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).

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.

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.

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.

Seizure outcome after epilepsy surgery in children and adolescents.

Few epilepsy surgery outcome data are available from series of pediatric patients. We studied seizure outcome in 136 pediatric patients who had surgery for intractable epilepsy at The Cleveland Clinic between January 1990 and June 1996, with a postoperative follow-up of 1 to 7.5 years (mean, 3.6 years). Sixty-two children (3 months to 12 years old at time of surgery) were compared with 74 adolescents (13-20 years old). Extratemporal or multilobar resections and hemispherectomies were similarly frequent among children (50%) and adolescents (44%), but these procedures strongly predominated in infancy (90% of patients 0-2 years of age). The remaining patients had temporal resection. Cortical dysplasia and low-grade tumor were the most common causes and hippocampal sclerosis was rare. Seizure-free outcome was achieved for 69% of adolescents, 68% of children, and 60% of the infant subgroup, overall; for 23 (74%) of 31 children and 33 (80%) of 41 adolescents after temporal resection; for 11 (58%) of 19 children and 15 (52%) of 29 adolescents after extratemporal or multilobar resection; and for 8 (67%) of 12 children and 3 (75%) of 4 adolescents after functional hemispherectomy. Seizure-free outcome was more frequent after temporal resection (56 of 72, 78%) than after extratemporal or multilobar resection (26 of 48, 54%; 41 of 48 with a focal lesion on magnetic resonance imaging), and among patients with tumor (36 of 44, 82%) versus cortical dysplasia (16 of 31, 52%). The frequency of seizure-free outcome after epilepsy surgery was similar for infants, children, and adolescents, and comparable with results from adult series. Most patients in each age, surgery type, and causal group were free from seizures after surgery. These results suggest that children should be considered for surgical evaluation at whatever age they manifest with severe, intractable, disabling localization-related epilepsy.

Neuropsychological effect of temporal lobe resection in preadolescent children with epilepsy.

PURPOSE: Numerous studies have demonstrated changes in cognitive, memory, and language functioning in adults and adolescents after temporal lobectomy, yet little information is available regarding neuropsychological outcome in preadolescent children. METHODS: We studied pre- and postoperative neuropsychological test results from 14 children who underwent temporal lobe resection for intractable epilepsy at age 7-12 years (mean 9.4 years). RESULTS: Thirteen patients (93%) had no seizures or less than one seizure a year at follow-up 23-48 months (mean 34 months) after operation. Postoperative neuropsychological testing was performed 6-9 months (mean 7 months) after surgery in 13 patients and 36 months after the first operation in 1 patient who underwent two-stage resection of a tumor. Verbal, Performance, and Full Scale IQ were initially in the low-average range, with no significant change across the pre- and postoperative evaluations. Immediate verbal memory performance decreased significantly in children who initially performed above the median preoperatively and tended to decrease in children who had left rather than right temporal lobe resection. Significant postoperative decreases in delayed memory scores were independent of preoperative ability or side of resection. CONCLUSIONS: Our small study suggests vulnerability to postoperative decline in immediate verbal memory scores in preadolescent children who have higher baseline immediate memory function or undergo left rather than right temporal lobe resection, similar to that observed in adolescents in adults. The entire group exhibited a statistically significant decrease in delayed verbal memory. Study of larger series of patients will be important to clarify further the short- and long-term risks and benefits of temporal lobe resection in childhood.

Histopathological correlates of epileptogenicity as expressed by electrocorticographic spiking and seizure frequency.

PURPOSE: To study the correlation between histopathology and epileptogenicity, as measured by seizure frequency and electrocorticography (EcoG), in patients with cortical dysplasia (CD) as compared with control patients with gangliogliomas or gliomas. METHODS: The influence of the histopathological classification and the presence of balloon cells in CD on the frequency and extension of five predefined patterns of ECoG spiking, seizure frequency, age of seizure onset and 6-month postoperative outcome were analyzed in 32 patients with focal epilepsy undergoing presurgical evaluation with chronically implanted subdural electrodes. RESULTS: Comparison of patients with CD, gangliogliomas, and gliomas showed that the seizure frequency was greatest in patients with CD and ECoG spiking and was most extensive in patients with gangliogliomas. The onset of epilepsy was earlier in patients with CD and with gangliogliomas. None of these differences was significant. However, in patients with CD, the presence of balloon cells was associated with significantly greater seizure frequency (p=0.009), and a significantly greater number of electrodes recording continuous frequent spiking (p=0.03). The presence of continuous very frequent spiking correlated with the duration of the epilepsy and the number of seizures recorded during monitoring. No significant correlation was detected between histopathology, seizure frequency, or ECoG activity and postoperative outcome, which was relatively favorable in patients with balloon cells. CONCLUSIONS: CD refers to a variety of histopathological patterns associated with different epileptogenicity. In CD, increased clinical and ECoG epileptogenicity correlates with the presence of balloon cells. This finding confirms that balloon cells should be considered in the histopathological classification of CD. The predefined ECoG were not specific for any of the histopathologies investigated.

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.

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.

MRS metabolic markers of seizures and seizure-induced neuronal damage.

PURPOSE: Proton magnetic resonance spectroscopy (MRS) was used to identify specific in situ metabolic markers for seizures and seizure-induced neuronal damage. Kainic acid (KA)-induced seizures lead to histopathologic changes in rat brain. The protective effect of cycloheximide treatment against neuronal damage caused by KA-induced seizures was studied, using in situ proton MRS imaging technique. METHODS: Rats were pretreated with placebo or cycloheximide 1 h before KA injection. Rat brains (n = 25) were scanned at the level of the hippocampus before, during, and 24 h after seizures. Spectra were recorded and the relative ratios of N-acetylaspartate (NAA), choline (cho), and lactate (Lac) to creatine (Cr) were calculated and compared between groups. RESULTS: A significant increase in Lac ratios was observed in KA-treated rats during and 24 h after seizure onset and this increase was prevented by cycloheximide pretreatment. NAA ratios were significantly higher during the ictal phase following KA treatment and this effect was not affected by cycloheximide pretreatment. Nissl staining confirmed previously reported prevention of KA-induced neuronal loss in CA3 and CA1 areas of the hippocampus by cycloheximide pretreatment. CONCLUSIONS: Our results suggest that in situ Lac increase is a marker of seizure-induced neuronal damage, whereas N-acetylaspartate (NAA) changes during and after status epilepticus may be a reflection of neuronal activity and damage, respectively.

Ganglioglioma and intractable epilepsy: clinical and neurophysiologic features and predictors of outcome after surgery.

PURPOSE: To review the clinical, neurophysiologic, and radiological data of patients with ganglioglioma who had undergone evaluation and surgery in our Epilepsy Program. METHODS: The medical and neurophysiologic records of 38 patients with intractable epilepsy and ganglioglioma were reviewed. Data underwent statistical analysis. RESULTS: There were 28 temporal and 10 extratemporal resections, with a mean age at seizure onset of 10.5 years and mean age at surgery of 22 years. Five tumor resections performed earlier were recorded. Twenty-nine patients had auras and 20 had secondarily generalized seizures. All 28 patients with temporal tumor had complex partial seizures. Preoperative MRI demonstrated the tumor in 36 of 36 patients: 17 of 29 demonstrated gadolinium enhancement, and 17 of 36 had mass effect. Scalp interictal sharp waves were present in 32 patients, and in 15 they were multiregional. In two patients, scalp EEG seizure onset was from the hemisphere contralateral to the tumor. Postoperatively, 79% of patients (30 of 38) were seizure-free (Engel's class I) at 6 months, 72% at 1 year (26 of 36), and 63% at 2 years (20 of 32). Excellent outcome was associated with a lower age at operation (p = 0.008), shorter duration of epilepsy (p = <0.01), absence of generalized seizures (p = <0.01), and no epileptiform discharges on a postoperative EEG (p = 0.01). CONCLUSIONS: Good surgical outcome is expected in patients with ganglioglioma despite years of medically resistant seizures. Good outcome may be achieved despite EEG findings that may conflict with tumor location, and is more likely when surgery is performed relatively soon after epilepsy onset.

The cortical generators of the contingent negative variation in humans: a study with subdural electrodes.

Contingent negative variations (CNVs) and Bereitschaftspotentials (BPs) were recorded from subdural electrodes implanted in 14 patients with intractable epilepsy. For recording CNVs, a Go/NoGo S2 choice reaction-time paradigm was employed. Two seconds after presentation of a low tone burst (S1), either a medium (S2m) or a high tone burst (S2h) was delivered at random. Patients were instructed to make middle finger extensions after S2m but not after S2h. For recording BPs, patients repeated self-paced middle finger extensions. BPs were recorded from the primary motor area (MI), the primary sensory area (SI) and the supplementary sensorimotor area (SSMA). CNVs showed a patchy distribution in the prefrontal area and SSMA for the early component and in the prefrontal area, MI, SI, temporal area, occipital area and SSMA for the late component. These results suggest that the CNV recorded from the scalp is the summation of multiple cortical potentials which have different origins and different functions. The cortical distribution of the late CNVs was different from that of BPs. Late CNVs are not equivalent to BPs and are not related to motor preparation alone. After S2, 3 kinds of potentials, probably related to decision making, somatosensory feedback and motor execution under specific conditions, respectively, were observed.

Temporal changes in proton MRS metabolites after kainic acid-induced seizures in rat brain.

PURPOSE: In situ 1H-magnetic resonance spectroscopy (MRS) was used to study temporal metabolic changes in a rat model of temporal lobe epilepsy (TLE) by using kainic acid (KA). METHODS: Rat brains were scanned at the level of the hippocampal body for MRS measurements. Relative ratios of N-acetyl groups (NA: N-acetylaspartate and N-acetylaspartyl glutamate), choline, and lactate (Lac) over creatine (Cr) were calculated. RESULTS: NA/Cr ratios increased significantly during the ictal phase. During the postictal and interictal phases, the NA/Cr ratio decreased. There was a significant and prolonged increase of the lactate/Cr ratio in the hippocampi of rats that started 1 h after the onset of KA-induced seizure activity and persisted up to 24 h after the injection. The prolonged lactate/Cr increase in an area susceptible to neuronal damage (e.g., hippocampus) correlated with the onset of seizure activity but remained elevated thereafter. CONCLUSIONS: The ictal and early postictal increase in lactate ratios may reflect increased cellular activity and metabolism resulting from KA excitotoxicity. Assuming that the changes in NA/Cr ratios are due to NAA increase, we speculate that an activation of the N-acetylaspartylglutamate (NAAG) dipeptidase pathway may explain the ictal increase in NA/Cr ratios. The late postictal decrease in NA/Cr ratios is a reflection of KA-induced neuronal cell loss.

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.

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.

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.

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)

Childhood ganglioglioma and medically intractable epilepsy. A clinicopathological study of 15 patients and a review of the literature.

Gangliogliomas are an increasingly recognized cause of epilepsy in children. Several studies have shown that early surgical treatment is beneficial, but controversy exists regarding the type of surgical treatment required for optimal seizure control and to prevent tumor recurrence. To address this issue, we performed a retrospective review of 15 children operated on at the Cleveland Clinic during a 7-year period with medically intractable epilepsy who were found to harbor a ganglioglioma during the course of their work-up. Nine patients with mostly nondominant hemisphere tumors underwent tumor resection without the use of electrocorticography to guide additional resection of epileptogenic foci, while 6 other patients with dominant hemisphere tumors had subdural electrode grids placed to extraoperatively map zones of ictal onset and eloquent areas. The extent of tumor resection was then correlated to seizure outcome and tumor recurrence. Of the 11 patients who received a gross total resection, 9 are seizure-free while 2 have a greater than 90% reduction in their seizure frequency (100% 'good' outcome). There was no tumor recurrence in this group. Of the 4 patients who underwent a subtotal tumor resection, 1 is seizure-free while 3 have persistent seizures (25% 'good' outcome). All patients in this group have stable disease on follow-up magnetic resonance imaging. In those patients who received subdural electrode grids, the extent of resection of the zones of ictal onset did not correlate with seizure outcome. The mean follow-up was 42 months. We conclude that complete tumor resection is the most important factor for optimal seizure control and to prevent tumor recurrence.