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Stress and epilepsy: Fact or fiction, and what can we do about it?
Abstract
People with epilepsy report that stress is their most common trigger for seizures and some believe it caused their epilepsy in the first place. The extensive preclinical, epidemiological and clinical studies examining the link between stress and epilepsy have given confusing results; the clinical studies in particular are fraught with confounders. However stress is clearly bad for health, and we now have substantial preclinical evidence suggesting that chronic stress worsens epilepsy; in selected cases it may even be a causal factor for epilepsy. Healthcare professionals working with people with epilepsy should pay more attention to stress in clinical practice. This review includes some practical advice and guidance for stress screening and management.
... Тем не менее доклинические, эпидемиологичес кие и клинические исследования связи стресса с эпилепсией дают довольно противоречивые ре зультаты. Экспериментальные результаты боль шинства доклинических исследований подтвер ждают, что хронический стресс усугубляет про явления эпилепсии, а в некоторых случаях мо жет служить ее причиной [27,28], однако дан ные клинических исследований не так одно значны. Негативное влияние депрессии на ГУЛЯЕВА контроль судорожных расстройств было задоку ментировано в различных исследованиях [29]. ...
... Анализ имеющихся к настоящему времени данных свидетельствует о том, что факторы стресса, действующие в раннем онтогенезе или на взрослый организм, могут являться эпилепто генными и инициировать развитие эпилепсии. Эти факторы могут быть хроническими и действовать при эпилептогенезе и развившемся заболевании, либо однократно, запуская моле кулярные процессы, лежащие в основе эпилеп сии и коморбидной депрессии (подробно рас смотрены в статьях [27,37,38]). На пациента с эпилепсией действует целый комплекс хрони СТРЕСС, ГИППОКАМП, ЭПИЛЕПСИЯ И КОМОРБИДНАЯ ДЕПРЕССИЯ ческих стрессорных факторов, психологических и физических. ...
... Указаны группы факторов, предрасполага ющих и усиливающих эпилептогенез, а также преципитирующих судорожные приступы. Схема составлена на основании данных, приведенных в работах [27,29,37,40]. ГК -глюкокортикоиды; ГГАКС -гипоталамо гипофизарно адренокор тикальная система; Ami -амигдала; Hip -гиппокамп; PFC -префронтальная кора. ...
В обзоре рассматриваются молекулярно�клеточные механизмы, общие для эпилептических и депрессивных расстройств. Коморбидные эпилепсия височной доли и депрессия ассоциированы с нарушениями функционирования гипоталамо-гипофизарно-адренокортикальной оси и вызванными избытком глюкокортикоидов нарушениями функции и структуры гиппокампа, ключевого региона мозга для обучения/памяти и эмоций. Селективная чувствительность гиппокампа к стрессу, опосредованная рецепцией секретируемых при стрессе глюкокортикоидных гормонов, является «ценой» высокой функциональной пластичности и плейотропности этой лимбической структуры. Общие молекулярно-клеточные механизмы включают нарушения функции глюкокортикоидных рецепторов, нейротрансмиттерных систем, нейротрофических факторов и развитие нейровоспаления, приводящие к нейродегенерации и гибели нейронов гиппокампа. На ряду с этим происходит нарушение нейрогенеза в субгранулярной нейрогенной нише и формирование аберрантных нейронных сетей. Эти глюкокортикоид�зависимые процессы лежат в основе измененной стресс-реактивности и развития ассоциированных с хроническим стрессом коморбидных патологий, в частности височной эпилепсии и депрессивных расстройств.
... However, preclinical, epi demiological, and clinical studies of the association between stress and epilepsy provide rather contradictory results. The data of clinical studies are the most contra dictory; however, the experimental results of preclinical studies mostly confirm that chronic stress exacerbates the manifestations of epilepsy, and, in some cases can cause it [27,28]. The negative impact of depression on the control of convulsive disorders has been documented in various studies [29]. ...
... Analysis of available data suggests that a wide variety of stress factors of different nature, acting in early onto genesis or on adulthood, are epileptogenic and can initi ate the development of epilepsy. These factors can be chronic and act through the course of epileptogenesis and the developed disease, or they can act once, but trigger molecular processes that become the basis for the patho genesis of epilepsy and comorbid depression (these fac tors are discussed in detail in articles [27,37,38]). A patient with developed epilepsy is affected by a complex of chronic stress factors, psychological and physical. ...
... Shared factors of development of epilepsy and comorbid psychopathology (based on the data from[27,29,37,40]). Groups of factors that determine predisposition to epileptogenesis, promote epileptogenesis, and precipitate seizures are indicated. ...
The review discusses molecular and cellular mechanisms common to the temporal lobe epileptogenesis/epilepsy and depressive disorders. Comorbid temporal lobe epilepsy and depression are associated with dysfunction of the hypothalamic-pituitary-adrenocortical axis. Excessive glucocorticoids disrupt the function and impair the structure of the hippocampus, a brain region key to learning, memory, and emotions. Selective vulnerability of the hippocampus to stress, mediated by the reception of glucocorticoid hormones secreted during stress, is the price of the high functional plasticity and pleiotropy of this limbic structure. Common molecular and cellular mechanisms include the dysfunction of glucocorticoid receptors, neurotransmitters, and neurotrophic factors, development of neuroinflammation, leading to neurodegeneration and loss of hippocampal neurons, as well as disturbances in neurogenesis in the subgranular neurogenic niche and formation of aberrant neural networks. These glucocorticoid-dependent processes underlie altered stress response and the development of chronic stress-induced comorbid pathologies, in particular, temporal lobe epilepsy and depressive disorders.
... Other early studies evaluated changes on the electroencephalogram (EEG) in response to stressful verbal stimuli in healthy controls and found that there were subtle EEG changes (narrowing of the bandwidth and regional changes in frequency), but large enough for a blinded reviewer to correctly identify 92% of stress stimuli on EEG [25,26]. Similarly, in epilepsy patients, stressful interviews induced EEG changes (exaggerated spiking, paroxysmal activity, or epileptiform complexes) in the majority [26,27]. ...
... Other early studies evaluated changes on the electroencephalogram (EEG) in response to stressful verbal stimuli in healthy controls and found that there were subtle EEG changes (narrowing of the bandwidth and regional changes in frequency), but large enough for a blinded reviewer to correctly identify 92% of stress stimuli on EEG [25,26]. Similarly, in epilepsy patients, stressful interviews induced EEG changes (exaggerated spiking, paroxysmal activity, or epileptiform complexes) in the majority [26,27]. There was also a case-series of five patients with epilepsy which demonstrated that stress-inducing audio and video recordings could induce seizures [28]. ...
... Other studies that addressed chronic stress or both acute and chronic stress as the seizure precipitant was the Webster article evaluating seizure frequency and major life events in epilepsy [23], Priviteras' evaluations in 2014 and 2015 of patients who self-reported stress-precipitated seizures [16,42], and Moon's case-control cross-sectional study evaluating perceived stress and its predictors in patients with epilepsy [43]. Differences in acute or chronic stress and stress as the precipitating or causative factor has different significance and different neurobiological underpinnings, as explored by Galtrey et al. [26]. Refer to Table 1 for a comprehensive summary of the studies included in this review. ...
Stress is a common and important seizure precipitant reported by epilepsy patients. Studies to date have used different methodologies to identify relationships between epilepsy and stress. Several studies have identified anxiety, depression, and childhood trauma as being more common in patients with epilepsy who report stress as a seizure precipitant compared to patients with epilepsy who did not identify stress as a seizure precipitant. In one survey study it was found that a majority of patients with stress-triggered seizures had used some type of stress reduction method on their own and, of those who tried this, an even larger majority felt that these methods improved their seizures. Additionally, small to moderate sized prospective trials, including randomized clinical trials, using general stress reduction methods have shown promise in improving outcomes in patients with epilepsy, but results on seizure frequency have been inconsistent. Based on these studies, we recommend that when clinicians encounter patients who report stress as a seizure precipitant, these patients should be screened for a treatable mood disorder. Furthermore, although seizure reduction with stress reduction methods has not been proven in a randomized controlled trial, other important endpoints like quality of life were improved. Therefore, recommending stress reduction methods to patients with epilepsy appears to be a reasonable low risk adjunctive to standard treatments. The current review highlights the need for future research to help further clarify biological mechanisms of the stress-seizure relationship and emphasizes the need for larger randomized controlled trials to help develop evidence based treatment recommendations for our epilepsy patients.
... Epilepsy is a health problem that is both a medical problem and a social problem. 12 It is a medical problem because epilepsy is a disease that requires close management and supervision in its treatment, while the psychosocial problems faced by epilepsy sufferers are greater than the medical problems they experience, where epilepsy patients are afraid that throughout their lives they will suffer from epilepsy. They are afraid to drive, afraid to swim, and the most frightening thing is having a seizure in public. ...
... Similarly, postnatal stress induced by separation of pups from their mother renders them more susceptible to later seizures, with kindling and chemoconvulsants. 12 Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological Ika Tristanti / The effect of stress on the epilepsy recurrence disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. ...
Epilepsy is a health problem that is both a medical problem and a social problem. This study aimed to determine the relationship between stress levels and recurrence rates in epilepsy patients at Dr Loekmonohadi Kudus Hospital. This research uses a descriptive correlation type of research, the approach method uses cross-sectional, the population in this study are all epilepsy patients and are registered in the medical record at Dr Loekmonohadi Kudus Regional Hospital in the period August 2023, there are 51 patients with a sample of 45 respondents. The measuring instrument used is the test. Spearman Rank Correlation. The results of the analysis showed a p-value of 0.094 > (α = 0.05). It can be concluded that Ha was rejected and Ho was accepted, so there is no relationship between stress levels and recurrence rates in epilepsy patients at Kudus Hospital in 2023
... Stress is commonly reported as a trigger for seizures in people with epilepsy (C.W. Lai and Trimble, 1997;Galtrey et al., 2016;Kotwas et al., 2017). While a seizure-provoking effect of specific emotion is considered rare (Gastaut and Tassinari, 1966), stress is identified as the most frequent patient-perceived triggering factor (Novakova et al., 2013). ...
... While a seizure-provoking effect of specific emotion is considered rare (Gastaut and Tassinari, 1966), stress is identified as the most frequent patient-perceived triggering factor (Novakova et al., 2013). Several authors have noted the inherent methodological difficulties in studying the stress-seizure relationship, related to difficulties in quantifying stress and tendency to reporting bias (C.W. Lai and Trimble, 1997;Novakova et al., 2013;Galtrey et al., 2016). Perceived triggering of seizures by stress has been particularly noted in patients with TLE, possibly reflecting a mechanistic role for limbic system dysfunction that alters seizure threshold (Reddy et al., 2021), although systematic studies are lacking. ...
Stress has been identified as a major contributor to human disease and is postulated to play a substantial role in epi-leptogenesis. In a significant proportion of individuals with epilepsy, sensitivity to stressful events contributes to dynamic symptomatic burden, notably seizure occurrence and frequency, and presence and severity of psychiatric comorbidities [anxiety, depression, posttraumatic stress disorder (PTSD)]. Here, we review this complex relationship between stress and epilepsy using clinical data and highlight key neurobiological mechanisms including the hypothala-mic-pituitary-adrenal (HPA) axis dysfunction, altered neuroplasticity within limbic system structures, and alterations in neurochemical pathways such as brain-derived neurotrophic factor (BNDF) linking epilepsy and stress. We discuss current clinical management approaches of stress that help optimize seizure control and prevention, as well as psychiatric comorbidities associated with epilepsy. We propose that various shared mechanisms of stress and epilepsy present multiple avenues for the development of new symptomatic and preventative treatments, including disease modifying therapies aimed at reducing epileptogenesis. This would require close collaborations between clinicians and basic scientists to integrate data across multiple scales, from genetics to systems biology, from clinical observations to fundamental mechanistic insights. In future, advances in machine learning approaches and neuromodulation strategies will enable personalized and targeted interventions to manage and ultimately treat stress-related epileptogenesis. Stress contributes to epileptogenesis, to seizure occurrence and to occurrence of psychiatric comorbidities such as anxiety and depression. In this review, we discuss current knowledge of both clinical aspects and neurobiological mechanisms of epilepsy and stress, and identify avenues for further research that could help reduce or prevent epileptogenesis.
... Stress is commonly reported as a trigger for seizures in people with epilepsy (C.W. Lai and Trimble, 1997;Galtrey et al., 2016;Kotwas et al., 2017). While a seizure-provoking effect of specific emotion is considered rare (Gastaut and Tassinari, 1966), stress is identified as the most frequent patient-perceived triggering factor (Novakova et al., 2013). ...
... While a seizure-provoking effect of specific emotion is considered rare (Gastaut and Tassinari, 1966), stress is identified as the most frequent patient-perceived triggering factor (Novakova et al., 2013). Several authors have noted the inherent methodological difficulties in studying the stress-seizure relationship, related to difficulties in quantifying stress and tendency to reporting bias (C.W. Lai and Trimble, 1997;Novakova et al., 2013;Galtrey et al., 2016). Perceived triggering of seizures by stress has been particularly noted in patients with TLE, possibly reflecting a mechanistic role for limbic system dysfunction that alters seizure threshold (Reddy et al., 2021), although systematic studies are lacking. ...
Stress has been identified as a major contributor to human disease and is postulated to play a substantial role in epileptogenesis. In a significant proportion of individuals with epilepsy, sensitivity to stressful events contributes to dynamic symptomatic burden, notably seizure occurrence and frequency, and presence and severity of psychiatric comorbidities [anxiety, depression, posttraumatic stress disorder (PTSD)]. Here, we review this complex relationship between stress and epilepsy using clinical data and highlight key neurobiological mechanisms including the hypothalamic-pituitary-adrenal (HPA) axis dysfunction, altered neuroplasticity within limbic system structures, and alterations in neurochemical pathways such as brain-derived neurotrophic factor (BNDF) linking epilepsy and stress. We discuss current clinical management approaches of stress that help optimize seizure control and prevention, as well as psychiatric comorbidities associated with epilepsy. We propose that various shared mechanisms of stress and epilepsy present multiple avenues for the development of new symptomatic and preventative treatments, including disease modifying therapies aimed at reducing epileptogenesis. This would require close collaborations between clinicians and basic scientists to integrate data across multiple scales, from genetics to systems biology, from clinical observations to fundamental mechanistic insights. In future, advances in machine learning approaches and neuromodulation strategies will enable personalized and targeted interventions to manage and ultimately treat stress-related epileptogenesis.
... We observed a significant increase in stress, depression, and anxiety in the refractory group when compared to the well-controlled group. Perceived stress is a common precipitant in people with epilepsy [37,70]. Alterations in sleep patterns, food intake, and mental attentiveness can lead to adverse mental health outcomes. ...
... Alterations in sleep patterns, food intake, and mental attentiveness can lead to adverse mental health outcomes. These observations suggest that more psychological support and counselling are required for PWE, especially those with refractory epilepsy [70,71]. Further our correlation analyses suggests that an increase in anxiety attacks makes the person more prone to atherosclerosis. ...
Objective:
Comparison of cardiovascular risk factors, atherosclerosis, and psychological distress among adults with refractory versus well-controlled epilepsy.
Methods:
The cross-sectional study consisted of two groups of 40 people each: Group I - People with well-controlled epilepsy, Group II - People with refractory epilepsy. Age- and gender-matched people of 20-50 years were recruited. People who were diabetic, smokers, hypertensive, alcoholic, pregnant, with infections, and lactating women were excluded from the study. Biochemical parameters, fasting glucose, lipid profile, fasting insulin, leptin, adiponectin, Lp[a], hsCRP, TyG INDEX, HOMA1-%S, HOMA1-IR, HOMA1-%B, QUICKI, FIRI, AIP, AC, CLTI, MLTI, CRI-I, CRI-II, and CIMT were estimated. Stress levels [PSS-10, GAD-7 & PHQ-9] were assessed based on the scoring system from the questionnaires.
Results:
The existence of metabolic syndrome, levels of triglycerides, TyG index, MDA, OSI, CIMT, AIP, and stress scores [PSS-10, GAD-7 & PHQ-9] were significantly higher in the refractory-epilepsy group in comparison to the well-controlled group. There were associations between LDL -C and CIMT as well as between GAD-7 and CIMT among all the study subjects. There were no significant differences in the levels of glucose homeostasis parameters, hsCRP, leptin, adiponectin, and Lp[a] between the two groups. Based on the ROC analysis, MDA [AUC = 0.853] and GAD-7 [AUC = 0.900] are useful in the differential diagnosis of the study groups.
Conclusion:
People with refractory epilepsy had increased levels of vascular risk factors, atherosclerosis, and stress levels compared to people with well-controlled epilepsy. Suitable disease management and therapeutic approaches to address cardiovascular and psychological distress could be planned out among people with refractory epilepsy to improve their quality of life.
... Stress is known to activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of corticotrophin-releasing hormone (CRH), adrenocorticotropic-releasing hormone (ACTH), and glucocorticoids like corticosterone [45]. Stress can often be a trigger for seizures in epilepsy [46,47], and exacerbates the severity and frequency of those seizures [47]. Indeed, activation of the HPA axis has been linked as a mechanism underlying limbic system seizures [48,49]. ...
... Previous studies [36] in mice that modeled neither epilepsy nor depression showed a decrease in exploratory novel environment responses following acute stress, suggesting that a low level of stress due to uncertainty may be adaptive, but larger levels of stress may blunt these information gathering or sensation seeking efforts. However, given that stress can exacerbate both epilepsy-and depression-related behaviors [46,47,[50][51][52], we predicted that it would also exacerbate responses to novel environment in the presence of this comorbidity. Unexpectedly, SwLo and SwHi rats showed no change in entries or rearing behavior in either area of the Open Field Test following restraint stress. ...
A bidirectional comorbidity exists between depression and epilepsy such that patients with epilepsy are at higher risk for developing depression, and vice versa. Each of these conditions individually can be complicated by behavioral effects that worsen quality of life, but less is known about these interactions within the comorbidity of depression and epilepsy. The SwLo rat has been selectively bred for depression-relevant behaviors and exhibits enhanced limbic seizure susceptibility. This study sought to characterize the effects of novelty and stress on the SwLo rodent model of this comorbidity. It was hypothesized that SwLo rats would exhibit altered responses to novelty, reflected in hyperactivity-, anxiety-, sensation seeking-, and/or compulsive behaviors, and that this would be exacerbated with stress.
Compared to the SwHi rat (their depression- and epilepsy-resistant counterparts), SwLo rats showed increased entries in all areas of the Open Field Test and spent significantly more time in the light compartment of the Light-Dark Box. SwLo rats also had a significantly higher number of rearing behaviors in the inner squares of the Open Field Test, the closed arms of the Elevated Plus Maze, and both areas of the Light-Dark Box. They demonstrated increased Nestlet shredding but showed no difference in a marble burying task or in latency to consume food in a novelty suppressed feeding task. Interestingly, restraint stress showed little effect on these behaviors, despite increasing corticosterone levels.
Combined, these results suggest an increase in exploratory sensation seeking and hypervigilant information-gathering behaviors in the SwLo rat that are not dependent on corticosterone levels. This shows the utility of this model for studying behavioral effects of comorbid depression and epilepsy and allows for their use in identifying underlying mechanisms or screening treatment strategies for this complex comorbidity.
... Unpredictable seizures make many normal activities, like driving a car or holding down certain jobs, impossible [2]. Stress is repeatedly reported as one of the most common seizure triggers in patients with an epilepsy diagnosis, including TLE [3][4][5][6][7][8][9]. Understanding the molecular mechanisms underlying this association may allow clinicians to predict seizure episodes and/or mitigate their disruptive effect. ...
... In a similar manner, under stressful situations, hyper-secretion of glucocorticoids and other stress hormones may contribute to reductions in seizure threshold and increased neuronal excitability in TLE. Enhanced excitability may provide a potential mechanism underlying the propensity for TLE patients to identify stress as a common seizure trigger [9]. In fact, in some patients, evoking an emotional stressful response (i.e. using audio and video recordings) is sufficient to trigger spontaneous seizures [163]. ...
Epilepsy is a common neurological disease, affecting 2.4 million people in the US. Among the many different forms of the disease, temporal lobe epilepsy (TLE) is one of the most frequent in adults. Recent studies indicate the presence of a hyperactive hypothalamopituitary- adrenocortical (HPA) axis and elevated levels of glucocorticoids in TLE patients. Moreover, in these patients, stress is a commonly reported trigger of seizures, and stress-related psychopathologies, including depression and anxiety, are highly prevalent. Elevated glucocorticoids have been implicated in the development of stress-related psychopathologies. Similarly, excess glucocorticoids have been found to increase neuronal excitability, epileptiform activity and seizure susceptibility. Thus, patients with TLE may generate abnormal stress responses that both facilitate ictal discharges and increase vulnerability for the development of comorbid psychopathologies. Here, we will examine the evidence that the HPA axis is disrupted in TLE, consider potential mechanisms by which this might occur, and discuss the implications of HPA dysfunction for seizuretriggering and psychiatric comorbidities.
... A stressed and depressive brain is more prone to epileptic seizures with high seizure intensity and frequency. All these findings correlate with already reported data (Espinosa-Garcia et al., 2021;Sawyer and Escayg, 2010;Galtrey et al., 2016). Reduction in cortisol concentration after chrysophanol treatment points towards the therapeutic effect of chrysophanol in the reduction of stress. ...
Background
Stress is among the most common comorbid conditions with epilepsy and a strong factor in the pathophysiology of seizures. An imbalance in neuronal circuits causes recurrent unprovoked seizures in epilepsy. Dysregulation of BDNF/VEGF expression, oxidative stress, increased levels of neuroinflammatory cytokines, and increased expression of apoptotic genes contribute to the underlying cause of the seizure.
Objectives
Chrysophanol, an anthraquinone, has broad-spectrum therapeutic potential. This study evaluated the neuroprotective effect of chrysophanol with underlying pathways in PTZ-induced epilepsy with stress as a comorbid condition.
Methods
Male mice were given 35 mg/kg of PTZ every other day to induce seizures. In addition, they were exposed to 120 min of daily restraint stress for 21 days to induce stress. Chrysophanol (0.1, 1, 10 mg/kg) was administered to the mice 30 min before the PTZ in the acute study. The most effective dose (10 mg/kg) was proceeded for the chronic epilepsy model. Following this, various tests were conducted, including behavioral assessments for memory impairment and stress, analysis of antioxidant levels, histopathological and immunohistochemistry examinations, measurement of cortisol levels using ELISA, and gene expression analysis using RT-PCR.
Results
Chrysophanol demonstrated a notable decrease in both the intensity and frequency of seizures. Additionally, it effectively boosted the levels of important antioxidants such as GSH, GST, and CAT, while simultaneously reducing the levels of MDA and Nitric oxide. The histopathological analysis also showed improvement in overall morphology and survival of neurons. Chrysophanol treatment effectively showed an increase in the expression of BCL-2, and Nrf-2 with a decrease in BAX expression confirmed by immunohistochemistry. Dysregulation of vascular permeability factor, production of inflammatory cytokines, and apoptotic gene expression was successfully reversed after chrysophanol treatment analyzed through RT-PCR. Cortisol concentration was decreased in treatment groups analyzed through Enzyme-linked immunoassay. Molecular docking of chrysophanol with different proteins declared the binding affinity of the ligands with the target sites of proteins.
Conclusion
In conclusion, chrysophanol demonstrated remarkable neuroprotective and antiepileptic effects at a dose of 10 mg/kg in stress-exacerbated PTZ-induced epilepsy following the TLR4/NFκB -Nrf2/HO-1 and BDNF/VEGF pathways.
... A global survey carried out by the WHO showed that 50 million people are affected by epilepsy (2) and 90% of them are found in low-income countries (3). Many studies have shown that epileptic patients significantly experience higher levels of psychiatric and psychological comorbidity (3)(4)(5)(6). Various studies have shown that the common comorbid psychiatric disorders reported could increase awareness of the comorbidity of mental illness with chronic health problems including epilepsy. Finally, the study could offer a direction to establish holistic treatment approaches in addition to the existing neurological services. ...
Introduction: Stress is a common psychological problem present in people with epilepsy and has a serious impact on the health-related satisfaction of people with epilepsy and their cohabiters. This study aimed to assess the magnitude and related factors of stress. Methods: A hospital-based cross-sectional study was carried out among 301 systematically chosen people with epilepsy. The seven stress-related items of the Depression, Anxiety, and Stress-21 questionnaire was used to measure stress. Data were entered using Epi Info and analyzed by SPSS version 25. Predictors with a p-value < 0.20 in the bivariate logistic regression were transferred into the multivariate model. A p-value of less than 0.05 was viewed as statistically significant. Result: The prevalence of stress symptoms in this study was 23.9%. Daily labor occupational status with Adjusted Odds ratio [(AOR) = 0.042, 95% CI: 0.004, 0.469], onset of illness at the age of 18 years and above (AOR = 0.188, 95% CI: 0.046, 0.771), perceived stigma (AOR = 3.320, 95% CI: 1.345, 8.200), the presence of anxiety symptoms (AOR = 8.275, 95% CI: 3.345, 20.471), and belief that the condition is untreatable (AOR = 6.360, 95% CI: 1.647, 24.562) were significantly associated factors. Conclusion: The occurrence of stress was high, and it reinforced that there is a requisite for the identification and handling of stress-related symptoms among people with epilepsy.
... A global survey carried out by the WHO showed that 50 million people are affected by epilepsy (2) and 90% of them are found in low-income countries (3). Many studies have shown that epileptic patients significantly experience higher levels of psychiatric and psychological comorbidity (3)(4)(5)(6). Various studies have shown that the common comorbid psychiatric disorders reported could increase awareness of the comorbidity of mental illness with chronic health problems including epilepsy. Finally, the study could offer a direction to establish holistic treatment approaches in addition to the existing neurological services. ...
Introduction
Stress is a common psychological problem present in people with epilepsy and has a serious impact on the health-related satisfaction of people with epilepsy and their cohabiters. This study aimed to assess the magnitude and related factors of stress.
Methods
A hospital-based cross-sectional study was carried out among 301 systematically chosen people with epilepsy. The seven stress-related items of the Depression, Anxiety, and Stress -21 questionnaire was used to measure stress. Data were entered using Epi Info and analyzed by SPSS version 25. Predictors with a p-value < 0.20 in the bivariate logistic regression were transferred into the multivariate model. A p-value of less than 0.05 was viewed as statistically significant.
Result
The prevalence of stress symptoms in this study was 23.9%. Daily labor occupational status with Adjusted Odds ratio [(AOR) = 0.042, 95% CI: 0.004, 0.469], onset of illness at the age of 18 years and above (AOR = 0.188, 95% CI: 0.046, 0.771), perceived stigma (AOR = 3.320, 95% CI: 1.345, 8.200), the presence of anxiety symptoms (AOR = 8.275, 95% CI: 3.345, 20.471), and belief that the condition is untreatable (AOR = 6.360, 95% CI: 1.647, 24.562) were significantly associated factors.
Conclusion
The occurrence of stress was high, and it reinforced that there is a requisite for the identification and handling of stress-related symptoms among people with epilepsy.
... In addition, the reduction of psychological stress after the intracranial foreign body was removed from the patient in this case may have contributed to the control of PTE also. As some studies have concluded that psychological stress is an important trigger and sometimes the cause of seizures 8) . However, the relationship between changes in psychological factors and the progression of PTE still needs to be confirmed by further clinical studies. ...
Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.
... It is also worth noting that migraine and epilepsy are often found to be comorbid (63), and changes in cerebellar output have been shown to be capable of initiating or aborting seizures in several animal models (64,65). Given the episodic nature of many forms of epilepsy and the prominent role of stress in triggering them (66), the role of the adrenergic pathway described here in triggering seizures merits further scrutiny. ...
Stress is the most common trigger among episodic neurologic disorders. In episodic ataxia type 2 (EA2), physical or emotional stress causes episodes of severe motor dysfunction that manifest as ataxia and dystonia. We used the tottering (tg/tg) mouse, a faithful animal model of EA2, to dissect the mechanisms underlying stress-induced motor attacks. We find that in response to acute stress, activation of α1-adrenergic receptors (α1-Rs) on Purkinje cells by norepinephrine leads to their erratic firing and consequently motor attacks. We show that norepinephrine induces erratic firing of Purkinje cells by disrupting their spontaneous intrinsic pacemaking via a casein kinase 2 (CK2)-dependent signaling pathway, which likely reduces the activity of calcium-dependent potassium channels. Moreover, we report that disruption of this signaling cascade at a number of nodes prevents stress-induced attacks in the tottering mouse. Together, our results suggest that norepinephrine and CK2 are required for the initiation of stress-induced attacks in EA2 and provide previously unidentified targets for therapeutic intervention.
... In this regard, chronic stress can result in the development or diagnosis of epilepsy. Several studies stated that fatigue, sleep deprivation, stress accompanying insomnia, and stress itself are among the independent factors that lead to epileptic seizures (23). Stress as a defense mechanism, if severe, can lead to changes in hormonal balance, reduce sexual activity, and lead to poor sexual function (11). ...
Epilepsy is one of the problems and diseases that accompanies a person for the rest of his/her life after diagnosis. This disease can severely affect a person’s physical condition and lead to psychological problems. Many patients with epilepsy suffer from psychological problems and are under the supervision of a psychiatrist, and they take medications to control the mental state. However, many patients are reluctant to take other medications, including psychiatric medications, due to long-term use of the drug. Therefore, in this study, we examined nonpharmacological treatments for psychological problems caused by epilepsy. In addition to developing epilepsy and receiving medications for the disease, these patients develop mental illnesses such as stress, depression, anxiety, and cognitive processes that require treatment. After searching for texts published in various English language databases, the required items were obtained. First, some of the psychosocial consequences of epilepsy, including negative attitude towards epilepsy, social stigma, family factors, quality of life, and sexual activity, were evaluated. Furthermore, the concurrency of psychological disorders (stress, depression, anxiety, cognitive processes, and theory of mind) along with non-pharmacological treatments were investigated.
... These effects include enhancing the permeability of the BBB, increasing central and peripheral inflammatory cytokines, and activating microglia (Kelly et al. 2015). Chronic stress can also lead to the dysfunction of the HPA-A, which is associated with the morbidity and progression of epilepsy (Galtrey et al. 2016;Kotwas et al. 2017;Mazarati et al. 2009;Zobel et al. 2004). In addition, a bidirectional connection between chronic stress and inflammation could activate neuroinflammatory responses, in turn further inducing HPA-A dysregulation (Gaillard 2001). ...
Honoured as the second genome in humans, the gut microbiota is involved in a constellation of physiological and pathological processes, including those related to the central nervous system. The communication between the gut microbiota and the brain is realized by a complex bidirectional connection, known as the "microbiota-gut-brain axis", via neuroendocrine, immunological, and direct neural mechanisms. Recent studies indicate that gut dysfunction/dysbiosis is presumably involved in the pathogenesis of and susceptibility to epilepsy. In addition, the reconstruction of the intestinal microbiome through, for example, faecal microbiota transplantation, probiotic intervention, and a ketogenic diet, has exhibited beneficial effects on drug-resistant epilepsy. The purposes of this review are to provide a brief overview of the microbiota–gut–brain axis and to synthesize what is known about the involvement of the gut microbiota in the pathogenesis and treatment of epilepsy, to bring new insight into the pathophysiology of epilepsy and to present a preliminary discussion of novel therapeutic options for epilepsy based on the gut microbiota.
... Since humans differ in their response to stressful life events depending on duration, intensity, and type of stressor, accurate stress measurements in the clinic are complex [7]. Animal studies have shown that exposure to acute stressors in most cases, protect against seizures; while exposure to chronic stressors increases seizure risk and frequency contributing to enhanced anxiety behavior or a depressive state [8][9][10][11]. Depression is the most frequent psychiatric comorbidity with epilepsy, affecting up to 62% of people with epilepsy, but remains underrecognized and undertreated [12][13][14][15]. Very recent reports from the National Institute of Neurological Disorders and Stroke/American Epilepsy Society (NINDS/AES) Committee [16] and the International League Against Epilepsy (ILAE) Psychology Task Force [17] have emphasized the need for a better understanding of psychiatric comorbidities to improve epilepsy management and quality of patient life. ...
Epilepsy, one of the most common neurological disorders worldwide, is characterized by recurrent seizures and subsequent brain damage. Despite strong evidence supporting a deleterious impact on seizure occurrence and outcome severity, stress is an overlooked component in people with epilepsy. With regard to stressor duration and timing, acute stress can be protective in epileptogenesis, while chronic stress often promotes seizure occurrence in epilepsy patients. Preclinical research suggests that chronic stress promotes neuroinflammation and leads to a depressive state. Depression is the most common psychiatric comorbidity in people with epilepsy, resulting in a poor quality of life. Here, we summarize studies investigating acute and chronic stress as a seizure trigger and an important factor that worsens epilepsy outcomes and psychiatric comorbidities. Mechanistic insight into the impact of stress on epilepsy may create a window of opportunity for future interventions targeting neuroinflammation-related disorders.
... While the incidence of stroke remained unchanged, presentations with epileptic seizures halved, possibly from lower stress and fewer external stimuli such as flashing lights and alcohol intoxication. 45 Overnight admissions with acute headache fell considerably, and perceived non-organic (functional) neurological disorders did not occur during the 2020 period. In parallel, our emergency department observed an 86% reduction in inappropriate attendances (Richards AJ, personal communication). ...
Large reductions in emergency department attendances and hospitalisations with non-COVID acute medical illness early during the pandemic were attributed to reluctance to seek medical help and higher referral thresholds. Here, we compare acute medical admissions with a comparison cohort from 2017. Deaths in the same geographic area were examined, and Wales-wide deaths during these 4 weeks in 2020 were compared with a seasonally matched period in 2019. There were 528 patients admitted with non-COVID illness in 2020, versus 924 in 2017 (a reduction of 43%). Deaths from non-COVID causes increased by 10.9% compared with 2017, over half this rise being from neurological causes including stroke and dementia. While far fewer patients required hospitalisation as medical emergencies, rises in local non-COVID deaths proved small. Wales-wide non-COVID deaths rose by just 1% compared with 2019. The findings suggest that changes in population behaviour and lifestyle during lockdown brought about unforeseen health benefits.
... Indeed, stress has been repeatedly identified as the most common trigger experienced prior to seizure initiation (Galtrey, Mula, & Cock, 2016;McKee & Privitera, 2017). However, much remains to be learned about the timing, duration, and nature of stress and its effects on epilepsy. ...
Epilepsy and stress are each significant concerns in today’s society, bearing heavy impacts on mental and physical health and overall quality of life. Unfortunately, the intersection between these is potentially even more concerning, as stress is a frequent trigger of seizures and may contribute to neural hyperexcitability. A growing body of research suggests a connection between early life stress (occurring in the prenatal or postnatal stage) and later development of epilepsy. While the larger part of this literature suggests that early life stress increases vulnerability for epilepsy development, there are a number of interacting factors influencing this relationship. These factors include developmental stage at which both stressor and seizure assessment occur, type of stressor, sex effects, and type of seizure (convulsive or non-convulsive). Additionally, a number of potential mechanisms have been identified, including activation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, altered inhibitory/excitatory balance, and temporal lobe structures. Developing a clearer understanding of this relationship between early life stress and epilepsy, the factors that influence it, and underlying mechanisms that may serve as targets for intervention is crucial to improving quality of life for persons with epilepsy.
... Identifying and managing depressive and anxiety disorders and stress has been highlighted as a crucial issue in patients with epilepsy (PWE), with a need to individualize treatment according to individual patient profiles [6]. In the present article we aim to present an overview of current knowledge of stress and epilepsy and then focus on the various health psychology tools available for characterizing patient profiles of depression, anxiety and stress and their capacity to cope with these. ...
The prevalence of psychological distress, especially depressive and anxiety disorders, is higher in epilepsy than in other chronic health conditions. These comorbid conditions contribute even more than epileptic seizures themselves to impaired quality of life in patients with epilepsy (PWE). The link between these comorbidities and epilepsy appears to have a neurobiological basis, which is at least partly mediated by stress through psychological and pathophysiological pathways. The impact of stress in PWE is also particularly important because it is the most frequently reported seizure trigger. It is therefore crucial for clinicians to take stress-related conditions and psychiatric comorbidities into account when managing PWE and to propose clinical support to enhance self-control of stress. Screening tools have been specially designed and validated in PWE for depressive disorders and anxiety disorders (e.g. NDDI-E, GAD-7). Other instruments are useful for measuring stress-related variables (e.g. SRRS, PSS, SCS, MHLCS, DSR-15, ERP-R, QOLIE-31) in order to help characterize the individual "stress profile" and thus orientate patients towards the most appropriate treatment. Management includes both pharmacological treatment and nonpharmacological methods for enhancing self-management of stress (e.g. mindfulness-based therapies, yoga, cognitive-behavioral therapies, biofeedback), which may not only protect against psychiatric comorbidities but also reduce seizure frequency.
... Например, ЧМТ может стать не только причиной развития эпилепсии, но и источником психологического дистресса, и как следствие привести к развитию посттравматического стрессового расстройства и ПП. С другой стороны, стресс может усугублять течение не только ПП, но и эпилепсии [60,61]. ...
A review of publications over the last two decades is presented. Psychogenic paroxysms develop in approximately 12% of patients with epilepsy. The analysis of social and demographic data, history details, semiological features and results of electrophysiological and neuroimaging studies does not unequivocally support the comorbidity of epilepsy and psychogenic paroxysms. The pathogenetic mechanisms of the development of comorbidity are various and depend on the presence of pharmacoresistance, psychological traumas in the past, intellectual disability etc. Video-EEG-monitoring is the gold standard in the diagnosis of comorbidity of epilepsy and psychogenic paroxysms. Treatment of such cases includes anticonvulsants and cognitive-behavioral therapy.
... Stress is associated with activation of the sympathetic adrenergic pathway of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis and is a commonly reported seizure trigger in people with epilepsy [12]. The relationship between catecholamines and seizures remains incompletely understood. ...
We describe the case of a 35-year-old man with focal epilepsy since age 16. Due to a refractory course, several treatments were tried over the years, including insertion of a deep brain stimulator. At the time of his first assessment at our unit, he had recently been diagnosed with hypertension. An MR scan of brain revealed multiple T2 hyperintense white matter lesions, and evidence of previous haemorrhage in the left basal ganglia and pons. On follow-up imaging, the changes were considered to be in keeping with hypertensive arteriopathy. He was referred for further assessment of his hypertension and was found to have a para-aortic paraganglioma. This was excised 16 months after his initial presentation to us. The surgery was associated with an improvement in his seizure control. This case serves as a reminder of the need to be vigilant about the possibility of coexisting conditions in people with epilepsy.
... For instance, mild traumatic brain injury is a risk factor for the development of not only epilepsy but also posttraumatic stress disorder and PNES [127]. On the other hand, although stress and adverse experience are considered established risk factors for the development of PNES in some individuals, they can also contribute to the development/exacerbation of epilepsy [128,129]. ...
Comorbid epilepsy and psychogenic nonepileptic seizures (PNES) represent a serious challenge for the clinicians. However, the frequency, associations, and outcomes of dual diagnosis of epilepsy and PNES are unclear. The aim of the review was to determine the frequency, correlates, and outcomes of a dual diagnosis. A systematic review of all published observational studies (from inception to Dec. 2016) was conducted to determine the frequency, correlates, and outcomes of dual diagnosis. We included studies of individuals of any age reporting a dual diagnosis of epilepsy and PNES. All observational study designs were included with the exception of case reports and case series with fewer than 10 participants. The mean frequency of epilepsy in patients with PNES across all studies was 22% (95% confidence intervals [CI] 20 to 25%, range: 0% to 90%) while the mean frequency of PNES in patients with epilepsy was 12% (95% CI 10 to 14%, range: 1% to 62%). High heterogeneity means that these pooled estimates should be viewed with caution. A number of correlates of dual diagnosis were reported. Some studies delineated differences in semiology of seizures in patients with dual diagnosis vs. PNES or epilepsy only. However, most of the correlates were inconclusive. Only a few studies examined outcome in patients with dual diagnosis. Dual diagnosis is common in clinical practice, especially among patients referred to specialized services, and requires careful diagnosis and management.
... However, the results of controlled studies examining the role of stress in triggering seizures in human are controversial. Possible explanations for the reported inconsistent results include lack of objective measures of stress, various inducers of stress, different intensities of stress and the length of period of exposure to stress [7]. As a subjective experience, exposure to the same stressful condition may induce different amount of stress in different persons, thus contributing to the inconsistent results. ...
Purpose:
A period of military conflict is characterized by high level of stress. In this study, we examined the seizure frequency in a civilian population of patients with seizures during a period of military conflict.
Methods:
This retrospective study investigated seizure frequency in patients with seizures seen at the epilepsy clinic of Barzilai Medical Center during the summer of 2014 when the military operation "Protective Edge" between Israel and Gaza took place. Data collected included age, gender, type of seizures, diagnosis, medications, geographic area of living, medical history, imaging, EEG findings and seizure frequency before, during and after the period of conflict. The study was approved by the local Institutional Review Board.
Results:
Sixty-three (35 men, 55%) patients were included in the study. No significant change in seizure frequency was seen in most patients Mean frequency of seizures was one/3 months during the military operation, not significantly different from seizure frequency before and after the period of conflict. Demographic data, disease duration, findings on MRI or EEG, drug therapy or distance from the Gaza Strip were not associated with change in seizure frequency. However, an increased seizure frequency during the period of military conflict was found in patients with Psychogenic Non-Epileptic Seizures (PNES) compared with patients with epileptic seizures (p = 0.04, Fisher's exact test).
Conclusion:
Our study did not show any significant change in seizure frequency during a period of military conflict in most of patients with epilepsy. However, the frequency of spells increased in patients with PNES during this period.
... The dysregulation of hypothalamo-pituitary-adrenocortical axis (HPA-A), which is hallmark of chronic stress, is associated with epilepsy and facilitates epileptic process [18][19][20][21] . There exists bidirectional connection between chronic stress and inflammation, whereby stress activates inflammatory responses, and conversely inflammation induces HPA-A dysregulation 22 . ...
There has been growing interest in the role of intestinal microbiome in brain disorders. We examined whether dysbiosis can predispose to epilepsy. The study was performed in female and male Sprague‐Dawley rats. To induce dysbiosis, the rats were subjected to chronic restraint stress (two 2‐hour long sessions per day, over two weeks). Cecal content from stressed and sham‐stressed donors was transplanted via oral gavage to recipients, in which commensal microbiota had been depleted by the antibiotics. The study included the following groups: (i) Sham stress, no microbiota transplant; (ii) Stress, no microbiota transplant; (iii) Sham‐stressed recipients transplanted with microbiota from sham‐stressed donors; (iv) Stressed recipients transplanted with microbiota from sham‐stressed donors; (v) Sham‐stressed recipients transplanted with microbiota from stressed donors; (vi) Stressed recipients transplanted with microbiota from stressed donors. After microbiota transplant, all animals were subjected to kindling of basolateral amygdala. Both chronic stress and microbiome transplanted from stressed to sham‐stressed subjects accelerated the progression, and prolonged the duration of kindled seizures. Microbiome from sham‐stressed animals transplanted to chronically stressed rats, counteracted pro‐epileptic effects of restraint stress. These findings directly implicate perturbations in the gut microbiome, particularly those associated with chronic stress, in the increased susceptibility to epilepsy.
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... L'association avec la psychose est également surprenante; la prévalence de la psychose interictale chez les épileptiques est estimée à 19.4% dans les épilepsies généralisées et à 15.2% dans l'épilepsie du lobe temporal [254]. Il est indispensable de dépister ces comorbidités chez les patients épileptiques au moyen d'échelles standardisées et de questionnaires validés afin d'améliorer et de personnaliser la prise en charge de ces malades [255][256][257][258][259][260]. ...
L’existence d’une composante génétique dans l’épilepsie est connue depuis des années grâce aux études épidémiologiques de concordance entre jumeaux et d’agrégation familiale, qui fournissent des preuves convaincantes pour l'héritabilité de l'épilepsie. En dépit des avancées majeures des techniques d’exploration pangénomique, les épilepsies génétiques n’ont pas encore livré tous leurs secrets. Cette étude avait pour objectifs de caractériser des variants génétiques de vulnérabilité à l’épilepsie, d’étudier les modes de transmission et d’analyser les relations génotype/phénotype chez des familles Algériennes.Il s’agit d’une étude prospective menée au service de Neurologie du CHU d’Oran sur une période de 05 ans. Des familles multigénérationnelles comportant chacune au moins deux individus épileptiques ont participé à l’étude. Les analyses génétiques réalisées consistaient en un séquençage exomique de nouvelle génération, la technique de Southern Blot, et la recherche de variations du nombre de copies d’ADN (CNV) par la technique de CGH-array. Parmi les quarante familles ayant participé à l’étude, six ont bénéficié d’études génétiques. Ces études ont permis d’identifier une mutation de novo (p.A39E) dans le gène GAL codant pour le neuropeptide galanine chez des jumeaux monozygotes atteints d’épilepsie du lobe temporal (ELT). Le rôle du peptide Galanine dans la régulation du processus d’épileptogénèse a été démontré il y a plus de deux décennies sur des modèles animaux, mais à ce jour, aucune mutation GAL en rapport avec un phénotype épileptique n’avait été décrite chez l’Homme. Nous avons complété l’étude génétique par des analyses in silico qui ont confirmé l’hypothèse de causalité de la mutation identifiée, et corrélé le génotype au phénotype dans cette famille. Nos résultats pourraient avoir des retombées directes sur le développement de molécules antiépileptiques à base de galanine et de traitements par thérapie génique. Nous avons analysé une deuxième famille au phénotype d’ELT et comorbidités psychiatriques. Le séquençage exomique a mis en évidence un variant (rs55689103) du gène RELN déjà incriminé dans l’épilepsie et la schizophrénie. Nous avons identifié deux autres familles au phénotype d’épilepsie myoclonique progressive de type 1. L’étude génétique par Southern Blot a confirmé l’expansion du dodécamère CCCCGCCCCGCG dans le gène EPM1. Par ailleurs, deux autres familles ont été analysées par CGH-array, mais aucun CNV pathogène n’a été identifié par cette technique. L’étude d’autres familles multigénérationnelles permettrait d'identifier de nouveaux variants génétiques des épilepsies.
... Identifying and managing depressive and anxiety disorders and stress has been highlighted as a crucial issue in patients with epilepsy (PWE), with a need to individualize treatment according to individual patient profiles [6]. In the present article we aim to present an overview of current knowledge of stress and epilepsy and then focus on the various health psychology tools available for characterizing patient profiles of depression, anxiety and stress and their capacity to cope with these. ...
The prevalence of psychological distress, especially depressive and anxiety disorders, is higher in epilepsy than in other chronic health conditions. These comorbid conditions contribute even more than epileptic seizures themselves to impaired quality of life in patients with epilepsy (PWE). The link between these comorbidities and epilepsy appears to have a neurobiological basis, which is at least partly mediated by stress through psychological and pathophysiological pathways. The impact of stress in PWE is also particularly important because it is the most frequently reported seizure trigger. It is therefore crucial for clinicians to take stress-related conditions and psychiatric comorbidities into account when managing PWE and to propose clinical support to enhance self-control of stress. Screening tools have been specially designed and validated in PWE for depressive disorders and anxiety disorders (e.g. NDDI-E, GAD-7). Other instruments are useful for measuring stress-related variables (e.g. SRRS, PSS, SCS, MHLCS, DSR-15, ERP-R, QOLIE-31) in order to help characterize the individual “stress profile” and thus orientate patients towards the most appropriate treatment. Management includes both pharmacological treatment and nonpharmacological methods for enhancing self-management of stress (e.g. mindfulness-based therapies, yoga, cognitive-behavioral therapies, biofeedback), which may not only protect against psychiatric comorbidities but also reduce seizure frequency.
... The link between stress and epilepsy remained quite controversial for a long time. There is now a substantial body of preclinical evidence suggesting that chronic stress can worsen seizures in established epilepsy and, in selected cases, may even be a causal factor in epilepsy [17]. The paper by Gelisse is definitely along these lines and further confirms the need for healthcare professionals working with people with epilepsy to pay more attention to stress in clinical practice. ...
Aim: The present study was performed to investigate the associations among perceived stress, spiritual well-being, and alexithymia in people with epilepsy.
Method: The study was performed with 140 patients diagnosed with epilepsy in the neurology clinic of a training and research hospital between May and December 2022. Personal Information Form, Perceived Stress Scale (PSS-14), Spiritual Well-Being Scale (FACIT Sp-12), and Toronto Alexithymia Scale (TAS-20) were used to collect the data. Descriptive statistical methods, simple and multiple regression analyses, and path analysis were used to analyze the data.
Results: The mean scores of the patients were 25.51±9.42 for PSS-14, 29.77±8.33 for FACIT Sp-12, and 56.55±16.87 for TAS-20. Concerning direct effects, a negative association was found between perceived stress and spiritual well-being, a positive association between perceived stress and alexithymia, and a negative association between spiritual well-being and alexithymia. The confirmed mediating effect was the role of spiritual well-being in the association between perceived stress and alexithymia. Perceived stress explained 28 % of spiritual well-being. In addition, the model explained 34 % of alexithymia in total.
Conclusion: Perceived stress levels of people with epilepsy were low, while alexithymia and spiritual well-being levels were found to be moderate. It was found that as the stress levels perceived by people with epilepsy increased, alexithymia levels also increased. It was also found that the negative impact of perceived stress on alexithymia was reduced through spiritual well-being. The study shows how important spiritual well-being is in decreasing the negative impacts of perceived stress on alexithymia in people with epilepsy.
Background
Patient stress is often overlooked in the care of patients with neurological problems. Nursing theorists have previously heralded stress assessment through conceptual clarification, while clinical nurses in the health care system hold an ideal position for implementation of assessment and coordination of support. Integrated with a hospital assessment and support scheme, recognition of stress as a target of systematic assessment can lead to improved clinical outcomes.
Objective
The aim of the study was to describe and compare patient-reported outcome measures suitable for assessment of the stress response as symptoms in neurological patients.
Design
This study is an integrative review and concept development of patient stress based on qualitative and quantitative analysis of available self-reporting instruments.
Methods
Instruments were retreived with a systematic search from PubMed, CINAHL, PsychINFO and Web of Science reference databases on August 2, 2021. Search terms associated with the concept of stress symptoms were used. Instrument inclusion was done with the guidance of authoritative symptom inventories, with partial confirmation by a second author to mitigate bias. In the analysis, the instruments included in the review were quantitatively described and compared. Insights from the instrument composition led to clarification of our concept of stress response to further refine the list of instruments suitable for self-assessment of the stress status. This study was not registered.
Results
Based on the inclusion criteria, 23 patient-reported outcome measures extending over a variety of stress concepts were included. The similarity of items among the instruments implied a symptom cluster delineated by 59 common symptom subclasses that were grouped together in a re-classification of instrument items. A comparative quantitative analysis prompted us to distinguish the concept of stress response from antecedent, consequent, and related concepts as a manifestation of mental, somatic, and behavioral domains. Ten instruments with items covering the three domains, each with unique qualities regarding number of items, measured spread, and letter count were described.
Conclusions
Within an organizational framework, effective allotment among types of support can be founded on the patient's stress status and the stressors. The stress status manifests itself as a set of measurable symptoms. Optimal instruments for use in systematic clinical assessment of neurological patients’ stress status should satisfy the suggested specification of the stress response with a minimal number of items and concise wording. Finding and including the relevant instruments for analysis were the main limitation of the study.
Tweetable abstract
Stress of neurological patients needs to be assessed and addressed. We ranked 10 suitable instruments that can be useful in the assessment.
Objective:
The Coronavirus disease 2019 (COVID-19) pandemic profoundly affected people worldwide, but little is known about how it impacted people with epilepsy (PWE). We examined the associations between COVID-19 stressors and health outcomes including increases in other health symptoms and fear of seizure among PWE.
Methods:
This cross-sectional study used data from an online survey that asked about demographic characteristics, health conditions, and potential life stressors during COVID-19. Data were collected from October 30 to December 8, 2020. COVID-19 stressors were anger, anxiety, stress, healthcare access, fear of seeking healthcare, social isolation, sense of control over their lives, and alcohol consumption. A binary variable was created for each of these measures to indicate whether PWEs experienced a negative change versus a neutral or positive change. We used multivariable logistic regression to assess the associations of COVID-19 stressors with primary outcomes: exacerbated co-occurring health conditions and increasing fear of seizure during the pandemic.
Results:
Of the 260 PWE included in the study, 165 (63.5%) were women; the average age was 38.7 years. During the survey administration period, 79 (30.3%) of the respondents reported exacerbated co-occurring health conditions, and 94 (36.2%) reported an increased fear of seizures. Regression results indicated that the fear of seeking healthcare during COVID-19 was associated with both exacerbated co-occurring health conditions (aOR 1.12; 95%CI 1.01-1.26) and increasing fear of seizure (aOR 2.31; 95%CI 1.14-4.68). Social isolation was associated with exacerbated co-occurring health conditions during COVID-19 (aOR 1.14; 95%CI 1.01-1.29). Reduced access to physical healthcare was associated with increasing fear of seizure (aOR 2.58; 95%CI 1.15-5.78).
Conclusion:
A considerable number of PWE experienced more symptoms of existing health conditions and fear of seizure during the initial year of the pandemic (2020). Fear of seeking healthcare services was associated with both negative outcomes. Assuring access to health care and reducing social isolation could potentially reduce negative outcomes for PWE. It is necessary to provide adequate support for PWE to reduce risks as COVID-19 continues to be a health concern.
Chronic immobilization stress (CIS) results in sex‐dependent changes in opioid peptide levels and receptor subcellular distributions within the rat dorsal hippocampus which are paralleled with an inability for males to acquire conditioned place preference (CPP) to oxycodone. Here, RNAScope in situ hybridization was used to determine the expression of hippocampal opioid peptides and receptors in unstressed (US) and CIS estrus female and male adult (~ 14 wk) Sprague Dawley rats. In all groups, dentate granule cells expressed PENK and PDYN; additionally, numerous interneurons expressed PENK. OPRD1 and OPRM1 were primarily expressed in interneurons, and to a lesser extent, in pyramidal and granule cells. OPRK1‐was expressed in sparsely distributed interneurons. There were few baseline sex differences: US females compared to US males had more PENK‐expressing and fewer OPRD1‐expressing granule cells and more OPRM1‐expressing CA3b interneurons. Several expression differences emerged after CIS. Both CIS females and males compared to their US counterparts had elevated: 1) PENK‐expressing dentate granule cells and interneurons in CA1 and CA2/3a; 2) OPRD1 probe number and cell expression in CA1, CA2/3a and CA3b and the dentate gyrus; and 3) OPRK1‐expressing interneurons in the dentate hilus. Also, CIS males compared to US males had elevated: 1) PDYN expression in granule cells; 2) OPRD1 probe and interneuron expression in CA2/3a; 3) OPRM1 in granule cells; and 4) OPRK1 interneuron expression in CA2/3a. The sex‐specific changes in hippocampal opioid gene expression may impact network properties and synaptic plasticity processes that may contribute to the attenuation of oxycodone CPP in CIS males.
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The domain of seizures, as many medical domains, is still plagued by Cartesian dualism. In this view, mind and brain are regarded as distinct entities, even when looked upon as integral parts of a larger whole. Both physicians and patients come to the consultation room with this dualistic mindset. Consequently, seizures are classified as either organic, psychogenic, or of a mixed nature and are treated as such. However, the reality is non-dualistic, mind and body being about two views upon the same entity. Taking this into consideration, a different landscape emerges for the domain of seizures, in which psyche and soma coincide. They are the same thing. This new landscape is in several ways more patient-friendly. As to the management of seizures, there are substantial consequences involved, respectfully putting the whole patient at the center of care in a way not possible from a dualistic standpoint.
Background: Epilepsy patients in developing countries is quite high. A person can have epilepsy within a certain time limit, but also not a few people who survive with this condition for life. This situation will affect cognitive function. Cognitive function impairment in epilepsy patients can be triggered by various factors related to aetiology, clinical, and others. Therefore, we tried to find the factors that influence the cognitive function in epilepsy patients.Methods: This study was an observational analytic study with a cross-sectional design. The study was conducted using primary data obtained from direct interviews and MMSE examination and secondary data obtained from medical records to confirm the diagnosis of epilepsy. Samples were collected based on the diagnosis of neurologist in the patient's medical record at the Regional General Hospital Dr. Zainoel Abidin Banda Aceh from October to December 2019. This study involved thirty-four epilepsy patients.Result: There were cognitive function decreased in recalling 47,1% and 26,5% in Attention and calculation. The relationship between the frequency of seizure (p = 0.028) and therapy (p = 0.012) on the MMSE .Conclusion: Politherapy was the dominant factor affecting the MMSE score of epilepsy patients.
Objective
Transient global amnesia (TGA) is characterized by sudden onset of larger anterograde and milder retrograde amnesia lasting up to 24 hours. We aimed to investigate the long-term risk of epilepsy up to 8 years in subjects after TGA in the population-based cohort study.
Patients and Methods
We conducted a control cohort study with an 8-year follow-up period. All data was collected retrospectively. From all potential participants more than 18 years of age without epilepsy and TGA history, we identified TGA subjects and non-TGA controls with age, gender and comorbidities matched in a 1:3 ratio. The yearly incidence of epilepsy was compared in TGA and non-TGA cohorts. The cumulative hazard ratio of epilepsy was estimated. The risk factors of epilepsy after TGA were investigated.
Results
A total of 185 TGA subjects and 555 non-TGA controls were included in the study. There were 7 epilepsy cases in the 185 TGA cohorts during the follow-up period with yearly incidence rates of 9.629 per 1000 person. The adjusted hazard ratio for epilepsy in TGA cohorts was 6.50 (95% confidence interval 1.87-22.68, p = 0.003) compared with non-TGA cohorts after adjusting for age, gender and comorbidities. No notable factor was significantly associated with epilepsy after TGA.
Conclusion
Our study highlighted TGA is associated with increased long-term risk of epilepsy.
Introduction
Epilepsy is a common neurological disorder, and the patients with epilepsy are heavily influenced by the psychological and social aspects of the illness. Therefore, patients try to use coping strategies to control their stress and tension in this situation. Given the importance of the issue of adaptation and coping with stress in patients with epilepsy, as well as the different factors affecting coping strategies in these patients, the present study aimed to investigate the relationship between coping strategies and emotional intelligence in patients with epilepsy.
Methods
This descriptive-analytic study conducted on 134 male and female patients with epilepsy referred to the Epilepsy Society of Isfahan, Iran. The consecutive sampling method was applied in this study. The data collection tool included a three-section questionnaire: the Demographic information, the Coping Inventory for Stressful Situations (CISS), and the Bar-On Emotional Quotient Inventory (EQ-i).
Results
The emotion-focused coping strategy was mostly used by 53.7% of the samples. The mean and standard deviation of the total score of emotional intelligence was 285.6 ± 39.5. Moreover, Pearson correlation test showed a significant difference between emotional intelligence variables and coping strategies (p < 0.001).
Conclusion
According to the relationship between emotional intelligence and coping strategies, it is suggested to consider ways to improve the emotional intelligence of patients with epilepsy in order to use more adaptive coping strategies.
At the interface between mind and body, psychiatry and neurology, functional neurological disorder (FND) remains poorly understood. Formerly dominant stress-related aetiological models have been increasingly challenged, in part due to cases without any history of past or recent trauma. In this perspective article, we review current evidence for such models, and how research into the role of traumatic stress in other disorders and the neurobiology of the stress response can inform our mechanistic understanding of FND. First, we discuss the association between stress and the onset or exacerbation of a variety of physical and mental health problems. Second, we review the role of hypothalamic-pituitary-adrenal axis dysfunction in the neurobiology of ill-health, alongside evidence for similar mechanisms in FND. Third, we advocate a stress-diathesis model, in which biological susceptibility interacts with early life adversity, where FND can be precipitated by traumatic events later in life and maintained by psychological responses. We hypothesise that greater biological susceptibility to FND is associated with less severe remote and recent stress, and that FND precipitated by more severe stress is associated with lower biological vulnerability. This would explain clinical experience of variable exposure to historical and recent traumatic stress among people with FND and requires empirical investigation. A testable, evidence-based stress-diathesis model can inform nuanced understanding of how biological and psychological factors interact at the individual level, with potential to inform personalised treatment pathways. Much-needed research to establish the aetiology of FND will enhance clinical care and communication, facilitate effective treatment and inform prevention strategies.
Epilepsy affects all age groups and is one of the most common and most disabling neurological disorders. The accurate diagnosis of seizures is essential as some patients will be misdiagnosed with epilepsy, whereas others will receive an incorrect diagnosis. Indeed, errors in diagnosis are common, and many patients fail to receive the correct treatment, which often has severe consequences. Although many patients have seizure control using a single medication, others require multiple medications, resective surgery, neuromodulation devices or dietary therapies. In addition, one-third of patients will continue to have uncontrolled seizures. Epilepsy can substantially impair quality of life owing to seizures, comorbid mood and psychiatric disorders, cognitive deficits and adverse effects of medications. In addition, seizures can be fatal owing to direct effects on autonomic and arousal functions or owing to indirect effects such as drowning and other accidents. Deciphering the pathophysiology of epilepsy has advanced the understanding of the cellular and molecular events initiated by pathogenetic insults that transform normal circuits into epileptic circuits (epileptogenesis) and the mechanisms that generate seizures (ictogenesis). The discovery of >500 genes associated with epilepsy has led to new animal models, more precise diagnoses and, in some cases, targeted therapies.
Purpose of review:
To review some aspects of the relationship between epilepsy and depression that have recently received increasing attention and may become major research topics in the near future.
Recent findings:
Epidemiological studies show that depression and suicide are, in some cases, premorbid symptoms preceding the onset of the epilepsy. Suicide is also three times more frequent in epilepsy than in the general population. Reliable screening instruments for depression and suicidality in patients with epilepsy are now available but data from real life clinical settings are needed to develop shared clinical pathways between neurology and psychiatry. Data in children with epilepsy are still limited although it is well known that, outside epilepsy, almost 50% of adult patients with mood and anxiety disorders have a previous history during childhood. Despite increasing attention to the problem, the additional stigma associated with mental health problems still represents one of the major barriers to prompt diagnosis and treatment.
Summary:
New studies will focus on the development of shared clinical pathways between neurology and psychiatry for mood disorders and suicide prevention. New global campaigns on the double stigma will support this process in areas where psychiatric comorbidities are still underdiagnosed and undertreated.
At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress (“burden of epilepsy”) explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy.
A genetic component to epilepsy has been recognized since Antiquity and is well established through twin and familial aggregation studies, which provide convincing evidence for the heritability of epilepsy. Despite major advances in genetic studies, genetic epilepsies have not yet revealed all their secrets. This prospective study aimed to identify genetic variants of epilepsy, to document the genotype/phenotype correlations and inheritance patterns in multigenerational Algerian families. Genetic analyzes included exome sequencing, CGH-array and Southern blotting.
We studied a family with a pair of monozygotic twins affected by temporal lobe epilepsy. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene encoding the galanin neuropeptide. This latter was found to act as a potent anticonvulsant and regulates epileptic seizures in animal models. However, until now its role in human epilepsy was not established. Functional analysis showed evidence that the mutant protein disrupts galanin signalling, and strongly supports GAL as the causal gene for the TLE in this family.
We identified two families with progressive myoclonus epilepsy type 1. Genetic studies by Southern blotting showed an expansion of dodecamer CCCCGCCCCGCG in EPM1 gene. In addition, two other families were analysed by CGH-array, but no pathogenic CNV was identified. The study of other multigenerational families would identify new genetic variants of epilepsy.
Keywords: epilepsy, genetics, phenotype, pedigree, polymorphism, mutation, CNV, CGH-array, exome sequencing.
To investigate the effectiveness of mindfulness-based therapy (MT) and social support (SS) in patients with drug-resistant epilepsy.
We performed an assessor-blinded randomized control trial. Sixty patients with drug-resistant epilepsy were randomly allocated to MT or SS (30 per group). Each group received 4 biweekly intervention sessions. The primary outcome was the change in the total score of the Patient-Weighted Quality of Life in Epilepsy Inventory (QOLIE-31-P). Secondary outcomes included seizure frequency, mood symptoms, and neurocognitive functions. The assessors were blinded to the patient's intervention grouping. Results were analyzed using general linear model with repeated measure.
Following intervention, both the MT (n = 30) and SS (n = 30) groups had an improved total QOLIE-31-P, with an improvement of +6.23 for MT (95% confidence interval [CI] +4.22 to +10.40) and +3.30 for SS (95% CI +1.03 to +5.58). Significantly more patients in the MT group had a clinically important improvement in QOLIE-31-P (+11.8 or above) compared to those who received SS (11 patients vs 4 patients). Significantly greater reduction in depressive and anxiety symptoms, seizure frequency, and improvement in delayed memory was observed in the MT group compared with the SS group.
We found benefits of short-term psychotherapy on patients with drug-resistant epilepsy. Mindfulness therapy was associated with greater benefits than SS alone in quality of life, mood, seizure frequency, and verbal memory.
This study provides Class II evidence that mindfulness-based therapy significantly improves quality of life in patients with drug-resistant epilepsy.
© 2015 American Academy of Neurology.
The aim of this study was to determine whether the reduction of seizures in patients with intractable epilepsy after self-regulation of slow cortical potentials (SCPs) was maintained almost 10 years after the end of treatment. Originally, 41 patients received training with SCP-neurofeedback. A control group of 12 patients received respiratory feedback while another group of 11 patients had their anticonvulsant medications reviewed. Nineteen patients in the experimental group participated at least in parts of the long-term follow-up, but only two patients from each control group agreed to do so. The follow-up participants completed the same seizure diaries as in the original study. Patients of the experimental group also took part in three SCP-training sessions at the follow-up evaluation. Due to the small sample size, the results of participants in the control groups were not considered in the analysis. A significant decrease in seizure frequency was found about 10 years after the end of SCP treatment. The clinical significance of this result is considered medium to high. All patients were still able to self-regulate their SCPs during the feedback condition. This success was achieved without booster sessions. This is the longest follow-up evaluation of the outcome of a psychophysiological treatment in patients with epilepsy ever reported. Reduced seizure frequency may be the result of patients continued ability to self-regulate their SCPs. Given such a long follow-up period, the possible impact of confounding variables should be taken into account. The small number of patients participating in this follow-up evaluation diminishes the ability to make causal inferences. However, the consistency and duration of improvement for patients who received SCP-feedback training suggests that such treatment may be considered as a treatment for patients with intractable epilepsy and as an adjunct to conventional therapies.
Epileptic seizures can be provoked by several factors. Better understanding of these factors may improve a patient's sense of control and could reduce seizures. In daily practice, the recognition of seizure precipitants relies heavily on clinical or video-EEG evidence, which can be difficult to obtain. Studies of seizure provocation are largely based on selected hospital-based patient populations, which may lead to biased occurrence estimates. Self-reported seizure precipitants are rarely studied, yet are necessary to understand the experiences of patients and improve epilepsy management. We performed a cross-sectional community-based study of 248 epilepsy patients, selected by pharmacy records of anti-epileptic drug use. Self-reported seizure precipitants and potential associated characteristics were assessed using questionnaires. Almost half of all patients (47 %) reported one or more seizure precipitants, of which stress, sleep deprivation, and flickering lights were the most common. In this community-based setting, light-provoked seizures were especially frequent compared to the literature. Idiopathic generalized epilepsy (IGE), a lower age at seizure onset, and having auras or prodromes were found to be important independent prognostic factors associated with provoked seizures. IGE and a younger age at seizure onset have been linked to provoked seizures in earlier reports. The finding of auras or prodromes as a prognostic factor was unexpected, though case reports have described provoked seizures in patients having auras. Assessment of these factors may facilitate the early recognition of seizure precipitants in daily clinical practice. This is important for the optimization of epilepsy management for a large group of patients, as provoked seizures are expected to occur frequently.
Growing evidence suggests a bidirectional interaction between epileptic seizures and psychological states, fuelling the interest in the development and application of psychobehavioral therapy for people with epilepsy (PWE). The objective of this article is to review the various psychobehavioral therapies in regard to their application, hypothesized mechanisms, and effectiveness. Most psychobehavioral therapy aims at improving psychological well-being and seizure control. Behavioral approaches, cognitive-behavioral therapy (CBT), and mind-body interventions are the most widely applied approaches for PWE. Cognitive-behavioral therapy, mind-body approaches, and multimodel educative interventions have consistently demonstrated positive effects on enhancing well-being. Nevertheless, the effects on seizure control remain inconsistent, partly attributable to small clinical trials and inadequate control groups. Assessor-blinded randomized controlled trials with sufficient power and carefully defined therapeutic components corresponding with objective and subjective outcome measures are recommended for future trial designs.
Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.
This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis.
Given the high burden of epilepsy on both health-related quality of life (HRQoL) and costs, identification of factors that are predictive of either reduced HRQoL or increased expenditure is central to the better future targeting and optimization of existing and emerging interventions and management strategies for epilepsy.
Searches of Medline, Embase, and Cochrane Library (up to July 2010) to identify studies examining the association between demographic, psychosocial, and condition-related factors and HRQoL, resource utilization or costs in adults with epilepsy. For each study, predictor factor associations were summarized on the basis of statistical significance and direction; the results were then combined across studies.
Ninety-three HRQoL and 16 resource utilization/cost studies were included. Increases in seizure frequency, seizure severity, level of depression, and level of anxiety and presence of comorbidity were strongly associated with reduced HRQoL. The majority of studies were cross-sectional in design and had an overall methodologic quality that was judged to be "moderate" for HRQoL studies and "poor" for health care resource or costs studies. In the 53 multivariate studies, age, gender, marital status, type of seizure, age at diagnosis, and duration of epilepsy did not appear to be associated with HRQoL, whereas the predictive influence of educational and employment status, number of antiepileptic drugs (AEDs) and AED side effects was unclear. The association between predictive factors and HRQoL appeared to be consistent across individuals whether refractory or seizures controlled or managed by AEDs. There were insufficient multivariate studies (five) to reliably comment on the predictors of resource utilization or cost in epilepsy.
In addition to seizure control, effective epilepsy management requires the early detection of those most at risk of psychological dysfunction and comorbidity, and the targeting of appropriate interventions. There is need for more rigorous studies with appropriate multivariate statistical methods that prospectively investigate the predictors of HRQoL, resource utilization, and costs in epilepsy.
Clinical and experimental data suggest that stress contributes to the pathology of epilepsy. We review mechanisms by which stress, primarily via stress hormones, may exacerbate epilepsy, focusing on the intersection between stress-induced pathways and the progression of pathological events that occur before, during, and after the onset of epileptogenesis. In addition to this temporal nuance, we discuss other complexities in stress-epilepsy interactions, including the role of blood-brain barrier dysfunction, neuron-glia interactions, and inflammatory/cytokine pathways that may be protective or damaging depending on context. We advocate the use of global analytical tools, such as microarray, in support of a shift away from a narrow focus on seizures and towards profiling the complex, early process of epileptogenesis, in which multiple pathways may interact to dictate the ultimate onset of chronic, recurring seizures.
Few studies have examined the effectiveness of cognitive behavior therapy to manage seizures and improve psychosocial functioning in older adults with epilepsy. This study evaluated the efficacy of a 6 week group CBT program in community dwelling adults with epilepsy who were aged over 60 years. A total of 37 participants were randomly assigned to either a CBT group or a control group. Measures of depression, dysthymia, psychosocial functioning and seizure frequency were completed at pre and post intervention. Seizure frequency was significantly reduced in the CBT group compared to the control group (Cohen's d 0.63). The results suggest that the relationship between seizure frequency and psychological and psychosocial well being in older adults requires further investigation. Although there were no significant between group differences on measures of depression and psychosocial functioning, both the CBT and control groups improved significantly from baseline.
About one third of patients with epilepsy do not benefit from medical treatment. For these patients electroencephalographic (EEG) biofeedback is a viable alternative. EEG biofeedback, or neurofeedback, normalizes or enhances EEG activity by means of operant conditioning. While dozens of scientific reports have been published on neurofeedback for seizure disorder, most have been case series with too few subjects to establish efficacy. The purpose of this paper is to meta-analyze existing research on neurofeedback and epilepsy.
We analyzed every EEG biofeedback study indexed in MedLine, PsychInfo, and PsychLit databases between 1970 and 2005 on epilepsy that provided seizure frequency change in response to feedback. Sixty-three studies have been published, 10 of which provided enough outcome information to be included in a meta-analysis. All studies consisted of patients whose seizures were not controlled by medical therapies, which is a very important factor to keep in mind when interpreting the results. Nine of 10 studies reinforced sensorimotor rhythms (SMR) while 1 study trained slow cortical potentials (SCP). All studies reported an overall mean decreased seizure incidence following treatment and 64 out of 87 patients (74%) reported fewer weekly seizures in response to EEG biofeedback. Treatment effect was mean log (post/pre) where pre and post represent number of seizures per week prior to treatment and at final evaluation, respectively. Due to prevalence of small groups, Hedges's g was computed for effect size. As sample heterogeneity was possible (Q test, p=.18), random effects were assumed and the effect of intervention was −0.233, SE= 0.057, z [Formula: see text] −4.11, p<.001.
Based on this meta-analysis, EEG operant conditioning was found to produce a significant reduction on seizure frequency. This finding is especially noteworthy given the patient group, individuals who had been unable to control their seizures with medical treatment.
The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re- establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.
To determine the effectiveness of systematic screening with a brief 19-item self-report instrument, the Adverse Events Profile (AEP), to reduce adverse effects of antiepileptic drugs (AEDs) and improve subjective health status.
The authors performed a prospective randomized trial comparing the use of the AEP with usual care without the AEP. Sixty-two patients with an AEP score of >or=45 were enrolled from a consecutive group of 200 consenting adults with epilepsy.
The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group (25% vs 5%; p < 0.01). Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups, but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score (24 vs 12 vs 3; analysis of variance, p < 0.008). More patients in the AEP group had a >15-point improvement in QOLIE-89 score (p < 0.03). Use of the AEP was associated with a 2.8-fold increase (95% CI, 1.7 to 4.8) in AED modifications. No difference in seizure rates was observed. Conclusions: Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status.
Direct vagus nerve stimulation (VNS) has proved to be an effective treatment for seizure disorder and major depression. However, since this invasive technique implies surgery, with its side-effects and relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a great step forward. We studied effects of non-invasive electrical stimulation of the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal afferences transcutaneously (t-VNS). Short-term changes in brain activation and subjective well-being induced by t-VNS were investigated by functional magnetic resonance imaging (fMRI) and psychometric assessment using the Adjective Mood Scale (AMS), a self-rating scale for current subjective feeling. Stimulation of the ear lobe served as a sham control.
fMRI showed that robust t-VNS induced BOLD-signal decreases in limbic brain areas, including the amygdala, hippocampus, parahippocampal gyrus and the middle and superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the thalamus. Psychometric assessment revealed significant improvement of well-being after t-VNS. Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or psychometric assessment. No significant effects on heart rate, blood pressure or peripheral microcirculation could be detected during the stimulation procedure.
Conclusions. Our study shows the feasibility and beneficial effects of transcutaneous nerve stimulation in the left auditory canal of healthy subjects. Brain activation patterns clearly share features with changes observed during invasive vagus nerve stimulation.
To explore the relationship of seizure occurrence with candidate seizure precipitants in a prospective diary study, and to determine the relationship of precipitants to seizure self-prediction.
Eligible subjects were 18 or older, had localization-related epilepsy, at least one seizure within 12 months, and were able to maintain a daily diary. Information collected included the occurrence, time and characteristics of all seizures, hours of sleep, medication compliance, stress, anxiety, alcohol use, menstruation, and seizure self-prediction. Each night, subjects reported their estimate of the likelihood of a seizure the next day (self-prediction). Logit-normal models with a random subject-specific intercept were used to estimate an OR for the association of precipitants with seizure occurrence.
Seventy-one subjects returned 15,179 complete diary days. For each hour of increased sleep on the preceding night, the relative odds of a seizure the following day decreased (OR 0.91, 95% CI 0.82, 0.99). One-unit increments of stress and anxiety (on a 10-point scale) were associated with an increased risk of seizure the following day (OR 1.06, 95% CI 1.01, 1.12 and OR 1.07; 95% CI 1.02, 1.12). With self-prediction included in the model, self-prediction (OR 3.7; 95% CI 1.8, 7.2) and hours of sleep for the night prior to the seizure (OR 0.90; 95% CI 0.82, 0.99) remained significant.
Lack of sleep and higher self-reported stress and anxiety levels were associated with seizure occurrence. In a model that included self-prediction, less sleep, and self-prediction had significant effects, whereas stress and anxiety did not. The psychological and biologic mechanisms which link stress and anxiety to self-prediction of seizures requires further exploration. Ultimately, seizure prediction based on precipitants, premonitory features, and self-prediction may provide a foundation for preemptive treatment.
The notion that stress, the physiological and/or behavioral response to event(s) interpreted as threatening to well-being, plays a role in triggering seizures or even causing epilepsy has been extensively studied in both experimental and clinical contexts. People with epilepsy consistently report stress as one of the most common triggers, although disentangling from confounders such as sleep deprivation, mood, and alcohol, and cause from effect has proved challenging. A great deal of effort (and money) has gone into pre-clinical and clinical research, including more recently functional imaging studies, such that we now have a good understanding of pathways and potential mechanisms. Similarly, there has been considerable work looking at ways to reduce stress, which can undoubtedly be of benefit in terms of psychological well-being, though may not improve seizure control. There has been very little consideration of cost-effectiveness or cost-utility thus far, which is of particular importance when there are inevitable limitations on resources. Thus beyond heightened awareness about the potential for stress and epilepsy to interact, little of this work has as yet translated into meaningful changes for clinical practice. Hopefully, further carefully directed preclinical and especially clinical research will lead to greater understanding of the interaction and benefit to patients.
The aim of this study was to investigate the potential role of an acute adverse stress as "trigger" for the onset of epilepsy.
Among 4618 consecutive patients, twenty-two reported a major life event within three months before the onset of epilepsy.
All patients had focal epilepsy except one with idiopathic generalized epilepsy. The temporal lobe was involved in 90% of patients with focal epilepsy. More precisely, 13 patients (62% of patients with focal epilepsy) had medial temporal lobe epilepsy (MTLE), two had lateral temporal lobe epilepsy, four had temporoparietooccipital junction epilepsy, and two patients had central lobe epilepsy. The mean age and the median age at onset of epilepsy for patients with MTLE were both 38years (range: 9.5-65years). Ten patients had right and three had left MTLE. Among patients with focal epilepsy, MRI was abnormal in 7 (33%) with hippocampal sclerosis in four, periventricular nodular heterotopia in two, and complex cortical dysgenesis in one. The mean age at onset of epilepsy for patients with brain lesions was 26years (range: 9.5-49). Twelve patients (54%) reported a death as a triggering factor for the onset of their epilepsy. Seven patients (32%) reported that a relationship of trust had been broken. Three patients (14%) had been subjects of violence. No patient reported sexual abuse as a triggering factor.
This study provides evidence that some patients (5/1000 patients) began their seizures in the wake of significant life events. The average age at onset of epilepsy is quite late, around age 30, even in the presence of brain lesions. These patients are emotionally and affectively more prone to have consequences of a stressful life event. The recognition and management of such situations may bring significant relief with improvement of the control of epilepsy.
Copyright © 2015 Elsevier Inc. All rights reserved.
The most commonly reported precipitating factor for seizures is stress. However, the underlying mechanisms whereby stress triggers seizures are not yet fully understood. Here we demonstrate a potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA (EGABA) associated with a dephosphorylation of the potassium chloride co-transporter, KCC2. Mice subjected to chronic restraint stress (30 min/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20 mg/kg). Following chronic stress, but not acute stress, we observe a dephosphorylation of KCC2 residue S940, which regulates KCC2 cell surface expression and function, in the hippocampus. To determine the impact of alterations in KCC2 expression following chronic stress, we performed gramicidin perforated patch recordings to measure changes in EGABA and neuronal excitability of principal hippocampal neurons. We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress. In addition, there is an increase in the intrinsic excitability of CA1 pyramidal neurons, evident by a shift in the input-output curve which could be reversed with the NKCC1 inhibitor, bumetanide. These data uncover a potential mechanism involving chronic stress-induced plasticity in chloride homeostasis which may contribute to stress-induced seizure susceptibility.
As captured by the proposed new definition, epilepsy is increasingly recognized as a disorder characterized not only by an enduring predisposition to recurrent seizures but explicitly also by the neurobiological, cognitive, psychological and social consequences of this condition. Further, both in the estimated 15 million people worldwide who have ongoing seizures despite optimal management and in a substantial proportion of those in remission, the consequences and comorbidities of epilepsy are the major determinants of quality of life. These include mood disorders such as anxiety and depression, dose related and longer term effects of antiepileptic drugs, including on prenatal development and bone health, and neurobehavioural effects. Whilst separating those that are part of an underlying condition or have unrelated contributors from those that are potentially remediable can be difficult, given the range of tools now available to assist with screening and management there is no excuse for not at least trying as part of standard care for people with epilepsy. Managing epilepsy well is about much more than controlling seizures and this needs to be recognized in planning and delivering services, as well as in prioritizing research.
Stress is commonly reported as a seizure precipitant in individuals with poorly controlled seizures including temporal lobe epilepsy. The aim of the study was to assess the neural and physiologic correlates of psychosocial stress response during functional magnetic resonance imaging (fMRI) and their relationship with seizure occurrence in patients with left temporal lobe epilepsy (LTLE). We enrolled 23 patients with LTLE and 23 age- and sex-matched healthy controls (HCs); all underwent fMRI with control math task (CMT) and stress math task (SMT) and pre-/post-fMRI salivary cortisol analysis (acute stress reactivity calculated as % reduction from post-stress to recovery baseline; dCORT). The Beck Depression Inventory-II (BDI-II) and Perceived Stress Scale (PSS-10) were administered. T-tests of performance and cortisol variables were performed. Processing and single-subject modeling of fMRI response to CMT positive feedback and SMT negative feedback, group comparisons, and whole-brain correlation of seizure occurrence and fMRI response in patients with poorly controlled LTLE were performed. Patients with LTLE and healthy controls were similar in demographics, math performance, heart rate, and PSS-10 scores (all p>0.05). Patients with LTLE exhibited greater dCORT (p=0.048) and lower BDI-II scores (p=0.016) compared with HCs. Patients with poorly controlled LTLE showed a positive association between seizure frequency and dCORT (r=0.73, p=0.016). Functional MRI activation to feedback was similar between groups, including midfrontal, temporal, parietal, and occipital regions. Regression analyses revealed no group differences to positive feedback, but, compared with HCs, patients with LTLE showed decreased activation to negative feedback in the left cerebellum/middle occipital/fusiform gyri, left hippocampus/parahippocampus, bilateral medial frontal/cingulate/superior frontal gyri, right postcentral gyrus/inferior parietal lobule, and right insula/postcentral gyrus (p<0.05, corrected). Patients with poorly controlled LTLE showed negative association between seizure frequency and activation in the bilateral subgenual anterior cingulate (p<0.05, corrected). This study is the first to characterize the cortical and physiologic responses to acute psychosocial stress and to show a significant relationship between seizure control in LTLE and both the hypothalamic-pituitary-adrenal axis and fMRI signal reactivity to acute psychosocial stress. These findings extend our understanding of the complex interplay between stress, physiologic stress markers, and seizures/epilepsy.
There are multiple definitions of stress. For this review, as a reference point, we will use the concept of acute emotional/psychosocial stress ("stress"). The presence of acute stress has been reported to have a significant effect on seizure control, with several studies showing patients with seizure disorders being able to predict with reasonable accuracy seizure occurrence within the following hours or days. However, neuroimaging investigations of the pathophysiological mechanisms underlying stress reactivity (e.g., hypothalamic-pituitary-adrenal (HPA) axis activation) in humans, in general, and in patients with seizure disorders, in particular, are scarce. The reasons for this are multiple and likely include difficulty with designing appropriate probes that test various aspects of stress response, obtaining approval for studies that induce stress in patients who are prone to having stress-induced seizures, difficulties with assessing the physiological response to stress inside the scanner (e.g., heart rate, respiratory rate, oxygenation, cortisol levels, and galvanic skin responses), participant identification, and choice of epilepsy syndrome for investigation. With the recent explosion of neuroimaging literature focusing on correlating stress of various types and levels with cortical activations in healthy and diseased populations, it is incumbent upon us to examine the available neuroimaging data in patients with seizure disorders in order to identify the existing gaps and the needs/directions for future investigations. This approach is consistent with the goals of several of the 2014 Benchmarks for Epilepsy Research for the National Institute of Neurological Disorders and Stroke and the American Epilepsy Society.
A subset of patients with epilepsy successfully self-predicted seizures in a paper diary study. We conducted an e-diary study to ensure that prediction precedes seizures, and to characterize the prodromal features and time windows that underlie self-prediction.
Subjects 18 or older with localization-related epilepsy (LRE) and ≥3 seizures per month maintained an e-diary, reporting a.m./p.m. data daily, including mood, premonitory symptoms, and all seizures. Self-prediction was rated by, "How likely are you to experience a seizure (time frame)?" Five choices ranged from almost certain (>95% chance) to very unlikely. Relative odds of seizure (odds ratio, OR) within time frames was examined using Poisson models with log normal random effects to adjust for multiple observations.
Nineteen subjects reported 244 eligible seizures. OR for prediction choices within 6 h was as high as 9.31 (CI 1.92-45.23) for "almost certain." Prediction was most robust within 6 h of diary entry, and remained significant up to 12 h. For nine best predictors, average sensitivity was 50%. Older age contributed to successful self-prediction, and self-prediction appeared to be driven by mood and premonitory symptoms. In multivariate modeling of seizure occurrence, self-prediction (2.84; CI 1.68-4.81), favorable change in mood (0.82; CI 0.67-0.99), and number of premonitory symptoms (1.11; CI 1.00-1.24) were significant.
Some persons with epilepsy can self-predict seizures. In these individuals, the odds of a seizure following a positive prediction are high. Predictions were robust, not attributable to recall bias, and were related to self-awareness of mood and premonitory features. The 6-h prediction window is suitable for the development of preemptive therapy.
A consistent and serious empirical issue in the epilepsy self-management literature involves dropout and attrition in intervention studies. One explanation for this issue revolves around "top-down" intervention designs (i.e., interventions generated by epilepsy clinicians and researchers) and the potential for disparity with patient interests, capabilities, and perceived needs. The purpose of this study was to extend the work of Fraser et al. (2011) [19] by comparing perceptions regarding self-management problems, topics, and program design, between two subgroups of adult patients with epilepsy (n=165) and epilepsy clinicians (n=20). Results indicate differences in problem severity ratings, program emphasis (i.e., goal-setting, coping, education), and program leadership between clinicians and each patient subgroup to varying degrees. These findings highlight some of the differences in opinion between patients and clinicians and emphasize the need for patient-involved planning with regard to self-management programs. Implications and explanations are offered as points for consideration in self-management program development.
We tested whether unpleasant life events increased seizure occurrence in persons with epilepsy. Forty-six subjects maintained daily diaries for 10–36 weeks in which they recorded seizures and life events. Mean age of subjects was 39 years; 78% were female; 83% had complex partial seizures (CPS). On the average, subjects reported 3.3 seizures a week. Analyses first were conducted within each subject and then in the sample overall. For each person, we tested whether seizure frequency increased within 24 h of the occurrence of unpleasant events, using Poisson regression analyses that adjusted for daily antiepileptic medication, sleep duration and quality, alcohol intake, menstrual status, and pleasant events. Rarity of events precluded analyses in 9 subjects. Events increased seizure frequency in 5 subjects (14%) (p < 0.05). Events decreased seizure frequency in 2 subjects (p < 0.05). When individual risk ratios were aggregated across subjects, unpleasant events were significantly associated with seizure increase only in men (RR = 1.67, 95% Confidence interval 1.09, 2.54). However, this finding must be interpreted with caution because of the limited number of men in the sample. In other aggregate analyses, events and seizures were not associated in subjects grouped by seizure type, age of seizure onset, current age, ethnicity, educational level, or marital status. Identification of factors that distinguish patients with and without event-triggered seizures requires further study.
Objective:
The goal of the study described here was to examine the interrelationship between psychological factors (anxiety, stress, and depression) and seizures.
Methods:
In this longitudinal cohort study, data on anxiety, depression, perceived stress, and seizure recency (time since last seizure) and frequency were collected at two time points using standard validated questionnaire measures. Empirically based models with psychological factors explaining change in (1) seizure recency and (2) seizure frequency scores across time were specified. We then tested how these psychological factors acted together in predicting seizure recency and frequency. Our data were used to test whether these models were valid for the study population. Latent variable structural equation modeling was used for the analysis.
Results:
Four hundred thirty-three of the 558 individuals who initially consented to participate provided two waves of data for this analysis. Stress (beta=0.25, P<0.01), anxiety (beta=0.30, P<0.01), and depression (beta=0.30, P<0.01) all predicted change in seizure recency. However, it was depression that mediated the relationship of both anxiety and stress with modeled change in seizure recency (beta=0.19, P<0.01) and seizure frequency (beta=0.30, P<0.01) over time.
Conclusion:
Depression mediates the relationship between stress and anxiety and change in seizure recency and seizure frequency. These findings highlight the importance of depression management in addition to seizure management in the assessment and treatment of epilepsy in an adult population.
The aim of this retrospective study is to describe changes of seizure frequency in epilepsy patients who participated in the Andrews/Reiter behavioral intervention for epilepsy. For this uncontrolled retrospective study, data were extracted from patients' medical journals. Intention-to-treat-analyses were restricted to patients with sufficient documentation supporting a diagnosis of probable or definite epilepsy. Main outcome variable was a comparison of mean seizure frequency at baseline and toward completion of the program. The seizure frequency of 30 (50%) patients showed a clinically meaningful improvement (>50% reduction of seizures) toward the end of the intervention. Twenty-two (37%) patients became seizure-free at the end of the intervention. In summary, a clinically meaningful reduction in reported seizure frequency was observed in epilepsy patients who received the Andrews/Reiter intervention for epilepsy. Prospective trials are needed to further investigate the program's efficacy and to study epileptic seizure triggers.
Stress and Health: Biological and Psychological Interactions, Second Edition examines the biological links between our emotions and changes in our health. Author William R. Lovallo provides an introduction to the concept of psychological stress, its physiological manifestations, and its effects on health and disease. The book concentrates on the psychophysiological relationship between cognitions, emotions, brain functions, and the peripheral mechanisms by which the body is regulated. Stress and Health is the only book on the biology of psychological stress for students and researchers in the behavioral sciences.
Epilepsy and depression share an unusually high coincidence suggestive of a common etiology. Disrupted production of adult-born hippocampal granule cells in both disorders may contribute to this high coincidence. Chronic stress and depression are associated with decreased granule cell neurogenesis. Epilepsy is associated with increased production - but aberrant integration - of new cells early in the disease and decreased production late in the disease. In both cases, the literature suggests these changes in neurogenesis play important roles in their respective diseases. Aberrant integration of adult-generated cells during the development of epilepsy may impair the ability of the dentate gyrus to prevent excess excitatory activity from reaching hippocampal pyramidal cells, thereby promoting seizures. Effective treatment of a subset of depressive symptoms, on the other hand, may require increased granule cell neurogenesis, indicating that adult-generated granule cells can modulate mood and affect. Given the robust changes in adult neurogenesis evident in both disorders, competing effects on brain structure are likely. Changes in relative risk, disease course or response to treatment seem probable, but complex and changing patterns of neurogenesis in both conditions will require sophisticated experimental designs to test these ideas. Despite the challenges, this area of research is critical for understanding and improving treatment for patients suffering from these disorders.
Epilepsy is a common neurologic condition with significant personal, societal, medical, and economic burdens. There are considerable gaps in the quality of care delivered. Measuring the quality of care delivered is the first step to its improvement. Performance measures are easily identified and quantitated ways to assess whether specific activities were carried out during a patient encounter. Therefore, epilepsy performance measures were derived through a standardized systematic process and may be the basis for pay-for-performance initiatives and maintenance of certification requirements.
Epilepsy measures were developed through the American Medical Association-convened Physician Consortium for Performance Improvement (PCPI) independent measure development process, which marked the first time a medical specialty society followed this process. Guidelines, measures, and consensus papers reviewed for the period 1998 to 2008 using the National Guidelines Clearinghouse, the National Quality Measures Clearinghouse, PubMed, MEDLINE, and the Cochrane Library were evaluated using a framework to determine the acceptability of each guideline or other evidence review document for measures development. Recommendation statements based on level of evidence, importance, validity, and gap in care were developed into candidate measures. A panel of experts from representative organizations vetted the measures. A period of public comment was followed by approval from the American Academy of Neurology and the PCPI.
Literature search identified 160 relevant recommendation statements from 19 guidelines and 2 consensus papers. Systematic assessment resulted in 20 recommendation statements that were refined to 8 candidate measures by the expert panel. The measures are relevant to seizure type and frequency, etiology or epilepsy syndrome, EEG, neuroimaging, antiepileptic drug side effects, safety issues, referral for refractory epilepsy, and issues for women of childbearing potential.
There is a reasonable evidence base, and consensus for, deriving performance measures for quality of epilepsy care. It is anticipated that implementation of these performance measures will improve care for patients with epilepsy if adopted by providers.
Human studies show a link between stress and epilepsy, with stress causing an increase in seizure frequency and severity in patients with epilepsy. Many different animal model systems have been used to better understand this connection and the possible mechanisms involved. This review highlights the results of such studies relating stress and seizure susceptibility, with a focus on the hypothalamic-pituitary-adrenal axis and its relationship to seizure generation. The effects of hypothalamic-pituitary-adrenal axis mediators, acute stress, chronic stress, and early life stress on the seizure phenotype are summarized. Results suggest that stress has both anticonvulsive and proconvulsive properties, depending on the animal strain and the stress/seizure induction paradigm used. Attempts to interpret the stress-epilepsy literature must take these variables into account. The growing availability of genetically modified mice that carry either human epilepsy mutations or mutations in stress pathway genes now provide the opportunity to examine the relationship between stress and epilepsy more directly.
Stress is among the most frequently self-reported precipitants of seizures in patients with epilepsy. This review considers how important stress mediators like corticotropin-releasing hormone, corticosteroids, and neurosteroids could contribute to this phenomenon. Cellular effects of stress mediators in the rodent hippocampus are highlighted. Overall, corticosterone--with other stress hormones--rapidly enhances CA1/CA3 hippocampal activity shortly after stress. At the same time, corticosterone starts gene-mediated events, which enhance calcium influx several hours later. This later effect serves to normalize activity but also imposes a risk for neuronal injury if and when neurons are concurrently strongly depolarized, for example, during epileptic activity. In the dentate gyrus, stress-induced elevations in corticosteroid level are less effective in changing membrane properties such as calcium influx; here, enhanced inhibitory tone mediated through neurosteroid effects on gamma-aminobutyric acid (GABA) receptors might dominate. Under conditions of repetitive stress (e.g., caused from experiencing repetitive and unpredictable seizures) and/or early life stress, hormonal influences on the inhibitory tone, however, are diminished; instead, enhanced calcium influx and increased excitation become more important. In agreement, perinatal stress and elevated steroid levels accelerate epileptogenesis and lower seizure threshold in various animal models for epilepsy. It will be interesting to examine how curtailing the effects of stress in adults, for example, by brief treatment with antiglucocorticoids, may be beneficial to the treatment of epilepsy.
This communication describes a technique of stimulated recall and video replay which has reduced the frequency of seizures in five epileptic patients. Each of the patients had long standing partial epilepsy with complex symptomatology of the psychomotor type. It was generally acknowledged that emotional factors played an important role in their poor seizure control. Previous psychotherapeutic efforts had been without benefit because ictal amnesia had erased the memory of the stressful antecedent message-input which had triggered the seizures. Creation of empathetically stressful responses to presentation of audio and video tape recordings of specific problematic social interactions was sufficient to induce seizures in these patients. Video tape recording of the seizure and the antecedant events provided by means by which the patients could acquire otherwise unrecognized or forgotten information. Once equipped with the identity of the specific emotional trigger, the patient could avoid the kinds of events which might be expected to induce a seizure and be better able to cope with threatening environmental cues when encountered in the future.
The present study evaluated the efficacy of group cognitive‐behavior therapy for the alleviation of psychosocial problems and reduction of seizures with adult epileptic patients. Twenty‐seven outpatients were randomly assigned to one of three groups: Cognitive‐Behavior Therapy, Supportive Counseling (attention‐placebo control), and Waiting list (no treatment control). The major outcome measures used were: patient's, neurologist's, and therapist's global ratings of psychological adjustment, patient's target complaints and weekly seizure frequency, patient's and neurologist's ratings of seizure control, the Minnesota Multiphasic Personality Inventory, the Washington Psychosocial Seizure Inventory, and the Beck Depression Inventory. No significant differences were found among the three groups on these measures except for therapist's global ratings of psychological adjustment, on which both the Cognitive‐Behavior Therapy and Supportive Counseling groups improved significantly after therapy, but the Waiting List control group did not. Overall, little support was found for the efficacy of group cognitive behavior therapy (eight 2‐h weekly sessions) for the reduction of psychosocial difficulties or seizures. Implications of the present findings are discussed, with the need for further controlled outcome research stressed.
RÉSUMÉ
Dans ce travail on a cherchéàévaluer l'efficacité d'une thérapie de groupe comportementale à médiation cognitive pour alléger les problèmes psychosociaux et réduire les crises chez des adultes épileptiques. Vingt sept malades externes ont été répartis au hasard en trois groupes: traitement comportemental à Médiation Cognitive, Conseils et Encouragements (pour contrǒler l'effet de l'attention bienveillante du thérapeute) et Liste d'Attente (groupe témoin sans aucun traitement). Les principales mesures utilisées étaient: évaluation globale de l'adaptation psychologique par le patient, le neurologue et le thérapeute, fréquence des plaintes majeures du patient, fréquence hebdomadaire des crises, évaluation du contrǒle des crises par le patient et par le neurologue, “Minneosta Multiphasic Personality Inventory,”“Washington Psychosocial Seizure Inventory” and “Beck Depression Inventory.” Aucune différence significative n'a été trouvée entre les trois groupes, sauf pour l'évaluation globale par le thérapeute de l'adaptation psychologique: il y avait une amélioration significative après traitement dans le groupe Traitement Comportemental à Médiation Cognitive et dans le groupe Conseils et Encouragements, alors qu'il n'y en avait pas dans le groupe Liste d'Attente. Surtout il y avait peu d'arguments pour l'efficacité du traitement de groupe comportemental à médiation cognitive (huit sessions de 2 heures par semaine) dans la réduction des difficultés psychosociales ou des crises. Les implications de ces résultats sont discutées, ainsi que la nécessité de continuer des études contrǒlées.
RESUMEN
El estudio actual valora la eficacia de la terapia conocimientoconducta, de grupo, con respecta a la mejoría de los problemas psicosociales y la reducción de los ataques en pacientes epilépticos adultos. Veintisiete pacientes ambulatorios fueron asignados aleatoriamente a uno de los tres grupos siguientes: Terapia Conocimiento‐Conducta, Apoyo mediante Consejos (atención‐control con placebo), y Lista de Espera (control sin tratamiento). Las medidas más importantes de los resultados fueron: las calificaciones globales de los pacientes, neurólogos y terapeutas con respecta al ajuste psicológico, las quejas fundamentales de los pacientes y la frecuencia semanal de los ataques, la cuantificación del control de los ataques por parte de los pacientes y los neurólogos, el Inventario de la Personalidad Multifásica de Minnesota, el Inventario de Washington para Ataques y Trastornos Psicosociales, y el Inventario de Beck para Depresión. Con estas medidas no se encontraron diferencias significativas entre los tres grupos con la excepción de la cuantificación global de los terapeutas con respecta al ajuste psicológico. En esta cuantificación mejoraron de modo significativo después de la terapia los grupos de Terapia Conocimiento‐Conducta y de Soporte mediante Consejos, pero no el grupo control de Lista de Espera. En general, se encontró escasa evidencia que apoyase la eficacia de la terapia de grupo de conocimiento‐conducta (ocho sesiones de dos horas a la semana) para la reducción de las dificultades psicosociales o de los ataques. Se discuten las implicaciones de los hallazgos presentados y se resalta la necesidad para realizer más investigación controlada de los resultados.
ZUSAMMENFASSUNG
Diese Arbeit untersucht die Wirkung einer Verhaltenstherapie in der Gruppe auf die Verminderung psychosozialer Probleme und epileptischer Anfälle bei Erwachsenen. 27 ambulante Patienten wurden zufällig einer der 3 Gruppen zugeordnet: Kognitive Verhaltenstherapie, unterstützende Beratung (Aufmerksamkeit‐Placebo‐Kontrolle) und Warteliste (keine Behandlungskontrolle). Geprüft wurden vor allem die Einschätzung der psychosozialen Anpassung durch den Patienten, den Neurologen und den Therapeuten, die Hauptbeschwerden des Patienten und die wöchentliche Anfallsfrequenz, die Einschätzung der Anfallskontrolle durch die Patienten und den Neurologen, das Minnesota Multiphasic Personality Inventory und Washington Psychosocial Seizure Inventory sowie das Beck Depression Inventory. Zwischen den 3 Gruppen wurden keine signifikanten Unterschiede hinsichtlich der angeführten Beurteilungskriterien gefunden mit Ausnahme der globalen Einschätzung der psychologischen Anpassung durch den Therapeuten: Sowohl die Gruppe mit kognitiver Verhaltenstherapie als auch die Gruppe mit unterstützender Beratung waren nach Therapie deutlich gebessert, nicht so die Gruppe der Warteliste. Insgesamt fand sich wenig Unterstützung für die Annahme einer Wirksamkeit der Gruppen‐Verhaltenstherapie (8 Zweistundensitzungen pro Woche) hinsichtlich der Reduktion psychosozialer Schwierigkeiten oder von Anfällen. Die Bedeutung der Ergebnisse werden diskutiert, auf die Notwendigkeit weiterer kontrollierter Untersuchungen hingewiesen.
Certain auto- and cross-spectral components of the EEG appear to be characteristic of responses to verbal stimuli. Employing a discriminant-analysis procedure applied to spectral parameters, it proved possible to separate subjectively stressful from non-stressful verbal stimuli, and to determine distinctive EEG responses to verbal stimuli of similar stress value differing only in semantic content. The EEG components characteristic of these response states were consistent over small populations, and the criteria developed for their identification proved valid over several different subjects without requiring individual calibration.Other, individual-specific characteristics of the EEG were observed consistently to parallel the cyclical occurrence of several constituent epochs in a twenty-item question-answer sequence.RésuméCertaines composantes auto et cross-spectrales de l'EEG paraissent caractéristiques des réponses aux stimuli verbaux. En utilisant un procédé d'analyse discriminative appliqué aux paramètres du spectre, il s'est révélé possible de séparer les stimuli verbaux subjectivement stressants des stimuli non stressants, et de déterminer des réponses EEG distinctes aux stimuli verbaux de valeur similaire de stress, ne diffèrant que par leur contenu sémantique. Les composantes EEG caractéristiques de ces réponses sont constantes sur de petites populations et les critères développés pour leur identification se sont montrés valables pour plusieurs sujets différents sans nécessiter de calibration individuelle.Par ailleurs, des caractéristiques EEG spécifiques d'un individu sont observées de façon constante parallèlement à la survenue cyclique de plusieurs époques constituants d'une séquence de 20 items question-réponse.
We tested whether unpleasant life events increased seizure occurrence in persons with epilepsy. Forty-six subjects maintained daily diaries for 10-36 weeks in which they recorded seizures and life events. Mean age of subjects was 39 years; 78% were female; 83% had complex partial seizures (CPS). On the average, subjects reported 3.3 seizures a week. Analyses first were conducted within each subject and then in the sample overall. For each person, we tested whether seizure frequency increased within 24 h of the occurrence of unpleasant events, using Poisson regression analyses that adjusted for daily antiepileptic medication, sleep duration and quality, alcohol intake, menstrual status, and pleasant events. Rarity of events precluded analyses in 9 subjects. Events increased seizure frequency in 5 subjects (14%) (p < 0.05). Events decreased seizure frequency in 2 subjects (p < 0.05). When individual risk ratios were aggregated across subjects, unpleasant events were significantly associated with seizure increase only in men (RR = 1.67, 95% Confidence interval 1.09, 2.54). However, this finding must be interpreted with caution because of the limited number of men in the sample. In other aggregate analyses, events and seizures were not associated in subjects grouped by seizure type, age of seizure onset, current age, ethnicity, educational level, or marital status. Identification of factors that distinguish patients with and without event-triggered seizures requires further study.
We evaluated self-perception of seizure precipitants in 149 adult subjects with epilepsy: 71% of the subjects reported at least one factor that, according to the perception, increased the risk of suffering from a seizure. The subjects most often reported psychological stress, change of weather and sleep deprivation. Among the disease-related factors, seizure frequency and the state of consciousness at the onset of the seizures influenced perception of precipitants. Furthermore the perception of some precipitants was dependent on such social variables as rural versus urban surroundings. It is argued that the perception of seizure precipitants is the result of a combination of physiologically based temporal and causal correlations and of beliefs of the patient about such relationships. Hence reports of seizure precipitants are determined by somatic as well as psychological factors. Efforts to clarify the relationship between possible precipitants and the occurrence of seizures should be intensified. In addition the great importance of seizure precipitants in lay theories of epilepsies should be considered in counselling patients with epilepsies.
The primary hormonal mediators of the stress response, glucocorticoids and catecholamines, have both protective and damaging effects on the body. In the short run, they are essential for adaptation, maintenance of homeostasis, and survival (allostasis). Yet, over longer time intervals, they exact a cost (allostatic load) that can accelerate disease processes. The concepts of allostasis and allostatic load center around the brain as interpreter and responder to environmental challenges and as a target of those challenges. In anxiety disorders, depressive illness, hostile and aggressive states, substance abuse, and post-traumatic stress disorder (PTSD), allostatic load takes the form of chemical imbalances as well as perturbations in the diurnal rhythm, and, in some cases, atrophy of brain structures. In addition, growing evidence indicates that depressive illness and hostility are both associated with cardiovascular disease (CVD) and other systemic disorders. A major risk factor for these conditions is early childhood experiences of abuse and neglect that increase allostatic load later in life and lead individuals into social isolation, hostility, depression, and conditions like extreme obesity and CVD. Animal models support the notion of lifelong influences of early experience on stress hormone reactivity. Whereas, depression and childhood abuse and neglect tend to be more prevalent in individuals at the lower end of the socioeconomic ladder, cardiovascular and other diseases follow a gradient across the full range of socioeconomic status (SES). An SES gradient is also evident for measures of allostatic load. Wide-ranging SES gradients have also been described for substance abuse and affective and anxiety disorders as a function of education. These aspects are discussed as important, emerging public health issues where the brain plays a key role.
Previous studies of patient-reported seizure precipitants have not evaluated whether different epilepsy syndromes are differentially affected.
Patients of a tertiary-care epilepsy center were consecutively surveyed with the use of a standardized questionnaire that lists precipitants that might trigger or exacerbate seizures (alcohol, caffeine, fasting, fatigue, fever or illness, flashing lights, heat or humidity, menstrual cycle, sleep, sleep deprivation, emotional stress, unknown, or other). Patients were classified into epilepsy syndromes according to International League Against Epilepsy criteria. Age and gender within groups defined by major precipitants were compared. Pearson's correlation was performed to evaluate common patterns of precipitants.
Of 400 patients, 62% cited at least one precipitant. In order of frequency, stress (30%), sleep deprivation (18%), sleep (14%), fever or illness (14%), and fatigue (13%) were noted by at least 10% of patients. Stress, fatigue, and sleep deprivation positively correlated, but sleep tended to negatively correlate with other major precipitants. Rankings of precipitants varied within epilepsy syndromes, with patients with temporal lobe epilepsy citing sleep infrequently compared with patients with other epilepsy syndromes. Menstrual effects were ranked highly within major precipitants among women over age 12 and were especially noted by women with temporal lobe epilepsy (28%).
Most patients with epilepsy identify a precipitant that triggers or exacerbates seizures. The high correlation of stress, sleep deprivation, and fatigue suggests that they act through common mechanisms to worsen seizure control. Through identification of the effect of both endogenous and exogenous precipitants among syndromes, more research and counseling can be directed to specific precipitants.
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, electroencephalogram (EEG) bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life.
To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life.
We searched the Cochrane Epilepsy Group trial register (11 June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 2, 2003), MEDLINE (on 11 June 2003) and cross references from identified publications.
Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy.
Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life.
We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies.
In view of methodological deficiencies and limited number of individuals studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.
Psychological interventions such as relaxation therapy, cognitive behaviour therapy, bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life.
To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life.
We searched the Cochrane Epilepsy Group's Specialized Register (July 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), and MEDLINE (1966 to March 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies.
Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for people with epilepsy.
Two review authors independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency and quality of life.
We found three small trials (50 participants) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and four of educational interventions did not provide sufficient information to assess their effect on seizure frequency. One small study of galvanic skin response biofeedback reported significant reduction in seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in individuals with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, coping with epilepsy, compliance to medication and social competencies.
In view of methodological deficiencies and limited number of individuals studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.
Whether eye movement desensitization and reprocessing (EMDR) treatment of posttraumatic stress disorder (PTSD) causes reactivation of epilepsy is as yet unclear. A 34-year-old woman was treated in an inpatient multimodal psychotherapeutic setting with EMDR for PTSD resulting from sexual harassment and for a moderate depressive episode. She had been diagnosed with idiopathic generalized absence epilepsy in childhood, but had experienced no seizures under lamotrigine medication since 1999. After the second EMDR session, clinical seizures in the form of absences occurred, and were validated by electroencephalography. The seizures ceased after medication with benzodiazepines and an increase in the lamotrigine level. She underwent four more sessions of EMDR treatment successfully without further seizures. Possible triggers are discussed, especially as to whether EMDR treatment played a role in reactivating epilepsy. Further research and publications on the application of EMDR in epilepsy patients are needed.
Antiepileptic drugs (AEDs) have been successfully used in the treatment of mood disturbances, leading clinicians and researchers to investigate their use in other psychiatric disorders. This article reviews the literature about the potential efficacy of AEDs in anxiety disorders. An updated MEDLINE search (January 1970 to September 2006) using the terms "panic disorder," "agoraphobia," "posttraumatic stress disorder," "obsessive-compulsive disorder," "generalized anxiety disorder," "social phobia," "phobia," "carbamazepine," "phenobarbital," "phenytoin," "valproate," "lamotrigine," "topiramate," "vigabatrin," "tiagabine," "gabapentin," "levetiracetam," and "pregabalin" showed more than 70 articles and 38 published studies. Only articles published in English were reviewed. We have assigned level 1 of evidence to meta-analysis and replicated randomized controlled trials, level 2 to at least 1 randomized controlled trial, level 3 to uncontrolled trials with 10 or more subjects, and level 4 to anecdotal case reports. The strongest evidence has been demonstrated for pregabalin in social phobia and generalized anxiety disorder, lamotrigine in posttraumatic stress disorder, and gabapentin in social anxiety. The available data about gabapentin in panic disorder are somewhat mixed, and more definitive conclusion would require additional studies. This review suggests that AEDs can be an alternative treatment in some anxiety disorders. Further investigation is needed to determine in what circumstances they should be used in individuals who are partially responsive or nonresponsive to conventional therapy.
The aim of this study was to determine the prevalence and nature of self-perceived seizure precipitants in epilepsy patients, and evaluate whether anxiety level, depression, or health locus of control influence self-perception of seizure precipitants.
Adults aged 18 and older who had epilepsy for at least 1 year were recruited in either the inpatient epilepsy monitoring unit or the outpatient epilepsy clinic at Thomas Jefferson University in 2006. Patients anonymously filled out a questionnaire, which included data about age, sex, education, seizure control, and three questionnaires including identification of seizure precipitants, Hospital anxiety and depression (HAD) scale, and Form C of the multidimensional health locus of control (MHLC). Discriminant function analysis was used for statistical analysis.
Two hundred patients participated, with a mean age of 40.3+/-16 years. One hundred thirty (65%) patients reported one or more seizure precipitants. Stress (49.5%), lack of sleep (35.5%), and fatigue (32.5%) were the most common seizure triggers reported. Seizure control, anxiety level, and powerful others subscale in HLC scores were significantly related to self-perception of seizure precipitants. Subjective seizure triggers (stress, lack of sleep) were related to psychological factors.
The perception that certain triggers precipitate seizures is related to anxiety, health locus of control, and seizure control. Hence, seizures might be misattributed to irrelevant precipitants because of an underlying psychological predisposition. Alternatively, there may be a physiological relationship between seizures and the triggers. Prospective studies are required to clarify the relationship between seizure precipitants and seizure occurrence.
A questionnaire was administered to patients in the Montefiore Medical Center outpatient epilepsy department to assess perceptions about stress, seizures, and stress reduction. Eighty-nine patients completed the questionnaire. Overall, 64% of patients reported the belief that stress increased the frequency of their seizures. This belief was not significantly associated with gender, age, location of care, epilepsy classification, or seizure control, but was significantly associated with a shorter duration of epilepsy (P=0.04). Thirty-two percent of subjects had tried stress reduction modalities for epilepsy. Of those who had not, 53% were willing to try, and this willingness was significantly associated with a greater number of seizures in the prior 2 months (P=0.006) and the belief that stress was associated with seizures (P=0.04). Both major and minor stressors were reported with equal frequency. The majority of our study population believe that stress and seizures are related, and are willing to try stress reduction techniques for seizure control. We believe that these findings indicate a need for a prospective study to evaluate the role of stress and stress reduction as an additional potential therapeutic modality for epilepsy.