Stimulus-induced arousal with transient electroencephalographic improvement distinguishes nonictal from ictal generalized periodic discharges.

In the case of suspicion of nonconvulsive status epilepticus (NCSE), reactivity on electroencephalograms (EEGs) can provide valuable diagnostic information. Reactivity refers to responses to auditory or somatosensory stimulation, with changes in amplitude and frequency of background activity. Because of self-perpetuating processes and the failure of self-terminating mechanisms, status epilepticus is unlikely to cease when patients spontaneously move, and it cannot typically be stopped by external stimulation (i.e., auditory and tactile stimuli). The defining EEG characteristic of absence status epilepticus is the presence of bilateral, synchronous, symmetric, rhythmic paroxysmal activity that shows little or no reactivity to sensory stimulation. On the other hand, in metabolic/toxic or multifactorial encephalopathies, triphasic waves (TWs) are influenced by the level of vigilance. TWs may be transiently abolished when patients increase their level of alertness from a drowsy/lethargic state to a state of wakefulness. This reactivity is only observed when patients can be aroused by a somatosensory or auditory stimulus. This reactivity tends to disappear with increasing severity of the disease and in comatose patients. In patients without preexisting developmental and epileptic encephalopathy, this pattern of stimulus-induced wakefulness with transient improvement of the EEG is a major criterion in determining that the EEG patterns are not ictal. This criterion of reactivity on EEGs, beyond the classical clinical/EEG criteria of NCSE (Salzburg criteria), should now be systematically added.

Electroencephalography in encephalopathy and encephalitis.

Electroencephalography (EEG) is a useful adjunct to clinical neurological examination, particularly as it may detect subtle or subclinical disturbance of cerebral function and it allows monitoring of cerebral activity over time. Continuous EEG combined with quantitative analysis and machine learning may help identify changes in real time, before the emergence of clinical signs and response to interventions. EEG is rarely pathognomonic in encephalopathy/encephalitis but when interpreted correctly and within the clinical context, certain phenotypes may indicate a specific pathophysiology (eg, lateralised periodic discharges in HSV-1, generalised periodic discharges in sporadic Creutzfeldt-Jakob disease, and extreme delta brushes in anti-n-methyl-D-aspartate receptor autoimmune encephalitis). EEG is included in some specialist guidelines for disease assessment, monitoring and prognostication (ie, hepatic, cancer immunotherapy, viral, prion, autoimmune encephalitis and hypoxic ischaemic encephalopathy). EEG is invaluable for confirming or excluding non-convulsive seizures or status epilepticus, particularly in critically ill patients, and in understanding new concepts such as epileptic encephalopathy and the ictal-interictal continuum.

Diagnosing nonconvulsive status epilepticus: Defining electroencephalographic and clinical response to diagnostic intravenous antiseizure medication trials.

OBJECTIVE: The Salzburg criteria for nonconvulsive status epilepticus (NCSE) and the American Clinical Neurophysiology Society (ACNS) Standardized Critical Care EEG Terminology 2021 include a diagnostic trial with intravenous (IV) antiseizure medications (ASMs) to assess electroencephalographic (EEG) and clinical response as a diagnostic criterion for definite NCSE and possible NCSE. However, how to perform this diagnostic test and assessing the EEG and clinical responses have not been operationally defined. METHODS: We performed a Delphi process involving six experts to standardize the diagnostic administration of IV ASM and propose operational criteria for EEG and clinical response. RESULTS: Either benzodiazepines (BZDs) or non-BZD ASMs can be used as first choice for a diagnostic IV ASM trial. However, non-BZDs should be considered in patients who already have impaired alertness or are at risk of respiratory depression. Levetiracetam, valproate, lacosamide, brivaracetam, or (if the only feasible drug) fosphenytoin or phenobarbital were deemed appropriate for a diagnostic IV trial. The starting dose should be approximately two thirds to three quarters of the full loading dose recommended for treatment of status epilepticus, with an additional smaller dose if needed. ASMs should be administered during EEG recording under supervision. A monitoring time of at least 15 min is recommended. If there is no response, a second trial with another non-BDZ or BDZs may be considered. A positive EEG response is defined as the resolution of the ictal-interictal continuum pattern for at least three times the longest previously observed spontaneous interval of resolution (if any), but minimum of one continuous minute. For a clinical response, physicians should use a standardized examination before and after IV ASM administration. We suggest a definite time-locked improvement in a focal deficit or at least one-step improvement on a new dedicated one-domain 10-level NCSE response scale. SIGNIFICANCE: The proposed standardized approach of a diagnostic IV ASM trial further refines the ACNS and Salzburg diagnostic criteria for NCSE.

Prediction of Postictal Delirium Following Status Epilepticus in the ICU: First Insights of an Observational Cohort Study.

OBJECTIVES: To identify early predictors of postictal delirium in adult patients after termination of status epilepticus. DESIGN: Retrospective study. SETTING: ICUs at a Swiss tertiary academic medical center. PATIENTS: Status epilepticus patients treated on the ICUs for longer than 24 hours from 2012 to 2018. INTERVENTIONS: None. METHODS: Primary outcome was postictal delirium during post-status epilepticus treatment defined as an Intensive Care Delirium Screening Checklist greater than or equal to 4. Associations with postictal delirium were secondary outcomes. A time-dependent multivariable Cox proportional hazards model was used to identify risks of postictal delirium. It included variables that differed between patients with and without delirium and established risk factors for delirium (age, sex, number of inserted catheters, illness severity [quantified by the Sequential Organ Failure Assessment and Status Epilepticus Severity Score], neurodegenerative disease, dementia, alcohol/drug consumption, infections, coma during status epilepticus, dose of benzodiazepines, anesthetics, and mechanical ventilation). MEASUREMENTS AND MAIN RESULTS: Among 224 patients, post-status epilepticus Intensive Care Delirium Screening Checklist was increased in 83% with delirium emerging in 55% with a median duration of 2 days (interquartile range 1-3 d). Among all variables, only the history of alcohol and/or drug consumption was associated with increased hazards for delirium in multivariable analyses (hazard ratio = 3.35; 95% CI, 1.53-7.33). CONCLUSIONS: Our study provides first exploratory insights into the risks of postictal delirium in adult status epilepticus patients treated in the ICU. Delirium following status epilepticus is frequent, lasting mostly 2-3 days. Our findings that with the exception of a history of alcohol and/or drug consumption, other risk factors of delirium were not found to be associated with a risk of postictal delirium may be related to the limited sample size and the exploratory nature of our study. Further investigations are needed to investigate the role of established risk factors in other status epilepticus cohorts. In the meantime, our results indicate that the risk of delirium should be especially considered in patients with a history of alcohol and/or drug consumption.

Status Epilepticus: Definition, Classification, Pathophysiology, and Epidemiology.

Status epilepticus (SE) is the state of continuous or repetitive seizures, which can occur with or without convulsions. Evolving definitions of SE take into account the concept that neuronal injury may occur at different times in different types of SE.SE that does not respond to initial treatment may become refractory or even super-refractory. Nonconvulsive SE is increasingly recognized in comatose patients in critical care units, with the growing use of continuous electroencephalogram monitoring. SE is a neurologic emergency that carries a high risk of mortality and morbidity.

Continuous Electroencephalographic Monitoring in the Intensive Care Unit: A Cross-Sectional Study.

OBJECTIVE: Research on continuous electro-encephalographic monitoring (cEEG) in the intensive care unit (ICU) has previously focused on neuroscience ICUs. This study determines cEEG utilization within a sample of specialty ICUs world-wide. METHODS: A cross-sectional electronic survey of attending level physicians across various intensive care settings. Twenty-five questions developed from consensus statements on the use of cEEG in the critically ill sent as an electronic survey. RESULTS: Of all, 9344 were queried and 417 (4.5%) responses were analyzed with 309 (74%) from the United States and 74 (18%) internationally. Intensive care units were: medical (10%), surgical (6%), neurologic/neurosurgical (12%), cardiac (4%), trauma (3%), pediatrics (29%), burn (<1%), multidisciplinary (30%), and other (5%). Intensive care units were: academic (65%), community (18%), public (3%), military (1%), and other (13%). Specialized cEEG teams were available in 71% of ICUs. Rapid 24/7 access and cEEG interpretation was available in 32% of ICUs. Interpretation changed clinical management frequently (28%) and sometimes (45%). CONCLUSIONS: Despite guideline recommendations for cEEG use, there is a discordance between availability, night coverage, and immediate interpretation. Only 27% have institutional protocols for indications and duration of cEEG monitoring. Furthermore, cEEG may be underutilized in nonneurologic ICUs as well as ICUs in smaller nonacademic affiliated hospitals and those outside of the United States.

Calorie Intake During Status Epilepticus and Outcome: A 5-Year Cohort Study.

OBJECTIVES: Recommendations regarding nutrition during status epilepticus are lacking, and it is unclear whether restriction of calorie intake would result in beneficial effects or potential harm. We thus aimed to investigate associations between daily calorie intake and outcome in adult status epilepticus patients deriving from a 5-year cohort with a systematic and prospective collection of nutritional data. DESIGN: Retrospective observational study. SETTING: Medical ICUs at a tertiary academic medical care center. PATIENTS: Consecutive patients with status epilepticus treated at the ICUs from 2012 to 2016 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients with status epilepticus were monitored regarding nutrition support provided according to the guidelines. Relative risks of no return to baseline were estimated by Poisson regression with robust error variance and adjusted for potential confounders. Of 203 patients, 86 (42%) had return to baseline. Metabolic characteristics of patients with and without return to baseline did not differ. Patients without return to baseline received more calories and proteins per status epilepticus day, and increasing nutritional support was associated with ventilator-associated pneumonia (relative risk, 1.19; 95% CI, 1.09-1.28). Multivariable regression analysis revealed significant increases in relative risks for no return to baseline with every percent of days with nutrition (relative risk, 1.35; 95% CI, 1.05-1.74), with every 100 kcal (relative risk, 1.01; 95% CI, 1.002-1.01), and gram of protein intake (relative risk, 1.01; 95% CI, 1.001-1.01) per status epilepticus day, independent of potential confounders (including fatal etiology, duration and severity of status epilepticus, Charlson comorbidity index, and treatment with anesthetics). CONCLUSIONS: Our results indicate that increased calorie intake during status epilepticus is independently associated with unfavorable outcome. These findings require further validation and investigations into potential mediators, such as induction of ketogenesis, immunomodulating effects, and/or reduction of ICU-associated complications, such as infections.

Prolonged status epilepticus: Early recognition and prediction of full recovery in a 12-year cohort.

OBJECTIVES: Early identification of patients who are at risk of prolonged status epilepticus (SE) and patients with high chances of full recovery despite prolonged SE may urge clinicians to intensify treatment rather than to withdraw care. We aimed to develop prediction models based on readily available clinical parameters to predict prolonged SE at seizure onset and to identify patients with high chances for full recovery. METHODS: From 2005 to 2016, all adult SE patients treated at the University Hospital Basel, a Swiss medical care center, were included. Multivariable Poisson regression was performed to identify predictors of prolonged SE (defined as SE for >12, >24, and >48 hours) and return to baseline from prolonged SE. The area under the receiver-operating characteristic curves (AUROC) for prediction models was calculated. RESULTS: Of 467 patients, the median age was 66.7 years and mortality was 12%. Relative risk (RR) for death was 1.06 (P < 0.0001) with every SE day. In multivariable analysis, nonconvulsive SE with coma, SE severity score ≥3, and acute brain lesions at SE onset independently predicted prolonged SE with an AUROC of 0.68 for >12, 0.67 for >24, and 0.72 for >48 hours of SE. Absence of nonconvulsive SE with coma and a decreasing Charlson comorbidity index were independent predictors for return to baseline in prolonged SE with an AUROC of 0.82 and 0.76 following cross-validation. Both associations remained significant despite adjustments for determinants of adverse outcome, such as anesthetics and vasopressors (nonconvulsive SE with coma RR = 0.24, 95% confidence interval [CI] 0.07-0.86; comorbidity index RR = 0.87, 95% CI 0.76-0.99). SIGNIFICANCE: Although our data indicate that identification of prolonged SE at seizure onset is unreliable, timely recognition of patients with high chances of good outcome despite prolonged SE is promising on the basis of comorbidities, type of SE, and level of consciousness. Further external validation of this prediction model is needed.

Illness severity scoring in status epilepticus-When STESS meets APACHE II, SAPS II, and SOFA.

OBJECTIVE: To characterize a critically ill cohort with status epilepticus (SE) by the illness severity scoring systems SAPS II (Simplified Acute Physiology Score II), APACHE II (Acute Physiology and Chronic Health Evaluation II), and SOFA (Sequential Organ Failure Assessment), and to compare their performance with the STESS (Status Epilepticus Severity Score) for outcome prediction. METHODS: The prospective cohort study was carried out at the University Hospital Basel, a Swiss tertiary academic medical care center. Consecutive adult SE patients hospitalized in the intensive care units from 2011 to 2016 were included. Illness severity scores and additional clinical data were recorded. Logistic regression models using automated variable selection were applied to identify scores associated with no return to functional and neurological baseline and death. Measures of discrimination and calibration were assessed. RESULTS: Among 184 patients, 33% returned to baseline. Median scores of the illness severity scores were within the lowest third of the possible scoring ranges, and all differed significantly between patients with and without return to baseline. The areas under the receiver operating curves for the prediction of no return to baseline and death ranged from 0.64 to 0.73, with the highest value for the STESS predicting no return to baseline. Measures of calibration revealed adequate model fit for all analyses. Among integral components of the scoring systems, only the Glasgow Coma Scale (GCS) differed significantly between patients with and without return to baseline. In multivariable analyses, decreasing GCS and increasing STESS had the strongest associations (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.77-0.93 and OR = 1.34, 95% CI = 1.05-1.68, respectively) with no return to baseline independent of all other scoring systems, whereas the APACHE II revealed the strongest association with death (OR = 1.15, 95% CI = 1.06-1.25). SIGNIFICANCE: Although complex illness severity scoring systems in SE patients facilitate benchmarking and comparisons with other severely ill patient cohorts, they offer no advantages over the STESS and GCS regarding prediction of no return to baseline.

Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.

OBJECTIVES: Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. DATA SOURCES: We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. STUDY SELECTION: All identified studies were screened for eligibility by two independent reviewers. DATA EXTRACTION: Key data were extracted using standardized data collection forms. DATA SYNTHESIS: Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. CONCLUSIONS: Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.

Estimating the False Positive Rate of Absent Somatosensory Evoked Potentials in Cardiac Arrest Prognostication.

OBJECTIVES: Absence of somatosensory evoked potentials is considered a nearly perfect predictor of poor outcome after cardiac arrest. However, reports of good outcomes despite absent somatosensory evoked potentials and high rates of withdrawal of life-sustaining therapies have raised concerns that estimates of the prognostic value of absent somatosensory evoked potentials may be biased by self-fulfilling prophecies. We aimed to develop an unbiased estimate of the false positive rate of absent somatosensory evoked potentials as a predictor of poor outcome after cardiac arrest. DATA SOURCES: PubMed. STUDY SELECTION: We selected 35 studies in cardiac arrest prognostication that reported somatosensory evoked potentials. DATA EXTRACTION: In each study, we identified rates of withdrawal of life-sustaining therapies and good outcomes despite absent somatosensory evoked potentials. We appraised studies for potential biases using the Quality in Prognosis Studies tool. Using these data, we developed a statistical model to estimate the false positive rate of absent somatosensory evoked potentials adjusted for withdrawal of life-sustaining therapies rate. DATA SYNTHESIS: Two-thousand one-hundred thirty-three subjects underwent somatosensory evoked potential testing. Five-hundred ninety-four had absent somatosensory evoked potentials; of these, 14 had good functional outcomes. The rate of withdrawal of life-sustaining therapies for subjects with absent somatosensory evoked potential could be estimated in 14 of the 35 studies (mean 80%, median 100%). The false positive rate for absent somatosensory evoked potential in predicting poor neurologic outcome, adjusted for a withdrawal of life-sustaining therapies rate of 80%, is 7.7% (95% CI, 4-13%). CONCLUSIONS: Absent cortical somatosensory evoked potentials do not infallibly predict poor outcome in patients with coma following cardiac arrest. The chances of survival in subjects with absent somatosensory evoked potentials, though low, may be substantially higher than generally believed.

Generalized nonmotor (absence) seizures-What do absence, generalized, and nonmotor mean?

OBJECTIVE: Clinical absences are now classified as "generalized nonmotor (absence) seizures" by the International League Against Epilepsy (ILAE). The aim of this paper is to critically review the concept of absences and to put the accompanying focal and motor symptoms into the context of the emerging pathophysiological knowledge. METHODS: For this narrative review we performed an extensive literature search on the term "absence," and analyzed the plethora of symptoms observed in clinical absences. RESULTS: Arising from the localization and the involved cortical networks, motor symptoms may include bilateral mild eyelid fluttering and mild myoclonic jerks of extremities. These motor symptoms may also occur unilaterally, analogous to a focal motor seizure with Jacksonian march. Furthermore, electroencephalography (EEG) abnormalities may exhibit initial frontal focal spikes and consistent asymmetries. Electroclinical characteristics support the cortical focus theory of absence seizures. Simultaneous EEG/functional magnetic resonance imaging (fMRI) measurements document cortical deactivation and thalamic activation. Cortical deactivation is related to slow waves and disturbances of consciousness of varying degrees. Motor symptoms correspond to the spike component of the 3/s spike-and-wave-discharges. Thalamic activation can be interpreted as a response to overcome cortical deactivation. Furthermore, arousal reaction during drowsiness or sleep triggers spikes in an abnormally excitable cortex. An initial disturbance in arousal mechanisms ("dyshormia") might be responsible for the start of this abnormal sequence. SIGNIFICANCE: The classification as "generalized nonfocal and nonmotor (absence) seizure" does not covey the complex semiology of a patient's clinical events.

Admission EEG findings in diverse paediatric cerebral malaria populations predict outcomes.

BACKGROUND: Electroencephalography at hospital presentation may offer important insights regarding prognosis that can inform understanding of cerebral malaria (CM) pathophysiology and potentially guide patient selection and risk stratification for future clinical trials. Electroencephalogram (EEG) findings in children with CM in Uganda and Malawi were compared and associations between admission EEG findings and outcome across this diverse population were assessed. Demographic, clinical and admission EEG data from Ugandan and Malawian children admitted from 2009 to 2012 with CM were gathered, and survivors assessed for neurological abnormalities at discharge. RESULTS: 281 children were enrolled (Uganda n = 122, Malawi n = 159). The Malawian population was comprised only of retinopathy positive children (versus 72.5% retinopathy positive in Uganda) and were older (4.2 versus 3.7 years; p = 0.046), had a higher HIV prevalence (9.0 versus 2.8%; p = 0.042), and worse hyperlactataemia (7.4 versus 5.2 mmol/L; p < 0.001) on admission compared to the Ugandan children. EEG findings differed between the two groups in terms of average voltage and frequencies, reactivity, asymmetry, and the presence/absence of sleep architecture. In univariate analyses pooling EEG and outcomes data for both sites, higher average and maximum voltages, faster dominant frequencies, and retained reactivity were associated with survival (all p < 0.05). Focal slowing was associated with death (OR 2.93; 95% CI 1.77-7.30) and a lower average voltage was associated with neurological morbidity in survivors (p = 0.0032). CONCLUSIONS: Despite substantial demographic and clinical heterogeneity between subjects in Malawi and Uganda as well as different EEG readers at each site, EEG findings on admission predicted mortality and morbidity. For CM clinical trials aimed at decreasing mortality or morbidity, EEG may be valuable for risk stratification and/or subject selection.

Caring for transgender patients with epilepsy.

OBJECTIVE: Approximately 25 million individuals older than age 15 identify as transgender, representing about 0.3-0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy. METHODS: We performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures. RESULTS: There are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated. SIGNIFICANCE: Transgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender-affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment.

Epilepsy.

The accurate diagnosis and classification of seizures is critical in informing prognosis and determining appropriate antiseizure treatments for patients with epilepsy. The electroencephalogram is the gold standard for diagnosis. Obtaining a thorough history, performing a careful physical examination, and selecting appropriate diagnostic studies are also essential in determining the underlying seizure etiology. The authors provide clinical pearls and pitfalls in the diagnosis and management of epilepsy.

What to see when you are looking at confusion: a review of the neuroimaging of acute encephalopathy.

Acute encephalopathy is a clinical conundrum in neurocritical care facing physicians with diagnostic and therapeutic challenges. Encephalopathy arises from several concurrent causes, and delayed diagnosis adds to its grim prognosis. Diagnosis is reached by melding clinical, neurophysiological and biochemical features with various neuroimaging studies. We aimed to compile the pathophysiology of acute encephalopathies in adults, and the contribution of cerebral CT, MRI, MR spectroscopy (MRS), positron emission tomography (PET) and single-photon emission CT (SPECT) to early diagnosis, treatment and prognostication. Reports from 1990 to 2013 were identified. Therefore, reference lists were searched to identify additional publications. Encephalopathy syndromes best studied by neuroimaging emerge from hypoxic-ischaemic injury, sepsis, metabolic derangements, autoimmune diseases, infections and rapidly evolving dementias. Typical and pathognomonic neuroimaging patterns are presented. Cerebral imaging constitutes an important component of diagnosis, management and prognosis of acute encephalopathy. Its respective contribution is dominated by rapid exclusion of acute cerebral lesions and further varies greatly depending on the underlying aetiology and the range of possible differential diagnoses. CT has been well studied, but is largely insensitive, while MRI appears to be the most helpful in the evaluation of encephalopathies. MRS may provide supplementary biochemical information and determines spectral changes in the affected brain tissue. The less frequently used PET and SPECT may delineate areas of high or low metabolic activity or cerebral blood flow. However, publications of MRS, PET and SPECT are limited only providing anecdotal evidence of their usefulness and sensitivity.

Can anesthetic treatment worsen outcome in status epilepticus?

Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus".

Significance of Parenchymal Brain Damage in Patients with Critical Illness.

BACKGROUND: To determine the prevalence, type, and significance of brain damage in critically ill patients with a primary non-neurological diagnosis developing acute brain dysfunction. METHODS: This retrospective cohort study was performed at the Johns Hopkins University School of Medicine, an academic tertiary care hospital. Medical records were reviewed of 479 consecutive ICU patients who underwent brain magnetic resonance imaging (MRI) over a 2-year period. Patients were selected for analysis if MRI was obtained to evaluate an acute onset of brain dysfunction (altered mental status, seizures, and/or focal neurological deficit). Subjects with a history of a central nervous system disorder were excluded. The principal clinical endpoint was Glasgow Outcome Scale (GOS) assessed at discharge. MRI-defined brain abnormalities were classified according to type and location. Factors associated with MRI-defined abnormalities were assessed in uni- and multivariable models. RESULTS: 146 patients met inclusion criteria (mean age 54 ± 7 years). Brain damage was detected in 130 patients (89%). The most prevalent lesions were white matter hyperintensities (104/146, 71%) and acute cerebral infarcts (59/146, 40%). In a multivariable model, lesions on brain MRI were independently associated with unfavorable outcome (GOS1-3 in 71% of patients with lesions vs. 44% in those without, p = 0.007). No adverse events occurred in relation to transport and MRI scanning. CONCLUSIONS: In critically ill patients without known neurological disease who have acute brain dysfunction, MRI reveals an unexpectedly high burden of underlying brain damage, which is associated with unfavorable outcome. The results indicate that brain damage could be an important and under-recognized factor contributing to critical illness brain dysfunction.