Late-onset temporal lobe epilepsy: insights from brain atrophy and Alzheimer's disease biomarkers.

Considering the growing age of the world population, the incidence of epilepsy in older adults is expected to increase significantly. It has been suggested that late-onset temporal lobe epilepsy (LO-TLE) may be neurodegenerative in origin and overlap with Alzheimer's Disease (AD). Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total and phosphorylated tau, and ß-amyloid) in a selected population of LO-TLE of unknown origin. We prospectively enrolled individuals with temporal lobe epilepsy onset after the age of 50 and no cognitive impairment. They underwent a structural MRI scan and CSF biomarkers measurement. Imaging and biomarkers data were compared to three retrospectively collected groups: (i) age-sex-matched healthy controls, (ii) patients with Mild Cognitive Impairment (MCI) and abnormal CSF AD biomarkers (MCI-AD), and (iii) patients with MCI and normal CSF AD biomarkers (MCI-noAD). From a pool of 52 patients, twenty consecutive eligible LO-TLE patients with a mean disease duration of 1.8 years were recruited. As control populations, 25 patients with MCI-AD, 25 patients with MCI-noAD, and 25 healthy controls were enrolled. CSF biomarkers returned normal values in LO-TLE, significantly different from patients with MCI due to AD. There were no differences in cortico-subcortical atrophy between epilepsy patients and healthy controls, while patients with MCI demonstrated widespread injuries of cortico-subcortical structures. Individuals with a late-onset form of temporal lobe epilepsy, characterized by short disease duration and normal CSF ß-amyloid and tau protein levels, showed patterns of cortical thickness and subcortical volumes not significantly different from healthy controls, but highly different from patients with MCI, either due to Alzheimer's Disease or not.

Futile recanalization is associated with increased risk of post-stroke epilepsy.

BACKGROUND: Endovascular treatment (EVT) is the standard of care of ischaemic stroke due to occlusion of large vessels. Although EVT can significantly improve short- and long-term outcomes, functional dependence can persist despite the achievement of a successful recanalization. The evidence about the predictors of post-stroke epilepsy (PSE) in patients with stroke treated by EVT is limited. We aimed to evaluate the relationship between futile recanalization and the risk of PSE. METHODS: We retrospectively identified consecutive adults with first-ever ischaemic stroke of anterior circulation who were treated with EVT. Futile recanalization was defined as poor 3-month functional status (modified Rankin scale score ≥ 3) despite complete or near-complete recanalization. Study outcome was the occurrence of PSE during the follow-up. RESULTS: The study included 327 patients with anterior circulation ischaemic stroke treated with EVT. Futile recanalization occurred in 116 (35.5%) patients and 26 (8.0%) developed PSE during a median follow-up of 35 [interquartile range, 22.7-55.2] months. Futile recanalization was more common among patients who developed PSE compared to those who did not (76.9% versus 31.9%; p < 0.001). Futile recanalization [hazard ratio (HR) = 5.63, 95% confidence interval (CI): 1.88-16.84; p = 0.002], large artery atherosclerosis (HR = 3.48, 95% CI: 1.44-8.40; p = 0.006), cortical involvement (HR = 15.51, 95% CI: 2.06-116.98; p = 0.008), and acute symptomatic status epilepticus (HR = 14.40, 95% CI: 2.80-73.98; p = 0.001) increased the risk of PSE. CONCLUSIONS: Futile recanalization after EVT is associated with increased risk of PSE in patients with ischaemic stroke due to occlusion of large vessel of the anterior circulation.

FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review.

FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

PSYCHOACOUSTICS-WEB: A free online tool for the estimation of auditory thresholds.

PSYCHOACOUSTICS-WEB is an online tool written in JavaScript and PHP that enables the estimation of auditory sensory thresholds via adaptive threshold tracking. The toolbox implements the transformed up-down methods proposed by Levitt (Journal of the Acoustical Society of America, 49, 467-477, (1971) for a set of classic psychoacoustical tasks: frequency, intensity, and duration discrimination of pure tones; duration discrimination and gap detection of noise; and amplitude modulation detection with noise carriers. The toolbox can be used through a common web browser; it works with both fixed and mobile devices, and requires no programming skills. PSYCHOACOUSTICS-WEB is suitable for laboratory, classroom, and online testing and is designed for two main types of users: an occasional user and, above all, an experimenter using the toolbox for their own research. This latter user can create a personal account, customise existing experiments, and share them in the form of direct links to further users (e.g., the participants of a hypothetical experiment). Finally, because data storage is centralised, the toolbox offers the potential for creating a database of auditory skills.

Botulinum neurotoxin as early treatment in acute-onset lesional hemiballism.

BACKGROUND: Hemiballism (HB) and hemichorea (HC) are the most frequent secondary movement disorders, usually caused by cerebrovascular diseases. In only a minority of cases, these involuntary movements are not self-limited, and they may severely compromise patients' quality of life, so that symptomatic treatments are required. Typical and atypical neuroleptics as well as tetrabenazine are considered therapies of choice. However, anecdotal reports of antiseizures medications and botulinum neurotoxin injection effectiveness have been described. METHODS: We described a case of severely disabling acute-onset lesional HB/HC, where high dosage of first- and second-line therapies was contraindicated due to patient's comorbidities. RESULTS: After botulin neurotoxin (BoNT) injections in his left upper limb muscles (biceps brachii, triceps brachii, teres major, and deltoid), the patient experienced gradual reduction of hyperkinetic movements. The gradual discontinuation of topiramate (TPM) did not worsen the clinical picture. DISCUSSION: The reduction of hyperkinetic movements led to rhabdomyolysis resolution as well as cutaneous injuries healing with renal function improvement, so that the patient was able to be eligible for rehabilitation, which was prevented by HB/HC itself. The clinical improvement was consistent with BoNT pharmacokinetic. The administration of BoNT early after the onset of lesional HB/HC remarkably modified the clinical management and drove toward comorbidities resolution and rehabilitation. CONCLUSION: The present case highlights the effectiveness of unconventional therapeutic options in disabling acute onset lesional HB/HC when first-line therapies are contraindicated. Particularly, this report may encourage BoNT application in the early stage of movement disorder emergencies.

The risk of unprovoked seizure occurrence after status epilepticus in adults.

OBJECTIVE: Status epilepticus (SE) may lead to long-term consequences. This study evaluated the risk and predictors of seizure occurrence after SE, with a focus on SE due to acute symptomatic etiologies. METHODS: Prospectively collected data about adults surviving a first non-hypoxic SE were reviewed. The outcome was the occurrence of unprovoked seizures during the follow-up. Kaplan-Meier survival curve analysis and log-rank test were used to analyze the time to seizure occurrence and determine the statistical significance between etiological groups. Three subcategories within acute etiology were considered according to the presence of the following: (1) structural lesion (acute-primary); (2) brain involvement during systemic disorders (acute-secondary); and (3) drug or alcohol intoxication/withdrawal (acute-toxic). Cox proportional hazards model was adopted to estimate hazard ratios (HRs) with the 95% confidence intervals (CIs). RESULTS: Two hundreds fifty-seven individuals were included. Fifty-four subjects (21.0%) developed seizures after a median of 9.9 (interquartile range 4.3-21.7) months after SE. The estimated 1-, 2-, and 5-year rates of seizure occurrence according to acute SE etiologies were 19.4%, 23.4%, and 30.1%, respectively, for acute-primary central nervous system (CNS) pathology; 2.2%, 2.2%, and 8.7%, respectively, for acute-secondary CNS pathology; and 0%, 9.1%, and 9.1%, respectively, for acute-toxic causes. Five-year rates of seizure occurrence for non-acute SE causes were 33.9% for remote, 65.7% for progressive, and 25.9% for unknown etiologies. In multivariate Cox regression model, progressive etiology (adjusted HR [adjHR] 2.27, 95% CI 1.12-4.58), SE with prominent motor phenomena evolving in non-convulsive SE (adjHR 3.17, 95% CI 1.38-7.25), and non-convulsive SE (adjHR 2.38, 95% CI 1.16-4.90) were independently associated with higher hazards of unprovoked seizures. Older people (adjHR .98, 95% CI .96-.99) and people with SE due to acute-secondary CNS pathology (adjHR .18, 95% CI .04-.82) were at decreased risk of seizure occurrence. SIGNIFICANCE: SE carries a risk of subsequent seizures. Both the underlying cause and epileptogenic effects of SE are likely to contribute.

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.

Remote seizures and drug-resistant epilepsy after a first status epilepticus in adults.

BACKGROUND AND PURPOSE: Long-term consequences after status epilepticus (SE) represent an unsettled issue. We investigated the incidence of remote unprovoked seizures (RS) and drug-resistant epilepsy (DRE) in a cohort of first-ever SE survivors. METHODS: A retrospective, observational, and monocentric study was conducted on adult patients (age ≥ 14 years) with first SE who were consecutively admitted to the Modena Academic Hospital, Italy (September 2013-March 2022). Kaplan-Meier survival analyses were used to calculate the probability of seizure freedom following the index event, whereas Cox proportional hazard regression models were used to identify outcome predictors. RESULTS: A total of 279 patients were included, 57 of whom (20.4%) developed RS (mean follow-up = 32.4 months). Cumulative probability of seizure freedom was 85%, 78%, and 68% respectively at 12 months, 2 years, and 5 years. In 45 of 57 patients (81%), the first relapse occurred within 2 years after SE. The risk of RS was higher in the case of structural brain damage (hazard ratio [HR] = 2.1, 95% confidence interval [CI] = 1.06-4.01), progressive symptomatic etiology (HR = 2.7, 95% CI = 1.44-5.16), and occurrence of nonconvulsive evolution in the semiological sequence of SE (HR = 2.9, 95% CI = 1.37-6.37). Eighteen of 57 patients (32%) developed DRE; the risk was higher in the case of super-refractory (p = 0.006) and non-convulsive SE evolution (p = 0.008). CONCLUSIONS: The overall risk of RS was moderate, temporally confined within 2 years after the index event, and driven by specific etiologies and SE semiology. Treatment super-refractoriness and non-convulsive SE evolution were associated with DRE development.

The Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19): Italian language translation and validation.

OBJECTIVE: Epilepsy surgery can be proposed as a treatment option in people with focal epilepsy, however satisfaction with epilepsy surgery in Italy remains unknown. We aimed to validate in Italy an instrument to measure patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). METHODS: Consecutive patients with epilepsy who received epilepsy surgery between the years 2018-2021 at Modena Academic Hospital were recruited and provided clinical and demographic data. The Italian version of the ESSQ-19 and other three questionnaires were completed to assess construct validity. To evaluate the validity and reliability of the tool Spearman's rank correlation, and internal consistency analysis were performed. RESULTS: 66 out of 79 eligible patients participated in the study (22 females; median age 37 years). The mean values of satisfaction for each domain of the IT-ESSQ-19 were: seizure control 83.4; (SD 16.7), psychosocial functioning 79.3 (SD 17.1), surgical complications 90.8 (SD 14.9), and recovery from surgery 81.4 (SD 16.9). The mean summary score was 83.7 (SD 13.3). The questionnaire was shown to have high internal consistency in the four domains (Cronbach's alpha = 0.82-0.93), and no significant floor/ceiling effects of the summary score. The ESSQ-19 scores significantly correlated with other instruments to support construct validity. It also demonstrated good discriminant validity for being seizure free [AUC 0.72; 95% CI = 0.56-0.88], and to endorse depression [AUC 0.76, 95% CI = 0.56-0.96]. SIGNIFICANCE: The Italian version of the ESSQ-19 is a reliable and valid self-reported questionnaire for assessing patient satisfaction with epilepsy surgery.

The role of the amygdala in ictal central apnea: insights from brain MRI morphometry.

OBJECTIVE: Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy. METHODS: We prospectively recruited focal epilepsy patients with recorded seizures during a video-EEG long-term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high-resolution T1-weighted images. Post-processing analyses included a whole-brain VBM analysis and segmentation algorithms performed with FreeSurfer. RESULTS: Forty-six patients were recruited (aged 15-60 years): 16 ICA and 30 noICA. The whole-brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub-segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034). INTERPRETATION: Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA.

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

OBJECTIVE: To 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. METHODS: We 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. RESULTS: Seven 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. CONCLUSIONS: EMSE 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.

BACKGROUND AND PURPOSE: 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). METHODS: Consecutive episodes of non-hypoxic status epilepticus (SE) in patients ≥ 14 years 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. RESULTS: 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). CONCLUSIONS: 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 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.

Exploring the relationship between amygdala subnuclei volumes and cognitive performance in left-lateralized temporal lobe epilepsy with and without hippocampal sclerosis.

Cognitive disruption is a debilitating comorbidity in Temporal Lobe Epilepsy (TLE). Despite recent advances, the amygdala is often neglected in studies that explore cognition in TLE. Amygdala subnuclei are differently engaged in TLE with hippocampal sclerosis (TLE-HS) compared to non-lesional TLE (TLE-MRIneg), with predominant atrophy in the first and increased volume in the latter. Herein, we aim to explore the relationship between the volumes of the amygdala and its substructures with respect to cognitive performances in a population of left-lateralized TLE with and without HS. Twenty-nine TLEs were recruited (14 TLE-HS; 15 TLE-MRIneg). After investigating the differences in the subcortical amygdalae and hippocampal volumes compared to a matched healthy control population, we explored the associations between the subnuclei of the amygdala and the hippocampal subfields with the cognitive scores in TLE patients, according to their etiology. In TLE-HS, a reduced volume of the basolateral and cortical amygdala complexes joined with whole hippocampal atrophy, was related to poorer scores in verbal memory tasks, while in TLE-MRIneg, poorer performances in attention and processing speed tasks were associated with a generalized amygdala enlargement, particularly of the basolateral and central complexes. The present findings extend our knowledge of amygdala involvement in cognition and suggest structural amygdala abnormalities as useful disease biomarkers in TLE.

Electrographic seizure duration and inter-seizure intervals in focal status epilepticus.

OBJECTIVE: To characterize the duration of seizures and inter-seizure intervals in focal status epilepticus (SE). METHODS: We reviewed consecutive scalp EEG recordings from adult patients who were admitted for a first episode of focal status epilepticus. We identified electrographic seizure duration and inter-seizure intervals in the first diagnostic pretreatment EEG. We also reviewed isolated focal self-limiting seizures in epilepsy patients, as a comparison group for seizure duration. RESULTS: We recorded 307 focal seizures in 100 consecutive focal SE episodes, with a median seizure duration of 107 s (IQR: 54-186), and 134 isolated focal self-limiting seizures in 42 epilepsy patients, with a median duration of 59 s (IQR: 30-90; p < .001). The only clinical feature of SE that significantly increased seizure duration was acute symptomatic etiology. In SE, 15% and 7% of seizures lasted longer than 300 and 600 s, respectively (t1 of the actual definition for tonic-clonic and focal SE), while only 1% of self-limiting seizures lasted longer than 300 s, and none lasted longer than 600 s. The analysis of inter-seizure intervals in SE with multiple seizures showed that 50% of the inter-seizure periods were shorter than 60 s, and 95% were shorter than 540 s (9 min). Patients who had an increase in seizure duration (last versus first) of at least 1.4 times showed an increased 30-day mortality. SIGNIFICANCE: Focal seizures within a SE episode showed a wide range of duration, partly overlapping with the duration of focal self-limiting seizures but with a longer median duration. Inter-seizure intervals within an episode of SE were shorter than 1 min in 50% of the seizures and never lasted more than 10 min. Finally, an increase in seizure duration could represent an "electrophysiological biomarker" of a more severe SE episode, which may require more aggressive and rapid treatment.

A retrospective multicentric study on the effectiveness of intravenous brivaracetam in seizure clusters: Data from the Italian experience.

OBJECTIVE: Nearly half of people with epilepsy (PWE) are expected to develop seizure clusters (SC), with the subsequent risk of hospitalization. The aim of the present study was to evaluate the use, effectiveness and safety of intravenous (IV) brivaracetam (BRV) in the treatment of SC. METHODS: Retrospective multicentric study of patients with SC (≥ 2 seizures/24 h) who received IV BRV. Data collection occurred from January 2019 to April 2022 in 25 Italian neurology units. Primary efficacy outcome was seizure freedom up to 24 h from BRV administration. We also evaluated the risk of evolution into Status Epilepticus (SE) at 6, 12 and 24 h after treatment initiation. A Cox regression model was used to identify outcome predictors. RESULTS: 97 patients were included (mean age 62 years), 74 (76%) of whom had a history of epilepsy (with drug resistant seizures in 49% of cases). BRV was administered as first line treatment in 16% of the episodes, while it was used as first or second drug after benzodiazepines failure in 49% and 35% of episodes, respectively. On the one hand, 58% patients were seizure free at 24 h after BRV administration and no other rescue medications were used in 75 out of 97 cases (77%) On the other hand, SC evolved into SE in 17% of cases. A higher probability of seizure relapse and/or evolution into SE was observed in patients without a prior history of epilepsy (HR 2.0; 95% CI 1.03 - 4.1) and in case of BRV administration as second/third line drug (HR 3.2; 95% CI 1.1 - 9.7). No severe treatment emergent adverse events were observed. SIGNIFICANCE: In our cohort, IV BRV resulted to be well tolerated for the treatment of SC and it could be considered as a treatment option, particularly in case of in-hospital onset. However, the underlying etiology seems to be the main outcome predictor.

Impact of an optimized epilepsy surgery imaging protocol for focal epilepsy: A monocentric prospective study.

OBJECTIVE: To evaluate in a real clinical scenario the impact of the ILAE-recommended "Harmonized neuroimaging of epilepsy structural sequences"- HARNESS protocol in patients affected by focal epilepsy. METHODS: We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS-MRI protocol (H-MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low-grade epilepsy-associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH-MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate. RESULTS: A total of 131 patients with H-MRI were included in the study. 100 patients out from this cohort had at least one previous noH-MRI scan. Of those, 92/100 were acquired at the same Hospital than H-MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH-MRI, 36 resulted positive with a significant difference (p < .001) compared to H-MRI. Similar findings were observed when accounting for the expert radiologists (H-MRI = 57 positive; noH-MRI = 33, p < .001) and the scanner field strength (H-MRI 43 = positive, noH-MRI = 23, p < .001), while clinical information were more present in H-MRI (p < .002). SIGNIFICANCE: The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy.

Neuro-glial degeneration in Status Epilepticus: Exploring the role of serum levels of Neurofilament light chains and S100B as prognostic biomarkers for short-term functional outcome.

BACKGROUND: The last ILAE definition of Status Epilepticus (SE) highlights that the persistence of the epileptic activity per se could determine irreversible brain damages that could be responsible for long-term consequences. The measurement of neuro-glial injury biomarkers could help in the identification of those patients who will eventually develop short- and long-term consequences of SE. At present none of the already studied biomarkers has been validated to be used in everyday clinical practice. In this study, we explore the role of NfL and S100B as a prognostic biomarkers to identify patients who will develop short-term disability after an episode of SE. METHODS: This is a retrospective assessment of the serum levels of both NfL and S100B in a cohort of 87 adult patients with SE prospectively collected in our SE registry (Modena Status Epilepticus Registry - MoSER -) at Baggiovara Civil Hospital (Modena, Italy). All samples were acquired during SE within 72 hours of SE diagnosis. The comparison groups were: healthy controls (HC, n = 27) and patients with epilepsy (PWE, n = 30). Demographic, clinical, and therapeutical information and thirty-days follow-up information regarding disability development were acquired for every included patient and analyzed in relation to NfL and S100B values. RESULTS: Serum levels of NfL were significantly higher in SE compared to those of PWE (median 7.35 pg/ml, IQR 6.4, p < 0.001) and HC (median 6.57 pg/ml, IQR 9.1, p < 0.001); S100B serum levels were higher in SE (median 0.11 ug/L, IQR 0.18) compared to PWE (median 0.03 ug/L, IQR 0.03, p < 0.001) and HC (median 0.02 ug/L, IQR 0.008, p < 0.001). However, only NfL serum levels were found to be an independent predictor of 30 days functional outcome whereas S100B levels did not. CONCLUSIONS: Our results suggest that NfL measurement in serum during SE could help predict the short-term functional outcome. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Retrospective External Validation of the Status Epilepticus Severity Score (STESS) to Predict In-hospital Mortality in Adults with Nonhypoxic Status Epilepticus: A Machine Learning Analysis.

BACKGROUND: The objective of this study was to validate the value of the Status Epilepticus Severity Score (STESS) in the prediction of the risk of in-hospital mortality in patients with nonhypoxic status epilepticus (SE) using a machine learning analysis. METHODS: We included consecutive patients with nonhypoxic SE (aged ≥ 16 years) admitted from 2013 to 2021 at the Modena Academic Hospital. A decision tree analysis was performed using in-hospital mortality as a dependent variable and the STESS predictors as input variables. We evaluated the accuracy of STESS in predicting in-hospital mortality using the area under the receiver operating characteristic curve (AUROC) with 95% confidence interval (CI). RESULTS: Among 629 patients with SE, the in-hospital mortality rate was 23.4% (147 of 629). The median STESS in the entire cohort was 2.9 (SD 1.6); it was lower in surviving compared with deceased patients (2.7, SD 1.5 versus 3.9, SD 1.6; p < 0.001). Of deceased patients, 82.3% (121 of 147) had scores of 3-6, whereas 17.7% (26 of 147) had scores of 0-2 (p < 0.001). STESS was accurate in predicting mortality, with an AUROC of 0.688 (95% CI 0.641-0.734) only slightly reduced after bootstrap resampling. The most significant predictor was the seizure type, followed by age and level of consciousness at SE onset. Nonconvulsive SE in coma and age ≥ 65 years predicted a higher risk of mortality, whereas generalized convulsive SE and age < 65 years were associated with a lower risk of death. The decision tree analysis using STESS variables correctly classified 90% of survivors and 34% of nonsurvivors after the SE, with an overall risk of error of 23.1%. CONCLUSIONS: This validation study using a machine learning system showed that STESS is a valuable prognostic tool. The score appears particularly accurate and effective in identifying patients who are alive at discharge (high negative predictive value), whereas it has a lower predictive value for in-hospital mortality.

Predicting the progression to super-refractory status epilepticus: A machine-learning study.

AIM: Super-refractory status epilepticus (SRSE) is a status epilepticus (SE) that continues or recurs ≥24 h after the onset of anesthesia. We aimed to identify the predictors of progression to SRSE and the risk of 30-day mortality in patients with SRSE by using a machine learning technique. METHODS: We reviewed consecutive SE episodes in patients aged ≥14 years at Baggiovara Civil Hospital (Modena, Italy) from 2013 to 2021. A classification and regression tree analysis was performed to develop a predictive model of progression to SRSE in SE patients. In SRSE patients, a multivariate analysis was conducted to identify predictors of 30-day mortality. RESULTS: We included 705 patients, 16% of whom (113/705) progressed to SRSE. Acute symptomatic hypoxic etiology and age ≤ 68.5 years predicted the highest risk (87.1%) of progression to SRSE. Etiology other than acute symptomatic hypoxic and absence of NCSE predicted the lowest risk (3.6%) of progression to SRSE. The predictive model was accurate in 96.1% of patients not evolving to SRSE and in 48.7% of those evolving to SRSE. Among patients with SRSE, 46.9% (53/113) died within 30 days compared to 25.2% (149/592) of patients without SRSE (p < 0.001). Among patients with SRSE, older age was associated with increased 30-day mortality (odds ratio 1.075; 95% confidence interval: 1.031-1.112; p = 0.001). CONCLUSIONS: Acute symptomatic hypoxic etiology and younger age are major predictors of progression to SRSE. In patients with SRSE, older age is associated with increased risk of short-term mortality.