Search Results (12)

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit. Full article

Background: FIRES is a rare and catastrophic presentation of a de novo refractory status epilepticus (RSE) in healthy individuals following mild febrile illness. It carries a high burden of morbidity and an estimated mortality of 12% in children. In over half of patients, an underlying cause is not discovered (cryptogenic FIRES). The theory that post-infectious inflammation promotes aberrant neuronal excitation has led to the use of immunomodulatory therapies as treatment for FIRES. High-dose glucocorticoids and intravenous immunoglobulin (IVIG) are used as first-line therapies but are ineffective in most cases. A comprehensive initial evaluation is critical in directing second-line therapies; however, an autoimmune and inflammatory workup is seldom completed prior to treatment. Despite recent trends toward using cytokine-directed therapies, outcomes remain poor. Methods: This single-institution retrospective case series describes three cases of FIRES in similarly aged children. Each patient experienced super-refractory status epilepticus (SRSE) resistant to first-line systemic immunotherapy (SIT). The novel use of baricitinib, a non-selective JAK inhibitor, proved effective for one patient, while IL-1 and IL-6 inhibition were effective in the other two. All patients suffered moderate-to-severe neurologic and cognitive impairment at the time of discharge. Conclusions: FIRES is a poorly understood catastrophic presentation of refractory status epilepticus (RSE) requiring a multimodal approach to treatment. Cytokine profiling can be helpful in identifying cryptogenic cases from those with an underlying cause if conducted early in the clinical course. The early use of second-line immunomodulatory therapies may aid in decreasing neuroinflammation and improve outcomes. Full article

Background: this study aimed to evaluate the role of early airway management and intubation in status epilepticus (SE) with out-of-hospital onset. Methods: We included all patients with out-of-hospital SE onset referred to the emergency department of the Academic Hospital of Modena between 2013 and 2021. Patients were compared according to out-of-hospital airway management (intubation versus non-intubation) and a propensity score was performed for clinical variables unevenly distributed between the two groups. Results: We evaluated 711 patients with SE. A total of 397 patients with out-of-hospital SE onset were eventually included; of these, 20.4% (81/397) were intubated before arrival at the hospital. No difference was found in the clinical characteristics of patients after propensity score matching. The 30-day mortality in the propensity group was 19.4% (14/72), and no difference was found between intubated (7/36, 19.4%) and non-intubated (7/36, 19.4%) patients. No difference was found in SE cessation. Compared to non-intubated patients, those who underwent out-of-hospital intubation had a higher risk of progression to refractory or super-refractory SE, greater worsening of mRS values between hospital discharge and admission, and lower probability of returning to baseline condition at 30 days after SE onset. Conclusions: Early intubation for out-of-hospital SE onset is not associated with improved patient survival even after balancing for possible confounders. Further studies should evaluate the timing of intubation and its association with first-line treatments for SE and their efficacy. In addition, they should focus on the settings and the exact reasons leading to intubation to better inform early management of SE with out-of-hospital onset. Full article

(1) Background: Increasing evidence supports the anti-inflammatory and neuroprotective role of perampanel (PER), mediated by decreased expression of pro-inflammatory cytokines and by interference with apoptosis processes. Therefore, the use of PER to treat status epilepticus (SE) with suspected inflammatory etiology is appealing and deserves further investigation. (2) Methods: We retrospectively analyzed seven patients (five F, two M; median age: 62 years) with refractory and super-refractory SE due to a probable or defined inflammatory etiology and treated with PER. (3) Results: PER was administered as the third (4/7) or fourth drug (3/7), with a median loading dose of 32 mg/day (range: 16–36 mg/day) and a median maintenance dose of 10 mg/day (range: 4–12 mg/day). In five cases, SE was focal, while in two patients, it was generalized. SE was caused by systemic inflammation in three patients, while in the other four subjects, it was recognized to have an autoimmune etiology. SE resolution was observed after PER administration in all cases, particularly within 24 h in the majority of patients (4/7, 57.1%). (4) Conclusions: Our data support the efficacy of PER in treating SE when first- and second-line ASMs have failed and suggest a possible earlier use in SE cases that are due to inflammatory/autoimmune etiology. Full article

Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE. Methods: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up. Results: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE. Discussion and Conclusions: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS’s potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights. Full article

Status epilepticus (SE) is a life-threatening condition and medical emergency which can have lifelong consequences, including neuronal death and alteration of neuronal networks, resulting in long-term neurologic and cognitive deficits in children. When standard pharmacological treatment for SE is not successful in controlling seizures, the condition evolves to refractory SE (rSE) and finally to super-refractory SE (srSE) if it exceeds 24 h despite using anaesthetics. In this systematic review, we present literature data on the potential uses of clinical neuromodulation techniques for the management of srSE in children, including electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation. The evaluation of these techniques is limited by the small number of published paediatric cases (n = 25, one with two techniques) in peer-reviewed articles (n = 18). Although neuromodulation strategies have not been tested through randomised, prospective controlled clinical trials, this review presents the existing data and the potential benefits of neuromodulation therapy, suggesting that these techniques, when available, could be considered at earlier stages within the course of srSE intending to prevent long-term neurologic complications. Clinical trials aiming to establish whether early intervention can prevent long-term sequelae are necessary in order to establish the potential clinical value of neuromodulation techniques for the treatment of srSE in children. Full article

Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations. Full article

We aimed to evaluate the current management of status epilepticus (SE) in intensive care units (ICUs) in Germany, depending on the different hospital levels of care and the ICU specialty. We performed a nationwide web-based anonymized survey, including all German ICUs registered with the German Society for Neurointensive and Emergency Care (Deutsche Gesellschaft für Neurointensiv- und Notfallmedizin; DGNI). The response rate was 83/232 (36%). Continuous EEG monitoring (cEEG) was available in 86% of ICUs. Regular written cEEG reports were obtained in only 50%. Drug management was homogeneous with a general consensus regarding substance order: benzodiazepines—anticonvulsants—sedatives. Thereunder first choice substances were lorazepam (90%), levetiracetam (91%), and propofol (73%). Data suggest that network structures for super-refractory SE are not permeable, as 75% did not transfer SE patients. Our survey provides “real world data” concerning the current management of SE in Germany. Uniform standards in the implementation of cEEG could help further improve the overall quality. Initial therapy management is standardized. For super-refractory SE, a concentration of highly specialized centers establishing network structures analogous to neurovascular diseases seems desirable to apply rescue therapies with low evidence carefully, ideally collecting data on this rare condition in registries and clinical trials. Full article

Refractory and super-refractory status epilepticus (RSE and SRSE) are life-threatening conditions requiring prompt initiation of appropriate treatment to avoid permanent neurological damage and reduce morbidity and mortality. RSE is defined as status epilepticus that persists despite administering at least two appropriately dosed parenteral medications, including a benzodiazepine. SRSE is status epilepticus that persists at least 24 h after adding at least one appropriately dosed continuous anesthetic (i.e., midazolam, propofol, pentobarbital, and ketamine). Other therapeutic interventions include immunotherapy, neuromodulation, ketogenic diet, or even surgical intervention in certain cases. Continuous electroencephalogram is an essential monitoring tool for diagnosis and treatment. In this review, we focus on the diagnosis and treatment of RSE and SRSE. Full article

Background: Status epilepticus (SE) carries an exceedingly high mortality and morbidity, often warranting an aggressive therapeutic approach. Recently, the implementation of a ketogenic diet (KD) in adults with refractory and super-refractory SE has been shown to be feasible and effective. Methods: We describe our experience, including the challenges of achieving and maintaining ketosis, in an adult with new onset refractory status epilepticus (NORSE). Case Vignette: A previously healthy 29-year-old woman was admitted with cryptogenic NORSE following a febrile illness; course was complicated by prolonged super-refractory SE. A comprehensive work-up was notable only for mild cerebral spinal fluid (CSF) pleocytosis, elevated nonspecific serum inflammatory markers, and edematous hippocampi with associated diffusion restriction on magnetic resonance imaging (MRI). Repeat CSF testing was normal and serial MRIs demonstrated resolution of edema and diffusion restriction with progressive hippocampal and diffuse atrophy. She required prolonged therapeutic coma with high anesthetic infusion rates, 16 antiseizure drug (ASD) trials, empiric immunosuppression and partial bilateral oophorectomy. Enteral ketogenic formula was started on hospital day 28. However, sustained beta-hydroxybutyrate levels >2 mmol/L were only achieved 37 days later following a comprehensive adjustment of the care plan. KD was challenging to maintain in the intensive care unit (ICU) and was discontinued due to poor nutritional state and pressure ulcers. KD was restarted again in a non-ICU unit facilitating ASD tapering without re-emergence of SE. Discussion: There are inconspicuous carbohydrates in commonly administered medications for SE including antibiotics, electrolyte repletion formulations, different preparations of the same drug (i.e., parenteral, tablet, or suspension) and even solutions used for oral care―all challenging the use of KD in the hospitalized patient. Tailoring comprehensive care and awareness of possible complications of KD are important for the successful implementation and maintenance of ketosis. Full article

Super-refractory status epilepticus (SRSE) represents a neurological emergency that is characterized by a lack of response to the third line of antiepileptic treatment, including intravenous general anesthetics. It is a medical challenge with high morbidity and mortality. Electroconvulsive therapy (ECT) has been recommended as a nonpharmacologic option of treatment after other alternatives are unsuccessful. Its effect on the cessation of SRSE has been minimally investigated. The objective of this article is to analyze the effect of ECT on SRSE. For this purpose, a multidisciplinary team created a protocol based on clinical guidelines similar to those described previously by Ray et al. (2017). ECT was applied to six patients with SRSE after the failure of antiepileptic treatment and pharmacologic coma.The objective of each ECT session was to elicit a motor seizure for at least 20 s. SRSE was resolved in all patients after several days of treatment, including ECT as a therapy, without relevant adverse effects. Thus, ECT is an effective and feasible option in the treatment of SRSE, and its place in the algorithm in treatment should be studied due to the uncommon adverse effects and the noninvasive character of the therapy. Full article

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. Full article