Improving first responders' psychogenic nonepileptic seizures diagnosis accuracy: Development and validation of a 6-item bedside diagnostic tool.

OBJECTIVE: Epileptic seizures (ES) are often seen as a medical emergency, and their immediate and accurate recognition are pivotal in providing acute care. However, a number of clinical situations may mimic ES, potentially leading to misdiagnosis at the emergency room and to inappropriate prescription of antiepileptic drugs (AED) in the acute and chronic settings. Psychogenic nonepileptic seizures (PNES) play a major role in this scenario and often delay the correct diagnosis and increase treatment morbidity and cost. First responders often conduct the initial assessment of these patients, and their impression may be decisive in the prehospital approach to seizures. We sought to investigate and improve the accuracy of PNES diagnosis among professionals involved in the initial assistance to patients with seizures. METHODS: Fifty-three registered nurses, 34 emergency physicians, 33 senior year medical students, and 12 neurology residents took a short training program consisting of an initial video-based seizure assessment test (pretest), immediately followed by a 30-minute presentation of a 6-item bedside diagnostic tool and then a video-based reassessment (posttest). Baseline status and learning curves were determined. RESULTS: The distinct professional categories showed no significant differences in their ability to diagnose PNES on both pretests and posttests. All groups improved diagnostic skills after the instructional program. SIGNIFICANCE: The findings helped determine the best identifiable PNES clinical signs and to provide initial validation to a novel diagnostic instrument. In addition, our results showed that educational measures might help in the identification of PNES by first responders, which may decrease the treatment gap.

Are children affected by epileptic neuropsychiatric comorbidities?

Childhood-onset epilepsy is associated with psychiatric and cognitive difficulties and with poor social outcomes in adulthood. Some antiepileptic drugs adversely affect behavior in susceptible children with easy-to-control or refractory epilepsies, contributing to a high risk of psychological and psychiatric disturbance. Studies had demonstrated that patients with benign rolandic epilepsy and absence epilepsy had more aggressive behavior, depression, and anxiety disorders than control children. Psychiatric comorbidities are strongly associated with a poor long-term health-related quality of life in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and long-term treatment for these conditions, even if seizures remit.

Looking for complexity in quantitative semiology of frontal and temporal lobe seizures using neuroethology and graph theory.

Epileptic syndromes and seizures are the expression of complex brain systems. Because no analysis of complexity has been applied to epileptic seizure semiology, our goal was to apply neuroethology and graph analysis to the study of the complexity of behavioral manifestations of epileptic seizures in human frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). We analyzed the video recordings of 120 seizures of 18 patients with FLE and 28 seizures of 28 patients with TLE. All patients were seizure-free >1 year after surgery (Engel Class I). All patients' behavioral sequences were analyzed by means of a glossary containing all behaviors and analyzed for neuroethology (Ethomatic software). The same series were used for graph analysis (CYTOSCAPE). Behaviors, displayed as nodes, were connected by edges to other nodes according to their temporal sequence of appearance. Using neuroethology analysis, we confirmed data in the literature such as in FLE: brief/frequent seizures, complex motor behaviors, head and eye version, unilateral/bilateral tonic posturing, speech arrest, vocalization, and rapid postictal recovery and in the case of TLE: presence of epigastric aura, lateralized dystonias, impairment of consciousness/speech during ictal and postictal periods, and development of secondary generalization. Using graph analysis metrics of FLE and TLE confirmed data from flowcharts. However, because of the algorithms we used, they highlighted more powerfully the connectivity and complex associations among behaviors in a quite selective manner, depending on the origin of the seizures. The algorithms we used are commonly employed to track brain connectivity from EEG and MRI sources, which makes our study very promising for future studies of complexity in this field.

Rey-Osterrieth complex figure test: Comparison of traditional and qualitative scoring systems after unilateral temporal lobectomy.

OBJECTIVE: We compared the performance on the Rey-Osterrieth Complex Figure Test (ROCF) of patients that had undergone unilateral anterior temporal lobectomy under both Taylor's and Loring's scoring systems to identify the sensitivity and specificity of each item for differentiating visuospatial memory deficits. METHOD: We administered the ROCF to evaluate the visual memory of 37 left anterior temporal lobectomy (LATL) and 38 right anterior temporal lobectomy (RATL) patients with unilateral temporal lobe epilepsy who had undergone a standard unilateral anterior temporal lobectomy between 1996 and 2010. Fisher's exact and Qui-Quadrado tests were used to analyze the relationships between the qualitative variables. The Mann-Whitney U test was used to compare the quantitative variables from the right and left sides. RESULTS: RATL patients performed worse than LATL patients based on the total score for delayed recall (DR) (p = 0.012). The scoring system's showed a specificity of 97.2% & 78.9% and sensitivity of 10.5% & 62.2% on DR, for the Taylor and Loring systems respectively. Our detailed analysis of certain items showed that some differed between the groups in terms of the presence/absence, correct reproduction, and errors of those items. Loring' errors I, IV, and X on DR and errors IV and X on immediate recall were more frequent in the RATL group. CONCLUSIONS: The use of these two scoring systems combined may help maximize sensitivity and specificity with clinical populations. Further, our analyses showed that items could be clustered better and different weights could be given to them to maximize sensitivity and specificity.

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy.

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged.

Addressing overtreatment in patients with refractory epilepsy at a tertiary referral centre in Brazil.

BACKGROUND: Patients with refractory epilepsy often have impaired quality of life (QOL) as a consequence of seizures and adverse effects of antiepileptic drugs. We assessed the impact of adverse effects on QOL and the utility of a structured instrument to help the physician manage adverse effects in patients with refractory epilepsy. METHODS: Clinical characteristics, drug treatment and adverse effects were evaluated in 102 patients with refractory epilepsy at a single tertiary referral centre. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE-31) questionnaires were completed at baseline and after six months. At baseline, patients with a high burden of adverse effects (AEP scores ≥45) were randomized to an intervention or control group. AEP scores in the intervention group were available to the physician as an instrument to help to reduce adverse effects. RESULTS: Ninety-five patients (93.1%) were on polytherapy. Sixty-six completed the questionnaires and, of these, 43 (65.1%) had a high AE burden and were randomized to the intervention and control group. QOLIE-31 scores were inversely correlated with AEP scores at both visits. Among randomized patients, AEP scores tended to decrease between the baseline and the final visit without significant differences between groups (intervention group: 54.1 ±â€Š6.1 vs 51.1 ±â€Š9.1; control group: 55.8 ±â€Š5.8 vs 50.5 ±â€Š12.2). QOLI-31 scores did not change substantially between visits (intervention group: 45.9 ±â€Š17.4 vs 48.4 ±â€Š14; control group: 47.5 ±â€Š15.7 vs 45.2 ±â€Š18.9). CONCLUSION: A significant proportion of patients had a high toxicity burden which had an impact on their QOL. Reduction of overtreatment is a difficult challenge which cannot be addressed solely by providing a structured assessment of adverse effects, but requires a more comprehensive approach aimed at optimizing the many components of the management strategy.

Tailored resections for intractable rolandic cortex epilepsy in children: a single-center experience with 48 consecutive cases.

OBJECTIVE: A single-center experience with pediatric patients who underwent surgery for intractable rolandic epilepsy was reviewed with the aim of identifying putative factors that could influence postoperative seizure outcome in this population. METHODS: Clinical data of 48 patients under 18 years of age with diagnosis of intractable rolandic epilepsy who underwent surgery from January 1996 to September 2009 were reviewed. RESULTS: Patients' mean age at surgery was 9.9 ± 5.3 years; mean age at epilepsy onset was 3.9 years; mean seizure duration prior to surgery was 6 years; and mean follow-up was 5.1 years. The most frequent etiologies were cortical dysplasia, astrogliosis, tumors, tuberous sclerosis complex, and Sturge-Weber syndrome, which were observed in 20/48 (41.6%), 10/48 (20.8%), 10/48 (20.8%), 5/48 (10.4%), and 3/48 (6.2%) of the patients, respectively. After surgery, 20 patients (41.6%) showed neurological deficits, which in turn recovered within no longer than 6 months after surgery. Seizure outcome was classified as Engel class I in 29 (60.4%), Engel class II in 10 (20.8%), and Engel class III in 9 (18.8%) of the patients. The factors significantly related with seizure outcome were histological features (tumor versus non-tumor cases, p = 0.04) and lesion site (focal lesions versus non-focal lesions, p = 0.04). CONCLUSIONS: Tailored resection of rolandic cortex for intractable epilepsy can be safely performed in children. Accurate mapping of both functional cortex and epileptogenic areas may lead to improved seizure outcome. Tumor as well as focal lesions in hand and face motor areas are associated with good seizure outcome.

Nonverbal fluency assessed by the five-point test in epilepsy patients with unilateral mesial temporal sclerosis-a Brazilian study.

OBJECTIVE: To investigate the performance of epilepsy patients diagnosed with unilateral mesial temporal sclerosis (MTS) on a nonverbal fluency measure using the five-point test (FPT). Our secondary aim was to investigate any differences in FPT and verbal fluency test (VFT) scores between left and right MTS. We hypothesized that scores on the FPT, commonly utilized in the assessment of individuals with presumed frontal lobe damage, would be lower in patients with temporal lobe dysfunction. METHOD: One hundred eighty patients diagnosed with temporal lobe epilepsy (TLE) and 150 healthy controls (HCs) were included in this retrospective study. We analyzed correlations between scores obtained from FPT and phonemic and semantic VFT, and scores according to the lateralization of epileptogenic focus in the TLE group. RESULTS: Overall, the TLE patients had lower performance than the HCs on the FPT, but no differences were observed on perseverance rates (p = 0.992). Statistically significant difference was found in both sections of the VFT in association with the lateralization of the epileptogenic zone (p < 0.001). As for the FPT, differences did not reach statistical significance (p = 0.0857). CONCLUSIONS: Our results support the hypothesis of involvement of the temporal areas on tasks such as the FPT, despite the lack of a lateralizing effect. Our findings also contribute to better understanding of the role of the FPT in assessment of executive function in patients with unilateral MTS, and provide further psychometric data on a native Brazilian population.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

The neurobiological substrates of behavioral manifestations during temporal lobe seizures: a neuroethological and ictal SPECT correlation study.

Ictal behavior coupled with SPECT findings during 28 seizures in patients with temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (13 left; 15 right) was displayed as flowcharts from right-sided (RTLE) plus left-sided (LTLE) seizures. Ictal SPECT was classified blind to neuroethology. Behaviors were categorized as ipsilateral to the epileptogenic zone (IL), contralateral to the epileptogenic zone (CL), or bilateral. SPECT intensity and region were categorized as IL or CL to the epileptogenic zone. All patients developed automatisms and had hyperperfusion in their temporal lobes. Patients' verbal responses to questions had statistical interactions in RTLE but not in LTLE sum. Most CL dystonic posturing was correlated to IL basal ganglia hyperperfusion. Basal ganglia activation occurred in seizures without dystonic posturing and CL manual automatisms, and lack of IL dystonic posturing and the presence of CL cerebellar hemispheric hyperperfusion were also observed. Coupling of neuroethology and SPECT findings reliably evaluates ictal behavior and functionality of associated brain areas.

Comparative role of neuropsychological testing in the presurgical evaluation of children with medically intractable epilepsies.

PURPOSE: In the present study, we evaluated the preoperative demographic, clinical, and neuropsychological variables that could predict postoperative seizure outcome in a group of pediatric epileptic patients. MATERIALS AND METHODS: We studied 40 consecutive pediatric patients, ages ranging from 6 to 16 years, that underwent resective surgery for the treatment of medically intractable epilepsy at the Clinical Hospital of Ribeirão Preto School of Medicine. We performed ictal electroencephalography (EEG), interictal EEG, magnetic resonance imaging (MRI), and a preoperative neuropsychological assessment in the presurgical workup. RESULTS: The following factors were correlated with seizure outcome: (1) duration of epilepsy, (2) surgery localization, (3) localized Neuropsychological (NPS) Evaluation, (4) ictal EEG, (5) interictal EEG, and (6) MRI. Mental retardation, NPS tests, and the other demographic variables failed to correlate with seizure reduction. CONCLUSIONS: The identification of predictor variables of epilepsy surgery outcome could improve the epileptic prognosis and guarantee the children's full potential development.

CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment.

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic-clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery.

In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed.

Neuromodulation in refractory epilepsy: Brazilian specialists consensus.

Epilepsy is a potentially devastating brain disorder characterized by a predisposition to spontaneous epileptic seizures. In patients with medically refractory epilepsy, new non-pharmacological therapeutic approaches may be considered. In this scenario, palliative surgery such as vagus nerve stimulation (VNS) or deep brain stimulation (DBS) may be indicated in a subset of patients. In this paper we make recommendations for the use of VNS and DBS in patients in Brazil with refractory epilepsy.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Neuromodulation in refractory epilepsy: Brazilian specialists consensus / Neuromodulação em epilepsia refratária: consenso dos especialistas brasileiros

ABSTRACT Epilepsy is a potentially devastating brain disorder characterized by a predisposition to spontaneous epileptic seizures. In patients with medically refractory epilepsy, new non-pharmacological therapeutic approaches may be considered. In this scenario, palliative surgery such as vagus nerve stimulation (VNS) or deep brain stimulation (DBS) may be indicated in a subset of patients. In this paper we make recommendations for the use of VNS and DBS in patients in Brazil with refractory epilepsy.

RESUMO Epilepsia é uma doença cerebral potencialmente devastadora caracterizada por predisposição em gerar crises epilépticas espontâneas. Em pacientes com epilepsia refratária novas abordagens terapêuticas, não farmacológicas, podem ser consideradas. Neste cenário, cirurgias paliativas, como a estimulação do nervo vago (VNS) ou estimulação cerebral profunda (DBS) podem ser indicadas em um subgrupo de pacientes. Neste trabalho sugerimos recomendações sobre as indicações de uso do VNS e do DBS em pacientes com epilepsia refratária no Brasil.

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery / Epilepsia refratária em crianças com tumores cerebrais. A urgência de neurocirurgia

ABSTRACT In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed.

RESUMO A fim de verificar os aspectos da indicação cirúrgica, vinte e sete pacientes com epilepsia refratária secundária a tumor cerebral, com idade de até 19 anos na cirurgia, operados entre 1996 e 2013 e seguidos por pelo menos um ano, foram estudados. O intervalo médio entre o início das crises e o diagnóstico do tumor foi de 3,6 anos, e deste para a cirurgia, 18 meses. A localização do tumor foi lobo temporal em 16, sendo ganglioglioma e DNET os tipos mais frequentes. Entre os pacientes, 92,5% e 90,4% estavam livres de crises no primeiro e no quinto ano após a cirurgia, respectivamente. Doze de 16 crianças obtiveram sucesso na retirada de drogas, com a média de tempo de 3,2 anos após o procedimento. A cirurgia provou ser potencialmente curativa e segura nestes casos, o que sugere que perante o diagnóstico de tumor esta não pode ser adiada.

Physical exercise in rats with epilepsy is protective against seizures: evidence of animal studies.

People with epilepsy have been discouraged from participating in physical activity due to the fear that it will exacerbate seizures. Clinical and animal studies indicate a reduction of seizure frequency as well as decrease susceptibility to subsequently evoked seizures after an exercise program. Analyses from experimental studies of animals with epilepsy submitted to physical training programs were performed. In all studies the physical training was able to reduce the number of spontaneous seizures in rats with epilepsy. Seizure occurrence during exercise was relatively absent in the majority of studies. No death was found in animals with epilepsy during 1680 h of exercise. Based on these results it is plausible encouraging persons with epilepsy to non-pharmacological treatments and preventative measures such as physical exercise.