Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors.

Gangliogliomas are generally low grade neoplasms composed of mixtures of neoplastic glial and neuronal elements whose origin and exact nature are still controversial. We studied a series of 60 intracranial gangliogliomas looking for coexistent cortical architectural abnormalities (cortical dysplasia, microdysgenesis) and to determine if tumor behavior correlates with MIB1 (marker of cellular proliferation) labeling. The patients included 34 males and 26 females who ranged in age from 6 months to 55 years (mean 20 years). Thirty-eight tumors (63%) were located in the temporal lobe and 6 (10%) in the frontal lobe. Fifty-four patients (90%) presented with seizures (most with intractable epilepsy) and the duration of seizures ranged from 1 to 38 years (mean 14 years). In all cases, the predominant glioma component resembled a low grade fibrillary astrocytoma. In 14 tumors (23%), an oligodendroglial component was present. In one case, the glial component resembled an anaplastic astrocytoma. The tumors were characterized variously by perivascular chronic inflammation (N = 45, 75%), vascular proliferation (N = 36, 60%), granular bodies (N = 54, 90%), binucleated neurons (N = 36, 60%), calcification (N = 28, 47%), and cystic degeneration (N = 26, 43%). Meningeal involvement by tumor was observed in five (8%) cases. In 38 patients, sufficient tissue was resected to evaluate for the presence of concomitant cortical architectural abnormalities. Cortical architectural abnormalities were identified near to but clearly separate from the tumor in 19 (50%) patients. Only four patients including the anaplastic tumor died with tumor progression. MIB1 indices (positive tumor cells/1,000 tumor cells counted) in 54 cases ranged from 0 to 10.2 (mean 1.1 +/- 1.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Induced expression of NMDAR2 proteins and differential expression of NMDAR1 splice variants in dysplastic neurons of human epileptic neocortex.

Immunocytochemistry was used to study the expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 splice variants, and AMPA Glu-R2/3 in human brain resected for intractable epilepsy associated with cortical dysplasia. NMDAR2A/B intensely labeled dysplastic neurons showing staining in both the cell bodies and dendritic profiles. However, nondysplastic neurons were not immunoreactive to NMDAR2A/B. The antibody selective to NMDAR1 splice variants of NR1-1a. -1b, -2a, and -2b labeled dysplastic neurons, but few nondysplastic neurons. In contrast, the antibody to splice variants of NR1-1a, -1b, 2a, -2b, -3a, -3b, -4a, and -4b labeled both dysplastic and nondysplastic neurons. The different labeling patterns by these two antibodies indicate that variants of NMDAR1-3a, -3b, -4a, and -4b are present in nondysplastic neurons. Both dysplastic neurons and nondysplastic neurons were immunoreactive to AMPA GluR2/3, but denser immunoreactivity was observed in dysplastic neurons. We also found that the locations of dysplastic neurons labeled by NMDAR2A/B were related to focal epileptic EEG seizure onsets or spiking and to focal behavioral seizure types. Our results suggest that there is hyperexcitability of dysplastic cortical regions, at least in part, from the presence of NMDAR2 subunits and selectively expressed NMDAR1 splice variants in dysplastic neurons.

Seizure outcome after surgery for epilepsy due to malformation of cortical development.

PURPOSE: To explore seizure outcome after surgery for focal epilepsy due to malformation of cortical development (MCD), with focus on the role of MRI. METHODS: Thirty-five patients who had surgery for intractable focal epilepsy due to MCD identified by preoperative MRI and confirmed by histopathologic analysis of resected tissue were studied. Patients were aged 3 months to 47 years (median, 14 years) at the time of surgery. Duration of follow-up was 1 to 7.9 (mean, 3.4) years. RESULTS: At latest follow-up, 17 patients (49%) had Engel Class I outcome with no seizures or auras only; eight patients (23%) had Class II outcome, with rare disabling seizures; seven patients (20%) had worthwhile improvement; and three patients (9%) had no improvement. Seizure-free outcome tended to be more frequent among patients who had complete resection of unilateral MCD (excluding hemimegalencephaly) based on postoperative MRI (7/12; 58%), compared with patients with unilateral MCD who had incomplete resection (3/11; 27%), but the difference was not significant. The frequency of seizure-free outcome did not differ significantly between children (8/14; 57%), adolescents (7/15; 47%) or adults (2/6; 33%); between patients who had daily (12/24; 50%), weekly (4/9; 44%), or monthly (1/2; 50%) seizures preoperatively; between patients who had temporal (2/6; 33%) or extratemporal or multilobar resections (14/28; 50%); or between patients who were (9/16; 56%) or were not (8/19; 42%) studied with subdural electrodes. Results for all analyses were similar when analyzed at latest available follow-up or at 1 year after surgery. CONCLUSIONS: Surgery can offer seizure-free outcome for approximately one half of carefully selected patients with intractable focal epilepsy due to MCD. Complete resection of the MRI-apparent lesion may improve the likelihood for favorable outcome. MRI evidence of hemimegalencephaly or bilateral MCD suggests a low likelihood for postoperative freedom from seizures.

Increased densities of AMPA GluR1 subunit proteins and presynaptic mossy fiber sprouting in the fascia dentata of human hippocampal epilepsy.

In human hippocampal epilepsy, there is a consistent pathology of cell loss and reactive synaptic reorganization of 'excitatory' mossy fibers (MF) into the inner molecular layer (IML) of the fascia dentata (FD). In this study, neo-Timm's histochemistry of MFs and immunocytochemistry of GluR1 were used to determine, in patients with or without hippocampal sclerosis (HS), if there was a correlation between aberrant supragranular (IML) mossy fiber sprouting and increased densities of AMPA GluR1 subunit proteins in the IML of the FD. Computerized quantified densitometric grey values of Timm and GluR1 densities were corrected for the densities of granule cell losses using cell counts. In the IML of the HS group, despite the losses of granule cells, mossy fiber sprouting was significantly greater (P<0.000001) and GluR1 protein densities were significantly higher (P<0.0005) than those of the non-HS group. Unlike supragranular mossy fiber sprouting, which was limited to the IML, the increased GluR1 stainings were distributed throughout the whole molecular layer. For all cases, MF synaptic reorganization in the supragranular ML was correlated with GluR1 subunit protein densities in the IML (R=0.784, P<0.0093). These data demonstrate that in the human epileptic fascia dentata, there are significantly increased AMPA GluR1 subunit proteins associated with aberrant MF synaptic reorganizations. This suggests that the hyperexcitability of sclerotic hippocampus occurs, at least in part, from the associated changes of both presynaptic mossy fiber glutamatergic neoinnervation and increased GluR1 subunit proteins in the dendritic domains of the FD.

The prevention of oxyhemoglobin-induced endothelial and smooth muscle cytoskeletal injury by deferoxamine.

The oxidized breakdown products of hemoglobin are important in the pathogenesis of cerebral vasospasm because of their effects on the endothelium and the smooth muscle of the arterial wall. Cytoskeletal changes in cultured vascular cells are sensitive indicators of oxidative injury. Cultured endothelial cells and smooth muscle cells showed a dose-related disruption of the cytoskeleton, particularly the F-actin and vimentin filaments, when exposed to 10(-5) M oxyhemoglobin. The cytoskeletal injury was prevented by the addition of 10(-3) M deferoxamine or 1% albumin. These experiments support a role for deferoxamine in the pharmacological treatment of vasospasm. Furthermore, cytoskeletal studies of cultured arterial endothelial and smooth muscle cells provide a novel in vitro approach by which to study the cellular mechanisms of oxidant injury initiated by the breakdown products of hemoglobin.

Effects of naloxone during high dose barbiturate anesthesia.

This experiment was performed to investigate the ability of naloxone to reverse high dose barbiturate anesthesia or produce cerebrovasodilation or changes in cerebral metabolism in dogs neuronally depressed by high doses of barbiturate. Six dogs were deeply anesthetized with sufficiently high doses of sodium pentobarbital to produce and then maintain isoelectric activity or cerebral silence on the electroencephalogram (EEG). Blood flows were determined using the radioactive microsphere technique both before and after the intravenous bolus injection of naloxone (10 mg/kg), which failed to produce any significant changes in cerebral blood flow, the cerebral metabolic rate of oxygen, cerebrovascular resistance, or EEG activity. Cardiovascular parameters were also essentially unchanged. Naloxone in a dose of 10 mg/kg i.v. produced no changes in the cerebral or systemic circulations or in brain metabolism during high dose sodium pentobarbital anesthesia.

Time-dependent changes in cerebral and cardiovascular parameters in isoflurane-nitrous oxide-anesthetized dogs.

The purpose of this study was to examine the time-dependent effects of isoflurane-nitrous oxide anesthesia on cerebral blood flow and metabolism and on cardiovascular parameters. Eleven 15-kg mongrel dogs were anesthetized with 0.8% isoflurane (approximately 1.3 MAC (minimal anesthetic concentration], 70% nitrous oxide, and 30% O2 and were paralyzed with pancuronium. Blood flow (using the radioactive microsphere technique) and cerebrovascular and cardiovascular parameters were measured 6 times at 30-minute intervals beginning 2 hours after the induction of anesthesia. In this experiment, cerebral blood flow was markedly elevated at 2 hours after the induction of anesthesia, but then declined progressively by 40 to 50% over the 2 1/2-hour time period investigated, approaching values for normal awake dogs. The decline was accompanied by a progressive decrease in the cerebral metabolic rate of oxygen and a constant rise in cerebrovascular resistance. Blood flow to organs outside the central nervous system declined progressively, but with more variability between tissues. The mean arterial pressure increased slightly, and the peripheral vascular resistance almost doubled, but cardiac index, cardiac work, and stroke volume all decreased gradually. We conclude that isoflurane-nitrous oxide anesthesia produces significant cerebral vasodilatation in dogs, but that this effect diminishes over time. These time-dependent circulatory changes merit further investigation in humans.

Cerebral and systemic vascular effects of naloxone in pentobarbital-anesthetized normal dogs.

In this study, 10 mongrel dogs were anesthetized with sodium pentobarbital and nitrous oxide. Blood flow was determined using the radioactive microsphere technique before and after the bolus intravenous injection of naloxone (10 mg/kg). Naloxone significantly increased cerebral blood flow to cerebral cortex and the total cerebral hemisphere without an associated change in the cerebral metabolic rate of oxygen. The increase in cerebral blood flow was proportional to the elevation in mean arterial pressure. There were no consistent changes in electrical activity as measured by electroencephalography (EEG) and Fourier analysis of EEG. Systemically, naloxone induced a proportional rise in mean arterial pressure and peripheral vascular resistance and also stimulated the myocardium, as evidenced by an improved cardiac index and stroke volume. These data suggest that naloxone may interfere with cerebral autoregulation or have direct vasodilatory effects on cerebral blood vessels that are not associated with opiate receptor blockade or changes in cerebral metabolism. In addition, naloxone did not appear to reverse the cerebral depressive effects of pentobarbital. Systemically, naloxone seemed to potentiate pentobarbital-induced vasoconstriction and reverse myocardial depression.

Effects of naloxone on cerebral blood flow and metabolism in isoflurane/nitrous oxide-anesthetized dogs.

The purpose of this study was to document the changes in the cerebral and systemic circulations that result from various doses of naloxone. Twenty-four dogs were anesthetized with 0.8% isoflurane and 70% nitrous oxide (1.3 minimal anesthetic concentration). Thirteen of the dogs received bolus injections of naloxone at logarithmically increasing doses 30 minutes apart. Blood flow to the brain and other organs was determined using the radioactive microsphere technique. Electrical activity was measured by electroencephalography (EEG). High dose naloxone increased both cerebral blood flow (CBF) and cerebral metabolism. The changes in CBF were most pronounced in structures containing a large amount of gray matter, particularly the cerebral cortex, brain stem, and cervical spinal cord. The increase in blood flow was proportionately greater than the increase in the cerebral metabolic rate of oxygen, and EEG activity was unchanged. Naloxone did not produce any significant cardiovascular changes or alterations in myocardial, renal, hepatic, stomach, jejunum, or temporalis and paraspinous muscle flow. Accordingly, it seems that naloxone may have direct cerebral vasodilator properties.

High dose naloxone produces cerebral vasodilation.

In this study, 12 dogs were anesthetized with sodium pentobarbital, and blood flows were determined using the radioactive microsphere technique. Ten dogs were first made acutely hypertensive by the infusion of norepinephrine and demonstrated preserved cerebral autoregulation. The administration of naloxone, 10 mg/kg i.v., in these animals produced a significant increase in cerebral blood flow and a proportional drop in cerebrovascular resistance with no change in the cerebral metabolic rate of oxygen or the electroencephalogram. Two additional spontaneously hypertensive dogs demonstrated a similar response to naloxone. These results suggest that high dose naloxone produces cerebrovasodilation either directly or through the inhibition of cerebral autoregulation.

Specific repression of the preproendothelin-1 gene in intracranial arteriovenous malformations.

Cerebrovascular arteriovenous malformations (AVMs) display abnormal vascular development and dysautoregulation of blood flow. Genetic mechanisms that contribute to the pathogenesis and phenotype of cerebral AVMs are unknown. As a first step in understanding the pathophysiology of AVMs, the authors investigated the hypothesis that endothelial dysfunction-specifically, deregulation of endothelin-1 (ET-1) secretion-contributes to the abnormal vascular phenotype and the lack of hemodynamic autoregulation elaborated by these lesions. Endothelin-1 peptide and preproendothelin-1 (ppET1) messenger RNA were not detected in the intranidal vasculature of all 17 patients with AVMs studied, but were prominently expressed in human control subjects with normal cerebrovasculature (p < 0.01). Although AVM vasculature lacked ET-1, its expression was prominent in vasculature distant from these lesions, suggesting local repression of the ppET-1 gene. Local repression of ET-1 was specific to AVMs; ET-1 in vascular malformations of patients with Sturge-Weber disease was actually elevated compared to normal controls (p < 0.01). Repression of the ppET-1 gene was an intrinsic phenotype of AVM endothelial cells and was not due to factors in the AVM microenvironment. The authors also showed that ETA receptor expression was low in AVM vasculature compared to normal controls. Together, these results demonstrate that the ppET-1 gene is locally repressed in AVM lesions and suggest a role for abnormal ppET-1 gene regulation in the pathogenesis and clinical sequelae of cerebral AVMs.

Phenoxybenzamine in the treatment of causalgia. Report of 40 cases.

Forty consecutive cases of causalgia treated during a 7-year period are presented. The patients ranged in age between 17 and 55 years, and all patients were males who received their nerve injuries from missile or shrapnel wounds. The greater occipital nerve was involved in two cases, median nerve in 10, sciatic nerve in 12, brachial plexus in seven, cauda equina in five, and multiple nerves in four cases. Each patient was treated with phenoxybenzamine, a postsynaptic alpha 1-blocker and presynaptic alpha 2-blocking agent. The drug was given orally in gradually increasing increments until a maximum daily dose of 40 to 120 mg was reached. Duration of treatment was usually 6 to 8 weeks. Total resolution of pain was achieved in all cases. The follow-up period ranged between 6 months and 6 years. Side effects of phenoxybenzamine were minimal and transient, consisting primarily of mild orthostatic hypotension and ejaculatory problems. We conclude that oral phenoxybenzamine is a simple, safe, and effective treatment of causalgia.

Cortical electrical stimulation in humans. The negative motor areas.

Summarizing, we have presented evidence in humans for two "negative motor areas" which we had speculated play a significant role in the planning of voluntary motor movements. A review of the more recent experimental literature shows that histological, physiological, and electrical stimulation studies in animals reveal the existence of two frontal regions that from the experimental data also seem to play an essential role in the preparation (as opposed to execution) of voluntary movements. Current available evidence suggests that these two areas (areas F5 and F6 of Rizzolatti et al.) correspond to the negative motor areas we have described in human studies. Also of interest is that Broca's area in the dominant hemisphere overlaps the corresponding negative motor area. This observation suggests that Broca's area has evolved from area F5 of monkeys specializing in the planning of fine movements necessary for speech production. We feel that current evidence suggests the existence of three mechanisms by which cortical stimulation (by electrical stimulation or by epileptic activation) can generate negative motor phenomena: 1. The "silent period," which is consistently contralateral, has a somatotopic distribution, and tends to affect predominantly muscles involved in fine movements. It is of relatively short duration and seems to be generated by the activation of cortical areas in the primary sensorimotor region. The H-reflex is not inhibited during the silent period, suggesting that the silent period is generated by a decrease in the excitatory input through direct corticospinal neurons on the spinal alpha motoneurons. It is possible that in normal individuals this system is used for fine tuning of fine distal movements. The negative myoclonus seen in some patients with focal cortical epilepsy is probably generated by this mechanism. The primary and supplementary "negative motor areas" described in this chapter. This effect also has a somatotopic distribution but can affect muscle bilaterally even if there is a clear predominance contralaterally. The negative motor effect does not influence postural tone and can be prolonged. The negative motor effect is probably produced by activation of agranular cortex immediately in front of the primary and supplementary face motor area. These cortical areas are probably used for organization and integration of fine motor movement. Activation of these areas would produce an apraxia of fine movements. Focal atonic seizures are probably generated by this mechanism. 3. The fast-conducting corticoreticulospinal pathways, which by activation of the brainstem inhibitory centers (NRPo, n.r. magnocellularis dorsal beta, and NRGc), tend to produce bilateral atonia of axial, postural muscles. This system probably does not depend on the presence of the direct corticospinal pathways. By analogy with cataplexy, which is probably produced by activation of similar brainstem inhibitory systems, we would expect the H-reflex to be markedly diminished or even to disappear during the atomic phase (64). This pathway would be used normally for postural adjustments and locomotion. The bilateral massive atonic seizures, seen most frequently in patients with severe and diffuse cortical lesions, are probably produced by this mechanism. However, the bilateral atonic seizures occasionally seen in patients with focal cortical lesions may also be produced by a similar mechanism.

Surgical management of pediatric tumor-associated epilepsy.

Brain tumors are a common cause of seizures in children. Early surgical treatment can improve seizure outcome, but controversy exists regarding the most appropriate type of surgical intervention. Some studies suggest tumor resection alone is sufficient, while others recommend mapping and resection of the surrounding epileptogenic foci to optimize seizure outcome. To address this issue, we reviewed the charts of 34 pediatric patients aged 18 months to 20 years with medically intractable epilepsy and primary brain tumors. The average age at operation was 12.6 years, and patients had seizures for an average of 6.4 years. The majority of tumors were located in the temporal lobe. Seventeen patients, because of tumor location near an eloquent area, underwent extraoperative mapping using subdural electrode grids prior to definitive tumor resection. Fourteen of these patients had a gross total tumor resection, yet only two had a distinct zone of ictal onset identified and resected. The remaining 17 patients had tumors either in the nondominant hemisphere or far removed from speech-sensitive areas, and therefore did not undergo extraoperative subdural electroencephalograph mapping. Fourteen of these patients also had a gross total tumor resection, while none had intraoperative electrocorticography to guide the resection of additional nontumoral tissue. Overall, of the 28 patients treated with a gross total tumor resection, 24 (86%) are seizure free, while the other four are significantly improved. Of the six patients who had a subtotal tumor removal, five have persistent seizures. The mean follow-up was 3.6 years. We conclude that in children and adolescents, completeness of tumor resection is the most important factor in determining seizure outcome. The routine mapping and resection of epileptogenic foci might not be necessary in the majority of patients. As a corollary, the use of subdural electrode grids in pediatric patients with tumor-associated epilepsy should be limited to cases requiring extraoperative cortical stimulation for localization of nearby eloquent cortex.

Epilepsy surgery in children with pervasive developmental disorder.

Pervasive developmental disorder (PDD) is occasionally associated with medically intractable complex partial seizures. The outcome of PDD was explored in three males and two females who underwent epilepsy surgery at 32 months to 8 years of age (mean = 4 years) after onset of epilepsy at 1 week to 21 months of age (mean = 11 months). Four children had temporal lobe resections (three right, one left; two for focal cortical dysplasia, and two for tumors), and one had a right temporoparieto-occipital resection (for focal cortical dysplasia). Each child underwent repeated evaluations by a pediatric neuropsychologist and psychiatrist. Fourteen to 47 months (mean = 23 months) after operation, one child with persistent seizures had moderate developmental and behavioral improvement, three children (two seizure free, one with rare staring spells) had mild developmental and behavioral improvement, and the remaining child (seizure free) experienced a worsening of her PDD. The four children with mild-to-moderate improvement in postoperative cognitive and behavioral development still demonstrated persistent delay. Cognitive gains were confirmed by neuropsychologic testing in the oldest patient but were not reflected in test results from the three younger children, who had more modest improvement. The child with worsening of her PDD had cognitive and emotional deterioration to babbling, echolalia, aggressiveness, decreased social interaction, and increased mouthing of objects beginning several months postoperatively. These results suggest that families should be counseled that PDD symptoms in children with focal epileptogenic lesions may or may not improve after epilepsy surgery, even if the surgery is successful with respect to seizure control.

Dysembryoplastic neuroepithelial tumor: a clinicopathologic and immunohistochemical study of 11 tumors including MIB1 immunoreactivity.

The dysembryoplastic neuroepithelial tumor (DNT) is a rare, recently recognized neoplasm, characterized by a mixed glial-neuronal cell proliferation. We studied 11 cases of DNT including 6 males and 5 females (age range 2.1-39.4 years, mean 13.8 years). All patients presented with chronic epilepsy of 4.8 years mean duration. Nine tumors were located in the temporal lobe and 2 in the frontal lobe. Four tumors were located on the right side and 7 on the left. All tumors were characterized by a predominant oligodendrocyte-like cell component with intermixed normal appearing neurons and astrocytes. All were focally microcystic and 7 of 9 evaluable tumors were multinodular. Other observed histologic features included a focal arcuate vascular pattern in 7 tumors, calcification in 4 tumors, and a rare mitotic figure in 2 tumors. Necrosis and vascular hyperplasia were not observed in any of the tumors. Cortical architectural disorganization (cortical dysplasia) was observed in 9 of 10 evaluable cases. MIB1 (a marker of cellular proliferation) immunostaining was performed in all 11 tumors and MIB1 indices (number of positive tumor cells/100 tumor cells counted) ranged from 0-0.6 (mean 0.2). Four patients required at least 1 additional surgical procedure for tumor recurrence, related to an incomplete initial excision 2.1-4.4 years after their initial operation. All patients are seizure-free at their last follow-up. DNTs are low grade neoplasms which typically present with chronic epilepsy, are most frequently located in the temporal lobe, and occur most frequently in pediatric patients. Their appearance and association with cortical dysplasia suggest a maldevelopmental origin. The generally slow growth and relatively benign nature of DNT is reflected by their low MIB1 index.

Spontaneous subdural haematoma in anabolic steroids dependent weight lifters: reports of two cases and review of literature.

Spontaneous subdural haematoma is very rare in young patients. The complications of anabolic steroid intake in weight lifters are numerous, yet subdural haematomas have not been reported. We report on two cases of spontaneous subdural haematomas in young weight lifters. Both patients underwent surgical evacuation and made a full recovery. A review of the literature on the complications associated with valsalva manoeuvres is also presented including hemodynamic and intracranial changes. We propose that patients on chronic anabolic steroids may have vascular changes that predispose them to bleeding during a Valsalva manoeuvre (VM).

Epilepsy surgery in infants.

PURPOSE: We report 12 infants who had frontal (n = 3), temporal (n = 2), or temporoparieto-occipital (n = 2) resection or functional hemispherectomies (n = 5) at age 2.5-29 (mean 15.3) months for catastrophic epilepsy due to focal cortical dysplasia (n = 5), Sturge-Weber syndrome (n = 3), ganglioglioma (n = 3), or hemimegalencephaly (n = 1). Seizures began at 1 day to 14 months (mean, 4.0 months) after birth, occurred frequently (often many times per day, and were refractory to antiepileptic drugs. Patients were evaluated for surgery at 2.5-24 (mean 12.4) months of age. Seven patients had hemiparesis and eight had slowed cognitive development. Seizures were characterized by arrest or marked reduction of behavioral motor activity with nuclear level of consciousness (n = 4, with temporal or temporoparietal EEG seizures), focal clonic activity (n = 3, with perirolandic EEG seizures), generalized tonic stiffening (n = 3, with temporoparieto-occipital, parietal, or frontal EEG seizures), or infantile spasms and hypsarrhythmia (n = 2, with a frontal tumor or temporoparieto-occipital cortical dysplasia). METHODS: Magnetic resonance imaging (MRI) revealed the epileptogenic lesion in all but two patients, both with cortical dysplasia localized by interictal positron-emission tomography (PET) and other clinical or EEG features and confirmed on histopathologic examination of resected tissue. RESULTS: At follow-up 4-86 (mean 32) months after surgery, six patients were seizure free (Engel outcome class I), three had rare seizures with none in at least the previous 6 months (Engel class II), and two had worthwhile improvement (Engel class III). Except for the severely developmentally delayed infant with hemimegalencephaly, several patients had marked "catch-up" developmental progress after class I, II, or III outcome. Postoperative complications included subdural hematoma over the contralateral hemisphere (one patient) and entrapment and enlargement of the ipsilateral temporal horn (one patient) after hemispherectomy, both corrected uneventfully with a second surgical procedure. One patient died of unexplained causes several hours after frontal lobectomy. No patients had new neurologic deficits after surgery, and one patient had resolution of progressive fluctuating hemiparesis after resection of temporoparieto-occipital cortical dysplasia. CONCLUSIONS: Our results agree with previous reports that epilepsy surgery can provide relief from catastrophic epilepsy in carefully selected infants.