Unprovoked Epileptic Seizures Research Articles

The bidirectional role of music effect in epilepsy: Friend or foe?

Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti-seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long-term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti-convulsant effect, some particular music would cause seizures inversely, indicating the pro-convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti-convulsant and pro-convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. PLAIN LANGUAGE SUMMARY: Epilepsy is an extremely severe neurological disorder. Although anti-seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro-convulsive, or anti-convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients. We employed a novel method for measurements of neuronal activity through the detection of a resonant oscillating field, stimulus-induced rotary saturation contrast (SIRS) at spin-lock frequencies of 120 and 240 Hz acquired at a single 3T MRI system. Within a prospective observational study, we conducted SIRS experiments in 55 patients within 7 days after a suspected first unprovoked epileptic seizure and 61 healthy control subjects. In this study, we report on the analysis of data from a single 3T MRI system, encompassing 35 first seizure patients and 31 controls. The SIRS method was applicable in all patients and healthy controls at frequencies of 120 and 240 Hz. We did not observe any significant age- or sex-related differences. Specificity of SIRS at 120 Hz was 90.3% and 93.5% at 240 Hz. Sensitivity was 17.1% at 120 Hz and 40.0% at 240 Hz. SIRS targets neuronal oscillating magnetic fields in patients with epilepsy. The coupling of presaturated spins to epilepsy-related magnetic field perturbations may serve as a-at this stage experimental-diagnostic test in first seizure patients to complement EEG findings as a standard screening test. Routine diagnostic tests carry several limitations when applied after a suspected first seizure. SIRS is a noninvasive MRI method to enable time-sensitive diagnosis of image correlates of epileptic activity with increased sensitivity compared to routine EEG.

First seizure in elderly patients: Need to treat? Evidence from a retrospective study

BackgroundThe risk of seizure recurrence after a first unprovoked epileptic seizure is reported to be approximately 40%. Little is known about the recurrence risk after a first seizure in elderly patients, who may be at higher risk due to an increased rate of structural lesions, encephalopathy, subcortical arteriosclerotic encephalopathy or brain atrophy.MethodsIn a retrospective approach, the recurrence rate in 304 patients aged 60 years and above who presented with a first seizure between 2004 and 2017 was analyzed. Hierarchical Cox regression was used to investigate the impact of EEG and neuroimaging results, age or the prescription of anti-seizure medication (ASM) on seizure recurrence.ResultsSeizure recurrence rates were 24.5% and 34.4% after one and two years, respectively. Anti-seizure medication was started in 87.8% of patients, in 28.8% despite the absence of clear epileptogenic lesions on neuroimaging or epileptiform potentials in the EEG. Medical treatment significantly reduced the risk of recurrence (hazard ratio = 0.47). Epileptiform potentials in the EEG, epileptogenic lesions in neuroimaging and age had no significant effect on seizure recurrence. Age and the presence of neurodegenerative and psychiatric comorbidities showed a significant association with ASM prescription.ConclusionsThe present data show a strong protective effect of ASM on seizure recurrence in patients above the age of 60, even in the absence of pathologic neuroimaging or EEG results needed for the diagnosis of epilepsy. Treatment with ASM therefore seems beneficial for reducing the recurrence risk in elderly patients. The lack of a significant association between seizure recurrence and epileptogenic lesions might be related to other confounding factors like encephalopathy, subcortical arteriosclerotic encephalopathy, neurodegenerative diseases or brain atrophy.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

Inhibiting acid-sensing ion channel exerts neuroprotective effects in experimental epilepsy via suppressing ferroptosis.

Epilepsy is a chronic neurological disease characterized by repeated and unprovoked epileptic seizures. Developing disease-modifying therapies (DMTs) has become important in epilepsy studies. Notably, focusing on iron metabolism and ferroptosis might be a strategy of DMTs for epilepsy. Blocking the acid-sensing ion channel 1a (ASIC1a) has been reported to protect the brain from ischemic injury by reducing the toxicity of [Ca2+ ]i . However, whether inhibiting ASIC1a could exert neuroprotective effects and become a novel target for DMTs, such as rescuing the ferroptosis following epilepsy, remains unknown. In our study, we explored the changes in ferroptosis-related indices, including glutathione peroxidase (GPx) enzyme activity and levels of glutathione (GSH), iron accumulation, lipid degradation products-malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) by collecting peripheral blood samples from adult patients with epilepsy. Meanwhile, we observed alterations in ASIC1a protein expression and mitochondrial microstructure in the epileptogenic foci of patients with drug-resistant epilepsy. Next, we accessed the expression and function changes of ASIC1a and measured the ferroptosis-related indices in the invitro 0-Mg2+ model of epilepsy with primary cultured neurons. Subsequently, we examined whether blocking ASIC1a could play a neuroprotective role by inhibiting ferroptosis in epileptic neurons. Our study first reported significant changes in ferroptosis-related indices, including reduced GPx enzyme activity, decreased levels of GSH, iron accumulation, elevated MDA and 4-HNE, and representative mitochondrial crinkling in adult patients with epilepsy, especially in epileptogenic foci. Furthermore, we found that inhibiting ASIC1a could produce an inhibitory effect similar to ferroptosis inhibitor Fer-1, alleviate oxidative stress response, and decrease [Ca2+ ]i overload by inhibiting the overexpressed ASIC1a in the invitro epilepsy model induced by 0-Mg2+ . Inhibiting ASIC1a has potent neuroprotective effects via alleviating [Ca2+ ]i overload and regulating ferroptosis on the models of epilepsy and may act as a promising intervention in DMTs.

19 Characterization of Neurodevelopmental Comorbidities within a Paediatric Population with a First Epileptic Seizure

Abstract Background Epilepsy is the most common paediatric neurological disorder. An estimated 4% of the general population will have an unprovoked epileptic seizure at least once in their lifetime. Of these, about 40% will experience a recurrence within two years. The International League Against Epilepsy (ILAE) established that one part of the definition of epilepsy was the onset of a first seizure with a recurrence risk of more than 60% over 10 years. However, except for epileptiform abnormalities and a structural-metabolic etiology present on the electroencephalogram (EEG), very few known factors are consistently associated with first epileptic seizures. Objectives Our study’s objective was to characterize neurodevelopmental comorbidities, namely attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), anxiety, depression, gross motor delay and language delay, in patients following a first epileptic seizure as compared to healthy controls. Design/Methods Children referred in neurology for a first suspected epileptic seizure, between June 2016 and June 2018 at the Centre Hospitalier Universitaire Sainte-Justine (CHUSJ), underwent EEG and neurological evaluations. For screening of comorbidities, parents completed age-appropriate M-CHAT-R/F, SCQ, ASQ-3, SCARED, and CES-DC questionnaires via a web platform adapted from CHADIS. Questionnaire scores were adjusted for age and sex and analyzed via a Student’s t-test. The prevalence of comorbidities was analyzed via a chi-square statistical test. Results A total of 72 subjects aged between 1 month and 18 years (42 males, 30 females) were enrolled in the study. Patients with a first epileptic seizure (n=37) showed significantly more comorbidities compared to the healthy subjects (54% vs. 31%, p&amp;lt;0.05). Patients with a first epileptic seizure had significantly more language delay (50%, p=0.015), ADHD (45%, p=0.008), and a significantly higher score in the Social Communication Questionnaire (SCQ) (p=0.03), compared to healthy subjects. Conclusion Our results confirm the increased rate of comorbidities in children with a first epileptic seizure and, thus, the importance of concomitant screening for those disorders at the time of the initial presentation.

Prevalence of anti-seizure medication nonadherence and its associated factors, among people with epilepsy in North Shewa, Ethiopia, 2021

BackgroundEpilepsy is a worldwide neurologic illness, characterized by recurrent unprovoked epileptic seizures and can affect people of all age groups. Patients who are receiving drug therapy for chronic diseases, such as epilepsy, must fit complex medication regimens into their everyday routines. Managing medication schedules may pose a significant burden on patients’ lives. Anti-seizure medication choices should therefore be tailored to patients’ factors that may limit medication use. The study aimed to determine the prevalence and Predictors of anti-seizure medication nonadherence among patients with epilepsy. MethodologyAn institutional-based cross-sectional study was conducted among 352 people with epilepsy who were selected by systematic random sampling method at government hospitals in North Shewa Ethiopia. Data were collected by reviewing patients’ charts and interviewing people with epilepsy by using structured and pretested questionnaires. Data obtained were encoded into EPI-INFO software and exported to SPSS version 25 for analysis. Logistic regression was employed to assess independent factors associated with medication non-adherence. ResultThe prevalence of anti-seizure medication non-adherence was 40%. Being female [AOR = 3.37, 95%, CI: 1.84, 6.18], Divorced [AOR = 9.13, 95%, CI: 1.80, 46.34], Being jobless [AOR = 7.33, 95%, CI: 3.24, 16.56], Perceived poor social support [AOR = 2.73, 95%, CI: 1.28, 5.82], perceived stigma [AOR = 5.07, 95%, CI: 2.40, 10.68], polytherapy [AOR = 2.23, 95%, CI: 1.06, 4.71], drug side effects[AOR = 6.03, 95%, CI: 3.17, 11.45], buying medications [AOR = 5.81, 95%, CI: 3.63,16.79] and duration of stay on treatment [AOR = 4.31, 95%, CI: 1.863, 9.97] were significant predictors of anti-seizure medication non-adherence. ConclusionNon-adherence to anti-seizure medication among people with epilepsy in the study area was relatively higher as compared with study reports from different parts of the country. Health and clinical, socio-economy, and patients’ psychological mindset were among the determinant factors affecting the consistency of epilepsy treatment adherence. Enhanced professional, health education for patients as well as for society and financial support, are basic pillars to reduce the constraints of effective treatment.

Quality of life indicators in children with non-traumatic and non-syncopal transient loss of consciousness and their families

Background. There are extremely limited research on the quality of life in children with non-traumatic and non-syncopal transient loss of consciousness (TLOC), which does not sufficiently reflect the impact of epilepsy, first unprovoked epileptic seizure or psychogenic TLOC on the parental quality of life and family functioning. The purpose was to provide a comparative analysis of quality of life in children with non-traumatic and non-syncopal TLOC, as well as to study the impact of these diseases on the family quality of life. Materials and methods. Twenty-two patients with epilepsy, 18 with first unprovoked epileptic seizure, and 18 with psychogenic TLOC aged 8–17 years were examined. The control group consisted of 40 apparently healthy children. Quality of life in children and their parents was assessed using the PedsQL™ 4.0 Generic Core Scales (child report, adolescent report, parent report), and the PedsQL™ 2.0 Family Impact Module (parent report). Results. Epilepsy and psychogenic TLOC have a negative impact on the quality of life of children. Epilepsy was accompanied by deterioration of physical (57.1 ± 5.2; 77.3 ± 4.8 points) and psychosocial health (60.7 ± 5.7; 76.3 ± 2.7 points), while psychogenic TLOC were characterized by only low physical health (55.0 ± 5.5; 77.3 ± 4.8 points) according to patient self-reports (p &lt; 0.01). The quality of life of children with epilepsy was influenced by age (r = –0.55; r = 0.007) and features of clinical manifestation of the epileptic seizure (r = –0.56; r = 0.007). The number of previous non-epileptic seizures had an impact on quality of life among patients with psychogenic TLOC (r = –0.60; r = 0.0008). The first unprovoked epileptic seizure was not accompanied by quality of life deterioration among children and parents. Only epilepsy was associated with a decrease in the quality of life of parents and family as a whole, mainly due to an increased anxiety (38.8 ± 4.5; 63.2 ± 4.0 points), a decrease in emotional functioning (47.5 ± 3.9; 66.9 ± 3.3 points), a lack of effective communication between family members (50.0 ± 4.8; 79.4 ± 2.9 points); p &lt; 0.01. Conclusions. The combined evaluation of quality of life in children and their parents helps better understand the impact of disease course peculiarities and treatment on the child’s and his family’s quality of life in order to provide timely medical and psychological assistance.

Prognosis of adults and children following a first unprovoked seizure.

Prognosis of adults and children following a first unprovoked seizure.

Preispitivanje uloge magnezijuma u istraživanjima epilepsije i zbrinjavanju pacijenata sa epilepsijom

Magnesium is a bioessential mineral with multiple neuroactive effects. Mg2+ ion stabilizes excitable membranes. Epilepsy is the third most frequent chronic neurological condition characterized by spontaneous reappearance of unprovoked epileptic seizures, whose underlying mechanisms are not completely understood yet. A literature review on the role of magnesium in basic and clinical epileptology has been made in order to enlighten the importance of magnesium deficiency in the mechanisms of epileptic brain hyperexcitability, as well as the significance of including magnesium into the management of epilepsy patients. Neuronal magnesium requirements are high. The concentration of magnesium in the cerebrospinal fluid (CSF) is even higher than in the blood. In experimental epilepsy research, perfusing hippocampal slices with artificial CSF containing low concentration of extracellular Mg2+ is a frequently used animal model of spontaneously induced epileptiform activity. Magnesium deficiency is the most frequent clinically unrecognized electrolyte disbalance, often overlooked in epilepsy patients. Serum and CSF Mg2+ concentrations are lower in patients with epilepsy, as compared to healthy controls. Hypomagnesaemia increases seizure frequency and the risk of sudden unexpected death in pharmacoresistant epilepsy. Oral magnesium supplements help achieve better seizure control. Parenterally administered Mg2+ efficiently controls seizures in several epileptic encephalopathies in adults and children (in eclampsia, uremia, porphyria, febrile seizures, infantile spasms), and also helps control status epilepticus. Subclinical magnesium deficiency, very frequent in general population, acts as a factor contributing to seizure generation in epilepsy. It is recommended to assess magnesium status in epilepsy patients. This literature review reveals the therapeutic potential of magnesium as a simple antiepileptic agent, which exceeds its current clinical use.

Acute symptomatic epileptic seizures and epilepsy after stroke

Acute symptomatic epileptic seizures occur within 7 days after the stroke onset. Acute symptomatic epileptic seizures occur in 6.3% of stroke cases: ischemic stroke 4.2%, cerebral infarction with hemorrhagic transformation 12.5%, intracerebral hemorrhage 16.2%. Cumulative risk of subsequent unprovoked epileptic seizure after the first acute symptomatic seizure at follow-up for 10 years is 18.7 %. In acute symptomatic epileptic seizure secondary prevention with antiepileptic drugs usually is not indicated. If antiepileptic drug treatment is initiated after a single acute symptomatic seizure, it should be discontinued after the acute period of the disease. The 10-years risk of subsequent unprovoked epileptic seizures after the single unprovoked epileptic seizure in stroke patients is 71.5%. In this situation the epilepsy diagnosis is reasonable and antiepileptic drug treatment should be initiated. The incidence of epilepsy after acute ischemic or hemorrhagic stroke is identical 1012%. The choice of the group of antiepileptic drugs should be based on clinical guidelines for patients with focal forms of epilepsy. Pharmacokinetic interactions between antiepileptic drugs and oral anticoagulants, antiplatelet agents, antihypertensive drugs, and other xenobiotics should be minimized. Thus antiepileptic drugs that induce or inhibit microsomal liver enzymes should also be avoided.

Application of Machine Learning Methods for Epilepsy Risk Ranking in Patients with Hematopoietic Malignancies Using.

Machine learning methods to predict the risk of epilepsy, including vascular epilepsy, in oncohematological patients are currently considered promising. These methods are used in research to predict pharmacoresistant epilepsy and surgical treatment outcomes in order to determine the epileptogenic zone and functional neural systems in patients with epilepsy, as well as to develop new approaches to classification and perform other tasks. This paper presents the results of applying machine learning to analyzing data and developing diagnostic models of epilepsy in oncohematological and cardiovascular patients. This study contributes to solving the problem of often unjustified diagnosis of primary epilepsy in patients with oncohematological or cardiovascular pathology, prescribing antiseizure drugs to patients with single seizure syndromes without finding a disease associated with these cases. We analyzed the hospital database of the V.A. Almazov Scientific Research Center of the Ministry of Health of Russia. The study included 66,723 treatment episodes of patients with vascular diseases (I10–I15, I61–I69, I20–I25) and 16,383 episodes with malignant neoplasms of lymphoid, hematopoietic, and related tissues (C81–C96 according to ICD-10) for the period from 2010 to 2020. Data analysis and model calculations indicate that the best result was shown by gradient boosting with mean accuracy cross-validation score = 0.96. f1-score = 98, weighted avg precision = 93, recall = 96, f1-score = 94. The highest correlation coefficient for G40 and different clinical conditions was achieved with fibrillation, hypertension, stenosis or occlusion of the precerebral arteries (0.16), cerebral sinus thrombosis (0.089), arterial hypertension (0.17), age (0.03), non-traumatic intracranial hemorrhage (0.07), atrial fibrillation (0.05), delta absolute neutrophil count (0.05), platelet count at discharge (0.04), transfusion volume for stem cell transplantation (0.023). From the clinical point of view, the identified differences in the importance of predictors in a broader patient model are consistent with a practical algorithm for organic brain damage. Atrial fibrillation is one of the leading factors in the development of both ischemic and hemorrhagic strokes. At the same time, brain infarction can be accompanied both by the development of epileptic seizures in the acute period and by unprovoked epileptic seizures and development of epilepsy in the early recovery and in a longer period. In addition, a microembolism of the left heart chambers can lead to multiple microfocal lesions of the brain, which is one of the pathogenetic aspects of epilepsy in elderly patients. The presence of precordial fibrillation requires anticoagulant therapy, the use of which increases the risk of both spontaneous and traumatic intracranial hemorrhage.

Outcome at age 7 of epilepsy presenting in the first 2 years of life. A population-based study.

ObjectiveExisting data suggest that epilepsy presenting in the first few years of life carries a worse prognosis than later onset. However, studies are few and methods differ, making interpretations of data uncertain. This study analyzes outcome at age 7 and potential prognostic factors in a well‐characterized population‐based cohort with epilepsy onset during the first 2 years of life.MethodsAn incidence cohort of 116 prospectively identified cases of epilepsy with seizure onset before age 2 years was described in Stödberg et al. (2020). Cases were originally retrieved from the Stockholm Incidence Registry of Epilepsy (SIRE), which registered all cases with a first unprovoked epileptic seizure from September 1, 2001, in Northern Stockholm. Data on treatment and outcome at age 7 years were collected from electronic medical records and through interviews with parents. Outcome and potential prognostic factors were analyzed with descriptive statistics and multivariable log binomial regression analysis.ResultsEleven children (9.5%) died before age 7. Polytherapy was common. Epilepsy surgery was performed in two children. At age 7 years, 61 of 116 children (53%) had been seizure‐free for the last 2 years or longer. Intellectual disability was diagnosed in 57 of 116 children (49%), autism spectrum disorder in 13 (11%), and cerebral palsy in 28 (24%). West syndrome had a similar seizure remission rate but a worse cognitive outcome. There was no difference in outcome between first and second year onset. Six predictors, including etiology, remained associated with two or more outcome variables after regression analysis.SignificanceAbout half of children with infantile‐onset epilepsy will become seizure‐free and half of them will have intellectual disability. Etiology was confirmed as a major independent predictor of outcome. Our study contributes to a more firm knowledge base when counseling parents of infants diagnosed with epilepsy.

Update on seizure and therapeutic drug monitoring in dogs and cats

Background: Epilepsy is defined as the propensity to suffer recurring unprovoked epileptic seizures and is one of the most frequently encountered neurological complaints seen in veterinary practice. Effective management of these cases requires accurate identification and diagnosis, appropriate client communication, as well as regular monitoring of seizure progression and response to therapy.Aim of the article: This article provides an update on the diagnosis of epileptic seizures and how to manage such cases with use of anti‐epileptic drugs, including imepitoin, which is a relatively recent addition to the range of available therapies.

Diagnostic Dynamics of Post-Traumatic Epilepsy in the Context of Comorbid Medical Conditions

Posttraumatic epilepsy is a form of epilepsy in which the formation of an epileptogenic and epileptic focus has a reliable causal relationship with previously suffered traumatic brain injury and associated CVD, which may clinically manifest as recurrent unprovoked epileptic seizures. This suggests that it is reasonable to identify patients with this form of the disease as a separate study group [1,3,5].

Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease

RationaleLate-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. MethodsTwenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. ResultsCompared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. ConclusionPatients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Management of a first unprovoked epileptic seizure in adolescence and adulthood.

An epileptic seizure is one of the causes of so-called "transient neurological events" (TNEs). The differential diagnosis of a TNE relies mainly on history and physical examination. Laboratory markers are less frequently useful. After diagnosing an epileptic seizure, a distinction must be made between an acute symptomatic and an unprovoked seizure, since they have different treatments and prognosis. History, physical examination and other examinations (laboratory and imaging) are paramount in this distinction. After the diagnosis of a first unprovoked seizure, an EEG should be requested which may aid in establishing the diagnosis, evaluating the recurrence risk or ascertaining the self-limited nature of the seizure. 3T-MRI with an epilepsy protocol can be considered when CT has not clarified the aetiology. The decision to treat should be discussed with the patient/relatives, taking into account the risk of recurrence, the clinical characteristics (aetiology, seizure type, age, job, epileptic seizure schedule, comorbidities and polymedication), probability of AED side effects, and stigmatization. Nowadays, the chosen regimen is usually monotherapy with a second-generation AED that better suits the patient's characteristics, comorbidities and concurrent medication. Counselling should include first aid, precipitating factors, sport and physical exercise in order to avoid possible driving restrictions, the need for therapy compliance, and risk of recurrence and SUDEP.

Informed DEcision for cerebrospinal fluid analysis after epiLeptic seizures- the IDEAL-score: A development and validation study

BackgroundThis observational study was done to develop a score based on clinical predictors that enables a guided decision for the necessity of cerebrospinal fluid (CSF) analysis after first unprovoked epileptic seizures and to validate this score in a retrospective patient cohort. MethodsClinical predictors were identified by two panels of epilepsy experts and selected according to content validity ratios. Based on these predictors a score was created and applied to a cohort of patients with first epileptic seizures. ResultsThe “IDEAL score” consists of 9 items (fever, prolonged disturbance of consciousness, headache, imaging results, cognitive dysfunction, status epilepticus, malignancy, autoimmune encephalitis symptoms) that are collected at two different time points (< 3 h [A-score]; > 3 h [B-score] after hospital admittance). A CSF analysis is recommended, if at least one clinical finding is present, either one of the items evaluated during the acute phase (A-score) or later in the diagnostic process (B-score). In 41 patients (13%) CSF analysis provided essential clues to the cause of the seizure. The combined IDEAL score reached a sensitivity of 98%, a specificity of 53%, a positive predictive value of 24% and a negative predictive value of 99% in this patient cohort. ConclusionsA CSF analysis after first epileptic seizures provided decisive etiological findings in only 13% of all investigated patients. The IDEAL score offers clinicians a simple and easy-to-implement algorithm to assess the necessity of a CSF analysis, and to prevent unnecessary diagnostic procedures.

Evidences for a Role of Gut Microbiota in Pathogenesis and Management of Epilepsy.

Epilepsy as a chronic neurological disorder is characterized by recurrent, unprovoked epileptic seizures. In about half of the people who suffer from epilepsy, the root cause of the disorder is unknown. In the other cases, different factors can cause the onset of epilepsy. In recent years, the role of gut microbiota has been recognized in many neurological disorders, including epilepsy. These data are based on studies of the gut microbiota–brain axis, a relationship starting by a dysbiosis followed by an alteration of brain functions. Interestingly, epileptic patients may show signs of dysbiosis, therefore the normalization of the gut microbiota may lead to improvement of epilepsy and to greater efficacy of anticonvulsant drugs. In this descriptive review, we analyze the evidences for the role of gut microbiota in epilepsy and hypothesize a mechanism of action of these microorganisms in the pathogenesis and treatment of the disease. Human studies revealed an increased prevalence of Firmicutes in patients with refractory epilepsy. Exposure to various compounds can change microbiota composition, decreasing or exacerbating epileptic seizures. These include antibiotics, epileptic drugs, probiotics and ketogenic diet. Finally, we hypothesize that physical activity may play a role in epilepsy through the modulation of the gut microbiota.

Immediate antiepileptic drug treatment, versus placebo, deferred, or no treatment for first unprovoked seizure

Background This is an updated version of the Cochrane review previously published in 2016. There is considerable disagreement about the risk of recurrence following a first unprovoked epileptic seizure. A decision about whether to start antiepileptic drug treatment following a first seizure should be informed by information on the size of any reduction in risk of future seizures, the impact on long‐term seizure remission, and the risk of adverse effects. Objectives To review the probability of seizure recurrence, seizure remission, mortality, and adverse effects of antiepileptic drug (AED) treatment given immediately after the first seizure compared to controls (placebo, deferred treatment, or no treatment) in children and adults. Search methods For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to May 24, 2019) on 28 May 2019. There were no language restrictions. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi‐randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organisation International Clinical Trials Registry Platform (ICTRP). Selection criteria Randomised controlled trials (RCTs) and quasi‐RCTs that could be blinded or unblinded. People of any age with a first unprovoked seizure of any type. Included studies compared participants receiving immediate antiepileptic treatment versus those receiving deferred treatment, those assigned to placebo, and those untreated. Data collection and analysis Two review authors independently assessed the studies identified by the search strategy for inclusion in the review and extracted data. The certainty of the evidence for the outcomes was classified in four categories according to the GRADE approach. Dichotomous outcomes were expressed as Risk Ratios (RR) with 95% confidence intervals (CI). Time‐to‐event outcomes were expressed as Hazard Ratios (HR) with 95% CI. Only one trial used a double‐blind design, and the two largest studies were unblinded. Most of the recurrences were generalised tonic‐clonic seizures, a major type of seizures that is easily recognised, which should reduce the risk of outcome reporting bias. Main results After exclusion of irrelevant papers, six studies (eleven reports) were selected for inclusion. Individual participant data were available from the two largest studies for meta‐analysis. Selection bias and attrition bias could not be excluded within the four smaller studies, but the two largest studies reported attrition rates and adequate methods of randomisation and allocation concealment. Only one small trial used a double‐blind design and the other trials were unblinded; however, most of the recurrences were generalised tonic‐clonic seizures, a type of seizure that is easily recognisable. Compared to controls, participants randomised to immediate treatment had a lower probability of relapse at one year (RR 0.49, 95% CI 0.42 to 0.58; 6 studies, 1634 participants; high‐certainty evidence), at five years (RR 0.78; 95% CI 0.68 to 0.89; 2 studies, 1212 participants; high‐certainty evidence) and a higher probability of an immediate five‐year remission (RR 1.25; 95% CI 1.02 to 1.54; 2 studies, 1212 participants; high‐certainty evidence). However, there was no difference between immediate treatment and control in terms of five‐year remission at any time (RR 1.02, 95% CI 0.87 to 1.21; 2 studies, 1212 participants; high‐certainty evidence). Antiepileptic drugs did not affect overall mortality after a first seizure (RR 1.16; 95% CI 0.69 to 1.95; 2 studies, 1212 participants; high‐certainty evidence). Compared to deferred treatment, treatment of the first seizure was associated with a significantly higher risk of adverse events (RR 1.49, 95% CI 1.23 to 1.79; 2 studies, 1212 participants; moderate‐certainty evidence). We assessed the certainty of the evidence as moderate to low for the association of higher risk of adverse events when treatment of the first seizure was compared to no treatment or placebo, (RR 14.50, 95% CI 1.93 to 108.76; 1 study; 118 participants) and (RR 4.91, 95% CI 1.10 to 21.93; 1 study, 228 participants) respectively. Authors' conclusions Treatment of the first unprovoked seizure reduces the risk of a subsequent seizure but does not affect the proportion of patients in remission in the long term. Antiepileptic drugs are associated with adverse events, and there is no evidence that they reduce mortality. In light of this review, the decision to start antiepileptic drug treatment following a first unprovoked seizure should be individualised and based on patient preference, clinical, legal, and sociocultural factors.