Episodes Of Status Epilepticus Research Articles

Ictal Direct Current Shifts Preceded Much Earlier Than High Frequency Oscillations After Status: Is It the Effect of Status or Antiseizure Medication?

While spikes and sharp waves are considered as markers of epilepsy in conventional electroencephalography, ictal direct current (DC) shifts and high-frequency oscillations (HFOs) appear to be useful biomarkers for epileptogenicity. We analyzed how ictal DC shifts and HFOs were affected by focal status epilepticus and antiseizure medications (ASMs). A 20-year-old female patient who underwent long-term intracranial electrode implantation for epilepsy surgery presented with 72 habitual seizures and a focal status epilepticus episode lasting for 4 h. Ten, 3, and 10 consecutive habitual seizures were analyzed before the status, after the status, and after ASM (valproate) loading, respectively. Before and immediately after the status, ictal DC shifts remained the same in terms of the amplitude, duration, and slope of DC shifts. High-frequency oscillations also remained the same in terms of the duration, frequency, and power except for the power of the lower frequency band. After ASM loading, the duration, amplitude, and slope of the ictal DC shift were significantly attenuated. The duration, frequency, and power of the HFOs were significantly attenuated. Furthermore, the interval between the DC onset and HFO onset was significantly longer and the interval between the HFO onset and ictal DC shift peak was significantly shorter. The attenuation of ictal DC shifts and HFOs after ASM loading implies that astrocyte and neuronal activity may be both attenuated by ASMs. This finding may help with our understanding of the pathophysiology of epilepsy and can aid with the discovery of new approaches for epilepsy management.

Double, Double Toil and Trouble: Recurrent Episodes of Status Epilepticus Are Associated With Increasingly Worse Outcomes

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Prophylactic antiseizure medications for recurrent status epilepticus in nonsyndromic childhood epilepsy

PurposeThe management of status epilepticus (SE) has mainly focused on the termination of ongoing SE episodes. However, long-term therapeutic strategies for the prevention of SE are lacking. This study aimed to investigate the effectiveness of prophylactic antiseizure medications (ASMs) for SEs in nonsyndromic childhood epilepsy. MethodsThis retrospective study was conducted at Jikei University Hospital. Patients <18 years of age, diagnosed with epilepsy, and experiencing three or more SE episodes within 1 year between April 1, 2017, and October 1, 2021, were included. ASMs introduced for seizure types that developed into SE were evaluated. The effectiveness of ASMs was determined by using the “Rule of Three”: An ASM was determined effective if patients were free of SE for a duration at least three times that of their longest SE interval in 12 months prior to intervention. ResultsThe investigation included a total of 32 ASMs administered to 13 patients. The longest interval between SE episodes before ASM administration was 28–257 d. The first SE interval after ASM administration was 12–797 d. Levetiracetam (LEV) and clobazam (CLB) showed effectiveness in 2/10 and 5/6 patients, respectively. Other ASMs were ineffective. The leading etiology of epilepsy was perinatal brain injury, identified in four patients, and CLB was effective in all of them. ConclusionsThe present study suggests that CLB and LEV may prolong the SE interval in some cases of nonsyndromic childhood epilepsy. CLB may be beneficial, particularly in patients with perinatal brain injury.

Immature Status Epilepticus Alters the Temporal Relationship between Hippocampal Interictal Epileptiform Discharges and High-frequency Oscillations

The aim was to investigate the long-term effects of a single episode of immature Status Epilepticus (SE) on the excitability of the septal and temporal hippocampus in vitro, by studying the relationship between interictal-like epileptiform discharges (IEDs) and high-frequency oscillations (HFOs; Ripples, Rs and Fast Ripples, FRs). A pentylenetetrazol-induced Status Epilepticus-(SE)-like generalized seizure was induced at postnatal day 20 in 22 male and female juvenile rats, sacrificed >40 days later to prepare hippocampal slices. Spontaneous IEDs induced by Mg2+-free ACSF were recorded from the CA3 area of temporal (T) or septal (S) slices. Recordings were band-pass filtered off-line revealing Rs and FRs and a series of measurements were conducted, with mean values compared with those obtained from age-matched controls (CTRs). In CTR S (vs T) slices, we recorded longer R & FR durations, a longer HFO-IED temporal overlap, higher FR peak power and more frequent FR initiation preceding IEDs (% events). Post-SE, in T slices all types of events duration (IED, R, FR) and the time lag between their onsets (R-IED, FR-IED, R-FR) increased, while FR/R peak power decreased; in S slices, the IED 1st population spike and the FR amplitudes, the R and FR peak power and the (percent) events where Rs or FRs preceded IEDs all decreased. The CA3 IED-HFO relationship offers insights to the septal-to-temporal synchronization patterns; its post-juvenile-SE changes indicate permanent modifications in the septotemporal excitability gradient. Moreover, these findings are in line to region-specific regulation of various currents post-SE, as reported in literature.

Status epilepticus in BRAF-related cardio-facio-cutaneous syndrome: Focus on neuroimaging clues to physiopathology.

Cardio-facio-cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical-radiological patterns and discuss the underlying physiopathology. We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic BRAF variants who experienced SE during a 5-year period. Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE/within 72 hours from SE termination in 5/7 events. Acute/early post-ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2/7, focal area of pcASL perfusion change in 2/7, focal cortical T2/FLAIR hyperintensity in 2/7. Follow-up images were available for 4/7 SE. No acute changes were detected in 2/7 (MRI performed 4 days after SE termination). Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long-term adverse neurological outcome. Cardio-facio-cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio-facio-cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio-facio-cutaneous syndrome patients from long-term brain damage.

Correlation between Persistent Serum Lactate Elevation and Brain Magnetic Resonance Imaging Abnormalities in Children with Status Epilepticus

Purpose: This study was conducted to evaluate the correlation between persistent serum lactate elevation and brain magnetic resonance imaging (MRI) in children with status epilepticus (SE). Methods: In this prospective analytical study, serum lactate levels were measured 24 hours after episodes of SE, and brain MRI was performed within 7 to 14 days after SE termination. MRI abnormalities were classified as acute encephalopathy (AE) grade I to III. The Kruskal-Wallis test was utilized for statistical analysis. Results: The study included 42 participants with SE, of whom 85.70% were boys, with a mean age of 4.94 years. Viral encephalitis was the most common diagnosis, accounting for 47.60% of cases. Elevated serum lactate levels were detected in 71.40% of patients, and approximately 47.60% exhibited abnormal MRI findings consistent with AE grade I. The median serum lactate levels for AE grades I, II, and III were 1.50, 3.10, and 0.78 mmol/L, respectively. Two patients died, and 66.70% experienced neurologic sequelae. A significant correlation (&lt;i&gt;P&lt;/i&gt;=0.021) was observed between persistent serum lactate elevation and abnormal brain MRI findings. Conclusion: In children with SE, AE grade I was the most common neuroimaging pattern observed, and persistently elevated serum lactate level was correlated with abnormal brain MRI findings.

A COMPARATIVE STUDY OF FIRST EPISODE STATUS EPILEPTICUS AND MULTIPLE EPISODES OF STATUS EPILEPTICUS IN EMERGENCY DEPARTMENT OF TERTIARY HOSPITAL OF BUNDELKHAND REGION, CENTRAL INDIA

Objective: Status epilepticus (SE) is a medical emergency that necessitates prompt and intensive treatment to prevent damage to the brain and other complications. SE can occur in any age group, but it is most observed in infants and the elderly. The diagnosis of convulsive SE is primarily clinical, but neuroimaging and laboratory studies are required to identify the underlying cause when convulsion is subsided. Bundelkhand region is a proposed state, located between Uttar Pradesh and Madhya Pradesh in central India, has a population of approximately 18 million, with around 14 million residing in rural areas (Census 2011). This region is infamous for its backward healthcare and education systems. This study aims to compare the outcomes of individuals experiencing their first episode of SE versus those with multiple episodes in terms of seizure control or progression to refractory or super-refractory status, considering the underlying causes. Methods: A total of 100 participants were selected for the study at MLB Medical College, Jhansi, between March 2020 and November 2021. Before participation, written informed consent was obtained after explaining the study’s objectives and procedures in detail. Data were recorded on an Excel sheet and analyzed using the Statistical Package for the Social Sciences software, applying appropriate statistical tests when necessary. Results: Among the 100 patients with SE, the common etiological factors were anticonvulsant drug withdrawal (33%) and central nervous system (CNS) infections (33%), followed by metabolic encephalopathy (17%), cerebral vascular accidents (12%), and hypoxemic encephalopathy (5%). The patients were managed according to standard protocols and drug availability. The outcomes were categorized as seizure control, hospital death, or development of refractory or super-refractory status. Among the patients, 35% developed refractory SE, and within that group, 29% progressed to super-refractory status. Conclusion: The fatality rate of SE was 14.0%. Predictors of higher mortality rates included the first episode of SE, patient’s age, lack of response to initial antiepileptic drugs, duration of convulsions, and untreatable underlying causes. Etiologies such as CNS infections and anticonvulsant drug withdrawal were considered preventable and have better outcomes.

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score

BackgroundThe risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. MethodsThe study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. ResultsWe included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE.A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13–4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03–4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07–3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40–5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3–84.3 %, p < 0.001). ConclusionsThe AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.

Cerebral hemiatrophy and hemiparesis following hemiclonic status epilepticus in Dravet syndrome.

Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior.

Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021. Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

Status epilepticus in patients with glioblastoma: Clinical characteristics, risk factors, and epileptological outcome.

Epilepsy is a common comorbidity in patients with glioblastoma, however, clinical data on status epilepticus (SE) in these patients is sparse. We aimed to investigate the risk factors associated with the occurrence and adverse outcomes of SE in glioblastoma patients. We retrospectively analysed electronic medical records of patients with de-novo glioblastoma treated at our institution between 01/2006 and 01/2020 and collected data on patient, tumour, and SE characteristics. In the final cohort, 292/520 (56.2%) patients developed seizures, with 48 (9.4% of the entire cohort and 16.4% of patients with epilepsy, PWE) experiencing SE at some point during the course of their disease. SE was the first symptom of the tumour in 6 cases (1.2%) and the first manifestation of epilepsy in 18 PWE (6.2%). Most SE episodes occurred postoperatively (n=37, 77.1%). SE occurrence in PWE was associated with postoperative seizures and drug-resistant epilepsy. Adverse outcome (in-house mortality or admission to palliative care, 10/48 patients, 20.8%), was independently associated with higher status epilepticus severity score (STESS) and Charlson Comorbidity Index (CCI), but not tumour progression. 32/48 SE patients (66.7%) were successfully treated with first- and second-line agents, while escalation to third-line agents was successful in 6 (12.5%) cases. Our data suggests a link between the occurrence of SE, postoperative seizures, and drug-resistant epilepsy. Despite the dismal oncological prognosis, SE was successfully treated in 79.2% of the cases. Higher STESS and CCI were associated with adverse SE outcomes.

It's Never Too Late for a Diagnosis.

Zellweger spectrum disorder (ZSD) (OMIM#214100) is a phenotypic continuum ranging from severe to mild presentations. ZSD is now used in all individuals with a defect in one of the 13 ZSD-PEX genes, regardless of phenotype. Diagnosis can be suggested by abnormal levels of very long-chain fatty acids, phytanic acid, pristanic acid, plasmalogens, pipecolic acid, or bile acids. However, false negatives are frequent, mostly in older patients. Definite diagnosis is established in a proband with suggestive clinical findings by identification of biallelic pathogenic variants in one of the 13 ZSD-PEX genes. A 39-year-old female patient had a global development delay since her first year of life. Never developed oral language but had sphincter control and was able to walk and laugh. At 8 years old, she had her first seizure and lost sphincter control when she was 20 years old. At 28 years old, she had an episode of status epilepticus, with severe prostration and became bedridden. She is currently mute, without capacity for communication or motor control. She has no consanguineous parents, has a 35 year old brother with global developmental delay and their mother had a history of an abortion, without other relevant family history. Brain MRI of the patient revealed severe leukodystrophy mainly periventricular, bilateral and symmetric, and less prominent in the cerebellar white matter, with severe cerebral and corpus callosum atrophy. Molecular study with a leukodystrophy gene panela identified a homozygotic pathogenic variant on PEX 1 gene (NM_000466.3) - c.2528G>A (p.(Gly843Asp)), confirming the diagnosis of ZSD. Homozygosity for PEX1 p.Gly843Asp seems to be associated with an intermediate/milder ZSD phenotype,with survival until adulthood. Some patients develop progressive degeneration of CNS myelin, a leukodystrophy pattern, like this patient, which may lead to regression. This girl with ZSD had a rapid and severe loss of previous skills after a seizure. Even though there is no specific treatment for this disease, a correct diagnosiswas very important for the parents and for family genetic counselling.

Acute symptomatic status epilepticus: Splitting or lumping? A proposal of classification based on real-world data.

This study aimed to group acute symptomatic etiologies of consecutive episodes of status epilepticus (SE) into different subcategories and explore their associations with clinical outcome. Etiologies were first categorized as "acute," "remote," "progressive," "SE in defined electroclinical syndromes," and "unknown." Four subcategories of acute etiologies were then defined: (1) withdrawal, low levels, or inappropriate prescription of antiseizure medications, or sleep deprivation in patients with pre-existing epilepsy; (2) acute insults to central nervous system (CNS; "acute-primary CNS"); (3) CNS pathology secondary to metabolic disturbances, systemic infection, or fever ("acute-secondary CNS"); and (4) drug/alcohol intoxication or withdrawal. Poor outcome at discharge, defined as worsening of clinical conditions (modified Rankin Scale [mRS] at discharge higher than mRS at baseline), was reported in 55.6% of cases. The etiological categories of acute-primary CNS (odds ratio [OR] = 3.61, 95% confidence interval [CI] = 2.11-6.18), acute-secondary CNS (OR = 1.80, 95% CI = 1.11-2.91), and progressive SE (OR = 2.65, 95% CI = 1.57-4.47), age (OR = 1.05, 95% CI = 1.04-1.06), nonconvulsive semiology with coma (OR = 3.06, 95% CI = 1.52-6.17), and refractoriness (OR = 4.31, 95% CI = 2.39-7.77) and superrefractoriness to treatment (OR = 8.24, 95% CI = 3.51-19.36) increased the odds of poor outcome. Heterogeneity exists within the spectrum of acute symptomatic causes of SE, and distinct etiological subcategories may inform about the clinical outcome.

Seizure enhances SUMOylation and zinc-finger transcriptional repression in neuronal nuclei

A single episode of pilocarpine-induced status epilepticus can trigger the development of spontaneous recurrent seizures in a rodent model for epilepsy. The initial seizure-induced events in neuronal nuclei that lead to long-term changes in gene expression and cellular responses likely contribute toward epileptogenesis. Using a transgenic mouse model to specifically isolate excitatory neuronal nuclei, we profiled the seizure-induced nuclear proteome via tandem mass tag mass spectrometry and observed robust enrichment of nuclear proteins associated with the SUMOylation pathway. In parallel with nuclear proteome, we characterized nuclear gene expression by RNA sequencing which provided insights into seizure-driven transcriptional regulation and dynamics. Strikingly, we saw widespread downregulation of zinc-finger transcription factors, specifically proteins that harbor Krüppel-associated box (KRAB) domains. Our results provide a detailed snapshot of nuclear events induced by seizure activity and demonstrate a robust method for cell-type-specific nuclear profiling that can be applied to other cell types and models.

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

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

How much refractory is 'refractory status epilepticus'? A retrospective study of treatment strategies and clinical outcomes.

This study aimed to evaluate whether differences in clinical outcomes exist according to treatments received and seizure activity resolution in patients with refractory status epilepticus (RSE). Consecutive episodes of non-hypoxic status epilepticus (SE) in patients ≥ 14years old were included. Episodes of RSE were stratified in: (i) SE persistent despite treatment with first-line therapy with benzodiazepines and one second-line treatment with antiseizure medications (ASMs), but responsive to successive treatments with ASMs (RSE-rASMs); (ii) SE persistent despite treatment with first-line therapy with benzodiazepines and successive treatment with one or more second-line ASMs, but responsive to anesthetic drugs [RSE-rGA (general anesthesia)]. Study endpoints were mortality during hospitalization and worsening of modified Rankin Scale (mRS) at discharge. Status epilepticus was responsive in 298 (54.1%), RSE-rASMs in 152 (27.6%), RSE-rGA in 46 (8.3%), and super-refractory (SRSE) in 55 (10.0%) out of 551 included cases. Death during hospitalization occurred in 98 (17.8%) and worsening of mRS at discharge in 287 (52.1%) cases. Multivariable analyses revealed increased odds of in-hospital mortality with RSE-rGA (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.27-7.35) and SRSE (OR 3.83, 95%. CI 1.73-8.47), and increased odds of worsening of mRS with RSE-rASMs (OR 2.06, 95% CI 1.28-3.31), RSE-rGA (OR 4.44, 95% CI 1.97-10.00), and SRSE (OR 13.81, 95% CI 5.34-35.67). In RSE, varying degrees of refractoriness may be defined and suit better the continuum spectrum of disease severity and the heterogeneity of SE burden and prognosis.

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment.

Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown. The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients. We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment. Patients had a mean valproate intravenous loading dose of 34.5mg/kg and a mean maintenance dose of 15.3mg/kg/d (1078mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p=0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone). Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.

Clinical characteristics and outcomes of patients with recurrent status epilepticus episodes

BackgroundMultiple studies have focused on medical and pharmacological treatments and outcome predictors of patients with status epilepticus (SE). However, a sufficient understanding of recurrent episodes of SE is lacking. Therefore, we reviewed recurrent SE episodes to investigate their clinical characteristics and outcomes in patients with relapses.MethodsIn this retrospective, multicenter study, we reviewed recurrent SE patient data covering 2011 to 2017 from the university hospitals of Frankfurt and Marburg, Germany. Clinical characteristics and outcome variables were compared among the first and subsequent SE episodes using a standardized form for data collection.ResultsWe identified 120 recurrent SE episodes in 80 patients (10.2% of all 1177 episodes). The mean age at the first SE episode was 62.2 years (median 66.5; SD 19.3; range 21–91), and 42 of these patients were male (52.5%). A mean of 262.4 days passed between the first and the second episode. Tonic–clonic seizure semiology and a cerebrovascular disease etiology were predominant in initial and recurrent episodes. After subsequent episodes, patients showed increased disability as indicated by the modified Rankin Scale (mRS), and 9 out of 80 patients died during the second episode (11.3%). Increases in refractory and super-refractory SE (RSE and SRSE, respectively) were noted during the second episode, and the occurrence of a non-refractory SE (NRSE) during the first SE episode did not necessarily provide a protective marker for subsequent non-refractory episodes. An increase in the use of intravenous-available anti-seizure medication (ASM) was observed in the treatment of SE patients. Patients were discharged from hospital with a mean of 2.8 ± 1.0 ASMs after the second SE episode and 2.1 ± 1.2 ASMs after the first episode. Levetiracetam was the most common ASM used before admission and on discharge for SE patients.ConclusionsThis retrospective, multicenter study used the mRS to demonstrate worsened outcomes of patients at consecutive SE episodes. ASM accumulations after subsequent SE episodes were registered over the study period. The study results underline the necessity for improved clinical follow-ups and outpatient care to reduce the health care burden from recurrent SE episodes.

Prediction of long-term unprovoked seizures after status epilepticus.

Possible long-term consequences of status epilepticus (SE) include cognitive and behavioral impairment and the development of chronic epilepsy. However, these aspects have not been systematically studied in clinical practice. We aimed to evaluate long-term seizure recurrence after SE and the potential risk factors for their development. Data were obtained from a prospective registry of all SE episodes occurring in adult patients who attended our center from February 2011 to April 2022. Clinical data, electroencephalographic findings, treatment, and long-term data were prospectively recorded. We performed a cross-sectional study of consecutive SE patients without previous epilepsy diagnosis, and analyzed the development of unprovoked remote seizures. A total of 849 patients were registered in the database. After excluding in-hospital mortality (198/849, 23.3%) and patients with prior epilepsy history (291/849, 44.7%), 360 patients (42.4%) with a first SE episode were included. The median age was 68 years (interquartile range [IQR] = 56-79), and 176 patients (48.9%) were women. The median time to first-line treatment initiation was 2 h (IQR = .7-7.4), and it was correlated with SE duration (R = .375, p < .001). One hundred nine patients (30.3%) presented unprovoked seizures during a median follow-up of 1.8 years (IQR = .5-4.3). After adjusting for identifiable confounders in a multivariable Cox regression analysis, progressive symptomatic etiology (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.33, p = .011), time to first-line treatment initiation > 1.5 h (HR = 1.89, 95% CI = 1.25-2.87, p = .003), and superrefractory SE (HR = 2.34, 95% CI = 1.26-4.33, p = .007) were independently associated with a greater risk of unprovoked seizure recurrence. In contrast, older patients (HR = .99, 95% CI = .97-.99, p = .021) and an acute symptomatic etiology (HR = .44, 95% CI .28-.68, p < .001) were at lower risk of unprovoked seizure recurrence. The etiology of SE, the delay in initiating SE treatment, and the presence of superrefractoriness have been identified as potentials factors associated with unprovoked remote seizures following a new onset SE. Therefore, prompt and appropriate management should be applied to avoid seizure recurrence.

Status Epilepticus in Children: Experience in a Portuguese Tertiary Hospital

Purpose: Status epilepticus (SE) is a life-threatening neurological emergency, frequently diagnosed in pediatric patients. We aimed to characterize our pediatric cases of SE in an 11-year period according to the 2015 International League Against Epilepsy report. Methods: Clinical electronic records were retrospectively reviewed. All pediatric SE cases admitted from January 2010 to December 2020 were included, excluding neonates. SE was considered refractory if it persisted despite the administration of two appropriate antiseizure medications at acceptable doses.Results: We included 102 episodes, 55 (53.9%) in boys. The median age was 2.5 years (interquartile range, 1.3 to 5.0). Most episodes were classified as SE with prominent motor features (92.2%), and the most frequent etiological classification was acute symptomatic cause (84.3%). A benzodiazepine was used as the first-line antiseizure medication in 99 (97%) cases, of which diazepam was preferred (93%). The preferred second-line medication was phenytoin (65.7%). Midazolam was the most frequently responsible for termination of SE when given in a continuous infusion (47%). Episodes of SE were classified as refractory in 81 (79.4%) cases. Episodes of &gt;60 minutes were more frequent in patients diagnosed with epilepsy (&lt;i&gt;P&lt;/i&gt;=0.036), focal motor SE (&lt;i&gt;P&lt;/i&gt;&lt;0.001), and non-convulsive SE (&lt;i&gt;P&lt;/i&gt;=0.037). The in-hospital mortality rate was 2.9%. Conclusion: Most of our findings are in accord with the current literature. Epilepsy, non-convulsive SE, and focal motor SE were associated with prolonged duration (&gt;60 minutes), which reinforces the significance of the underlying neurological disease and semiological standardization in pediatric SE.