Localizing Seizure-Onset Zones in Presurgical Evaluation of Drug-Resistant Epilepsy by Electroencephalography/fMRI: Effectiveness of Alternative Thresholding Strategies

Simultaneous EEG/fMRI is an effective noninvasive tool for identifying and localizing the SOZ in patients with focal epilepsy. In this study, we evaluated different thresholding strategies in EEG/fMRI for the assessment of hemodynamic responses to IEDs in the SOZ of drug-resistant epilepsy.

Intracranial neoplasia in 61 cats: localisation, tumour types and seizure patterns

The purpose of this study was to analyse retrospectively a feline population with intracranial neoplastic diseases, to document seizure patterns in these animals and to determine whether partial seizures were more frequently associated with structural brain lesions then generalised seizures. In addition, a comparison was made within the population with intracranial neoplasia between two groups of cats: one with and one without seizures. Special emphasis was given to the evaluation of tumour type, localisation and size of the lesion and its correlation with seizure prevalence. Sixty-one cats with histopathological diagnosis of intracranial tumour were identified. Fourteen cats (23%; group A) had a history of seizure(s). Forty-seven cats (77%; group B) had no history of seizure(s). Generalised tonic-clonic seizures were seen in eight cats (57%) and were the most common seizure pattern in our cats with intracranial neoplasia. Clusters of seizures were observed in six cats. Status epilepticus was observed in one patient. The mean age of the cats was 7.9 years within group A (median 8.5) and 9.3 years (median 10) within group B. The cats with lymphoma within both groups were significantly younger than cats with meningioma. In both groups meningioma and lymphoma were confirmed to be the most frequent tumour type, followed by glial cell tumours. The prevalence of the seizures in patients with glial cell tumours was 26.7%, 26.3% in patients with lymphomas and 15% in cases with meningiomas. In 33 cases (54.1%) the tumours were localised in the forebrain, 15 tumours (24.6%) were in the brainstem, four (6.6%) in the cerebellum and nine tumours (14.7%) had multifocal localisation. Parietal lobe and basal ganglia mostly affected group A. In group B tumours were most frequently located in the parietal and frontal lobes as well as in the diencephalon. A positive association was documented between the localisation of a tumour in the forebrain and seizure occurrence.

[69-year-old patient with seizure of unknown origin]

Diseases associated with cobalamin deficiency often present a variety of neurological disorders apart from the well known megaloblastic anaemia as haematological manifestation. The peripheral and the central nervous system can be affected in different levels by the metabolic changes due to an impaired Vitamin B12 metabolism. Based upon an observed case we discuss the manifestation of cerebral convulsion possibly due to a secondarily acquired cobalamin deficiency. We conclude that in de novo cerebral convulsion in the elderly a cobalamin deficiency could play an important role.

Cortical local and long-range synchronization interplay in human absence seizure initiation

Brain activity relies on transient, fluctuating interactions between segregated neuronal populations. Synchronization within a single and between distributed neuronal clusters reflects the dynamics of these cooperative patterns. Thus absence epilepsy can be used as a model for integrated, large-scale investigation of the emergence of pathological collective dynamics in the brain. Indeed, spike-wave discharges (SWD) of an absence seizure are thought to reflect abnormal cortical hypersynchronization. In this paper, we address two questions: how and where do SWD arise in the human brain? Therefore, we explored the spatio-temporal dynamics of interactions within and between widely distributed cortical sites using magneto-encephalographic recordings of spontaneous absence seizures. We then extracted, from their time-frequency analysis, local synchronization of cortical sources and long-range synchronization linking distant sites. Our analyses revealed a reproducible sequence of 1) long-range desynchronization, 2) increased local synchronization and 3) increased long-range synchronization. Although both local and long-range synchronization displayed different spatio-temporal profiles, their cortical projection within an initiation time window overlap and reveal a multifocal fronto-central network. These observations contradict the classical view of sudden generalized synchronous activities in absence epilepsy. Furthermore, they suggest that brain states transition may rely on multi-scale processes involving both local and distant interactions.

Seizure activity occurring in two dogs after S-ketamine-induction.

Two healthy dogs were anaesthetized to undergo elective orthopaedic procedures. After premedication with methadone and acepromazine, general anaesthesia was induced with midazolam and S-ketamine. Immediately after anaesthetic induction, seizures occurred in both dogs. In the first dog the syndrome was characterized by tonic and clonic motor activity, muscular hypertone, hypersalivation, urination, defecation and hyperthermia. In the second dog muscular twitches of the temporal and masseter regions were observed, followed by increased skeletal muscles tone, hypersalivation, spontaneous urination and increase in body temperature. Recoveries from anaesthesia were uneventful and no seizures were observed. Considering the temporal association between anaesthetic induction and occurrence of seizures, and the fact that other causative factors could not be identified, it is hypothesized that S-ketamine played a role in determining the convulsive phenomena observed in these patients. S-ketamine might carry the potential for inducing seizures in otherwise healthy dogs, despite the concomitant use of GABA-ergic drugs.

Seizure termination

A better understanding of the mechanisms by which most focal epileptic seizures stop spontaneously within a few minutes would be of highest importance, because they could potentially help to improve existing and develop novel therapeutic measures for seizure control. Studies devoted to unraveling mechanisms of seizure termination often take one of the two following approaches. The first approach focuses on metabolic mechanisms such as ionic concentrations, acidity, or neuromodulator release, studying how they are dependent on, and in turn affect changes of neuronal activity. The second approach uses quantitative tools to derive functional networks from electrophysiological recordings and analyzes these networks with mathematical methods, without focusing on actual details of cell biology. In this chapter, we summarize key results obtained by both of these approaches and attempt to show that they are complementary and equally necessary in our aim to gain a better understanding of seizure termination.

The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms: A Prospective Cohort Study.

BACKGROUND We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA). OBJECTIVE To determine the risk of seizure after discharge from surgery for UIA. METHODS A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases. There were 726 cases of UIA (excluding cases proximal to the superior cerebellar artery on the vertebrobasilar system) identified and analyzed. Cox proportional hazards regression models and Kaplan-Meier life table analyses were generated assessing risk factors. RESULTS Preoperative seizure history and complication of aneurysm repair were the only risk factors found to be significant. The risk of first seizure after discharge from hospital following surgery for patients with neither preoperative seizure, treated middle cerebral artery aneurysm, nor postoperative complications (leading to a modified Rankin Scale score >1) was <0.1% and 1.1% at 12 months and 7 years, respectively. The risk for those with preoperative seizures was 17.3% and 66% at 12 months and 7 years, respectively. The risk for seizures with either complications (leading to a modified Rankin Scale score >1) from surgery or treated middle cerebral artery aneurysm was 1.4% and 6.8% at 12 months and 7 years, respectively. These differences in the 3 Kaplan-Meier curves were significant (log-rank P < .001). CONCLUSION The risk of seizures after discharge from hospital following surgery for UIA is very low when there is no preexisting history of seizures. If this result can be supported by other series, guidelines that restrict returning to driving because of the risk of postoperative seizures should be reconsidered. ABBREVIATIONS MCA, middle cerebral arterymRS, modified Rankin ScaleUIA, unruptured intracranial aneurysms.

Bok Is Not Pro-Apoptotic But Suppresses Poly ADP-Ribose Polymerase-Dependent Cell Death Pathways and Protects against Excitotoxic and Seizure-Induced Neuronal Injury.

UNLABELLED Bok (Bcl-2-related ovarian killer) is a Bcl-2 family member that, because of its predicted structural homology to Bax and Bak, has been proposed to be a pro-apoptotic protein. In this study, we demonstrate that Bok is highly expressed in neurons of the mouse brain but thatbokwas not required for staurosporine-, proteasome inhibition-, or excitotoxicity-induced apoptosis of cultured cortical neurons. On the contrary, we found thatbok-deficient neurons were more sensitive to oxygen/glucose deprivation-induced injuryin vitroand seizure-induced neuronal injuryin vivo Deletion ofbokalso increased staurosporine-, excitotoxicity-, and oxygen/glucose deprivation-induced cell death inbax-deficient neurons. Single-cell imaging demonstrated thatbok-deficient neurons failed to maintain their neuronal Ca(2+)homeostasis in response to an excitotoxic stimulus; this was accompanied by a prolonged deregulation of mitochondrial bioenergetics.bokdeficiency led to a specific reduction in neuronal Mcl-1 protein levels, and deregulation of both mitochondrial bioenergetics and Ca(2+)homeostasis was rescued by Mcl-1 overexpression. Detailed analysis of cell death pathways demonstrated the activation of poly ADP-ribose polymerase-dependent cell death inbok-deficient neurons. Collectively, our data demonstrate that Bok acts as a neuroprotective factor rather than a pro-death effector during Ca(2+)- and seizure-induced neuronal injuryin vitroandin vivo SIGNIFICANCE STATEMENT Bcl-2 proteins are essential regulators of the mitochondrial apoptosis pathway. The Bcl-2 protein Bok is highly expressed in the CNS. Because of its sequence similarity to Bax and Bak, Bok has long been considered part of the pro-apoptotic Bax-like subfamily, but no studies have yet been performed in neurons to test this hypothesis. Our study provides important new insights into the functional role of Bok during neuronal apoptosis and specifically in the setting of Ca(2+)- and seizure-mediated neuronal injury. We show that Bok controls neuronal Ca(2+)homeostasis and bioenergetics and, contrary to previous assumptions, exerts neuroprotective activitiesin vitroandin vivo Our results demonstrate that Bok cannot be placed unambiguously into the Bax-like Bcl-2 subfamily of pro-apoptotic proteins.

Chronic impact of topiramate on acid-base balance and potassium in childhood

Topiramate, which is commonly prescribed for seizure disorders and migraine prophylaxis, sometimes causes metabolic acidosis and hypokalemia. Since the effects of topiramate on acid-base balance and potassium levels have not been well explored in children, acid-base balance, anion gap and potassium were assessed in 24 patients (8 females and 16 males) aged between 4.6 and 19 years on topiramate for more than 12 months and in an age-matched control group. Plasma bicarbonate (21.7 versus 23.4 mmol/L; P<0.03), carbon dioxide pressure (39.7 versus 43.2mm Hg; P<0.05), and potassium (3.7 versus 4.0 mmol/L; P<0.03) were on the average lower and chloride (109 versus 107 mmol/L; P<0.03) higher in patients treated with topiramate than in controls. Blood pH, plasma sodium and the anion gap were similar in patients on topiramate and in controls. In patients on topiramate no significant correlation was observed between the dosage of this agent and plasma bicarbonate or potassium as well as between topiramate blood level and the mentioned electrolytes. In conclusion long-term topiramate treatment is associated with a mild, statistically significant tendency towards compensated normal anion gap metabolic acidosis and hypokalemia.

Analyzing spatio-temporal patterns of genuine cross-correlations

In multivariate time series analysis, the equal-time cross-correlation is a classic and computationally efficient measure for quantifying linear interrelations between data channels. When the cross-correlation coefficient is estimated using a finite amount of data points, its non-random part may be strongly contaminated by a sizable random contribution, such that no reliable conclusion can be drawn about genuine mutual interdependencies. The random correlations are determined by the signals' frequency content and the amount of data points used. Here, we introduce adjusted correlation matrices that can be employed to disentangle random from non-random contributions to each matrix element independently of the signal frequencies. Extending our previous work these matrices allow analyzing spatial patterns of genuine cross-correlation in multivariate data regardless of confounding influences. The performance is illustrated by example of model systems with known interdependence patterns. Finally, we apply the methods to electroencephalographic (EEG) data with epileptic seizure activity.

Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model

Generalised epileptic seizures are frequently accompanied by sudden, reversible transitions from low amplitude, irregular background activity to high amplitude, regular spike-wave discharges (SWD) in the EEG. The underlying mechanisms responsible for SWD generation and for the apparently spontaneous transitions to SWD and back again are still not fully understood. Specifically, the role of spatial cortico-cortical interactions in ictogenesis is not well studied. We present a macroscopic, neural mass model of a cortical column which includes two distinct time scales of inhibition. This model can produce both an oscillatory background and a pathological SWD rhythm. We demonstrate that coupling two of these cortical columns can lead to a bistability between out-of-phase, low amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli can cause state-dependent transitions from background into SWD. In an extended local area of cortex, spatial heterogeneities in a model parameter can lead to spontaneous reversible transitions from a desynchronised background to synchronous SWD due to intermittency. The deterministic model is therefore capable of producing absence seizure-like events without any time dependent adjustment of model parameters. The emergence of such mechanisms due to spatial coupling demonstrates the importance of spatial interactions in modelling ictal dynamics, and in the study of ictogenesis.