Epilepsy and exercise: An experimental study in female rats.

OBJECTIVE: Epilepsy is the most common neurological chronic condition worldwide, affecting about 2% of world population. Temporal lobe epilepsy (TLE) reaches 40% of all cases of this condition, and it is highly refractory to pharmacological treatment. Physical activity has been suggested as complementary therapy for epilepsy. However, there is no consistent information whether all these effects are plenty applicable to females, since clinical and experimental studies concerning physical exercise and epilepsy are largely performed in males. Females are worthy of special attention due to gender specific particularities such as hormonal cyclical rhythm and possible pregnancy. Therefore, this study aimed to investigate the impact of two types of exercise programs (Forced and Voluntary) in female Wistar rats submitted to temporal lobe epilepsy induced by pilocarpine. METHODS: Animals were divided into four groups: Control (healthy), Epilepsy, Epilepsy/Forced (exercise in a treadmill) and Epilepsy/Voluntary (free access to wheel). Behavioral and histological analyses were evaluated among groups. RESULTS: Voluntary exercise was able to reduce seizure frequency and anovulatory estrous cycle occurrence. Yet, both types of exercise attenuated the mossy fiber sprouting in dentate gyrus. CONCLUSION: Our results indicate that voluntary exercise exerts a positive effect on epilepsy in female gender. Further investigations are necessary to better elucidate mechanisms involved in these responses, since these effects do not act in the same manner in male and female rats.

Intracranial stimulation for children with epilepsy.

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary.

Optimizing memory function in temporal lobe epilepsy.

PURPOSE: The study aimed to assess whether engagement in a memory training programme and performing internet brain training exercises improve memory function in people with temporal lobe epilepsy (TLE). METHODS: Seventy-seven people with TLE, complaining of memory difficulties, completed the study. Participants ranged in age from 19 to 67 years and 40 had left TLE. Participants were randomised to one of four conditions; Group 1: traditional memory training, Group 2: Lumosity, an on-line cognitive training programme, Group 3: traditional memory training and Lumosity, and Group 4: no training. Memory efficiency and mood were assessed at baseline and three months later. RESULTS: Group analyses indicated improved verbal recall after training (p<0.001) and improved subjective ratings (p<0.007). More participants reported a lessening of the memory burden (p<0.007) after training; differences were significant between Groups 1 and 3 compared to Group 4. Lumosity use was not associated with changes in the memory outcome measures but there was a relationship with depression ratings and the number of memory games played (p<0.01). Conventional memory training, IQ, and post-surgical status were associated with positive memory outcomes. CONCLUSIONS: The study indicates traditional memory rehabilitation techniques can help reduce the burden of memory impairment in TLE. There was no evidence that Lumosity the on-line cognitive training programme had specific advantages. Positive change was not universal and larger studies will be required to explore factors associated with successful outcomes.

Slow-oscillatory Transcranial Direct Current Stimulation Modulates Memory in Temporal Lobe Epilepsy by Altering Sleep Spindle Generators: A Possible Rehabilitation Tool.

BACKGROUND: Temporal lobe epilepsy (TLE) is often associated with memory deficits. Given the putative role for sleep spindles memory consolidation, spindle generators skewed toward the affected lobe in TLE subjects may be a neurophysiological marker of defective memory. Slow-oscillatory transcranial direct current stimulation (sotDCS) during slow waves sleep (SWS) has previously been shown to enhance sleep-dependent memory consolidation by increasing slow-wave sleep and modulating sleep spindles. OBJECTIVE/HYPOTHESIS: To test if anodal sotDCS over the affected TL prior to a nap affects sleep spindles and whether this improves memory consolidation. METHODS: Randomized controlled cross-over study. 12 people with TLE underwent sotDCS (0.75 Hz; 0-250 µV, 30 min) or sham before daytime nap. Declarative verbal and visuospatial learning were tested. Fast and slow spindle signals were recorded by 256-channel EEG during sleep. In both study arms, electrical source imaging (ESI) localized cortical generators. Neuropsychological data were analyzed with general linear model statistics or the Kruskal-Wallis test (P or Z < 0.05), and neurophysiological data tested with the Mann-Whitney t test and binomial distribution test (P or Z < 0.05). RESULTS: An improvement in declarative (P = 0.05) and visuospatial memory performance (P = 0.048) emerged after sotDCS. SotDCS increased slow spindle generators current density (Z = 0.001), with a shift to the anterior cortical areas. CONCLUSIONS: Anodal sotDCS over the affected temporal lobe improves declarative and visuospatial memory performance by modulating slow sleep spindles cortical source generators. SotDCS appears a promising tool for memory rehabilitation in people with TLE.

Cognitive rehabilitation in epilepsy: An evidence-based review.

AIM OF THE STUDY: To review the modalities of cognitive rehabilitation (CR), outcome endpoints, and the levels of evidence of efficacy of different interventions. METHODS: A systematic research in Pubmed, Psychinfo, and SCOPUS was performed assessing the articles written in the entire period covered by these databases till December 2013. Articles in English, Spanish or French were evaluated. A manual research evaluated the references of all of the articles. The experimental studies were classified according to the level of evidence of efficacy, using a standardized Italian method (SPREAD, 2007), adopting the criteria reported by Cicerone et al. (2000, 2011). RESULTS: Eighteen papers were classified into two reviews, four papers dealing with the principles and efficacy of CR in epilepsy, a methodological paper, a single-case report, a multiple-case report, and nine experimental papers. Most studies involved patients with temporal lobe epilepsy. Different types of CR were used to treat patients with epilepsy. A holistic rehabilitation approach was more useful than selective interventions to treat memory and attention disturbances. CONCLUSIONS: CR may be a useful tool to treat cognitive impairment in patients with epilepsy. However, the modalities of treatment and outcome endpoints are important concerns of clinical care and research. Controlled studies are needed to determine the efficacy of rehabilitation in well-defined groups of patients with epilepsy.

Effects of an inpatient rehabilitation program after temporal lobe epilepsy surgery and other factors on employment 2 years after epilepsy surgery.

OBJECTIVE: To evaluate the effects of a postsurgical rehabilitation program on employment status 2 years after temporal lobe epilepsy surgery in relation to other predictors. METHODS: Employment outcome 2 years after temporal lobe resection in a group of 232 adult patients with the offer of a 3-week inpatient rehabilitation program immediately after surgery ("Reha group") was compared to a group of 119 patients who had surgery before such a rehabilitation program existed. One hundred thirty-nine (59.9%) of the Reha group patients attended the rehabilitation program. Further predictors for employment outcome were analyzed using multivariate logistic regression analysis. RESULTS: Preoperatively, the groups did not differ significantly in variables relevant for employment, including employment rate. Two years after surgery, the rate of those not being employed had decreased in the Reha group from 38.4% to 27.6% (p < 0.001, McNemar test), and slightly increased in the control group (37.8-42.0%; n.s.), resulting in a difference of 14.4% in favor of the Reha group (p = 0.008). General unemployment rates during the two observation periods were similar. In addition to the offer of rehabilitation support ("Reha group") and preoperative employment, the following other variables were shown as significant predictors of employment post surgery in multivariate regression analysis: seizure outcome, diagnosis of a personality disorder preoperatively, and age at surgery (all, p < 0.01; Nagelkerkes R(2) = 0.59). SIGNIFICANCE: Independently from other factors, a 3-week inpatient rehabilitation program after temporal lobe epilepsy surgery seems to improve employment status 2 years after surgery.

Assessing the driving performance of a person with epilepsy presurgery and postsurgery.

Occupational therapists and certified driving rehabilitation specialists are uniquely skilled to assess functional abilities underlying driving performance. However, little information exists on the utility of clinical assessments to determine driving performance in people with epilepsy. This case study demonstrates how an occupational therapy evaluation battery was used to examine differences in visual and cognitive abilities and simulated driving performance before and after epilepsy surgery. Specifically, a 43-yr-old White man with right anterior lobe epilepsy underwent temporal lobectomy and had his driving-related abilities and simulated driving performance assessed pre- and postsurgery. The occupational therapy evaluation indicated improvements in executive skills, attention, and information processing speed postsurgery. Visuospatial abilities worsened after surgery, likely contributing to the modest increase in vehicle position errors on the driving simulator. Nevertheless, simulated driving performance improved after temporal lobectomy. Reductions in the number of visual scanning, lane maintenance, and speed regulation errors were recorded.

Memory rehabilitation and brain training for surgical temporal lobe epilepsy patients: a preliminary report.

The short term impact of a memory rehabilitation programme on verbal memory test performance and subjective ratings of memory in everyday life was assessed in healthy controls and left temporal lobe epilepsy (LTLE) surgical patients. The intervention involved training in the use of external and internal memory support strategies. Half of the sample in addition undertook computerised brain training exercises as homework. LTLE patients were seen either before surgery or 3-6 months after their operation. Improvements in verbal memory were observed in both groups. An effect of brain training was recorded but this did not occur in a consistent direction. Subjective ratings of memory indicated improvements that were significant for the LTLE group but not the controls. Positive changes in the memory outcome measures were associated with improvements in mood. Pre-operative memory rehabilitation was not associated with better outcomes than post-operative intervention. Further research is needed to explore the persistence of the changes observed and to explore if pre-operative rehabilitation offsets post-operative memory decline.

Cardiorespiratory and electroencephalographic responses to exhaustive acute physical exercise in people with temporal lobe epilepsy.

We evaluated physiological and electroencephalographic responses during a cardiopulmonary exercise test (CPET) in people with epilepsy. Behavioral outcomes of people with epilepsy were also compared with those of healthy controls. Thirty-eight subjects (19 people with epilepsy and 19 controls) participated in this study. Poor outcomes in the behavioral analyses (habitual level of physical activity and quality of life) were observed in the people with epilepsy. With respect to the CPET, V.O(2max) (14.6%) and V.O(2) at anaerobic threshold (16.1%) were significantly lower in the epilepsy group than in the control group. Although not statistically significant, a decrease in the number of epileptiform discharges was observed between the rest state and exercise (82%) and between the rest state and recovery period (74%). In conclusion, the lower aerobic fitness in people with epilepsy observed may be associated with their sedentary habits. Moreover, our findings reinforce the hypothesis that exhaustive exercise is not a seizure-inducing factor.

Physical exercise in rats with epilepsy is protective against seizures: evidence of animal studies / Exercício físico em ratos com epilepsia como fator protetor contra crises epilépticas: evidencias de estudos em animais

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.

Pessoas com epilepsia têm sido desencorajadas da prática de atividade física por receio do exercício físico exacerbar as crises epilépticas. Estudos clínicos e em animais mostram uma redução da frequência de crises, assim como diminuição da susceptibilidade a crises subseqüentes após programa de exercício físico. Neste estudo realizamos uma análise de estudos experimentais de animais com epilepsia submetidos a programas de exercício físico. Em todos os estudos, o treinamento físico foi capaz de reduzir o número de crises espontâneas em ratos com epilepsia. A ocorrência de crises durante o exercício físico foi relativamente ausente na maioria dos estudos. Nenhuma morte foi encontrada em animais com epilepsia durante 1680 h de exercício físico. Baseados nestes resultados parece aceitável encorajar as pessoas com epilepsia a tratamentos não farmacológicos e medidas preventivas como o exercício físico.

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.

Trans-Sylvian selective amygdalohippocampectomy for medically intractable temporal lobe epilepsy: a single-centre experience.

Selective amygdalohippocampectomy (SelAH) is now widely used in the surgical treatment of patients with medically intractable medial temporal lobe epilepsy (MTLE). We present our single-centre experience of a uniform series of drug-resistant MTLE patients treated exclusively with SelAH. A retrospective study of 50 adult patients (25 males, 25 females, mean age 34 years) suffering from medically intractable MTLE was conducted. All patients has been investigated under the same protocol and operated by SelAH performed by one surgeon. Immediate and long-term follow-up was also available and is presented. Forty-two patients (84%) became seizure free (Engel's I); eight of them (16%) were classified as Engel's II; four (8%) as Engel's III; and one as Engel's IV (2%). In 42 of them the final result has been achieved after a single operation, while in the rest eight after a second or third surgical procedure. The mean follow-up period was 6.2 years. Two permanent complications (4%) with no treatment-related mortality have been detected. SelAH performed in well selected cases, where concordance between electrophysiological and MR findings exists, can be a safe and effective surgical treatment method for medically intractable MTLE.

The longitudinal course of adjustment after seizure surgery.

Surgical alleviation of chronic epilepsy can give rise to a process of adjustment as the chronically ill patient learns to become well. This process can manifest clinically as an array of symptoms which we have previously described as the 'burden of normality'. The aim of this study was to explore the longitudinal course of post-operative adjustment by mapping the incidence of symptoms of the burden of normality over a period of 2 years, and examining symptom occurrence relative to seizure outcome. A series of 90 anterior temporal lobectomy (ATL) patients was drawn from our Seizure Surgery Follow-up and Rehabilitation Program. All patients were prospectively assessed using the Austin CEP Interview, which covers symptoms of the burden of normality. In total, 66% of patients reported symptoms at some time within the first 2 years of surgery. Symptoms often emerged by the 3 month review, but were still seen frequently in the second year. At the 24 month review, patients who had been seizure free or experienced auras only within the previous 18 months were significantly more likely to report symptoms compared to patients who had experienced complex partial and/or generalized tonic-clonic seizures (P = 0.03). Surgical alleviation of seizures in chronic epilepsy brings with it the burden of normality. Recognition of this syndrome is essential in maximizing patient outcome.

Recommendation of early surgery from the viewpoint of daily quality of life.

We surveyed pre- and postoperative levels of satisfaction with a range of the daily quality-of-life (QOL) domains in 132 sets of epilepsy surgery patients and their families. All patients underwent resective surgery for temporal lobe epilepsy and were monitored for > 2 years. Patient and family assessments showed patients' overall QOL markedly improves after surgery, depending on freedom from seizures. However, factors such as social contacts, family relations, or financial status improved little. Some families and patients were not satisfied with the postsurgical status, despite freedom from seizures. Patients who had surgery at a later age were not so satisfied with their postsurgical status as were patients who had surgery at a younger age, particularly on the QOL domains of role activities, memory function, leisure activities, or emotional well-being. This lower satisfaction level in older patients likely results from a variety of problems affecting patients during the long-lasting epileptic process; social handicaps, psychologic conflicts, and deterioration of cognitive/behavioral functions. Based on each case, we recommend that investigations start at an early stage of the illness, so that surgical intervention may be considered as early as possible.

University students with epilepsy: a study of social aspects.

Improved control of epilepsy has permitted an increasing number of young persons with epilepsy to attend university. This study was designed to assess the impact of epilepsy on their education, employment, family and social life. We studied fifteen randomly selected full time university students, aged 20-28 years, who had a well documented history of partial or generalized epilepsy. One third still had seizures, over 90% were taking antiepileptic medication and all were followed by a neurologist. Interviews were conducted according to a standard open-ended questionnaire lasting 1.5 hours. After an initial adjustment period, most did not feel that epilepsy constituted a handicap to their education. They learned about epilepsy, did independent research and one quarter chose careers in the health sciences. Most reported occasional negative experiences, but were reluctant to interpret this as evidence of discrimination. All felt that they had had equal opportunities at school and at work. They were selective about imparting knowledge about their seizures to students, staff and employers, but did not hide their epilepsy. Subjects had high vocational aspirations and academic motivation reflecting good intelligence and previous educational achievements. Their positive attitude, enthusiasm and denial of difficulties were striking. This reflects improved seizure control as well as family and social support in this group of young people.

Temporal lobe epilepsy: social and psychological considerations.

The diagnosis of temporal lobe epilepsy (TLE) holds significant psychosocial ramifications for the patient and family. TLE is a type of seizure disorder which challenges the usual notions of epilepsy. Patients with TLE may never experience the stereotypical convulsion; rather, TLE seizures are more likely to take the form of changes in behavior and deepened emotionality. The symptoms are confusing and often frightening for the patient, his family and the larger community. This article explores the patient's and the family's reactions to TLE--myths that influence them, the practical and emotional dilemmas that confront them, and the benefits of social work intervention.

Temporal lobe epilepsy. Social conditions and rehabilitation after surgery.

A social investigation was performed of 74 patients with temporal lobe epilepsy resistant to medication, who underwent unilateral temporal lobectomy 1960-1969. The patients were compared to their sibilings and to the general population in Denmark. Comparatively many patients were born out of wedlock. The level of schooling achieved was lower than expected, and this was most pronounced in patients with an early onset of epilepsy. The number of patients having received further education was also smaller than calculated. At the time of the operation all patients were socially incapacitated by their epilepsy; this was most pronounced in males, of whom 30 per cent were institutionalized and 32 per cent were receiving disablement pension; at follow-up the figures were 6 per cent and 52 per cent, respectively. Working capacity was markedly improved postoperatively, and at follow-up 39 per cent were in full-time employment. Relief from seizures (or almost complete relief), normal intelligence, normal psychiatric status, and operation before the age of 18 years were factors which favourably influenced the postoperative working capacity. The majority of the patients were unmarried or divorced, and few of the group had children. Their housing conditions were inferior to those of their siblings and of the general population. Parental social class distribution showed an excess in the highest and lowest social classes compared to the Danish population. The patients were subjected to downward social mobility, presumably caused by their illness, as their siblings displayed an upward mobility, which was most marked in the females.