Neurostimulation in the treatment of refractory and super-refractory status epilepticus

Abstract Status epilepticus (SE) is a life-threatening condition with a mortality of up to 60% in the advanced and comatose forms of SE. In one out of five adults, first and second line fails to control epileptic activity, leading to refractory status epilepticus (RSE) and in around 3% to super-refractory status epilepticus (SRSE), where SE continues despite anesthetic treatment for 24 h or more. In this rare but devastating condition, innovative and safe treatments are needed. In a recent review on the use of vagal nerve stimulation in RSE and SRSE, a 74% response rate for abrogation of SE was reported. Here, we review the currently available evidence supporting the use of neurostimulation, including vagal nerve stimulation, direct cortical stimulation, transcranial magnetic stimulation, electroconvulsive therapy, and deep brain stimulation in RSE and SRSE. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures"

Antiepileptic drug use in Austrian nursing home residents

AbstractPurposeCurrently around 30% of all newly developed seizures are diagnosed in persons older than 65 years. Five to 17% of nursing home-residents take antiepileptic drugs. The aim of our study was to analyze the type and frequency of prescribed antiepileptic drugs, as well as their indication, co-morbidities and co-medications in institutionalized elderly in Austria.MethodsThis was a retrospective, cross-sectional study, which included all residents of the seven public nursing homes in Innsbruck, Austria. The data of 828 probands were extracted from the charts at site and maintained anonymously. The data collection was followed by descriptive statistics.Key findings70 (8.5%; 26 M/44 F) of the 828 (192 M/636 F) residents took at least one antiepileptic medication. In 51.5% the reason for the prescription were epileptic seizures – yielding a minimum prevalence of 4.5%. The most often used antiepileptic drugs were gabapentin (37%), levetiracetam (24%) and valproate (18.5%). The three most common co-morbidities were arterial hypertension (49%), ischemic stroke (36%) and other cerebrovascular diseases (29%). Six to nine co-medications were prescribed in 41%, 26% had more than 10 additional drugs and 91% were treated with proconvulsive co-medications (64/70, median 2, range 0–6).SignificanceAustrian nursing home residents receive more frequently newer antiepileptic drugs compared to other countries, but co-prescription of proconvulsive drugs is common

Neurostimulation for drug-resistant epilepsy : a systematic review of clinical evidence for efficacy, safety, contraindications and predictors for response

Purpose of review: Neurostimulation is becoming an increasingly accepted treatment alternative for patients with drug-resistant epilepsy (DRE) who are unsuitable surgery candidates. Standardized guidelines on when or how to use the various neurostimulation modalities are lacking. We conducted a systematic review on the currently available neurostimulation modalities primarily with regard to effectiveness and safety. Recent findings: For vagus nerve stimulation (VNS), there is moderate-quality evidence for its effectiveness in adults with drug-resistant partial epilepsies. Moderate-to-low-quality evidence supports the efficacy and safety of deep brain stimulation (DBS) and responsive neurostimulation (RNS) in patients with DRE. There is moderate-to-very low-quality evidence that transcranial direct current stimulation (tDCS) is effective or well tolerated. For transcutaneous vagus nerve stimulation (tVNS), transcranial magnetic stimulation (TMS) and trigeminal nerve stimulation (TNS), there are insufficient data to support the efficacy of any of these modalities for DRE. These treatment modalities, nevertheless, appear well tolerated, with no severe adverse events reported. Summary: Head-to-head comparison of treatment modalities such as VNS, DBS and RNS across different epileptic syndromes are required to decide which treatment modality is the most effective for a given patient scenario. Such studies are challenging and it is unlikely that data will be available in the near future. Additional data collection on potentially promising noninvasive neurostimulation modalities like tVNS, TMS, TNS and tDCS is warranted to get a more precise estimate of their therapeutic benefit and long-term safety

Sequencing patterns of ventilatory indices in less trained adults

Submaximal ventilatory indices, i.e., point of optimal ventilatory efficiency (POE) and anaerobic threshold (AT), are valuable indicators to assess the metabolic and ventilatory response during cardiopulmonary exercise testing (CPET). The order in which the ventilatory indices occur (ventilatory indices sequencing pattern, VISP), may yield additional information for the interpretation of CPET results and for exercise intensity prescription. Therefore, we determined whether different VISP groups concerning POE and AT exist. Additionally, we analysed fat metabolism via the exercise intensity eliciting the highest fat oxidation rate (Fatmax) as a possible explanation for differences between VISP groups. 761 less trained adults (41–68 years) completed an incremental exercise test on a cycle ergometer until volitional exhaustion. The ventilatory indices were determined using automatic and visual detection methods, and Fatmax was determined using indirect calorimetry. Our study identified two VISP groups with a lower work rate at POE compared to AT in VISPPOE < AT but not in group VISPPOE = AT. Therefore, training prescription based on POE rather than AT would result in different exercise intensity recommendations in 66% of the study participants and consequently in unintended physiological adaptions. VISPPOE < AT participants were not different to VISPPOE = AT participants concerning VO2peak and Fatmax. However, participants exhibiting a difference in work rate (VISPPOE < AT) were characterized by a higher aerobic capacity at submaximal work rate compared to VISPPOE = AT. Thus, analysing VISP may help to gain new insights into the complex ventilatory and metabolic response to exercise. But a methodological framework still must be established

Infections in status epilepticus: A retrospective 5-year cohort study

AbstractPurposeStatus epilepticus (SE) has attracted renewed interest lately, and efforts are made to optimize every treatment stage. For refractory SE, optimal supporting care involves mechanical ventilation and intensive care unit (ICU) admission. Infections often complicate SE and recently a single-centre observational study demonstrated an association between infections and poor short-term outcome of SE in a cohort of severely ill patients. We have here attempted to replicate those findings in a different cohort.MethodWe performed a retrospective observational study and included all patients with a diagnosis of SE during 2008–2012 at a Swedish tertiary referral centre.ResultsThe cohort consisted of 103 patients (53% female, 47% male, median age 62 years, range 19–87 years). In house mortality was less than 2 and 70% of the patients’ were discharged home. The most common aetiologies of SE were uncontrolled epilepsy (37%) and brain tumours (16%). A total of 39 patients suffered infections during their stay. Presence of infection was associated with mechanical ventilation (OR 3.344, 95% CI 1.44–7.79) as well as not being discharged home (OR2.705, 95% CI 1.14–6.44), and duration of SE was significantly longer in patients with infection (median 1 day vs. 2.5 days, p<0.001).ConclusionWe conclude that the previously described association between infections, a longer SE duration, and an unfavourable outcome of SE seems valid also in SE of less severe aetiology

MEEGIPS—A modular EEG investigation and processing system for visual and automated detection of high frequency oscillations

High frequency oscillations (HFOs) are electroencephalographic correlates of brain activity detectable in a frequency range above 80 Hz. They co-occur with physiological processes such as saccades, movement execution, and memory formation, but are also related to pathological processes in patients with epilepsy. Localization of the seizure onset zone, and, more specifically, of the to-be resected area in patients with refractory epilepsy seems to be supported by the detection of HFOs. The visual identification of HFOs is very time consuming with approximately 8 h for 10 min and 20 channels. Therefore, automated detection of HFOs is highly warranted. So far, no software for visual marking or automated detection of HFOs meets the needs of everyday clinical practice and research. In the context of the currently available tools and for the purpose of related local HFO study activities we aimed at converging the advantages of clinical and experimental systems by designing and developing a comprehensive and extensible software framework for HFO analysis that, on the one hand, focuses on the requirements of clinical application and, on the other hand, facilitates the integration of experimental code and algorithms. The development project included the definition of use cases, specification of requirements, software design, implementation, and integration. The work comprised the engineering of component-specific requirements, component design, as well as component- and integration-tests. A functional and tested software package is the deliverable of this activity. The project MEEGIPS, a Modular EEG Investigation and Processing System for visual and automated detection of HFOs, introduces a highly user friendly software that includes five of the most prominent automated detection algorithms. Future evaluation of these, as well as implementation of further algorithms is facilitated by the modular software architecture.This work was supported by the Austrian Science Fund (FWF): KLI 657-B31 and by the PMU-FFF: A-18/01/029-HÖL.Peer reviewe

Acute symptomatic seizures caused by electrolyte disturbances

In this narrative review we focus on acute symptomatic seizures occurring in subjects with electrolyte disturbances. Quite surprisingly, despite its clinical relevance, this issue has received very little attention in the scientific literature. Electrolyte abnormalities are commonly encountered in clinical daily practice, and their diagnosis relies on routine laboratory findings. Acute and severe electrolyte imbalances can manifest with seizures, which may be the sole presenting symptom. Seizures are more frequently observed in patients with sodium disorders (especially hyponatremia), hypocalcemia, and hypomagnesemia. They do not entail a diagnosis of epilepsy, but are classified as acute symptomatic seizures. EEG has little specificity in differentiating between various electrolyte disturbances. The prominent EEG feature is slowing of the normal background activity, although other EEG findings, including various epileptiform abnormalities may occur. An accurate and prompt diagnosis should be established for a successful management of seizures, as rapid identification and correction of the underlying electrolyte disturbance (rather than an antiepileptic treatment) are of crucial importance in the control of seizures and prevention of permanent brain damage.(VLID)214854

Vagus nerve stimulation in refractory and super-refractory status epilepticus - A systematic review.

Abstract Rationale Refractory status epilepticus (RSE) is the persistence of status epilepticus despite second-line treatment. Super-refractory SE (SRSE) is characterized by ongoing status despite 48 h of anaesthetic treatment. Due to the high case fatality in RSE of 16–39%, off label treatments without strong evidence of efficacy in RSE are often administered. In single case-reports and small case series totalling 28 patients, acute implantation of VNS in RSE was associated with 76% and 26% success rate in generalized and focal RSE respectively. We performed an updated systematic review of the literature on efficacy of VNS in RSE/SRSE by including all reported patients. Methods We systematically searched EMBASE, CENTRAL, Opengre.eu, and ClinicalTrials.gov , and PubMed databases to identify studies reporting the use of VNS for RSE and/or SRSE. We also searched conference abstracts from AES and ILAE meetings. Results 45 patients were identified in total of which 38 were acute implantations of VNS in RSE/SRSE. Five cases had VNS implantation for epilepsia partialis continua, one for refractory electrical status epilepticus in sleep and one for acute encephalitis with refractory repetitive focal seizures. Acute VNS implantation was associated with cessation of RSE/SRSE in 74% (28/38) of acute cases. Cessation did not occur in 18% (7/38) of cases and four deaths were reported (11%); all of them due to the underlying disease and unlikely related to VNS implantation. Median duration of the RSE/SRSE episode pre and post VNS implantation was 18 days (range: 3–1680 days) and 8 days (range: 3–84 days) respectively. Positive outcomes occurred in 82% (31/38) of cases. Conclusion VNS can interrupt RSE and SRSE in 74% of patients; data originate from reported studies classified as level IV and the risk for reporting bias is high. Further prospective studies are warranted to investigate acute VNS in RSE and SRSE

Deactivation of the Default Mode Network as a Marker of Impaired Consciousness: An fMRI Study

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation – a third main feature of the DMN – has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness

Ictal unilateral eye blinking and contralateral blink inhibition — A video-EEG study and review of the literature

AbstractIntroductionThere is limited information on ictal unilateral eye blinking (UEB) as a lateralizing sign in focal seizures. We identified two patients with UEB and propose a novel mechanism of UEB based on a review of the literature.Materials and methodsWe report on two patients with intractable focal epilepsy showing UEB among 269 consecutive patients undergoing noninvasive video-EEG monitoring from October 2011 to May 2013.ResultsUnilateral eye blinking was observed in 0.7% (two of 269) of our patients. Patient one had four focal seizures. Semiological signs in all of her seizures were impaired consciousness, bilateral eye blinking (BEB), and UEB on the right. During one seizure, BEB recurred after UEB with a higher blink frequency on the right. Patient two had ten focal seizures. Among them were one electrographic seizure and nine focal seizures with BEB (in 3/10) and UEB on the left (in 1/10 seizures, respectively). Both patients did not display any clonic activity of the face. In seizures with UEB, ictal EEG onset was observed over the ipsilateral frontotemporal region in both of the patients (over F8 in 2/4, Fp2-F8 in 1/4, Sp2-T2 in 1/4, and F7 in 1/1 seizures, respectively). Ictal pattern during UEB showed bilateral ictal activity (in 4/4) and ictal discharges over the ipsilateral frontal region (maximum over F3 in 1/1 seizure). Interictal EEG showed sharp waves over the same regions.DiscussionUnilateral eye blinking was ipsilateral to the frontotemporal ictal EEG pattern in both patients. The asymmetric blink frequency during BEB in patient one leads to the hypothesis that ictal UEB is caused by contralateral blink inhibition due to activation in frontotemporal cortical areas and mediated by trigeminal fibers