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Objectives To determine the prevalence and prognostic value of MGMT promoter methylation and IDH1 mutation in glioblastoma multiforme (GBM) patients from the Middle East. Patients and methods Records of patients diagnosed between 2003 and 2015 were reviewed. MGMT promoter methylation was measured using methylation-specific polymerase chain reaction and IDH-1 mutation was reported. The primary endpoint was overall survival (OS). Results A total of 110 patients were included. The median age was 51 years and 71 patients (64.5%) were males. The median diameter of GBM was 4.6 cm and 29 patients (26.4%) had multifocal disease. Gross total resection was achieved in 38 patients (24.9%). All patients received adjuvant radiation therapy, and 96 patients (91.4%) received concomitant temozolomide. At a median follow up of 13.6 months, the median OS was 17.2 months, and the OS at 1 and 2 years were 71.6% and 34.8%, respectively. On multivariate analysis, age at diagnosis (HR 1.019; P = 0.044) and multifocality (HR 2.373; P = 0.001) were the only independent prognostic variables. MGMT promoter methylation was found in 28.2% of patients but did not significantly correlate with survival (HR 1.160; P = 0.635). IDH-1 mutation was found in 10% of patients was associated with a non-significant trend for survival improvement (HR 0.502; P = 0.151). Conclusion Patients with GBM from the Middle East have adequate survival outcomes when given the optimal treatment. In our patient population, MGMT promoter methylation did not seem to correlate with outcomes, but patients with IDH1 mutation had numerically higher survival outcomes.

Investigate if quality of life (QOL) normalizes on long-term follow-up after surgery for partial epilepsy in children.This is a cohort study with controls in which a consecutive cohort of nineteen 2-14-year-old children who underwent focal resections for intractable partial seizures between 1996 and 2006, were matched with 19 non-surgery intractable partial epilepsy patients, and with 19 healthy subjects. The two epilepsy groups were matched for age, sex, socio-economic status (SES), cognitive level, seizure type, and seizure frequency. The healthy group was matched with the two epilepsy groups for age, sex, SES, and cognitive level. QOL was assessed using the QOLCE (Quality of Life in Childhood Epilepsy Questionnaire).In the surgery group (follow-up 3.84+/-2.26 years), 78.9% had Engel class-I versus 21.1% in non-surgery (p=0.01) (follow-up 3.44+/-2.95 years). Surgery patients were similar to healthy subjects in the social, emotional, cognitive, behavioral, and overall QOL (p0.05) but had lower scores in the total QOL, physical, and health domains (p0.05). Surgery patients scored better than non-surgery in the behavioral domain and the HASES (Hague Side Effects Scale) score (p0.05). Non-surgery patients scored worse than healthy in total QOL, physical, behavioral, health, and overall QOL (p0.05). IQ, HASS (Hague Seizure Severity Scale), and HASES scores were positively associated with total QOL score (p0.05). Subgroup analysis on seizure-free surgery patients showed that they did not differ from healthy subjects in any of QOL domains (p0.05, power0.8).Our data indicate that epilepsy surgery for partial seizures in children is associated with better QOL as compared to children with intractable epilepsy who are not operated on, and suggest that in those who achieve seizure freedom normal QOL may at least potentially be possible.

We report a case of a young girl with early onset pantothenate kinase-kssociated neurodegeneration (PKAN) whose initial clinical manifestation was ataxia at the age of 2.5 years. Subsequently the patient presented to us with refractory severe dystonia resulting in essentially complete loss of motor control. She had a mutation in PANK2 gene consisting of an aminoacid change of Alanine to Valine in exon 5 (A382V). After Globus Pallidus deep brain stimulation (DBS) at the age of 11 years, the patient regained useful motor function and speech with a marked decrease in the severity of the dystonia. The patient's condition gradually returned to her pre-DBS status when the device had to be removed 3 months later due to infection. Our case is the sixth case with classical PKAN that was treated by Globus Pallidus stimulation, the fifth one to have a favorable response to it and the only one in whom response was proven by the inadvertent removal of the DBS device due to infection. In addition, our case had a novel mutation and novel clinical features (onset with ataxia, occurrence of early seizure activity) on top of her other symptoms that were otherwise typical of early onset disease.

Summary: Purpose: The goal of epilepsy surgery is not merely to control previously intractable seizures, but also to improve quality of life (QOL). Our goals were to assess, in our Middle Eastern population, the QOL of adults with temporal lobe epilepsy (TLE) 3 years after temporal lobectomy as compared with matched TLE patients who did not undergo surgery and with healthy individuals in the same community. Methods: Twenty consecutive TLE patients who underwent temporal lobectomy 3 years previously were matched in the following variables: age, sex, seizure frequency, seizure duration, age at onset of epilepsy, duration of epilepsy, and number of medications, with 17 TLE patients who underwent the presurgical evaluation and subsequent optimization of medical therapy but did not undergo surgery. They were also matched for age, sex, educational level, income, and residence with 20 healthy individuals. All groups were interviewed by using the ESI-55 questionnaire. Results: Compared with the nonsurgery group, QOL was significantly better in the surgery group (85% seizure free) in the well-being, functioning, and role-limitation domains. QOL was similar in the surgery and healthy control groups in all domains and scales. The nonsurgery group scored significantly lower than healthy controls in the functioning and role-limitation domains. Conclusions: Intractable TLE was associated with marked impairments in QOL despite continued attempts to optimize medical therapy. Three years after temporal lobectomy QOL in our patient population achieved levels similar to those of matched healthy individuals. To our knowledge, this is the first study to report normalization of QOL after temporal lobectomy, in any population. Key Words: QOL—temporal lobe epilepsy— Lobectomy.

We report a case of recurrent partial seizures that were often precipitated by looking up a flight of stairs and included spitting as well as repetitive affectionate kissing automatisms. These seizures were shown by long-term video/EEG monitoring to be of right temporal origin and completely subsided after right temporal lobectomy. This case is unique because: (1) The patient had partial rather than primarily generalized pattern-induced seizures. (2) Affectionate kissing automatisms were a part of his partial seizures and, to our knowledge, have not been reported in the literature before.

The purpose of this study was to investigate which areas of quality of life (QOL) change after epilepsy surgery and generate QOL data specific to the Lebanese population. The QOL of 20 consecutive patients 1 year after surgery was compared (using the ESI-55 scale) with that of 20 matched patients who underwent the same presurgical evaluation, but no surgery. Overall QOL improved in both groups, but was greater in the surgery group (85% seizure free as compared to 0% in nonsurgery group). Significant differences were noted within the "well-being" domain including health perception (5/9 items), energy-fatigue (2/4), and emotional well-being (2/5). Differences were less common in the "functioning" domain including physical (1/10 items), social (1/2), and cognitive (0/5) functioning scales, and in the role limitation domain (1/17 items). Our patients experienced, 1 year after epilepsy surgery, improvements similar to those reported in Western populations after a similar period: they had marked improvements in overall QOL, health perception, well-being, and cognitive functioning areas. They had less remarkable improvements in social functioning and role limitation areas.

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. ( J Child Neurol 1999;14:15-25).

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.

Summary: 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.

Summary: 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 CA1 and CA 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.

Summary: Purpose: We studied temporal changes of brain sodium and apparent diffusion coefficient (ADC) in a temporal lobe epilepsy (TLE) rat model using kainic acid (KA). Methods: In situ three-dimensional 23Na magnetic resonance imaging (MRI) and proton diffusion-weighted imaging (DWI) were used. KA at a dose of 10 mg/kg body weight and 12 adult Sprague Dawley rats weighing 228–318 g (268 ± 25 g) were used. Results: Twenty-four hours after KA injection, magnetic resonance (MR) visible sodium levels increased in both the pyriform cortex (+90%) and amygdala (+68%) and increased insignificantly in the hippocampus (+18%) and caudate-putamen (12%). The ADC in the pyriform cortex showed a −9% decrease at 5 h postictally, reaching −30% at 24 h, whereas in the amygdala decreases were −8 and −26% respectively. A significant decrease in ADC (−7%) in the hippocampus was also observed 24 h postically. Seven days later, sodium increases persisted, whereas ADC returned to normal level. Conclusions: The increase in MR visible sodium, associated with the decrease in ADC is consistent with the hypothesis that sequential seizures caused an increase in sodium influx and perturbation of membrane ion homeostasis, which eventually evolved into an irreversible phase of cellular edema, with increased MR visible intracellular sodium and decreased ADC. Return of ADC to near-control level and persistent high sodium level at 7 days may be explained by the increase in extracellular space and tissue necrosis.

Summary: 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 unclear 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, 11, 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.

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). Mortality did not reliably correlate with the MIB1 index; however, the highest index was observed in the anaplastic tumor. The high incidence of associated architectural abnormalities suggests that gangliogliomas may arise on a maldevelopmental basis. Although generally benign and slow-growing tumors, as indicated by the generally low MIB1 indices, gangliogliomas can rarely behave in a malignant fashion. It is not possible to reliably predict prognosis on the basis of histologic features or MIB1 immunoreactivity.

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 surgic

We present our 10-year experience and preoperative predictors of outcome in 93 adults and children who underwent epilepsy surgery at the American University of Beirut. Presurgical evaluation included video-EEG monitoring, MRI, neuropsychological assessment with invasive monitoring, and other tests (PET, SPECT, Wada). Surgeries included temporal (54%), extratemporal (22%), and multilobar resections (13%), hemispherectomy (4%), vagal nerve stimulation (6%), and corpus callosotomy (1%). Mesial temporal sclerosis was the most common aetiology (37%). After resective surgery, 70% had Engel class I, 9% class II, 14% class III, and 7% class IV. The number of antiepileptic drugs before surgery was the only preoperative factor associated with Engel class I (p=0.005). Despite the presence of financial and philanthropic aid, many patients could not be operated on for financial reasons. We conclude that advanced epilepsy presurgical workups, surgical procedures, and favourable outcomes, comparable to those of developed countries, are achievable in developing countries, but that issues of financial coverage remain to be addressed.

Focal cortical dysplasia is an important pathologic substrate in patients with epilepsy, but its clinical spectrum has not yet been completely defined. We retrospectively studied 30 epilepsy surgery patients with focal abnormalities of neuronal migration as the only histopathologic finding in resected tissue. Patients comprised two clinical groups. Seventeen patients with extratemporal epilepsy had early (median age, 7.0 years) extratemporal resection or hemispherectomy for severe epilepsy (47% of patients with > 10 partial seizures a day) that began in infancy or early childhood (median age, 1.0 year), usually in the setting of mental retardation or developmental delay (59% of patients), and often with magnetic resonance imaging (MRI) evidence of focal neuronal migration abnormality (44% of patients). In contrast, 13 patients with temporal lobe epilepsy were significantly older at age of seizure onset (median, 8.0 years; p = 0.001) and surgery (median, 22.0 years; p = 0.001), with less severe epilepsy (no patients with an average of > 10 seizures a day; p = 0.004), and without mental retardation or MRI evidence of neuronal migration abnormality ( p = 0.001). In both groups, positron emission tomography (PET) was more sensitive than MRI and showed focal hypometabolism in seven patients with normal MRI. Seizure-free outcome tended to be more common after temporal lobectomy (77%) than after extratemporal resection or hemispherectomy (53%). Pathologic abnormalities were more severe in patients with extratemporal epilepsy than in patients with temporal lobe epilepsy. The clinical spectrum of focal cortical dysplasia included not only infants and children with severe extratemporal epilepsy and mental retardation, but also older patients with temporal lobe epilepsy and at least boderline IQ. Preoperative diagnosis may be difficult in cases with less severe pathologic abnormality, but high-resolution MRI and PET can increase the yield.

Twenty-three infants and children underwent cortical resection (n = 15) or hemispherectomy (n = 8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow-up (range 4-67 months; mean 28.3 months), 15 children were seizure-free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.

Aim. Assess quality-of-life after vagal nerve stimulation and determine patient characteristics associated with improvement in quality-of-life. Methods. Sixteen patients (11 children, 5 adults) who had vagal nerve stimulation at our center were studied. Quality-of-life was assessed pre- and post-vagal nerve stimulation using the Quality-of-Life in Childhood Epilepsy questionnaire for children and the Epilepsy Surgery Inventory-55 for adults. Results. Sixteen patients who did not qualify for resective surgery were included; seven (43.75%) were males and 9 (56.25%) were females. Mean age at onset of seizures was 3.96 ± 4.00 years and at surgery was 15.78 ± 10.78. Follow-up time was 1.26 ± 0.92 years. Fourteen patients (87.5%) were mentally retarded. Ten (62.5%) had cryptogenic etiology and 6 patients (37.5%) symptomatic etiology. Fifty percent had localization-related epilepsy. Six of 7 patients with generalized cryptogenic etiology (85.71%) had Lennox-Gastaut syndrome. Seizures dropped from 122.31 ± 159.49 to 67.84 ± 88.22 seizures/month. Seizure reduction (> 50%) correlated with improvement in total quality-of-life (p = 0.034). Post-vagal nerve stimulation, the total group scored significantly higher in the social domain (p = 0.039). In patients with localization-related epilepsy, significant improvements were detected in the social domain (p = 0.049) and in total quality-of-life (p = 0.042). Conclusion. Despite a diverse and small population size, we observed significant improvements in the social domain 1.26 years post-vagal nerve stimulation. In addition, there was an improvement in total quality-of-life amongst patients with partial seizures. Finally, seizure reduction was associated with quality-of-life improvement. Our results support previous studies from the West reporting improvement in quality-of-life following vagal nerve stimulation, contradict those studies that did not show such differences, and are the first coming from a developing country.

Twenty-five consecutive patients who underwent the Wada test using propofol as anesthetic were compared with 15 randomly selected patients who were tested using amobarbital. Time to verbal and nonverbal responses and time to motor power 3/5 did not differ between the two groups (P > 0.05). The number of doses received by each patient and the percentage of patients needing more than one dose were significantly greater in the propofol group (P < 0.005). Only one patient developed confusion, combativeness, and agitation. Despite the need for multiple doses, our patients had no residual drowsiness within 10 to 15 minutes of the propofol injection. This allowed us to perform the test on both sides on the same day separated only by 45 minutes. Propofol is an effective alternative to amobarbital in the Wada test, and may be used successfully in multiple repeated injections within the same test without significant residual sedation or significant adverse effects.

In this first study comparing epilepsy-specific quality-of-life measures of children after epilepsy surgery (2.4 years after focal resection) with those of a matched comparison group of nonoperated patients, seizure severity, medication side effects, overall quality of life, general health, physical activity, and well-being were better in surgical patients (70.6% seizure free vs 8.3%). Cognitive, social, and behavioral functioning did not differ, suggesting that these may require additional interventions during postsurgical follow-up.

Despite recent technical advances, the surgical management of epileptic foci in the primary motor area, especially the motor hand area, continues to represent a significant challenge because of the risk of permanent neurological deficit. We describe the case of a 19-year-old woman with intractable epilepsy secondary to cortical dysplasia of the motor hand area who was treated with surgical resection. The patient showed immediate complete motor deficit, started improving at around 1 month of follow-up, and had a substantial recovery at 6 months, with only mild limitations of fine hand movements. At the latest follow-up (3 years), she remained seizure-free. This case demonstrates that, in selected cases, resections in the primary motor cortex can be performed and that the immediately observed motor deficit is transient. We discuss the proposed mechanisms for recovery based on available data from experimental animal and clinical human studies.

To assess short- and long-term seizure freedom, the authors reviewed 371 patients who underwent anterior temporal lobectomy to treat pharmacoresistant epilepsy. The mean follow-up duration was 5.5 years (range 1 to 14.1 years). Fifty-three percent of patients were seizure free at 10 years. The authors identified multiple predictors of recurrence. Results of EEG performed 6 months postoperatively correlated with occurrence and severity of seizure recurrence, in addition to breakthrough seizures with discontinuation of antiepileptic drugs.

MRI features were correlated with postsurgical seizure outcome in patients with hemispheric malformations of cortical development (MCD). After functional hemispherectomy, 5 of 6 patients (83%) with hemimegalencephaly had persistent, although markedly improved, seizures; 5 of 6 patients (83%) with relative preservation of part of one lobe or atrophy were seizure free. Hemimegalencephaly and other types of hemispheric MCD appear to differ in prognosis for freedom from seizures after functional hemispherectomy.

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.

Summary: 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.

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

Summary: 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 NNCr ratios is a reflection of KA-induced neuronal cell loss.

Summary: Purpose: Invasive ictal EEG recording is often necessary to delineate epileptogenic areas in patients with intractable partial epilepsy, but even intracranial ictal recordings often reveal ill-defined onset zones in neocortical epilepsy. We studied the physiologic significance of ictal direct current (DC) potentials recorded intracranially in human epilepsy. Methods: We made intracranial ictal EEG recordings in three patients with intractable partial seizures arising from frontal, lateral temporal, and parietal neocortical areas by using closely spaced subdural electrodes (platinum in two patients and stainless steel in one patient) with both standard (1.5 Hz) and open (0.016 Hz) low-frequency filter (LFF) settings. Results: The initial ictal pattern was localized to two to nine subdural electrodes and characterized by very low voltage and high-frequency rhythmic activity (“electrode-cremental pattern”). A slow-rising negative potential (DC potential) was seen in a slightly more restricted area (two to six electrodes) and occurred 1–10 s before the initial ictal EEG discharges in two patients. Conclusions: These results agree with those of previous studies of ictal DC shifts in animals and suggest that ictal DC shifts may be helpful in delineating the epileptogenic area more precisely in human epilepsy.

We report an infant who had successful epilepsy surgery for intractable infantile spasms in the setting of bilateral periventricular leukomalacia and remote germinal matrix hemorrhage. Although MRI gave evidence of a diffuse cerebral insult and EEG showed hypsarrhythmia, focal epileptogenicity was suggested by previous partial seizures with onset over the right temporoparietal-occipital region and PET hypometabolism in that same area. Right temporoparietal and lateral occipital resection at 15 months resulted in seizure freedom and dramatic developmental progress at 1-year follow-up. Histopathologic examination of resected tissue showed cortical dysplasia, possibly due to the same insult that also resulted in the bilateral periventricular leukomalacia. From an etiologic perspective, this is one of very few reported cases strongly implicating acquired focal cortical dysplasia in response to a prenatal insult. From a clinical perspective, the case illustrates that the spectrum of potential surgical candidacy in infants may be broader than usually suspected.

Rationale Language function often develops in the right hemisphere following an acute left hemispheric insult in early childhood. Little is known, however, about lateralization of language function in patients with early childhood tumors near potential left hemisphere language areas. Issues of language dominance are important in the strategy for resection of left temporal and frontal tumors. Methods We studied 12 patients who had determination of hemispheric language dominance by the intracarotid amobarbital procedure prior to resection of a left inferolateral frontal or left mid or posterior temporal tumor that (1) was near a classic language area and (2) first manifested with partial seizures by age 6 years (mean, 3.7). Results Hemispheric language dominance was left in 10 patients (83%), right in one patient, and bilateral in one patient. Six patients with left temporal tumors had localization of Wernicke9s area with cortical stimulation, and in five the language area was posterior to the tumor. In one patient, the tumor infiltrated Wernicke9s area. Eleven of the 12 patients had complete tumor resection (mean age at operation, 11.8 years) and were seizure-free at follow-up (mean, 3.1 years). Neuropsychological testing showed a tendency for improved language function after operation, and no patient had new overt language deficits. Conclusions Early low-grade left frontal and temporal tumors usually did not result in transfer of language dominance to the contralateral hemisphere. Tumors may grow slowly along with the developing brain in young children, with continued left hemisphere language development in regions separate from the neoplasm. Successful tumor resection can be accomplished, but it may require cortical stimulation for localization and sparing of nearby language areas.

To explore the electroclinical features of temporal lobe epilepsy (TLE) in early childhood, we studied results of video-EEG and other tests of 14 children aged 16 months to 12 years selected by seizure-free outcome after temporal lobectomy. Four children had mesiotemporal sclerosis, 1 had cortical dysplasia, and 9 had low-grade temporal neoplasms. The children had complex partial seizures (CPS) with symptomatology similar to that of adults with TLE, including decreased responsiveness and automatisms. Automatisms tended to be simpler in the younger children, typically limited to lip smacking and fumbling hand gestures. Scalp/sphenoidal EEG showed anterior/inferior temporal interictal sharp waves and unilateral temporal seizure onset in the 4 children with mesiotemporal sclerosis and in the child with cortical dysplasia, but EEG findings in 9 children with low-grade temporal tumors were complex, including multifocal interictal sharp waves or poorly localized or falsely lateralized EEG seizure onset. In children without tumors, video-EEG was critical to localization of the epileptogenic zone for resection, but in patients with tumors video-EEG was less localizing and its main value was to confirm that the reported behaviors were epileptic seizures with semiology typical of temporal lobe onset.

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.

Extensive surgical resections of neocortical cerebral tissue (including hemispherectomies) from 13 infants and children with infantile spasms showed that 12 of 13 specimens contained either malformative and dysplastic lesions of the cortex and white matter (sometimes with associated hamartomatous proliferation of globular cells), or destructive lesions possibly acquired as a result of anoxic-ischemic injury, or a combination of the two. In brain tissue from 4 patients, coarse neuronal cytoplasmic fibrils resembling neurofibrillary tangles were seen in areas of dysplastic brain on silver-stained (Bielschowsky technique) sections. Immunohistochemical (immunoperoxidase) study of cortical lesions containing globular cells employing primary antibodies to glial fibrillary acidic protein and synaptophysin as markers of astrocytic and neuronal differentiation, respectively, revealed that many cells showed astrocytic and/or neuronal features, suggesting the local proliferation of primitive or multipotential neuroectodermal cells as one substrate for this seizure disorder. Morphological abnormalities of a severe degree and wide extent in the resected tissue (e.g., in one patient with hemimegalencephaly) often showed features to suggest that they may represent variants of tuberous sclerosis. These most likely result from abnormal movement and/or local proliferation of neuroectodermal precursors that have migrated from the germinal matrix to the cortical mantle. Cellular, molecular and neurophysiological study of these abnormalities is likely to yield information about basic molecular mechanisms of brain malformation and injury important in the pathogenesis of infantile spasms and other forms of focal or generalized epilepsy.

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 immuno-reactivity 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.

Corrigendum to ‘‘Exacerbation of vocal tics after temporal lobectomy’’ [Epilepsy Behav 2006;9:211–213] D. Sinno , H. Al-Amin , Y. Comair , M.A. Mikati a,* a Department of Pediatrics, American University of Beirut—Medical Center, Beirut, Lebanon b Department of Psychiatry, American University of Beirut—Medical Center, Beirut, Lebanon c Department of Surgery, American University of Beirut—Medical Center, Beirut, Lebanon

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.

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.

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.

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.

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.

The pharmacological action of a leukotriene antagonist FPL 55712 was studied on canine cerebral arterial segments. FPL 55712 at concentrations of 10(-6)M and 10)-5)M showed dose-dependent inhibition of the constrictor responses of the artery to prostaglandin F2 alpha. The constrictor responses of the artery to either serotonin or haemoglobin were suppressed by 10(-5)M FPL 55712, while 10(-6)M FPL 55712 failed to alter the responses. The KCL-induced constriction was not affected by treatment with either 10(-6)M or 10(-5)M FPL 55712. The present results suggest that FPL 55712 has vasodilator properties other than those related to the inhibition of leukotrienes.