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Objectives To describe the characteristics of epilepsy in patients with Neurofibromatosis type 1 (NF1). Methods Analysis of a cohort of consecutive NF1 patients seen in our NF1 clinic during a three-year period. Results Of the 184 NF1 patients seen during that period, 26 had epilepsy and three had febrile seizures. Of the 26, 17 (65%) had localization-related epilepsy, seven of whom (41%) were drug resistant. Six (23%) had apparently primary generalized epilepsy (0/6 drug resistant), two (8%) Lennox-Gastaut syndrome, and one (4%) West syndrome (all three were drug-resistant). As compared to the patients with no epilepsy, those with epilepsy were more likely to have MRI findings of mesial temporal sclerosis (MTS) (23% vs. 5%, p = 0.0064), and cerebral hemisphere tumors (31% vs. 10%, p = 0.0079), but not of the other MRI findings including neurofibromatosis bright objects, or optic gliomas. Three of the six patients with MTS underwent temporal lobectomy with subsequent control of their seizures with confirmation of MTS on pathology in 3/3 and presence of coexisting focal cortical dysplasia (FCD) in 2/3. We also have observed three additional patients outside the above study with the association of NF1, MTS, and intractable epilepsy. Significance Epilepsy is relatively common in NF1, often occurs in patients with brain tumors or with MTS which can coexist with FCD, can be associated with multiple types of epilepsy syndromes, and when localization-related is often drug-resistant. Patients with NF1 and MTS can respond to medial temporal lobectomy and may have coexisting medial temporal lobe cortical dysplasia.

Summary Background The Epilepsy Genetics (EPIGEN) Consortium was established to undertake genetic mapping analyses with augmented statistical power to detect variants that influence the development and treatment of common forms of epilepsy. Methods We examined common variations across 279 prime candidate genes in 2717 case and 1118 control samples collected at four independent research centres (in the UK, Ireland, Finland, and Australia). Single nucleotide polymorphism (SNP) and combined set-association analyses were used to examine the contribution of genetic variation in the candidate genes to various forms of epilepsy. Findings We did not identify clear, indisputable common genetic risk factors that contribute to selected epilepsy subphenotypes across multiple populations. Nor did we identify risk factors for the general all-epilepsy phenotype. However, set-association analysis on the most significant p values, assessed under permutation, suggested the contribution of numerous SNPs to disease predisposition in an apparent population-specific manner. Variations in the genes KCNAB1, GABRR2, KCNMB4, SYN2 , and ALDH5A1 were most notable. Interpretation The underlying genetic component to sporadic epilepsy is clearly complex. Results suggest that many SNPs contribute to disease predisposition in an apparently population-specific manner. However, subtle differences in phenotyping across cohorts, combined with a poor understanding of how the underlying genetic component to epilepsy aligns with current phenotypic classifications, might also account for apparent population-specific genetic risk factors. Variations across five genes warrant further study in independent cohorts to clarify the tentative association.

To establish the number of monitoring days needed to distinguish psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES) in adult patients admitted for video/EEG monitoring (VEM), we performed a retrospective chart review on 199 consecutive admissions for behavioral event diagnosis with VEM. Of the 199 adult patients admitted for VEM, 83.9% (n = 167) had a clinical event during admission, and a definitive diagnosis was made in 75.9% (n = 151). Of patients who had clinical events, 87.7% (n = 143) had their first event on admission day 1 or 2. Factors associated with ES (vs PNES) included an abnormal baseline EEG (P < 0.001), an abnormal brain MRI (P = 0.01), and history of events lasting less than 1minute (P = 0.01). There was no association between time to first event and discharge diagnosis. VEM differentiated between ES and PNES in the majority of adult patients evaluated. Most behavioral events were characterized within 2 days of admission.

Juvenile myoclonic epilepsy (JME) is often exquisitely responsive to treatment with valproic acid (VPA). However, a subset of patients does not respond to this medication and often has intractable seizures. We wanted to identify differences between these two subsets of JME patients . Charts of all JME patients followed at the Duke Epilepsy Center were reviewed. Clinical parameters, electroencephalogram (EEG) findings and magnetic resonance imaging (MRI) data were reviewed. These features were compared between patients with VPA sensitive and VPA resistant JME. Thirty-three patients with JME were identified: 23 (70%) were VPA sensitive (13 females, 10 males; mean age of onset 15.9 years) and 10 (30%) were VPA resistant (5 females, 5 males; mean age of onset 14.1 years). The VPA resistant group had a higher frequency of EEG asymmetries (40% vs. 10%); atypical seizure characteristics including auras and post-ictal confusion (30% vs. 4%); and intellectual deficiency (20% vs. 0%). Clinical characteristics combined with EEG data may help in predicting which JME patients will respond favorably to VPA. This study also raises the issue whether VPA resistant JME is in fact a localization-related epilepsy.

Much has been written about sexual dysfunction in men with epilepsy. We wanted to determine the frequency and nature of sexual disorders in our highly selected population of male veterans. Charts of the 184 men with epilepsy followed in the Neurodiagnostic Clinic, Veterans Affairs Medical Center, Durham, NC were reviewed to determine reports of sexual dysfunction. Demographics, type of epilepsy, localization, and antiepileptic drugs (AEDs) at the time of complaints were noted. These patients were compared to 20 men with epilepsy without reported sexual dysfunction (control group). Forty-one (22%) patients complained of sexual dysfunction (impotence 56%, decreased libido 37%, difficulty maintaining erection 22%, and other disorders 15%). Mean age at evaluation was 48.3 years for patients and 44.8 years for controls. Mean age of onset of seizures was 34.0 and 29.3 years for patients and controls, respectively. 93% of patients and 95% of controls had partial seizures. The AEDs (phenytoin, carbamazepine, valproate, phenobarbital, and primadone) were used with approximately equal frequency in both groups. Fifty-nine percent of patients and 65% of controls were on monotherapy, 34% and 25% on dual therapy, 5% each on triple therapy, and 2% and 5% on no medication. Sexual dysfunction is a common problem in our population of veteran men with epilepsy. Age of onset and type of seizures and the medications used were comparable in patients and controls.

We report clinical and EEG features of 65 probands with juvenile myoclonic epilepsy (JME) and the occurrence and character of epilepsy among 664 blood relatives of 26 of the 65 probands with a positive family history of seizures. Forty-six families from India and 19 families from the United States were investigated. Among the probands, sex distribution was equal; the mean age at onset of generalized tonic-clonic seizures (GTCS) and myoclonic jerks was 14.2 and 14.3 years, respectively; myoclonic jerks alone occurred in 2 (3%); 5 (8%) had absence seizures; and bilaterally symmetrical polyspike and wave complexes were evident during interictal EEG in 50 (77%). Twenty-six probands (40%) had blood relatives with seizures. Clinical and EEG features were similar in Indian and American probands and in probands with and without a family history of seizures. Sixty-two blood relatives had seizures: 38 (61%) had idiopathic generalized epilepsy (IGE), including 11 (18%) with JME; 9 (15%) had single, spontaneous generalized seizures before age 30 years; and the remainder had febrile convulsions (4, 6%) or symptomatic, partial or unclassified epilepsy (11, 18%). Both the proportion of family members observed to have epilepsy and the epilepsy syndrome expressed in family members varied as a function of the degree of relation. First-degree relatives had greater occurrence of epilepsy, IGE, and JME than did more distant blood relatives. These data suggest that JME is a complex genetic disorder and support a multigenic pattern of inheritance.

We performed temporal lobectomy in 23 young patients with intractable complex partial seizures (CPS) at an average age of 14.5 years. At a mean follow-up interval of 4.8 years, we reevaluated the patients to assess the surgical outcome; 74% were seizure-free. Cognitive testing showed slight improvement in Full-scale I.Q. scores and in some subtest scores. Wechsler Memory Scales had not changed significantly from the preoperative scores. Both pre- and postoperative Minnesota Multiphasic Personality Inventories 168 (MMPIs) were obtained in nine patients; and only postoperative MMPIs were obtained in 18. Pre- and postoperative social function, reported by the patients in a structured interview with a clinical psychologist (H.S.S.), was scored by a rating scale. All patients reported postoperative improvement in social function, although of variable degree. Patients were divided into a well-adjusted and a poorly adjusted group based on their postoperative social function. As compared with the well-adjusted group, the poorly adjusted group reported more preoperative social problems, had lower preoperative and postoperative I.Q. scores, had poorer postoperative seizure control, and had higher postoperative MMPI scores.

Sixty consecutive patients admitted for possible surgical treatment of intractable epilepsy underwent 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) as part of a standardized presurgical protocol. Patients were classified as having temporal lobe or extratemporal epilepsy based on all available information excluding PET. Of 35 patients categorized as having temporal lobe epilepsy, 27 (77%) had unilateral temporal lobe hypometabolism that always correlated with electrophysiologic localization of the seizure focus. In 19 patients categorized as having extratemporal epilepsy, only six (32%) had an abnormal PET study and in only one patient did PET assist in subsequent localization of the seizure focus. Four patients with extratemporal epilepsy had falsely localizing information obtained on PET. The results of this study demonstrate that PET is of less clinical utility in the presurgical evaluation of patients with extratemporal epilepsy as compared to patients with temporal lobe epilepsy.

We report a patient with lateralized right-sided ictal scalp EEG activity contralateral to left mesial temporal seizure onset as documented by depth electrodes. Subsequent left temporal lobectomy revealed mesial temporal sclerosis and resulted in a marked reduction (97%) in seizure frequency. This case illustrates the frequently discussed, but rarely documented, occurrence of false lateralization of scalp EEG seizure onset in a patient with temporal lobe epilepsy.

We compared scalp ictal EEG in complex partial seizures originating in extratemporal regions with seizures originating in the temporal lobe. All patients were seizure-free for 2 or more years after appropriate cortical resection confirming focus of seizure onset. The electroencephalographer reviewing seizures was blind to patient identity. Extratemporal seizures were shorter, more difficult to lateralize, and had postictal slowing less often. Confident lateralization of seizure onset could not be made in 19% of the seizures, usually because onset was diffuse or artifact obscured the seizure. When lateralization judgments were thought possible, lateralization errors occurred in only 3% of the seizures. Five percent of the seizures had no detectable scalp ictal changes.