Psychogenic nonepileptic seizure: An empathetic, practical approach.

Psychogenic nonepileptic seizure (PNES) is often misdiagnosed as epilepsy, leading to unnecessary treatments and procedures, as well as failure to engage patients in needed mental health care. To establish an accurate diagnosis, video electroencephalography (EEG) in the context of and simultaneous with a comprehensive neurologic and psychosocial evaluation is recommended for any patient with seizures that are not responding to treatment. Delivering the diagnosis with empathy and respect is a crucial component of care that helps patients establish trust with caregivers and follow treatment recommendations. Effective treatment is available, highlighting the importance of early diagnosis to avoid unnecessary and potentially harmful treatment. But there are many barriers to care, including provider misperceptions, lack of acceptance of the diagnosis, poor patient engagement with treatment, and lack of access to care.

Telepsychology May Improve Treatment Adherence in Patients with Psychogenic Nonepileptic Seizures.

Introduction: Access to mental health care is a significant challenge in patients with psychogenic nonepileptic seizures (PNES). Telepsychology can curb the access barriers and improve adherence but the role of telepsychology in improving adherence has not been well investigated. The current study examines the utility of telepsychology during the COVID-19 pandemic and treatment adherence in PNES patients. Materials and Methods: Patients with PNES admitted to a 12-week counseling program were offered two visit types: telepsychology and in-office. Visit type, visit status, and demographic information were obtained from department database. Follow-up visits in 6 months were used to examine the effect of visit type on visit status. Adherence to treatment was measured by higher attendance of scheduled visits and less cancellation and no-show rates. Results: Two hundred fifty-seven (n) patients who scheduled virtual or telepsychology visits were included in the study. After adjusting for demographic variables, and accounting for repeated measures, telepsychology visits were significantly more likely to be attended (odds ratio [OR] = 2.40, 95% confidence interval [CI] = 1.69-3.41, p < 0.001) and were significantly less likely to be canceled (OR = 0.43, 95% CI = 0.29-0.64, p < 0.001). The regression model showed patients in the telepsychology visit group attended more than three times as many visits as in-office patients (incidence rate ratios = 3.16, 95% CI = 2.13-4.73, p < 0.001). Conclusions: Patients with PNES have logistical and psychological barriers that can impede their ability to attend counseling treatment. Receiving care remotely may have been associated with higher engagement with mental health treatment compared to having to travel to counseling clinics. Considering the symptom-related restrictions patients with PNES have and the barriers presented by the COVID-19 pandemic, telepsychology played a key role for continuation of mental health treatment.

Neurological disorder-associated genetic variants in individuals with psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are diagnosed in approximately 30% of patients referred to tertiary care epilepsy centers. Little is known about the molecular pathology of PNES, much less about possible underlying genetic factors. We generated whole-exome sequencing and whole-genome genotyping data to identify rare, pathogenic (P) or likely pathogenic (LP) variants in 102 individuals with PNES and 448 individuals with focal (FE) or generalized (GE) epilepsy. Variants were classified for all individuals based on the ACMG-AMP 2015 guidelines. For research purposes only, we considered genes associated with neurological or psychiatric disorders as candidate genes for PNES. We observe in this first genetic investigation of PNES that six (5.88%) individuals with PNES without coexistent epilepsy carry P/LP variants (deletions at 10q11.22-q11.23, 10q23.1-q23.2, distal 16p11.2, and 17p13.3, and nonsynonymous variants in NSD1 and GABRA5). Notably, the burden of P/LP variants among the individuals with PNES was similar and not significantly different to the burden observed in the individuals with FE (3.05%) or GE (1.82%) (PNES vs. FE vs. GE (3 × 2 χ2), P = 0.30; PNES vs. epilepsy (2 × 2 χ2), P = 0.14). The presence of variants in genes associated with monogenic forms of neurological and psychiatric disorders in individuals with PNES shows that genetic factors are likely to play a role in PNES or its comorbidities in a subset of individuals. Future large-scale genetic research studies are needed to further corroborate these interesting findings in PNES.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy (GE) with second- and third-generation antiepileptic drugs (AEDs). Methods: The 2004 AAN criteria was used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. Recommendations: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years with new-onset focal epilepsy. Unless there are compelling adverse-effect-related concerns, ethosuximide (ETS) or valproic acid (VPA) should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (Level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To update the 2004 American Academy of Neurology (AAN) guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). Methods: 2004 criteria were used to systematically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. Results: Forty-two articles were included. Recommendations: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment; rufinamide for Lennox-Gastuat syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month to 16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6-17 years); oxcarbazepine for TRCFE (1 month to 4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent FDA strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

Patient experience with patient-reported outcome measures in neurologic practice.

OBJECTIVE: To quantify the neurologic patient experience with patient-reported outcome measures (PROMs) and identify factors associated with a positive PROMs experience. METHODS: This retrospective study included all patients seen in 6 neurologic clinics who completed patient experience questions at least once between October 2015 and September 2016. Questions assessed overall satisfaction with PROMs, as well as 4 facets of the PROM experience: usefulness of questions, ease of understanding, effect on communication with provider, and effect on control of their own care. Clinic and patient characteristics were summarized across questions and predictors of response were identified using multivariable proportional odds models. RESULTS: A total of 16,157 patients answered generic and condition-specific PROMs, as well as questions on their experience with completing PROMs. The majority of patients agreed/strongly agreed questions were easy to understand (96%), useful (83%), and improved communication (78%) and control (71%). After adjustment for other factors, being younger, black, or depressed, or having lower household income, were independent predictors of high satisfaction with PROMs. Patients who indicated the system improved communication and control of care were more often male, black, and lower income. Variability in responses was shown by clinic. CONCLUSION: Given the growing importance of patient satisfaction in health care, the patient experience with PROMs is a critical component of their successful implementation and utilization. Findings from this study support the feasibility of collecting PROMs in neurologic practice and the potential as a tool to optimize patient-centered neurologic care.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To update the 2004 American Academy of Neurology (AAN) guideline for treating new-onset focal or generalized epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS: The 2004 AAN criteria were used to systematically review literature (January 2003-November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS: Several second-generation AEDs are effective for new-onset focal epilepsy. Data are lacking on efficacy in new-onset generalized tonic-clonic seizures, juvenile myoclonic epilepsy, or juvenile absence epilepsy, and on efficacy of third-generation AEDs in new-onset epilepsy. RECOMMENDATIONS: Lamotrigine (LTG) should (Level B) and levetiracetam (LEV) and zonisamide (ZNS) may (Level C) be considered in decreasing seizure frequency in adults with new-onset focal epilepsy. LTG should (Level B) and gabapentin (GBP) may (Level C) be considered in decreasing seizure frequency in patients ≥60 years of age with new-onset focal epilepsy. Unless there are compelling adverse effect-related concerns, ethosuximide or valproic acid should be considered before LTG to decrease seizure frequency in treating absence seizures in childhood absence epilepsy (level B). No high-quality studies suggest clobazam, eslicarbazepine, ezogabine, felbamate, GBP, lacosamide, LEV, LTG, oxcarbazepine, perampanel, pregabalin, rufinamide, tiagabine, topiramate, vigabatrin, or ZNS is effective in treating new-onset epilepsy because no high-quality studies exist in adults of various ages. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years old and perampanel as monotherapy received FDA approval.

Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs). METHODS: 2004 criteria were used to systemically review literature (January 2003 to November 2015), classify pertinent studies according to the therapeutic rating scheme, and link recommendations to evidence strength. RESULTS: Forty-two articles were included. RECOMMENDATIONS: The following are established as effective to reduce seizure frequency (Level A): immediate-release pregabalin and perampanel for TR adult focal epilepsy (TRAFE); vigabatrin for TRAFE (not first-line treatment); rufinamide for Lennox-Gastaut syndrome (LGS) (add-on therapy). The following should be considered to decrease seizure frequency (Level B): lacosamide, eslicarbazepine, and extended-release topiramate for TRAFE (ezogabine production discontinued); immediate- and extended-release lamotrigine for generalized epilepsy with TR generalized tonic-clonic (GTC) seizures in adults; levetiracetam (add-on therapy) for TR childhood focal epilepsy (TRCFE) (1 month-16 years), TR GTC seizures, and TR juvenile myoclonic epilepsy; clobazam for LGS (add-on therapy); zonisamide for TRCFE (6-17 years); oxcarbazepine for TRCFE (1 month-4 years). The text presents Level C recommendations. AED selection depends on seizure/syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. This evidence-based assessment informs AED prescription guidelines for TR epilepsy and indicates seizure types and syndromes needing more evidence. A recent Food and Drug Administration (FDA) strategy allows extrapolation of efficacy across populations; therefore, for focal epilepsy, eslicarbazepine and lacosamide (oral only for pediatric use) as add-on or monotherapy in persons ≥4 years of age and perampanel as monotherapy received FDA approval.

Evaluating subjective cognitive impairment in the adult epilepsy clinic: Effects of depression, number of antiepileptic medications, and seizure frequency.

OBJECTIVE: Subjective cognitive complaints are a frequent concern of patients with epilepsy. The Aldenkamp-Baker Neuropsychological Assessment Schedule (ABNAS) is a patient-reported scale validated to measure adverse cognitive effects of antiepileptic drugs (AEDs). The goals of this study were to identify predictors of patient-reported cognitive dysfunction and to assess the relationship between subjective and objective cognitive impairment. METHODS: The Cleveland Clinic Knowledge Program Data Registry was used to identify adult patients seen in outpatient epilepsy clinic from January to May 2015 and who completed the following scales: ABNAS for subjective cognitive impairment, Patient Health Questionnaire (PHQ-9) for depression, Generalized Anxiety Disorder 7-item (GAD-7) scale, Quality of Life in Epilepsy (QOLIE-10), and EuroQOL five dimensions questionnaire (EQ-5D) for health-related quality of life. Topiramate (TPM) was considered a high-risk medication for cognitive impairment. Patients were categorized into groups based on total ABNAS score: subjective cognitive impairment (ABNAS>15; N=270) and no subjective cognitive impairment (ABNAS≤15; N=400). Multivariable logistic regression models were constructed to identify independent predictors of subjective cognitive impairment. In a subset of patients who had neuropsychological testing within 6months of completing the ABNAS (N=60), Pearson correlations and multivariable logistic regression models, controlling for number of AEDs, depression, and anxiety, assessed the relationship between subjective cognitive impairment and objective cognitive performance on measures of intelligence, attention/working memory, verbal fluency, naming, processing speed, manual dexterity, visuomotor processing, and verbal memory. RESULTS: Forty percent of patients in the overall sample (N=270/670) reported cognitive impairment. The variables most strongly associated with subjective cognitive impairment were PHQ-9 score, number of AEDs, and seizure frequency. In the subset of patients with neuropsychological testing, ABNAS score was correlated with anxiety (r=0.44), depression (r=0.38), and attention/working memory (r=-0.31). After adjusting for depression and anxiety, patients who endorsed subjective cognitive impairment scored significantly lower on measures of nonverbal intelligence and attention/working memory, but not on other cognitive measures. CONCLUSIONS: Subjective cognitive impairment as reported on the ABNAS is most strongly associated with depressive symptomatology, number of AEDs, and seizure frequency, but not with most objective cognitive measures. Identifying these three predictors provides a clear framework to understand and address subjective cognitive complaints in adult patients with epilepsy.

Bridging a clinical gap in psychogenic nonepileptic seizures: Mental health provider preferences of biopsychosocial assessment approaches.

Management of psychogenic nonepileptic seizures (PNES) is complex, requiring multidisciplinary care. A standardized assessment and formulation approach to PNES is lacking, yet use of a comprehensive model may alleviate problems such as mental health aftercare noncompliance. Although a biopsychosocial (BPS) approach to PNES balancing predisposing, precipitating, and perpetuating (PPP) variables has been described and has been recently tested in pilot form, it is unclear how this assessment style is perceived among community mental health practitioners such as psychotherapists (including psychologists, counselors, and social workers). We predicted preference of a comprehensive "BPS/PPP" assessment style by those most involved in PNES care (i.e., community psychotherapists). One hundred and forty-three community-based social workers and counselors completed a survey featuring a fictional PNES case followed by assessment style options ("Multiaxial," "Narrative," and "BPS/PPP"). Respondents clearly preferred the robust BPS/PPP approach over less-comprehensive multiaxial and narrative assessments (p<0.0001). Reasons for choosing the BPS/PPP by respondents include ease of organization, clear therapeutic goals, and comprehensive nature. This assessment of acceptability of a BPS/PPP approach to PNES assessment among community mental health practitioners may provide a patient-centered mechanism to enhance referrals from the neurological to mental health setting. Implications and future directions are explored.

Diagnostic assessment and case formulation in psychogenic nonepileptic seizures: A pilot comparison of approaches.

Management of psychogenic nonepileptic seizures (PNES) is complex, requiring multidisciplinary care. A standardized assessment approach to PNES is lacking, yet use of a comprehensive model may alleviate problems such as mental health aftercare noncompliance. Although a biopsychosocial (BPS) approach to PNES balancing predisposing, precipitating, and perpetuating (PPP) variables has been described, it is unclear how this formulation style is perceived amongst clinicians. We predicted preference of a comprehensive, "BPS/PPP" assessment style by those most involved in PNES diagnosis and care (i.e., neurologists and psychologists). Sixty epileptologists, psychiatrists, and psychologists completed a survey featuring a fictional PNES case followed by assessment style options ("Multiaxial," "Narrative," and "BPS/PPP"). Epileptologists and psychologists ("nonpsychiatrists") differed from psychiatrists in PNES case formulation choice, with nonpsychiatrists preferring the robust BPS/PPP approach and with psychiatrists opting for less comprehensive Multiaxial and Narrative assessments (p=0.0009). Reasons for choosing the BPS/PPP by nonpsychiatrists included ease of organization, clear therapeutic goals, and comprehensive nature. Alternatively, psychiatrists cited time constraints and familiarity as reasons to prefer briefer Multiaxial or Narrative approaches. This pilot assessment of acceptability of a BPS/PPP approach to PNES case formulation, thus, reveals important gaps in formulation priorities between neurologists and psychiatrists. Implications and future directions are explored.

De novo mutations in epileptic encephalopathies.

Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.

Addressing genetic heterogeneity in complex disease: finding seizure genes in systemic lupus erythematosus.

Complex genetic disease is inherently difficult to study due to an imperfect relationship between genotype and phenotype. One important reason for this imperfect relationship is genetic heterogeneity, the occurrence of different genetic factors underlying the same clinical syndrome. One method of addressing genetic heterogeneity is covariate-based linkage analysis, which allows the use of additional phenotypic features to define genetically distinct subsets of patients. Systemic lupus erythematosus (SLE) is one example of a complex genetic disease affecting multiple organ systems including the central nervous system. We report here the use of covariate-based linkage analysis to detect a potential genetic locus on chromosome 15 influencing the development of seizures in individuals with SLE. The use of covariates increases the power to detect linkage in the presence of genetic heterogeneity.

Mechanism of increased open probability by a mutation of the BK channel.

A missense mutation (D434G) has recently been identified in the alpha subunit of the human large-conductance calcium-activated potassium (BK) channel. Interestingly, although the mutation causes an increase in open probability, individuals that carry the mutation have epilepsy and/or paroxysmal dyskinesia, disorders of increased brain excitability. To define the mechanisms of the mutation, we have used recordings from single channels and measurement of macroscopic conductances to examine the gating of the alpha subunit, modulation by the regulatory beta4 subunit, and the effect of Mg2+ on channel properties. Although there was relatively little difference in open dwell times for the mutant and wild-type alpha subunits, the mutant channel spent less time in a long-lived closed state. Co-expression of the beta4 subunit caused the wild-type channel to be less sensitive to calcium at low Ca2+ concentrations but had little effect on the mutant channel, further accentuating the difference between the wild-type and the mutant channels. In the absence of Ca2+, there was no difference in Mg2+ or voltage sensitivity of the mutant and wild-type channels, whereas in 2 mM Ca2+, the mutant channel had greater open probability at every Mg2+ concentration tested. We conclude that the D434G mutation modifies Ca2+ -dependent activation, but we find no evidence of a direct effect on activation by Mg2+ or voltage. The resulting enhancement of BK channel function leads to an increase in brain excitability, possibly due to more rapid repolarization of action potentials.

Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.

The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the alpha subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca(2+) sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease.

Linkage analysis of alcoholism-related electrophysiological phenotypes: genome scans with microsatellites compared to single-nucleotide polymorphisms.

P300 amplitude is an electrophysiological quantitative trait that is correlated with both alcoholism and smoking status. Using the Collaborative Study on the Genetics of Alcoholism data, we performed model-free linkage analysis to investigate the relationship between alcoholism, P300 amplitude, and habitual smoking. We also analyzed the effect of parent-of-origin on alcoholism, and utilized both microsatellites (MS) markers and single-nucleotide polymorphisms (SNPs). We found significant evidence of linkage for alcoholism to chromosome 10; inclusion of P300 amplitude as a covariate provided additional evidence of linkage to chromosome 12. This same region on chromosome 12 showed some evidence for a parent-of-origin effect. We found evidence of linkage for the P300 phenotype to chromosome 7 in non-smokers, and to chromosome 17 in alcoholics. The effects of alcoholism and habitual smoking on P300 amplitude appear to have separate genetic determinants. Overall, there were few differences between MS and SNP genome scans. The use of covariates and parent-of-origin effects allowed detection of linkage not seen otherwise.

Focal cortical dysplasia and intractable epilepsy in adults: clinical, EEG, imaging, and surgical features.

PURPOSE: The clinical features of focal cortical dysplasia (FCD) in adults are poorly understood. The purpose of this report is to describe the clinical, electrographic, and neuroimaging characteristics of adults with FCD undergoing surgical resection for intractable epilepsy. METHODS: Case series of 55 patients, aged 17-57 years, with a histopathological diagnosis of FCD. Medical history, neurological examination, non-invasive video-EEG, neuroimaging, and surgical outcome data were analyzed retrospectively. RESULTS: There were 36 patients with temporal, 19 with extra-temporal lobe resections. Mean age at surgery was 29 years. Mean age at epilepsy onset was 10 years. Dual pathology was seen in 56% of patients, with 68% of these having hippocampal sclerosis (HS). Epilepsy risk factors included febrile seizures (16%), head trauma (16%), CNS infections (11%), and perinatal stroke (4%). Interictal EEG showed regional epileptiform activity in 89% of patients. Only 24% were diagnosed with FCD pre-operatively. Of those with dual pathology, only 6% were suspected of having FCD pre-operatively. Of those patients with >12 months follow-up, surgical outcomes were as follows: 65% seizure-free, 19% significant improvement, 16% without significant improvement. CONCLUSIONS: In this series of adult patients with intractable epilepsy and FCD, a significant number have other seizure risk factors, normal neurological examinations and neuroimaging, and regional EEG findings. Dual pathology was common in patients with FCD. FCD should be considered as an etiology of epilepsy even in patients whose evaluation suggests other mechanisms.