Predictors of long-term memory and network connectivity 10 years after anterior temporal lobe resection.

OBJECTIVE: Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long-term network plasticity remain underexplored. Ten years post-ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function. METHODS: Twenty-five ATLR patients (12 left-sided) and 10 healthy controls underwent a memory-encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed-effect models probed preoperative phenotypes' effects on long-term memory outcomes. RESULTS: Ten years post-ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long-term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL-seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration. SIGNIFICANCE: Our findings underscore the enduring nature of functional network reorganizations to provide long-term cognitive support. Ten years post-ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long-term memory prediction and strategies for lasting memory rehabilitation.

The impact of suppressing puberty on neuropsychological function: A review.

AIM: Concerns have been raised regarding the impact of medications that interrupt puberty, given the magnitude and complexity of changes that occur in brain function and structure during this sensitive window of neurodevelopment. This review examines the literature on the impact of pubertal suppression on cognitive and behavioural function in animals and humans. METHODS: All studies reporting cognitive impacts of treatment with GnRH agonists/antagonists for pubertal suppression in animals or humans were sought via a systematic search strategy across the PubMed, Embase, Web of Science and PsycINFO databases. RESULTS: Sixteen studies were identified. In mammals, the neuropsychological impacts of puberty blockers are complex and often sex specific (n = 11 studies). There is no evidence that cognitive effects are fully reversible following discontinuation of treatment. No human studies have systematically explored the impact of these treatments on neuropsychological function with an adequate baseline and follow-up. There is some evidence of a detrimental impact of pubertal suppression on IQ in children. CONCLUSION: Critical questions remain unanswered regarding the nature, extent and permanence of any arrested development of cognitive function associated with puberty blockers. The impact of puberal suppression on measures of neuropsychological function is an urgent research priority.

Sex differences in the pre and postoperative neuropsychological function of epilepsy surgery candidates.

Objective: As programs expand globally, epilepsy surgery is becoming increasingly available as an effective treatment for some people with medically intractable seizures. Prospective candidates require careful neuropsychological evaluation and follow-up. The aim of this study was to examine the sex differences in neuropsychological function in presurgical presentation and postoperative outcomes in people with temporal lobe epilepsy referred for epilepsy surgery. Methods: Three hundred and seventy-two patients (202 Female; 170 Male) with a homogenous underlying pathology (hippocampal sclerosis) underwent a preoperative assessment on tests of intellectual, language, and memory function and were followed up one year after undergoing a unilateral temporal lobe resection; n = 169 Right (RTL), n = 203 Left (LTL). Results: There was no impact of sex or laterality of surgery on seizure outcome; 84% of males and 80% of females were seizure free at follow-up. Before surgery, sex effects were evident on tests of verbal memory with females performing better than males. Declines in verbal memory function following surgery were greater in females than males. Being female had a stronger association with postoperative decline on immediate prose recall (partial eta squared η2 = 0.029), than side of surgery (η2 = 0.018) albeit with a small effect size. Conclusions: There are subtle but significant sex differences in the neuropsychological profiles of people with temporal lobe epilepsy, before and following surgery. Whilst females generally perform better than males on tests of verbal memory function before surgery they demonstrate greater post-operative declines on these measures following surgery.

What are we really predicting with fMRI in epilepsy surgery?

While memory and language functional magnetic resonance imaging (fMRI) paradigms are becoming evermore refined, the measures of outcome they predict following epilepsy surgery tend to remain single scores on pencil and paper tests that were developed decades ago and have been repeatedly shown to bear little relation to patients' subjective reports of memory problems in the real world. The growing imbalance between the increasing sophistication of the predictive paradigms on the one hand and the vintage measures of the outcome on the other in the fMRI epilepsy surgery literature threatens the clinical relevance of studies employing these technologies. This paper examines some of the core principles of assessing neuropsychological outcomes following epilepsy surgery and explores how these may be adapted and applied in fMRI study designs to maximize the clinical relevance of these studies.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Timing of referral to evaluate for epilepsy surgery: Expert Consensus Recommendations from the Surgical Therapies Commission of the International League Against Epilepsy.

Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.

Preoperative predictors of postoperative satisfaction with surgery.

BACKGROUND: Patient reported outcome measures (PROMs) are an important metric in the assessment of outcomes following elective treatments such as epilepsy surgery. The Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a new (2020), valid, and reliable measure of patient satisfaction that provides measures of satisfaction in multiple domains. This study examined preoperative psychiatric predictors of ESSQ-19 scores. METHODS: All patients who underwent epilepsy surgery at our center in the decade between January 2010 and 2020 and who were at least one year out from surgery were invited to complete the ESSQ-19 (n = 284). RESULTS: Responses were received from 29% of the sample. Non responders did not differ from responders in age, type of surgery, sex, or seizure outcome, but had a lower Verbal Comprehension Index score. Reported satisfaction rates were high in each ESSQ-19 domain (Seizure control, mean = 83.9; Psychosocial function, mean = 72.4; Surgical Complications, mean = 86.4; Recovery from surgery, mean = 77.4; Overall satisfaction, mean = 80.8) and broadly comparable to those reported in the original validation sample for the ESSQ-19. Preoperative levels of anxiety predicted postoperative satisfaction with recovery from surgery and psychosocial outcomes, with high levels of preoperative anxiety associated with higher levels of dissatisfaction in both sub domains. CONCLUSIONS: Satisfaction with some aspects of postoperative outcome is not just dependent upon postoperative factors, but can be predicted from preoperative levels of anxiety. Clinicians offering preoperative counseling and preparation with respect to patients' expectations of surgical outcome should be cognizant of the possible impact of anxiety on postoperative satisfaction, particularly with respect to psychosocial function.

Uses and abuses of the neuropsychological assessment in the presurgical evaluation of epilepsy surgery candidates.

Recent guidelines from the International League Against Epilepsy (ILAE) delineating the role of the neuropsychologist in the assessment of epilepsy surgery patients stress the collaborative contribution neuropsychologists should make to seizure characterization, lateralization and localization in the pre-surgical setting. The role they should play in the comprehensive counselling of surgical candidates, including exploration of the patient's expectations of surgical treatment is also mandated. In this paper we present two contrasting case studies which illustrate the importance of these roles and the impact they can have on patient outcomes. In Case A we describe the patient journey of a 69-year-old women with left hippocampal sclerosis and concordant neurophysiology and seizure semiology. We present the series of discussions and decisions which led her to reject the surgical option following a detailed exploration of her motivations for surgery and the likely cognitive consequences of the procedure. In Case B we describe the series of errors and omissions which led to the failure of a clinical team to correctly interpret and integrate neuropsychological findings into the larger clinical picture of a 19-year-old woman with a seven year history of seizures. These errors ultimately culminated in the patient undergoing a right temporal lobe resection to treat psychogenic nonepileptic seizures (PNES). The extent of integration of the data from the clinical neuropsychological assessment in the full presurgical evaluation was critical in determining the outcomes in both of these cases. Surgery did not solve Case B's problems and left her with the lifelong cognitive vulnerabilities that are associated with unilateral temporal lobe resection. In contrast, Case A was a good surgical candidate, but comprehensive integration of the neuropsychological findings into the larger clinical picture established that surgery was not the best solution to the problem she wished to solve.

Optimal Surgical Extent for Memory and Seizure Outcome in Temporal Lobe Epilepsy.

OBJECTIVE: Postoperative memory decline is an important consequence of anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), and the extent of resection may be a modifiable factor. This study aimed to define optimal resection margins for cognitive outcome while maintaining a high rate of postoperative seizure freedom. METHODS: This cohort study evaluated the resection extent on postoperative structural MRI using automated voxel-based methods and manual measurements in 142 consecutive patients with unilateral drug refractory TLE (74 left, 68 right TLE) who underwent standard ATLR. RESULTS: Voxel-wise analyses revealed that postsurgical verbal memory decline correlated with resections of the posterior hippocampus and inferior temporal gyrus, whereas larger resections of the fusiform gyrus were associated with worsening of visual memory in left TLE. Limiting the posterior extent of left hippocampal resection to 55% reduced the odds of significant postoperative verbal memory decline by a factor of 8.1 (95% CI 1.5-44.4, p = 0.02). Seizure freedom was not related to posterior resection extent, but to the piriform cortex removal after left ATLR. In right TLE, variability of the posterior extent of resection was not associated with verbal and visual memory decline or seizures after surgery. INTERPRETATION: The extent of surgical resection is an independent and modifiable risk factor for cognitive decline and seizures after left ATLR. Adapting the posterior extent of left ATLR might optimize postoperative outcome, with reduced risk of memory impairment while maintaining comparable seizure-freedom rates. The current, more lenient, approach might be appropriate for right ATLR. ANN NEUROL 2022;91:131-144.

The clinical utility of a memory specialization index in epilepsy surgery patients with unilateral hippocampal sclerosis.

OBJECTIVE: Although group studies provide some support for the material-specific model of memory function, there are considerable individual variations in memory function in people with temporal lobe epilepsy, even in those with the same underlying pathology. In this proof-of-concept study, we examined the sensitivity and specificity of a single measure of an individual's relative strength for the encoding of verbal or visual learning. METHODS: Six hundred ninety-two patients with left hemisphere language dominance and unilateral hippocampal sclerosis completed verbal and visual encoding tasks with similar test structures as part of their presurgical evaluation. Three hundred one patients had right hippocampal sclerosis (RHS), and 391 patients had left hippocampal sclerosis (LHS). A memory specialization index (MSI) was calculated by subtracting the Visual Learning z-score from the Verbal Learning z-score. A positive value on the MSI indicates a relative strength in verbal learning. A negative score indicates a relative strength in visual learning. RESULTS: Employing cut-offs of ±1, the MSI had a positive predictive value of 71% (confidence interval [CI] 95% 0.64-0.77) for LHS and 64% (CI 95% 0.55-0.74) for RHS and was superior to the standalone z-scores from the verbal and visual tests in each respect. In the LHS group, the MSI was significantly correlated with age and duration of epilepsy. Older patients who had a longer duration of epilepsy were more likely to demonstrate a similar level of impairment in both verbal and visual learning, with a decreasing discrepancy between the scores on the two tasks over time. SIGNIFICANCE: Our MSI provides a measure with high specificity for RHS. The pattern of strengths and weaknesses in visual and verbal encoding may evolve with age and duration of epilepsy, and clinicians should be aware of these factors when interpreting the lateralizing significance of test scores, particularly in a presurgical setting.

The association of cognitive phenotypes with postoperative outcomes after epilepsy surgery in patients with temporal lobe epilepsy.

INTRODUCTION: The concept of cognitive phenotypes has been developed to categorize the heterogeneity of neuropsychological profiles in patients with temporal lobe epilepsy (TLE). This study examines the utility of cognitive phenotypes derived from clinical criteria in the prediction of postoperative outcomes. METHODS: Scores from 9 standardized neuropsychological tests were used to sample preoperative performance in 4 core domains (intellectual, memory, language, & executive function) in 445 patients with TLE (206 right: 236 left). Patients were grouped into 3 clinical phenotypes using clinical criteria: 1. intact cognition, 2. isolated memory and/or language impairment, and 3. widespread impairment. Patients who did not meet the criteria for these phenotypes were characterized as having a mixed profile phenotype. RESULTS: Approximately half of the sample had intact cognitive function, with one-quarter demonstrating isolated impairments in language and memory function. The remainder demonstrated widespread impairment or a mixed pattern of cognitive impairments. The clinically derived cognitive phenotypes were associated with demographic and clinical characteristics. Patients with widespread cognitive impairments had an earlier onset of seizures than those with other cognitive phenotypes. They also reported higher levels of depression. Higher levels of anxiety were reported in those with isolated memory/language impairments. Phenotypes were not associated with postoperative seizure outcome or postoperative declines in verbal memory or language function, but an intact phenotype was associated with a greater risk of decline in visual learning than right-sided surgery. CONCLUSIONS: Distinct cognitive phenotypes in TLE can be identified using clinical criteria and may reflect neurodevelopmental influences and mood in addition to progression of the disease. Phenotype may be a more powerful predictor of postoperative decline in visual memory than laterality of surgery.

Hippocampal Shape Is Associated with Memory Deficits in Temporal Lobe Epilepsy.

OBJECTIVE: Cognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface-shape patterns to verbal and visual learning. METHODS: We analyzed hippocampal surface shapes on high-resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age- and sex-matched healthy volunteers. RESULTS: Both left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline. INTERPRETATION: Memory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170-182.

Cognitive rehabilitation and prehabilitation in people with epilepsy.

Epilepsy is now recognized as a network disorder of the brain that can impact cognition beyond the periictal disturbance associated with seizures. While there is a large literature on the assessment of cognitive functions, particularly memory, in people with epilepsy, there are far fewer studies looking at the efficacy of treatments for cognitive dysfunction in this population. Reviews of the cognitive rehabilitation literature in epilepsy have begun to outnumber original studies. This paper examines the possible reasons for this unsatisfactory ratio in the literature and examines the unique challenges and opportunities for cognitive rehabilitation in this population, with a particular focus on epilepsy surgical candidates. The concept of prehabilitation in this population is described. While traditional cognitive rehabilitation is implemented after a patient has developed a neuropsychological deficit, in surgical candidates, prehabilitation uses intact functions before they are lost to establish compensatory strategies and routines prior to surgery in preparation for postoperative changes. The likely postoperative neuropsychological profile for individual patients can now be modeled using preoperative data. These predictions can guide and inform the prehabilitation process. Rather than concluding with a generic call for more research, the paper presents a framework for a rehabilitation program with practical solutions to address cognitive difficulties in both surgical and nonsurgical populations of people with epilepsy.

The cognitive costs, contraindications and complications of epilepsy surgery in adults.

PURPOSE OF REVIEW: Access to epilepsy surgery is rapidly growing throughout the world. While it is an established and effective treatment for seizures, epilepsy surgery has the potential to exacerbate cognitive comorbidities of the condition. RECENT FINDINGS: Not all surgical patients experience a postoperative decline in cognitive function. Postoperative cognitive function depends upon the functional integrity of the tissue to be removed and the functional reserve of the structures that remain in situ. While developments in surgical technique can reduce the cognitive morbidity of epilepsy surgery, the same procedure may result in different cognitive outcomes for different candidates, depending on their preoperative characteristics and postoperative trajectories. Multivariate models can be used to identify those most at risk of cognitive decline. There remains a significant lack of research into clinical interventions aimed at reducing the impact of surgically induced cognitive deficits on the lives of the patients who experience them. SUMMARY: Accurate identification of the cognitive risks associated with surgery, based on an individual's personal risk profile rather than the generic risks associated with the procedure, is now recognized as a mandatory part of the preoperative evaluation and is one of the pillars of informed consent for the procedure.

Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults.

In our first paper in this series (Epilepsia 2015; 56(5): 674-681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence-based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long-term assessment of these changes following surgery should form an integral part of the postoperative follow-up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.

Association of Piriform Cortex Resection With Surgical Outcomes in Patients With Temporal Lobe Epilepsy.

Importance: A functional area associated with the piriform cortex, termed area tempestas, has been implicated in animal studies as having a crucial role in modulating seizures, but similar evidence is limited in humans. Objective: To assess whether removal of the piriform cortex is associated with postoperative seizure freedom in patients with temporal lobe epilepsy (TLE) as a proof-of-concept for the relevance of this area in human TLE. Design, Setting, and Participants: This cohort study used voxel-based morphometry and volumetry to assess differences in structural magnetic resonance imaging (MRI) scans in consecutive patients with TLE who underwent epilepsy surgery in a single center from January 1, 2005, through December 31, 2013. Participants underwent presurgical and postsurgical structural MRI and had at least 2 years of postoperative follow-up (median, 5 years; range, 2-11 years). Patients with MRI of insufficient quality were excluded. Findings were validated in 2 independent cohorts from tertiary epilepsy surgery centers. Study follow-up was completed on September 23, 2016, and data were analyzed from September 24, 2016, through April 24, 2018. Exposures: Standard anterior temporal lobe resection. Main Outcomes and Measures: Long-term postoperative seizure freedom. Results: In total, 107 patients with unilateral TLE (left-sided in 68; 63.6% women; median age, 37 years [interquartile range {IQR}, 30-45 years]) were included in the derivation cohort. Reduced postsurgical gray matter volumes were found in the ipsilateral piriform cortex in the postoperative seizure-free group (n = 46) compared with the non-seizure-free group (n = 61). A larger proportion of the piriform cortex was resected in the seizure-free compared with the non-seizure-free groups (median, 83% [IQR, 64%-91%] vs 52% [IQR, 32%-70%]; P < .001). The results were seen in left- and right-sided TLE and after adjusting for clinical variables, presurgical gray matter alterations, presurgical hippocampal volumes, and the proportion of white matter tract disconnection. Findings were externally validated in 2 independent cohorts (31 patients; left-sided TLE in 14; 54.8% women; median age, 41 years [IQR, 31-46 years]). The resected proportion of the piriform cortex was individually associated with seizure outcome after surgery (derivation cohort area under the curve, 0.80 [P < .001]; external validation cohorts area under the curve, 0.89 [P < .001]). Removal of at least half of the piriform cortex increased the odds of becoming seizure free by a factor of 16 (95% CI, 5-47; P < .001). Other mesiotemporal structures (ie, hippocampus, amygdala, and entorhinal cortex) and the overall resection volume were not associated with outcomes. Conclusions and Relevance: These results support the importance of resecting the piriform cortex in neurosurgical treatment of TLE and suggest that this area has a key role in seizure generation.

Ability to knit may be impaired following right temporal lobe resection for drug-resistant epilepsy.

•The ability to knit may be compromised following a right or non-dominant temporal lobe resection.•Non-lesional patients may be at particular risk.•It is important to disseminate knowledge of impact of epilepsy surgery on specialist skills, via case studies.

Neuropsychological assessment in epilepsy.

The role of the neuropsychological assessment in the management of people with epilepsy has evolved considerably over the past 25 years. This paper describes some of the most common applications of a neuropsychological assessment in the diagnosis, management and treatment of people with epilepsy. It describes the factors that influence the interpretation of neuropsychological test scores in this patient group and outlines the limitations of the investigation. It gives guidelines for the optimal timing of a referral, together with timelines and indications for reassessment, and provides a checklist to help the referring clinician get the most from a neuropsychological assessment for their patients with epilepsy.

Red flags in epilepsy surgery: Identifying the patients who pay a high cognitive price for an unsuccessful surgical outcome.

Preoperative estimates of cognitive and seizure outcome must be as accurate as possible if the candidate is to make an informed decision about epilepsy surgery. Significant declines in memory function are reported in approximately 30% of temporal lobe surgery patients. The percentage varies according to the ways in which a postoperative deterioration is defined but since the majority of outcome studies do not take into account the patient's capacity to deteriorate if they are functioning at or close to the floor of a memory test prior to surgery, the published percentages may be an underrepresentation of the true extent of memory decline following epilepsy surgery. We examined the cognitive 'cost' of epilepsy surgery in a consecutive series of 474 patients who underwent elective surgery for medically intractable epilepsy. All patients underwent a presurgical assessment prior to and 1year after the surgery. Reliable change indices were used to identify significant postoperative memory decline. Postoperative outcome was dichotomized using the ILAE 2008 classification. All patients in class one were classified as seizure-free (67.5% of the sample). Excluding patients already functioning at or below the 2nd percentile on standardized memory tests, 37.8% experienced a significant postoperative decline in memory function. Twelve percent experienced the 'double hit' of significant postoperative memory decline and ongoing seizures following surgery. Patients with pathologies other than hippocampal sclerosis and with signs of limited cognitive reserve, both in terms of memory function and overall intellectual ability were most likely to suffer a double hit. Our results indicate that caution should be exercised when operating on these patients and preoperative counseling should be tailored to reflect the likely risk/benefit ratio of a temporal lobe resection for medically intractable epilepsy in this group.