Psychiatric outcomes of epilepsy surgery: a systematic review

Purpose: The objective of this systematic review was to identify: (1) prevalence and severity of psychiatric conditions before and after resective epilepsy surgery, (2) incidence of postsurgical psychiatric conditions, and (3) predictors of psychiatric status after surgery. Methods: A literature search was conducted using PubMed, EmBase, and the Cochrane database as part of a larger project on the development of an appropriateness and necessity rating tool to identify patients of all ages with potentially resectable focal epilepsy. The search yielded 5,061 articles related to epilepsy surgery and of the 763 articles meeting the inclusion criteria and reviewed in full text, 68 reported psychiatric outcomes. Thirteen articles met the final eligibility criteria. Key Findings: The studies demonstrated either improvements in psychiatric outcome postsurgery or no changes in psychiatric outcome. Only one study demonstrated deterioration in psychiatric status after surgery, with higher anxiety in the context of continued seizures post‐surgery. One study reported a significantly increased rate of psychosis after surgery. The two main predictors of psychiatric outcome were seizure freedom and presurgical psychiatric history. De novo psychiatric conditions occurred postsurgery at a rate of 1.1–18.2%, with milder psychiatric issues (e.g., adjustment disorder) being more common than more severe psychiatric issues (e.g., psychosis). Significance: Overall, studies demonstrated either improvement in psychiatric outcomes postsurgery or no change. However, there is a need for more prospective, well‐controlled studies to better delineate the prevalence and severity of psychiatric conditions occurring in the context of epilepsy surgery, and to identify specific predictors of psychiatric outcomes after epilepsy surgery.     

Diffusion tensor imaging findings and their correlation with neuropsychological deficits in patients with temporal lobe epilepsy and interictal psychosis

PURPOSE: To examine frontotemporal white-matter integrity in patients with temporal lobe epilepsy (TLE) and interictal psychosis. METHOD: Patients with TLE and interictal psychosis (IP; n = 20) were compared with age-matched TLE patients without psychosis (NIP; n = 20). Patients had either no focal lesions or hippocampal sclerosis on conventional MRI. Complete diffusion tensor imaging (DTI) data were available in 18 IP and 20 NIP patients. A region-of-interest (ROI) approach was used to determine the DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), in the middle frontal and middle temporal gyri. The relation between the DTI measures and neuropsychological tests previously identified as impaired in the IP group was examined. RESULTS: The IP group had significantly lower FA values in both frontal and temporal regions and significantly higher MD in bilateral frontal regions. We found that performance on some neuropsychological tests was significantly related to frontotemporal FA reductions. CONCLUSIONS: Our findings suggest that subtle abnormalities in the frontotemporal white matter of patients with interictal psychosis may be undetectable on conventional MRI. These abnormalities may contribute to the cognitive deficits detected in these patients.     

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. Methods: In this study we present all adult MRI‐negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high‐resolution MRI were included in this study. Results: Among the 38 patients who finally underwent surgery, at the latest follow‐up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure‐free (Engel class IA). Twenty‐one (55%) of 38 patients had poor outcomes (Engel class III–IV). Outcomes did not change compared to 12‐month follow‐up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR‐negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). Discussion: Our results suggest that epilepsy surgery outcomes in MRI‐negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long‐term also remain stable. Modern imaging techniques could further improve the postsurgical seizure‐free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.     

Prognostic significance of serial postoperative EEG in extratemporal lobe epilepsy surgery

Objective

To assess the prognostic value of postoperative EEG in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.

Methods

We studied 63 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 ± 2.3 years, range 2–12). Follow-up evaluations were performed 2, 12, and 24 months after surgery, and included standard EEG (at 2 months) and long-term video-EEG monitoring during both wakefulness and sleep (at 12 and 24 months). Seizure outcome was determined at each follow-up evaluation, and then at yearly intervals. Patients who were in Engel Class I at the last contact were classified as having a good outcome.

Results

Seizure outcome was good in 39 patients (62%). The presence of interictal epileptiform discharges (IED) in postoperative EEG at each time point was found to be associated with poor outcome. The strength of this association was greater for awake plus sleep recording as compared with awake recording alone. In a multiple regression model including all pre- and post-operative factors identified as predictors of outcome in univariate analysis, the presence of early (2 months after surgery) EEG epileptiform abnormalities was found to be independently associated with poor seizure outcome.

Conclusions

Postoperative IED may predict long-term outcome in patients undergoing resective surgery for ET epilepsy.

Significance

The increase in risk of unfavourable outcome associated with EEG epileptiform abnormalities detected as early as two months after surgery may have substantial practical importance. Serial postoperative EEGs including sleep recording may add further predictive power and help making decision about antiepileptic drug discontinuation.     

High Rates of Psychiatric Co-Morbidity in PDD-NOS

Rates of co-morbid psychiatric conditions in children with Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) are hardly available, although these conditions are often considered as more responsive to treatment than the core symptoms of PDD-NOS. Ninety-four children with PDD-NOS, aged 6–12 years were included. The DISC-IV-P was administered. At least one co-morbid psychiatric disorder was present in 80.9% of the children; 61.7% had a co-morbid disruptive behavior disorder, and 55.3% fulfilled criteria of an anxiety disorder. Compared to those without co-morbid psychiatric disorders, children with a co-morbid disorder had more deficits in social communication. Co-morbid disorders occur very frequently in children with PDD-NOS, and therefore clinical assessment in those children should include assessment of co-morbid DSM-IV disorders.     

Magnetoencephalography and ictal SPECT in patients with failed epilepsy surgery

Objective

Selected patients with intractable focal epilepsy who have failed a previous epilepsy surgery can become seizure-free with reoperation. Preoperative evaluation is exceedingly challenging in this cohort. We aim to investigate the diagnostic value of two noninvasive approaches, magnetoencephalography (MEG) and ictal single-photon emission computed tomography (SPECT), in patients with failed epilepsy surgery.

Posttraumatic stress disorder and psychiatric co-morbidity following stroke: the role of alexithymia

More research is needed to further our understanding of posttraumatic stress disorder symptoms (PTSD) and psychiatric co-morbidity following stroke, especially the trajectories of such symptoms over time. Previous studies suggest that exposure to a traumatic experience such as stroke is not sufficient to explain the etiology of PTSD. Alexithymia may be involved, but its relationships with PTSD and psychiatric co-morbidity following stroke remains unclear. This study aims to address these knowledge gaps. While in hospital, stroke patients (n = 90) completed questionnaires assessing PTSD symptoms, psychiatric co-morbidity, alexithymia and physical disability. PTSD symptoms and psychiatric co-morbidity were re-assessed approximately 3 months post-stroke (n = 78). The severity of post-stroke PTSD did not change significantly over time, while psychiatric co-morbidity reduced significantly. Alexithymia, in particular difficulty in identifying feelings, was associated with severity of post-stroke PTSD and psychiatric co-morbidity at baseline, but after adjusting for these, there was no significance 3 months post-stroke. We suggest that patients' difficulty in identifying feelings had a role to play in influencing relatively short-term rather than long-term PTSD and co-morbid psychiatric symptoms. Alternatively, PTSD could be interpreted as driving the alexithymic characteristics.     

Mortality in a population-based cohort of epilepsy surgery patients

PURPOSE: To investigate mortality and especially the incidence of sudden unexpected death in epilepsy (SUDEP) in a population-based cohort of epilepsy surgery patients. METHODS: All patients who underwent epilepsy surgery treatment between January 1990 and December 1998 (surgery patients) or whose presurgical evaluation started, although not leading to an operation, during the same period (nonsurgery patients) were identified through the Swedish National Epilepsy register. All subjects were followed up through the Cause of Death Register until December 1998. Standardized mortality ratios (SMRs) for all causes of death and incidence of SUDEP were calculated. RESULTS: During the study period, 651 surgical operations were carried out on 596 patients (316 male). Of those, 14 patients died (six in SUDEP), rendering a total SMR of 4.9 [95% confidence interval (CI), 2.7-8.3]. SUDEP incidence was 2.4 per 1,000 person years. No major differences were found in SMRs or SUDEP rates between subgroups when stratifying for type of operation and for seizure outcome 2 years after surgery. SMR and SUDEP rates were higher in right-sided temporal lobe resections for gliosis than in left-sided, but the number of deaths was small. Among 212 nonsurgery patients, five died (four in SUDEP). The SMR for all causes was 7.9 (2.6-18.4), and SUDEP incidence, 6.3 per 1,000 person years. CONCLUSIONS: In this large and strictly population-based cohort, SMR for all causes and SUDEP incidence among surgery patients were similar to those of other studies. No differences in overall mortality emerged by seizure outcome, but none of the SUDEP cases was seizure free at the time of death. Four of five deaths in the nonsurgery group occurred during the surgery evaluation period. Mortality appeared to be lower for surgery than for nonsurgery patients, and the interpretation of this finding is discussed.     

Psychosis after epilepsy surgery: report of three cases

Temporal lobe epilepsy surgery has become a successful alternative in patients with refractory epilepsy. However, the outcome of epilepsy surgery may be affected by the occurrence of postsurgical psychiatric symptoms, such as psychosis. This report describes three cases of refractory temporal lobe epilepsy and hippocampal sclerosis, which, after anterior temporal lobectomy, presented with acute psychosis. One of them had a history of acute psychosis, and all of them met criteria for Cluster A personality disorder (schizoid/schizotypal) during psychiatric assessment prior to surgery. The three cases had a good seizure outcome (Engel I), but, on follow-up during the first year after surgery, developed an acute psychotic episode compatible with schizoaffective disorder; brief psychotic disorder; and a delusional disorder, respectively, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Treatment with low-dose risperidone was successful.     

Neuropsychological results in pediatric patients with epilepsy surgery in the parietal cortex

This study evaluated pre- and postoperatively cognitive functions in 15 pediatric patients with surgically treated parietal lobe epilepsy (PLE). Seizure outcome was very satisfying with 87% seizure-free patients 1 year after surgery, and 82% in the long-term follow-up. Preoperative intelligence was in the subaverage range. Impairments in specific cognitive functions (memory, attention, executive functions) were evident preoperatively for 39-66% of patients. Behavioral disorders were rare. No side differences (left versus right PLE) were indicated pre- or postoperatively. Postoperative improvements were found in behavior and attention; other cognitive functions were unchanged. All in all, this preliminary study indicated a satisfactory neuropsychological outcome in pediatric patients with PLE.     

Psychiatric comorbidity in epilepsy: a population-based analysis

PURPOSE: The estimated prevalence of mental health disorders in those with epilepsy in the general population varies owing to differences in study methods and heterogeneity of epilepsy syndromes. We assessed the population-based prevalence of various psychiatric conditions associated with epilepsy using a large Canadian national population health survey. METHODS: The Canadian Community Health Survey (CCHS 1.2) was used to explore numerous aspects of mental health in persons with epilepsy in the community compared with those without epilepsy. The CCHS includes administration of the World Mental Health Composite International Diagnostic Interview to a sample of 36,984 subjects. Age-specific prevalence of mental health conditions in epilepsy was assessed using logistic regression. RESULTS: The prevalence of epilepsy was 0.6%. Individuals with epilepsy were more likely than individuals without epilepsy to report lifetime anxiety disorders or suicidal thoughts with odds ratio of 2.4 (95% CI = 1.5-3.8) and 2.2 (1.4-3.3), respectively. In the crude analysis, the odds of lifetime major depression or panic disorder/agoraphobia were not greater in those with epilepsy than those without epilepsy, but the association with lifetime major depression became significant after adjustment for covariates. CONCLUSIONS: In the community, epilepsy is associated with an increased prevalence of mental health disorders compared with the general population. Epilepsy is also associated with a higher prevalence of suicidal ideation. Understanding the psychiatric correlates of epilepsy is important to adequately manage this patient population.     

Long-term developmental outcome in patients with West syndrome after epilepsy surgery

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.     

Impact of severe epilepsy on development: Recovery potential after successful early epilepsy surgery

Purpose: Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure‐free after surgery performed before the age of 6 years. Methods: The children were followed prospectively for a median of 5 years with serial neuropsychological assessments correlated with electroencephalography (EEG) and surgery‐related variables. Results: Short‐term follow‐up revealed rapid cognitive gains corresponding to cessation of intense and propagated epileptic activity [two with early catastrophic epilepsy; two with regression and continuous spike‐waves during sleep (CSWS) or frontal seizures]; unchanged or slowed velocity of progress in six children (five with complex partial seizures and frontal or temporal cortical malformations). Longer‐term follow‐up showed stabilization of cognitive levels in the impaired range in most children and slow progress up to borderline level in two with initial gains. Discussion: Cessation of epileptic activity after early surgery can be followed by substantial cognitive gains, but not in all children. In the short term, lack of catch‐up may be explained by loss of retained function in the removed epileptogenic area; in the longer term, by decreased intellectual potential of genetic origin, irreversible epileptic damage to neural networks supporting cognitive functions, or reorganization plasticity after early focal lesions. Cognitive recovery has to be considered as a “bonus,” which can be predicted in some specific circumstances.     

难治性癫痫外科治疗的长期效果:一项6年随访研究结果

目的总结分析难治性癫痫外科治疗的方法及效果,为进一步的临床实践提供指导。方法综合临床症状学、神经电生理和神经影像学等方法,对66例难治性癫痫患者进行致痫灶定位和外科手术治疗,术后进行长期随访,平均随访时间为6年。结果 1例患者在随访期间因意外窒息死亡,余结果如下:谭启富标准:满意22例(33.8%),显著改善33例(50.8%),良好6例(9.2%),较差2例(3.1%),无改善2例(3.1%);Engel标准:Ⅰ级21例(32.3%),Ⅱ级13例(20.0%),Ⅲ级24例(36.9%),Ⅳ级7例(7.8%)。术后出现的并发症有偏瘫、失语、感染等,但均在短期内恢复。结论综合临床症状、神经电生理和神经影像学检查,可以精确定位癫痫患者的致痫灶,进一步选择合适的手术方法可以使难治性癫痫的外科治疗获得良好的效果。     

Aicardi syndrome: epilepsy surgery as a palliative treatment option for selected patients and pathological findings

The optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo‐pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1–3 isolated spasms per day. Case 2 had a right fronto‐parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.     

VNS in patients with previous unsuccessful resective epilepsy surgery: antiepileptic and psychotropic effects

OBJECTIVES: To assess the efficacy of vagus nerve stimulation (VNS) in patients with medically and surgically intractable complex partial seizures (CPS). PATIENTS AND METHODS: Sixteen patients with previous temporal [15] and frontal [one] resections were treated with VNS between 1994 and 1999 at King's College Hospital, London, UK. Post-operative video-electroencephalogram telemetry had shown that CPS started from the operated side in 12 patients, contralaterally in three and bilaterally independently in one. RESULTS: Three patients (18.75%) had 50% or more reduction in seizure frequency, but one showed severe worsening of epilepsy, which remitted upon VNS discontinuation. The antiepileptic effect of VNS was not different with respect to the type of operation (anterior temporal lobectomy vs amygdalohippocampectomy), the side of operation, or the side of seizure onset. We observed psychotropic effects in two patients with post-ictal psychosis, in two others with depression, and in a child with severe behavioral disorder. CONCLUSIONS: VNS may have a rather limited antiepileptic role to play in patients with persistent seizures following epilepsy surgery, but may independently possess useful antipsychotic and mood-stabilizing properties.