizure-induced neuronal death.

Outcome of epilepsy surgery in the first three years of life.

PURPOSE: We analyzed our experience over a 6-year period with early-childhood patients who had undergone epilepsy surgery, and investigated the surgical outcomes. METHOD: We reviewed the medical records of 23 children, ages 0-3 years, who underwent epilepsy surgery between 1991 and 1996. RESULTS: Twenty children had partial seizures; two had infantile spasms; and one had generalized tonic-clonic seizures at onset. The mean age at onset of seizures was 4.7 months, and the mean age at time of surgery was 15.3 months. A total of 32 operations (21 focal cortical resections and 11 hemispherectomies) was performed. Five of 12 children with seizures secondary to a neuronal migration disorder had reoperations, including three who ultimately underwent complete hemispherectomy. The pathology consisted of hemimegalencephaly in three patients, focal cortical dysplasia (FCD) in eight, tuberous sclerosis in one, Sturge-Weber syndrome (SWS) in five, infarction in two, low-grade glioma (LGG) in three, and post-herpes simplex virus encephalitis (HSE) in one. The follow-up period ranged from 1 to 6.5 years (mean, 3.2 years) from patients' last operation. The seizure outcome according to Engel's criteria was class I in 12 patients, class II in three, class III in six and class IV in two. CONCLUSIONS: Seizure outcomes after surgery were less favorable in infants with FCD than in those with SWS and LGG. Seizure outcome for the patients with hemispherectomies was excellent, compared with those who had focal cortical resections.

Interhemispheric interactions analyzed by coherence during flexor spasms.

OBJECTIVE: We used coherence analysis to test for leading discharges on an ipsilateral right mesial temporal lesion in a 5 year old boy with flexor spasms. METHOD: Digital EEG analysis with video-EEG telemetry was performed preparatory to epilepsy surgery. RESULTS: Study of 10 spasms with head drop and subsequent flexion of both arms demonstrated an interhemispheric time lag with secondary bilateral synchrony, with a mean difference of 17 ms. The right hemisphere led. After a lesionectomy with resection of epileptic regions (performed with electrocorticographical guidance), the patient has been seizure-free for 4 years. Pathology confirmed a low-grade mixed glioma and cortical dysgenesis. CONCLUSION: The coherence analysis demonstrated a pathway of secondary generalization, confirming that the lesional side was leading during ictal generalized discharges in flexor spasms.

Regionalized sensorimotor plasticity after hemispherectomy fMRI evaluation.

This study demonstrates the transfer of both motor and sensory functions from one hemisphere to the other in children who had an entire cortical hemisphere surgically removed. The areas of the cortex responsible for these new functions in the remaining hemisphere are associative motor and sensory areas and do not include the typical primary motor and somatosensory regions, thus suggesting the regionalization of brain plasticity. This regionalization can be evaluated with functional magnetic resonance imaging, supporting this technique as an effective tool in the study of brain plasticity.

Infantile spasms: seasonal onset differences and zeitgebers.

The health records of 76 infants with infantile spasms (IS) were reviewed retrospectively. The distribution of seizure onset was examined with respect to calendar month, annual changes in day length (photoperiod), and global solar radiation (GSR). IS onset was more frequent during the months with low GSR and short photoperiods. The greatest frequency of IS onset was in December and January (22 cases, 29%); the lowest was in April and May (8 cases, 10.5%). IS onset frequency (f) was more than twice as great in the months with a short photoperiod (10Light-14Dark) and a low GSR (f = 11) as compared with months with a long photoperiod (16Light-8Dark) and a high GSR (f = 5). IS onset frequency was 2.2-fold greater in months with a short photoperiod and a low GSR. This finding suggests that environmental photoperiodic factors (zeitgebers) may play a role in the onset of IS.

Positive epileptiform discharges in children with neuronal migration disorders.

Most epileptiform abnormalities show a negative polarity on EEG. Focal positive spike waves have rarely been identified in seizure disorders and are generally associated with physiological and neurological impairment. Results of EEG, computed tomography, MRI, and pathologic studies of 15 children with focal neuronal migration disorders who underwent surgery for refractory localization-related epilepsy were compared to examine the association between positive discharges and other findings. Subjects were studied both ictally and interictally by scalp EEG with the International 10-20 system and zygomatic or sphenoidal electrodes, and video EEG telemetry. The 5 children with positive discharges were significantly more likely to develop hemiparesis during the preoperative period (P < or = .025). Correlations were observed between positive discharges and lesions apparent on MRI situated around the rolandic fissure (P < or = .025). Children with positive discharges had a significantly less favorable outcome after surgical treatment (P < or = .025). Positive epilepti-form discharges in children with neuronal migration disorders may signal a more dysfunctional cortex leading to a focal neurological deficit or a more extended lesion than is detected on MRI. This would explain the less favorable outcome of seizures after surgery, since the epileptogenic areas and neuronal migration lesions cannot be completely resected.

Amygdala-kindled convulsions in suspended rats.

Amygdala-kindled Long-Evans rats were suspended in a harness--with all four feet off the ground--and their convulsions were triggered, videotaped, and scored. In the suspended subjects, it was found that kindled convulsions involve the hindlimbs as well as the forelimbs and that they involve tonus as well as clonus. These data contradict the commonly held view that kindled convulsions consist only of face and forelimb clonus. They suggest that kindled convulsions resemble the generalized, whole-body convulsions observed in the maximal electroshock model and other "maximal" seizure models.

Epileptic blindness in children: a localizing sign of various epileptic disorders.

UNLABELLED: The ictal manifestations, EEG, CT, and MRI correlates, as well as the management and outcome of 11 children with epileptic blindness are presented. Seven males and four females, aged 3 months to 12 years, experienced single or recurrent episodes of acute visual obscuration. Ictal blindness was the solitary epileptic phenomenon in only two children. The rest had other focal or generalized motor epileptic manifestations. Six children had either focal motor phenomena and/or unilateral EEG disturbances, with a normal head CT. The drug of choice in this group was carbamazepine and all became asymptomatic. Two patients had structural abnormalities of the brain, of which one had a low-grade occipital astrocytoma which was resected. His blindness abated shortly following initiation of carbamazepine, even prior to surgery. Status epilepticus amauroticus and focal motor seizures, secondary to focal cortical dysplasia, was detected in another 3-month-old infant. These required cortical resection and she regained full vision. Three patients had generalized epileptiform discharges on EEG, of which two were photic-induced. Blindness was accompanied with motor seizures and myoclonic jerks. Full seizure control could be achieved in only one child. CONCLUSION: our data suggest a relatively benign nature and a favorable outcome in most children with ictal blindness. Resection of a secondary temporo-parietal focus, as occurred in an infant with status epilepticus amauroticus which originated in the occipital region, may result in complete cessation of seizures and visual recovery.

Infantile spasms: cerebral blood flow abnormalities correlate with EEG, neuroimaging, and pathologic findings.

This ongoing study examines abnormalities of cerebral perfusion in a consecutive series of children with infantile spasms and correlates cerebral blood flow (CBF) abnormalities with electroencephalographic (EEG), neuroimaging, and pathologic findings. A consecutive series of children with infantile spasms, diagnosed by standard clinical and EEG criteria, had cerebral perfusion studies using 99Tc-HmPAO single photon emission computed tomography (SPECT), together with neuroimaging studies using computed tomography (CT) and/or magnetic resonance imaging (MRI), interpreted independently and correlated with surgical pathologic findings. Twenty children aged 2-13 months (mean 9.3 months) were studied over a 4-year period; 60% had symptomatic infantile spasms due to cerebral dysgenesis (33%), other congenital lesions (25%), tuberous sclerosis (17%), or other causes (25%), and the remaining patients were cryptogenic (40%). CBF abnormalities were present in 85%: multifocal decrease (40%), focal increase (25%), diffuse decrease (15%), and focal increase (10%), while the remaining 15% had normal cerebral blood flow. Focal cortical lesions may lead to infantile spasms, even in cryptogenic patients diagnosed by functional neuroimaging such as 99Tc-HmPAO SPECT. In selected patients, surgical excision of the cortical lesions leads to improved seizure control and possibly outcome. The localization and surgical excision of focal cortical lesions in infantile spasms required further investigation with functional and structural neuroimaging, EEG, and intraoperative electrocorticography.

Location of epileptic foci on interictal and immediate postictal single photon emission tomography in children with localization-related epilepsy.

Several neuroimaging techniques that supplement electrophysiologic methods of evaluating pediatric patients with localization-related epilepsies before surgery assess both structural and functional abnormalities. For example, single photon emission computed tomography (SPECT) with technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) has been used to demonstrate abnormal cerebral perfusion. States of cerebral perfusion during the interictal and immediate postictal periods have been reported to correlate with epileptiform foci identified by electroencephalogram (EEG). Between January 1987 and March 1993, we studied 55 pediatric patients with intractable seizures with prolonged video EEG telemetry in the epilepsy monitoring unit, followed by computed tomography, magnetic resonance imaging, and SPECT, before surgery to determine whether SPECT studies with 99mTc-HMPAO improved the accuracy of locating the epileptic focus. Interictal SPECT was performed on all patients, and immediate postictal SPECT (within 10 minutes after seizure ended) on 17 patients monitored in the epilepsy monitoring unit. In 15 (88%) of the 17, the combination of interictal and postictal SPECT studies yielded results corresponding to the EEG abnormality, a result significantly better than that obtained from interictal studies alone: 21 (55%) of 38 (chi 2 = 5.647, P = .0175). SPECT scans showed localized abnormal perfusion in the ipsilateral temporal lobe in all six patients with mesial temporal sclerosis, but precise results were not obtained in cases of dual pathology and neuronal migration disorders. Depiction of cerebral perfusion by interictal and immediate postictal SPECT studies can lead to greater accuracy in the localization of epileptic foci.

Use of frameless stereotaxy with location of electroencephalographic electrodes on three-dimensional computed tomographic images in epilepsy surgery.

Epileptiform activity corresponding to structural lesions was identified by three-dimensional (3D) imaging using computed tomographic (CT) scan data concurrently with scalp EEG electrodes. The electrodes, placed according to the international 10-20 system, were used to record interictal and ictal epileptogenic foci in eight patients. Electrodes placed where marked or moderate epileptiform activity was detected were replaced with markers detectable on CT. Scans with these markers on the skin were obtained and the data transferred to a 3D imaging system, and correlated with underlying cerebral structures. The reformatted images were used to assess the relation among intracranial lesions, brain surface structures, and epileptogenic zones depicted by the markers. The images help the surgeon plan a craniotomy with enough space for both lesionectomy and resection of the epileptogenic zone. In the central regions where crucial motor functions are located, the markers indicate the central fissure or postcentral gyrus. An intraoperative 3D frameless stereotactic pointing device helps in directing further examination of the epileptogenic zone. This system improves on the precision available through intraoperative electrocorticographic recording in the extratemporal lobes, thus avoiding only approximate excision of lesion and epileptogenic zone and enabling the neurosurgeon to perform epilepsy surgery with greater confidence.

Neuroimaging studies in children with temporal lobectomy.

Twenty-eight children with intractable seizures who subsequently underwent a temporal lobectomy were studied by electroencephalogram (EEG), prolonged video EEG telemetry, computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) for the localization of epileptogenic foci. MRI showed abnormalities indicating epileptogenic foci in 21/25 patients and a increased signal intensity in 7/11 patients with mesial temporal sclerosis (MTS). SPECT showed corresponding abnormalities in 17/22 patients, including an interictal decrease in regional cerebral blood flow corresponding to the epileptogenic zone in 15. CT showed localized abnormalities in 16/28. All 12 patients with benign, slow-growing neoplasms showed an abnormality on CT scan. In children, MRI is essential in localizing epileptogenic abnormalities, especially MTS and cortical dysplasia. SPECT contributes to the localization of epileptogenic foci, which are often coincident with EEG abnormalities, particularly in single pathology. CT depicts benign neoplasms with calcification in the temporal lobe, which are likely to provoke complex partial seizures.

Phenotypic expression of benign familial neonatal convulsions linked to chromosome 20.

OBJECTIVES: To determine whether the syndrome of benign familial neonatal convulsions in a large family was linked to markers on chromosome 20q and to study the seizure patterns in affected individuals. DESIGN: A clinical and molecular biologic study of a single large family in which the probands were identical twins with benign familial neonatal convulsions. PATIENTS: Thirteen living affected family members and 27 living unaffected family members were evaluated. RESULTS: Multipoint linkage analysis with use of the chromosome 20q markers CMM6 and RMR6 gave a maximum lod score of 3.13 at theta = 0.063, indicating linkage in this family. Of the 13 affected members, 10 had known neonatal seizures. Four subjects had febrile seizures, of whom only two had known neonatal seizures. Two members had afebrile seizures later, one of whom had not previously suffered neonatal or febrile seizures. CONCLUSION: The phenotypic heterogeneity in this family, with an epilepsy syndrome determined by a single gene, was striking. This suggests that molecular genetic approaches to the common forms of idiopathic epilepsy, involving patients with clinically similar phenotypes from unrelated families, may be inappropriate.

Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups.

We reviewed the outcome (developmental, neurologic, and seizure) and prognostic factors of 57 cases of infantile spasms (17 cryptogenic, 40 symptomatic). The mean developmental score of the cryptogenic group (71.2 +/- 24.2) was significantly higher than that of the symptomatic group (48.4 +/- 24.5), as assessed by the Griffith Mental Developmental Scale. A resultant neurologic deficit was present in 23.5% of the cryptogenic group and 75.0% of the symptomatic group. Coexistence of other forms of seizures was observed in 35.3% of the cryptogenic group and 57.5% of the symptomatic group. Outcome was affected by the coexistence of other seizures, presence of neurologic deficit, time lag in initiation of treatment (cognitive outcome only), poor response to ACTH treatment, and persistent EEG abnormality. Character of spasms and time lag in initiation of treatment (seizure outcome only) did not have any significant effect on outcome.

Pathology of temporal lobectomy for refractory seizures in children. Review of 20 cases including some unique malformative lesions.

Significant pathological abnormalities were encountered in a series of 20 temporal lobectomies in children with intractable complex partial seizures. In particular, "dual pathology" (mesial temporal sclerosis with other lesions) was found rather than mesial temporal sclerosis as the only lesion. Unusual pathological findings included capillary penetration of neurons in a neuronal heterotopia in one patient, and foci of extensive cortical disorganization in some cases of mixed tumors and gangliogliomas. A high proportion of neuronal migration disorders was also seen with overlapping pathological features between cortical dysplasia and tuberous sclerosis. In this correlative clinical, radiological, electroencephalographic, and pathological study, some of the pathological lesions in children did not fit the classical categories of neoplasia and malformation and transitional forms were rarely encountered.

Focal cortical dysplasia in children with localization-related epilepsy: EEG, MRI, and SPECT findings.

A retrospective analysis was conducted of 9 children with focal cortical dysplasia and localization-related epilepsy who underwent epilepsy surgery. Focal cortical dysplasia includes malformed lesions with extensive abnormalities of neuronal morphology, architecture, and lamination. The patients were examined by EEG and video EEG telemetry, CT, MRI, and SPECT using 99mTc-HmPAO. EEG disclosed interictal localized epileptiform activity in 8 patients and nonepileptiform activity with slow waves in 1. Ictal EEG telemetry demonstrated a predominantly localized seizure onset in 8 patients and MRI demonstrated an abnormal loss of gray and white matter distinction in 6. Decreased regional cerebral blood flow (rCBF) was detected in 4 patients by interictal SPECT, and increased rCBF in the same epileptogenic focus in 2 by postictal SPECT. Pathologic analysis found focal cortical dysplasia in 8 patients. One had extensive focal polymicrogyria, pachygyria, and extensive white matter heterotopias. It is concluded that MRI can detect focal cortical dysplasia, which corresponds to the epileptogenic focus on EEG, and SPECT may help to detect a functional abnormality in the same region.

Detection and management of gangliogliomas in children.

Forty-two children treated for gangliogliomas were reviewed to identify the best methods of detection and management. Thirty-two of the tumors were supratentorial, four infratentorial, and six were in the spinal cord. Twenty-five patients presented with seizures; the mean duration of symptoms was 5 years in contrast to 1 year in non-seizure patients. Of 31 children studied by computed tomography (CT), calcification in the tumor lesion was found in 19. Magnetic resonance imaging (MRI) showed abnormal high-signal intensity on T2 imaging in six of eight patients. All patients underwent surgical resection and were diagnosed pathologically. Twenty-four patients had total resection, and 14 underwent temporal lobectomies including hippocampectomy. The management of this tumor remains surgical resection without the need for any adjuvant therapy.

The anticonvulsant effects of vitamin E: a further evaluation.

Vitamin E (d-alpha-tocopherol) has proven to be a useful adjunct to anticonvulsant drugs in clinical studies. Improvement has occurred even in patients with complex partial seizures, which are often resistant to drug therapy. In animals, vitamin E is effective against ferrous chloride seizures, hyperbaric oxygen seizures and penicillin-induced seizures. It has failed, however, to show anticonvulsant effects in the standard animal models used for drug screening--the maximal electroshock and threshold pentylenetetrazol tests. The present experiments were designed to further explore the anti-epileptic actions of vitamin E in animals. Three models related to complex partial epilepsy were used: 1) the development of amygdala-kindled seizures; 2) the development of electrically-induced status in kindled animals; and 3) the development of kainic-acid seizures. Vitamin E failed to produce significant effects in any of the models.