A randomized, controlled trial of surgery for temporal-lobe epilepsy.

BACKGROUND: Randomized trials of surgery for epilepsy have not been conducted, because of the difficulties involved in designing and implementing feasible studies. The lack of data supporting the therapeutic usefulness of surgery precludes making strong recommendations for patients with epilepsy. We conducted a randomized, controlled trial to assess the efficacy and safety of surgery for temporal-lobe epilepsy. METHODS: Eighty patients with temporal-lobe epilepsy were randomly assigned to surgery (40 patients) or treatment with antiepileptic drugs for one year (40 patients). Optimal medical therapy and primary outcomes were assessed by epileptologists who were unaware of the patients' treatment assignments. The primary outcome was freedom from seizures that impair awareness of self and surroundings. Secondary outcomes were the frequency and severity of seizures, the quality of life, disability, and death. RESULTS: At one year, the cumulative proportion of patients who were free of seizures impairing awareness was 58 percent in the surgical group and 8 percent in the medical group (P<0.001). The patients in the surgical group had fewer seizures impairing awareness and a significantly better quality of life (P<0.001 for both comparisons) than the patients in the medical group. Four patients (10 percent) had adverse effects of surgery. One patient in the medical group died. CONCLUSIONS: In temporal-lobe epilepsy, surgery is superior to prolonged medical therapy. Randomized trials of surgery for epilepsy are feasible and appear to yield precise estimates of treatment effects.

Does the intracarotid amobarbital procedure predict global amnesia after temporal lobectomy?

PURPOSE: The intracarotid amobarbital procedure (IAP) is widely used to help predict who might be at risk for postoperative amnesia after unilateral temporal lobectomy for intractable seizures. We describe the memory outcome in 10 patients who underwent standard temporal lobectomy, including mesial temporal structures, despite failing the memory portion of the IAP after injections both ipsilateral and contralateral to the resected seizure focus. METHODS: Data for seven of the study subjects were obtained through a retrospective review of patients assessed on a surgical epilepsy unit during a 15-year period who failed the Montreal Neurological Institute IAP memory protocol after both ipsilateral and contralateral injections and subsequently underwent unilateral temporal lobectomy. More recently, we have studied temporal lobectomy patients who failed the Medical College of Georgia memory protocol after both ipsilateral and contralateral injections (n = 3). Preoperative and postoperative memory test scores were compared, and data regarding seizure outcome and self-perception of postoperative memory were collected. RESULTS: At follow-up, none of the patients presented with a pattern indicative of a global amnesia, and 80% demonstrated >90% improvement in their seizure disorder or were seizure-free. CONCLUSIONS: These findings indicate that bilateral memory failure on the IAP does not preclude the removal of an epileptogenic temporal lobe or a successful surgical outcome. In addition, the findings raise questions regarding the validity of the IAP and the possibility that memory may be reorganized in patients with a long history of temporal lobe epilepsy.

Communication and mental preparation issues for the epilepsy surgery patient.

This paper reviews the importance of adequate communication between the treatment team and the patient and family in epilepsy surgery. Ensuring that patient and family adequately understand the diagnosis, natural history, management alternatives and the risks and outcomes of surgery is a challenge for each epilepsy team. Guidelines as to process and content from the authors' experience and the participants in the workshop are presented.

Surgical pitfalls, their consequences, transient complications.

The methodology of this paper is based entirely on the experiential backgrounds of the authors. It outlines those factors which have become recognized as potentially important issues to patients who are considering recommendations of surgical treatment for their intractable epilepsy. Thus, on the one hand, it includes the important generic aspects of Informed Consent, while on the other hand there must be a very comprehensive and, when the operation is to be carried out under local anesthesia, a very detailed explanation of the preparation and the sequential steps in the surgical procedure. This should also entail a brief description of the roles of the various "team" members during the operative procedure. There are well-recognized complications associated with the various surgical procedures for the treatment of epilepsy. Further, there are predictable deficits following some of these procedures, some of which might be permanent and some of which may be transient. These pitfalls are briefly discussed.

Malignant transformation of a dysembryoplastic neuroepithelial tumor. Case report.

A 29-year-old man presented in 1984 with a recent onset of partial seizures marked by speech arrest. Electroencephalography identified a left frontotemporal dysrhythmia. Computerized tomography (CT) scanning revealed a superficial hypodense nonenhancing lesion in the midleft frontal convexity, with some remodeling of the overlying skull. The patient was transferred to the London Health Sciences Centre for subtotal resection of what was diagnosed as a "fibrillary astrocytoma (microcystic)." He received no chemotherapy or radiation therapy and remained well for 11 years. The patient presented again in late 1995 with progressive seizure activity. Both CT and magnetic resonance imaging demonstrated a recurrent enhancing partly cystic lesion. A Grade IV astrocytoma was resected, and within the malignant tumor was a superficial area reminiscent of a dysembryoplastic neuroepithelial tumor (DNT). Data on the lesion that had been resected in 1984 were reviewed, and in retrospect the lesion was identified as a DNT of the complex form. It was bordered by cortical dysplasia and contained glial nodules, in addition to the specific glioneuronal element. The glial nodules were significant for moderate pleomorphism and rare mitotic figures. The Ki67 labeling index averaged 0.3% in the glial nodules and up to 4% focally. Cells were rarely Ki67 positive within the glioneuronal component. This case is the first documented example of malignant transformation of a DNT. It serves as a warning of the potential for malignant transformation in this entity, which has been traditionally accepted as benign. This warning may be especially warranted when confronted with complex forms of DNT. The completeness of resection in the benign state is of paramount importance.

Arctic and Antarctic exploration including the contributions of physicians and effects of disease in the polar regions.

A history of Arctic and Antarctic exploration, whether to find a Northwest Passage, North Pole, or South Pole, is a story of triumph and tribulation. The hardship experienced by polar explorers in the last 1000 years permeates the tales of achievement. Physicians and surgeons have played prominent roles in all major polar explorations. No significant Arctic voyage, particularly in the last 300 years, was made without a member of the party trained in the management of medical emergencies and in basic surgery. During times of health, surgeons functioned as the voyage naturalists with expertise in biology, botany, zoology, and the writing of scientific catalogs. Spurred by our interest and fascination with the history of polar exploration, we reviewed the roles of physicians and natural scientists in Arctic and Antarctic adventures.

MR in temporal lobe epilepsy: analysis with pathologic confirmation.

PURPOSE: We evaluated the MR findings in patients with temporal lobe epilepsy to determine the predictive value of MR imaging in assessing patient outcome. METHODS: MR studies from 186 of 274 consecutive patients who underwent temporal lobectomy for intractable epilepsy were reviewed retrospectively. Images were interpreted by an experienced neuroradiologist, who was blinded to the side of seizure activity and to pathologic findings. RESULTS: MR imaging exhibited 93% sensitivity and 83% specificity in detecting hippocampal/amygdalar abnormalities (n = 121), and 97% sensitivity and 97% specificity in detecting abnormalities in the rest of the temporal lobe (n = 60). Abnormal high signal of the hippocampus on T2-weighted images had a sensitivity of 93% and specificity of 74% in predicting mesial temporal sclerosis (n = 115). The presence of hippocampal atrophy on MR correlated with the duration of seizures. Sensitivity and specificity of MR imaging in detecting temporal lobe tumors (n = 42) were 83% and 97%, respectively, based on abnormal signal and mass effect. After surgery, 63% of patients were seizure free and 28% had a significant reduction of seizure frequency at an average of 24 months (range, 12 to 78 months) after surgery. Patients with a single lesion in the anterior temporal lobe or hippocampus/amygdala had a better outcome than patients with multiple lesions (n = 22). Interrater agreement varied from 0.4 to 0.93, with best agreement for tumors or abnormal hippocampal signal on T2-weighted images. CONCLUSION: MR imaging is highly sensitive in detecting and locating abnormalities in the temporal lobe and the hippocampus/amygdala in patients with temporal lobe epilepsy. Hippocampal atrophy appears to correspond to the duration of seizure disorder.

Propofol sedation during awake craniotomy for seizures: electrocorticographic and epileptogenic effects.

This prospective study evaluated the effects of propofol sedation on the incidence of intraoperative seizures and the adequacy of electrocorticographic (ECoG) recordings during awake craniotomy performed for the management of refractory epilepsy. Thirty patients scheduled for temporal or frontal lobectomy for epilepsy under bupivacaine scalp block were randomized to receive patient-controlled propofol sedation (PCS) combined with a basal infusion of propofol (n = 15) or neurolept analgesia using an initial bolus dose of fentanyl (0.7 microg/kg) and droperidol (0.04 mg/kg) followed by a fentanyl infusion (n = 15). Propofol administration was suspended 15 min before ECoG recording in the PCS group. The occurrence of inappropriate intraoperative seizures was noted and, based on blind review, the adequacy of ECoG recordings was compared. A higher incidence of intraoperative seizures was noted among the neurolept patients (6 vs 0, P = 0.008). Intraoperatively, ECoG recordings were adequate to proceed with resection in both groups. Evidence of low spike activity on ECoG did not correlate with the type of sedation administered. Higher frequency background ECoG activity was noted among patients who received propofol, but this did not interfere with ECoG interpretation. The use of propofol sedation does not appear to interfere with ECoG during epilepsy surgery, provided administration is suspended at least 15 min before recording.

Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia.

This prospective study evaluated the safety and efficacy of patient-controlled sedation (PCS) using propofol during awake seizure surgery performed under bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept analgesia using an initial bolus dose of fentanyl and droperidol followed by a fentanyl infusion (n = 17). Both groups received supplemental fentanyl and dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were made between groups for sedation, memory, and cognitive function, patient satisfaction, and incidence of complications. Levels of intraoperative sedation and patient satisfaction were similar between groups. Memory and cognitive function were well preserved in both groups. The incidence of transient episodes of ventilatory rate depression (<8 bpm) was more frequent among the propofol patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid. Intraoperative seizures were more common among the neurolept patients (7 vs 0, P = 0.002). PCS using propofol represents an effective alternative to neurolept analgesia during awake seizure surgery performed in a monitored care environment.

Health-related quality of life and seizure control in temporal lobe epilepsy.

We conducted a prospective study over 24 months to compare health-related quality of life in surgically and medically treated patients with intractable temporal lobe epilepsy. Seizure frequency and health-related quality of life were assessed in 81 patients before and 6, 12, and 24 months after treatment. Using the Epilepsy Surgery Inventory 55 (ESI-55), we compared (1) different seizure outcome groups and (2) temporal lobectomy with continuing medical management. Follow-up was satisfactory in 72 patients (89%), 51 treated with temporal lobectomy and 21 with no surgery. Pretreatment seizures and health-related quality of life were comparable in the two groups. Seizure outcome was significantly better at 6, 12, and 24 months after surgery. At 24 months, seizure-free patients and those with at least a 90% reduction in seizure frequency reported significant improvements in health-related quality of life (on 5 of 10 subscales and overall Epilepsy Surgery Inventory 55 scale). Deterioration in quality of life occurred with less than 90% seizure reduction. Only one Epilepsy Surgery Inventory 55 subscale at 6 months and two subscales at 12 months showed a significant difference. Patients with good seizure outcome experience improved health-related quality of life after treatment. Since temporal lobectomy results in considerably better seizure control than continued medical management, the findings support surgery as the preferred treatment, although changes in health-related quality of life may not be evident until the second postoperative year.

Effective temporal lobectomy in childhood without invasive EEG.

Temporal lobectomy abolished complex partial seizures (CPSs) in 14 consecutive children (12 years or younger) whose presurgical evaluation included clinical analysis, scalp EEG, and neuroimaging. Seizures of 13 of 14 patients began with a simple partial component whose symptoms were suggestive of limbic system involvement. EEG recorded clinically typical seizures arising from the ultimately operated on temporal lobe in seven (50%) and never falsely lateralized seizure origin. Most active interictal spikes arose from the epileptogenic temporal lobe in 13 (93%) and never falsely lateralized epileptogenesis. Neuroimaging disclosed epileptogenic lesions in all: magnetic resonance imaging (MRI; 11 patients) and computed tomography (CT; three patients). Children may obtain relief from CPSs by temporal lobectomy without invasive electroencephalography.

Altered seizure patterns after temporal lobectomy.

PURPOSE: We compared features of seizures occurring after temporal lobectomy with those of preoperative seizures in the same patients to determine whether aspects of postoperative partial seizures presage ultimate seizure control. METHODS: Seizure descriptions of 100 consecutive patients who underwent anterior temporal lobectomy (ATL) were obtained by our epileptologists before and after surgery. Follow-up for seizure control for all patients was obtained for a median of 5.5 years. RESULTS: Twenty-six of the 100 patients had at least one diurnal complex partial seizure (CPS) after lobectomy. The proportion of patients with an aura for their CPS decreased from 86% preoperatively to 58% postoperatively. Fifty-five percent had two or more aura features before surgery, as compared with 31% after lobectomy. Eleven of 18 (61%) with fewer than two postoperative aura features, as compared with 2 of 8 (25%) with two or more aura features ultimately had >90% seizure reduction postoperatively. Nineteen (95%) of 20 patients with only simple partial seizures (SPS) postoperatively ultimately obtained > or =90% reduction, and 7 (35%) of them became seizure-free. Although generalized tonic-clonic seizures (GTCS) decreased from 70% to 39% after lobectomy, 7 (23%) of 30 patients who had not had GTCS preoperatively had at least one after lobectomy, usually while receiving a lesser amount of antiepileptic drug (AED) therapy. Among the 27 patients with residual CPS, ultimate outcome was better among patients with removal of >6 cm as measured along the inferior temporal gyrus than among those with less extensive resections. CONCLUSIONS: In addition to eliminating or reducing the frequency of temporal lobe seizures, lobectomy may simplify or eliminate the aura features of residual CPS. The number of CPS aura features correlated inversely with ultimate postoperative seizure reduction. Ultimate seizure control among patients with only SPS was better than that of patients with CPS postoperatively. First-ever GTCS may occur when AED dosages are reduced after surgery.

Psychiatric disorders in candidates for surgery for epilepsy.

OBJECTIVE: To provide a descriptive analysis of the prevalence and pattern of psychiatric morbidity among 300 consecutive epileptic patients refractive to treatment and admitted during a six year period for evaluation of their candidature for surgery. METHODS: Patients underwent detailed observation of their seizure and standardised psychiatric assessment. Patients were considered to be refractory to treatment if they continued to manifest seizures with an average frequency of at least once every month even with polytherapy using up to three different anti-convulsants for a period of at least two years. Of the 300 patients, 231 had a temporal lobe focus, 43 had a non-temporal lobe focus, and 26 patients had a generalised and multifocal seizure onset. RESULTS AND CONCLUSIONS: With the DSM-III-R criteria 142 (47.3%) patients emerged as psychiatric cases. A principal axis I diagnosis was made in 88 (29.3%), and an axis II diagnosis (personality disorder) in another 54 (18.0%) patients. The most common axis I diagnosis was anxiety disorders (10.7%). A schizophrenia-like psychosis was seen in 13 (4.3%). Most patients with personality disorders showed dependent and avoidant personality traits. There was a significantly higher psychotic subscore on the present state examination in the temporal than with the non-temporal group of patients. These findings were not significant when compared with patients with a generalised and multifocal seizure disorder. There were no significant findings between the different seizure focus groups on the neurotic subscores. The findings with regard to laterality of seizure focus and the neurotic or psychotic subscores were not significant.

Symptomatic osteolipoma of the tuber cinereum.

Intracranial osteolipomas are rare lesions which occur in the region of the tuber cinereum. All cases reported to date have been incidental autopsy findings. We describe a patient who presented with a variety of neurological symptoms and had a typical osteolipoma surgically removed.

Significance of spikes at temporal lobe electrocorticography.

Among 87 consecutive patients operated on under local anesthesia, few aspects of pre- and posttemporal lobe resection electrocorticograms (ECoG) yielded prognostic data. Preresection spikes were most common in the hippocampus, followed in order of frequency by the anterior temporal convexity and the inferior temporal surface. Moderately frequent (>10 spikes/100 s) preresection spikes appeared beyond the subsequent resection line in the posterior temporal region in 16 of 87 (18%) and in orbital frontal cortex in 12 of 87 (14%). Although many hippocampus spikes portended a favorable outcome and rare spikes an unfavorable one, preresection spike quantity otherwise failed to distinguish outcome groups. Absolute quantity of postresection spikes and change from preresectrion quantity in any region did not correlate with outcome except for the insula, where relatively abundant spikes portended favorable outcomes. Postresection electrographic seizures were rare but occurred equally in all outcome groups. No significant change in spike incidence occurred between the first and last 10-min epoch of the 30-min postresection recording.

Mesial temporal lobe seizures presenting as anxiety disorders.

Five patients had brief simple partial seizures that mimicked panic disorder. The following features assisted diagnosis: Seizures were briefer and more stereotyped than panic attacks; some progressed to typical complex partial seizures; and aphasia and dysmnesia occurred during seizures in some patients. Each patient had one mesial temporal structural lesion. Routine waking EEG was normal in 2 patients. Inadequate response to anti-epileptics necessitated partial temporal lobectomy in 4 patients, 3 of whom remain seizure free.

Spreading depression of Leão in rodent and human cortex.

Spreading depression (SD) has been implicated in the pathophysiology of a number of neurological conditions. The same methodology was used to elicit SD in anesthetized rats and in non-anesthetized patients undergoing cortical resections for intractable epilepsy. A slowly spreading DC potential shift (mean -9 mV) occurred in the cortex of 10 of 15 rats in association with attenuation of the electrocorticogram but this could not be reproduced in any of the human cortices (n = 23) where the mean potential shift was -0.56 mV (P < 0.0001). SD is more difficult to elicit in human than rodent cortex and may not occur in man.

Amygdaloid sclerosis in temporal lobe epilepsy.

Hippocampal sclerosis is the sole abnormality found in approximately 65% of all temporal lobe specimens resected for intractable temporal lobe epilepsy. Up to 27% of en bloc temporal lobectomy specimens, however, show no definitive pathological changes. The lateral amygdaloid nucleus from 8 consecutive patients who underwent temporal lobectomy in whom no definitive hippocampal pathology was present and corresponding tissue from 8 consecutive patients with hippocampal sclerosis were subjected to quantitative estimation of neuronal density and astrogliosis. As compared to amygdaloid tissue from autopsy control subjects with no history of neurological disease, both the patient group with and that without hippocampal sclerosis consistently exhibited severe neuronal loss and gliosis with no quantitative differences between the two groups. Blinded clinical review of both groups of patients revealed that the development of hippocampal sclerosis was associated with a history of early brain insult; this history was absent in patients with isolated amygdaloid sclerosis. Neuropsychological testing prior to surgery demonstrated that patients with hippocampal sclerosis displayed a greater degree of memory impairment than did those without hippocampal sclerosis. We conclude that amygdaloid sclerosis occurs in the absence of hippocampal sclerosis, and that these patients form a distinct group with no history of early brain insult and milder memory impairment than that seen in patients afflicted with hippocampal sclerosis.

Rasmussen's chronic encephalitis in adults.

OBJECTIVE: Rasmussen's chronic encephalitis, a cause of intractable epilepsy in childhood, is described in three adults. SETTING: Inpatient epilepsy unit. PATIENTS: Of 11 patients with pathological confirmation of Rasmussen's encephalitis, three were adults with intractable seizures, progressive sensorimotor deficits, and cognitive decline beginning at the ages of 36, 24, and 16 years. RESULTS: Clinical, electroencephalographic, and magnetic resonance imaging findings indicated patchy, multifocal involvement of primarily one hemisphere, but the adults had more evidence of disease in the opposite hemisphere than occurs in children. The sensorimotor deficit that the adults developed was greater and the cognitive decline was less than in children. Seizure control following multilobe resection was proportionate to the amount of tissue removed. Cytomegalovirus genome was found in the resected cortical tissue of all three patients. CONCLUSIONS: Rasmussen's encephalitis is a cause of intractable epilepsy with progressive neurological deficit in adults as well as children. Cytomegalovirus may be involved in the pathogenesis of the disease.