Cryptogenic New-onset Refractory Status Epilepticus with Hyperintensity of T1-weighted Magnetic Resonance Imaging in the Bilateral Basal Ganglia: An Autopsy Report.

We present a 76-year-old man with cryptogenic new-onset refractory status epilepticus (C-NORSE) with an initial abnormal signal in the nucleus accumbens and a remarkable hyperintense signal on T1-weighted magnetic resonance imaging in the bilateral basal ganglia (BG). His status epilepticus did not respond to most anti-epileptic therapies or immunotherapies, and he died of sepsis. An autopsy revealed severe neuronal loss and hypertrophic astrocytes in the BG and limbic system, with no signs of inflammation or malignancy. This case suggests that lesions in the BG may reflect secondary degeneration and predict poor outcomes in C-NORSE.

Progression to refractory status epilepticus: A machine learning analysis by means of classification and regression tree analysis.

BACKGROUND AND OBJECTIVES: to identify predictors of progression to refractory status epilepticus (RSE) using a machine learning technique. METHODS: Consecutive patients aged ≥ 14 years with SE registered in a 9-years period at Modena Academic Hospital were included in the analysis. We evaluated the risk of progression to RSE using logistic regression and a machine learning analysis by means of classification and regression tree analysis (CART) to develop a predictive model of progression to RSE. RESULTS: 705 patients with SE were included in the study; of those, 33 % (233/705) evolved to RSE. The progression to RSE was an independent risk factor for 30-day mortality, with an OR adjusted for previously identified possible univariate confounders of 4.086 (CI 95 % 2.390-6.985; p < 0.001). According to CART the most important variable predicting evolution to RSE was the impaired consciousness before treatment, followed by acute symptomatic hypoxic etiology and periodic EEG patterns. The decision tree identified 14 nodes with a risk of evolution to RSE ranging from 1.5 % to 90.8 %. The overall percentage of success in classifying patients of the decision tree was 79.4 %; the percentage of accurate prediction was high, 94.1 %, for those patients not progressing to RSE and moderate, 49.8 %, for patients evolving to RSE. CONCLUSIONS: Decision-tree analysis provided a meaningful risk stratification based on few variables that are easily obtained at SE first evaluation: consciousness before treatment, etiology, and severe EEG patterns. CART models must be viewed as potential new method for the stratification RSE at single subject level deserving further exploration and validation.

Evaluation of levetiracetam loading dose in adult patients with benzodiazepine-refractory status epilepticus.

BACKGROUND: Status epilepticus (SE) is a neurologic emergency defined as continued seizure activity greater than five minutes or recurrent seizure activity without return to baseline. Benzodiazepine-refractory SE is continuous seizure activity despite treatment with a benzodiazepine. Treatment of benzodiazepine-refractory SE includes levetiracetam with loading doses ranging from 20 mg/kg to 60 mg/kg up to a maximum dose of 4500 mg. While levetiracetam has minimal adverse effects, there is currently a lack of studies directly comparing the safety and efficacy of various loading doses of levetiracetam. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of three loading doses of levetiracetam in the setting of benzodiazepine-refractory SE. METHODS: This was a single center, retrospective cohort study of adult patients with benzodiazepine-refractory SE who were treated with levetiracetam from April 1, 2016, to August 31, 2023. Patients with documented hypersensitivity to levetiracetam, those who were pregnant or incarcerated and patients who received an alternative antiepileptic drug (AED) prior to levetiracetam were excluded. Patients with other identifiable causes of SE including hyperglycemia, hypoglycemia, hyponatremia or who were post cardiac arrest were also excluded. Patients were divided into three arms based on loading dose of levetiracetam administered (≤20 mg/kg [LEVlow], 21--39 mg/kg [LEVmed] or ≥40 mg/kg [LEVhigh]). The primary endpoint was the rate of seizure termination, defined as the lack of need for an additional AED within 60 min following levetiracetam administration. Secondary outcomes included the rate of intubation, and recurrent seizure activity 60 min to 24 h post seizure termination as defined by positive EEG results or need for an additional AED. Subgroup analyses were performed to assess the influence of adequate loading doses of benzodiazepines, and outpatient levetiracetam use. RESULTS: Overall, 740 patients were screened for inclusion, with 218 patients being included in the primary analysis. Patients were divided into three groups with an average levetiracetam loading dose of 14.5 mg/kg in the LEVlow group, 28.8 mg/kg in the LEVmed group, and 48.8 mg/kg in the LEVhigh group. There was no difference in rates of seizure termination at 60 min (92.9% LEVlow vs 89.3% LEVmed vs 84.7% LEVhigh; p = 0.377). Additionally, no difference was found in rates of recurrent seizure activity between 60 min and 24 h post levetiracetam loading dose (32.1% LEVlow vs 32.0% LEVmed vs 28.8% LEVhigh; p = 0.899). However, the LEVhigh group did have a higher rate of intubation (45.8%) compared to the LEVmed (28.2%) and LEVlow (26.8%) group (p = 0.040). CONCLUSION: The loading of levetiracetam did not result in a statistically significant difference in rate of seizure termination at 60 min nor did it appear to impact the rate of recurrent seizures at 24 h. However, we did find higher rates of intubation in patients who received levetiracetam >40 mg/kg. Further research is warranted to determine the optimal loading dose of levetiracetam in benzodiazepine-refractory SE.

Communication trends over time in new-onset refractory status epilepticus (NORSE): Interim analysis from the NORSE/FIRES Family Registry.

The new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) Family Registry contributes to a systematic effort to collect clinical and epidemiological information on individuals affected by NORSE/FIRES. We explore diagnostic and prognostic information provided to patients and their families, their satisfaction with the communication, and utilisation of palliative care services during acute hospitalization. Communication about the diagnosis of NORSE/FIRES to families has improved since the publication of consensus definitions in 2018, with families being more likely to be told about NORSE/FIRES after 2018. Families rate the quality of prognostic information as being moderate. Palliative care services were involved in a minority of patients. Understanding and characterizing the prevalence and satisfaction of diagnostic and prognostic conversations is important for improving overall care, the quality of physician-patient-family relationships, and the recovery process for those affected by NORSE/FIRES.

Status epilepticus in tuberculous meningitis.

OBJECTIVE: There is paucity of information about status epilepticus (SE) in tuberculous meningitis (TBM). In this communication, we report SE semiology, response to antiseizure medication (ASM) and outcome of the TBM patients with SE. METHODS: The diagnosis of TBM was based on clinical, cerebrospinal fluid and MRI findings. The clinical details, severity of meningitis, and MRI and electroencephalography findings were noted. The type of SE, onset from the meningitis symptoms, number of ASMs required to control SE and outcomes were noted. RESULTS: During study period from august 2015 to march 2023, 143 TBM patients were admitted and 10 (6.9 %) had SE, whose age ranged between 12 and 45 years. MRI revealed exudates in six, hydrocephalus in three, infarctions in seven and tuberculoma in six patients. Median (interquartile range) duration of SE after meningitis symptoms was 65 (43.7-100.5) days. Three had generalized convulsive SE, three epileptia partialis continua (EPC), three focal convulsive SE with bilateral convulsion, and one had non-convulsive SE. Two (20 %) patients responded to two ASMs, six (60 %) had refractory SE whose seizure continued after benzodiazepine and one ASM, and two (20 %) had super-refractory SE having seizures for ≥ 24 h despite use of intravenous anesthetic agent. Four (40 %) patients died; uncontrolled SE resulted death in one, and the remaining patients died due to primary disease. Only 2 (20 %) patients had good recovery and 4 (40 %) had poor recovery at 6 months. CONCLUSION: Status epilepticus in TBM is uncommon and can be refractory or super-refractory resulting in poor outcome.

IT-DEX and B cell depletion in a child with anti-GAD 65 autoimmune encephalitis presenting as NORSE: A case report.

New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies.

New onset status epilepticus and its long-term outcome: A cohort study.

PURPOSE: New onset status epilepticus (NOSE), a subtype of status epilepticus, is a neurological emergency associated with significant morbidity and mortality. This study aimed to analyze the phenotypic spectrum and outcomes of patients presenting with NOSE. METHODS: This prospective and retrospective descriptive study included patients presenting with NOSE over a 10-year period. Data collected included patient demographics, phenotypic characteristics of SE and its etiology, Status Epilepticus Severity Score (STESS), SE classification Axis-II, and Modified Rankin Scale (mRS) scores at admission and discharge. Functional outcomes and seizure status were assessed at least 6 months post-discharge. Prognostic factors for mortality and the development of epilepsy were also analyzed. RESULTS: A total of 208 patients were included, with a mean age of 41.97 ± 21.66 years, and a male predominance (57.1 %). Focal to bilateral tonic-clonic seizures were observed in 47.5 % of patients. The etiology was acute symptomatic in 35.57 % and remote symptomatic in 24 %. The median hospital stay was 4 days (range: 2.25-10.75 days). The mortality rate was 26.5 %, and 23 % of patients developed epilepsy with a median follow-up of 9 months. Higher age (≥ 50 years), elevated STESS, ICU admission, use of anesthetic agents, refractory status epilepticus (RSE), and new-onset refractory status epilepticus (NORSE) were significant risk factors for mortality (p<0.05). The development of epilepsy was associated with a higher number of antiseizure medications (ASM) at discharge, ICU admission, use of anesthetic agents, RSE, and NORSE (p<0.05). CONCLUSION: NOSE is a neurological emergency with a variable etiology and significant long-term consequences. Approximately one-fourth of patients presenting with NOSE died, and another quarter developed epilepsy during a median follow-up of 9 months. Identifying and addressing the predictors of mortality and epilepsy development following NOSE may improve long-term outcomes.

Hemophagocytic lymphohistiocytosis in an adult patient with super-refractory status epilepticus.

This case report presents a 38-year-old male patient who, after a febrile infection, developed super-refractory status epilepticus and multiorgan failure, and died in 2 weeks despite the best possible intensive care. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH). This case shows that a rare immunological cause such as HLH may cause febrile infection-related epilepsy syndrome (FIRES), and complications of intensive care can mask the physiological and laboratory changes in HLH. PLAIN LANGUAGE SUMMARY: This case report presents a 38-year-old man who, after a febrile infection, developed intractable epileptic activity requiring intensive care treatment. During the intensive care, the patient showed signs of multiple organ damage and died in 2 weeks despite the best possible treatment. Autopsy revealed findings suggestive of hemophagocytic lymphohistiocytosis (HLH), which is a rare immune system regulation disorder leading to persistent inflammatory state and organ damages. This case shows that an immunological disorder like HLH may underlie treatment resistant fever-related epileptic seizures.

Successful use of Fenfluramine in super-refractory status epilepticus in a patient with tuberous sclerosis complex and Lennox-Gastaut syndrome.

A 24-year-old female patient with pre-existing refractory epilepsy caused by tuberous sclerosis (TSC) and electroclinical features of Lennox-Gastaut syndrome (LGS) was referred to our hospital from an external clinic. Upon arrival, she presented with super-refractory status epilepticus (SRSE) since anaesthetics had already been used in the referring clinic. Despite various changes in ASM-treatment and continuous administration of anaesthetics for more than two weeks, SRSE could not be terminated. On treatment day 24, we started Fenfluramin (FFA) which was soon titrated to a dose of 0,7 mg/kg/day. A few days after beginning the treatment with FFA, EEG and clinical situation improved dramatically. The following 6 weeks of treatment went without reported seizures. This case illustrates the successful use of FFA in SRSE in TSC and LGS and, to the best of our knowledge, represents the first report of FFA in this clinical context.

Super-refractory status epilepticus in a woman with Aeromonas caviae meningitis: a rare case report and review of the literature.

Currently, there is a lack of knowledge regarding Aeromonas caviae meningitis. We report the first case of super-refractory status epilepticus (SRSE) in a woman with Aeromonas caviae meningitis. The case report demonstrates that this condition can lead to severe SRSE. Effective treatment for epilepsy is crucial for improving the prognosis for similar patients. According to Gomes et al.'s consensus protocol for SRSE, using a combination of up to one anesthetic drug and three non-anesthetic anti-epileptic drugs may be helpful and important in managing SRSE that is caused by Aeromonas caviae meningitis.

Thiamylal serum concentration for refractory convulsive status epilepticus while associated decreased concentrations of concomitant antiepileptics: a case report.

BACKGROUND: Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs. CASE PRESENTATION: A 72-year-old healthy man developed RSE. Despite the administration of various AEDs, his seizures were not resolved. Thiamylal was then administered at an initial bolus dose of 2.1 mg/kg, followed by a continuous infusion of 4.2-5.2 mg/kg/h. The initial thiamylal concentration was observed at 7.8 µg/mL, increasing to 35.2 µg/mL before decreasing after dose reduction and cessation. Concurrently, the concentration of concomitant carbamazepine decreased from 5.59 µg/mL to 2.1 µg/mL and recovered as thiamylal concentration decreased. Lesser impacts were noted for other AEDs. CONCLUSIONS: This case report underscored the efficacy of thiamylal in treating RSE. However, it also highlighted the need for clinicians to closely monitor the concentrations of concurrent AEDs, especially carbamazepine, during thiamylal therapy.

Identification of etiologies according to baseline clinical features of pediatric new-onset refractory status epilepticus in single center retrospective study.

PURPOSE: New-onset refractory status epilepticus (NORSE) is defined as a state of prolonged seizure activity that does not improve despite the appropriate administration of medications, with underlying causes unknown after the initial diagnosis of status epilepticus. Because episodes of NORSE are accompanied by severe complications and a high risk of mortality, the prompt identification of the underlying cause is crucial for effective treatment and outcome prediction. This study assessed the relationship of NORSE etiologies with baseline clinical features in pediatric population. METHODS: Seventy-one pediatric patients, under 18 years of age at the initial diagnosis (4.50 ± 4.04, mean ± standard deviation), who experienced at least one episode of NORSE and underwent a comprehensive diagnostic evaluation between January 2005 and June 2020 at our center, were retrospectively selected. We reviewed clinical features at disease onset and long-term follow-up data. Uniform manifold approximation and projection (UMAP) was used to distinguish etiological clusters according to baseline clinical characteristics, and further analysis was performed based on underlying etiologies. RESULTS: Two distinct etiological groups-genetic and non-genetic-were identified based on the UMAP of clinical characteristics. Dravet syndrome (12/15, 80%) was more predominant in patients with a genetic diagnosis, whereas cryptogenic NORSE and encephalitis were prevalent in patients without a genetic diagnosis. The analysis of etiological categories revealed that age at the onset of status epilepticus (P=0.021) and progression to super refractory status epilepticus (SRSE) (P=0.038) were independently associated with differences in etiologies. CONCLUSION: Several clinical features in patients with NORSE, including the age of onset and the development of SRSE, can help identify underlying causes, which necessitate prompt and adequate treatment.

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Status epilepticus in POLG disease: a large multinational study.

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE.

Ketamine reduces seizure and interictal continuum activity in refractory status epilepticus: a multicenter in-person and teleneurocritical care study.

BACKGROUND: There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage, and influence of other variables on seizure cessation while on ketamine infusions are not well studied. We aimed to characterize ketamine effect on RSE, including interictal activity on electroencephalogram (EEG) and when done by Teleneurocritical care (TNCC). METHODS: We conducted a multicenter, retrospective study from August 2017 to October 2022. Patients 18 years or older who had RSE and received ketamine were included. The primary outcome was effect of ketamine on RSE including interictal activity; secondary outcomes were effect of other variables on RSE, care by TNCC, ketamine infusion dynamics, adverse events, and discharge outcomes. Logistic regression was used. RESULTS: Fifty-one patients from five hospitals met inclusion criteria; 30 patients had RSE and interictal activity on EEG. Median age was 56.8 years (IQR 18.2) and 26% had previously diagnosed epilepsy. Sixteen (31%) patients were treated virtually by TNCC. In those with RSE on EEG, ketamine was added as the fourth antiseizure medication (mean 4.4, SD 1.6). An initial bolus of ketamine was used in 24% of patients (95 mg, IQR 47.5), the median infusion rate was 30.8 mcg/kg/min (IQR 40.4), and median infusion duration was 40 h (IQR 37). Ketamine was associated with 50% cessation of RSE and interictal activity at 24 h in 84% of patients, and complete seizure cessation in 43% of patients. In linear regression, ASMs prior to ketamine were associated with seizure cessation (OR 2.6, 95% CI 0.9-6.9, p = 0.05), while the inverse was seen with propofol infusions (OR 0.02, 95% CI 0.001-0.43, p = 0.01). RSE management by in-person NCC versus virtual by TNCC did not affect rates of seizure cessation. CONCLUSIONS: Ketamine infusions for RSE were associated with reduced seizure burden at 24 h, with 84% of patients having 50% seizure reduction. Similar efficacy and safety was observed irrespective of underlying RSE etiology or when done via TNCC vs in-person NCC.

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

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

The efficacy and safety of ketamine in the treatment of super-refractory status epilepticus: a systematic review.

BACKGROUND: Ketamine, as an anesthetic, has been considered for terminating status epilepticus (SE); however, due to the urgency and severity of the condition, there are currently no randomized controlled trials internationally assessing the efficacy of ketamine for treating super-refractory status epilepticus. Similarly, there appears to be a lack of systematic reviews addressing this topic in the literature. Therefore, this systematic review aims to explore the effectiveness and safety of ketamine for terminating super-refractory status epilepticus. METHODS: We conducted a systematic search on PubMed, EMBASE, and Web of Science databases. Manuscripts unrelated to the research on super-refractory status epilepticus were excluded, as were manuscripts published in non-English languages. The quality assessment and risk of bias were evaluated using the MINORS criteria. Data extraction was limited to qualitative synthesis due to the unsuitability of the data for meta-analysis. RESULTS: Out of 782 studies retrieved from electronic databases, 11 met the inclusion criteria. Among them, 10 studies were retrospective, and 1 study was prospective. Patient data for inclusion were sourced from the case registries of the researchers' respective hospitals. Across all included studies, the administration of ketamine significantly reduced the duration of status epilepticus and demonstrated higher safety compared to patients not receiving ketamine treatment for super-refractory status epilepticus. Additionally, early administration of ketamine correlated with improved treatment outcomes. The risk of bias across all studies was deemed low. CONCLUSION: This systematic review suggests that ketamine may be a feasible treatment option for super-refractory status epilepticus. However, given the critical nature of super-refractory status epilepticus, clinicians should prioritize its termination over evaluating the efficacy of specific medications, ensuring patient safety remains paramount. If feasible in real-world medical settings, future research should focus on designing randomized controlled trials to observe the specific efficacy and mechanisms of ketamine. Careful validation is necessary before considering ketamine as a first-line treatment for super-refractory status epilepticus.

High-definition transcranial direct current stimulation desynchronizes refractory status epilepticus.

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 â€‹Hz ("gamma") and lesser power in frequency bands lower than 30 â€‹Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, -5.25%, -1.88%, -1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p â€‹= â€‹0.0001); and +4.13%, -5.44%, -1.81%, -3.23%, and +5.41% in the referential Laplacian montage (p â€‹= â€‹0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: -2.74%, +4.20%, +1.74%, +1.75%, and -4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p â€‹= â€‹0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and -5.12% in the referential Laplacian montage (p â€‹= â€‹0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE.

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

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

Status epilepticus: Is there a Stage 1 plus?

In status epilepticus (SE), "time is brain." Currently, first-line therapy consists of benzodiazepines (BDZs) and SE is classified by the response to treatment; stage 2 or established SE is defined as "BDZ-resistant SE." Nonetheless, this classification does not always work, especially in the case of prolonged convulsive SE, where many molecular changes occur and γ-aminobutyric acid signaling becomes excitatory. Under these circumstances, BDZ therapy might not be optimal, and might be possibly detrimental, if given alone; as the duration of SE increases, so too does BDZ resistance. Murine models of SE showed how these cases might benefit more from synergistic combined therapy from the start. The definition of Stage 1 plus is suggested, as a stage requiring combined therapy from the start, which includes prolonged SE with seizure activity going on for >10 min, the time that marks the disruption of receptor homeostasis, with increased internalization. This specific stage might require a synergistic approach from the start, with a combination of first- and second-line treatment.