Individual Seizure Research Articles

Reduced intra-cortical inhibition after sleep deprivation: A transcranial magnetic stimulation study

Sleep deprivation has multiple effects on brain function. It increases the risk for epileptic seizures both in healthy individuals and in patients with epilepsy. Furthermore it represents an effective antidepressive intervention with rapid onset. However, the mechanisms underlying these effects are still largely unknown [2]. Transcranial magnetic stimulation (TMS) can be used as a non-invasive method for the measurement of motor cortex excitability. Here we used TMS for assessing sleep deprivation effects on cortical excitability in healthy individuals. Before and after 24 h of sleep deprivation, parameters of cortical excitability (resting motor threshold, short intracortical inhibition, intracortical facilitation, cortical silent period) were measured in a sample of 15 healthy volunteers (11 women, 4 men, aged between 21 and 30 years with a mean of 24.3 ± 2.7 years). We detected a significant ( p = 0.042) reduction of short intracortical inhibition (SICI) after sleep deprivation. Motor threshold, intracortical facilitation and contralateral silent period remained unchanged. Our results confirm previous studies which have demonstrated changes of SICI after sleep deprivation. Our findings further suggest that the increased risk for epileptic seizures after sleep deprivation is mediated by a reduction of intracortical inhibition. Whether this mechanism is also involved in mediating the antidepressant effect of sleep deprivation has to be addressed by further studies in depressive patients.

Neonatal seizure recognition – Comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings

Objectives This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. Methods Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. Results A total of 265 paired epochs from 38 simultaneous recording were assessed. Forty-one seizure episodes were diagnosed in 31 epochs in the cEEG recordings of 10 infants. Sensitivity and specificity ranged from 68% to 84% and from 71% to 84%, respectively, per detection of epochs with seizures and from 71% to 84% and from 36% to 96% per detection of individual seizures. No agreement was found between the observations of the student, and those of the fellow or neonatologist. Substantial agreement was found between the fellow and neonatologist. Before cEEG was commenced, seizures were detected by aEEG in 22 infants. Conclusions aEEG has high sensitivity and specificity in the hands of experienced users. Inexperienced new users may have a high rate of misdiagnosed seizures. Early recording of high-risk infants can help in the early diagnosis and treatment of seizures. Significance Diagnosis and treatment of seizures in aEEG should be carried out by experienced users and should be supplemented with cEEG when available.

Epilepsy: the quintessential pathology of consciousness.

Alterations in consciousness are central to epileptic manifestations, and involve changes in both the level of awareness and subjective content of consciousness. Generalised seizures are characterised by minimal responsiveness and subjective experience whereas simple and complex partial seizures demonstrate more selective disturbances. Despite variations in ictal origin, behaviour and electrophysiology, the individual seizure types share common neuroanatomical foundations generating impaired consciousness. This article provides a description of the phenomenology of ictal consciousness and reviews the underlying shared neural network, dubbed the 'consciousness system', which overlaps with the 'default mode' network. In addition, clinical and experimental models for the study of the brain correlates of ictal alterations of consciousness are discussed. It is argued that further investigation into both human and animal models will permit greater understanding of brain mechanisms and associated behavioural consequences, possibly leading to the development of new targeted treatments.

Epilepsy: The Quintessential Pathology of Consciousness

Alterations in consciousness are central to epileptic manifestations, and involve changes in both the level of awareness and subjective content of consciousness. Generalised seizures are characterised by minimal responsiveness and subjective experience whereas simple and complex partial seizures demonstrate more selective disturbances. Despite variations in ictal origin, behaviour and electrophysiology, the individual seizure types share common neuroanatomical foundations generating impaired consciousness. This article provides a description of the phenomenology of ictal consciousness and reviews the underlying shared neural network, dubbed the 'consciousness system', which overlaps with the 'default mode' network. In addition, clinical and experimental models for the study of the brain correlates of ictal alterations of consciousness are discussed. It is argued that further investigation into both human and animal models will permit greater understanding of brain mechanisms and associated behavioural consequences, possibly leading to the development of new targeted treatments.

The role of inflammation in epilepsy

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.

Longitudinal Change in Outcome of Frontal Lobe Epilepsy Surgery

Although the outcome of epilepsy surgery changes with time, few studies have considered longitudinal changes after frontal lobe epilepsy (FLE) surgery. To assess the longitudinal changes after FLE surgery. Resection of the seizure onset zone was performed in 76 patients with FLE. Invasive monitoring was performed in 56 of these 76. Awake craniotomy was performed in 43 of the 76 patients. More than 50% of patients were followed up for at least 7 years. The mean follow-up was 81 months. For all patients, the seizure-free rate was 79% at 6 months, 64% at 1 year, 55% at 2 years, and 55% at 7 years. For patients with cortical dysplasia, the seizure-free rate was 72% at 6 months, 53% at 1 year, 51% at 2 years, and 46% at 7 years. For patients with tumor, the seizure-free rate was 89% at 6 months, 83% at 1 year, 83% at 2 years, and 74% at 7 years. Patients with tumor showed better outcome than those with cortical dysplasia (P = .04). Although the overall seizure-free rate became stable after 2 years, individual status changed for up to 5 years. Seizures recurred in 11 patients within 1 year (early recurrence) and in 12 patients by 1 to 5 years (late recurrence). Antiepileptic drug (AED) medication was adjusted in all patients with recurrence. Patients with late recurrence had a more favorable response (Engel class I or II) than early recurrence (P < .01). The overall seizure outcome changes mostly during the first year. However, individual seizure status changes for up to 5 years. The outcome of late recurrence is favorable to AED adjustment.

Newer Anticonvulsant Medications in Pediatric Neurology

Antiepileptic drugs (AEDs) are the mainstay of treatment for recurrent seizures. Uncontrolled seizures may cause medical, developmental, and psychological disturbances. The medical practitioner should thus strive to eliminate or minimize seizures. Treatment advances in epilepsy include 1) identification of the basic mechanisms of epilepsy and action of AEDs, 2) the introduction of new AEDs, and 3) the use of neurostimulation, including vagus nerve stimulation. Treatment with AEDs involves balancing each AED's efficacy against its side effects. In some patients, effective AEDs must be discontinued because of intolerable side effects. Although all AEDs have a proven efficacy, the choice of AEDs should be based on better efficacy for individual seizure types or epilepsy syndromes. Side effects also differ from drug to drug and must be taken into account. This article focuses on studies and expert opinion consensus to guide the choice of AEDs.

EPILEPSY SURGERY AND ELECTRONIC DEVICES

Epilepsy is a chronic disorder characterized by recurrent and unprovoked seizures. The lifetime risk of developing epilepsy is 4%. Approximately 90% of the incident cases in adults have partial epilepsy. The initial response to medication is of prognostic importance. Patients with symptomatic neurologic disease, foreign-tissue lesion, or developmental delay are less likely to be rendered seizure free. The goal of treatment is to render the individual seizure free. Many patients with partial epilepsy will not attain a seizure remission with antiepileptic drug therapy. Epilepsy surgery is an effective and safe alternative form of therapy for selected patients with intractable partial epilepsy. Electronic stimulation is being considered for patients with partial seizures who are not candidates for a focal cortical resection.

Experimental status epilepticus in animals: What are we modeling?

Experimental status epilepticus in animals: What are we modeling?

Biomarkers to Predict Alcohol Withdrawal Seizures - A Review of Current Literature

Alcohol withdrawal seizures are one major complication during detoxification treatment of alcohol dependent patients. Anticonvulsive pharmaceutical treatment can be administered but is associated with side-effects like nausea or hyponatriemia. Recent studies have identified different biomarkers that have been associated with the risk of alcohol withdrawal seizures. The aminoacid homocysteine as well as prolactin have been described to be associated with this individual seizure risk. Furthermore, markers of alcohol dependence like carbohydrate deficient transferrin (CDT) have been studied in this context. Also, genetic variants like the apolipoprotein E genotype have been found to be related to the history of withdrawal seizures. Knowledge and critical valuation of these recent findings on biomarkers may help to establish an assessment of the individual risk for withdrawal seizures and therefore may have important clinical implications.

Therapeutic experiences with 947 epileptic out-patients in oxcarbazepine treatment.

Efficacy and tolerability of the new antiepileptic drug oxcarbazepine, was evaluated in a retrospective multicentre study. The records of all 947 epilepsy patients treated with oxcarbazepine in the eight participating centres from 1981 through 1990 were examined. The median daily dose of oxcarbazepine was 30 mg/kg in children, 18 mg/kg in adults, and 15 mg/kg in elderly patients, given b.i.d. or t.i.d. The mean plasma levels of the main active metabolite of oxcarbazepine was 88, 79, and 68 mumol/l in children, adults, and elderly, respectively. In patients shifted to oxcarbazepine treatment, seizure frequency was unchanged in 51-66%, 32-48% had a decrease, and 1-10% an increase in seizure frequency, considering the individual seizure types separately. Adverse events were reported in one third of patients, most frequently affecting the CNS (dizziness: 6%; sedation: 6%; fatigue: 6%). Rash was reported in 6% of patients, half of these patients had previously had an allergic reaction to carbamazepine. Hyponatremia was found in about a quarter of the patients from whom data were available. No congenital malformations were seen in nine live-born, first trimester oxcarbazepine-exposed children.

Early follow-up data from seizure diaries can be used to predict subsequent seizures in same cohort by borrowing strength across participants

Accurate prediction of seizures in persons with epilepsy offers opportunities for both precautionary measures and preemptive treatment. Previously identified predictors of seizures include patient-reported seizure anticipation, as well as stress, anxiety, and decreased sleep. In this study, we developed three models using 30 days of nightly seizure diary data in a cohort of 71 individuals with a history of uncontrolled seizures to predict subsequent seizures in the same cohort over a 30-day follow-up period. The best model combined the individual's seizure history with that of the remainder of the cohort, resulting in 72% sensitivity for 80% specificity, and 0.83 area under the receiver operating characteristic curve. The possibility of clinically relevant prediction should be examined through electronic data capture and more specific and more frequent sampling, and with patient training to improve prediction.

Activation of cerebral cortical astrocytes by basal forebrain stimulation

A single stimulus applied once daily to the limbic system commonly leads to convulsive seizures yet seizures are relatively infrequent during intracranial self-stimulation (ICSS), a procedure that involves many hundreds of similar stimuli. The present study examined the possible role of electrode site, interstimulus interval, afterdischarge and reinforcement thresholds and postictal refractoriness in accounting for this paradox. Electrode location was an overriding factor: seizures were never seen with hypothalamic implants posterior to the level of the ventromedial nucleus but were elicited by the majority of more rostral reward sites. Frequent repeated stimulation by ICSS did not in itself prevent subsequent kindling or reverse the effects of earlier kindling; on the contrary, seizures induced by ICSS showed a progressive increase in severity similar to the progression produced by conventional kindling. Individual convulsive seizures, as in previous studies, conferred transient protection against further seizures whether from ICSS or from kindling. More prolonged protection occasionally developed after repeated convulsive seizures: protection was accompanied by continuous EEG slow-waves corresponding in presentation to clinical petit mal status. Prolonged resistance to seizures has also been reported after tonic-clonic status epilepticus causing temporal lobe damage. The relative infrequency of seizures during ICSS ordinarily appears to depend on the siting of the electrodes, on distinct short- and long-term postictal refractory states, and on the rat learning to restrict stimulus input to subseizural levels.

Listening to people with seizures: How can linguistic analysis help in the differential diagnosis of seizure disorders?

Despite advances in medical technology, the patients' history remains the most crucial tool in the differential diagnosis of epileptic or non-epileptic seizures (NES). The distinction of these two types of seizures is a common and important task for neurologists. Whereas epileptic seizures would be treated with antiepileptic drugs, non-epileptic seizures are thought to be a manifestation of psychological or social distress and can improve with psychotherapy. This paper summarizes the findings of a series of multidisciplinary research studies undertaken at the Bethel Epilepsy Centre and the University of Bielefeld in Germany in which linguistic analysis was carried out to identify and describe linguistic and interactional features in clinical exchanges between doctors and patients with seizures. Two distinct communication profiles emerged in these studies based on the analysis of transcripts of over 110 doctor-patient encounters. Epileptic seizure descriptions are characterized by formulation effort, provide the doctor with a coherent account of individual seizures, relate subjective seizure experiences and use consistent metaphoric conceptualizations. Patients with NES tend not to volunteer subjective seizure symptoms, give accounts of their seizures which are difficult to understand and are inconsistent in their choice of metaphors.

Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat

Objective To test the anticonvulsive potential of a range of repetitive transcranial magnetic stimulation (rTMS) frequencies by novel methods for simultaneous EEG and rTMS in a rat seizure model. Methods Seizures were triggered by intraperitoneal kainic acid (KA; 10 mg/kg). Rats ( n = 21) were divided into three groups in which individual seizures were treated with rTMS trains at one of three frequencies: 0.25, 0.5 or 0.75 Hz. EEG was continuously viewed by an operator who identified each seizure onset. Consecutive seizures in each animal were (1) treated with active rTMS, (2) treated with sham rTMS, or (3) were untreated. EEG was re-analyzed post hoc by visual inspection, and seizure durations were compared within and between treatment groups. Results KA-induced seizures were abbreviated by 0.75 Hz ( P = 0.019) and 0.5 Hz ( P = 0.033) active EEG-guided rTMS. In contrast, neither active 0.25 Hz rTMS nor the control conditions affected seizure duration ( P > 0.2). Conclusions We demonstrate that EEG-guided rTMS can suppress seizures in the rat KA epilepsy model, and that the effect is frequency dependent, with 0.75 and 0.5 Hz rTMS being superior to 0.25 Hz rTMS. Significance These data support the use of rat seizure models in translational research aimed at evaluation and development of effective rTMS anticonvulsive protocols. We also offer a proof of principle that real-time analysis of EEG can be used to guide rTMS to suppress individual seizures.

Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents

In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug-drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals.

Seizures in HIV‐seropositive individuals: NIMHANS experience and review

Seizures are not uncommon in patients with human immunodeficiency virus (HIV) infection, and with the upsurge in HIV infection this may be an important cause for acute symptomatic seizures. Seizures may rarely be the presenting manifestation of HIV infection. Opportunistic infections such as toxoplasmosis, tuberculosis, progressive multifocal leucoencephalopathy (PML), cryptococcal meningitis and polymicrobial infections, metabolic and electrolyte disturbances, and drugs are common causes of new-onset seizures in HIV-seropositive individuals. In the absence of any cause, primary HIV infection may be considered responsible for seizures. Because seizures tend to recur in and because they are a poor prognostic indicator in HIV infection, treatment with antiepileptic drugs (AEDs) is the norm. The treatment of HIV-infected individuals with seizures comprises of the administration of AEDs, specific treatment of the underlying conditions, and antiretroviral drugs. Clinicians must consider both therapy-compromising drug-drug and drug-disease interactions while choosing appropriate AEDs. The ideal AED in this setting is one that does not affect viral replication, have limited protein binding, and have no effects on the hepatic cytochrome P450 enzyme system. The risks for AED-induced allergic skin rash appears to be high in HIV-seropositive individuals.

Conversation analysis can help to distinguish between epilepsy and non-epileptic seizure disorders: A case comparison

Purpose Factual items in patients’ histories are of limited discriminating value in the differential diagnosis of epilepsy and non-epileptic seizures (NES). A number of studies using a transcript-based sociolinguistic research method inspired by Conversation Analysis (CA) suggest that it is helpful to focus on how patients talk. Previous reports communicated these findings by using particularly clear examples of diagnostically relevant interactional, linguistic and topical features from different patients. They did not discuss the sequential display of different features although this is crucially important from a conversation analytic point of view. This case comparison aims to show clinicians how the discriminating features are displayed by individual patients over the course of a clinical encounter. Methods CA-inspired brief sequential analysis of two first 30-min doctor–patient encounters by a linguist blinded to all medical information. A gold standard diagnosis was made by the recording of a typical seizure with video-EEG. Results The patient with epilepsy volunteered detailed first person accounts of seizures. The NES patient exhibited resistance to focusing on individual seizure episodes and only provided a detailed seizure description after repeated prompting towards the end of the interview. Although both patients also displayed some linguistic features favouring the alternative diagnosis, the linguist's final diagnostic hypothesis matched the diagnosis made by video-EEG in both cases. Conclusion This study illustrates the importance of the time point at which patients share information with the doctor. It supports the notion that close attention to how patients communicate can help in the differential diagnosis of seizures.

Alterations in the contents of consciousness in partial epileptic seizures

Epilepsy research suffers from a deficiency of systematic studies concerning the phenomenology of the contents of consciousness during seizures, partially because of the lack of suitable research methods. The Phenomenology of Consciousness Inventory (PCI), a standardized, valid, and reliable questionnaire, was used here to study which dimensions of the contents of consciousness are distorted during partial epileptic seizures compared with baseline. Further, the similarity of the altered pattern of subjective experiences across recurring seizures was also explored. Our results indicate that patients with epilepsy report alterations on most dimensions of the contents of consciousness in conjunction with seizures, but individual seizure experiences remain similar from one seizure to another. The PCI was found suitable for the assessment of subjective experiences during epileptic seizures and could be a valuable tool in providing new information about phenomenal consciousness in epilepsy in both the research and clinical settings.

Addressing genetic heterogeneity in complex disease: Finding seizure genes in systemic lupus erythematosus

Complex genetic disease is inherently difficult to study due to an imperfect relationship between genotype and phenotype. One important reason for this imperfect relationship is genetic heterogeneity, the occurrence of different genetic factors underlying the same clinical syndrome. One method of addressing genetic heterogeneity is covariate-based linkage analysis, which allows the use of additional phenotypic features to define genetically distinct subsets of patients. Systemic lupus erythematosus (SLE) is one example of a complex genetic disease affecting multiple organ systems including the central nervous system. We report here the use of covariate-based linkage analysis to detect a potential genetic locus on chromosome 15 influencing the development of seizures in individuals with SLE. The use of covariates increases the power to detect linkage in the presence of genetic heterogeneity.