Neuronal supersensitivity to acetylcholine induced by kindling in the rat hippocampus.

Kindling is an experimental model of epilepsy in which periodic brain stimulation induces the progressive development of electrical and behavioral seizures. A kindling-induced electrical seizure (afterdischarge) in the rat hippocampus produces prolonged neuronal supersensitivity to microiontophoretically applied acetylcholine after a latency of 40 to 60 minutes. Neuronal acetylcholine supersensitivity is correlated with the further progression of kindling. A larger hippocampal after-discharge is elicited by a subsequent kindling stimulus delivered in the presence of acetylcholine supersensitivity, but not by one delivered before the onset of the supersensitivity. The results suggest that alteration of synaptic sensitivity to acetylcholine may contribute to kindling and epileptogenesis.

Local-regional anesthesia during childbirth: effect on newborn behaviors.

Administration of local-regional anesthesia during norgnal deliveries was correlated significantly with newborn behaviors as evaluated by the Brazelton neonatal assessment scale. Three days after birth, infants whose mothers received local-regional anesthesia were more irritable and motorically less mature than those infants whose mothers were not medicated.

Complex partial seizures of infancy.

Ictal manifestations of complex partial seizures in infancy have not been described previously. Using long-term video/electroencephalographic and telemetric monitoring techniques, 187 seizures were recorded in 14 infants under 2 years of age. With one exception, the infants were profoundly delayed with intractable seizures. Nine had marked bilateral abnormalities on computed tomographic scan. The seizure manifestations noted most frequently consisted of behavioral arrest with forced lateralized deviation of the head and eyes and tonic upper-extremity extensor stiffening. Complex facial automatisms such as chewing, sucking, mouthing, and blinking were relatively common. Ictal paroxysmal onset was always lateralized on electroencephalograms, whereas the interictal recordings revealed multifocal epileptic discharges, generalized slowing, and voltage attenuation. The ictal behavioral manifestations and electric seizure patterns were quite distinctive yet were often undiagnosed on routine evaluations.

Seizures after convulsive therapy: a retrospective case survey.

We reviewed all documented cases of spontaneous seizures that followed convulsive therapy. Nineteen studies provided information in 81 cases. The average annual incidence of spontaneous seizures was 114 per 100,000, 5 times more frequent than an age-adjusted nonpsychiatric cohort. Host susceptibility rather than treatment features influenced seizure development. A longer latency to first seizure was associated with greater likelihood of seizure recurrence, a relationship also observed in posttraumatic epilepsy.

Dysplastic gangliocytoma and intractable partial seizures in childhood.

We describe the clinical, radiologic, and EEG features of 3 children who had dysplastic gangliocytomas of the cerebral hemispheres and drug resistant partial seizures that began in infancy. Following cortical resection, 2 are seizure-free and the third almost seizure-free. The dysplastic gangliocytoma may be an important and surgically remediable cause of very early malignant partial seizures.

Cognitive outcome of children with epilepsy and malformations of cortical development.

OBJECTIVE: To assess intellectual functioning (IQ) in 54 children and adolescents with intractable epilepsy who later underwent cortical resection due to unilateral malformations of cortical development acquired in utero. METHODS: Lesion type was classified into circumscribed mass lesions and diffuse cortical dysplasia based on histopathologic analysis of surgical tissue. Cortical dysplastic lesions were further graded as mild, moderate, or severe according to specific microscopic features. Laterality of lesion was determined through neurologic examination and electrophysiologic and neuroradiologic procedures. Classification of lesion type was corroborated by its significant relationship with other disease-related variables known to be related to clinical severity (age at seizure onset, age at resection, and extent of lesion). RESULTS: Analyses of covariance revealed that circumscribed lesions had a less deleterious effect on nonverbal IQ than did diffuse cortical dysplasia, after controlling for age at seizure onset and extent of lesion. This effect was also found on verbal IQ measures, but only in subjects with right-sided lesions. Subjects with left-sided lesions performed significantly more poorly on verbal IQ measures than those with right-sided lesions. Additionally, younger age at onset and greater extent of lesion were associated with poorer cognitive outcome. CONCLUSIONS: Cortical dysplasia and early left hemisphere lesions have a significantly worse impact on cognitive functioning than circumscribed lesions or right hemisphere developmental lesions in children with epilepsy.

Focal resection for malignant partial seizures in infancy.

There is little experience with excisional surgery for drug-resistant partial seizures in very young patients. We describe our experience with 5 infants under 1 year of age with malignant partial seizures and deteriorating developmental status. All were experiencing frequent daily seizures that did not respond to 1st-line antiepileptic medications at high therapeutic serum levels and considerable medication toxicity. Three infants had complete resection of epileptic tissue (frontal corticectomy and prefrontal lobectomy) and are seizure-free. Two underwent partial resection (lateral temporal lobectomy, frontal corticectomy with anterior callosotomy) and have experienced a significant reduction in seizure frequency. Surgery did not result in any significant neurologic deficit or lead to compromise of developmental status. From these data, we tentatively conclude that excisional surgery can be performed safely in selected infants with medically uncontrolled malignant partial seizures and may significantly improve long-term seizure status. Referral to a tertiary center specializing in early childhood epilepsy surgical evaluation may be considered in these circumstances.

Surgery for intractable epilepsy: issues and outcome.

For certain forms of childhood epilepsy that remain uncontrolled despite adequate treatment with standard antiepileptic medication, surgical therapy should be considered as a potential avenue of treatment. The prognosis for seizure control after early surgery is generally favorable and is at least comparable with that of adults. Remissions are often long-standing or permanent. The results are particularly beneficial if a discrete region of abnormal epileptogenic tissue can be excised. The three major procedures--focal resection, corpus callosotomy, and hemispherectomy--have all been performed successfully in children, and their complication rates are low. With the exception of the obvious benefit conferred by alleviating seizures at a younger age, earlier surgery also improves later psychosocial status and adaptive function. By contrast, persistent seizure activity decreases the likelihood of achieving a functionally independent and economically productive adult life. The psychosocial benefits therefore constitute the most important argument in favor of early surgical intervention. Although relatively little is known about the neuropsychologic consequences of early surgery, there are few deleterious long-term cognitive or behavioral deficits if surgery is uncomplicated. However, relatively little is known about neural reorganization after early surgical excision or hemispheric disconnection, and this remains the greatest challenge for the future.

Rapid sequential phenobarbital treatment of neonatal seizures.

The optimal serum concentration of phenobarbital in newborns and its safety at high doses are not well established. The dose response relationship of rapid sequential phenobarbital loading in the newborn was examined and the efficacy of high-dose monotherapy was compared with the addition of a second anticonvulsant for persistent seizure activity. A single loading dose of phenobarbital 15 to 20 mg/kg was initially administered to 120 newborns. Nonresponders received sequential bolus doses of 5 to 10 mg/kg until seizures ceased or a serum concentration of 40 micrograms/mL was obtained. Infants with refractory seizures received additional phenobarbital to a maximum serum concentration of 100 micrograms/mL. The seizures of 48 babies (40%) were controlled after initial loading and 37 of the remaining 72 subjects (51%) responded at serum concentrations of as great as 40 micrograms/mL. The seizures of only seven subjects were controlled at greater concentrations. A second anticonvulsant controlled seizures in 13 of the 28 subjects (46%) whose seizures were refractory to phenobarbital. A gestational age of less than 32 weeks was associated with a significantly better response to phenobarbital. Serum phenobarbital concentrations greater than 50 micrograms/mL produced only occasional feeding difficulty and sedation. It was concluded that sequentially administered IV phenobarbital controls seizures in both term and preterm newborns (77%). This therapeutic effect is dose dependent but plateaus at a serum concentration of 40 micrograms/mL. At greater serum concentrations, unresponsive patients should receive a second antiepileptic agent.

Placement of intracerebral depth electrodes during excisional surgery for epilepsy: value of intraoperative ultrasound.

The authors describe the use of intraoperative US for directing placement of depth electrodes for the localization of seizure foci prior to temporal lobectomy. They used this technique in seven patients (six undergoing temporal and one frontal resection), and encountered no complications.

Intensive monitoring in the epileptic child.

Techniques for intensively monitoring epileptic seizures are being increasingly applied to childhood seizure problems. This article reviews the salient features of the past and present monitoring methodologies and discusses their relevance for studying the pediatric age group. Clinical applications of intensive monitoring presently include differential diagnosis and characterization of attacks, topographic localization of paroxysmal discharges, spike frequency studies, therapeutic re-evaluation, and neuropsychological testing. Petit mal, infantile spasms, and pseudoseizure disorders have been studied in greatest detail. The particular problems associated with studies of infants and children are noted. To date, intensive monitoring has primarily been carried out in adult populations. However, pediatric applications are likely to become more prevalent as monitoring studies continue to demonstrate that new information can be generated that would otherwise be unobtainable by conventional recording techniques.

A safe and effective paradigm to functionally map the cortex in childhood.

Conventional cortical stimulation based on pulses of fixed duration briefer than the chronaxie rarely elicit responses in infants and young children. We developed a stimulation paradigm that relies on increments in both stimulus intensity and pulse duration. This approach ensures that stimulation parameters converge to the chronaxie by mathematically minimizing the energy required to elicit a response. In six patients, this paradigm successfully elicited clinical responses and/or afterdischarges at thresholds 5-8 mA below the standard paradigm and at up to 64% lower energy levels. Furthermore, three patients under age 5 years who did not respond to maximal fixed duration stimulation demonstrated afterdischarges and clinical responses when longer pulse durations were utilized. These findings indicate that a paradigm based on dual increments is effective for cortical mapping in children. Furthermore, by ensuring responses at lower energy levels, it may be more efficient for mapping the cortex at all ages.

Localization of epileptogenic foci using a simple reference-subtraction montage to document small interchannel time differences.

We present a modified EEG montage that detects small interchannel time differences and assists in localizing the epileptogenic focus. Regions with apparently synchronous epileptic discharges are displayed simultaneously in referential and subtraction derivations. The subtraction derivation is a bipolar configuration of two regions of interest that are not necessarily adjacent. The referential derivation reveals the polarity, voltage, and morphology of the two discharges, and the subtraction derivation detects asynchrony; the combined reference-subtraction derivation thus indicates the region that is activated first.

Long term cassette EEG monitoring of childhood seizures.

We studied the clinical efficacy of 4-channel cassette recording of the EEG for 105 children being evaluated for possible seizures or further clarification of a known seizure disorder. Compared to the conventional EEG, 24 hour cassette EEG (C-EEG) studies yielded new diagnostic electroclinical information for 21 percent of the children (22 patients). For 41 percent of cases, the C-EEG findings considerably broadened the clinical knowledge of the disorder and provided a basis for therapy modification. In the remaining 38 percent, no significant electrical or clinical events occurred so that C-EEG studies yielded no new important information. The utility of C-EEG was greatest for younger patients with generalized epilepsies whereas older children with partial epilepsies constituted the majority of diagnostic failures. These findings demonstrate that C-EEG recording may contribute useful information concerning childhood paroxysmal disorders, and underscore the importance of careful patient selection.

Video EEG diagnosis of repetitive behavior in early childhood and its relationship to seizures.

Differentiating seizures from pseudoseizures frequently is challenging in very young children manifesting repetitive, stereotypic behavior. Using video electroencephalographic recording, we evaluated 60 patients, younger than 10 years of age, with episodic signs and symptoms believed to be seizures despite repeatedly normal routine electroencephalograms. Nine patients (15%) had simple partial and atypical absence seizures. Twenty-four patients (40%) had pseudoseizures presenting as rhythmic movements or staring. Pseudoseizure frequency was greater than the frequency of true seizures; brief staring episodes were common. Motor pseudoseizures usually were of longer duration than true seizures and could be brought on with verbal encouragement. Furthermore, the stereotypic motor presentations were quite different from those of true motor seizures but were difficult to recognize from historic, clinical, and routine electroencephalographic data. Symptomatic patients can be clinically diagnosed by analyzing confirmed episodes with video electroencephalography.

[Results of surgery treatment of epilepsy]. / Resultados del tratamiento quirúrgico de la epilepsia.

The recent advances in the surgical treatment of epilepsy have resulted in great improvement in the overall outcome of these patients. The pediatric group has probably benefited the most as patients who previously were not candidate for this form of treatment are now able to undergo epilepsy surgery with results which are as good as those of adults. In fact, children may now benefit the most, as the control of their epilepsy and our ability to stop their anticonvulsants may allow them to better develop from a psychosocial aspect. Also, because of their plasticity, young children may tolerate surgery involving loss of eloquent cortex without subsequent permanent deficits. The most recent reported results from different centers indicate that 68-90% of patients undergoing temporal lobectomy remain seizure free while the percentage of patients remaining seizure free after extratemporal resections is approximately 50-66%. However, one of the problems with these results is that they vary significantly from one center to another because of the methodology used to evaluate results and the selection of patients depending on the strength of the centers. At present we do not have an optimal method to evaluate results of epilepsy surgery that takes in consideration not only seizure control but also psychosocial outcome. It is our goal to develop such method which will ultimately help us identify the best surgical candidates and predict their outcome.

[Neuropathology of refractory epilepsy in children]. / Neuropatología de la epilepsia refractaria en niños.

INTRODUCTION AND OBJECTIVES: The pathological findings in surgical material from children with refractory epilepsy has not offered yet a clear understanding of its role in this condition. The objective of this paper is to report our findings to further expand our knowledge about refractory epilepsy in children. MATERIAL AND METHODS: Results of microscopic examination of the surgical specimen obtained from 80 children, ages 12 or younger, who had surgery for intractable epilepsy at Miami Children's Hospital between 1990 and 1996 were reviewed. RESULTS: Examination was normal only in one. The rest revealed ectopic neurons (1), dysplastic cells with ectopic neurons (2), dyslamination with large neurons (7), dyslamination with ectopic neurons (18), dyslamination with dysplastic cells (10), pachygyria (2), encephalomalacia (9), gliosis with ectopic neurons (10), gliosis without ectopic neurons (3), developmental ectodermal tumor (6), ganglioglioma (2), tumors (3), and Rasmussen encephalitis (4). Lesions were located to the temporal lobe in 34 children. CONCLUSIONS. Extratemporal lesions are more frequent than temporal one, including hyppocampal sclerosis. Ectopic neurons, the most frequent pathological findings, rather than a cause of seizure may be a marker other highly epileptogenic cortical malformations.