Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Guidelines for Neuroprognostication in Critically Ill Adults with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted. RESULTS: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis. CONCLUSIONS: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication.

Guidelines for neuroprognostication in adults with traumatic spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (tSCI) impacts patients and their families acutely and often for the long term. The ability of clinicians to share prognostic information about mortality and functional outcomes allows patients and their surrogates to engage in decision-making and plan for the future. These guidelines provide recommendations on the reliability of acute-phase clinical predictors to inform neuroprognostication and guide clinicians in counseling adult patients with tSCI or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting question was framed as "When counseling patients or surrogates of critically ill patients with traumatic spinal cord injury, should < predictor, with time of assessment if appropriate > be considered a reliable predictor of < outcome, with time frame of assessment >?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development, and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations addressed essential principles of neuroprognostication that could not be framed in the Population/Intervention/Comparator/Outcome/Timing/Setting format. Throughout the guideline development process, an individual living with tSCI provided perspective on patient-centered priorities. RESULTS: Six candidate clinical variables and one prediction model were selected. Out of 11,132 articles screened, 369 met inclusion criteria for full-text review and 35 articles met eligibility criteria to guide recommendations. We recommend pathologic findings on magnetic resonance imaging, neurological level of injury, and severity of injury as moderately reliable predictors of American Spinal Cord Injury Impairment Scale improvement and the Dutch Clinical Prediction Rule as a moderately reliable prediction model of independent ambulation at 1 year after injury. No other reliable or moderately reliable predictors of mortality or functional outcome were identified. Good practice recommendations include considering the complete clinical condition as opposed to a single variable and communicating the challenges of likely functional deficits as well as potential for improvement and for long-term quality of life with SCI-related deficits to patients and surrogates. CONCLUSIONS: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context.

Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage.

BACKGROUND: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication. METHODS: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format. RESULTS: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality. CONCLUSIONS: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale.

Guidelines for Neuroprognostication in Adults with Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Guidelines for Neuroprognostication in Comatose Adult Survivors of Cardiac Arrest.

BACKGROUND: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

Status Epilepticus in Older Adults: Diagnostic and Treatment Considerations.

Status epilepticus (SE) is one of the leading life-threatening neurological emergencies in the elderly population, with significant morbidity and mortality. SE presents unique diagnostic and therapeutic challenges in the older population given overlap with other causes of encephalopathy, complicating diagnosis, and the common occurrence of multiple comorbid diseases complicates treatment. First-line therapy involves the use of rescue benzodiazepine in the form of intravenous lorazepam or diazepam, intramuscular or intranasal midazolam and rectal diazepam. Second-line therapies include parenteral levetiracetam, fosphenytoin, valproate and lacosamide, and underlying comorbidities guide the choice of appropriate medication, while third-line therapies may be influenced by the patient's code status as well as the cause and type of SE. The standard of care for convulsive SE is treatment with an intravenous anesthetic, including midazolam, propofol, ketamine and pentobarbital. There is currently limited evidence guiding appropriate therapy in patients failing third-line therapies. Adjunctive strategies may include immunomodulatory treatments, non-pharmacological strategies such as ketogenic diet, neuromodulation therapies and surgery in select cases. Surrogate decision makers should be updated early and often in refractory episodes of SE and informed of the high morbidity and mortality associated with the disease as well as the high probability of subsequent epilepsy among survivors.

Short-Acting Neuromuscular Blockade Improves Inter-rater Reliability of Median Somatosensory Evoked Potentials in Post-cardiac arrest Prognostication.

BACKGROUND: Although median nerve somatosensory evoked potentials are routinely used for prognostication in comatose cardiac arrest survivors, myogenic artifact can reduce inter-rater reliability, leading to unreliable or inaccurate results. To minimize this risk, we determined the benefit of neuromuscular blockade agents in improving the inter-rater reliability and signal-to-noise ratio of SSEPs in the context of prognostication. METHODS: Thirty comatose survivors of cardiac arrest were enrolled in the study, following the request from an intensivist to complete an SSEP for prognostication. Right and left median nerve SSEPs were obtained from each patient, before and after administration of an NMB agent. Clinical histories and outcomes were retrospectively reviewed. The SSEP recordings before and after NMB were randomized and reviewed by five blinded raters, who assessed the latency and amplitude of cortical and noncortical potentials (vs. absence of response) as well as the diagnostic quality of cortical recordings. The inter-rater reliability of SSEP interpretation before and after NMB was compared via Fleiss' κ score. RESULTS: Following NMB administration, Fleiss' κ score for cortical SSEP interpretation significantly improved from 0.37 to 0.60, corresponding to greater agreement among raters. The raters were also less likely to report the cortical recordings as nondiagnostic following NMB (40.7% nondiagnostic SSEPs pre-NMB; 17% post-NMB). The SNR significantly improved following NMB, especially when the pre-NMB SNR was low (< 10 dB). Across the raters, there were three patients whose SSEP interpretation changed from bilaterally absent to bilaterally present after NMB was administered (potential false positives without NMB). CONCLUSIONS: NMB significantly improves the inter-rater reliability and SNR of median SSEPs for prognostication among comatose cardiac arrest survivors. To ensure the most reliable prognostic information in comatose post-cardiac arrest survivors, pharmacologic paralysis should be consistently used before recording SSEPs.

Hospital to Hospital Transfers of Cerebral Hemorrhage: Characteristics of Early Withdrawal of Life-Sustaining Treatment.

BACKGROUND: Large intracerebral hemorrhages (ICHs) are associated with significant morbidity and mortality. Patient transfer to higher level centers is common, but care in these centers rarely demonstrably improves morbidity or reduces mortality. Patients may rapidly progress to brain death, but a large number die shortly after transferring because of withdrawal of life-sustaining treatment (WOLST). This outcome may result in poor resource use and unnecessary cost to patients, families, and institutions. We sought to determine clinical and radiographic predictors of early death or WOLST that may alter potential transfer. METHODS: We performed a retrospective review of patients admitted from outside medical centers to the neurosciences intensive care unit at Saint Marys Mayo Clinic Hospital in Rochester, MN, from January 2014 to December 2019. Patients ≥ 18 years old with a spontaneous ICH were included. Exclusion criteria included trauma, subarachnoid hemorrhage, and subdural hematoma. We identified patients who died or underwent WOLST within 24 h of transfer. Descriptive characteristics of patients and ICH were collected. Data were analyzed with univariable, multivariable, and logistic regression. Predictive modeling was performed. An additional case-matched study was completed to evaluate for characteristics further. RESULTS: A total of 317 consecutive patients were identified. Forty-two patients were found with early death or WOLST within 24 h of transfer. Do not resuscitate/do not intubate (DNR/DNI) code status (odds ratio [OR] 5.23, confidence interval [CI] 3.31-8.28), anticoagulation use (OR 2.11, CI 1.09-4.09), and lower level of consciousness at presentation based on Glasgow Coma Score (OR 1.41, CI 1.29-1.54) and Full Outline of Unresponsiveness (FOUR) score (OR 1.34, CI 1.26-1.46) were associated with WOLST. Associated characteristics on the computed tomography scan included midline shift (OR 4.64, CI 2.32-9.29), hydrocephalus (OR 9.30, CI 4.56-18.96), and intraventricular extension (OR 5.27, CI 2.60-10.68). Case matching restricted to midline shift demonstrated similarity between patients with aggressive care and WOLST. DNR/DNI code status, warfarin use, ICH score, and composite FOUR score were the best predictive characteristics (area under the curve 0.942). CONCLUSIONS: Early death or WOLST after ICH within 24 h of presentation was most associated with DNR/DNI code status, warfarin use, ICH score, and lower level of consciousness at presentation. These characteristics may be used by clinicians to guide conversations prior to transfer to tertiary care centers.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

BACKGROUND AND OBJECTIVES: Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings. METHODS: Patients with RSE treated with midazolam or propofol between January 2015 and December 2018 were retrospectively identified among 9 centers across 4 continents from upper-middle-income economies in Latin America and high-income economies in North America, Europe, and Asia. Demographics, Status Epilepticus Severity Score, etiology, treatment details, and discharge modified Rankin Scale (mRS) were collected. The primary outcome measure was good functional outcome defined as a mRS score of 0-2 at hospital discharge. RESULTS: Three hundred eighty-seven episodes of RSE (386 patients) were included, with 162 (42%) from upper-middle-income and 225 (58%) from high-income economies. Three hundred six (79%) had acute and 79 (21%) remote etiologies. Initial RSE management included midazolam in 266 (69%) and propofol in 121 episodes (31%). Seventy episodes (26%) that were initially treated with midazolam and 42 (35%) with propofol required the addition of a second anesthetic to treat RSE. Baseline characteristics and outcomes of patients treated with midazolam or propofol were similar. Breakthrough (odds ratio [OR] 1.6, 95% CI 1.3-2.0) and withdrawal seizures (OR 2.0, 95% CI 1.7-2.5) were associated with an increased number of days requiring continuous intravenous anticonvulsant medications (cIV-ACMs). Prolonged EEG monitoring was associated with fewer days of cIV-ACMs (1-24 hours OR 0.5, 95% CI 0.2-0.9, and >24 hours OR 0.7, 95% CI 0.5-1.0; reference EEG <1 hour). This association was seen in both, high-income and upper-middle-income economies, but was particularly prominent in high-income countries. One hundred ten patients (28%) were dead, and 80 (21%) had good functional outcomes at hospital discharge. DISCUSSION: Outcomes of patients with RSE managed in the intensive care unit with propofol or midazolam infusions are comparable. Prolonged EEG monitoring may allow physicians to decrease the duration of anesthetic infusions safely, but this will depend on the implementation of RSE management protocols. Goal-directed management approaches including EEG targets may hold promise for patients with RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III data that propofol and midazolam are equivalently efficacious for RSE.

Diabetic ketoacidosis, cerebral venous sinus thrombosis and fulminant cerebral oedema in COVID-19 infection complicated by Klebsiella pneumoniae infection.

We present an unusual case of a woman in her 30s who was admitted for diabetic ketoacidosis (DKA) in the setting of newly diagnosed but late COVID-19 infection with associated Klebsiella pneumoniae infection. Her altered mental status, out of proportion with her metabolic decompensation, revealed a superimposed cerebral venous sinus thrombosis (CVST) with fulminant cerebral oedema and ultimately brain death. This unusual and fulminant case of cerebral oedema in the setting of COVID-19 infection with bacterial infection, DKA and CVST was the perfect storm with multiple interwoven factors. It offered diagnostic and treatment challenges with an unfortunate outcome. This unique case is a reminder that it is important to consider a broad neurological differential in patients with COVID-19 with unexplained neurological manifestations, which may require specific neurointensive care management.

Incidence and Predictive Factors Associated with Beta-Lactam Neurotoxicity in the Critically Ill: A Retrospective Cohort Study.

BACKGROUND: Beta-lactam neurotoxicity is a relatively uncommon yet clinically significant adverse effect in critically ill patients. This study sought to define the incidence of neurotoxicity, derive a prediction model for beta-lactam neurotoxicity, and then validate the model in an independent cohort of critically ill adults. METHODS: This retrospective cohort study evaluated critically ill patients treated with ≥ 48 h of cefepime, piperacillin/tazobactam, or meropenem. Two separate cohorts were created: a derivation cohort and a validation cohort. Patients were screened for beta-lactam neurotoxicity by using search terms and diagnosis codes, followed by clinical adjudication using a standardized adverse event scoring tool. Multivariable regression models and least absolute shrinkage and selection operator were used to identify surrogates for neurotoxicity and develop a multivariable prediction model. RESULTS: The overall incidence of beta-lactam neurotoxicity was 2.6% (n/N = 34/1323) in the derivation cohort and 2.1% in the validation cohort (n/N = 16/767). The final multivariable neurotoxicity assessment tool included weight, Charlson comorbidity score, age, and estimated creatinine clearance as predictors of neurotoxicity. Incidence of neurotoxicity reached 4% in those with a body mass index more than 30 kg/m2. Use of the candidate variables in the neurotoxicity assessment tool suggested that a score more than 35 would identify a patient at high risk for neurotoxicity with 75% sensitivity and 54% specificity. CONCLUSIONS: In this single center cohort of critically ill patients, beta-lactam neurotoxicity was demonstrated less frequently than previously reported. We identified obesity as a novel risk factor for the development of neurotoxicity. The prediction model needs to be further refined before it can be used in clinical practice as a tool to avoid drug-related harm.

A Disclosure About Death Disclosure: Variability in Circulatory Death Determination.

INTRODUCTION: Circulatory-respiratory death declaration is a common duty of physicians, but little is known about the amount of education and physician practice patterns in completing this examination. METHODS: An online survey of physicians was conducted evaluating the rate of formal training and specific examination techniques used in the pronouncement of circulatory-respiratory death. Data, including the level of practice, training received in a formal death declaration, and examination components, were collected. RESULTS: Respondents were attending physicians (52.4%), residents (30.2%), fellows (10.7%), and interns (6.7%). Most respondents indicated they had received no formal training in death pronouncement; however, most reported self-perceived competence. When comparing examination components used by the study's cohort, 95 different examination combinations were used for death pronouncement. CONCLUSIONS: Formal training in death pronouncement was uncommon and clinical practice varied. Implementation of formal training and standardization of the examination are necessary to improve physician competence and reliability in death declarations.

Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

BACKGROUND: Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA. METHODS: Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic. RESULTS: There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions. CONCLUSIONS: This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.

How to Help Your Patients Enroll in the New-Onset Refractory Status Epilepticus (NORSE) and Febrile Infection-Related Epilepsy Syndrome (FIRES) Family Registry, and Other Rare Epilepsy Registries.

New-onset refractory status epilepticus (NORSE) is a rare clinical presentation of refractory status epilepticus (RSE) that occurs in people without active epilepsy or preexisting neurologic disorder. Febrile infection-related epilepsy syndrome (FIRES) is a subcategory of NORSE. New-onset refractory status epilepticus/FIRES are becoming increasingly recognized; however, information pertaining to disease course, clinical outcomes, and survivorship remains limited, and mortality and morbidity are variable, but often high. The objective of the NORSE/FIRES Family Registry is to (1) provide an easily accessible and internationally available multilingual registry into which survivors or NORSE/FIRES surrogates or family members of people affected by NORSE/FIRES or their physicians can enter data in a systematic and rigorous research study from anywhere in the world where internet is available; and (2) to examine past medical history, outcomes, and quality of life for people affected by NORSE/FIRES.