Seizure freedom but not epilepsy surgery is associated with fewer neuropsychiatric difficulties in patients with tuberous sclerosis.

BACKGROUND: Drug-resistant epilepsy (DRE) in selected individuals with the rare tuberous sclerosis complex (TSC) may benefit from resective epilepsy surgery. Furthermore, associated neuropsychiatric disorders (TAND) are common in patients with TSC; however, long-term data on how surgery affects neuropsychiatric comorbidities are sparse. MATERIALS AND METHODS: Two retrospective approaches were used to identify children with TSC and DRE with onset at < 18 years of age. The study group (surgical) was identified through the Swedish National Epilepsy Surgery Registry (n = 17), a registry with complete national coverage since 1990 and prospective patient enrolment since 1995. The reference group (non-surgical) was identified by searching medical records retrieved from the tertiary hospital of Southern Sweden (n = 52). Eligible participants were invited to complete the validated TAND lifetime checklist. Those who did not complete the checklist, never had DRE, or were aged < 7 years old were excluded from the study. The reference group was balanced with the study group for putative confounders, in the following hierarchical order: DRE at the survey, age at seizure onset, age at follow-up, and sex. RESULTS: After the balancing procedure, both groups comprised 13 participants. The median time from epilepsy onset to the survey was 18.5 (range: 7.75-40.25) and 16.0 (7.33-33.5) years in the study and reference groups, respectively. The median time from surgery to the survey was 13 years (range: 4-22). No significant differences were found in behavioural problems, autism spectrum disorder diagnosis or symptoms, or intellectual disability between the groups, regardless of surgery. Seizure-free individuals (n = 11) performed better in social skills (p = 0.016), intellectual skills (p = 0.029), and overall TAND scores (p = 0.005) than the non-seizure-free group (n = 15). CONCLUSION: This is the first study to evaluate TAND comorbidities during the long-term follow-up after epilepsy surgery in patients with TSC. We found no evidence of the adverse effects of TAND comorbidities after tuberectomy. However, a larger study that allows for a better adjustment for confounders is needed. Following previous studies, seizure-free individuals had fewer symptoms within most TAND domains compared with the group with uncontrolled epilepsy, indicating less severe symptomatology.

Listening to anxiety in persons with epilepsy. Development of an integrative assessment model based on qualitative interviews.

OBJECTIVE: The differentiation and assessment of anxiety in persons with epilepsy is the subject of current research. There is no consensus on which forms of anxiety are epilepsy-specific, what pathological significance they have, and how they should be conceptually systematized. The aim of this study was to detect formal landmarks that organize and further distinguish the clinical multitude of epilepsy-related anxiety, thereby establishing a basis on which an integrative assessment of epilepsy-specific fears can be developed. METHOD: Twenty-six patients with epilepsy-related fears were recruited for qualitative interviews at the Epilepsy Center of Freiburg in Germany. Prevalent types of anxiety included both periictal and interictal anxiety. Patients reported how living with epilepsy is associated with anxiety and to what extent. After an open interview, semi-structured questions were asked concerning epilepsy-specific anxiety, referring to established concepts and items. The contents of the interviews relating to anxiety were transcribed. RESULTS: The reported fears associated with epilepsy reflect the individual "pathography" of each patient. The potentially anxiety-inducing events within this pathography include the first seizure(s), especially in cases involving the amygdalae; the process of diagnostic procedures; therapy, including side effects of antiseizure medication, surgery as a therapeutic option, or a difficult physician-patient relationship; and the further course of the disease, including the fear of disease progression with brain damage, cognitive deterioration, or professional and social disintegration. The integrative assessment model derived from the pathography of the interviewed patients thus reflects the dynamics and quality of epilepsy-specific fears, especially in relation to the healthcare system, without instantly pathologizing them. It highlights that anxiety, to a variable degree, is perceived as an adequate and comprehensible emotion and might be a problem long before the diagnosis is made in the case of ictal fear. Furthermore, anxiety symptoms may (re-)emerge, consolidate, modulate, diminish, or even aggravate during the course of the disease. The integrative assessment model maps crucial events inherent to the healthcare system that may become relevant as objects of prevention, intervention, and therapy. CONCLUSION: The integrative assessment model can serve as a heuristic framework from which an integrative self-report questionnaire of epilepsy-specific anxiety might be designed. On the one hand, this would help to better understand the interrelation between epilepsy and anxiety in terms of their temporal occurrence and interdependence scientifically. On the other hand, it would allow for the enhancement of individual preventive and therapeutic measures for affected patients.

Seizures as a Struggle between Life and Death: An Existential Approach to the Psychosocial Impact of Seizures in Candidates for Epilepsy Surgery.

INTRODUCTION: Mental health comorbidities such as depression and anxiety are common in epilepsy, especially among people with pharmacoresistant epilepsy who are candidates for epilepsy surgery. The Psychology Task Force of the International League Against Epilepsy advised that psychological interventions should be integrated into comprehensive epilepsy care. METHODS: To better understand the psychological impact of epilepsy and epileptic seizures in epilepsy surgery candidates, we analysed interviews with this subgroup of patients using Karl Jaspers' concept of limit situations, which are characterised by a confrontation with the limits and challenges of life. These are especially chance, randomness, and unpredictability, death and finitude of life, struggle and self-assertion, guilt, failure, and falling short of one's aspirations. RESULTS: In 43 interviews conducted with 15 people with drug-resistant epilepsy who were candidates for epilepsy surgery, we found that these themes are recurrent and have a large psychosocial impact, which can result in depression and anxiety. For some people, epileptic seizures appear to meet the criteria for traumatic events. CONCLUSION: Understanding epilepsy and seizures as existential challenges complements the neurobiological explanations for psychological comorbidities and can help tailor psychological interventions to the specific needs of people with epilepsy, especially those who are candidates for surgical treatment.

Nonepileptic attacks in patients with brain tumor-related epilepsy.

Epileptic seizures are well recognized as a presenting symptom in patients with brain tumors, however much less is known about coexisting nonepileptic attack disorder (NEAD) in this population. Establishing a diagnosis of NEAD can be challenging, especially in those with concomitant epilepsy. Nonepileptic attack disorder is associated with a high rate of morbidity, often due to coexisting psychological factors which may require the input of multiple services. In an era where early aggressive management of tumors is enabling patients to live longer, the associated psychological impact of adjusting to physical disease is increasingly apparent. In this case series, we present a narrative summary of 9 patients referred to neurology with brain tumor-related epilepsy (BTRE) over a five-year period (2015-2020) who also experienced NEAD. We describe their tumor characteristics, treatment course, and factors potentially contributing to their presentation. We conducted a case note review of patients presenting to the epilepsy service with BTRE, in whom NEAD was diagnosed based on clinical features and correlation with their EEG. Patients ranged in age from 26 to 63 years. Two patients were diagnosed with grade 1, three with grade 2 and four with grade 3 tumors. Tumors localized to frontal or temporal regions in seven cases. All patients presented initially with BTRE and developed nonepileptic seizures subsequently. Four patients developed NEAD within 1 month of their tumor diagnosis. One patient developed NEAD 79 months following diagnosis. The diagnosis of NEAD was established in 8 patients by direct visualization of attacks (two during concomitant EEG recording). In the remaining patient, diagnosis was based on history (patient and witness). Six patients were diagnosed with concomitant low mood and/ or anxiety and three were commenced on antidepressant medication. At the time of last review, the predominant attacks were nonepileptic in all but one patient.

Long-term outcomes of children with drug-resistant epilepsy across multiple cognitive domains.

AIM: To simultaneously evaluate long-term outcomes of children with drug-resistant epilepsy (DRE) across multiple cognitive domains and compare the characteristics of participants sharing a similar cognitive profile. METHOD: Participants were adolescents and young adults (AYAs) diagnosed with DRE in childhood, who completed a comprehensive neuropsychological battery evaluating intelligence, memory, academic, and language skills at the time of surgical candidacy evaluation and at long-term follow-up (4-11y later). Hierarchical k-means clustering identified subgroups of AYAs showing a unique pattern of cognitive functioning in the long-term. RESULTS: Participants (n=93; mean age 20y 1mo [standard deviation {SD} 4y 6mo]; 36% male) were followed for 7 years (SD 2y 4mo), of whom 65% had undergone resective epilepsy surgery. Two subgroups with unique patterns of cognitive functioning were identified, which could be broadly categorized as 'impaired cognition' (45% of the sample) and 'average cognition' (55% of the sample); the mean z-score across cognitive measures at follow-up was -1.86 (SD 0.62) and -0.23 (SD 0.54) respectively. Surgical and non-surgical patients were similar with respect to seizure control and their long-term cognitive profile. AYAs in the average cognition cluster were more likely to have better cognition at baseline, an older age at epilepsy onset, and better seizure control at follow-up. INTERPRETATION: The underlying abnormal neural substrate and seizure control were largely associated with long-term outcomes across cognitive domains.

Cognitive disorders in epilepsy I: Clinical experience, real-world evidence and recommendations.

This is the first of two narrative reviews on cognitive disorders in epilepsy (companion publication : Cognitive disorders in epilepsy II: Clinical targets, indications and selection of test instruments). Its focus is on clinical experience, real-world evidence, and clinical recommendations. Cognitive disorders are a common comorbidity in children and adults with epilepsy. These cognitive disturbances may preceed the onset of seizures and are multifactorial including contributions by pre-existing brain damage, seizures, interictal epileptic discharges, and treatments including medications and surgery. Comorbid cognitive impairments can have a negative impact on the quality of life in people with epilepsy. They are under-identified and frequently not treated. Comorbid psychiatric disorders, such as ADHD can also contribute to a worse cognitive performance and can benefit from pharmacotherapy with CNS stimulants. Likewise, mood disorders cause a subjective perception of poor memory and attention, which can be reversed with antidepressants of the SSRI family. This narrative review discusses these issues from a real-world clinical perspective in children and adults with newly diagnosed and chronic epilepsy. The need for further research to understand and treat these disorders is noted.

Efficacy and pharmacokinetics evaluation of 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as an anti-seizure agent.

Epilepsy is a common chronic neurological disease characterized by recurrent epileptic seizures. A seizure is an uncontrolled electrical activity in the brain that can cause different levels of behavior, emotion, and consciousness. One-third of patients fail to receive sufficient seizure control, even though more than fifty FDA-approved anti-seizure drugs (ASDs) are available. In this study, we attempted small molecule screening to identify potential therapeutic agents for the treatment of seizures using seizure-induced animal models. Through behavioral phenotype-based screening, 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) was identified as a prototype. GM-90432 treatment effectively decreased seizure-like behaviors in zebrafish and mice with chemically induced seizures. These results were consistent with decreased neuronal activity through immunohistochemistry for pERK in zebrafish larvae. Additionally, electroencephalogram (EEG) analysis revealed that GM-90432 decreases seizure-specific EEG events in adult zebrafish. Moreover, we revealed the preferential binding of GM-90432 to voltage-gated Na+ channels using a whole-cell patch clamp technique. Through pharmacokinetic analysis, GM-90432 effectively penetrated the blood-brain barrier and was distributed into the brain. Taken together, we suggest that GM-90432 has the potential to be developed into a new ASD candidate.

Behavioral problems and family distress in tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have a large impact on patients and their families. Improving intellectual ability outcomes using preventive vigabatrin (VGB) treatment has recently been reported. AIM: The aim of this study was to investigate the severity of behavioral problems and degree of distress among families of patients with TSC with and without a history of VGB treatment. METHOD: The study enrolled 21 children and adolescents who were patients with TSC from four hospitals: 14 in the VGB group and 7 in the no-VGB group. To evaluate patients' psychiatric and neurological symptoms, we used the TAND Checklist, Aberrant Behavior Checklist (ABC), Social Communication Questionnaire (SCQ), and Social Responsive Scale-2nd edition (SRS-2). RESULTS: All VGB-group patients were administered VGB after the onset of epileptic seizures. No obvious differences were observed between the VGB and no-VGB groups in behavioral problem scores on the TAND Checklist, or on the ABC, SCQ, and SRS-2 total scores. Behavioral problem scores were lower in patients with normal intelligence than in those with mild intellectual disability (ID; P = 0.042). Degrees of family distress assessed with the TAND Checklist were not correlated with the intelligence quotient/developmental quotient (IQ/DQ) or seizure frequency but were correlated with the total SRS-2 scores (P = 0.022). For several patients, there were large discrepancies between familial and physician ratings of the TAND impact score. CONCLUSION: Children and adolescents with TSC may present with significant behavioral difficulties and family distress, regardless of whether they were treated with VGB or not after the onset of seizures. Difficulties in social communication may have the strongest "TAND impact" on families.

Seizure and neuropsychological outcomes in a large series of selective amygdalohippocampectomies with a minimally invasive subtemporal approach.

OBJECTIVE: Debate continues over proper surgical treatment for mesial temporal lobe epilepsy (MTLE). Few large comprehensive studies exist that have examined outcomes for the subtemporal selective amygdalohippocampectomy (sSAH) approach. This study describes a minimally invasive technique for sSAH and examines seizure and neuropsychological outcomes in a large series of patients who underwent sSAH for MTLE. METHODS: Data for 152 patients (94 women, 61.8%; 58 men, 38.2%) who underwent sSAH performed by a single surgeon were retrospectively reviewed. The sSAH technique involves a small, minimally invasive opening and preserves the anterolateral temporal lobe and the temporal stem. RESULTS: All patients in the study had at least 1 year of follow-up (mean [SD] 4.52 [2.57] years), of whom 57.9% (88/152) had Engel class I seizure outcomes. Of the patients with at least 2 years of follow-up (mean [SD] 5.2 [2.36] years), 56.5% (70/124) had Engel class I seizure outcomes. Preoperative and postoperative neuropsychological test results indicated no significant change in intelligence, verbal comprehension, perceptual reasoning, attention and processing, cognitive flexibility, visuospatial memory, or mood. There was a significant change in word retrieval regardless of the side of surgery and a significant change in verbal memory in patients who underwent dominant-side resection (p < 0.05). Complication rates were low, with a 1.3% (2/152) permanent morbidity rate and 0.0% mortality rate. CONCLUSIONS: This study reports a large series of patients who have undergone sSAH, with a comprehensive presentation of a minimally invasive technique. The sSAH approach described in this study appears to be a safe, effective, minimally invasive technique for the treatment of MTLE.

'In the best case seizure-free' - Parental hopes and worries before and satisfaction after their child's epilepsy surgery.

OBJECTIVE: The objective of this study was to gain a better understanding of parental hopes and worries before and subsequent experiences two years after their child had undergone epilepsy surgery. METHODS: The parents of 107 children and young people who underwent epilepsy surgery at a single center completed surveys focusing on hopes and concerns before surgery and subsequent experiences at two-year follow-up. Responses were analyzed by thematic analysis. RESULTS: Before surgery, parental hopes focus on not only seizure freedom or reduction but also potential improvements in child development and emotional-behavioral functioning. Worries before surgery include not only potential injury or loss of skills but also a concern that the surgical procedure would not lead to an improvement in the child's seizures. The vast majority of parents experienced positive aspects at the two-year follow-up including seizure freedom or reduction but also perceived improvements in behavior, development, and sleep. This suggests that for many, expectations for the surgery were met. A small number of parents reported negative effects of surgery including loss of skills, worsening/lack of improvement in seizure frequency, or negative impact on development. SIGNIFICANCE: For the majority of parents whose children undergo surgery, expectations are met, and fears are not realized. Knowledge of parental hopes and worries before surgery as well as experiences after the operation is useful for improving pre- and postsurgical counseling.

The coexistence of psychogenic nonepileptic and epileptic seizures in the same patient is more frequent than expected: Is there any clinical feature for defining these patients?

OBJECTIVES: This study aimed to investigate the prevalence of psychogenic nonepileptic seizures (PNES) and PNES-epilepsy coexistence within all video-electroencephalography (EEG) monitoring unit (VEMU) referrals and to identify semiological and electrophysiological features to differentiate patients with PNES-epilepsy coexistence from PNES-only. METHODS: We retrospectively reviewed medical files, VEMU reports, and videos of 1983 adult patients. Demographical, historical, clinical, neuroimaging, and electrophysiological parameters of all patients were recorded. We classified patients into five groups as definite PNES-only, definite PNES-epilepsy coexistence, definite PNES-probable epilepsy coexistence, probable PNES-definite epilepsy coexistence, and probable PNES-only. We defined a "definite" group when we saw the ictal EEG and/or video recording of the seizure. The "probable" term is used when there is strong evidence from the history of a particular seizure type and suggestive interictal EEGs without video recordings. RESULTS: Two hundred and three of 1983 patients (10.23%) had PNES. Sixty-six of patients with PNES (32.51%) had definite PNES-epilepsy coexistence. When probable cases were included, the PNES-epilepsy coexistence ratio was 53.69% within all patients with PNES. The prevalence of PNES-epilepsy coexistence was 3.32% within all our VEMU referrals. Lower high school graduation rate, earlier age of disease onset, history of status epilepticus, febrile convulsion and brain surgery, use of three or more antiepileptic drugs, and abnormal magnetic resonance imaging (MRI) findings supported PNES-epilepsy coexistence (p < 0.05). On the contrary, seizure duration longer than 10 min was in favor of PNES-only (p < 0.05). CONCLUSIONS: The prevalence of PNES-epilepsy coexistence might be more frequent in VEMUs than expected. Some demographic and semiological features and electrophysiological findings might be useful in differentiating patients with PNES-epilepsy coexistence from patients with PNES-only.

The effect of left and right long-term amygdala kindling on interictal emotionality and Fos expression.

Clinical observations have often reported that patients with seizures arising from limbic structures on the right side of the brain have a higher incidence of emotional disturbances, such as fear and anxiety, than those who have seizures lateralized to limbic structures on the left side. However, there have been some inconsistent reports regarding the presence of these laterality effects. The use of animal models of epilepsy can help circumvent many of the methodological and ethical issues that arise from human clinical studies. In the present study, we examined the unique contribution of left- or right-sided long-term kindling of the amygdala on the development of interictal emotional disturbances. Following kindling to 99 electrical stimulations, male kindled and control rats were examined on a series of behavioral tests - open-field exploration, elevated plus maze, forced swim, and social interaction. Our results revealed that long-term amygdala kindling, irrespective of the hemisphere stimulated, increased general behavioral hyperactivity and fearful behavior. Interestingly, rats that were kindled from the left amygdala showed greater social avoidance and defensive behaviors during interactions with another kindled conspecific. To examine the brain structures that support long-term kindling, we also examined the expression of the immediate early gene product Fos 1 h after rats received their last electrical stimulation. Compared with control rats, kindled rats had increased Fos expression in several brain regions (e.g., piriform, frontal motor cortex, perirhinal cortex) involved in the generation and development of epilepsy. However, decreased Fos expression was also observed in several subregions of the hippocampus and amygdala that are known to be important fear behavior and memory. These findings suggest that both left and right amygdala kindling produce similar changes in emotional behavior and support the idea that the development of kindled fear may result from reduced activation of specific hippocampal and amygdaloid circuits.

TrkB hyperactivity contributes to brain dysconnectivity, epileptogenesis, and anxiety in zebrafish model of Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC) is a rare genetic disease that manifests with early symptoms, including cortical malformations, childhood epilepsy, and TSC-associated neuropsychiatric disorders (TANDs). Cortical malformations arise during embryonic development and have been linked to childhood epilepsy before, but the underlying mechanisms of this relationship remain insufficiently understood. Zebrafish have emerged as a convenient model to study elementary neurodevelopment; however, without in-depth functional analysis, the Tsc2-deficient zebrafish line cannot be used for studies of TANDs or new drug screening. In this study, we found that the lack of Tsc2 in zebrafish resulted in heterotopias and hyperactivation of the mTorC1 pathway in pallial regions, which are homologous to the mammalian cortex. We observed commissural thinning that was responsible for brain dysconnectivity, recapitulating TSC pathology in human patients. The lack of Tsc2 also delayed axonal development and caused aberrant tract fasciculation, corresponding to the abnormal expression of genes involved in axon navigation. The mutants underwent epileptogenesis that resulted in nonmotor seizures and exhibited increased anxiety-like behavior. We further mapped discrete parameters of locomotor activity to epilepsy-like and anxiety-like behaviors, which were rescued by reducing tyrosine receptor kinase B (TrkB) signaling. Moreover, in contrast to treatment with vigabatrin and rapamycin, TrkB inhibition rescued brain dysconnectivity and anxiety-like behavior. These data reveal that commissural thinning results in the aberrant regulation of anxiety, providing a mechanistic link between brain anatomy and human TANDs. Our findings also implicate TrkB signaling in the complex pathology of TSC and reveal a therapeutic target.

Sema7A, a brain immune regulator, regulates seizure activity in PTZ-kindled epileptic rats.

AIMS: Semaphorin7A (Sema7A) plays an important role in the immunoregulation of the brain. In our study, we aimed to investigate the expression patterns of Sema7A in epilepsy and further explore the roles of Sema7A in the regulation of seizure activity and the inflammatory response in PTZ-kindled epileptic rats. METHODS: First, we measured the Sema7A expression levels in patients with temporal lobe epilepsy (TLE) and in rats of a PTZ-kindled epilepsy rat model. Second, to explore the role of Sema7A in the regulation of seizure activity, we conducted epilepsy-related behavioral experiments after knockdown and overexpression of Sema7A in the rat hippocampal dentate gyrus (DG). Possible Sema7A-related brain immune regulators (eg, ERK phosphorylation, IL-6, and TNF-α) were also investigated. Additionally, the growth of mossy fibers was visualized by anterograde tracing using injections of biotinylated dextran amine (BDA) into the DG region. RESULTS: Sema7A expression was markedly upregulated in the brain tissues of TLE patients and rats of the epileptic model after PTZ kindling. After knockdown of Sema7A, seizure activity was suppressed based on the latency to the first epileptic seizure, number of seizures, and duration of seizures. Conversely, overexpression of Sema7A promoted seizures. Overexpression of Sema7A increased the expression levels of the inflammatory cytokines, IL-6 and TNF-α, ERK phosphorylation, and growth of mossy fibers in PTZ-kindled epileptic rats. CONCLUSION: Sema7A is upregulated in the epileptic brain and plays a potential role in the regulation of seizure activity in PTZ-kindled epileptic rats, which may be related to neuroinflammation. Sema7A promotes the inflammatory cytokines TNF-α and IL-6 as well as the growth of mossy fibers through the ERK pathway, suggesting that Sema7A may promote seizures by increasing neuroinflammation and activating pathological neural circuits. Sema7A plays a critical role in epilepsy and could be a potential therapeutic target for this neurological disorder.

Missed opportunities for epilepsy surgery referrals in Bhutan: A cohort study.

OBJECTIVE: To quantify the missed opportunities for epilepsy surgery referral and operationalize the Canadian Appropriateness of Epilepsy Surgery (CASES) tool for use in a lower income country without neurologists. METHODS: People with epilepsy were recruited from the Jigme Dorji Wangchuck National Referral Hospital from 2014-2016. Each participant was clinically evaluated, underwent at least one standard EEG, and was invited to undergo a free 1.5 T brain MRI. Clinical variables required for CASES were operationalized for use in lower-income populations and entered into the free, anonymous website tool. FINDINGS: There were 209 eligible participants (mean age 28.4 years, 56 % female, 179 with brain MRI data). Of the 179 participants with brain MRI, 43 (24.0 %) were appropriate for an epilepsy surgery referral, 21 (11.7 %) were uncertain, and 115 (64.3 %) were inappropriate for referral. Among the 43 appropriate referral cases, 36 (83.7 %) were "very high" and 7 (16.3 %) were "high" priorities for referral. For every unit increase in surgical appropriateness, quality of life (QoL) dropped by 2.3 points (p-value <0.001). Among the 68 patients who took >1 antiepileptic drug prior to enrollment, 42 (61.8 %) were appropriate referrals, 14 (20.6 %) were uncertain, and 12 (17.6 %) were inappropriate. CONCLUSION: Approximately a quarter of Bhutanese epilepsy patients who completed evaluation in this national referral-based hospital should have been evaluated for epilepsy surgery, sometimes urgently. Surgical services for epilepsy are an emerging priority for improving global epilepsy care and should be scaled up through international partnerships and clinician support algorithms like CASES to avoid missed opportunities.

Hemispherectomy in adults and adolescents: Seizure and functional outcomes in 47 patients.

OBJECTIVE: To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents. METHODS: We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed. RESULTS: Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes. SIGNIFICANCE: Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

Determinants of quality of life in patients with drug-resistant focal epilepsy.

INTRODUCTION: Focal drug-resistant epilepsy (DRE) has been associated with a significant burden of psychiatric comorbidity and low health-related quality of life (HRQoL). There is ample disagreement in previous studies as to which factors decisively influence HRQoL in this population. Here, we sought to assess the relationship between sociodemographic factors, epilepsy-related variables, and psychiatric comorbidity with HRQoL in a well-defined group of patients with focal DRE. METHODS: We consecutively recruited a sample of adult patients with confirmed focal DRE being considered for epilepsy surgery in a reference center in Lisbon, Portugal. Psychiatric diagnoses were defined according to the Mini-International Neuropsychiatric Interview (M.I.N.I.), and HRQoL was measured using the Quality-of-Life in Epilepsy Inventory (QOLIE-31). Associations with QOLIE-31 total score were tested using regression models. RESULTS: Among the forty patients included in the study, being diagnosed with a mood disorder was significantly associated with a lower total QOLIE-31 score (ß = -21.18, p = 0.001) in univariate analysis. Multivariate analysis additionally identified female gender as a second determinant of lower HRQoL (ß = -21.22, p = 0.001 for being diagnosed with a mood disorder; ß = -8.98, p = 0.048 for female gender; adjusted R2 = 0.290). Sociodemographic and epilepsy-related variables were not associated with HRQoL. CONCLUSIONS: In our sample of adult patients with focal DRE, female gender and being diagnosed with a mood disorder were the only factors significantly associated with a poorer HRQoL. While clinical care often focuses on seizure control, epilepsy-related factors such as seizure frequency were not shown to have a significant influence on HRQoL. We suggest that an early comprehensive psychiatric evaluation and intervention can help improve HRQoL in these patients.

Development of a patient-reported outcome measure for psychotherapeutic interventions in people with seizures: A mixed methods study.

BACKGROUND: Generic or even disease-specific quality of life measures are unlikely to be equally responsive to different epilepsy treatment modalities, such as pharmacotherapy, surgery, or psychotherapy. The purpose of the present study was to summarize the development of a patient-reported outcome measure (PROM) designed to be particularly sensitive to change mediated by psychotherapeutic interventions in people with seizures. METHODS: The development of this instrument involved seven steps: (1) Development of a candidate item set based on the outcome of previous qualitative research, (2) initial quantitative-descriptive study yielding an assessment of content validity by clinical experts, (3) qualitative-descriptive posttherapy cognitive debriefing interviews with patients with epileptic and/or nonepileptic seizures (NES), (4) English translation, (5) elicitation of qualitative feedback from international experts, (6) assessment of internal consistency and correlation with similar previously validated generic and epilepsy-specific measures in a pilot study, and (7) final expert content validity rating. RESULTS: (1) The candidate item set comprised 29 stem items; five of which were followed by a follow-up (FU) item that refers to the statement of the stem item. (2) Eight clinical experts assessed content validity. Informed by rating and experts' qualitative comments, 15 items remained unchanged, eleven underwent substantial revisions, three were excluded, and six added. (3) Cognitive debriefing interviews were conducted with 14 patients with epilepsy and/or NES. Based on the interviewees' feedback, 29 of 32 items remained unchanged, two were excluded, one reworded, and four added. (4) The forwards-backwards English translation prompted substantial revision of two items because the verbatim back translation of the corresponding English items was conceptually more convincing than the original German wording. (5) The international experts identified problems with item comprehensibility/clarity of four stem and three FU items that were subsequently reworded. Ten items were added to incorporate their qualitative feedback resulting in a total of 44 items. (6) Thirty-one patients with epilepsy participated in the pilot study. The overall internal consistency of the self-Efficacy, Assertiveness, Social support, self-awareness, and hElpful thinking in people with seizures (EASE) was very good (α = 0.92). Analysis at item-level revealed problems with inverted and self-evident items. Based on this analysis, three items were eliminated and two items were revised (one FU item was turned into a stem item) resulting in a total of 42 items. (7) The second content validity rating showed final item-content validity indices (I-CVIs) between 0.38 and 1 and an excellent mean CVI of 0.92 at scale level (S-CVI/ave). Fourteen stem items were substantially revised by incorporating the experts' qualitative feedback, three items with low I-CVIs were excluded, and one item was added. The final questionnaire consisted of 40 stem items; eight of which include at least one FU item. CONCLUSION: Based on these results, the EASE is valid in terms of content, internally consistent, clear, and acceptable to patients with seizures. The measure has now been developed to the stage at which the validity and reliability as well as the psychometric properties and factorial structure of the new instrument can be assessed in larger patient groups in a prospective clinical study.

Management of prolonged epileptic seizures and status epilepticus in palliative care patients.

Prolonged seizures and status epilepticus (SE) are relevant problems in palliative care. Timely recognition and effective early treatment with first- and second-line antiepileptic drugs (AEDs) may prevent unnecessary hospitalizations. Seizures should be recognized and addressed like any other symptom that causes discomfort or reduces quality of life. Use of alternative AED administration routes (buccal, intranasal, or subcutaneous) may offer possibilities for effective and individualized AED therapy, even during the last days of life. In hospice or home care, however, also intravenous treatment is possible via vascular access devices for long-term use. Aggressive unlimited intensive care unit (ICU) treatment of refractory SE in palliative patients is mostly not indicated. At worst, intensive care can be futile and possibly harmful: death in the ICU is often preceded by long and aggressive treatments. Metastatic cancer, old age, high severity of acute illness, overall frailty, poor functional status before hospital admission, and the presence of severe comorbidities all increase the probability of poor outcome of intensive care. When several of these factors are present, consideration of withholding intensive care may be in the patient's best interests. Anticipated outcomes influence patients' preferences. A majority of patients with a limited life expectancy because of an incurable disease would not want aggressive treatment, if the anticipated outcome was survival but with severe functional impairment. Doctors' perceptions about their patients' wishes are often incorrect, and therefore, advance care planning including seizure management should be done early in the course of the disease. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".