Emergent Management of Status Epilepticus.

OBJECTIVE: Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control. LATEST DEVELOPMENTS: Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option. ESSENTIAL POINTS: As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.

The influence of biological rhythms on the initial onset of status epilepticus in critically ill inpatients and the study of its predictive Model.

This study aims to explore the relationship between the circadian rhythms of critically ill patients and the incidence of Status Epilepticus (SE), and to develop a predictive model based on circadian rhythm indicators and clinical factors. We conducted a diurnal rhythm analysis of vital sign data from 4413 patients, discovering significant differences in the circadian rhythms of body temperature, blood oxygen saturation, and heart rate between the SE and non-SE groups, which were correlated with the incidence of SE. We also employed various machine learning algorithms to identify the ten most significant variables and developed a predictive model with strong performance and clinical applicability. Our research provides a new perspective and methodology for the study of biological rhythms in critically ill patients, offering new evidence and tools for the prevention and treatment of SE. Our findings are consistent or similar to some in the literature, while differing from or supplementing others. We observed significant differences in the vital signs of epileptic patients at different times of the day across various diagnostic time groups, reflecting the regulatory effects of circadian rhythms. We suggest heightened monitoring and intervention of vital signs in critically ill patients, especially during late night to early morning hours, to reduce the risk of SE and provide more personalized treatment plans.

Periodic discharges and status epilepticus: A critical reappraisal.

OBJECTIVE: Periodic Discharges (PDs) in Status Epilepticus (SE) are historically related to negative outcome, and the Epidemiology-based Mortality Score in SE (EMSE) identifies PDs as an EEG feature associated with unfavorable prognosis. However, supportive evidence is conflicting. This study aims to evaluate the prognostic significance of interictal PDs during and following SE. METHODS: All 2020-2023 non-hypoxic-ischemic SE patients with available EEG during SE were retrospectively assessed. Interictal PDs during SE (SE-PDs) and PDs occurring 24-72 h after SE resolution (post-SE-PDs) were examined. In-hospital death was defined as the primary outcome. RESULTS: 189 SE patients were finally included. SE-PDs were not related to outcome, while post-SE-PDs were related to poor prognosis confirmed after multiple regression analysis. EMSE global AUC was 0.751 (95%CI:0.680-0.823) and for EMSE-64 cutoff sensitivity was 0.85, specificity 0.52, accuracy 63%. We recalculated EMSE score including only post-SE-PDs. Modified EMSE (mEMSE) global AUC was 0.803 (95%CI:0.734-0.872) and for mEMSE-64 cutoff sensitivity was 0.84, specificity 0.68, accuracy 73%. CONCLUSION: Interictal PDs during SE were not related to outcome whereas PDs persisting or appearing > 24 h after SE resolution were strongly associated to unfavorable prognosis. EMSE performed well in our cohort but considering only post-SE-PDs raised specificity and accuracy for mEMSE64 cutoff. SIGNIFICANCE: This study supports the utility of differentiating between interictal PDs during and after SE for prognostic assessment.

Ictal Cotard delusion as a manifestation of nonconvulsive status epilepticus: A case report and commentary.

Psychosis of epileptic origin can present a wide range of cognitive and affective symptoms and is often underrecognized. Usually occurring in the inter- and postictal phase, epileptic psychosis is mostly related to temporal lobe epilepsy. Here, we describe the clinical presentation and diagnostic workup including routine EEG recording and brain MRI of a 63-year-old woman expressing isolated nihilistic delusions comprising belief of being dead and denial of self-existence. EEG showed an ictal pattern fulfilling the Salzburg criteria of nonconvulsive status epilepticus and brain MRI revealed extensive peri-ictal hyperperfusion. Delusional symptoms and EEG abnormalities subsided after acute antiseizure treatment. Our case illustrates how nihilistic delusions can occur as a direct clinical correlate of seizure activity, thereby expanding the spectrum of ictal neuropsychiatric phenomena in temporal lobe epilepsy and highlighting the need to consider an epileptic origin in patients presenting with psychotic symptoms.

[Long-term follow-up of adult patients with serial and status course of epileptic seizures]. / Dolgosrochnyi katamnez vzroslykh patsientov s epilepsiei s epilepticheskim statusom ili seriinymi pristupami.

OBJECTIVE: To study the follow-up of adult patients with status epilepticus or a history of serial seizures, assessing the likelihood of achieving long-term remission and identifying predictors of treatment effectiveness. MATERIAL AND METHODS: The study included 280 patients divided into 137 patients with epilepsy with a series of seizures or a history of status epilepticus (group 1) and 143 patients, who had not previously received therapy and did not have a series of seizures or a history of status epilepticus (group 2). A clinical and neurological examination, analysis of medical documentation data, electroencephalography, and MRI were performed. RESULTS: After correction of therapy, remission in patients in group 1 was achieved in 21.9%, improvement in 30%, no effect was observed in 48.1%; in group 2 the indicators were 51%, 28.7%, 20.3%, respectively. The onset of epilepsy in childhood, frequent seizures, and regional epileptiform activity were associated with the lack of treatment effect. CONCLUSION: The results confirm the main role of the clinical examination in determining the prognosis of epilepsy in a particular patient. Currently available instrumental techniques have limited predictive value.

Using scalp EEG to predict seizure recurrence and electrical status epilepticus in children with idiopathic focal epilepsy.

PURPOSE: Some individuals with idiopathic focal epilepsy (IFE) experience recurring seizures accompanied by the evolution of electrical status epilepticus during sleep (ESES). Here, we aimed to develop a predictor for the early detection of seizure recurrence with ESES in children with IFE using resting state electroencephalogram (EEG) data. METHODS: The study group included 15 IFE patients who developed seizure recurrence with ESES. There were 17 children in the control group who did not experience seizure recurrence with ESES during at least 2-year follow-up. We used the degree value of the partial directed coherence (PDC) from the EEG data to predict seizure recurrence with ESES via 6 machine learning (ML) algorithms. RESULTS: Among the models, the Xgboost Classifier (XGBC) model achieved the highest specificity of 0.90, and a remarkable sensitivity and accuracy of 0.80 and 0.85, respectively. The CATC showed balanced performance with a specificity of 0.85, sensitivity of 0.73, and an accuracy of 0.80, with an AUC equal to 0.78. For both of these models, F4, Fz and T4 were the overlaps of the top 4 features. CONCLUSIONS: Considering its high classification accuracy, the XGBC model is an effective and quantitative tool for predicting seizure recurrence with ESES evolution in IFE patients. We developed an ML-based tool for predicting the development of IFE using resting state EEG data. This could facilitate the diagnosis and treatment of patients with IFE.

Responsive neurostimulation as a therapy for epilepsy following new-onset refractory status epilepticus: Case series and review of the literature.

OBJECTIVE: To report clinical outcomes of patients who presented with new-onset refractory status epilepticus (NORSE), developed drug-resistant epilepsy (DRE), and were treated with responsive neurostimulation (RNS). METHODS: We performed a retrospective review of patients implanted with RNS at our institution and identified three who originally presented with NORSE. Through chart review, we retrieved objective and subjective information related to their presentation, workup, and outcomes including patient-reported seizure frequency. We reviewed electrocorticography (ECoG) data to estimate seizure burden at 3, 6, 12, and 24 months following RNS implantation. We performed a review of literature concerning neurostimulation in NORSE. RESULTS: Use of RNS to treat DRE following NORSE was associated with reduced seizure burden and informed care by differentiating epileptic from non-epileptic events. CONCLUSIONS: Our single-center experience of three cases suggests that RNS is a safe and potentially effective treatment for DRE following NORSE. SIGNIFICANCE: This article reports outcomes of the largest case series of NORSE patients treated with RNS. Since patients with NORSE are at high risk of adverse neuropsychiatric and cognitive sequelae beyond seizures, a unique strength of RNS over other surgical options is the ability to distinguish ictal or peri-ictal from non-epileptic events.

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.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication.

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

Brain connectivity in status epilepticus as a predictor of outcome: A diffusion tensor imaging study.

BACKGROUND AND PURPOSE: We aimed to explore structural connectivity in status epilepticus. METHODS: We enrolled participants who underwent diffusion tensor imaging. We applied graph theory to investigate structural connectivity. We compared the structural connectivity measures between patients and healthy controls and between patients with poor (modified Rankin Scale [mRS] >3) and good (mRS ≤3) admission outcomes. RESULTS: We enrolled 28 patients and 31 healthy controls (age 65.5 vs.62.0 years, p = .438). Of these patients, 16 and 12 showed poor and good admission outcome (age 65.5 vs.62.0 years, p = .438). The assortative coefficient (-0.113 vs. -0.121, p = .021), mean clustering coefficient (0.007 vs.0.006, p = .009), global efficiency (0.023 vs.0.020, p = .009), transitivity (0.007 vs.0.006, p = .009), and small-worldness index (0.006 vs.0.005, p = .021) were higher in patients with status epilepticus than in healthy controls. The assortative coefficient (-0.108 vs. -0.119, p = .042), mean clustering coefficient (0.007 vs.0.006, p = .042), and transitivity (0.008 vs.0.007, p = .042) were higher in patients with poor admission outcome than in those with good admission outcome. MRS score was positively correlated with structural connectivity measures, including the assortative coefficient (r = 0.615, p = .003), mean clustering coefficient (r = 0.544, p = .005), global efficiency (r = 0.515, p = .007), transitivity (r = 0.547, p = .007), and small-worldness index (r = 0.435, p = .024). CONCLUSION: We revealed alterations in structural connectivity, showing increased integration and segregation in status epilepticus, which might be related with neuronal synchronization. This effect was more pronounced in patients with a poor admission outcome, potentially reshaping our understanding for comprehension of status epilepticus mechanisms and the development of more targeted treatments.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Microstructural evaluation of the brain with advanced magnetic resonance imaging techniques in cases of electrical status epilepticus during sleep (ESES).

Background/aim: The cause and treatment of electrical status epilepticus during sleep (ESES), one of the epileptic encephalopathies of childhood, is unclear. The aim of this study was to evaluate possible microstructural abnormalities in the brain using advanced magnetic resonance imaging (MRI) techniques in ESES patients with and without genetic mutations. Materials and methods: This research comprised 12 ESES patients without structural thalamic lesions (6 with genetic abnormalities and 6 without) and 12 healthy children. Whole-exome sequencing was used for the genetic mutation analysis. Brain MRI data were evaluated using tractus-based spatial statistics, voxel-based morphometry, a local gyrification index, subcortical shape analysis, FreeSurfer volume, and cortical thickness. The data of the groups were compared. Results: The mean age in the control group was 9.05 ± 1.85 years, whereas that in the ESES group was 9.45 ± 2.72 years. Compared to the control group, the ESES patients showed higher mean thalamus diffusivity (p < 0.05). ESES patients with genetic mutations had lower axial diffusivity in the superior longitudinal fasciculus and gray matter volume in the entorhinal region, accumbens area, caudate, putamen, cerebral white matter, and outer cerebellar areas. The superior and middle temporal cortical thickness increased in the ESES patients. Conclusion: This study is important in terms of presenting the microstructural evaluation of the brain in ESES patients with advanced MRI analysis methods as well as comparing patients with and without genetic mutations. These findings may be associated with corticostriatal transmission, ictogenesis, epileptogenesis, neuropsychiatric symptoms, cognitive impairment, and cerebellar involvement in ESES. Expanded case-group studies may help to understand the physiology of the corticothalamic circuitry in its etiopathogenesis and develop secondary therapeutic targets for ESES.

Phenotype of heterozygous variants of dehydrodolichol diphosphate synthase.

AIM: To further identify and broaden the phenotypic characteristics and genotype spectrum of the dehydrodolichol diphosphate synthase (DHDDS) gene. METHOD: Pathogenic variants of DHDDS were identified by whole-exome sequencing; clinical data of 10 patients (six males, four females; age range 2-14y; mean age 5y 9mo, SD 3y 3mo) were collected and analysed. RESULTS: All patients had seizures, and myoclonic seizures could be seen in eight patients, with myoclonic status epilepticus in three. The interictal electroencephalogram (EEG) in four patients at seizure onset showed generalized slow waves, slow wave mixed spikes, and spike and waves. Tremor, ataxia, and hypertonia was observed in six, five, and three patients respectively. The results of short-latency somatosensory evoked potential in two patients were normal, and the symptom of tremor was captured on EEG without time-locked discharges in one patient, suggesting that the tremor in both patients was a motor impairment rather than myoclonic seizures. Global developmental delay occurred in all patients, among whom nine showed severe intellectual disability and one moderate. Five DHDDS variants were identified, three of which have not been reported previously. INTERPRETATION: Myoclonic seizure is the most common seizure type in heterozygous DHDDS variants, while myoclonic status epilepticus can also occur. The pattern of interictal EEG discharges is characterized by slow waves rather than spike and waves, and generalized discharges was prominent.

Clinical findings, etiological factors, and prognosis markers in status epilepticus: a university hospital experience.

OBJECTIVE: To determine the factors affecting mortality and disability in status epilepticus (SE) and to evaluate the prediction ability of the Status Epilepticus Severity Score (STESS) for disability and mortality. MATERIALS AND METHOD: The demographic and clinical characteristics, prognosis and prognosis predictors of 72 patients who were diagnosed with SE between 2013 and 2018 were retrospectively evaluated. The STESS was used to predict prognosis, and the modified Rankin scale (mRS) was used to determine the disability at discharge. RESULTS: The study population had a mean age of 45.4 ± 20.7, and it was found that mortality was 22.2% and acute symptomatic etiology played a 54.1% role in etiology. Advanced age, refractory SE or super-refractory SE, acute symptomatic etiology, and a history of epilepsy were related to mortality, symptomatic etiology (acute, progressive, remote), a history of hospitalization and epilepsy in intensive care or in other departments other than the neurology department were associated with disability. The sensitivity of STESS in predicting mortality was 100%, specificity was 69%, accuracy was 76.4%, positive predictive value (PPV) was 48.5%, and the negative predictive value (NPV) was 100%. The sensitivity of STESS in predicting mobilization during discharge was 55.6% with a 63.9% specificity and 59.7% accuracy, PPV was 60.6%, and NPV was 59%. CONCLUSION: It was observed that STESS strongly predicts a good prognosis; however, it was not found to be useful in predicting motor disability during discharge. Thus, new studies should be conducted to predict and evaluate mobility in SE patients at discharge.

Acute encephalopathy with biphasic seizures and late reduced diffusion: Predictive EEG findings.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a common type of acute encephalopathy in Japan; the condition is clinically characterized by prolonged seizures as the initial neurological symptom, followed by late seizures 4-6 days later. It is difficult to differentiate AESD from prolonged febrile seizures (PFSs). Here, we explored the use of electroencephalography to differentiate AESD from PFSs. METHODS: We studied the electroencephalograms (EEGs) of children <6 years of age diagnosed with AESD or PFSs; all EEGs were recorded within 48 h of seizure onset (i.e., before the late seizures of AESD). Two pediatric neurologists evaluated all EEGs, focusing on the basic rhythm, slowing during wakefulness/arousal by stimuli, spindles, fast waves, and slowing during sleep. RESULTS: The EEGs of 14 children with AESD and 31 children with PFSs were evaluated. Spindles were more commonly reduced or absent in children with AESD than in those with PFSs (71% vs. 31%, p = 0.021). Fast waves were also more commonly reduced or absent in children with AESD (21% vs. 0%, p = 0.030). The rates of all types of slowing did not differ between children with AESD and those with PFSs, but continuous or frequent slowing during sleep was more common in the former (50% vs. 17%, p = 0.035). CONCLUSIONS: EEG findings may usefully differentiate AESD from PFSs. Reduced or absent spindles/fast waves and continuous or frequent slowing during sleep are suggestive of AESD in children with prolonged seizures associated with fever.

Progression of alternating hemiplegia of childhood-related focal epilepsy to electrical status epilepticus in sleep with reversible encephalopathy.

Mutations in the ATP1A3 gene (which encodes the main α subunit in neuronal Na+/K+-ATPases) cause various neurological syndromes including alternating hemiplegia of childhood. This rare disorder is characterized by paroxysmal episodes of hemiplegia, dystonia, oculomotor abnormalities, and occasionally developmental regression. Approximately 50% of alternating hemiplegia of childhood patients also have epilepsy, which is either focal or generalized. Seizures are often drug resistant. We report a 10-year-old girl with the D801N ATP1A3 mutation and alternating hemiplegia of childhood who manifested with drug-resistant focal seizures as an infant and throughout childhood. At the age of about10.5 years, her epilepsy evolved into electrical status epilepticus in sleep with generalized discharges. These changes coincided with developmental regression consistent with epileptic encephalopathy. Additionally, MRI and MR spectroscopy showed new cortical atrophy and markedly depressed N-acetyl aspartate peaks compared to previous normal studies. Electrical status epilepticus in sleep resolved after medication adjustments. She, now, only four months after her diagnosis of electrical status epilepticus in sleep, has regained most of the skills that were lost only a few months earlier. Our observations document that alternating hemiplegia of childhood can result in the above-described unique features; particularly, progression of focal epilepsy to electrical status epilepticus in sleep with generalized features and reversible epileptic encephalopathy.

Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice.

Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg/kg; i.p.) as a standard drug and chondroitin sulfate (100 & 200 mg/kg, p.o.) significantly (p < 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1ß, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1ß, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.