Search Results (6)

Status epilepticus (SE) is a neurological emergency. Current evidence dictates a step-by-step approach with a first line of therapy consisting of benzodiazepines (BDZs). In many situations, the currently approved approach does not terminate a BDZ-resistant SE. This happens in Stage 1 Plus, a framework designed by the author to recognize cases of probable benzodiazepine-resistant status epilepticus even before treatment initiation. These cases include Prolonged SE (SE lasting > 10 min), the absence of prominent motor phenomena, and acute etiology (primary central nervous system etiologies most of all). BDZ-refractory SE cases (Stage 1 Plus) might require a different approach, one targeting the unresponsive GABA signaling state mediated by NMDA/AMPA receptors, such as combined polytherapy with Ketamine from the start. These considerations stem from the receptor trafficking hypotheses: in prolonged seizure activity and primary central nervous system etiologies, GABA receptors get internalized and move away from synapses, and therefore, SE becomes resistant to BDZ. A rational polytherapy that might restore the unresponsiveness to BDZ in SE should include NMDA antagonists, such as Ketamine. Ketamine has proven effective in many experimental models of status epilepticus, and much evidence is gathering supporting its use in humans, especially in refractory and super-refractory SE. We lack studies evaluating combined polytherapy in SE, especially in the early phases. The author suggests here that Ketamine should be used along with first-line BDZ in the early SE stage falling in the category of Stage 1 Plus and as a first-line anesthetic infusion drug in refractory SE, especially in cases progressing from Stage 1 Plus, eventually adding continuous midazolam/propofol infusion in later phases. This systematic review’s objective is to summarize the presently available evidence of the early use of combined polytherapy that includes Ketamine, along with the currently available evidence of Ketamine use in early, established, and refractory SE. Nine studies were included. Boluses of Ketamine and Midazolam are effective in pediatric convulsive Stage 1 Plus SE. The results show that earlier Ketamine administration (especially within 12 h of SE onset) was significantly associated with improved seizure control, with a more favorable safety profile than Midazolam in refractory SE. Notably, a dosage of less than 0.9 mg/kg/h proves ineffective in terminating SE. Ketamine has the advantage of preventing intubation, possibly shortening the length of stay in the intensive care unit. Full article

Background/Objectives: Brain magnetic resonance imaging (MRI) often reveals acute peri-ictal abnormalities (PMAs) during or shortly after status epilepticus (SE) but also following single seizures (SiS) or clusters of seizures (CS). However, the incidence, characteristics, and progression remain not clearly known. This study aimed to investigate incidence, clinical correlations, and evolution of PMAs in SE, CS, and SiS patients. Methods: This prospective observational study enrolled patients with SE, CS, and SiS who underwent MRI within 120 h of the ictal event. Demographic, clinical, EEG, and MRI data were collected. Patients with PMAs (PMAs+) underwent serial follow-up MRI. Incidence, association with clinical characteristics, and progression of PMAs were analyzed across the three groups. Results: Among 76 patients (30 SE, 22 CS, 24 SiS), PMAs were observed in 31 (41%), with a significant difference between groups (p = 0.011), as PMAs were less frequent in SiS (17%) compared to SE (57%) and CS (45%) patients. Acute symptomatic SE/seizures were significantly more common in PMAs+ compared to PMAs− in the overall cohort (52% vs. 29%; p = 0.045) and in the SiS group (100% vs. 25%; p = 0.031). History of epilepsy was less frequent in PMAs+ in the whole cohort (13% vs. 40%; p = 0.011) and in SE in particular (12% vs. 46%, p = 0.049). No association between PMAs and seizure type, SE duration, etiology, time to MRI, and EEG findings (p > 0.005) was found. The temporal cortex and hippocampus were most frequently affected by PMAs. Follow-up MRI performed in 16 patients showed resolution of PMAs in 75% (5/7 SE, 3/6 CS, 3/3 SiS) within a median time of 24 days (IQR: 8–39). Conclusions: PMAs were more common in SE and CS than in SiS. Acute underlying pathology was frequently associated with PMAs. While duration of ictal activity is an important factor, it was not the sole determinant. Most PMAs resolved, particularly in SiS. Further studies are needed to clarify the pathophysiological mechanism and clinical implications of PMAs. Full article

Stage 1 Plus is defined here as a naïve, previously untreated, status epilepticus (SE) that is probably refractory to Benzodiazepines (BDZ). These cases include not only prolonged SE as previously proposed by the author (SE lasting > 10 min) but also other cases notoriously associated with BDZ refractoriness such as the absence of prominent motor phenomena and acute etiology (especially primary central nervous system etiology). Interestingly, the absence of prominent motor phenomena as is the case of non convulsive SE might implicitly fall in the category of prolonged SE due to the delay in recognition and treatment. Future studies should help identify other factors associated with BDZ refractoriness, therefore widening the definition of Stage 1 Plus. The appropriate timing for defining prolonged SE may also differ depending on different etiology. Consequently, in future tailored models of SE, the definition of prolonged SE could be enhanced by defining it for a longer duration than Tx, a time point that changes based on different etiologies (x), Tx being much shorter than 10 min in acute etiologies. These cases of naïve probably BDZ refractory SE (Stage 1 Plus) might require a different approach: combined polytherapy from the start. The objective of this review is to provide pathophysiological and pre-clinical evidence, mostly from animal studies, for the different approach of combined polytherapy from the start for those cases of SE falling in the definition of Stage 1 Plus. Full article

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of this study was to identify the prevalence of electrographic seizures and the impact of monitoring in neonates with a high risk of encephalopathy. Methods: We conducted this prospective cohort study in a tertiary neonatal intensive care unit over a 4-year period. Neonates with a high risk of encephalopathy who were receiving continuous video EEG monitoring were eligible. The patients were divided into 2 groups: (1) acute neonatal encephalopathy (ANE) and (2) other high-risk encephalopathy conditions (OHRs). The neonates’ demographic characteristics, etiologies, EEG background feature, presence of electrographic seizures and the impact of monitoring were analyzed. Results: A total of 71 neonates with a high risk of encephalopathy who received continuous video EEG monitoring were enrolled. In this consecutive cohort, 42 (59.2%) were monitored for ANE and 29 (40.8%) were monitored for OHRs. At the time of starting EEG monitoring, 54 (76.1%) of the neonates were term infants. The median gestational age at monitoring was 39 weeks (interquartile range, 37–41 weeks). The median total EEG monitoring duration was 64.7 h (interquartile range, 22.2–72.4 h). Electrographic seizures were captured in 25 of the 71 (35.2%) neonates, of whom 20 (80%) had electrographic-only seizures without clinical correlation. Furthermore, of these 20 neonates, 13 (65%) developed electrographic status epilepticus. Electrographic seizures were most commonly found in the ANE group (17, 40.5%) than in the OHRs group (8, 27.6%) (p = 0.013). Besides, normal/mild abnormality and inactive EEG background were less electrographic seizure than moderate and major abnormality EEG background (2 of 30, 6.7% vs. 23 of 41, 56.1%, p < 0.001). Finally, continuous video EEG monitoring excluded the diagnosis of electrographic seizures in two-thirds of the monitored neonates who had paroxysmal events mimicking seizures and led to a change in clinical management in 39.4% of the neonates. Conclusions: Our findings showed that monitoring could accurately detect seizures, and that it could be used to guide seizure medication management. Therefore, continuous video EEG monitoring has important clinical management implications in neonates with a high risk of encephalopathy. Full article

Objective: This study aimed to identify temporal time trends and risk factors associated with mortality for hospitalized older adults with status epilepticus (SE). Design: A retrospective study was performed. Setting: Hospitalized patients were identified utilizing an administrative database—The Nationwide Inpatient Sample database from 1998 through September 2015. Patients: Patients were older adults 65 years and older with SE. Interventions: No interventions were undertaken. Measurements and Main Results: Demographic, temporal trends, clinical characteristics, and outcome data were abstracted. The results indicated that hospitalized elderly Americans with SE increased over the 11-year study period. Univariate and multivariate analyses were performed to evaluate risk factors associated with mortality in the study cohort. From the weighted sample, 130,109 subjects were included. Overall mortality was 19%. For age subgroups, the mortality was highest for the >85 years age group (24.1%) compared to the 65–75 years (19%) and 75–85 years (23%) age groups. Among investigated etiologies, the three most common causes of SE were acute ischemic stroke (11.2% of total) followed by non-traumatic brain hemorrhage (5.4%) and malignant brain lesions (4.9%). The highest mortality by etiology was noted for acute traumatic brain injury (TBI) (31.5%), non-traumatic brain hemorrhage (31%), and acute ischemic stroke (AIS) (30.1%). Multivariate analysis indicated that non-survivors when compared to survivors were more like to have the following characteristics: older age group, acute TBI, brain neoplasms, non-traumatic brain hemorrhage, AIS and central nervous system (CNS) infections, and utilization of mechanical ventilation. Associated conditions significantly increasing risk of mortality were sodium imbalance, cardiac arrest, anoxic brain injury, pneumonia, and sepsis. Comorbidities associated with increased risk of mortality included valvular heart disease, renal failure, liver disease, and neoplasms. Conclusions: The number of hospitalized elderly Americans with SE increased over the 11-year study period. Overall mortality was 19%, with even higher mortality among various patient subsets. Several demographic and co-morbid factors are associated with increased mortality in this age group. Full article

The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care. Full article