Epileptic Etiology Research Articles

Efficacy and safety of adjunctive cenobamate based on patient etiology: Post-hoc analysis of YKP3089C017 randomized clinical trial

IntroductionAdjunctive cenobamate was effective and safe for the treatment of uncontrolled focal onset seizures in a randomized, double-blind, placebo-controlled, phase 2 study (YKP3089C017; NCT01866111). This post-hoc analysis assessed the efficacy of adjunctive cenobamate in the treatment of patients with different epileptic etiologies during the study. MethodsAdult patients with uncontrolled focal seizures who previously received 1 to 3 antiseizure medications (ASMs) were randomly assigned in a ratio of 1:1:1:1 to receive placebo or cenobamate 100, 200 or 400 mg/day. Patients were further stratified based on their etiologic causes as genetic/presumed genetic, unknown cause, structural cause, and not reported (NR) groups. The frequency per 28 days for an 18-week double-blind treatment period, responder rates (≥50 %, ≥75 %, ≥90 %, and 100 %) during the maintenance phase (12 weeks), and safety were assessed. ResultsA total of 394 patients were categorized into the genetic/presumed genetic (n = 9; 2.28 %), unknown cause (n = 199; 50.51 %), structural cause (n = 177; 44.92 %), and NR (n = 13; 3.30 %) groups, with 4 patients were classified into either of the two etiological causes each. The baseline characteristics were comparable. The percentage of reduction in seizure frequency per 28 days was significantly higher in the cenobamate-treated structural (p = 0.01) and unknown cause (p = 0.0003) groups compared with the placebo group. Responder rates of ≥50 %, ≥75 %, ≥90 %, and 100 % were also higher with cenobamate therapy. Notably, no serious treatment-emergent adverse events (TEAEs) were observed in the genetic/presumed genetic group treated with cenobamate. The most common TEAEs (≥10 %) occurring in patients treated with cenobamate were nervous system disorders by system organ class, and somnolence was the most commonly reported TEAE. ConclusionCenobamate reduces seizures in adult patients previously treated with ASMs, with high responder rates and acceptable safety, regardless of underlying causes.

Could Coronavirus Disease 2019 Vaccine Be a New Terminology in Epileptic Seizure Etiology?

Could Coronavirus Disease 2019 Vaccine Be a New Terminology in Epileptic Seizure Etiology?

SEIZURES IN DOGS AND CATS

When dogs or cats get seizures, epileptic seizures and epilepsy are usually thought of. However, it is important to take into account the existence of seizures that are similar to epileptic seizures but do not belong to epileptic seizures (non-epileptic seizures). Nonepileptic seizures occur suddenly, are short-term, disappear as quickly as they occur, recur and have no epileptic etiology and can be of non-neurological and neurological origin. Unlike non-epileptic seizures, epileptic seizures have a specific neural origin and represent excessive, synchronous, usually self-limiting epileptic activity of brain neurons. Epileptic seizures should be distinguished from reactive seizures because reactive seizures occur as a natural response of a healthy brain to transient disorders (metabolic or toxic in nature) and they disappear after the cause ceases to act. Absolute confirmation that it is an epileptic seizure can be difficult because it requires both visualization of the seizure and registration of changes on the EEG. In practice, the suspicion that epileptic seizures occurs is based on information from the medical history and videos. In making a differential diagnosis when an seizure occurs, it is necessary to take into account the age of infected animals, the presence of clinical signs other than the seizure, the presence or absence of disease progression, video recording, blood counts and blood biochemical parameters results, CST test results, and X-ray, MRI or CT findings. The first step in a diagnosis is to determine whether the lesion that leads to the onset of the seizure is localized extracranially or intracranially. If the lesion is localized extracranially, it should be determined whether the problem originates outside the body (poisoning with xylitol, organophosphates, chocolate) or from the body (hypothyroidism, hypocalcemia, kidney disease, etc.). If the process is localized intracranially, it should be determined whether the process is progressive (tumor, inflammation, hydrocephalus, etc.) or not.

Ending the pain of children with severe epilepsy? An audit of the impact of medical cannabis in 10 patients

Background Scientific and anecdotal evidence suggest that whole plant cannabis extracts are effective in reducing seizure frequency in individuals with a range of epileptic etiologies. We report a case series of 10 individuals using CBMPs in the UK to treat their conditions. Methods In this retrospective study, we report on patients (aged 2-48) with severe, intractable, childhood onset epilepsies using combined cannabinoid therapy. Carers of patients provided details through the charity ‘End our Pain’ and these data were subsequently analysed. Our primary objective was to assess changes in monthly seizure frequency pre and post initiation of CBMPs. We also report on previous and current AED, CBD:THC daily dose, quality of life and financial costs associated with CBMP private prescription. Change in monthly seizure frequency were assessed using a Wilcoxon Signed-ranks test. Results Of the 10 patients enrolled in the study there was an 97% mean reduction in monthly seizure frequency post initiation of CBMPs which was statistically significant (Z = 0, p < 0·01). We showed a reduction in AED use following initiation of CBMPs from a mean of 8 (±5·98) to 1 (±1·05). All patients were using either Bedrolite or Bedica (Bedrocan International) as their CBMP. Individual daily doses of THC ranged from 6·6mg – 26·5mg and for CBD, 200 mg – 550 mg. Average monthly cost of CBMP was £1816·20. Interpretation Our findings suggest a combination of CBD and THC based products are effective in reducing seizure frequency in a range of epileptic conditions. We highlight the inefficacy of the healthcare system in supporting these patients who bare great personal and financial burdens. We encourage specialist physicians and relevant bodies to permit greater ease of access of these medications to those patients where efficacy has been shown.

Rufinamide efficacy and association with phenotype and genotype in children with intractable epilepsy: A retrospective single center study

ObjectiveTo assess long-term efficacy and tolerability of rufinamide in children with epilepsy and a broad spectrum of underlying epileptic etiologies. MethodsPatients with epilepsy treated with rufinamide between 1/1/2009 and 1/1/2018 at Seattle Children’s Hospital were included. Data were collected via retrospective chart review. Rufinamide efficacy was defined as seizure reduction from baseline including seizure free, >50% reduction, any reduction, no reduction, or worsening seizures. Pearson’s chi-square test was used for statistical analysis. Results183 patients (70 females and 113 males) with a broad spectrum of epileptic aetiologies (genetic/metabolic, hypoxic-ischemic, structural and others) were included. 45.9% of the patients had Lennox Gastaut syndrome. Rate of any seizure reduction was at 47.5%, seizure reduction >50% at 35%, and seizure free at 3.3%. Mean rufinamide dosage was 33.9 mg/kg/d (SD = 14.12). Mean duration of treatment was 44.48 months (SD 32.33). Suspected adverse effects occurred at 10.9%, most often as fatigue. Rufinamide achieved better seizure reduction in girls compared to boys [OR = 0.52, 95% CI (0.28, 0.97), p = 0.038]. Seizures were activated in a patient with a SCN1A mutation, fully controlled in a patient with a SCN8A mutation. Patients with certain genetic abnormalities such as DEPDC5, KCNQ2, SPATA5, and 47XYY achieved significant seizure reduction. ConclusionsRufinamide is an effective and well-tolerated drug for long-term treatment in pediatric patients with intractable epilepsy. Certain genotypes such as SCN8A showed good response to rufinamide. Girls seemed to respond better than boys.

CT perfusion and EEG patterns in patients with acute isolated aphasia in seizure-related stroke mimics

PurposeIsolated speech impairment is one of the most challenging clinical manifestations of stroke mimic (SM). We aimed to investigate perfusional and EEG pattern of isolated aphasia to better differentiate between vascular and epileptic etiology in emergency settings. MethodWe retrospectively analyzed 481 cases with acute focal neurological symptoms admitted to our Stroke Unit. The patients showing isolated aphasia and confirmed ischemic infarction or SM with seizure etiology on follow-up were included for subsequent analysis of clinical, neuroimaging, and EEG data. We investigated differences in CT Perfusion maps between ROI in the anatomical area compatible with clinical presentation, contralateral ROI and EEG in order to evaluate perfusion and brain oscillatory activity abnormalities. Results45 patients presented isolated aphasia as principal neurological symptom: 27 cases due to acute ischemic event, 11 due to seizure SM, while 7 were SM due to other etiologies. Out of 11 SM patients with seizure etiology, significant hyperperfusion on CTP maps (MTT AI%<-10%) and sharp EEG waves were observed in 8 patients, while in 3 patients slight hypoperfusion (MTT AI%<20%) and slow EEG rhythms were detected. 24 out of 27 ischemic stroke patients presented severe hypoperfusion with MTT AI above the stroke threshold (MTT AI > 45%). All ischemic stroke patients presented slower EEG rhythms. ConclusionsThe main finding of this study is the identification of different clinical and neuroimaging patterns of isolated aphasia with epileptic or ischemic etiology in emergency settings.

GAD65 autoantibody characteristics in patients with co-occurring type 1 diabetes and epilepsy may help identify underlying epilepsy etiologies

BackgroundAutoantibodies against the smaller isoform of glutamate decarboxylase (GAD65Ab) reflect autoimmune etiologies in Type 1 diabetes (T1D) and several neurological disorders, including Stiff Person Syndrome (SPS). GAD65Ab are also reported in cases of epilepsy, indicating an autoimmune component. GAD65Ab in patients with co-occurring T1D, epilepsy or SPS may be part of either autoimmune pathogenesis. To dissect the etiologies associated with GAD65Ab, we analyzed GAD65Ab titer, epitope specificity and enzyme inhibition in GAD65Ab-positive patients diagnosed with epilepsy (n = 28), patients with epilepsy and T1D (n = 10), patients with SPS (n = 20), and patients with T1D (n = 42).ResultsGAD65Ab epitope pattern in epilepsy differed from T1D and SPS patients. Four of 10 patients with co-occurring T1D and epilepsy showed GAD65Ab profiles similar to T1D patients, while lacking GAD65Ab characteristics found in GAD65Ab-positive epilepsy patients. One of these patients responded well to anti-epileptic drugs (AEDs), while another patient did not require medication for seizure control. The third patient was refractory due to a diagnosis of meningioma. The response of the remaining patient to AEDs was unknown. GAD65Ab in the remaining six patients with T1D and epilepsy showed profiles similar to those in epilepsy patients.ConclusionsDifferent autoimmune responses associated with T1D, epilepsy and SPS are reflected by disease-specific GAD65Ab patterns. Moreover, the epileptic etiology in patients diagnosed with both T1D and epilepsy may present two different etiologies regarding their epileptic condition. In one group T1D co-occurs with non-autoimmune epilepsy. In the other group GAD65Ab are part of an autoimmune epileptic condition.

The Identification of Torsades de Pointes via CEEG: A Case Report on a Patient with Physiologically Provoked Nonepileptic Events

ABSTRACTContinuous electroencephalography (CEEG) is chiefly performed at The Medical University of South Carolina (MUSC) for identifying seizures, including its refined use within the epilepsy monitoring unit (EMU) as a differentiator between epileptic and psychogenic etiologies. CEEG also provides critical data that carry implications outside the bounds of both epilepsy and psychogenic events, such as the characterization of unorthodox clinical phenomena that are of physiological (though nonepileptic) origins. Although nonepileptic events (NEEs) are primarily linked with psychogenic phenomena (conversion disorder, malingering) that can mimic epileptic activity, they, like seizures, have diverse semiologies and etiologies. Although it is reasonable for seasoned neurodiagnostics professionals to develop an expectation that NEEs are of psychogenic origin, it is essential to acknowledge that they include etiologies that lay beyond those of psychiatric influence. Such a case is presented in which a 74-year-old female patient who, though initially suspected of having either psychogenic or epileptic seizures, was found to be having frequent episodes of the life-threatening cardiac convulsive syncope torsades de pointes (TdP). The patient had several known risk factors for TdP, including a prolonged QT complex, female gender, advancing age, active medications known to provoke TdP, and electrolyte imbalances (low magnesium and potassium) (Trinkley et al. 2013). TdP was first suspected through the CEEG by a combination of remarkable EEG background changes, recorded video evidence of clinical features, and accompanying single-lead electrocardiogram (ECG) data captured during the events. Upon proper diagnosis, the patient was urgently treated with restorative measures, including electrolyte replenishment, pacemaker implantation, and cessation of provocative medications.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy.

Protocolo terapéutico de las crisis epilépticas en Urgencias

Seizures are one of the most common neurological emergencies. Not all of them have epileptic etiology but can also be secondary to systemic processes such as infections, arrhythmias, changes in acid-base balance or consuming toxic. It is important a good history and careful physical examination for differential diagnosis. The investigations include an analytical whole blood (with antiepileptic drug levels if the patient takes chronically), electrocardiogram and cranial computed tomography in the case of a first episode. Most crises are self-limiting in less than 5minutes. If a longer duration is necessary to start treatment with benzodiazepines and different antiepileptic drugs to prevent progression to status, leading to significant morbidity and mortality and may require admission to intensive care. In general, after an isolated crisis should not pautar chronic antiepileptic treatment unless the risk of recurrence is high.

Clinical analysis on the relationship between febrile seizure and epileptic etiology in adolescents

Objective To analyze the clinical characteristics and treatment of young epileptic patients with febrile seizure (FS) history, and to investigate the relationship between febrile seizure and epileptic attack in adolescents. Methods The clinical data of epileptic patients with the onset age < 18 from Chinese PLA General Hospital during October 2002 to July 2010 and their epileptic etiology were collected and retrospectively analyzed. The clinical characteristics, accessory examination results and treatment of these patients with simple febrile seizure (SFS) and complex febrile seizure (CFS) were analyzed. Results According to diagnostic criteria of epilepsy, 2699 cases (58.74%) with the onset age < 18 were collected from 4595 cases, including 1573 cases (58.28%) with idiopathic epilepsy and 1126 cases (41.72%) with secondary epilepsy. Febrile seizure (297 cases, 26.38%) was the main cause of adolescent secondary epilepsy, including simple febrile seizure in 200 cases and complex febrile seizure in 97 cases. Partial seizure was the main attack type ( χ 2 = 4.933, P = 0.026). The abnormal rate of neuroimaging ( χ 2 = 38.083, P = 0.000) and neuroelectrophysiological ( χ 2 = 4.469, P = 0.035) in patients with febrile seizure history were obviously increased. The rate of antiepileptic drugs (AEDs) therapy was 66.67% (198/297), and patients who had taken traditional antiepileptic drugs accounted for 70.20% (139/198). Conclusions The causes of secondary epilepsy in adolescents were various, with febrile seizure as the major one. Partial seizure was the main attack type in both simple febrile seizure and complex febrile seizure. Traditional antiepileptic drugs therapy was chosen more. However, nearly one?third patients took no medicine or took their medicine irregularly. doi: 10.3969/j.issn.1672-6731.2014.12.009

A protective effect of musical expertise on cognitive outcome following brain damage?

The current review examines the possibility that training-related changes that take place in the brains of musicians may have a beneficial effect on their cognitive outcome and recovery following neurological damage. First, we propose three different mechanisms by which training-related brain changes might result in relatively preserved function in musicians as compared to non-musicians with cerebral lesions. Next, we review the neuropsychological literature examining musical ability in professional musicians following brain damage, specifically of vascular, tumoral and epileptic aetiology. Finally, given that assessment of musician patients can greatly inform our understanding of the influence of premorbidexperience on postmorbidrecovery, we suggest some basic guidelines for the future evaluation of relevant patients.

Er EEG en nyttig undersøkelse i voksenpsykiatrien?

We present a brief overview of the use of EEG in psychiatry, with particular emphasis on differential diagnosis examination in case of acute psychiatric conditions. The article is based on a literature search in PubMed and the authors' own collections of articles and personal experience. Onset of epilepsy, encephalitis or other cerebral diseases may be accompanied by psychiatric or cognitive symptoms. Slow EEG activity may be an unspecific sign of cerebral disease. Psychiatric patients are also at an increased risk of epilepsy. In case of seizure symptoms such as convulsions or conditions with rapid changes in affective states, epileptiform activity during EEG is a specific sign of epileptic aetiology or comorbidity. Quantitative frequency analysis (QEEG) is useful for research purposes and in exceptional cases also in a clinical context. No QEEG method has as yet become accepted as providing reliable, independent markers for psychiatric disease or treatment response. EEG should be undertaken in case of newly occurring psychoses and for conditions with a fluctuating or progradiating loss of cognitive function. Adult psychiatric patients with seizure symptoms or rapid changes in affective states should also be referred to EEG.

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

Neuropsychiatric Symptoms as a Putative Crescendo Warning of a Striatocapsular Infarct?

1881 – Hallucinations and delusions in a hospitalized patient in a stroke unit: seizures or delirium?

Sometimes psychotic symptoms may occur as a consequence of epileptic discharges. Complex visual hallucinations have been described in patients with occipito-temporal and anteromedial temporal epileptic activity. The potential atypical character of seizures’ manifestations in elderly patients,a reduced tendency to secondary generalization, associated with the high frequency of confusional syndromes, makes the interpretation of perception and thought disturbances a challenge. Patient 76 years, male gender, with hypertension, light alcohol consumption and without prior history of cognitive impairment. Medicated with benzodiazepines for insomnia (suspended during hospitalization). History of one episode of generalized seizure in his youth. Admitted to the stroke unit with a left occipital hematoma diagnosed after a sudden onset headache. The neurological examination was unremarkable. On the 2nd day of hospitalization initiated episodes of nocturnal restlessness, disorientation and persecutory delusions accompanied by visual and auditory hallucinations which were scenic and stereotyped. This clinical picture was initially interpreted as an acute confusional syndrome and haloperidol was administered. These episodes lasted about 20 minutes and did not respond to therapy. There was interepisodic full recovery and no other clinical or analytical abnormalities. Considering the nature of these episodes an EEG was performed, which revealed right anterior temporal intercritical epileptic activity. Therapy with neuroleptic was discontinued with resolution of symptoms. We intend to point out that in cases of stereotyped hallucinations epileptic etiology should be considered as a differential diagnosis for the clinical pictures with psychotic symptoms, which are often interpreted as acute psychosis or delirium , especially in elderly hospitalized patients.

Care of older people with epilepsy

This article provides an overview of epileptic seizures, aetiology, diagnosis and treatment. It aims to explore relevant clinical management issues when caring for older people with epilepsy and also highlights the important role of the specialist nurse.

Unilateral mydriasis during temporal lobe seizures

Autonomic signs and symptoms are a common feature of epileptic seizures. Although sympathetic activation responses are predominant, we can also find sympathetic inhibition and even an activation of the parasympathetic division of the autonomic nervous system, especially in partial seizures. These autonomic symptoms during seizures are thought to be the result of neuronal discharges arising from or spreading to cortical areas of the central autonomic network. Mydriasis, most commonly bilateral, is one of the most frequent findings. The patient described, a middle-aged man with a focal lesion in the right temporal lobe extended to the adjacent hypothalamus, presented with episodes of autonomic symptoms including prominent unilateral mydriasis, finally evolving into a state of decreased alertness. An ictal electroencephalogram and a simultaneous video recording supported the clinical impression of an epileptic aetiology. Unilateral mydriasis is a rare condition during epileptic seizures and very few cases have been reported in the past.

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.

Panic Attacks in an Individual With Bilateral Selective Lesions of the Amygdala

To describe the unique case of a patient with panic attacks and bilateral selective amygdala lesions due to Urbach-Wiethe disease. Case report. Epilepsy Monitoring Unit, Medical University of Vienna. Patient A 38-year-old man with Urbach-Wiethe disease developed spontaneous panic attacks and depressive mood, which ceased after antidepressive treatment. Video electroencephalography monitoring, magnetic resonance imaging, and neuropsychological testing. Extended video electroencephalography monitoring excluded an epileptic etiology of the panic attacks. Results of cranial magnetic resonance imaging showed bilateral selective calcifications of the whole amygdaloid complex. Neuropsychological testing revealed selective memory impairment of autobiographic episodes with preserved memory for autobiographic facts. Our findings indicate that the occurrence of panic attacks does not critically depend on the integrity of the amygdala. Furthermore, the neuropsychological findings in our patient suggest that the amygdala represents an essential neural substrate for the processing of episodic autobiographic memories.