Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

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.

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.

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.

Establishing the cross-cultural applicability of a harmonized approach to cognitive diagnostics in epilepsy: Initial results of the International Classification of Cognitive Disorders in Epilepsy in a Spanish-speaking sample.

OBJECTIVE: This study was undertaken to evaluate the cross-cultural application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to a cohort of Spanish-speaking patients with temporal lobe epilepsy (TLE) living in the United States. METHODS: Eighty-four Spanish-speaking patients with TLE completed neuropsychological measures of memory, language, executive function, visuospatial functioning, and attention/processing speed as part of the Neuropsychological Screening Battery for Hispanics. The contribution of demographic and clinical variables to cognitive performance was evaluated. A sensitivity analysis was conducted by examining the base rates of impairment across several impairment thresholds. The IC-CoDE taxonomy was then applied, and the base rate of cognitive phenotypes for each cutoff was calculated. The distribution of phenotypes was compared to the published IC-CoDE taxonomy data, which utilized a large, multicenter cohort of English-speaking patients with TLE. RESULTS: Across the different impairment cutoffs, memory was the most impaired cognitive domain, with impairments in list learning ranging from 50% to 78%. Application of the IC-CoDE taxonomy utilizing a -1.5-SD cutoff revealed an intact cognitive profile in 47.6% of patients, single-domain impairment in 23.8% of patients, bidomain impairment in 14.3% of patients, and generalized impairment in 14.3% of the sample. This distribution was comparable to the phenotype distribution observed in the IC-CoDE validation sample. SIGNIFICANCE: We demonstrate a similar pattern and distribution of cognitive phenotypes in a Spanish-speaking epilepsy cohort compared to an English-speaking sample. This suggests stability in the underlying phenotypes associated with TLE and applicability of the IC-CoDE for guiding cognitive diagnostics in epilepsy research that can be applied to culturally and linguistically diverse samples.

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

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.

Anhedonia in epilepsy.

BACKGROUND: Anhedonia, the impaired ability to experience pleasure, is a core feature of major depressive disorder, one of the most common comorbidities in epilepsy. It is also reported as a clinical feature independent of depression in a number of other neurological conditions. This study aimed to establish the prevalence of anhedonia in a sample of people with epilepsy, with and without a diagnosis of depression, and to examine the clinical and demographic characteristics of those who present with this symptom. METHODS: A consecutive sample of 211 people (118 female, 93 male, mean age 38.09 years) completed the Snaith-Hamilton Pleasure Scale (SHAPS) to determine the presence of anhedonia and the Hospital Anxiety and Depression Scale to determine levels of anxiety and depression. The majority of patients had focal epilepsy (n = 165), and the remaining patients had generalized epilepsy (n = 22), or unclassified epilepsy (n = 24). Sixteen percent of the sample had a clinical diagnosis of depression at the time of the study. RESULTS: Over one in three of the sample (35%) reported significant anhedonia on the SHAPS. While these patients were more likely to have a diagnosis of depression (p < 0.01), 30% of people without a diagnosis of depression also reported significant anhedonia. Difficulties gaining pleasure on 12 of the 14 items on the SHAPS were associated with cognitive difficulties, with those reporting an inability to feel pleasure on the item scoring significantly lower on tests of cognitive function than those who were able to gain pleasure. Of the three cognitive domains examined (overall intellectual ability, verbal memory, and processing speed), a poor memory had the strongest relationship; with lower memory function associated with an impaired ability to experience pleasure on 9 of the 14 items. CONCLUSION: While anhedonia is well recognized as a feature of depression, our data suggests that it can be present in up to a third of people with epilepsy who do not have a diagnosis of depression. Cognitive difficulties, particularly impaired memory function may mediate some features of anhedonia. The implications of these findings for the clinical management of anhedonia in people with epilepsy are discussed.

Application of the International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) to frontal lobe epilepsy using multicenter data.

RATIONALE: The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) was recently introduced as a consensus-based, empirically-driven taxonomy of cognitive disorders in epilepsy and has been effectively applied to patients with temporal lobe epilepsy (TLE). The purpose of this study was to apply the IC-CoDE to patients with frontal lobe epilepsy (FLE) using national multicenter data. METHODS: Neuropsychological data of 455 patients with FLE aged 16 years or older were available across four US-based sites. First, we examined test-specific impairment rates across sites using two impairment thresholds (1.0 and 1.5 standard deviations below the normative mean). Following the proposed IC-CoDE guidelines, patterns of domain impairment were determined based on commonly used tests within five cognitive domains (language, memory, executive functioning, attention/processing speed, and visuospatial ability) to construct phenotypes. Impairment rates and distributions across phenotypes were then compared with those found in patients with TLE for which the IC-CoDE classification was initially validated. RESULTS: The highest rates of impairment were found among tests of naming, verbal fluency, speeded sequencing and set-shifting, and complex figure copy. The following IC-CoDE phenotype distributions were observed using the two different threshold cutoffs: 23-40% cognitively intact, 24-29% single domain impairment, 13-20% bi-domain impairment, and 18-33% generalized impairment. Language was the most common single domain impairment (68% for both thresholds) followed by attention and processing speed (15-18%). Overall, patients with FLE reported higher rates of cognitive impairment compared with patients with TLE. CONCLUSIONS: These results demonstrate the applicability of the IC-CoDE to epilepsy syndromes outside of TLE. Findings indicated generally stable and reproducible phenotypes across multiple epilepsy centers in the U.S. with diverse sample characteristics and varied neuropsychological test batteries. Findings also highlight opportunities for further refinement of the IC-CoDE guidelines as the application expands.

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.

Theta power and theta-gamma coupling support long-term spatial memory retrieval.

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations to support long-term memory. Here we asked 10 presurgical epilepsy patients undergoing intracranial EEG recording to perform a long-term spatial memory task in desktop virtual reality and found that increased theta power in two discrete bands ("low" 2-5 Hz and "high" 6-11 Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between "low" theta phase and gamma amplitude during the same period was associated with improved task performance. Finally, low and high gamma amplitude appeared to peak at different phases of the theta cycle; providing a novel connection between human hippocampal function and rodent data. These results help to elucidate the role of theta oscillations and theta-gamma phase-amplitude coupling in human long-term memory.

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.

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.

Epilepsy: Lessons for clinicians from popular memes on social media.

Memes are a very effective, visual means of communication on social media sites. In this study, we examined some of the most popular memes posted on Instagram labeled with an epilepsy hashtag, in order to gain an insight into the thoughts, feelings and concerns of people with epilepsy. 'Awareness', 'warrior' and 'sucks' were the three most common words paired with epilepsy in the hashtag search. The most popular (liked or shared) #epilepsy memes could be classified into 9 broad categories: Seeking advice, Raising awareness, Inspirational quotes, Celebrations of seizure free milestones, Living with Epilepsy, Sharing the diagnosis, Experience of seizures, Medications and Doctor/patient interactions. Popular memes in this latter category highlighted people's difficulties in taking in information with respect to both the breadth and complexity of the discussions in neurological consultations. Other memes in this category depicted the social and psychological challenges associated with some investigations, particularly video-telemetry studies. Analyses of some of the most popular memes posted on social media point to a number of ways in which we can improve the patient/clinician interaction. Practical strategies to address some of these issues are discussed. Memes posted on social media by people with epilepsy provide a valuable source of feedback for clinicians which enables us to improve the care we provide for this group.

Epilepsy & gambling: Risk factors for problem gambling behaviors in people with epilepsy.

OBJECTIVE: Problem gambling results from the complex interaction of neurological factors with psychological, demographic, and socioeconomical influences. The vulnerabilities of people with epilepsy to many of these influences may increase their susceptibility to developing problematic gambling behaviors. The aim of this study was to establish the frequency of gambling participation and the clinical correlates of problem gambling behaviors in people with epilepsy. METHODS: Lifestyle questions, including the Lie/Bet screening questionnaire were administered to 250 consecutive attendees at a neurology clinic. Valid data were available for 174 adults with epilepsy and 65 adults with other neurological conditions. RESULTS: With the exception of people with frontal lobe epilepsy (FLE), gambling participation rates in people with epilepsy and those with other neurological conditions were lower than those reported in the general population. While the overall levels of gambling participation were relatively low in this sample, the number of gamblers who responded positively to the lie/bet questionnaire was ten times higher than that seen in the general population, with one in three gamblers in our series reporting signs of escalation. All had epilepsy and were more likely to be taking Levetiracetam or Brivaracetam than the other gamblers in our series. While epilepsy classification was not related to gambling escalation, patients with FLE were overrepresented in this group due to their significantly higher baseline levels of participation in gambling. CONCLUSIONS: People with FLE may have a heightened vulnerability to developing problem gambling behaviors. The role of the neurological consultation in managing these risks is discussed.

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.

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 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.

Memory complaints in the epilepsy clinic.

Cognitive complaints in people with epilepsy are usually multifactorial in their nature and origin. While antiepileptic medications are an important consideration, we explore other ways in which neurologists can address cognitive problems in this population. It is never too early to ask about cognitive impairment, and the answers can have diagnostic significance. Understanding and accepting that cognitive problems may result, at least in part, from the same pathological process that generates seizures is an important part of the rehabilitation process. Patients referred for neurorehabilitation for cognitive difficulties who have realistic expectations and goals tend to benefit more from the intervention than those expecting a cure. Developing an understanding of this and managing patient expectations should start in the neurology clinic. Although we focus primarily on memory function, the principles we discuss in this paper apply to the broad spectrum of cognitive and neurobehavioral problems that accompany the many diagnoses of epilepsy.