Cessation Of Status Epilepticus Research Articles

Association of early general anesthesia with outcome in adults with status epilepticus: A propensity-matched observational study.

General anesthesia (GA) earlier than recommended (as first- or second-line treatment) was recently described to improve status epilepticus (SE) outcome. We aimed to assess the impact of early GA on outcome in matched groups. Data from a multicenter, prospective cohort of 1179 SE episodes in 1049 adults were retrospectively analyzed. Incident SE episodes were categorized as "early anesthesia" (eGA; GA as first- or second-line treatment) or "non-early anesthesia" (neGA; GA after second-line treatment or not at all). Using propensity score matching, eGA episodes were paired 1:4 with neGA episodes. We assessed survival, functional outcomes at discharge (good: modified Rankin Scale = 0-2 or no worsening), SE cessation rate, SE duration, and hospital stay. Among 1049 SE episodes, 55 (5.2%) received eGA, and 994 constituted the neGA group; 220 represented the matched controls. Patients receiving eGA were younger (median = 63, interquartile range [IQR] = 56-76 vs. median = 70, IQR = 54-80 years, p = .004), had deeper consciousness impairment (80% vs. 40% stuporous/comatose, p < .001), and had more severe SE forms (89% vs. 54% generalized convulsive SE/nonconvulsive SE in coma, p < .001). Mortality, functional outcome, SE cessation rate, and duration of SE and hospital stay were similar between the eGA group and matched controls. We conclude that early anesthesia for SE treatment did not influence prognosis.

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

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. 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. 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). 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.

Outcome of emergency neurosurgery in patients with refractory and super-refractory status epilepticus: a systematic review and individual participant data meta-analysis.

Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up. A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance (p = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], p = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], p = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], p = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], p = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], p = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified. Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines.

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

BackgroundNovel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE.MethodsA case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search.ResultsFour case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases.ConclusionsBased on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations.Key pointsWe summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine.Refractory SE resolved after 4–7 days on fenfluramine.Swift fenfluramine up-titration was well-tolerated during SE treatment.Treatment-emergent adverse events on fenfluramine were not observed.Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.

The Role of Early Intubation in Status Epilepticus with Out-of-Hospital Onset: A Large Prospective Observational Study.

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.

Comparison of the status epilepticus severity score and the epidemiology-based mortality score in predicting 30-day mortality and status epilepticus cessation

ObjectiveTo evaluate the role of the Status Epilepticus Severity Score (STESS) and the Epidemiology-based Mortality score (EMSE) in predicting 30-day mortality and SE (Status epilepticus) cessation, and their prognostic performance in subgroups of patients with specific characteristics. MethodsWe reviewed consecutive episodes of SE occurring in patients aged ≥14 years at Baggiovara Civil Hospital (Modena, Italy) from 2013 to 2021. We evaluated the predictive accuracy of EMSE and STESS for 30-day mortality and SE cessation through stepwise regression binary logistic models adjusted for possible univariate clinical confounders. ResultsSeven hundred and eleven patients were enrolled. The mean value of STESS was 3.2 (SD 1.7) and of EMSE was 80.1 (SD 52.6). Within 30 days of the onset of SE, 28.4% of patients (202/711) died. EMSE had higher discriminatory ability for 30-day mortality compared with STESS (AUROC: 0.799; 95% CI: 0.765–0.832 versus 0.727; 95% CI: 0.686–0.766, respectively; p = 0.014). SE cessation within 1 h for convulsive SE and within 12 h for nonconvulsive SE was achieved in 35.3% (251/711) of patients. No significant difference was found between EMSE and STESS in discriminatory ability for SE cessation (AUROC: 0.516; 95% CI: 0.488–0.561 and 0.518; 95% CI: 0.473–0.563, respectively; p = 0.929). EMSE was superior to STESS in predicting 30-day mortality in patients with specific characteristics. No difference between the two scores was found in predicting SE cessation in subgroups of patients with specific characteristics. ConclusionsEMSE seems superior to STESS in predicting 30-day mortality, particularly in specific patient categories. Conversely, there is no difference in the ability of these scores in predicting SE cessation, which is overall rather low.

512: THE IMPACT OF LEVETIRACETAM LOADING DOSES ON SUCCESSFUL SEIZURE CESSATION

Introduction: Loading doses of 20 mg/kg of levetiracetam are commonly employed for refractory status epilepticus however, recent studies utilizing higher loading doses of 40-60 mg/kg have prompted a change in practice. This study aims to establish whether higher loading doses of levetiracetam lead to more rapid cessation of status epilepticus and reduced need for additional antiepileptic drugs. Methods: This was an IRB-approved, single-center, retrospective cohort study of patients admitted to a tertiary care academic medical center between April and September 2021. Patients were included if they were > 18 years of age and received levetiracetam as a loading-dose for cessation of status epilepticus. Patients were excluded if levetiracetam was administered for seizure prophylaxis. The primary outcome was unsuccessful seizure termination, defined as a requirement of an additional loading dose or an increase in maintenance doses of levetiracetam. Secondary outcomes included ICU and hospital length of stay, mortality, and need for third line treatment. Results: Of 390 patients screened for inclusion, 206 met inclusion criteria and were included in the primary analysis. Amongst patients who received a loading < 20 mg/kg, 50% had a diagnosis of epilepsy prior to admission, compared to 37.3% in the 20-40 mg/kg group and 42% in the ≥ 40 mg/kg group. Rates of ICU admission were 20%, 37.3% and 36.3%, respectively (p = 0.163). There was a statistically significant difference in ICU (3.5, 8.9, 13.5; p = 0.03) and hospital length of stay (13.1, 22.5, 30.7, p = 0) among groups. The primary outcome, unsuccessful seizure termination, was 13.8% in the < 20 mg/kg group, 12% in the 20-40 mg/kg group, and 34% in the > 40 mg/kg group. The rates of third-line therapy administration in each group was 5% vs. 13.3% vs. 22%, respectively. Conclusions: Among patients treated with loading-doses of levetiracetam > 40 mg/kg, there was a statistically significant increase in maintenance dose of levetiracetam and a trend towards more frequent administration of third-line agents. There was a longer ICU length of stay among patients administered >40 mg/kg loading dose which could have led to increased monitoring and increases in maintenance dosing of levetiracetam among that population.

Association of ictal imaging changes in status epilepticus and neurological deterioration.

In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge. The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes. Of 261 eligible patients, 101 received at least one MRI during SE or within 7 days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n= 20) and without (n= 81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24 h and hardly seen >5 days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies. In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.

Reponse of second-line treatment in focal status epilepticus: A tertiary hospital experience

ObjectiveTo investigate the response to various antiseizure medications (ASMs) in the treatment of focal status epilepticus (SE) in the established phase, and the effect of administering several ASMs prior to sedation. MethodsAll SE cases in patients aged > 16 years treated with non-BZDs ASMs were prospectively collected in our centre from February 2011 to April 2019. In total, 281 episodes were analysed. ResultsMedian age at SE onset was 65.1 years; 47 % were focal motor and 53 % focal non-motor episodes. SE cessation was achieved in 79 % episodes with second-line drugs, whereas a third line (anesthetics) was required in 47 episodes. SE cessation was achieved in only 27 % with the first ASM, 48 % with the second, and 51 % with the third. Prompt resolution of the SE episode with a first or second ASM was associated with a better outcome than episodes requiring a larger number of drugs (p = 0.024). The first option in our sample was levetiracetam in 70 % of cases. Among the total of non-responding SE cases treated with levetiracetam as the first ASM option, 107 were subsequently given lacosamide (seizure cessation in 53.3 %) and 34 valproic acid (seizure cessation in 29.4 %) (p = 0.015). ConclusionOur findings further support the notion that early termination of SE with a first or second ASM confers a better functional outcome. The large difference in response between the first ASM and consecutive ones suggests that the sum of different ASMs might be the key to resolving focal SE.

Out‐of‐hospital versus in‐hospital status epilepticus: The role of etiology and comorbidities

Background and purposeOur objectives were to identify differences in clinical characteristics between patients with out‐of‐hospital and in‐hospital status epilepticus (SE) onset, and to evaluate the influence of SE onset setting on 30‐day mortality and SE cessation.MethodsWe included consecutive patients with SE admitted from 2013–2021 at Modena Academic Hospital. A propensity score was obtained with clinical variables unevenly distributed between the two groups.ResultsSeven hundred eleven patients were included; 55.8% (397/711) with out‐of‐hospital and 44.2% (314/711) with in‐hospital onset. Patients with in‐hospital SE onset were older and had a higher frequency of comorbidities, acute and/or potentially fatal etiologies, impaired consciousness before treatment, and nonconvulsive or myoclonic SE. No difference was found in SE cessation between the groups. Patients with in‐hospital SE had higher 30‐day mortality (127/314, 62.9% vs. 75/397, 37.1%; p < 0.001). In‐hospital onset was an independent risk factor for 30‐day mortality (adjusted odds ratio = 1.720; 95% confidence interval = 1.107–2.674; p = 0.016). In the propensity group (n = 244), no difference was found in 30‐day mortality and SE cessation between out‐of‐hospital and in‐hospital SE onset groups (36/122, 29.5% vs. 34/122, 27.9%; p = 0.888; and 47/122, 38.5% vs. 39/122; 32%; p = 0.347, respectively).ConclusionsIn‐hospital SE is associated with higher 30‐day mortality without difference in SE cessation. The two groups differ considerably for age, acute and possibly fatal etiologies, comorbidities, and SE semiology. The patient location at SE onset is an important prognostic predictor. However, the increased mortality is probably unrelated to the setting of SE onset and reflects intrinsic prognostic predictors.

Levetiracetam for Status Epilepticus in Adults: A Systematic Review.

Status epilepticus (SE) is a neurologic emergency with potential for substantial mortality and morbidity. Parenteral benzodiazepine is the established first-line treatment but fails to control SE in about one-third of patients. Levetiracetam may be used for SE that is refractory to benzodiazepine therapy. To examine, by means of a systematic review, the role of IV levetiracetam for the treatment of SE in adults. MEDLINE, Embase, CENTRAL, and CINAHL databases were searched, from inception to August 18, 2020. Included in this review were prospective randomized controlled trials comparing levetiracetam with another antiepileptic drug, given with or after a benzodiazepine, in adult patients with SE. The primary outcome was cessation of SE. Quality of evidence was assessed with the Cochrane risk-of-bias tool. Characteristics of the included studies were reported using descriptive statistics. Five studies compared IV levetiracetam with valproic acid, phenytoin (or its prodrug fosphenytoin), or both. All 5 studies found no statistically significant differences in efficacy or safety end points. There were numerically more cases of hypotension and respiratory failure with phenytoin, and more cases of psychiatric adverse effects (e.g., post-ictal psychosis) with levetiracetam. Available evidence suggests that levetiracetam is as effective as valproic acid or phenytoin for the cessation of SE in adults. Other factors should therefore dictate the choice of antiepileptic drug for patients with SE, such as adverse effect profile, logistics of administration, drug cost, inclusion on hospital formularies, and drug availability.

Histopathology of new-onset refractory status epilepticus (NORSE) in adults

Objectivenew-onset refractory status epilepticus (NORSE) is defined as de novo refractory seizures occurring in previously healthy adults, without a clear underlying etiology. Due to refractory seizures and insufficient understanding of pathophysiology, management of these patients remains challenging and often leads to poor clinical outcomes. Various infectious and autoimmune mechanisms have been proposed but have not been validated and a large number of patients are thus labeled ‘cryptogenic’. Moreover, histopathological findings have rarely been described in NORSE and are usually autopsy evaluations. In this paper, we describe the clinical correlates and histopathological findings in patients presenting with NORSE. MethodsA case series of five patients with NORSE who underwent neurosurgical intervention and had histopathological examination during their acute clinical course. ResultsIn all patients,status epileptics was refractory to treatment with antiseizure drugs (ASDs) and anesthetic agents. Autoimmune work-up revealed elevated titer of anti-GAD antibody in one patient but was unremarkable in others. Empiric use of immunomodulation therapy in three patients did not lead to cessation of status epilepticus (SE). Due to failure of prolonged medical management, three patients underwent palliative surgery for resection of epileptogenic tissue whereas the other two had diagnostic brain biopsy. Histopathology obtained during biopsy revealed evidence of vasculitis in one and necrotizing vasculopathy in another. The patient with anti-GAD antibodies had evidence of lymphocytic infiltration in limbic structures. The remaining two had nonspecific histopathological findings. SignificanceAlthough our findings are limited by a small number of patients, it adds to the growing premise of NORSE being related to an underlying autoimmune process. Additional studies, especially with histopathological data are needed to better understand this devastating disorder.

Time is Brain

Status epilepticus (SE) is a serious complication of epilepsy that warrants both rapid and appropriate emergency management for better outcomes in terms of mortality and morbidity. The initial management of SE in emergency department (ED) involves a rapid neurological assessment and initiation of supportive therapy. Benzodiazepines are the recommended first-line treatment based on high-quality evidence, among them intramuscular (IM) midazolam IM was found to be as effective as intravenous lorazepam. However, it is important to understand that speedy drug delivery and adequate initial dose are of prime importance than selection of drug. Recent evidence shows all three second-line drugs, namely, valproate, fosphenytoin, and levetiracetam are alike in cessation of SE with similar incidence of adverse events. In refractory SE, the therapeutic options include the use of bolus dose followed by infusion of propofol, midazolam, ketamine, lacosamide, and phenobarbital. Magnesium sulfate is safe and superior in the management of eclamptic SE prompt and appropriate management in ED is the key to early cessation of SE, leading to better outcomes.

Understanding status epilepticus and its treatment in the community

Status epilepticus (SE) is a complication of epilepsy characterised by prolonged or repeated seizures. It is a life-threatening condition that requires the immediate administration of a rescue medicine. If given promptly, rescue medicines can reduce the duration of seizures and support SE cessation. Buccal midazolam is the recommended first-line treatment for SE in the community in people who have had a previous episode of prolonged or serial convulsive seizures. Therefore, it is crucial that all those who care for people with learning disabilities who have epilepsy in the community – including family members, friends and professional carers – receive support, training and guidance in the administration of buccal midazolam. This article provides an overview of the treatment of SE in the community, including the administration of buccal midazolam.

Compliance with status epilepticus management protocol and effect on clinical outcomes in children with status epilepticus

BackgroundGuidelines for the management of status epilepticus (SE) aid in rationalising the treatment for a better clinical outcome; however, published literature regarding the use of antiepileptics and compliance is limited,...

Will MRI replace the EEG for the diagnosis of nonconvulsive status epilepticus, especially focal?

Magnetic resonance imaging (MRI) can now be used to diagnose or to provide confirmation of focal nonconvulsive status epilepticus (NCSE). Approximately half of patients with status epilepticus (SE) have signal changes. MRI can also aid in the differential diagnosis with generalized NCSE when there is a clinical or EEG doubt, e.g. with metabolic/toxic encephalopathies or Creutzfeldt-Jakob disease. With the development of stroke centers, MRI is available 24h/24 in most hospitals. MRI has a higher spatial resolution than electroencephalography (EEG). MRI with hyperintense lesions on FLAIR and DWI provides information related to brain activity over a longer period of time than a standard EEG where only controversial patterns like lateralized periodic discharges (LPDs) may be recorded. MRI may help identify the ictal nature of LPDs. The interpretation of EEG tracings is not easy, with numerous pitfalls and artifacts. Continuous video-EEGs require a specialized neurophysiology unit. The learning curve for MRI is better than for EEG. It is now easy to transfer MRI to a platform with expertise. MRI is more accessible than single photon emission computed tomography (SPECT) or positron emission tomography (PET). For the future, it is more interesting to develop a strategy with MRI than SPECT or PET for the diagnosis of NCSE. With the development of artificial intelligence, MRI has the potential to transform the diagnosis of SE. Additional MRI criteria beyond the classical clinical/EEG criteria of NCSE (rhythmic versus periodic, spatiotemporal evolution of the pattern…) should now be systematically added. However, it is more complicated to move patients to MRI than to perform an EEG in the intensive care unit, and at this time, we do not know how long the signal changes persist after the end of the SE. Studies with MRI at fixed intervals and after SE cessation are necessary.

Factors predicting cessation of status epilepticus in clinical practice – data from a prospective observational registry (SENSE)

Objective To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. Methods Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. Results Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. Interpretation In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

BackgroundThe choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.MethodsIn a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents — levetiracetam, fosphenytoin, and valproate — in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.ResultsA total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.ConclusionsIn the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.)

Systematic review of ketogenic diet use in adult patients with status epilepticus.

Status epilepticus (SE) is a medical emergency that is associated with a significant morbidity and mortality. Recently, there has been significant interest in the use of ketogenic diets (KD) in the management of SE. KD is a high‐fat, low‐carbohydrate, and adequate protein diet that has been shown to be a safe and effective adjuvant to present SE management in patients with refractory epilepsy. Many case reports and case series have demonstrated the potential safety and effectiveness of KD for the acute treatment of SE; however, quality studies remain scarce on this topic. The purpose of this systematic review is to summarize the available evidence for the safety and effectiveness of KD in adults with SE. A literature search was performed in MEDLINE, EMBASE, Cochrane Library, and CINAHL (September 14, 2018). The search was repeated on March 27, 2019, to include any studies published since the original search. Keywords related to KD and SE were used. Studies were selected based on the reported use of the KD in SE. The search resulted in a total of 954 records. After screening and full‐text review, 17 articles were included in this review: four observational studies, 10 case reports, and 3 case series. Based on the observational studies, a total of 38 Patients with SE have been reported. KD was successful in achieving cessation of SE in 31 Patients (82%). The most common adverse effects reported were metabolic acidosis, hyperlipidemia, and hypoglycemia. The current limited evidence suggests that KD might be considered as an option for adult patients with SE. Although promising, the results need to be interpreted with caution due to the inherent bias, confounding and small sample size of the included studies. A randomized controlled trial is recommended to establish role of KD in the management of SE in adults.

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature.

Novel treatments are needed to control treatment-resistant status epilepticus (SE). We present a summary of clinical cases where oral topiramate (TPM) was used in refractory SE (RSE) and superrefractory SE (SRSE). A review of medical records was carried out to detect TPM administration in SE patients treated in Frankfurt and Marburg between 2011 and 2016. The primary outcome question concerned SE resolution after TPM initiation. In total, TPM was used in 106 of 854 patients having a mean age of 67.4±18.1years, 61 of whom were female (57.5%). The median latency from SE onset to TPM initiation was 8.5days. Patients with SE had previously failed a median of five other antiepileptic drugs. The median initial TPM dose was 100mg/d, which was uptitrated to a median maintenance dose of 400mg/d. Treatment with TPM was continued for a median time of 12days. TPM was the last drug provided to 42 of 106 (39.6%) patients, with a resultant response attributed to TPM observed in 29 of 106 (27.4%) patients. A response was attributed to TPM in 21 (31.8%) of 66 RSE cases and eight (20%) of 40 SRSE cases. Treatment-emergent adverse events were attributed to TPM usage in two patients, one each with pancreatitis and hyperchloremic acidosis, and in 38 patients (35.8%), hyperammonemia was seen. Thirty-four of these patients received a combination of TPM and valproate and/or phenobarbital. The intrahospital mortality rate was 22.6% (n=24). The rate of SE cessation attributed to TPM treatment (27.4%) represents a relevant response given the late treatment position of TPM and the treatment latency of more than8 days. Based on these results and in line with the findings of other case series, TPM can be considered an alternative option for treating RSE and SRSE.