Treatment of the interictal psychoses.

BACKGROUND: The interictal "schizophrenia-like" psychoses of epilepsy conventionally are treated with antipsychotic medication with uncertain results. In patients with these psychoses, a preceding and concomitant dysphoric disorder usually can be documented. Effectiveness of the pharmacologic treatment by the combination of drugs that is effective for severe interictal dysphoric disorders is demonstrated in a series of patients with interictal psychosis. METHOD: Patients were treated with the combination of a tricyclic antidepressant and a selective serotonin reuptake inhibitor, enhanced if necessary by a small amount of the atypical neuroleptic risperidone. The series consisted of 8 consecutive patients with interictal psychosis seen over a 20-month period. Two additional patients seen over the past 10 years who required a different therapeutic intervention were also included. RESULTS: Five of the 8 consecutive patients achieved full remission of their psychosis; 3 patients could not be reached for the full treatment effort. One patient with a malignant psychosis had been treated successfully (prior to the series reported) by surgical removal of a left frontal epileptogenic zone; a second patient (treated after the series) recovered only upon elimination of the antiepileptic drug that had suppressed clinical seizures but had resulted in an alternating psychosis. CONCLUSION: Interictal psychoses can be viewed as severe interictal dysphoric disorders with psychotic features. The same combination of psychotropic medication that is effective for severe interictal dysphoric disorders serves as the primary therapy for interictal psychoses. The interictal psychiatric disorders presumably result from seizure-suppressing mechanisms that are the targets of the proconvulsant drugs. Upon suppression of seizures, some patients with interictal psychosis may require modification of the antiepileptic medication responsible for excessive inhibition. Complete surgical removal of the epileptogenic zone can eliminate a chronic interictal psychosis upon postoperative fading of inhibitory mechanisms.

Prediction of verbal memory loss in individuals after anterior temporal lobectomy.

PURPOSE: Decreased memory function represents the area of greatest neuropsychological morbidity after anterior temporal lobectomy (ATL), particularly for left ATL candidates. We wished to identify easily derived demographic and neuropsychological predictors of risk of pre- to postoperative memory decline using only information available preoperatively. METHODS: We assessed decline in memory as measured by the California Verbal Learning Test (CVLT) by deriving multiple regression equations using the following measures as independent variables: age at onset, chronological age at time of surgery, sex, Full Scale IQ (FSIQ), level of education, and preoperative memory scores. In all, 203 patients (93 males, 110 females), undergoing ATL (107 left, 96 right) with preoperative and 6-month postoperative testing, were examined. RESULTS: The combination of age, FSIQ, sex, side of surgery and preoperative score was highly predictive (p-values < 0.0001) of postoperative memory scores. Higher postoperative scores were associated with higher preoperative score, younger chronological age, higher FSIQ, female sex, and right side of resection. Reliable change index (RCI) values were used to estimate meaningful decline on the total score across five trials. Logistic regression analysis showed preoperative score and age to be predictors of RCI decline for left-sided resections. Sensitivity of decline (> or =90th centile RCI) prediction was 56%, and specificity was 95%. Validation in 30 patients from a separate population of patients undergoing left ATL produced similar figures. CONCLUSIONS: The derived regression equations can accurately predict verbal memory decline on a list-learning task in approximately 50% of individual patients undergoing ATL, and false-positive prediction errors are very rare.

Temporal ictal electroencephalographic frequency correlates with hippocampal atrophy and sclerosis.

We studied 328 complex partial seizures (CPS) in 63 consecutive patients with temporal lobe epilepsy who underwent scalp electroencephalography/video monitoring, magnetic resonance imaging (MRI), and surgery. The initial ictal discharge (IID), defined as the first sustained electrical seizure pattern localized to the surgical site, was determined. If the IID was rhythmic waves, the median frequency was measured. To determine if IID frequency correlates with hippocampal atrophy (HA) or sclerosis (HS), hippocampal volume ratios (HVRs) were measured (n = 52) or assessed visually (n = 11) on MRI, and mesial temporal histopathology specimens (n = 22) were graded for HS. Sixteen patients (25%) had no or mild HA (HVR = 0.78-1.02), and 47 patients (75%) had moderate-to-marked unilateral (HVR = 0.33-0.76), or bilateral, HA. Theta frequency IIDs were significantly more commonly associated with moderate-to-marked HA than were delta IIDs. Theta frequency IIDs occurred in 19% of patients with mild or no HA, and 79% of patients with moderate-to-marked HA; delta IIDs occurred in 63% of patients with little to no HA, and 13% of those with moderate-to-marked HA. In addition, the median IID frequency inversely correlated with HVR and directly correlated with HS severity. In conclusion, faster frequency rhythmic IIDs during temporal lobe CPS correlate with greater degrees of ipsilateral HA on MRI, and higher grades of HS.

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression-based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed.

Recent advances in epilepsy surgery: temporal lobectomy and multiple subpial transections.

THIS ARTICLE REVIEWS four major advances in epilepsy surgery, especially the most frequently performed surgery, temporal lobectomy, as follows: 1) the ability to preoperatively identify (using magnetic resonance imaging) the pathological condition of hippocampal sclerosis (a key component to the syndrome of mesial temporal lobe epilepsy, 2) the ability to identify preoperatively which temporal lobe candidates are at risk for postoperative memory problems, 3) the standardization of temporal lobectomy with respect to how much hippocampus should be resected, 4) a validation of the novel surgical technique of multiple subpial transections. This technique allows surgeons to attack foci within nondispensible cortex and therefore enlarges the applicability of surgical treatment to otherwise inoperable patients and potentially improves outcome.

Recent advancements in epilepsy.

This article reviews selected medical and surgical advances that the authors view as important to improving the treatment of patients with epilepsy. This includes a review of six new antiepileptic drugs (fosphenytoin, felbamate, gabapentin, lamotrigine, toprimimate, and vigabatrin), recent studies of the surgical technique of Multiple Subpial Transections, and a summary of a prospective longitudinal study on anterior temporal lobectomy.

Intractable epilepsy due to meningitis: results of surgery and pathological findings.

Between 1986 and 1992, among a total of 668 craniotomies performed for intractable epilepsy, 13 (1.9%) patients had a presumed aetiology of a previous episode of meningitis. Twelve were investigated with chronic electrocorticography with subdural electrodes which showed mesial temporal onset in eight, regional temporal onset in three and bilateral diffuse onset in one. One patient underwent corpus callosotomy and 12 anterior temporal lobectomy (ATL) (6L, 6R). The pathology in the resection cases was hippocampal sclerosis in six and gliosis in six. Mean length of follow up was 3 years (range 1-6 years). Ten of the 12 (83%) ATL patients were seizure free (six off medications). Two ATL patients and the callosotomy patient were significantly improved. It is concluded that in patients where the presumed aetiology of intractable epilepsy is meningitis and widespread damage may therefore be expected, this does not necessarily indicate multifocality, and the prognosis following resective surgery appears to be good.

Empirical techniques for determining the reliability, magnitude, and pattern of neuropsychological change after epilepsy surgery.

PURPOSE: We assessed test-retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression-based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy. METHODS: Forty patients with complex partial seizures (CPS) who did not undergo epilepsy surgery were administered a comprehensive neuropsychological battery on two occasions. Their test-retest data were used to compute both RCIs and regression-based norms for change for each neuropsychological index. RCIs corrected for practice effects provide a confidence interval (CI) indicating the degree of performance change required to exceed the variability attributable to sources of error (e.g., practice, test-retest reliability). Regression-based norms for change also correct for several sources of measurement error and examine observed versus expected test-retest changes on a common metric, thereby facilitating determination of the degree and relative magnitude of change across cognitive domains. RESULTS: Mean changes in test-retest performance were generally modest, but were evident across several test measures. Our data indicate a considerable degree of individual variability in test-retest performance. CONCLUSIONS: RCIs and regression-based norms are complementary indexes and can be particularly useful in examining the test-retest performance of individual patients who undergo epilepsy surgery as well as in the more general investigation of cognitive outcome after epilepsy surgery.

Hippocampal sclerosis and verbal encoding ability following anterior temporal lobectomy.

Previous research has shown that the degree of verbal memory decline following left anterior temporal lobectomy (ATL) is inversely related to the extent of neuronal dropout in resected left hippocampus. The goal of this investigation was to clarify further the nature of the free recall impairment and to determine the relative contribution of verbal retrieval and encoding processes. Seventy-six patients who underwent left (n = 46) or right (n = 30) ATL were classified according to the presence or absence of hippocampal sclerosis and pre- to postoperative changes in free recall, cued recall and recognition memory for verbal material were examined. Surgically induced free recall impairments were selectively associated with resection of nonsclerotic left hippocampus and represented a 29-35% decline in verbal learning ability. These free recall deficits were due to postoperative impairment in verbal encoding efficiency, not retrieval difficulties. Assessment of false positive recognition errors indicated that resection of nonsclerotic left hippocampus selectively impaired the ability to encode stimulus uniqueness within correct semantic fields. The clinical and theoretical significance of these results are discussed.

Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients.

Controversy exists as to whether hippocampal sclerosis (HS) is a preexisting cause or a consequence of seizures. We investigated 122 consecutive patients who underwent anterior temporal lobectomy for intractable epilepsy between 1989 and 1992. MRI scans were normal apart from evidence of HS in 5 cases. The degree of HS was graded from 0 to 4. There was a significant inverse correlation between age of seizure onset and grade of HS (P < 0.0001), and a positive correlation between duration of epilepsy and grade of HS (P < 0.001). Using a dichotomous grouping of HS (HPSC - for grades 0 and 1 [no/mild HS], and HPSC + for grades 3 and 4 [moderate/marked HS]), there was a positive correlation between HPSC + and a history of childhood febrile seizures (CFS) (P = 0.003), earlier age of onset of epilepsy (P < 0.001) and longer duration of epilepsy (P < 0.001). There was no correlation with history of particularly prolonged individual seizures. Partial correlations after controlling for age at onset of epilepsy showed that there was no longer a significant relationship between HPSC + and duration of epilepsy. After controlling for duration of epilepsy, the relationship between HPSC + and age of onset remained significant (P < 0.001). The correlation between HPSC + and CFS, controlling for age at onset, was not significant. A series of logistic regression analyses showed age at onset to be the only predictor of HPSC +. It is concluded that this is supportive evidence for preexisting HS being a cause of temporal lobe epilepsy and not a consequence of seizures.

Cataplexy and monoamine oxidase deficiency in Norrie disease.

Norrie disease (ND) is an X-linked recessive disorder causing ocular atrophy, mental retardation, deafness, and dysmorphic features. Virtually absent monoamine oxidase (MAO) type-A and -B activity has been found in some boys with chromosome deletions. We report the coexistence of cataplexy and abnormal REM sleep organization with ND. Three related boys, referred for treatment of medically refractory atonic spells and apneas, underwent extended EEG-video-polysomnographic monitoring. They demonstrated attacks of cataplexy and inappropriate periods of REM sleep during which they were unarousable. One boy also had generalized tonic-clonic seizures. Previous testing revealed that all three have complete ND gene deletions. In all subjects, platelet MAO-B activity was absent, serum serotonin levels were markedly increased, and plasma catecholamine levels were normal. Data from the canine narcolepsy syndrome model implicate abnormal catecholaminergic and cholinergic activities in the pathogenesis of cataplexy. Our findings suggest that abnormal MAO activity or an imbalance between serotonin and other neurotransmitter levels may be involved in the pathogenesis of human cataplexy.

Multiple subpial transections for partial seizures in sensorimotor cortex.

We report six patients with complex partial seizures arising from the primary sensorimotor cortex who underwent invasive long-term ictal electroencephalogram/video monitoring and brain mapping and then multiple subpial transections. Although four patients demonstrated no abnormalities on magnetic resonance imaging, each patient showed moderate to marked gliosis in cortex biopsied from the site of ictal onset. Extensive preoperative and postoperative neuropsychological tests demonstrated no functional deficits resulting from surgery. Only one patient failed to derive significant postoperative seizure improvement, and he subsequently underwent additional subpial sectioning without further significant improvement. We propose a modification for this surgical technique and hypothesize that these patients may represent a syndrome of central cortical epilepsy.

Extent of medial temporal resection on outcome from anterior temporal lobectomy: a randomized prospective study.

WE REPORT A prospective, randomized, blinded clinical trial comparing seizure and neuropsychological outcomes from anterior temporal lobectomies between two groups of patients. One group (n = 34) underwent hippocampal resection posteriorly to the anterior edge of the cerebral peduncle (partial hippocampectomy). In the other group (n = 36), the hippocampus was removed further to the level of the superior colliculus (total hippocampectomy). The amount of lateral cortical resection was the same between groups. Patients were and neuropsychological morbidity. At 1 year postoperatively, the total hippocampectomy group had a statistically superior seizure outcome compared with the partial hippocampectomy group (69 versus 38% seizure-free), and examination of time to first seizure (survival analysis) revealed significantly superior outcomes associated with total hippocampectomy. There was no increased neuropsychological morbidity associated with the more extensive hippocampal resection.

Wechsler adult intelligence scale-revised in the evaluation of anterior temporal lobectomy candidates.

We wished to (a) determine the ability of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to discriminate between patients with epilepsy of left or right temporal lobe (LTLE, RTLE) origin and (b) examine the ability of Kaufman's (1990) WAIS-R short forms to estimate actual Full-Scale IQ (FSIQ). We administered the WAIS-R to 215 nonretarded, left hemisphere dominant patients with invasively verified epilepsy of unilateral TL origin without lesions demonstrated by magnetic resonance imaging (MRI) (excluding mesial temporal sclerosis, MTS). LTLE (n = 106) and RTLE (n = 109) groups were compared on the WAIS-R subtests and summary IQ scores. Verbal-Performance IQ (VIQ-PIQ) discrepancies of various magnitudes, and Verbal Comprehension (VC) and Perceptual Organization (PO) scores derived by factor analysis. The LTLE group scored significantly lower on the Vocabulary subtest, and none of the other indexes reliably distinguished LTLE from RTLE patients. The Kaufman 2, 3, and 4 subtest short forms were significant predictors of FSIQ, with the 4 subtest short form having the highest correlation and lowest error of estimate.

Relationship of age at onset, chronologic age, and adequacy of preoperative performance to verbal memory change after anterior temporal lobectomy.

We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.

Reports by patients and their families of memory change after left anterior temporal lobectomy: relationship to degree of hippocampal sclerosis.

Memory decline represents the primary neuropsychological morbidity of anterior temporal lobectomy. Recent investigations using laboratory tests of memory have reported an association between the neuropathological status of the resected left mesial temporal region and memory outcome, with adverse memory outcome associated with a lack of significant left hippocampal pathology. The purpose of this investigation was to examine the relationship between the reports by the patients and their families of observed postoperative changes in day-to-day memory function and the degree of hippocampal sclerosis in resected left mesial temporal lobes. Twenty patients and a close family member (parent or spouse) of each of the patients completed standardized questionnaires assessing pre- to postoperative changes in verbal and spatial memory; these were related to the neuropathological findings. The results indicated that patients without left hippocampal sclerosis reported significantly worse memory outcome than those with hippocampal sclerosis. The ratings provided by the relatives of the patients yielded a comparable effect, and objective memory tests supported the reports by the patients and their families. The neuropsychological findings associated with left hippocampal pathology are of clinical significance and should be considered in surgical evaluation and in the counseling process.

Surgery for intractable epilepsy secondary to viral encephalitis.

In a series of 668 craniotomy cases for intractable epilepsy, in 11 patients (1.6%) the presumed aetiology was a previous episode of viral encephalitis, a widespread cerebral inflammation, which may therefore produce multifocal epilepsy. Seven patients had chronic ictal electrocorticography (ECoG). Two of these had a generalized onset, one bilateral temporal independent onset, and four unilateral mesial temporal onset. Three patients underwent corpus callosotomy. Eight had resections (seven anterior temporal lobectomy (ATL), and one ATL and frontal resection). Pathology was hippocampal sclerosis in four, neocortical gliosis in three and one specimen was normal. Of the resection patients, three (37%) were seizure-free at a mean of 3 years postoperatively and three (37%) unchanged. It is concluded that where the aetiology of intractable epilepsy is viral encephalitis the possibility of multifocal epilepsy should be considered. Chronic ECoG is recommended. Nevertheless, unilateral hippocampal sclerosis can also be produced and the results of ATL in these cases can be rewarding.