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.

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.

A profile of azetukalner for the treatment of epilepsy: from pharmacology to potential for therapy.

INTRODUCTION: Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability. AREAS COVERED: A literature review on the pharmacology, efficacy, tolerability, and safety of azetukalner (XEN1101), a second-generation opener of neuronal potassium channels currently in Phase 3 development as ASM. EXPERT OPINION: Results from the phase 2b clinical trial strongly support the ongoing clinical development of azetukalner as a new ASM. Its pharmacokinetic properties support convenient once-daily dosing, eliminating the need for titration at initiation or tapering at the conclusion of treatment. CYP3A4 is the main enzyme involved in its metabolism and drug-drug interactions can affect the drug exposure. Preliminary analysis of an ongoing open-label study reveals no reported pigmentary abnormalities. The upcoming Phase 3 clinical trials are expected to provide further insight into the efficacy, tolerability, and safety of azetukalner in treating focal-onset and primary generalized tonic-clonic seizures. Structurally distinct from currently marketed ASMs, azetukalner has the potential to be the only-in-class Kv7.2/7.3 opener on the market upon regulatory approval.

Development and validation of a nomogram for assessing comorbidity and frailty in triage: a multicentre observational study.

Assessing patient frailty in the Emergency Department (ED) is crucial; however, triage frailty and comorbidity assessment scores developed in recent years are unsatisfactory. The underlying causes of this phenomenon could reside in the nature of the tools used, which were not designed specifically for the emergency context and, thus, are difficult to adapt to the emergency environment. The objective of this study was to create and internally validate a nomogram for identifying different levels of patient frailty during triage. Multicenter, prospective, observational exploratory study conducted in two ED. The study was conducted from April 1 to October 31, 2022. Following the triage assessment, the nurse collected variables related to the patient's comorbidities and chronic conditions using a predefined form. The primary outcome was the 90-day mortality rate. A total of 1345 patients were enrolled in this study; 6% died within 90 days. In the multivariate analysis, the Charlson Comorbidity Index, an altered motor condition, an altered cognitive condition, an autonomous chronic condition, arrival in an ambulance, and a previous hospitalization within 90 days were independently associated with death. The internal validation of the nomogram reported an area under the receiver operating characteristic of 0.91 (95% CI 0.884-0.937). A nomogram was created for assessing comorbidity and frailty during triage and was demonstrated to be capable of determining comorbidity and frailty in the ED setting. Integrating a tool capable of identifying frail patients at the first triage assessment could improve patient stratification.

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.

Diagnosing epileptic seizures in patients with Alzheimer's disease and deciding on the appropriate treatment plan.

INTRODUCTION: Alzheimer's disease (AD) is the predominant cause of dementia and a significant contributor to morbidity among the elderly. Patients diagnosed with AD face an increased risk of epileptic seizures. AREAS COVERED: Herein, the authors review the challenges in the diagnosis of seizures in patients with AD, the risks of seizures related to medications used in AD and the pharmacological treatment of seizures in AD. The authors also provide the reader with their expert opinion on the subject matter and future perspectives. EXPERT OPINION: Healthcare professionals should maintain a vigilant approach to suspecting seizures in AD patients. Acute symptomatic seizures triggered by metabolic disturbances, infections, toxins, or drug-related factors often have a low risk of recurrence. In such cases, addressing the underlying cause may suffice without initiating antiseizure medications (ASMs). However, unprovoked seizures in certain AD patients carry a higher risk of recurrence over time, warranting the use of ASMs. Although data is limited, both lamotrigine and levetiracetam appear to be reasonable choices for controlling seizures in elderly AD patients. Decisions should be informed by the best available evidence, the treating physician's clinical experience, and the patient's preferences.

Is the National Early Warning Score able to identify nursing activity load? A prospective observational study.

BACKGROUND: The National Early Warning Score scale correlates well with the intensity of the patient's acute condition. It could also correlate with the nursing activity load and prove useful in defining and redistributing nursing resources based on the acuity of patients. AIM: To assess whether patients' National Early Warning Score at hospital admission correlates with objective nursing demands and can be used to optimize the distribution of available care resources. METHODS: This single-center prospective study included patients admitted to the Department of Internal Medicine at the Civil Hospital in Altovicentino (Italy) between September 1 and December 31, 2022. Nursing activities were recorded for the first three days after admission and standardized to the daily mean as performance/5 min/patient/day. Linear regression was used to assess the correlation between nursing demands for different National Early Warning Scores. RESULTS: This study included 333 patients. Their mean National Early Warning Score was 3.9 (standard deviation: 2.9), with 61 % (203/333) in the National Early Warning Score <5 category, 19.5 % (65/333) in the National Early Warning Score 5-6 category, and 19.5 % (65/333) in the National Early Warning Score >6 category. Their average daily care requirements increased from 22 (16-30) activities/5 min/patient/day in the low National Early Warning Score category to 30 (20-39) activities/5 min/patient/day in the intermediate National Early Warning Score category (p < 0.001) and 35 (23-45) activities/5 min/patient/day in the high National Early Warning Score category (p < 0.001). CONCLUSION: The National Early Warning Score correlates with nursing care activities for patients with an acute condition and can be used to optimize the distribution of available care resources.

The role of lactate-to-albumin ratio to predict 30-day risk of death in patients with sepsis in the emergency department: a decision tree analysis.

BACKGROUND: Accurately estimating the prognosis of septic patients on arrival in the emergency department (ED) is clinically challenging. The lactate-to-albumin ratio (LAR) has recently been proposed to improve the predictive performance of septic patients admitted to the ICU. OBJECTIVES: This study aims to assess whether the LAR could be used as an early prognostic marker of 30-day mortality in patients with sepsis in the ED. METHODS: A prospective observational study was conducted in the ED of the Hospital of Merano. All patients with a diagnosis of sepsis were considered. The LAR was recorded on arrival in the ED. The primary outcome measure was mortality at 30 days. The predictive role of the LAR for mortality was evaluated with the area under the ROC curve, logistic regression adjusted for the Charlson Comorbidity Index value, National Early Warning Score, and Sequential Organ Failure score, and with decision tree analysis. RESULTS: 459 patients were enrolled, of whom 17% (78/459) died at 30 days. The median LAR of the patients who died at 30 days (0.78 [0.45-1.19]) was significantly higher than the median LAR of survivors (0.42 [0.27-0.65]) (p < 0.001). The discriminatory ability of the LAR for death at 30 days was 0.738, higher than that of lactate alone (0.692), and slightly lower than that of albumin alone (0.753). The decision trees confirmed the role of the LAR as an independent risk factor for mortality. CONCLUSION: The LAR can be used as an index to better predict the 30-day risk of death in septic patients.

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.

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.

Estimated plasma volume status is a simple and quick tool that could help define the severity of patients with infection on arrival at the emergency department.

BACKGROUND: Infectious states are subtle and rapidly evolving conditions observed daily in the emergency department (ED), and their prognostic evaluation remains a complex clinical challenge. Recently, estimated plasma volume status (ePVS) has been suggested to have a prognostic role in conditions where volemic alteration is central to the pathophysiology. The aim of this study was to verify whether ePVS recorded at ED admission can provide prognostic indications of 30-day mortality in patients with infection. METHODS: A prospective observational study was performed between 1 January 2021 and 31 December 2021 at the ED of the Merano Hospital. All patients with infection were enrolled. ePVS values were derived from haemoglobin and haematocrit measured on the immediate arrival of patients in the ED. The predictive power of ePVS for 30-day mortality was assessed using a multivariate model adjusted for severity, comorbidity and urgency. Kaplan-Meier analysis was also performed. RESULTS: Of the 949 patients with infection enrolled in the study (47.9%, SOFA ≥2), 8.9% (84/949) died at 30 days. The median ePVS value was higher in patients who died at 30 days than in patients who survived (5.83 vs. 4.61, p < 0.001). Multivariate analysis revealed that ePVS in both continuous and categorical form around the median was an independent risk factor for 30-day mortality even after adjusting for severity, comorbidity and urgency. Kaplan-Meier analysis confirmed an increased risk of death in patients with high ePVS values. CONCLUSIONS: ePVS recorded on ED admission of patients with infection was an independent predictor of risk for 30-day mortality.

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.

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.

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.

Real requirements of nursing activities and patient-related factors related to nursing overload in an internal medicine department.

Adequate nursing care can be decisive for the outcome of a patient admitted to an internal medicine ward. Individual prediction of nursing activity at the time of a patient's admission could improve the work process. This study aimed to assess the objectively assessed nursing requirements of patients admitted to a medical setting and to identify clinical factors that correlate with high demands. This is a prospective and pragmatic observational study that enrolled patients admitted to the Internal Medicine ward at the Altovicentino Civil Hospital (Italy) between September 1 and December 31, 2022. Nursing activities were recorded for the first 3 days of hospitalization and standardized as performance/5 min/patient. Patients requiring more than the 75th percentile of performance/5 min/patient were considered nursing over-activities. Multivariable models were used to assess patient-related risk factors associated with nursing over-activity. This study enrolled 333 patients (mean age: 74.2; 55.6% male). Their mean Charlson Comorbidity Index (CCI), Clinical Frailty Scale (CFS), Chronic Barthel Index, and Sistema Informtativo della Performance Infermieristica (SIPI) scores were 5.3, 4.2, 62.4, and 53.7, respectively. Mean National Early Warning System (NEWS) on admission was 3.9 (standard deviation: 2.8). A median of 73 (interquartile range [IQR]: 54-109) nursing care activities/5 min/patient were performed. NEWS score (odds ratio [OR]: 1.372, 95% confidence interval [95%CI]: 1.216-1.547, p < 0.001) and Acute Barthel Index (OR: 0.983, 95%CI: 0.967-0.999, p = 0.041) were independent risk factors for nursing over-activities. NEWS and the Acute Barthel Index could help reorganize nursing resources within internal medicine wards, allowing for an equal distribution between patients who require more resources and those who require less.

Herbis, non verbis, fiunt medicamenta vitae: The Italian botanist Arturo Nannizzi (1887-1961) and his contribution to the treatment of parkinsonism following encephalitis lethargica.

We describe the Italian contribution to the description and treatment of parkinsonism following encephalitis lethargica (EL): postencephalitic parkinsonism (PEP). Special attention is devoted to the description of postencephalitic symptoms by Giuseppe Panegrossi (1871-1953) and to the treatment based on Atropa belladonna introduced in Italy and extensively supported by Arturo Nannizzi (1887-1961), who was charged by the queen of Italy with conducting research into this plant and advocating its cultivation for healing purposes. This article gives us the unique opportunity to revisit the figure of this distinguished botanist, providing a summary of his biography, interests, and achievements.

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.