Refractory Convulsive Status Epilepticus Research Articles

Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report

BackgroundTreating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs.Case presentationA 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2–5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 μg/mL, increasing to 35.2 μg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 μg/mL to 2.1 μg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs.ConclusionsThis case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.

Management strategies for refractory status epilepticus

Refractory status epilepticus (RSE) is defined as the persistence of either clinical or electrographic seizures despite the administration of appropriate doses of an initial benzodiazepine and suitable second-line antiepileptic drugs (AEDs). The Neurocritical Care Society and the American Epilepsy Society have proposed a treatment paradigm for the management of convulsive status epilepticus (CSE). The third-line therapy in refractory CSE may involve general anesthesia using intravenous midazolam, propofol, or other agents, while recent evidence supports the use of ketamine to manage RSE in both adults and children. However, although these treatment strategies are frequently employed in nonconvulsive status epilepticus (NCSE), the efficacy of AEDs and anesthetics in NCSE has not been thoroughly investigated. Recent evidence has demonstrated the safety and efficacy of newer AEDs, including levetiracetam and lacosamide, in the treatment of status epilepticus (SE) and RSE, which also encompasses NCSE. Use of multiple combinations of various intravenous AEDs can also be considered in NCSE before the administration of general anesthesia. In addition, AEDs alone exhibit limited effectiveness in managing SE for new-onset RSE (NORSE) and its subset, febrile infection-related epilepsy syndrome. Therefore, in cases of refractory status, it is imperative to explore treatment options beyond AEDs, including immunotherapy and the incorporation of a ketogenic diet. The present review suggests treatment approaches for RSE based on subgroups, including CSE, NCSE, and NORSE. A discussion of recent clinical studies on AEDs and anesthetics in the management of RSE, as well as proposed treatment methods for NORSE, is also provided.

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series.

Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation. In this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation. We present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24h of ketamine administration. A total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26-72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%)cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to along term acute care hospital, and one patient to hospice. The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chartreview.

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort)

PurposeDelayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). MethodsRetrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month–21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. ResultsWe included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5–7.3) years. The median time from seizure onset to hospital arrival was 45 (30–67) minutes, with a median time cared for by EMS of 24 (15–36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72–6.12, p<0.001). ConclusionIn this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

Management and outcomes of critically ill adult patients with convulsive status epilepticus and preadmission functional impairments

ObjectiveFunctional status is among the criteria relevant to decisions about intensive care unit (ICU) admission and level of care. Our main objective was to describe the characteristics and outcomes of adult patients requiring ICU admission for Convulsive Status Epilepticus (CSE) according to whether their functional status was previously impaired. MethodsWe retrospectively analyzed data from consecutive adults who were admitted to two French ICUs for CSE between 2005 and 2018 and then included them retrospectively in the Ictal Registry. Pre-existing functional impairment was defined as a Glasgow Outcome Scale (GOS) score of 3 before admission. The primary outcome measure was a loss of ≥1 GOS score point at 1 year. Multivariate analysis was used to identify factors associated with this measure. ResultsThe 206 women and 293 men had a median age of 59 years [47–70 years]. The preadmission GOS score was 3 in 56 (11.2%) patients and 4 or 5 in 443 patients. Compared to the GOS-4/5 group, the GOS-3 group was characterized by a higher frequency of treatment-limitation decisions (35.7% vs. 12%, P < 0.0001), similar ICU mortality (19.6 vs. 13.1, P = 0.22), higher 1-year mortality (39.3% vs. 25.6%, P < 0.01), and a similar proportion of patients with no worsening of the GOS score at 1 year (42.9 vs. 44.1, P = 0.89). By multivariate analysis, not achieving a favorable 1-year outcome was associated with age above 59 years (OR, 2.36; 95%CI, 1.55–3.58, P < 0.0001), preexisting ultimately fatal comorbidity (OR, 2.92; 95%CI, 1.71–4.98, P = 0.0001), refractory CSE (OR, 2.19; 95%CI, 1.43–3.36, P = 0.0004), cerebral insult as the cause of CSE (OR, 2.75; 95%CI, 1.75–4.27, P < 0.0001), and Logistic Organ Dysfunction score ≥ 3 at ICU admission (OR, 2.08; 95%CI, 1.37–3.15, P = 0.0006). A preadmission GOS score of 3 was not associated with a functional decline during the first year (OR, 0.61; 95%CI, 0.31–1.22, P = 0.17). SignificancePreadmission functional status in adult patients with CSE is not independently associated with a functional decline during the first postadmission year. This finding may help physicians make ICU admission decisions and adult patients write advance directives.Study Registration: #NCT03457831.

Non convulsive refractory status epilepticus induced by thiocolchicoside (TCC) intrathecal injection: A case report

TCC is a semisynthetic molecule widely used in clinical settings as a pain killer and myorelaxant. Several neurological side effects have been reported in association with TCC treatment including somnolence, confusion and seizure, the latter in a lower percentage of patients. Some previous reports described seizure onset after TCC intake in adulthood. However, major epileptological complication, namely status epilepticus, has never been previously reported in association with TCC treatment. In our report, we describe a case of acute refractory non‐convulsive status epilepticus (NCSE) in the context of a TCC‐induced acute toxic encephalopathy (ATE) in a woman without any previous neurological or physical comorbidities.

Time Elapsed from Onset of Pediatric Convulsive Status Epilepticus to Antiepileptic Administration-An Experience of Single Institute.

Data regarding time elapsed from the onset of pediatric convulsive status epilepticus (CSE) to antiepileptic (AED) administration remains scarce after the adoption of standard treatment-guidelines in Indian healthcare settings. A prospective observational analysis was performed on 52 children presenting to anurban, academic tertiary care teaching hospital diagnosed with CSE and evolving to refractory CSE (RCSE). Time frames of AED administration were compared to the adopted 'Status Epilepticus Management Protocol'. Fifty-two patients [36 (69.2%) male] were enrolled, with a median age of 4.1 y. After CSE onset, the median (p25-p75) time until the administration of the first-line, second-line, and third-line therapy phases of AED doses were 30 (25-37) min, 68 (48-79) min, and 105 (100-135) min, respectively. The second dose of non-BZD AED was administered at a median (p25-p75) of 90 (71-95) min. Twenty-six (50%) patients received at least one continuous infusion. The time elapsed from CSE onset to AED administration and escalation from one class to another was delayed.

Determinants of mortality and long-term outcome in children with refractory and super refractory status epilepticus

AimTo evaluate factors associated with progression of convulsive refractory status epilepticus(RSE) to super refractory status epilepticus(SRSE) and long term outcome in children. Materials and methodsIn this open cohort study, data of children admitted with convulsive RSE from 2010 to 2018 was retrospectively analyzed. The outcome at two years was graded according to the Glasgow outcome scale(GOS). ResultsFifty six children formed study population, 24 progressed to SRSE. The mean age of the study population was 9.38 ± 4.28(2–16) years. There was no significant difference for age between SRSE and RSE children (9.53 ± 4.50 years vs. 9.17 ± 4.06 years; p = 0.756). Acute symptomatic aetiology was the most common aetiology for RSE (57.1%) and SRSE (54.2%). There were no differences for aetiology between children who progressed to SRSE and those who did not. Mean length of stay in the NICU was 13.54 ± 17.53 days and children who progressed to SRSE had a longer length of stay in NICU (4.78 ± 3.03 days vs. 25.21 ± 21.77 days; p < 0.001). The mortality was 14.2%. Acidosis was more common in children who died (27.1% vs. 87.5%;p < 0.001). There was no significant difference in the mortality between RSE and SRSE (9.4% vs. 20.8%; p = 0.268). At latest follow up 34 (60.7%) children had good outcome. Poor outcome was more common in children who progressed to SRSE(29.4% vs. 63.6%;p < 0.015). ConclusionAcute symptomatic etiology is more frequent in children with RSE and SRSE. Progression to SRSE did not significantly increase mortality but associated with poor GOS outcome. Encouragingly, 60% of children had good outcome.

An ultra-long new onset refractory status epilepticus: Winning the battle but losing the war?

New onset refractory status epilepticus (NORSE), is a rare and challenging condition occurring in previously healthy people. The etiology often remains undiscovered and is frequently associated with an unfavorable outcome. We report the electroclinical and neuroradiological evolution of an ultra-long case of NORSE of unknown etiology. A 38-year-old woman with a prodrome of fever, vomiting and diarrhea was admitted to our Intensive Care Unit for refractory convulsive status epilepticus (SE). Her past medical history was unremarkable. Extensive examinations were negative for potential viral, autoimmune and metabolic etiologies. Despite multiple therapeutical attempts with antiseizures medications, anesthetics and immunotherapy, seizures persisted. After nearly 6 months of enduring seizures, SE finally ceased and the patient gradually recovered to a minimum state of awareness. She was then able to communicate through one-word utterances and to understand simple tasks. At a three-years follow-up, she developed multifocal drug-resistant epilepsy, subcortical myoclonus and severe spastic quadraparesis, becoming completely dependent for activities of daily living. To our knowledge, this represents one of the longest cases of NORSE with final status resolution at this time. However, ultra-long SE in this case led to severe and disabling neurological sequelae. Future studies focused on disease modifying treatments for refractory SE are needed.

Determinants of nutritional status and outcome in adults with RCSE: a retrospective cohort study

BackgroundThis study aimed to investigate the association between nutritional characteristics in patients with refractory convulsive status epilepticus.MethodsWe retrospectively enrolled 73 patients with refractory convulsive status epilepticus over 18 years of age at the West China Hospital between January 2017 and May 2019. All patients met the 2016 International League Against Epilepsy diagnostic criteria for refractory convulsive status epilepticus. A logistic regression model was used to evaluate the association between malnutrition and refractory convulsive status epilepticus.ResultsOf the 73 patients with refractory convulsive status epilepticus, 33 (45.21 %) suffered from malnutrition during hospitalization, and duration of hospitalization in days (OR = 1.251; 95 % CI,–1.067–1.384; P = 0.007), nasal feeding (OR = 22.623; 95 % CI: 1.091-286.899; P = 0.013), and malnutrition on admission (OR = 30.760; 95 % CI: 1.064–89.797; P = 0.046) were significantly associated with malnutrition in patients with refractory convulsive status epilepticus.ConclusionsMalnutrition is a common complication during hospitalization in patients with refractory convulsive status epilepticus. The duration of hospitalization (days), nasal feeding, and malnutrition at admission are associated with malnutrition in patients with refractory convulsive status epilepticus. Further longitudinal studies are needed to identify the relationship between refractory convulsive status epilepticus and adverse outcomes.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

ObjectiveThis study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non‐BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE).MethodsThis retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non‐BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non‐BZD ASM.ResultsWe included 293 patients with a median (interquartile range) age of 3.8 (1.3–9.3) years. Thirty‐six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997–.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out‐of‐hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73–3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40–6.03, p < .0001) compared to patients with in‐hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01–2.06, p = .04). Forty‐seven percent of patients (n = 94) with out‐of‐hospital onset did not receive treatment before hospital arrival. Among patients with out‐of‐hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival.SignificanceFailure to escalate from BZDs to non‐BZD ASMs occurs mainly in out‐of‐hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non‐BZD ASMs after two BZD doses during handoffs between prehospital and in‐hospital settings.

Efficacy of Home Anticonvulsant Administration for Second-Line Status Epilepticus Treatment

To investigate whether receiving a second-line anticonvulsant medication that is part of a patient's home regimen influences outcomes in benzodiazepine-refractory convulsive status epilepticus. Using the Established Status Epilepticus Treatment Trial data, allocation to a study drug included in the patient's home anticonvulsant medication regimen was compared to receipt of an alternative second-line study medication. The primary outcome was cessation of clinical seizures with improved consciousness by 60 minutes after study drug initiation. Secondary outcomes were seizure cessation adjudicated from medical records and adverse events. We performed inverse probability of treatment-weighted (IPTW) logistic regressions. Of 462 patients, 232 (50%) were taking 1-2 of the 3 study medications at home. The primary outcome was observed in 39/89 (44%) patients allocated to their home medication vs 76/143 (53%) allocated to a nonhome medication (IPTW odds ratio [OR] 0.66, 95% confidence interval [CI] 0.39-1.14). The adjudicated outcome occurred in 37/89 (42%) patients vs 82/143 (57%), respectively (IPTW OR 0.52, 95% CI 0.30-0.89). There was no interaction between study levetiracetam and home levetiracetam and there were no differences in adverse events. There was no difference in the primary outcome for patients who received a home medication vs nonhome medication. However, the retrospective evaluation suggested an association between receiving a nonhome medication and seizure cessation. This study provides Class II evidence that for patients with refractory convulsive status epilepticus, use of a home second-line anticonvulsant compared to a nonhome anticonvulsant did not significantly affect the probability of stopping seizures.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. Retrospective cohort study with prospectively collected data between June 2011 and January 2019. Seventeen academic hospitals in the United States. We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. None. We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

Time to Treatment in Pediatric Convulsive Refractory Status Epilepticus: The Weekend Effect

BackgroundTime to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency. MethodsWe performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus. ResultsWe included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01). ConclusionsThe time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.

Treatment of Super-Refractory Status Epilepticus: A Review.

Purpose:Super-refractory status epilepticus (SRSE) presents management challenges due to the absence of randomized controlled trials and a plethora of potential medical therapies. The literature on treatment options for SRSE reports variable success and quality of evidence. This review is a sequel to the 2020 American Epilepsy Society (AES) comprehensive review of the treatment of convulsive refractory status epilepticus (RSE).Methods:We sought to determine the effectiveness of treatment options for SRSE. We performed a structured literature search (MEDLINE, Embase, CENTRAL, CINAHL) for studies on reported treatments of SRSE. We excluded antiseizure medications (ASMs) covered in the 2016 AES guideline on the treatment of established SE and the convulsive RSE comprehensive review of the 2020 AES. Literature was reviewed on the effectiveness of vagus nerve stimulation, ketogenic diet (KD), lidocaine, inhalation anesthetics, brain surgery, therapeutic hypothermia, perampanel, pregabalin (PGB), and topiramate in the treatment of SRSE. Two authors reviewed each therapeutic intervention. We graded the level of the evidence according to the 2017 classification scheme of the American Academy of Neurology.Results:For SRSE (level U; 39 class IV studies total), insufficient evidence exists to support that perampanel, PGB, lidocaine, or acute vagus nerve stimulation (VNS) is effective. For children and adults with SRSE, insufficient evidence exists to support that the KD is effective (level U; 5 class IV studies). For adults with SRSE, insufficient evidence exists that brain surgery is effective (level U, 7 class IV studies). For adults with SRSE insufficient, evidence exists that therapeutic hypothermia is effective (level C, 1 class II and 4 class IV studies). For neonates with hypoxic-ischemic encephalopathy, insufficient evidence exists that therapeutic hypothermia reduces seizure burden (level U; 1 class IV study). For adults with SRSE, insufficient evidence exists that inhalation anesthetics are effective (level U, 1 class IV study) and that there is a potential risk of neurotoxicity.Conclusion:For patients with SRSE insufficient, evidence exists that any of the ASMs reviewed, inhalational anesthetics, ketogenic diet, acute VNS, brain surgery, and therapeutic hypothermia are effective treatments. Data supporting the use of these treatments for SRSE are scarce and limited mainly to small case series and case reports and are confounded by differences in patients’ population, and comedications, among other factors.

Reader Response: Association of Guideline Publication and Delays to Treatment in Pediatric Status Epilepticus.

Sánchez Fernández et al.1 reported that the publication of evidence on delays in treatment of pediatric refractory convulsive status epilepticus (rSE) was not associated with improvement in time to treatment of rSE (TTTSE). They propose interventions to reduce TTTSE. We would like to share a successful model that we implemented. In 2013, we identified delays in TTTSE in our institution.2 We saw no improvement in TTTSE after a dual intervention consisting of educational programs for healthcare professionals and the development of an electronic SE order set.3 This prompted us to develop an SE alert system that was modeled after our “code stroke” protocol.4 When an inpatient is suspected to have SE, the SE alert is activated by calling an operator who simultaneously pages the neurology and pharmacy house staff, the rapid response team, and the manager responsible for bed assignment. Use of this alert system led to considerable reduction in time to administration of second-line antiseizure medications (22.21 ± 3.44 minutes) compared with standard care (58.30 ± 6.72 minutes; p < 0.0001).4 Because many hospitals have alert protocols for management of acute stroke, SE alert systems could be replicated with local resources to facilitate timely management and coordinated care of SE in adults and children.

P0728 / #2117: IMMUNE ENCEPHALITIS IN TWO PATIENTS AFTER HEMATOPOIETIC CELL TRANSPLANTATION

Aims & Objectives: To report two pediatric cases with non-infectious encephalitis after an allogeneic hematopoietic cell transplantation (allo-HSCT). Methods: Case report in a pediatric intensive care unit (PICU) in a tertiary hospital. Results: A 12-year-old boy, with history of acute myeloid leukemia and mild gastrointestinal graft-versus-host disease (GvHD) after an allo-HSCT, was admitted to our PICU with acute neurological symptoms. Initially, an infectious etiology was suspected as he was lymphopenic, but all laboratory tests, microbiological serum and CSF studies were normal except for Coronavirus HKU1 in a nasopharyngeal sample. MRI revealed a rhomboencephalitis with supratentorial involvement, electroencephalogram showed moderate diffuse encephalopathy. Response to cefotaxime, foscarnet, corticoids and immunoglobulins was poor. Five days after donor lymphocytes infusion, clinical and electroencephalographic improvement was noted. A 6-year-old girl with a primary immunodeficiency developed a severe GvHD with multiple organ involvement after an allo-HSCT. She required PICU admission with a refractory convulsive status epilepticus. Electroencephalogram showed epileptiform discharges and unspecific atrophy was described in MRI. All complementary tests were negative except for CSF lymphocytosis and 14-3-3 protein. Empiric treatment with intravenous immunoglobulins, plasmapheresis and corticosteroids was initiated, but failed to improve the patient’s condition. A ventilator-associated pneumonia lead to patient’s death at day 10. On autopsy, CNS findings were consistent with immune encephalitis, CNS GvHD was postulated as a possible diagnosis. No histological findings were suggestive of Creutzfeldt-Jakob disease. Conclusions: Recent research highlights the CNS immunological function. Faced with neurological deterioration in a patient who has received a hematological stem cell transplant, GvHD must be considered as a possible cause.

Continuous EEG monitoring in the follow-up of convulsive status epilepticus patients: A proposal and preliminary validation of an EEG-based seizure build-up score (EaSiBUSSEs)

Continuous electroencephalography (EEG) is a major tool for monitoring patients admitted to the intensive care unit after refractory convulsive status epilepticus, following control of convulsive movements. We review the values of different EEG patterns observed in critically ill patients for prognosis and seizure risk, together with proposed criteria for non-convulsive status epilepticus diagnosis (Salzburg Criteria), the EEG scores for prognosis (Epidemiology-based Mortality score in Status Epilepticus, EMSE) and for seizure risk (2HELPS2B). These criteria and scores, based partially on continuous EEG, are not tailored to repetitively monitor the progressive build-up leading to seizure or status epilepticus recurrence. Therefore, we propose a new EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs), based on the morphology and the prevalence of the EEG patterns observed in the follow-up of convulsive status epilepticus patients. It displays subscores from the least (no interictal activity) to the most associated with seizures (focal or generalized status epilepticus). We then evaluated the performance of the EaSiBUSSEs in a cohort of eleven patients who were admitted to intensive care unit for convulsive status epilepticus and who underwent continuous EEG recording. The receiver operating curve revealed good accuracy in identifying patients who would have seizures in the next 24 h, with excellent intra- and inter-rater reliability. We believe that this score is simple to perform, and suitable for repeated monitoring of EEG following refractory convulsive status epilepticus, with quantitative description of major EEG changes leading to seizures.

Automated identification and quality measurement for pediatric convulsive status epilepticus.

Treatment delays for refractory convulsive status epilepticus (RCSE) are associated with worse outcomes. In the United States, treatment for pediatric RCSE is slower than guidelines recommend. To address this gap, the American Academy of Neurology and Child Neurology Society (AAN/CNS) developed a quality measure: the percentage of RCSE patients that receive third-line treatment within 60minutes. We aimed to develop computable phenotypes for convulsive status epilepticus (CSE) and RCSE to automate calculation of the quality measure. From an observational cohort of children presenting to the emergency department for seizures or epilepsy, we identified presentations of RCSE and its precursors: CSE and benzodiazepine-resistant status epilepticus (BRSE). These served as a gold standard for computable phenotype development. Using multivariate analyses, we constructed and evaluated statistical models for case identification. We then evaluated adherence to the AAN/CNS RCSE quality measure. From 664 charts, we identified 56 patients with CSE, 36 with BRSE, and 18 with RCSE. Four predictors were used: International Classification of Diseases (ICD) codes, and receiving first-, second-, or third-line agents shortly after presentation to the emergency department (ED). Combinations of these predictors identified CSE with 84% sensitivity and 81% positive predictive value (PPV), BRSE with 67% sensitivity and 89% PPV, and RCSE with 94% sensitivity and 85% PPV. Median (interquartile range [IQR]) time to treatment for first-line agent was 13 (5-27) minutes for CSE, second-line for BRSE was 24 (9.5-43.5) minutes, and third-line for RCSE was 52 (27-87) minutes. Sixty percent of RCSE patients received a third-line agent within 60minutes of ED arrival. RCSE and its precursors can be identified automatically with high fidelity allowing automated calculation of time to treatment and the RCSE quality measure. This has the potential to facilitate quality improvement work and improve care for RCSE.

Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea.

Background and PurposeThe aim of this study was to survey the expert opinions on treatments for convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE) in adults.MethodsForty-two South Korean epileptologists participated in this survey. They completed an online questionnaire regarding various patient scenarios and evaluated the appropriateness of medications used to treat CSE and NCSE.ResultsInitial treatment with a benzodiazepine (BZD) followed by either a second BZD or an antiepileptic drug (AED) monotherapy was the preferred treatment strategy. More than two-thirds of the experts used a second BZD when the first one failed, and consensus was reached for 84.8% of the survey items. The preferred BZD was intravenous (IV) lorazepam for the initial treatment of status epilepticus. IV fosphenytoin and IV levetiracetam were chosen for AED monotherapy after the failure of BZD. The treatments for NCSE were similar to those for CSE. Continuous IV midazolam infusion was the treatment of choice for iatrogenic coma in refractory CSE, but other AEDs were preferred over iatrogenic coma in refractory NCSE.ConclusionsThe results of this survey are consistent with previous guidelines, and can be cautiously applied in clinical practice when treating patients with CSE or NCSE.