Seizures and Sepsis: A Narrative Review

Patients with sepsis-associated encephalopathy (SAE) can develop convulsive or nonconvulsive seizures. The cytokine storm and the overwhelming systemic inflammation trigger the electric circuits that promote seizures. Several neurologic symptoms, associated with this disease, range from mild consciousness impairment to coma. Focal or generalized convulsive seizures are frequent in sepsis, although nonconvulsive seizures (NCS) are often misdiagnosed and prevalent in SAE. In order to map the trigger zone in all patients that present focal or generalized seizures and also to detect NCS, EEG is indicated but continuous EEG (cEEG) is not very widespread; timing, duration, and efficacy of this tool are still unknown. The long-term risk of seizures in survivors is increased. The typical stepwise approach of seizures management begins with benzodiazepines and follows with anticonvulsants up to anesthetic drugs such as propofol or thiopental, which are able to induce burst suppression and interrupt the pathological electrical circuits. This narrative review discusses pathophysiology, clinical presentation, diagnosis and treatment of seizures in sepsis.

COMPARISON OF VARIOUS EEG ELECTRODE PLACEMENT SYSTEMS TO DETECT EPILEPTIFORM ABNORMALITIES IN INFANTS

Background: Technical difficulties in placement of whole 10-20 electrode system is not uncommon in neonates and infants. Apart from the full channel many centers uses the modified and amplitude integrated EEG montages to identify seizures. Objective: Efficacy of standard, modified and amplitude integrated EEG electrode placement in infants to detect epileptiform abnormalities. Methods: All routine EEGs from June 2015 to April 2018 were taken. Age ≤ 2years at the time of recoding was the inclusion criteria. Digital EEG was performed according to standard 10-20 electrode placement system in all patients. Abnormal EEGs were reanalyzed in different montages like A) 21 electrodes- full channel, B) 10 electrodes- modified long distance and C)4 electrodes- (centro/parietal) respectively. Inter ictal epileptiform discharges (IEDs), seizures, periodic complexes and non-specific dysfunctions were tabulated in all patients. Full channel montages are considered bench mark for the analysis Results: A total 129 EEGs analyzed. A) Full channel standard 21 electrodes montages could identify IEDs in 35, non-specific electrophysiological dysfunction in 9 and burst-suppression pattern in 2 EEGs. B) Modified electrode placement consists of 10 electrodes could identify IEDs only in 26 EEGs and non-specific electro physiological dysfunction in 6 EEGs. A total of 28 nonconvulsive seizures (NCS) recorded in 6 patients; 20 numbers of NCS (71.4%) seen in modified electrode placement (B) and only 16 (57.1%) seen in centro/parietal electrode placement (C).. Conclusion: Standard EEG electrode placement has higher yield in detecting epileptiform abnormalities.

DIagnostic Subdural EEG electrodes And Subdural hEmatoma (DISEASE): a study protocol for a prospective nonrandomized controlled trial

Background Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit. Methods In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study’s primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2–4 years of follow-up. Discussion The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs. Trial registration ClinicalTrials.gov identifier no. NCT04211233.

Targeting Ionotropic Glutamate Receptors In The Treatment Of Epilepsy

Background: A dysfunction in glutamate neurotransmission is critical for seizure. Glutamate is the major excitatory drive in the cerebral cortex, where seizures occur. Glutamate acts via (i) ionotropic (iGlu) receptors, which are ligand-gated ion channels mediating fast excitatory synaptic transmission; and (ii) G proteins coupled metabotropic (mGlu) receptors. Objective: To overview the evidence on the role of iGlu receptors in the onset, duration, and severity of convulsive and nonconvulsive seizures to lay the groundwork for novel strategies for drug-resistant epilepsy. Methods: We used PubMed crossed-search for “glutamate receptor and epilepsy” (sorting 3,170 reports), searched for “ionotropic glutamate receptors”, “AMPA receptors”, “NMDA receptors”, “kainate receptors”, “convulsive seizures”, “absence epilepsy”, and selected those papers focusing this Review’s scope. Results: iGlu receptors antagonists inhibit, whereas agonists worsen experimental seizures in various animal species. Clinical development of iGlu receptor antagonists has been limited by the occurrence of adverse effects caused by inhibition of fast excitatory synaptic transmission. To date, only one drug (perampanel) selectively targeting iGlu receptors is marketed for the treatment of focal epilepsy. However, other drugs, such as topiramate and felbamate, inhibit iGlu receptors in addition to other mechanisms. Conclusion: This review is expected to help dissecting those steps induced by iGlu receptors activation, which may be altered to provide antiepileptic efficacy without altering key physiological brain functions, thus improving safety and tolerability of iGlu-receptor directed antiepileptic agents. This effort mostly applies to drug resistant seizures, which impact the quality of life and often lead to status epilepticus, which is a medical urgency.

Epileptiform Discharge and Electrographic Seizures during the Hypothermia Phase as Predictors of Rewarming Seizures in Children after Resuscitation

The aim of this study was to determine the frequency, timing, and predictors of rewarming seizures in a cohort of children undergoing therapeutic hypothermia after resuscitation. We retrospectively reviewed consecutive pediatric patients undergoing therapeutic hypothermia after resuscitation admitted to our pediatric intensive care unit between January 2000 and December 2019. Continuous electroencephalographic monitoring was performed during hypothermia (24 h for cardiac aetiologies and 72 h for asphyxial aetiologies), rewarming (72 h), and then an additional 12 h of normothermia. Thirty comatose children undergoing therapeutic hypothermia after resuscitation were enrolled, of whom 10 (33.3%) had rewarming seizures. Two (20%) of these patients had their first seizure during the rewarming phase. Four (40%) patients had electroclinical seizures, and six (60%) had nonconvulsive seizures. The median time from starting rewarming to the onset of rewarming seizures was 37.3 h (range 6 to 65 h). The patients with interictal epileptiform activity and electrographic seizures during the hypothermia phase were more likely to have rewarming seizures compared to those without interictal epileptiform activity or electrographic seizures (p = 0.019 and 0.019, respectively). Therefore, in high-risk patients, continuous electroencephalographic monitoring for a longer duration may help to detect rewarming seizures and guide clinical management.