Patient-reported outcomes in adults after status epilepticus: A systematic review.

Impairments after status epilepticus have generally been assessed by physicians, using generic scales. Patient-reported outcomes (PROs) directly reflect each patient's experience and are therefore recommended to improve patient-centered care. The objective of this systematic review was to compile the available information on patient-reported outcomes of adults after status epilepticus. We used Medical Subject Headings terms to search PubMed, Embase, and the Cochrane Library from database inception to February 2023. We excluded reviews, case reports, abstract-only reports, editorials, and publications in languages other than English or French. Studies reporting PROs in adults after SE were eligible. Bias in included studies was assessed using the Newcastle-Ottawa Scale (NOS). Given the heterogeneity in assessment tools and outcomes, most of the results are presented separately for each included study. Only three studies met our criteria. All used an observational cohort design. Two were retrospective and one prospective. Of the 141 patients (76 males and 65 females, mean age 43-63 years), 105 (74.4 %) had a history of epilepsy before status epilepticus. The studies used four epilepsy-specific and five generic tools to assess five patient-reported outcomes: quality of life (n = 141), mental health (depression, n = 81, or anxiety, n = 49), physical health including fatigue (n = 130), return to work (n = 49), and side effects of antiepileptic drugs (n = 81). A single study (n = 81) was of good methodological quality. Health-related quality of life (HRQOL) and mental health were the most extensively studied outcomes, and both were impaired. HRQOL scores ranged from 41.7 ±â€¯11.5 to 48.3 ±â€¯24.5. The prevalence of depression and anxiety varied from 30 % to 36 %, and from 22 % to 62 %, respectively. However, data were not collected before the status epilepticus episode, and the possible impact of this last on the outcomes cannot therefore be assessed. Information on PROs of adults after status epilepticus is extremely scant. Patient-reported outcomes should be collected more widely in adults after status epilepticus.

Status epilepticus and psychosis: Lessons from SEEG.

Psychotic manifestations are a classic feature of non-convulsive status epilepticus (NCSE) of temporal origin. For several decades now, the various psychiatric manifestations of NCSE have been described, and in particular, the diagnostic challenges they pose. However, studies using stereotactic-EEG (SEEG) recordings are very rare. Only a few cases have been reported, but they demonstrated the anatomical substrate of certain manifestations, including hallucinations, delusions, and emotional changes. The post-ictal origin of some of the manifestations should be emphasized. More generally, SEEG has shown that seizures affecting the temporal and frontal limbic systems can lead to intense emotional experiences and behavioural disturbances.

Intellectual functioning and adaptive behaviour in children with Dravet syndrome: A population-based study.

AIM: To identify, on a population basis, the prevalence of intellectual disability in children with Dravet syndrome, profiles on a measure of adaptive behaviour, and factors associated with intellectual functioning and adaptive behaviour. METHOD: Forty-two out of 48 children with Dravet syndrome living in Sweden, born between 1st January 2000 and 31st December 2018, underwent assessment of intellectual functioning and adaptive behaviour. Factors associated with level of intellectual functioning and adaptive behaviour were analysed. RESULTS: Eight-six per cent (n = 36) of the children fulfilled DSM-5 criteria for intellectual disability (29% [n = 12] mild intellectual disability, 24% [n = 10] moderate intellectual disability, 33% [n = 14] severe intellectual disability, 0% profound intellectual disability) and 93% (n = 39) had an adaptive behaviour composite more than two standard deviations below the mean. Communication was a significant weakness compared with daily living skills (p < 0.001; mean difference 95% confidence interval [CI] -8.193 to -4.092) and socialization (p = 0.001; mean difference 95% CI 6.511 to -1.775) on the Vineland Adaptive Behavior Scales, Second Edition. The only factors significantly associated with both decreased adaptive behaviour and presence of severe intellectual disability was the presence of increased autistic symptoms and younger age. INTERPRETATION: Children with Dravet syndrome have a very high level of intellectual disability and almost all have significant deficits in adaptive behaviour. Greater deficits in adaptive behaviour and greater severity of intellectual disability are associated with the presence of increased autistic symptoms, highlighting the need for comprehensive neurodevelopmental assessment for all affected children. WHAT THIS PAPER ADDS: Eighty-six per cent (n = 36) of children with Dravet syndrome fulfilled criteria for intellectual disability. Ninety-three per cent (n = 39) of children with Dravet syndrome had significant deficits in adaptive behaviour. Communication was a significant weakness on a measure of adaptive behaviour. Increased autistic symptoms were associated with greater deficits in cognition/adaptive behaviour. Older age and earlier status epilepticus were associated with decreased adaptive behaviour.

Evaluation of the prognostic factors in school age children who experienced neonatal seizures.

BACKGROUND: This prospective study aimed to evaluate long-term neurodevelopmental outcomes and risk factors of the previously reported cohort, at their school age. METHOD: We included neonates whose seizures were directly observed by the child neurologist or neonatologist based on clinical observations. They were assessed for cognitive and neurological outcomes at the age of 9-11 years. The test battery included a neurological examination, the Wechsler Intelligence Scale for Children-Revised (WISC-R) test, and patients with the diagnosis of cerebral palsy (CP) were graded according to the Gross Motor Function Classification System (GMFCS). The primary outcome of this study was to determine risk factors for the long-term prognosis of neonatal seizures. RESULTS: For the long-term follow-up, 97 out of 112 patients of the initial cohort were available (86.6%). We found that 40 patients (41%) have the normal prognosis, 22 patients (22.7%) have the diagnosis of CP, and 30 patients (30.9%) were diagnosed as having epilepsy. Twelve out of 22 patients with CP had the diagnosis of epilepsy. The WISC-R full-scale IQ scores were <55 points in 27 patients (27.8%) and were >85 points in 40 patients (41.2%). According to GMFCS, 10 patients were classified as levels 1-2, and 12 patients were classified as levels 3-5. In multivariate regression analyses, 5-min APGAR score <6 was found to be an independent risk factor for CP, and 5-min APGAR score <6 and neonatal status epilepticus were independent risk factors for epilepsy. CONCLUSIONS: This prospective cohort study reveals that abnormal school age outcome after neonatal seizures are significantly related to 5-min APGAR score <6 and neonatal status epilepticus.

PNESSE 1: Psychogenic status and status epilepticus: Could they be distinguished retrospectively? A survey among neurologists.

OBJECTIVE: The aim of this study was to evaluate neurologists' reliability in recognizing retrospectively a diagnosis of psychogenic status and status epilepticus (SE) based solely on clinical semiology, as reported in medical charts. METHODS: This is a retrospective analysis of medical records of patients with suspected SE, diagnosed with psychogenic status and SE, proven by video-electroencephalography (EEG) monitoring, over a two-year period, from January 1st 2012 to December 31st 2013. Eight additional patients outside this time frame were included in this series because they had video-EEG proven psychogenic status, and they met all the inclusion criteria. The group with SE was divided into symptomatic SE (SSE) if a precipitating factor was identified, and undetermined SE (USE) if none were identified. Twenty-two neurologists from the CHU de Grenoble-Alpes were asked to fill out a survey where they were asked to score, for each patient, their agreement, using Likert scales, for the respective diagnoses of psychogenic status and SE. Their opinions were based on a provided written sheet summarizing the clinical description of the event and patients' clinical context. Neurologists were blinded to video-EEG monitoring results and final diagnosis. The level of agreement, disagreement, and the homogeneity of neurologist's responses according to the final diagnosis were then calculated. Finally, clinical data, as provided in the event's clinical description and context, considered as highly relevant by neurologists to establish an accurate diagnosis were gathered. RESULTS: Eighteen neurologists completed the survey for 48 patients, including 11 diagnosed with psychogenic status and 37 with SE (30 with SSE and 7 with USE). For patients diagnosed with SE, the presence of a precipitating factor increased the likelihood and the homogeneity among neurologists of a diagnosis of SE (77%), with a specificity (Sp) of 96% and a positive predictive value of 95%. The lack of a precipitating factor significantly decreased the diagnosis likelihood of SE (55%) with a predictive value of 82%. For patients diagnosed with psychogenic status, most of neurologists agreed with the diagnosis of psychogenic status (69%) with a predictive value of 82%, although heterogeneity in the diagnosis was found. According to neurologists participating in this study, most significant terms, found in the medical charts, helping to distinguish SE from psychogenic status were "stereotypical movements", "limb myoclonus", "epilepsy", and "vigilance alteration". To differentiate psychogenic status from SE, most relevant terms used by neurologists were "resistance to eyes opening", "anarchic movements", "prolonged motor manifestations", "limb tremor" and "opisthotonus". However, analysis of the distribution of the terms among the different groups (SSE, USE, and psychogenic status) showed no significant difference. SIGNIFICANCE: This study is in line with previous literature highlighting the difficulty in retrospectively differentiating SE from psychogenic status based on clinical events description recorded in the medical chart.

Long-term effects of status epilepticus during infancy in male rats: Sexual behavior and brain response upon exposure to sexually receptive females.

Previous research in female rats showed that induction of status epilepticus (SE) during infancy impairs proceptive sexual behavior at the long run in adulthood but temporarily, since full proceptivity is recovered after four mating trials. In male rats, such equivalent effects have not been explored yet. Thus, SE was experimentally induced by injecting lithium chloride (3 mEq/kg, i.p.) in thirteen-day-old (P13) male pups and then, on P14, pilocarpine hydrochloride (100 mg/kg, s.c.). Controls received the same volume of saline. For Experiment 1, at P90, we analyzed c-Fos immunoreactivity (c-Fos-IR) as a measure of unconditioned brain activity after exposing them to sexually receptive females, but without physical contact. For Experiment 2, a different group of males was tested for locomotor activity, and their sexual behavior was assessed during five trials. Then, serum testosterone and corticosterone levels were measured. Our results showed that a lower proportion of SE males performed mounts, intromissions, and ejaculations, and repeated training did not improve their behavior. The levels of testosterone in SE males were reduced, but corticosterone, c-Fos-IR, and locomotion were similar to controls. These results suggest that SE during infancy impairs adult sexual behavior by reducing testosterone.

Subcortical nuclei volumes are associated with cognition in children post-convulsive status epilepticus: Results at nine years follow-up.

PURPOSE: The purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). METHODS: Structural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE+, n = 22) and those without (CSE-, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ <85) while adjusting for etiology, age, socioeconomic status, sex, CSE duration, and intracranial volume (ICV); Bonferroni correction was applied for the analysis of individual subcortical nuclei. RESULTS: Seventy subjects (11.8 ±â€¯3.4 standard deviation (SD) years; 34 males) and 72 controls (12.1 ±â€¯3.0SD years; 29 males) underwent analysis. Significantly smaller volumes of the left thalamus, left caudate, right caudate, and SCV were found in subjects with CSE+ compared with HC, after adjustment for intracranial, gray matter (GM), or cortical/cerebellar volume. When compared with subjects with CSE-, subjects with CSE+ also had smaller volumes of the left thalamus, left pallidum, right pallidum, and SCV. Individual subcortical nuclei were not associated, but SCV was associated with FSIQ (p = 0.005) and GMS (p = 0.014). Intracranial volume and etiology were similarly predictive. CONCLUSIONS: Nine years post-CSE, SCV is significantly lower in children who have LCA compared with those that do not. However, in this cohort, we are unable to determine whether the relationship is independent of ICV or etiology. Future, larger scale studies may help tease this out.

Antioxidant treatment after epileptogenesis onset prevents comorbidities in rats sensitized by a past stressful event.

OBJECTIVE: Unresolved past stressful events can induce a state of vulnerability to epilepsy and comorbidities. Using an experimental model of stress-induced vulnerability to depression, we tested whether an antioxidant treatment applied after the onset of epileptogenesis was disease modifying and could prevent the occurrence of comorbidities. METHODS: We used social defeat (SD) to trigger a state of vulnerability in half of the SD-exposed population of rats. One month after SD, we used repeated injections of kainic acid to trigger status epilepticus (SE). One subset of animals was treated after SE during 2 weeks with Tempol, a strong antioxidant. Supradural 24/7 recordings were used to assess the development of epilepsy. We assessed spatial and nonspatial memory as well as a depressionlike profile 6 weeks after SE. RESULTS: Serum brain-derived neurotrophic factor (BDNF) levels decreased after SD in all animals and recovered to pre-SD levels 1 month later in half of them (SDN group). The other half kept low serum BDNF levels (SDL group). At that stage, SDN and SDL animals do not present a depressionlike profile. The SDL group was more sensitive than the SDN group to epileptogenic conditions. Following SE, the SDL group displayed accelerated epileptogenesis, a depressionlike profile, and severe cognitive deficits as compared to SDN rats. Transient Tempol treatment was disease-modifying, reducing the number of seizures, and prevented the development of comorbidities in the SDL group. Tempol treatment normalized oxidative stress in the SDL group to SDN levels. SIGNIFICANCE: This study illustrates the disease-modifying effect of antioxidant treatment after the onset of epileptogenesis in a population rendered vulnerable by past stressful events. The transient treatment decreased seizure burden and had long-term effects, preventing the occurrence of a depressionlike profile and cognitive deficits. We propose that vulnerability to comorbidities can be reversed after the onset of epilepsy.

Toward evidence-based severity assessment in rat models with repeated seizures: III. Electrical post-status epilepticus model.

OBJECTIVE: Ethical approval of experiments in chronic epilepsy models requires a careful balancing of the expected gain-in-knowledge with the level of distress. Thus recommendations for evidence-based severity assessment and classification are urgently needed for preclinical epilepsy research. METHODS: Therefore, we have completed a comprehensive analysis of alterations in behavioral, biochemical, and physiological parameters in a rat electrical post-status epilepticus model. Selected parameters were repeatedly analyzed during different experimental phases to obtain information about the level of distress throughout the course of the model. RESULTS: Behavioral patterns comprised an increase in activity along with a reduction in risk assessment behavior, active social interaction, saccharin preference as well as nonessential, but evolutionary-determined behavior such as nest building and burrowing. Among the biochemical parameters, fecal corticosterone metabolites proved to be increased in different phases of the experiment. In the early post-insult phase, this increase was reflected by elevated serum corticosterone concentrations. Telemetric recordings demonstrated increases in home cage activity and heart rate in selected experimental phases but argued against relevant changes in heart rate variability. Comparison between animals with tethered or telemetric recordings including a principal component analysis revealed differences between both groups. SIGNIFICANCE: The present findings further confirm that burrowing behavior and saccharin preference might serve as valid parameters for severity assessment in chronic epilepsy models. Considering the course of alterations providing evidence for a more pronounced level of distress in the early phase following status epilepticus (SE), we suggest a classification of the electrical post-SE model as severe. This suggestion may serve as a guidance for laboratory-specific evaluations. Comparison between data from animals with tethered and telemetric recordings indicated an impact of the mode of recordings. However, further research is necessary to analyze the validity of telemetry as a putative refinement measure.

Weaning from antiseizure drugs after new onset status epilepticus.

OBJECTIVE: In patients with status epilepticus (SE) without prior epilepsy, there are limited data on the safety of discontinuing antiseizure drugs (ASDs) after seizure control. We aimed to describe seizure recurrence when weaning from ASDs following new onset SE (NOSE). METHODS: Retrospective review of adult patients with NOSE admitted to Mayo Clinic, Rochester, Minnesota between January 1, 1990 and December 31, 2015 was performed. Weaning was defined as a discontinuation of ASDs following discharge. Patient demographics, SE characteristics, timing of ASD withdrawal, and seizure recurrence were collected. RESULTS: One hundred seventy-seven patients with mean age 63 ± 18 years were identified; 96 (54.2%) patients had refractory SE (RSE), and 81 (45.8%) had nonrefractory SE. Mean follow-up was 3.8 ± 3.2 years for those successfully weaned off ASDs. One hundred thirty (73.4%) with outpatient follow-up were included in the analysis; 128 (98.5%) patients were discharged on an ASD; 44 of 128 (34.4%) patients underwent weaning from at least 1 ASD following discharge, including 27 of 128 (21.1%) who were completely weaned off of all ASDs. Younger patients (P = 0.009) and those with RSE (P = 0.048, odds ratio = 2.12, 95% confidence interval = 1.00-4.48) tended to undergo weaning. Six of 44 (13.6%) patients had seizure recurrence when weaned off of any ASD, and two of 27 (7.4%) patients completely weaned off all ASDs had seizure recurrence. Two of seven (28.6%) patients who underwent attempted barbiturate weaning experienced seizure recurrence. SIGNIFICANCE: We found a rate of 13.6% for late seizure recurrence after weaning from at least one ASD in patients with NOSE; seizure recurrence was more likely in patients with RSE treated with barbiturates. Systematic collection of longitudinal data in patients requiring multiple ASDs for NOSE control will provide more conclusive guidance on weaning from ASDs.

The ADAN scale: a proposed scale for pre-hospital use to identify status epilepticus.

BACKGROUND AND PURPOSE: The prognosis of status epilepticus (SE) depends on the time between onset and the diagnosis and start of treatment. Our aim was to design a scale with predictive value for pre-hospital diagnosis of SE. METHODS: This was a retrospective study of 292 patients who attended the emergency department for an epileptic seizure. A total of 49 patients fulfilled the criteria for SE. We recorded the patients' history and clinical features. Variables independently associated with SE were combined to design a clinical scale. The performance of the scale was evaluated in a validation dataset of 197 patients. RESULTS: A total of 50.3% of the patients were male and the mean age was 55.9 years. The following features were more prevalent in patients with SE: abnormal speech (79.6% vs. 18.9%, P < 0.001), eye deviation (69.4% vs. 14.0%, P < 0.001), automatism (22.4% vs. 6.3%, P < 0.001), hemiparesis (24.5% vs. 10.9%, P = 0.011), state of stupor/coma (46.9% vs. 4.2%, P < 0.001) and number of pre-hospital seizures, i.e. two (34.7% vs. 4.5%, P < 0.001) or more than two (51.0% vs. 0.4%, P < 0.001). Based on these findings, we designed a scale that scored 1 point each for presence of abnormal speech, eye deviation, automatism and two seizures, and 2 points for more than two seizures. The predictive capacity of the scale for identifying SE in the validation dataset was 98.7% (95% confidence interval, 97.3%-100%) and 85.4% of patients with a score >1 had SE. CONCLUSIONS: A score >1 on the ADAN scale is a robust predictor of the diagnosis of SE in patients who experience an epileptic seizure. This scale may be a useful tool for clinical use and warrants further investigation.

Long-term outcomes after childhood convulsive status epilepticus.

PURPOSE OF REVIEW: It is widely accepted that childhood convulsive status epilepticus (CSE) has associated short-term and long-term mortality and morbidity. However, the role of CSE itself on subsequent adverse outcomes is still debated. In addition, whether prolonged seizures cause any long-term hippocampal injury and developmental or memory impairment is uncertain. In this review, we aim to provide an overview of long-term outcomes after childhood CSE, highlighting data from recent literature on this subject. RECENT FINDINGS: Long-term outcome after childhood CSE is favorable in previously normal children, with low incidence of epilepsy, motor and intellectual disability, behavioral impairment and need for special educational provision. Mesial temporal sclerosis is uncommon in children after prolonged febrile seizures. There is substantial morbidity after childhood CSE, but this is seen primarily in children with symptomatic causes and preexisting neurological abnormalities. Cause is the primary determinant of outcomes after childhood CSE and the additional effect of CSE characteristics such as seizure duration seems to be less than previously believed. SUMMARY: Childhood CSE is associated with substantial neurological, cognitive and behavioral morbidity. Early identification of these difficulties and appropriate intervention are likely to have a major positive impact on their quality of life.

Intelligence and memory outcomes within 10 years of childhood convulsive status epilepticus.

Long-term intelligence and memory outcomes of children post convulsive status epilepticus (CSE) have not been systematically investigated despite evidence of short-term impairments in CSE. The present study aimed to describe intelligence and memory outcomes in children within 10 years of CSE and identify potential risk factors for adverse outcomes. In this cohort study, children originally identified by the population-based North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) were prospectively recruited between July 2009 and February 2013 and invited for neuropsychological assessments and magnetic resonance imaging (MRI) scans. Full-scale intelligence quotients (FSIQs) were measured using the Wechsler Abbreviated Scales of Intelligence (WASI), and global memory scores (GMS) was assessed using the Children's Memory Scale (CMS). The cohort was analyzed as a whole and stratified into a prolonged febrile seizures (PFS) and non-PFS group. Their performance was compared with population norms and controls. Regression models were fitted to identify predictors of outcomes. With a mean of 8.9 years post-CSE, 28.5% of eligible participants were unable to undertake testing because of their severe neurodevelopmental deficits. Children with CSE who undertook formal testing (N = 94) were shown to have significantly lower FSIQ (p = 0.001) and GMS (p = 0.025) from controls; the PFS group (N = 34) had lower FSIQs (p = 0.022) but similar memory quotients (p = 0.88) with controls. Intracranial volume (ICV), developmental delay at baseline, and active epilepsy at follow-up were predictive of long-term outcomes in the non-PFS group. The relationship between ICV and outcomes was absent in the PFS group despite its presence in the control and non-PFS groups. Post-CSE, survivors reveal significant intelligence and memory impairments, but prognosis differs by CSE type; memory scores are uncompromised in the PFS group despite evidence of their lower FSIQ whereas both are compromised in the non-PFS group. Correlations between brain volumes and outcomes differ in the PFS, non-PFS, and control groups and require further investigation.

Idiopathic encephalopathy related to status epilepticus during slow sleep (ESES) as a "pure" model of epileptic encephalopathy. An electroclinical, genetic, and follow-up study.

OBJECTIVE: The objective of the study was to investigate electroclinical and neuropsychological features, genetic background, and evolution of children with idiopathic encephalopathy with status epilepticus during slow sleep (ESES), including Landau-Kleffner syndrome (LKS). MATERIAL AND METHODS: All children diagnosed with idiopathic ESES at the Danish Epilepsy Centre between March 2003 and December 2014 were retrospectively reviewed. Repeated 24-hour electroencephalography (24-h EEG) recordings, neuropsychological assessments, and clinical-neurological evaluation were performed throughout the follow-up in all patients. In 13 children, genetic investigations were performed. RESULTS: We collected 24 children (14 males and 10 females). Mean age at ESES diagnosis was 6 years, and mean ESES duration was 2 years and 7 months. Twenty-one children had epileptic seizures. Three children had LKS. Topography of sleep-related EEG epileptic abnormalities was diffuse in 3 subjects, hemispheric in 6, multifocal in 9, and focal in 6. During the active phase of ESES, all children presented with a heterogeneous combination of behavioral and cognitive disturbances. In 14 children, a parallel between severity of the clinical picture and spike-wave index (SWI) was observed. We could not find a strict correlation between the type and severity of neurobehavioral impairment and the side/topography of sleep-related EEG discharges during the active phase of ESES. At the last follow-up, 21 children were in remission from ESES. Complete recovery from neurobehavioral disorders was observed in 5 children. Genetic assessment, performed in 13 children, showed GRIN2A variant in two (15.4%). SIGNIFICANCE: Our patients with idiopathic ESES showed a heterogeneous pattern of epileptic seizures, neurobehavioral disorders, and sleep EEG features. Only one-fourth of children completely recovered from the neuropsychological disturbances after ESES remission. Lack of correlation between severity/type of cognitive derangement and SWI and/or topography of sleep EEG epileptic abnormalities may suggest the contribution of additional factors (including impaired sleep homeostasis due to epileptic activity) in the neurobehavioral derangement that characterize ESES.

Management of prolonged epileptic seizures and status epilepticus in palliative care patients.

Prolonged seizures and status epilepticus (SE) are relevant problems in palliative care. Timely recognition and effective early treatment with first- and second-line antiepileptic drugs (AEDs) may prevent unnecessary hospitalizations. Seizures should be recognized and addressed like any other symptom that causes discomfort or reduces quality of life. Use of alternative AED administration routes (buccal, intranasal, or subcutaneous) may offer possibilities for effective and individualized AED therapy, even during the last days of life. In hospice or home care, however, also intravenous treatment is possible via vascular access devices for long-term use. Aggressive unlimited intensive care unit (ICU) treatment of refractory SE in palliative patients is mostly not indicated. At worst, intensive care can be futile and possibly harmful: death in the ICU is often preceded by long and aggressive treatments. Metastatic cancer, old age, high severity of acute illness, overall frailty, poor functional status before hospital admission, and the presence of severe comorbidities all increase the probability of poor outcome of intensive care. When several of these factors are present, consideration of withholding intensive care may be in the patient's best interests. Anticipated outcomes influence patients' preferences. A majority of patients with a limited life expectancy because of an incurable disease would not want aggressive treatment, if the anticipated outcome was survival but with severe functional impairment. Doctors' perceptions about their patients' wishes are often incorrect, and therefore, advance care planning including seizure management should be done early in the course of the disease. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Review: Post-Intensive Care Syndrome: Unique Challenges in the Neurointensive Care Unit.

Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in survivors and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in survivors and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences. Next, keeping in mind the distinction between disease-related neurocognitive changes and those that are associated directly with the experience of a critical illness, we review the neuropsychological sequelae among patients with common neurocritical illnesses. We acknowledge the clinical factors contributing to the difficulty in studying PICS in the neurocritical care patient population, provide recommendations for future lines of research, and encourage collaboration among critical care physicians in all specialties to facilitate continuity of care and to help elucidate mechanism(s) of PICS and PICS-F in all critical illness survivors. Finally, we discuss the importance of early detection of PICS and PICS-F as an opportunity for multidisciplinary interventions to prevent and treat new neuropsychological deficits in the neurocritical care population.

Imaging biomarkers of behavioral impairments: A pilot micro-positron emission tomographic study in a rat electrical post-status epilepticus model.

OBJECTIVE: In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET). METHODS: Behavioral and biochemical variables were cross-correlated with the results from two µPET scans using the tracers [18 F]fluoro-2-deoxy-D-glucose ([18 F]FDG) and 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18 F-fluoro-benzamidoethylpiperazine ([18 F]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrically induced post-status epilepticus rat model of epilepsy. RESULTS: In rats with epilepsy, µPET analysis revealed a local reduction in hippocampal [18 F]FDG uptake, and a local increase in [18 F]MPPF binding. These changes exhibited a correlation with burrowing as a "luxury" behavior, social interaction, and anxiety-associated behavioral patterns. Interestingly, hippocampal [18 F]FDG uptake did not correlate with spontaneous recurrent seizure activity. SIGNIFICANCE: In the electrically induced post-status epilepticus rat model, we demonstrated hippocampal hypometabolism and its correlation with a range of neurobehavioral alterations. These findings require further confirmation in other preclinical models and patients with epilepsy and psychiatric disorders to address the value of [18 F]FDG uptake as an imaging biomarker candidate for psychiatric comorbidities in patients as well as for severity assessment in rodent epilepsy models.

Long-term outcomes of status epilepticus: A critical assessment.

We reviewed 37 studies reporting long-term outcomes after a status epilepticus (SE) episode in pediatric and adult populations. Study design, length of follow-up, outcome measures, domains investigated (mortality, SE recurrence, subsequent epilepsy, cognitive outcome, functional outcome, or quality of life), and predictors of long-term outcomes are summarized. Despite heterogeneity in the design of prior studies, overall risk of poor long-term outcome after SE is high in both children and adults. Etiology is the main determinant of outcome, and the effect of age or SE duration is often difficult to distinguish from the underlying cause. The effect of the treatment on long-term outcome after SE is still unknown.

Status epilepticus associated with acute encephalitis: long-term follow-up of functional and cognitive outcomes in 72 patients.

BACKGROUND AND PURPOSE: Continued care in patients with encephalitis and prolonged status epilepticus (SE) is controversial. Limited data are available on the functional and cognitive outcomes. METHODS: In a prospective cohort study from 2007 to 2016, patients with acute encephalitis and SE were reviewed. Long-term outcomes including motor disability (modified Rankin Scale, mRS), daily living skills (activities of daily living, ADL), cognitive ability (modified Telephone Interview for Cognitive Status, TICS-M) and epilepsy sequelae were evaluated in survivors at the 12-month follow-up. RESULTS: At the 12-month follow-up, 72 patients were recruited who got a median score of 14 on the total ADL. 68% patients remained independent in their daily activities (mRS ≤ 2). Post-SE symptomatic epilepsy was observed in 49% of patients. Sixty-two patients achieved a median score of 40 on the TICS-M and 14 on the TICS-M Memory. Patients with autoimmune encephalitis were less prone to post-SE symptomatic epilepsy (18% vs. 58%, P = 0.005) but had lower TICS-M Memory score than those with viral encephalitis (8.5 vs. 15, P = 0.017). Compared to non-refractory status epilepticus (non-RSE), patients with RSE had a longer stay in the neurocritical care unit (39 vs. 26, P = 0.002), more in-hospital complications and post-SE symptomatic epilepsy (67% vs. 33%, P = 0.005). Long-term outcomes including ADL, mRS and TICS-M were not significantly different between patients with RSE and non-RSE or between patients with long (≥4 h) and short (<4 h) duration of SE. CONCLUSIONS: Survival with favorable functional recovery was promising after prolonged RSE in patients with acute encephalitis.

The etiology and prognosis of super-refractory convulsive status epilepticus in children.

BACKGROUND: Both refractory convulsive status epilepticus (SE) and super-refractory SE are medical emergencies. However, there are limited data on super-refractory SE in children. Thus, this study focuses on characterizing the demographics, outcomes, and prognostic factors for super-refractory SE in children. METHODS: This study was a retrospective analysis of super-refractory SE treated in a tertiary referral center in Taiwan. The functional outcome was evaluated by modified Rankin scale (mRS). Significant functional decline was defined as an mRS difference (before hospital admission and at discharge) of more than 2. The variates and the follow-up mRS values were then analyzed statistically. RESULTS: We enrolled 134 patients with 191 episodes of convulsive SE and identified 30 patients with 38 episodes of convulsive super-refractory SE. The incidence of convulsive super-refractory SE in the group with SE was 19.9%, and the age ranged from 2.5 months to 17 years. In-hospital mortality was 13.3%, which was much lower than that of adult cohorts. Newly acquired epilepsy and cognitive deficit occurred in 100% and 88.5%, respectively. Newly acquired epilepsy, as a sequel of super-refractory SE, was observed in all 18 patients (100%) who survived and had no history of epilepsy. Significant functional decline (mRS difference of more than 2) at discharge occurred in 76.7%. Poor functional outcome was associated with acute symptomatic etiology (P < 0.001) and the number of anesthetic agents (P = 0.002). The functional outcome improved after 1 year of follow-up in our population. CONCLUSIONS: Super-refractory SE is associated with significant morbidity and mortality in children. However, the in-hospital mortality rate is much lower compared with adults. The functional outcome in children is associated with acute symptomatic etiology and the number of anesthetic agents and may improve after long-term follow-up.