Adult epilepsy.

Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.

Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

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.

Neutrophil to lymphocyte ratio and early seizures after ischemic stroke: A case-control study.

BACKGROUND: Early post-stroke seizures (EPSS) are associated with an increased risk of mortality and post-stroke epilepsy. This study aimed to identify potential risk factors for EPSS, focusing on blood parameters, such as the neutrophil-to-lymphocyte ratio (NLR), which is a biomarker for inflammation. METHODS: Patients treated for ischemic stroke between 2017 and 2019 were retrospectively identified. 44 of them had a first epileptic seizure within 7 days after the stroke. They were matched 1:2 for age and sex with controls who had a stroke but no EPSS. Information on demographics, stroke characteristics, and blood parameters were collected on admission. Logistic regression was used to identify variables associated with EPSS and the area under the receiver operating characteristic curve (AUROC) to estimate their predictive accuracy. RESULTS: The NLR value (p = 0.035), National Institutes of Health Stroke Scale (NIHSS) (p = 0.016) and cortical localization of stroke (p = 0.03) were significantly correlated with the occurrence of EPSS in univariate logistic regression. In multivariable logistic regression, after adjusting for age, sex, baseline NIHSS, and stroke localization, the NLR values [adjusted odds ratio 1.097, 95% confidence interval (CI): 1.005-1.197; p = 0.038] were independently associated with the occurrence of EPSS. The AUROC for NLR was 0.639 (95% CI: 0.517-0.761) with 2.98 as the best predictive cut-off value. There was a significant positive relationship between NLR and NIHSS, rS(87) = 0.383, p = <0.001. CONCLUSION: Higher NLR values were associated with increased risk of EPSS. This biomarker appears useful to assess the risk of developing EPSS.

Safe delivery, perinatal outcomes and breastfeeding in women with epilepsy.

Safe delivery and optimal peripartum and postpartum care in women with epilepsy (WWE) is a major concern which has received limited attention in recent years. A diagnosis of epilepsy per se is not an indication for a planned cesarean section or induction of labor, even though epidemiological studies indicate that cesarean delivery is more common among WWE compared to the general population. Pregnancy in WWE is associated with an increased risk of obstetrical complications and increased perinatal morbidity and mortality, and these risks may be greater among WWE taking ASMs. Wherever feasible, pregnant WWE should be directed to specialist care. Risk minimization includes, when appropriate, dose adjustment to compensate for pregnancy-related changes in the pharmacokinetics of some ASMs. With respect to postpartum management, WWE should be advised that the benefits of breastfeeding outweigh the small risk of adverse drug reactions in the infant.

Impact of the COVID-19 pandemic, its related social restriction measures and vaccination campaign on emergency department attendances for epileptic seizures: An interrupted time-series analysis.

AIM: To investigate the impact of the outbreak of the COVID-19 pandemic, its related social restriction measure (national lockdown) and vaccination campaign on emergency department (ED) accesses for epileptic seizures. METHODS: Retrospective observational analysis conducted on a consecutive cohort of patients who sought medical care at the ED of the General Hospital of Merano, Italy, from January 1, 2015, to December 31, 2021. We investigated the monthly ED attendances for epileptic seizures between the periods before and after the outbreak of the COVID-19 pandemic and the national lockdown (March 2020) using an interrupted time-series analysis with data standardized for 1000 accesses/month. As a further temporal cutoff, we used the start of the national vaccination campaign. RESULTS: Between January 1, 2015, and December 31, 2021, a total of 415,005 ED attendances were recorded; 1,254 (0.3 %) were due to epileptic seizures. No significant difference was found in the rate of standardized ED accesses for epileptic seizures in March 2020 (time point of interest) to the pre-pandemic trend (0.33/1000; 95 %CI: -1.05 to 1.71; p = 0.637). Similarly, there was no difference between the pre- and post-pandemic trends (-0.02/1000; 95 %CI: -0.11 to 0.06; p = 0.600). When adopting January 2021 as time point of interest, we found no difference to the pre-vaccination trend (0.83/1000; 95 %CI: -0.48 to 2.15), and no difference in the pre- and post-vaccination trends (-0.12/1000; 95 %CI: -0.27 to 0.04). CONCLUSIONS: The COVID-19 pandemic and its related social restrictions (lockdown), as well as the COVID-19 national vaccination campaign, had little impact on ED accesses for epileptic seizures.

"Qui la voce sua soave": "Maria Callas' dermatomyositis"-art beyond disease and its stigma.

Not available for a historical note.

Back to the future: encephalitis lethargica as an autoimmune disorder?

More than 100 years after its emergence, the exact pathophysiological mechanisms underlying encephalitis lethargica (EL) are still elusive and awaiting convincing and complete elucidation. This article summarizes arguments proposed over time to support or refute the hypothesis of EL as an autoimmune neuropsychiatric disorder triggered by an infectious process. It also provides a critical evaluation of modern cases labeled as EL and a comprehensive differential diagnosis of autoimmune neurological conditions that could mimic EL. The evidence supporting the autoimmune nature of historical EL is sparse and not entirely convincing. It is possible that autoimmune mechanisms were involved in the pathogenesis of this disease as an idiosyncratic response to a yet unidentified infectious agent in genetically predisposed individuals. Although there has been an increase in the incidence of presumed autoimmune encephalomyelitis since the peak of EL pandemics, most evidence does not support an underlying autoimmune mechanism. There are significant differences between historical and recent EL cases in terms of clinical symptomatology, epidemiology, and neuropathological features, suggesting that they are different entities with only superficial similarity. The term "encephalitis lethargica," still frequently used in the medical literature, should not be used for cases occurring at present in the sporadic form. Historical EL should be kept apart from recent EL, as they differ in important aspects.

Prognostic role of albumin, lactate-to-albumin ratio and C-reactive protein-to-albumin ratio in infected patients.

INTRODUCTION: The prognostic evaluation of the septic patient has recently been enriched by some predictive indices such as albumin concentration, lactate/albumin ratio (LAR) and C-reactive protein/albumin ratio (CAR). The performance of these indices has been evaluated in septic patients in intensive care, but until now their performance in infected patients in the Emergency Department (ED) has not been evaluated. AIM: To investigate the potential prognostic role of albumin, LAR and CAR in patients with infection in the ED. METHODS: Single-centre prospective study performed between 1 January 2021 and 31 December 2021 at the ED of the Merano Hospital (Italy). All patients with infection were enrolled. The study outcome was death within 30 days. The predictive ability of albumin, LAR and CAR was assessed by area under the receiver operating characteristic curves (AUROCs). A multivariate logistic regression model was used to examine the association of the indices with 30-day mortality, with comorbidity, acute urgency and severity of infection as covariates. RESULTS: The study enrolled 962 patients with an infectious status. The overall 30-day mortality rate was 8.9% (86/962). The AUROC of albumin was 0.831 (95% CI 0.795-868), while for LAR this was 0.773 (CI95% 0.719-0.827) and for CAR 0.718 (CI95% 0.664-0.771). The odds ratio for 30-day mortality for albumin was 3.362 (95% CI 1.904-5.936), for ln(LAR) 2.651 (95% CI 1.646-4.270) and for ln(CAR) 1.739 (95% CI 1.326-2.281). CONCLUSIONS: All three indices had a good discriminatory ability for the risk of short-term death in patients with infection, indicating their promising use in the ED as well as in the ICU. Further studies are needed to confirm the better performance of albumin compared to LAR and CAR.

Human intelligence versus Chat-GPT: who performs better in correctly classifying patients in triage?

INTRODUCTION: Chat-GPT is rapidly emerging as a promising and potentially revolutionary tool in medicine. One of its possible applications is the stratification of patients according to the severity of clinical conditions and prognosis during the triage evaluation in the emergency department (ED). METHODS: Using a randomly selected sample of 30 vignettes recreated from real clinical cases, we compared the concordance in risk stratification of ED patients between healthcare personnel and Chat-GPT. The concordance was assessed with Cohen's kappa, and the performance was evaluated with the area under the receiver operating characteristic curve (AUROC) curves. Among the outcomes, we considered mortality within 72 h, the need for hospitalization, and the presence of a severe or time-dependent condition. RESULTS: The concordance in triage code assignment between triage nurses and Chat-GPT was 0.278 (unweighted Cohen's kappa; 95% confidence intervals: 0.231-0.388). For all outcomes, the ROC values were higher for the triage nurses. The most relevant difference was found in 72-h mortality, where triage nurses showed an AUROC of 0.910 (0.757-1.000) compared to only 0.669 (0.153-1.000) for Chat-GPT. CONCLUSIONS: The current level of Chat-GPT reliability is insufficient to make it a valid substitute for the expertise of triage nurses in prioritizing ED patients. Further developments are required to enhance the safety and effectiveness of AI for risk stratification of ED patients.

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.

Prevalence of ictal injuries in functional (psychogenic nonepileptic) seizures: A systematic review and meta-analysis.

OBJECTIVE: Ictal injuries have long been considered typical signs of epileptic seizures. However, studies have shown that patients with functional seizures (FS)-also named psychogenic nonepileptic seizures-can also present these signs, misleading physicians and delaying a correct diagnosis. This systematic review aimed to assess the prevalence of injuries from FS. METHODS: A literature search was performed in PubMed, Embase, LILACS (Latin American and Caribbean Health Sciences Literature), Scopus, Web of Science, PsycINFO, Google Scholar, OpenGrey, and ProQuest. Observational studies were included. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for studies reporting prevalence data. RStudio was used for meta-analyses. Cumulative evidence was evaluated according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: From the 2607 identified records, 41 studies were included in the qualitative synthesis, and 28 were included in meta-analyses. A meta-analysis of 13 studies, including 1673 individuals, resulted in an overall lifetime prevalence of injuries due to FS per person of 25% (95% confidence interval [CI] = 19%-32%, I2 = 88%). Considering a limited period (video-electroencephalographic [VEEG] monitoring days), a meta-analysis of 13 studies, including 848 individuals, resulted in an injury prevalence due to FS per person of .7% (95% CI = 0%-3%, I2 = 73%). Also, a meta-analysis of eight studies, including 1000 individuals, resulted in a prevalence of injuries per FS of .1% (95% CI = 0%-.98%, I2 = 49%). The certainty in cumulative evidence assessed by GRADE was rated "very low" for lifetime prevalence of injuries per person, "low" for prevalence per person during VEEG monitoring, and "moderate" for prevalence per number of FS. SIGNIFICANCE: Overall pooled lifetime prevalence of injuries due to FS per person was 25%. In comparison, the prevalence of injuries per person during VEEG monitoring and per functional seizure was .7% and .1%, respectively. [Correction added on 07 October 2023, after first online publication: In the preceding sentence, 'consecutively' was corrected to 'respectively'.] The evidence of the occurrence of injuries due to FS breaks the paradigm that epileptic seizures can cause injuries but FS cannot.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Acute symptomatic seizures after stroke: A scoping review on primary prevention, treatment with antiseizure medications and drug discontinuation.

AIM: To evaluate and synthesize the evidence and knowledge gaps on primary prevention and treatment of post-stroke acute symptomatic seizures (ASSs) using antiseizure medications (ASMs). METHODS: We systematically searched of EMBASE, MEDLINE (accessed from PubMed), and the Cochrane Central Register of Controlled Trials (CENTRAL) to include randomized, double- or single-blinded trials (RCTs) on primary prophylaxis and treatment of post-stroke ASSs with ASMs. The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Two placebo-controlled RCTs (totaling 114 participants) evaluating valproate or levetiracetam as primary prophylaxis of ASSs due to hemorrhagic stroke were included. In one RCT, post-stroke ASS occurred in 1/36 patients (2.7%) on valproate and in 4/36 patients (7%) on placebo (p = 0.4). In the other RCT, ASSs were only electrographic and occurred in 3/19 (16%) with levetiracetam and in 10/23 (43%) with placebo (p = 0.043). We found no RCTs on the treatment of post-stroke ASSs or discontinuation of ASMs administered for the treatment of post-stroke ASSs. CONCLUSION: Evidence to support primary prophylaxis of ASSs is sparse and of very low quality and is insufficient to recommend it routinely. Secondary prevention of post-stroke ASSs is usually not recommended except in selected cases (the most relevant being acute symptomatic status epilepticus, which carries a high risk of subsequent poststroke seizures (PSE)). The choice of which ASM to administer and for how long is not based on solid RCT evidence. Management of post-stroke PSE should be done according to an evidence-based framework, considering the individuality of the patient and the pharmacological properties of the drugs.

Clinical scores and clusters for prediction of outcomes in status epilepticus.

Status epilepticus (SE) is a life-threatening condition and may have long-term negative sequelae. Short- and long-term outcomes encompass mortality, deterioration of functional status compared to baseline, refractoriness to treatment, recurrence of SE, and development of epilepsy, cognitive impairment, and behavioral disturbances. So far, the greatest amount of evidence is available for the prediction of short-term mortality. Conversely, the knowledge regarding long-term consequences among SE survivors is still scarce and several issues have not yet been resolved. The heterogeneity of SE renders the prognostication of outcomes challenging. Although aetiology is the main determinant of the outcome, different prognostic predictors have been identified. In this regard, data on group effects need to be integrated into prognostic scores to allow individual risk stratification. Importantly, many of the present scores are not designed to enable repetition to follow patient evolution. A new paradigm for the assessment of SE outcomes should consider variables that become available and/or can be retested during the course of SE. Neuroimaging findings, serum biomarkers, treatment characteristics, complications during SE, peri-ictal and postictal characteristics after SE cessation look as promising determinants of outcome and are suitable for inclusion in future models to enhance the quality and increase the reliability of prediction. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

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.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.

Anti-seizure medications for neonates with seizures.

BACKGROUND: Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive. OBJECTIVES: 1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials) Treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months. We report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons. AUTHORS' CONCLUSIONS: Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.

B-mode transorbital ultrasonography for the diagnosis of idiopathic intracranial hypertension: an updated systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the role of B-mode transorbital ultrasonography (TOS) for the diagnosis of idiopathic intracranial hypertension (IIH) in adults. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) (1966-May 2022) were searched to identify studies reporting ultrasonographic data about the optic nerve sheath diameter (ONSD) and optic disc elevation (ODE) in adults with IIH compared to subjects without IIH. The quality of the included studies was evaluated by the Newcastle-Ottawa Quality. RESULTS: Fifteen studies were included (total of 439 patients). The values of ODE ranged from 0.6 to 1.3 mm in patients with IIH. The values of ONSD ranged from 4.7 to 6.8 mm in IIH patients and from 3.9 to 5.7 mm in controls. In IIH patients, the ONSD was significantly higher compared to controls (standardized mean difference: 2.5 mm, 95% confidence interval (CI): 1.6-3.4 mm). Nine studies provided data about the presence of papilledema and the pooled prevalence was 95% (95% CI, 92-97%). CONCLUSIONS: In adults, the thickness of ONSD and the entity of ODE were significantly associated with IIH. B-mode TOS enables to noninvasively detect increased ICP and should be performed, potentially routinely, in any patient with suspected IIH.

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.