Refractory Status Epilepticus in a Patient With Aducanumab-Induced Amyloid-Related Imaging Abnormalities.

OBJECTIVE: To report a case of fatal super-refractory status epilepticus associated with amyloid-related imaging abnormalities (ARIA). METHODS: We describe the history, neuroimaging, EEG, and brain pathology findings of a 75-year-old patient with mild cognitive impairment due to Alzheimer disease (homozygous ε4 apolipoprotein status) and a remote history of 3 asymptomatic ARIA episodes, who developed super-refractory status epilepticus related to severe ARIA. RESULTS: The patient was participating in an extended open-label trial of aducanumab when she was admitted to hospital for focal seizures and ARIA in 2 noncontiguous regions of the left frontal and occipital lobes. Despite aggressive treatment with high-dose corticosteroids, sedation, and antiseizure medications, she died from refractory focal status epilepticus. In retrospect, routine surveillance brain magnetic resonance imaging performed 11 weeks before hospitalization had signs of ARIA, which had not been identified. DISCUSSION: Clinicians should be aware that anti-amyloid therapies may cause rare serious adverse events. A high degree of vigilance is required in the interpretation of surveillance imaging for ARIA. Longitudinal studies are justified to further characterize the safety profile of anti-amyloid antibody therapies and identify participants at high risk of serious adverse events.

Potential neuroprotective and autophagy-enhancing effects of alogliptin on lithium/pilocarpine-induced seizures in rats: Targeting the AMPK/SIRT1/Nrf2 axis.

BACKGROUND: Status epilepticus (SE) as a severe neurodegenerative disease, greatly negatively affects people's health, and there is an urgent need for innovative treatments. The valuable neuroprotective effects of glucagon-like peptide-1 (GLP-1) in several neurodegenerative diseases have raised motivation to investigate the dipeptidyl peptidase-4 (DPP-4) inhibitor; alogliptin (ALO), an oral antidiabetic drug as a potential treatment for SE. ALO has shown promising neuroprotective effects in Alzheimer's and Parkinson's diseases, but its impact on SE has not yet been studied. AIM: The present study aimed to explore the repurposing potential for ALO in a lithium/pilocarpine (Li/Pil)-induced SE model in rats. MAIN METHODS: ALO (30 mg/kg/day) was administered via gavage for 14 days, and SE was subsequently induced in the rats using a single dose of Li/Pil (127/60 mg/kg), while levetiracetam was used as a standard antiepileptic drug. KEY FINDINGS: The results showed that ALO reduced seizure severity and associated hippocampal neurodegeneration. ALO also increased γ-aminobutyric acid (GABA) levels, diminished glutamate spikes, and corrected glial fibrillary acidic protein (GFAP) changes. At the molecular level, ALO increased GLP-1 levels and activated its downstream signaling pathway, AMP-activated protein kinase (AMPK)/sirtuin-1 (SIRT1). ALO also dampened the brain's pro-oxidant response, curbed neuroinflammation, and counteracted hippocampal apoptosis affording neuroprotection. In addition, it activated autophagy as indicated by Beclin1 elevation. SIGNIFICANCE: This study suggested that the neuroprotective properties and autophagy-enhancing effects of ALO make it a promising treatment for SE and can potentially be used as a management approach for this condition.

Enteral Ketamine for Status Epilepticus in Children with Epilepsy.

BACKGROUND: Approximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy. METHODS: Patient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed. RESULTS: Nine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations. CONCLUSIONS: Enteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time.

Electroencephalographic and Behavioral Effects of Intranasal Administration of a Na+, K+-ATPase-Activating Antibody after Status Epilepticus.

Status epilepticus (SE) is a medical emergency associated with high mortality and morbidity. Na+, K+-ATPase, is a promising therapeutic target for SE, given its critical role in regulation of neuron excitability and cellular homeostasis. We investigated the effects of a Na+, K+-ATPase-activating antibody (DRRSAb) on short-term electrophysiological and behavioral consequences of pilocarpine-induced SE. Rats were submitted to pilocarpine-induced SE, followed by intranasal administration (2 µg/nostril). The antibody increased EEG activity following SE, namely, EEG power in theta, beta, and gamma frequency bands, assessed by quantitative analysis of EEG power spectra. One week later, DRRSAb-treated animals displayed less behavioral hyperreactivity in pick-up tests and better performance in novel object recognition tests, indicating that the intranasal administration of this Na+, K+-ATPase activator immediately after SE improves behavioral outcomes at a later time point. These results suggest that Na+, K+-ATPase activation warrants further investigation as an adjunctive therapeutic strategy for SE.

Neuroprotective potential of topiramate, pregabalin and lacosamide combination in a rat model of acute SE and intractable epilepsy: Perspectives from electroencephalographic, neurobehavioral and regional degenerative analysis.

The lithium-pilocarpine model is commonly used to recapitulate characteristics of human intractable focal epilepsy. In the current study, we explored the impact of topiramate (TPM) alone and in combination with pregabalin and lacosamide administration for 6 weeks on the evolution of spontaneous recurrent seizures (SRS) and disease-modifying potential on associated neuropsychiatric comorbidities. In addition, redox impairments and neurodegeneration in hippocampus regions vulnerable to temporal lobe epilepsy (TLE) were assessed by cresyl violet staining. Results revealed that acute electrophysiological (EEG) profiling of the ASD cocktail markedly halted sharp ictogenic spikes as well as altered dynamics of brain wave oscillations thus validating the need for polytherapy vs. monotherapy. In TLE animals, pharmacological intervention for 6 weeks with topiramate 10 mg/kg in combination with PREG and LAC at the dose of 20 mg/kg exhibited marked protection from SRS incidence, improved body weight, offensive aggression, anxiety-like behavior, cognitive impairments, and depressive-like behavior (p < 0.05). Moreover, combination therapy impeded redox impairments as evidenced by decreased MDA and AchE levels and increased activity of antioxidant SOD, GSH enzymes. Furthermore, polytherapy rescued animals from SE-induced neurodegeneration with increased neuronal density in CA1, CA3c, CA3ab, hilus, and granular cell layer (GCL) of the dentate gyrus. In conclusion, early polytherapy with topiramate in combination with pregabalin and lacosamide prompted synergy and prevented epileptogenesis with associated psychological and neuropathologic alterations.

Status epilepticus-Therapeutic management at the pediatric emergency department.

INTRODUCTION: Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus. METHODS: Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus. RESULTS: One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05). CONCLUSIONS: Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.

Emergent Management of Status Epilepticus.

OBJECTIVE: Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control. LATEST DEVELOPMENTS: Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option. ESSENTIAL POINTS: As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.

Immunotherapy in a case of low titre GAD65 antibody-associated spectrum neurological disorders.

We present a rare case of low titre GAD65 antibody-associated autoimmune encephalitis and status epilepticus in a young woman. She initially presented with left arm dystonic movements, contractures and status epilepticus. Due to the concern of autoimmune encephalitis and seizures, the patient received intravenous immunoglobulin empirically. After the detection of low serum GAD65 antibodies, the patient underwent immunomodulation therapy with significant improvement. This case demonstrated that in autoimmune encephalitis, it is important to monitor serum GAD65 antibodies levels and consider immunotherapy, despite mildly elevated serum levels. The patient's history of left arm dystonic movements without impaired awareness may have been due to limb dystonia, a presenting symptom of stiff person syndrome (SPS), despite SPS more commonly affecting axial muscles. This case further demonstrates that GAD65 antibody-related syndromes can manifest with different neurological phenotypes including co-occurrence of epilepsy with possible focal SPS despite low GAD65 antibodies titres.

Rat strain differences in seizure frequency and hilar neuron loss after systemic treatment with pilocarpine.

At least 3 months after systemic treatment with pilocarpine to induce status epilepticus, Long-Evans and Sprague-Dawley rats were video-EEG monitored for seizures continuously for 1 month. Rats were then perfused, hippocampi were processed for Nissl staining, and hilar neurons were quantified. Seizure frequency in Long-Evans rats was 1/10th of that in Sprague-Dawley rats, and more variable. Hilar neuron loss was also less severe in Long-Evans rats. However, there was no correlation between hilar neuron loss and seizure frequency in either strain. The low and variable seizure frequency suggests limited usefulness of pilocarpine-treated Long-Evans rats for some epilepsy experiments.

Early Subclinical Status Epilepticus May Contribute to Developmental Delays in Infants With Tuberous Sclerosis Complex.

We present a case of a newborn with a prenatally discovered cardiac rhabdomyoma leading to early genetic diagnosis of tuberous sclerosis complex (TSC). This early diagnosis prompted a presymptomatic electroencephalography (EEG) that revealed subclinical seizures meeting the definition for status epilepticus on day 1 of life. Antiseizure medications (ASMs), including vigabatrin, were started. The EPISTOP and PREVeNT trials demonstrated that early life initiation of vigabatrin may reduce the degree of refractory epilepsy and epileptic spasms (ES) in this population (TSC). Although neonatal seizures are a known entity in TSC, continuous neonatal EEG monitoring is not standard at birth. This case supports early consideration for neonatal EEG monitoring to identify and treat neonatal seizures, reduce risk for infantile spasms, and potentially improve neurodevelopmental outcomes.

Morbidity Associated with Deviation from Pediatric Status Epilepticus Guidelines.

Treatment guidelines for the management of pediatric status epilepticus (PSE) are often institution-specific. We aim to characterize deviation from our hospital-based PSE treatment guidelines, the total dosage of benzodiazepines administered, and the need for intubation. The study population included all patients with an ICD -10 code for PSE who required admission to the Pediatric Intensive Care Unit (PICU) from April 2019 to April 2022. There were 66 PICU admissions. All patients with concern for PSE and altered mental status are admitted to the PICU. The cohort was divided between those treated according to the PSE protocol (benzodiazepine dose (0.05 mg/kg- 0.2 mg/kg) versus those who had low dose (≤0.05 mg/kg) and high-dose benzodiazepine (> 0.2 mg/kg) totals. The dosage was calculated as the total dose of benzodiazepines received pre-hospital and in the ED before intubation or transport. Forty-one (62 %) of patients received high-dose benzodiazepines (median 0.34 mg/kg [IQR 0.29-0.56], 19 (29 %) received recommended-dose benzodiazepines (median 0.13 mg/kg [IQR 0.09,0.15] and 6 (9 %) received low-dose (median 0.05 mg/kg [IQR 0.03,0.05]. The high-dose group was 15.9 (95 % CI = 3.7, 99.9) times more likely to be intubated controlling for the location of care (tertiary versus community hospital), and the age of the patient. The recommended-dose and low-dose groups required intubation with much less frequency.

Regional determinants for outcome and cost of status epilepticus.

OBJECTIVE: Status epilepticus (SE) requires informed management. Since regional differences exist in practice and outcome, we aimed to characterize the epidemiology of SE and identify the factors associated with cost-effective management at the sole level IV epilepsy center of Central New York (CNY). METHODS: We searched for patients aged 18 years or older admitted at our center's hospitals from February 2018 to November 2019 with the discharge diagnosis of SE. Seventy-seven individuals with definite SE were included. We constructed models to determine the main factors that impact the refractoriness of SE, the clinical outcome, and the estimated cost of hospitalization. RESULTS: The rate of SE-related disability was 20.8% and the all-cause mortality 36.4%. Our analysis showed that initial anti-seizure medication (ASM) choice did not have a significant influence on the clinical outcome; nor did it affect the refractoriness of SE. Likewise, our anesthetic regimen did not alter the disease course or outcome. In line with prior studies, we demonstrated that age carried a negative predictive value to the SE-related disability and mortality (CI95% [-0.02, 0], p < 0.001). Interestingly, we found that use of midazolam (CI95% [-20.8, -0.08], p = 0.05) and anoxic brain injury as the underlying etiology (CI95% [-33.5, -1.59], p = 0.03) were marginally associated with shorter hospitalizations and reduced cost. The latter might reflect the rapidly-deteriorating course of anoxic brain injury, complicated by its higher likelihood of refractoriness (CI95% [0.14, 0.79], p = 0.006), and consequently, the decision to withdraw care. CONCLUSION: Taken together, we described the demographics, management, and prognosis of SE locally and further defined the potential determinants for the cost-effective care. We found that similar to other studies, age was the main determinant factor in prognosis. We also noticed that midazolam usage was associated with shorter hospital stay, suggesting that strategic use of midazolam may reduce the direct cost of management of SE. These findings can be adopted to optimize SE management in CNY.

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

A systematic review and meta-analysis of ketamine in pediatric status epilepticus.

OBJECTIVE: Status epilepticus (SE) is a common neurological medical emergency in the pediatric population, with 10%-40% of cases progressing to refractory SE (RSE), requiring treatment with anesthetic infusions. We present a systematic review and meta-analysis of the use of ketamine for the treatment of pediatric SE and its potential advantages over other anesthetic infusions. METHODS: This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic databases, including PubMed, Cochrane Library, Ovid, Embase, and Google Scholar, were searched with the keywords "pediatrics," "status epilepticus," and "ketamine treatment." Randomized trials, prospective and retrospective cohort studies, and case reports were considered for inclusion. RESULTS: Eighteen publications met the initial inclusion criteria. The 18 publications comprise 11 case reports, one nonconclusive clinical trial, two case series, and four retrospective cohorts. After excluding the case reports because of reporting bias, only the six case series and cohorts were included in the final analysis. There were 172 patients in the six included studies. The weighted age was 9.93 (SD = 10.29) years. The weighted maximum dose was 7.44 (SD = 9.39) mg/kg/h. SE cessation was attained in 51% (95% confidence interval = 43-59) of cases with the addition of ketamine. The heterogeneity was I2 = 0%, t2 = 0, χ2 (5) = 3.39 (p = .64). SIGNIFICANCE: Pediatric RSE is difficult to treat, resulting in increased morbidity and mortality. Without strong recommendations and evidence regarding preferred agents, this review provides evidence that ketamine may be considered in managing SE in the pediatric population.

Efficacy of second-line anticonvulsant agents with adult status epilepticus: A systematic review and network meta-analysis.

BACKGROUND: Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs. OBJECTIVE: We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs. METHODS: We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework. RESULTS: Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest. CONCLUSIONS: PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was "very low", and careful interpretation is essential.

Status epilepticus management in patients with brain tumors. A cohort study.

PURPOSE: Status epilepticus (SE) represents a neurological emergency with significant morbidity and mortality. SE in patients with primary brain tumors received only limited attention to date; detailed analysis of treatment flow is lacking, especially as compared to other SE causes. This study aims to describe the frequency and treatment flow of tumor-related SE and compare it to other SE etiologies. METHODS: Retrospective cohort study based on an institutional SE registry (SERCH) comprising adult SE (excluding post-anoxic causes), treated between January 2013 and December 2022, comparing SE management, frequency of refractory SE, and clinical outcome, among four patients' groups stratified by SE etiology: Non-neoplastic, Gliomas, Brain metastases, Other brain tumors. RESULTS: We analyzed 961 episodes in 831 patients (Non-neoplastic: 649, Gliomas: 85, Metastases: 77, Other brain tumors: 20). Although tumor-patients presented more often with focal episodes and less consciousness impairment than non-neoplastic patients, administration of benzodiazepines as first-line treatment (>75% across all groups), and utilization of second-line ASM were similar across groups. Treatment adequacy was marginally higher in glioma patients compared to the non-neoplastic population (p: 0.049), while refractory SE was comparable in all groups (p: 0.269). No significant differences in clinical outcomes were observed (mortality: non-neoplastic (89/649, 13.7%), glioma (8/85, 9.4%), metastases (14/77, 18.2%), other tumors (5/20, 25.0%), p: 0.198; non-neoplastic vs. glioma, p: 0.271) CONCLUSION: Tumor-associated SE represents 1/5 of all SE episodes, and is managed similarly to other SE causes. Treatment responsiveness and short-term clinical outcomes also exhibit comparable results.

Sustained Inhibition of GABA-AT by OV329 Enhances Neuronal Inhibition and Prevents Development of Benzodiazepine Refractory Seizures.

γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the adult brain which mediates its rapid effects on neuronal excitability via ionotropic GABAA receptors. GABA levels in the brain are critically dependent upon GABA-aminotransferase (GABA-AT) which promotes its degradation. Vigabatrin, a low-affinity GABA-AT inhibitor, exhibits anticonvulsant efficacy, but its use is limited due to cumulative ocular toxicity. OV329 is a rationally designed, next-generation GABA-AT inhibitor with enhanced potency. We demonstrate that sustained exposure to OV329 in mice reduces GABA-AT activity and subsequently elevates GABA levels in the brain. Parallel increases in the efficacy of GABAergic inhibition were evident, together with elevations in electroencephalographic delta power. Consistent with this, OV329 exposure reduced the severity of status epilepticus and the development of benzodiazepine refractory seizures. Thus, OV329 may be of utility in treating seizure disorders and associated pathologies that result from neuronal hyperexcitability.

Practical approach to inhaled sedation in the critically ill patient. Sedation, analgesia and Delirium Working Group (GTSAD) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC).

The use of sedatives in Intensive Care Units (ICU) is essential for relieving anxiety and stress in mechanically ventilated patients, and it is related to clinical outcomes, duration of mechanical ventilation, and length of stay in the ICU. Inhaled sedatives offer benefits such as faster awakening and extubation, decreased total opioid and neuromuscular blocking agents (NMB) doses, as well as bronchodilator, anticonvulsant, and cardiopulmonary and neurological protective effects. Inhaled sedation is administered using a specific vaporizer. Isoflurane is the recommended agent due to its efficacy and safety profile. Inhaled sedation is recommended for moderate and deep sedation, prolonged sedation, difficult sedation, patients with acute respiratory distress syndrome (ARDS), status asthmaticus, and super-refractory status epilepticus. By offering these significant advantages, the use of inhaled sedatives allows for a personalized and controlled approach to optimize sedation in the ICU.

Clinical analysis of developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary care center experience in China.

PURPOSE: To analyze the electroclinical features of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE/EE-SWAS) and study the efficacy of different therapies on seizure control, electroencephalogram (EEG) improvements of electrical status epilepticus during sleep (ESES), and cognition outcomes. METHODS: Patients with DEE/EE-SWAS who underwent at least one follow-up EEG 3 months after therapy were retrospectively enrolled. The demographic and clinical characteristics of the patients were analyzed. Variables that influenced the outcomes were evaluated using logistic regression models. RESULTS: In total, 87 patients (47 males) were included. The median age at ESES recognition was 81.0 months (IQR 64.0, 96.0). Forty-six patients were diagnosed with self-limited focal epilepsies (SeLFEs) before ESES recognition, 24 with developmental and epileptic encephalopathies with spike-and-wave activation in sleep (DEE-SWAS), and 17 with other epilepsies. Steroids, benzodiazepines, and antiseizure medications (ASMs) were the initial treatment options for ESES. Patients with structural etiologies or slow EEG backgrounds at the time of ESES recognition were less likely to respond to treatment than other patients. However, only children with slow EEG backgrounds had lower odds of response in logistic regression models. Children with clinical or EEG response showed improvements in cognition. CONCLUSION: Steroids, benzodiazepines, and ASMs are effective treatments for patients with DEE/EE-SWAS. Children with structural etiologies or slow EEG backgrounds at the time of ESES recognition may have a poor long-term prognosis. The efficacy of seizure reduction and EEG improvement is associated with cognitive improvement.

Seizure suppression and neuroprotection in soman-exposed rats following delayed intramuscular treatment of adenosine A1 receptor agonist as an adjunct to standard medical treatment.

Soman produces excitotoxic effects by inhibiting acetylcholinesterase in the cholinergic synapses and neuromuscular junctions, resulting in soman-induced sustained status epilepticus (SSE). Our previous work showed delayed intramuscular (i.m.) treatment with A1 adenosine receptor agonist N-bicyclo-[2.2.1]-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone suppressed soman-induced SSE and prevented neuropathology. Using this same rat soman seizure model, we tested if delayed therapy with ENBA (60 mg/kg, i.m.) would terminate seizure, protect neuropathology, and aid in survival when given in conjunction with current standard medical countermeasures (MCMs): atropine sulfate, 2-PAM, and midazolam (MDZ). Either 15- or 30-min following soman-induced SSE onset, male rats received atropine and 2-PAM plus either MDZ or MDZ + ENBA. Electroencephalographic (EEG) activity, physiologic parameters, and motor function were recorded. Either 2- or 14-days following exposure surviving rats were euthanized and perfused for histology. All animals treated with MDZ + ENBA at both time points had 100% EEG seizure termination and reduced total neuropathology compared to animals treated with MDZ (2-day, p = 0.015 for 15-min, p = 0.002 for 30-min; 14-day, p < 0.001 for 15-min, p = 0.006 for 30-min), showing ENBA enhanced MDZ's anticonvulsant and neuroprotectant efficacy. However, combined MDZ + ENBA treatment, when compared to MDZ treatment groups, had a reduction in the 14-day survival rate regardless of treatment time, indicating possible enhancement of MDZ's neuronal inhibitory effects by ENBA. Based on our findings, ENBA shows promise as an anticonvulsant and neuroprotectant in a combined treatment regimen following soman exposure; when given as an adjunct to standard MCMs, the dose of ENBA needs to be adjusted.