Nocturnal hypermotor seizures, suggesting frontal lobe epilepsy, can originate in the insula

PURPOSE: To report three patients with drug-resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex. METHODS: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites. RESULTS: In all three patients, a low-voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high-amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2). CONCLUSIONS: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug-resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.     

How Confident Are We of the Diagnosis of Epilepsy?

Summary:  The diagnosis of a first seizure or epilepsy may be subject to interobserver variation and inaccuracy with possibly far-reaching consequences for the patients involved. We reviewed the current literature.
  Studies on the interobserver variation of the diagnosis of a first seizure show that such a diagnosis is subject to considerable interobserver disagreement. Interpretation of the electroencephalogram (EEG) findings is also subject to interobserver disagreement and is influenced by the threshold of the reader to classify EEG findings as epileptiform. The accuracy of the diagnosis of epilepsy varies from a misdiagnosis rate of 5% in a prospective childhood epilepsy study in which the diagnosis was made by a panel of three experienced pediatric neurologists to at least 23% in a British population-based study, and may be even higher in everyday practice. The level of experience of the treating physician plays an important role. The EEG may be helpful but one should be reluctant to make a diagnosis of epilepsy mainly on the EEG findings without a reasonable clinical suspicion based on the history.
  Being aware of the possible interobserver variation and inaccuracy, adopting a systematic approach to the diagnostic process, and timely referral to specialized care may be helpful to prevent the misdiagnosis of epilepsy.     

REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy

More than one in three adult patients suffering from narcolepsy-cataplexy experience rapid eye movement (REM) behavior disorder (RBD), while RBD in childhood is extremely rare. We present the cases of two girls (aged 9 and 7 years old) with narcolepsy-cataplexy, in whom RBD was one of the first symptoms of the disease. The coincidence of RBD was seen by nocturnal video-polysomnography (v-PSG), and narcolepsy was diagnosed from short sleep latency and multiple sleep onset REMs (SOREMs) during a multiple sleep latency test (MSLT). Both girls were human leukocyte antigen (HLA)-DQB1 *0602 positive, and their cerebrospinal fluid (CSF) hypocretin level (Hcrt-1) was extremely low.     

Comorbid epilepsy and psychogenic non-epileptic seizures: How well do patients and caregivers distinguish between the two

PurposeTo determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification.MethodsAdult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients’ epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated.ResultsTwenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (±12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient.ConclusionA significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.     

Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden: First report from the Stockholm Incidence Registry of Epilepsy (SIRE)

Purpose:   To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE).
Methods:   From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records.
Results:   After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%.
Conclusions:   We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.     

Validation of two prognostic models predicting outcome at two years after diagnosis in a new cohort of children with epilepsy: the Dutch Study of Epilepsy in Childhood

PURPOSE: To validate two prognostic models for childhood-onset epilepsy designed to predict a terminal remission of <6 months at 2 years after diagnosis in children referred to the hospital. METHODS: A hospital-based cohort of children with newly diagnosed epilepsy was recruited and followed up for 2 years to validate previously developed models. One model was based on variables collected at intake, and the other was based on intake variables plus variables collected during the first 6 months of follow-up. The accuracy of both models was estimated by measuring the area under the receiver-operant-characteristic curves (ROC area). RESULTS: The ROC area of the model developed with intake variables was 0.69 [95% confidence interval (CI), 0.64-0.74] for the original cohort and 0.62 (95% CI, 0.55-0.69) for the validation cohort. The best combination of sensitivity and specificity for the original cohort was 61.6% and 69.1%, whereas it was 60.0% and 61.4% for the validation cohort. For the model with intake and 6-month variables combined, the ROC area was 0.78 (95% CI, 0.73-0.82) for the original cohort and 0.71 (95% CI, 0.64-0.78) for the validation cohort. The sensitivity and specificity were 72.6% and 73.1%, respectively, for the original cohort and 67.4% and 60.2%, respectively, for the validation cohort. CONCLUSIONS: Although both models predict outcome better than chance, they are insufficiently accurate to be of practical value. Both models performed marginally less well with the validation cohort than with the original cohort, but in both instances, the model based on intake and 6-month variables was more accurate.     

国际抗癫痫联盟关于发作和癫痫分类框架术语及概念最新修订版的解读

国际抗癫痫联盟(International League Against Epilepsy,ILAE)分类和术语委员会2010年制定的发作和癫痫分类框架术语及概念修订版旨在进一步建立和规范发作和癫痫分类术语及概念的国际共识,反映术语与分类的基本关系,以指导临床实践,尤其是指导制定更合适的治疗方案。对于以往的全面性发作和局灶性发作分类法,目前强调依据网络的起源方式重新进行定义,其中双侧起源为全面性发作,局限于一侧为局灶性发作。此外,建议使用遗传性、结构性/代谢性和未知病因这3个术语以替代原来的特发性、症状性和隐源性。新的报告还首次使用了一些特定的术语,如电-临床综合征、相对明确的癫痫群体和癫痫性脑病等。本文对ILAE关于发作和癫痫分类框架术语及概念最新修订版进行了解读。     

Significance of the EEG in the decision to initiate antiepileptic treatment in patients with epilepsy: A perspective on recent evidence

The significance of electroencephalography in the prediction of seizure recurrence after a first unprovoked seizure remains a topic of debate. Opinion on the initiation of antiepileptic treatment after a first seizure also remains divided. However, in view of recent evidence, this article is intended to highlight the significance of a properly performed EEG in the decision to initiate antiepileptic drug treatment as early as possible to prevent further morbidity and other consequences.     

Epilepsy,seizures, physical exercise,and sports: A report from the ILAE Task Force on Sports and Epilepsy

People with epilepsy (PWEs) are often advised against participating in sports and exercise, mostly because of fear, overprotection, and ignorance about the specific benefits and risks associated with such activities. Available evidence suggests that physical exercise and active participation in sports may favorably affect seizure control, in addition to producing broader health and psychosocial benefits. This consensus paper prepared by the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy offers general guidance concerning participation of PWEs in sport activities, and provides suggestions on the issuance of medical fitness certificates related to involvement in different sports. Sports are divided into three categories based on potential risk of injury or death should a seizure occur: group 1, sports with no significant additional risk; group 2, sports with moderate risk to PWEs, but no risk to bystanders; and group 3, sports with major risk. Factors to be considered when advising whether a PWE can participate in specific activities include the type of sport, the probability of a seizure occurring, the type and severity of the seizures, seizure precipitating factors, the usual timing of seizure occurrence, and the person's attitude in accepting some level of risk. The Task Force on Sports and Epilepsy considers this document as a work in progress to be updated as additional data become available.     

Psychogenic nonepileptic seizures: characterization of two distinct patient profiles on the basis of trauma history

This prospective study investigated and compared psychiatric features of 25 consecutive patients with psychogenic nonepileptic seizures (PNES) on the basis of presence of reported trauma. The “trauma” group comprised 19 patients (76%) and the “no-trauma” group comprised 6 patients (34%). We compared history of PNES, psychiatric comorbidity, alexithymia, and symptoms of dissociation. The study clearly characterized two distinct profiles of patients with PNES on the basis of trauma history. Patients with trauma had at least one psychiatric comorbidity or antecedent (vs 0% in the no-trauma group NT, P < 0.001) and a higher median score of dissociation (P < 0.001). Patients without trauma had more frequent “frustration situations” as a factor triggering PNES and subsequent sick leaves as perpetuating factors (P = 0.001). Trauma antecedents correlated with a high rate of psychiatric comorbidity and a strong dissociative mechanism. Patients without trauma had no psychiatric comorbidity and a weaker dissociative mechanism.     

Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE – Commission on European Affairs and the European Epilepsy Monitoring Unit Association

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)—Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.     

A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy

PURPOSE: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated. RESULTS: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups. CONCLUSIONS: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.     

Functional connectome fingerprinting accuracy in youths and adults is similar when examined on the same day and 1.5‐years apart

Pioneering studies have shown that individual correlation measures from resting‐state functional magnetic resonance imaging studies can identify another scan from that same individual. This method is known as “connectotyping” or functional connectome “fingerprinting.” We analyzed a unique dataset of 12–30 years old (N = 140) individuals who had two distinct resting state scans on the same day and again 12–18 months later to assess the sensitivity and specificity of fingerprinting accuracy across different time scales (same day, ~1.5 years apart) and developmental periods (youths, adults). Sensitivity and specificity to identify one's own scan was high (average AUC = 0.94), although it was significantly higher in the same day (average AUC = 0.97) than 1.5‐years later (average AUC = 0.91). Accuracy in youths (average AUC = 0.93) was not significantly different from adults (average AUC = 0.96). Multiple statistical methods revealed select connections from the Frontoparietal, Default, and Dorsal Attention networks enhanced the ability to identify an individual. Identification of these features generalized across datasets and improved fingerprinting accuracy in a longitudinal replication data set (N = 208). These results provide a framework for understanding the sensitivity and specificity of fingerprinting accuracy in adolescents and adults at multiple time scales. Importantly, distinct features of one's “fingerprint” contribute to one's uniqueness, suggesting that cognitive and default networks play a primary role in the individualization of one's connectome.