Fluid Biomarkers of Neuro-Glial Injury in Human Status Epilepticus: A Systematic Review

As per the latest ILAE definition, status epilepticus (SE) may lead to long-term irreversible consequences, such as neuronal death, neuronal injury, and alterations in neuronal networks. Consequently, there is growing interest in identifying biomarkers that can demonstrate and quantify the extent of neuronal and glial injury. Despite numerous studies conducted on animal models of status epilepticus, which clearly indicate seizure-induced neuronal and glial injury, as well as signs of atrophy and gliosis, evidence in humans remains limited to case reports and small case series. The implications of identifying such biomarkers in clinical practice are significant, including improved prognostic stratification of patients and the early identification of those at high risk of developing irreversible complications. Moreover, the clinical validation of these biomarkers could be crucial in promoting neuroprotective strategies in addition to antiseizure medications. In this study, we present a systematic review of research on biomarkers of neuro-glial injury in patients with status epilepticus

New onset status epilepticus in influenza associated encephalopathy: The presenting manifestation of genetic generalized epilepsy

We hereby present a case of a young woman with no history of seizures or epilepsy who experienced a de novo generalized Non Convulsive Status Epilepticus (NCSE) followed by encephalopathy lasting for several days during influenza B infection. Influenza can have a broad spectrum of presentation ranging from an uncomplicated illness to many serious conditions as is the case of influenza associated encephalitis/encephalopathy (IAE). In this context however, it is possible to observe seizures and/or status epilepticus as the presenting manifestation of a genetic generalized epilepsy

Case Report: Ictal Central Apnea as First and Overlooked Symptom in Temporal Lobe Seizures

Ictal respiratory changes have been mainly described following generalized tonic-clonic seizures and recently considered to be a biomarker to assess the risk of sudden unexplained death in epilepsy (SUDEP). Nonetheless, modification of respiratory pattern can be related also to focal seizures, especially arising from the temporal lobe. Changes in cardiac function such as tachycardia or bradycardia could be often associated. We report a short case series of four patients with temporal lobe epilepsy admitted to our Epilepsy Monitoring Unit (EMU) presenting with an ictal central apnea as the first clinical manifestation of their seizures. None of these patients was aware of the occurrence of respiratory arrest. Age at onset ranged from 15 to 29 years. One patient had seizures with prolonged central apnea accompanied by a significant decrease in oxygen saturation. Neuroimaging in two patients showed alterations of mesial temporal lobe structures, including the amygdala. Recent neurophysiological studies supported the existence of a cortical network involving the limbic system that modulates downstream brainstem respiratory centers. Monitoring for respiratory changes and oxygen saturation in focal seizures is warranted for their potential value in identifying the epileptogenic zone and for a better understanding of ictal respiratory changes that could potentially define a subgroup of patients with high risk of seizure-related autonomic changes

A WebGIS tool for the dissemination of earthquake data

In 2004 a new seismic hazard map of Italy (MPS Working Group, 2004) has been released by a task force that produced an amount of new or updated data, such as a new version of the earthquake catalogue (CPTI04; CPTI Working Group, 2004) and an updated seismogenic zonation. A set of WebGIS tools has been designed for the data dissemination to the scientific community and the general public. The design of the WebGIS tools focused first on the consultation of the DBM04 macroseismic database (DBM Working Group, 2005), which contains the macroseismic intensity data-points (IDP) of the earthquakes listed in the CPTI04 catalogue. The WebGIS tool design and development process had to fulfill: 1) simplicity, 2) responsiveness and 3) readiness for future extensions. The specific requirements for the macroseismic database consultation interface were: - data access by place and by earthquake; - IDP maps with queryable points; - data download in both tabular and map format; - easily upgradable content; - quick and user friendly interface

Seismic hazard in the Po Plain and the 2012 Emilia earthquakes

The Emilia earthquakes of May 20, 2012 (ML 5.9, INGV; MW 6.11, http://www.bo.ingv.it/RCMT/) and May 29, 2012 (ML 5.8, INGV; MW 5.96, http://www.bo.ingv.it/RCMT/) struck an area that in the national reference seismic hazard model [MPS04; http://zonesismiche.mi.ingv.it, and Stucchi et al. 2011] is characterized by expected horizontal peak ground acceleration (PGA) with a 10% probability of exceedance in 50 years that ranges between 0.10 g and 0.15 g (Figure 1), which is a medium level of seismic hazard in Italy. The strong impact of the earthquakes on a region that is not included among the most hazardous areas of Italy, and the ground motion data recorded by accelerometric networks, have given the impression to the population and the media that the current seismic hazard map is not correct, and thus needs to be updated. Since the MPS04 seismic hazard model was adopted by the current Italian building code [Norme Tecniche per le Costruzioni 2008, hereafter termed NTC08; http://www.cslp. it/cslp/] as the basis to define seismic action (the design spectra), any modification to the seismic hazard model would also affect the building code. The aim of this paper is to briefly present the data that support the seismic hazard model in the area, and to perform some comparisons between recorded ground motion with seismic hazard estimates and design spectra. All of the comparisons presented in this study are for the horizontal components only, as the Italian hazard model did not perform any estimates for the vertical component

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

The Role of Early Intubation in Status Epilepticus with Out-of-Hospital Onset: A Large Prospective Observational Study

Background: this study aimed to evaluate the role of early airway management and intubation in status epilepticus (SE) with out-of-hospital onset. Methods: We included all patients with out-of-hospital SE onset referred to the emergency department of the Academic Hospital of Modena between 2013 and 2021. Patients were compared according to out-of-hospital airway management (intubation versus non-intubation) and a propensity score was performed for clinical variables unevenly distributed between the two groups. Results: We evaluated 711 patients with SE. A total of 397 patients with out-of-hospital SE onset were eventually included; of these, 20.4% (81/397) were intubated before arrival at the hospital. No difference was found in the clinical characteristics of patients after propensity score matching. The 30-day mortality in the propensity group was 19.4% (14/72), and no difference was found between intubated (7/36, 19.4%) and non-intubated (7/36, 19.4%) patients. No difference was found in SE cessation. Compared to non-intubated patients, those who underwent out-of-hospital intubation had a higher risk of progression to refractory or super-refractory SE, greater worsening of mRS values between hospital discharge and admission, and lower probability of returning to baseline condition at 30 days after SE onset. Conclusions: Early intubation for out-of-hospital SE onset is not associated with improved patient survival even after balancing for possible confounders. Further studies should evaluate the timing of intubation and its association with first-line treatments for SE and their efficacy. In addition, they should focus on the settings and the exact reasons leading to intubation to better inform early management of SE with out-of-hospital onset

Temporal Lobe Spikes Affect Distant Intrinsic Connectivity Networks

Objective: To evaluate local and distant blood oxygen level dependent (BOLD) signal changes related to interictal epileptiform discharges (IED) in drug-resistant temporal lobe epilepsy (TLE). Methods: Thirty-three TLE patients undergoing EEG–functional Magnetic Resonance Imaging (fMRI) as part of the presurgical workup were consecutively enrolled. First, a single-subject spike-related analysis was performed: (a) to verify the BOLD concordance with the presumed Epileptogenic Zone (EZ); and (b) to investigate the Intrinsic Connectivity Networks (ICN) involvement. Then, a group analysis was performed to search for common BOLD changes in TLE. Results: Interictal epileptiform discharges were recorded in 25 patients and in 19 (58%), a BOLD response was obtained at the single-subject level. In 42% of the cases, BOLD changes were observed in the temporal lobe, although only one patient had a pure concordant finding, with a single fMRI cluster overlapping (and limited to) the EZ identified by anatomo-electro-clinical correlations. In the remaining 58% of the cases, BOLD responses were localized outside the temporal lobe and the presumed EZ. In every patient, with a spike-related fMRI map, at least one ICN appeared to be involved. Four main ICNs were preferentially involved, namely, motor, visual, auditory/motor speech, and the default mode network. At the single-subject level, EEG–fMRI proved to have high specificity (above 65%) in detecting engagement of an ICN and the corresponding ictal/postictal symptom, and good positive predictive value (above 67%) in all networks except the visual one. Finally, in the group analysis of BOLD changes related to IED revealed common activations at the right precentral gyrus, supplementary motor area, and middle cingulate gyrus. Significance: Interictal temporal spikes affect several distant extra-temporal areas, and specifically the motor/premotor cortex. EEG–fMRI in patients with TLE eligible for surgery is recommended not for strictly localizing purposes rather it might be useful to investigate ICNs alterations at the single-subject level

Serum neurofilament light as biomarker of seizure-related neuronal injury in status epilepticus

Biomarkers of neuronal damage in status epilepticus (SE) would be of great relevance for clinical and research purposes. In a retrospective cross-sectional study, serum neurofilament light chain (NfL) levels were measured in patients with SE (30 subjects), patients with drug-resistant epilepsy (30 subjects), and healthy controls (30 subjects). Serum NfL levels were higher in patients with SE (median = 26.15 pg/ml) compared to both epilepsy patients (median = 7.35 pg/ml) and healthy controls (median = 6.81 pg/ml; p <.001). In patients with SE, serum NfL levels showed a high correlation with cerebrospinal fluid (CSF) NfL (τ =.68, p <.001) as well as with CSF total tau (t-tau) levels (τ =.627, p <.001); they were higher in SE lasting >24 h (p =.013), in refractory/superrefractory SE (p =.004), and in patients who died within 30 days or who presented a worsening of clinical conditions (p =.001). Values of >28.8 pg/ml predicted 30-day clinical worsening or death (odds ratio [OR] = 10.83, 95% confidence interval [CI] = 1.96–59.83, p =.006) and SE refractoriness (OR = 9.33, 95% CI = 1.51–57.65, p =.016). In conclusion, serum NfL levels are increased in SE and correlate with SE treatment response, duration, and outcomes, therefore representing a promising biomarker of seizure-related neuronal damage