Predictors of outcome after temporal lobectomy for the treatment of intractable epilepsy.

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.

Assessment of motoneuron excitability using recurrent inhibition and paired reflex depression protocols: a test of reliability.

Motor output may be regulated by both pre- and post-synaptic mechanisms. The purpose of this study was to investigate the reliability of two measurement protocols, which purport to examine spinal mechanisms responsible for gating motoneuron excitability. Nine subjects (aged 29 +/- 5 years) were tested using two soleus H-reflex protocols; 1) recurrent inhibition (RI) and 2) paired reflex depression (PRD). The dependent variable for each protocol was the peak-to-peak amplitude of the conditioned Hoffmann reflex (H-reflex). Seven trials were obtained for each subject under each condition as well as control values to assess test-retest reliability. After all trials were collected the subjects rested for at least five minutes after which the process was repeated. Each subject returned to the lab after a period of no less than 24 hours at which time the process was repeated. Protocol #1: Control reflexes (20% of maximal motor response) were obtained during quiet stance. After obtaining control trials two reflex responses were elicited which were separated by 10 ms on each trial to assess recurrent inhibition (Pierrot-Deseilligny et al., 1976; Bussel and Pierrot-Deseilligny, 1977). Protocol #2: Again a double-pulse technique was used to assess reflex activation history on motoneuron pool output (Trimble et al., 2000). This protocol utilized two reflex stimuli of the same intensity separated by 80 ms. The peak-to-peak amplitude of the control, RI conditioned and PRD conditioned H-reflexes exhibited intraclass reliability estimates of .97, .97 and .93 respectively. To achieve a reliability of rI > or = .80, it is recommended that a minimum of 2 trials be used for the RI protocol and that 4 trials be used for the PRD protocol. The results indicate that both techniques provide a means to objectively and reliably measure spinal mechanisms for gating motoneuron pool output.

Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

The effects of lamotrigine on sleep in patients with epilepsy.

PURPOSE: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in REM, slow-wave sleep (SWS) and sleep latency, and increased percentage of light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of lamotrigine (LTG) on sleep. METHODS: Ten adults with focal epilepsy, in whom the decision was made to add LTG to either phenytoin (PHT) or carbamazepine (CBZ) for control of seizures, were the subjects of this study. Patients underwent pre- and posttreatment polysomnography (PSG) and completed sleep questionnaires. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon sign rank test. RESULTS: Seven patients were taking CBZ, and three were treated with PHT. All subjects were titrated to an LTG dose of 400 mg/day. Treatment with LTG produced a significant decrease in SWS and an increase in stage 2 sleep percentage. No significant difference in ESS or any of the other polygraphic variables was observed. However, LTG treatment was associated with a reduction in arousals and stage shifts and an increase in REM periods. No subjects reported insomnia with treatment. CONCLUSIONS: LTG appears to be less disruptive to sleep than some of the older AEDs.

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.

Somatosensory evoked high-frequency oscillations recorded directly from the human cerebral cortex.

OBJECTIVE: To elucidate the generator sources of high-frequency oscillations of somatosensory evoked potentials (SEPs), we recorded somatosensory evoked high-frequency oscillations directly from the human cerebral cortex. SUBJECTS AND METHODS: Seven patients, 6 with intractable partial epilepsy and one with a brain tumor, were studied. With chronically implanted subdural electrodes, we recorded SEPs to median nerve stimulation in all patients, and also recorded SEPs to lip and posterior tibial nerve stimulation in one. High-frequency oscillations were recorded using a restricted bandpass filter (500-2000 Hz). RESULTS: For the median nerve oscillations, all oscillation potentials were maximum at the electrodes closest to the primary hand sensorimotor area. Most oscillations were distributed similar to or more diffusely than P20/N20. Some later oscillations after the peak of P20 or N20 were present in a very restricted cortical area similar to P25. We investigated the phase change of each oscillation potential around the central sulcus. One-third of the oscillations showed phase reversal around the central sulcus, while later oscillations elicited in a restricted cortical area did not. High-frequency oscillations to posterior tibial nerve and lip stimulation were also maximum in the sensorimotor areas. Most of the lip oscillations showed phase reversal around the central sulcus, but most of the posterior tibial nerve oscillations did not. CONCLUSION: High-frequency oscillations are generated near the primary sensorimotor area. There are at least two different generator mechanisms for the median nerve high-frequency oscillations. We suspect that most oscillations are derived from the terminal segments of thalamocortical radiations or from the primary sensorimotor cortex close to the generator of P20/N20, and some later oscillations from the superficial cortex close to the generator of P25.

Potential fluconazole-induced carbamazepine toxicity.

OBJECTIVE: To report a case of carbamazepine toxicity resulting from a drug interaction with fluconazole, and to review the possible mechanisms of this interaction. DATA SOURCES: Medical record review. DATA SYNTHESIS: A 33-year-old white man with a history of mental retardation and seizures experienced stupor due to carbamazepine toxicity after fluconazole was initiated. The patient had been taking carbamazepine for several years and maintained stable therapeutic concentrations. He started fluconazole therapy after developing a rash presumably due to candidiasis. After admission to the hospital for carbamazepine toxicity, both fluconazole and carbamazepine were withheld and the patient returned to his normal baseline mental status once the carbamazepine concentration declined to a therapeutic range. Carbamazepine was restarted and the patient experienced no further adverse events. Carbamazepine is metabolized by the cytochrome P450 3A4 isoenzyme. Fluconazole is renally excreted but has been noted to inhibit CYP3A4. Fluconazole has also been noted to increase phenytoin concentrations. CONCLUSIONS: Fluconazole may cause carbamazepine toxicity presumably by inhibiting the cytochrome P450 3A4 isoenzyme.

Successful treatment with gabapentin in the presence of hypersensitivity syndrome to phenytoin and carbamazepine: a report of three cases.

We report three consecutive patients with hypersensitivity syndrome (HSS) due to phenytoin and carbamazepine and successful treatment with gabapentin. HSS is a rare but potentially fatal reaction to multiple drugs including several anticonvulsants. Cross-reactivity among drugs may occur. Immediate withdrawal of the offending drug is the most important step in treatment. Benzodiazepines acutely and, after resolution of the hepatitis, valproic acid have been successfully used for seizure control in patients with HSS. Our cases indicate that gabapentin is also a safe anticonvulsant in HSS.

Hypersensitivity syndrome to antiepileptic drugs: a review including new anticonvulsants.

Anticonvulsant hypersensitivity syndrome, a potentially fatal but rare reaction, manifests as rash, fever, tender lymphadenopathy, hepatitis, and eosinophilia. To manage hypersensitivity syndrome successfully, one must recognize the symptoms early, stop the offending drug immediately, and substitute a safe, alternative anticonvulsant medication. Hypersensitivity syndrome has not been described in patients taking benzodiazepines or the newer anticonvulsants gabapentin or topiramate, and these appear to be safe substitutes for drugs that cause the reaction.

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.

Anaplastic pleomorphic xanthoastrocytoma.

Well-documented cases of malignant degeneration in pleomorphic xanthoastrocytoma and of anaplastic pleomorphic xanthoastrocytoma are rare in the literature. We report 2 cases of pleomorphic xanthoastrocytoma, 1 of which demonstrated clear evidence of malignant degeneration in the absence of prior radiation therapy over an 18-year period. Both anaplastic tumors were characterized by foci of necrosis and increased mitotic activity (3 and 2 mitotic figures/10 high-power fields). Both tumors demonstrated focal positive staining for glial fibrillary acidic protein and showed marked reticulin deposition. An MIB-1 labeling index (marker of cell proliferation) in the initial low-grade-appearing tumor in case 1 was 0.1%. The recurrent tumor in case 1 had an MIB-1 labeling index of 4.9%, and the anaplastic tumor in case 2 had an MIB-1 labeling index of 5.4%. Significant cyclin D1 immunoreactivity was not observed in either anaplastic tumor. Two percent to 3% of tumor cells stained positive with p53 protein antibody in the recurrent anaplastic tumor in case 1. Although histology may not reliably predict aggressive behavior in pleomorphic xanthoastrocytomas, the presence of increased mitosis, necrosis, and increased cell proliferation labeling indices may be indicative of a higher grade tumor.

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.

Sensitivity and specificity of asymmetric recall on WADA test to predict outcome after temporal lobectomy.

Some reports suggest that the intracarotid amobarbital test (IAT) is useful for predicting good seizure outcome after temporal lobectomy. The sensitivity, specificity, and predictive value of the IAT in this condition has not been previously studied. We designed this study to establish the value of memory recall asymmetry on the IAT as a predictor of outcome after temporal lobectomy. We studied memory recall on the IAT in 108 consecutive patients with intractable epilepsy who underwent presurgical evaluation for temporal lobectomy and had at least 1 year follow up after surgery. At a level of 30% asymmetry of recall, specificity for favorable outcome (Engel Class I and II) was 100% (95% confidence interval [CI], 85 to 100), sensitivity 51% (95% CI, 40 to 62), positive predictive value 100% (95% CI, 92 to 100), and negative predictive value 34% (95% CI, 23 to 47). At the same level of asymmetry, specificity for seizure-free outcome (Engel Class I) was 88% (95% CI, 68-95), sensitivity 37% (95% CI, 40 to 64), positive predictive value 87% (95% CI, 71 to 96), and negative predictive value 38% (95% CI, 27 to 50). Asymmetric recall on the IAT is highly specific but not very sensitive in predicting outcome after temporal lobectomy.

Pharmacokinetics of new anticonvulsants in psychiatry.

The newer AEDs have potential in the treatment of psychiatric disorders. In light of this expanding spectrum of activity, it is necessary to refine and focus the safety and efficacy of the use of these agents among a wider population. The classic AEDs had numerous problems, ranging from inconvenient dosing schedules to frequent side effects due to active metabolites and common drug interactions; newer agents have been developed to avoid some of these pitfalls. Indeed, a generation of drugs that appears to have relatively simple pharmacokinetics and limited drug interactions--making them safer and easier to administer--is now available. The use of these agents in psychiatry will necessitate additional investigation into their dosing and administration guidelines, as well as their interactions with other common psychiatric or concomitant drugs. Certainly, over time, they will be evaluated for these parameters in the newer indications. In the meantime, a review of the established pharmacokinetic and pharmacodynamic activities of these agents is the first step in defining their optimal uses and limitations in the psychiatric setting.

Gabapentin monotherapy: I. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 88/89.

We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.

Usefulness of ictal and interictal 99mTc ethyl cysteinate dimer single photon emission computed tomography in patients with refractory partial epilepsy.

PURPOSE: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in approximately 90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for approximately 6 h. facilitating the performance of ictal studies. METHODS: In a prospective, open-label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of 99mTc-ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal 99mTc-ECD SPECT. RESULTS: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases. CONCLUSIONS: 99mTc-ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc-ECD are similar to those reported with 99mTc-HMPAO. Because 99mTc-ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.

Epilepsy after central nervous system infection: clinical characteristics and outcome after epilepsy surgery.

Fifty-six (5.8%) patients with partial epilepsy secondary to central nervous system (CNS) infection (meningitis = 20 and encephalitis = 36) were identified from 963 patients studied with prolonged video-EEG monitoring. Twenty-seven (48.2%) patients had unilateral mesial temporal lobe epilepsy (UMTLE), 9 (16.1%) had bilateral mesial temporal lobe epilepsy (BMTLE), and 20 (35.7%) had neocortical epilepsy (NE). Younger age at infection and prolonged latency between the time of infection and development of epilepsy were predictive factors for UMTLE. Predictors for BMTLE were late age of infection and short latency between infection and epilepsy development. Development of NE was associated with short latency between infection and epilepsy, and younger age at infection. When outcome after temporal lobectomy was compared between the UMTLE group and a control group with UMTLE without history of CNS infection, no statistically significant differences were found. Central nervous system infection may lead to epilepsy, which in many cases, is generated by a single portion of the brain. In such cases, epilepsy surgery should be considered, as in patients without history of CNS infection.

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

UNLABELLED: PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. METHODS: Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. RESULTS: Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. CONCLUSION: The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

Reliability and comparison of RPE during variable and constant exercise protocols performed by older women.

The purposes of this study were to assess if women 60 to 75 years of age perceived a series of exercise intensities differently from selected intensities in that series and to determine if a particular intensity was perceived more reliably. Twenty-four women (65 +/- 3.8 yr) completed a walking VO2max treadmill test. Subjects were either assigned to a variable, randomly ordered exercise protocol (GP1) or to one of three constant exercise protocols (Gps2-4). Each subject performed relative exercise intensities of 30, 50, and 70% of peak VO2 for three 5 min work bouts over 3 test days. Differences in RPE (p < 0.05) were found between each intensity and between the same intensities from both protocols. Women in GP1 rated exercise higher than women who exercised at a constant exercise intensity (p < 0.05). Intraclass correlation coefficients indicated that the exercise intensity of 50% of maximum was more reliable regardless of the protocol (Gp1: R = 0.97, Gp3: r = 0.94). When the RPE-HR correlation coefficients were transformed into a log scale, neither protocol had a stronger association (p > 0.05) between RPE-HR. It was concluded that older women should be given a range of exercise intensities that include the 50% relative exercise intensity as a perceptual marker in order to reach a reliable rate of exertion.