Patient-reported outcomes in epilepsy: a case study exploring their usage and impact.

Background: This study aimed to obtain insights from epilepsy specialists on the use of Patient-Reported Outcome (PRO) measures and how they can affect the management of people with epilepsy and healthcare resource utilization. Methods: The heads of two referral units for people with epilepsy at one tertiary care hospital were invited to respond to a structured survey. Results: Paper-based questionnaires and face-to-face interviews were the main modalities used to measure the quality of life of people with epilepsy. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31), the Adverse Event Profile (adult centre), the Generalized Anxiety Disorder-7, Short-Form Health Survey 36, PSY-Flex, SAFA and Child Behavior Checklist (paediatric centre) were the most used scales. There was consensus about the favourable impact of PRO upon patient management, disease management and measurement of the success of a treatment. Both respondents considered the PRO as important as other main indicators like efficacy and tolerability of the treatment. Lack of time, personnel and economic resources was identified as a barrier on the use of PRO. The PRO could reduce the number of visits, exams and treatments, and increase the time spent on each patient and the number of neuropsychological, psychological and rehabilitation services. The standardized use of PRO was considered useful and the increase in human resources was considered a priority to achieve this goal. Conclusions: Despite the heterogeneity in the actual collection of PRO, there was a uniform perception about their role to optimize the care of people with epilepsy.

Innovative LC-MS/MS method for therapeutic drug monitoring of fenfluramine and cannabidiol in the plasma of pediatric patients with epilepsy.

We present a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying fenfluramine (FFA), its active metabolite norfenfluramine (norFFA), and Epidyolex®, a pure cannabidiol (CBD) oral solution in plasma. Recently approved by the EMA for the adjunctive treatment of refractory seizures in patients with Dravet and Lennox-Gastaut syndromes aged above 2 years, FFA and CBD still do not have established therapeutic blood ranges, and thus need careful drug monitoring to manage potential pharmacokinetic and pharmacodynamic interactions. Our method, validated by ICH guidelines M10, utilizes a rapid extraction protocol from 100 µL of human plasma and a reversed-phase C-18 HPLC column, with deuterated internal standards. The Thermofisher Quantiva triple-quadrupole MS coupled with an Ultimate 3000 UHPLC allowed multiple reaction monitoring detection, ensuring precise analyte quantification. The assay exhibited linear responses across a broad spectrum of concentrations: ranging from 1.64 to 1000 ng/mL for both FFA and CBD, and from 0.82 to 500 ng/mL for norFFA. The method proves accurate and reproducible, free from matrix effect. Additionally, FFA stability in plasma at 4 °C and -20 °C for up to 7 days bolsters its clinical applicability. Plasma concentrations detected in patients samples, expressed as mean ± standard deviation, were 0.36 ± 0.09 ng/mL for FFA, 19.67 ± 1.22 ng/mL for norFFA. This method stands as a robust tool for therapeutic drug monitoring (TDM) of FFA and CBD, offering significant utility in assessing drug-drug interactions in co-treated patients, thus contributing to optimized patient care in complex therapeutic scenarios.

Current challenges in focal epilepsy treatment: An Italian Delphi consensus.

BACKGROUND: Epilepsy, a globally prevalent neurological condition, presents distinct challenges in management, particularly for focal-onset types. This study aimed at addressing the current challenges and perspectives in focal epilepsy management, with focus on the Italian reality. METHODS: Using the Delphi methodology, this research collected and analyzed the level of consensus of a panel of Italian epilepsy experts on key aspects of focal epilepsy care. Areas of focus included patient flow, treatment pathways, controlled versus uncontrolled epilepsy, follow-up protocols, and the relevance of patient-reported outcomes (PROs). This method allowed for a comprehensive assessment of consensus and divergences in clinical opinions and practices. RESULTS: The study achieved consensus on 23 out of 26 statements, with three items failing to reach a consensus. There was strong agreement on the importance of timely intervention, individualized treatment plans, regular follow-ups at Epilepsy Centers, and the role of PROs in clinical practice. In cases of uncontrolled focal epilepsy, there was a clear inclination to pursue alternative treatment options following the failure of two previous therapies. Divergent views were evident on the inclusion of epilepsy surgery in treatment for uncontrolled epilepsy and the routine necessity of EEG evaluations in follow-ups. Other key findings included concerns about the lack of pediatric-specific research limiting current therapeutic options in this patient population, insufficient attention to the transition from pediatric to adult care, and need for improved communication. The results highlighted the complexities in managing epilepsy, with broad consensus on patient care aspects, yet notable divergences in specific treatment and management approaches. CONCLUSION: The study offered valuable insights into the current state and complexities of managing focal-onset epilepsy. It highlighted many deficiencies in the therapeutic pathway of focal-onset epilepsy in the Italian reality, while it also underscored the importance of patient-centric care, the necessity of early and appropriate intervention, and individualized treatment approaches. The findings also called for continued research, policy development, and healthcare system improvements to enhance epilepsy management, highlighting the ongoing need for tailored healthcare solutions in this evolving field.

Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.

Brivaracetam use in clinical practice: a Delphi consensus on its role as first add-on therapy in focal epilepsy and beyond.

BACKGROUND: Antiseizure medications remain the cornerstone of treatment for epilepsy, although a proportion of individuals with the condition will continue to experience seizures despite appropriate therapy. Treatment choices for epilepsy are based on variables related to both the individual patient and the available medications. Brivaracetam is a third-generation agent antiseizure medication. METHODS: We carried out a Delphi consensus exercise to define the role of brivaracetam in clinical practice and to provide guidance about its use as first add-on ASM and in selected clinical scenarios. A total of 15 consensus statements were drafted by an expert panel following review of the literature and all were approved in the first round of voting by panelists. The consensus indicated different clinical scenarios for which brivaracetam can be a good candidate for treatment, including first add-on use. RESULTS: Overall, brivaracetam was considered to have many advantageous characteristics that render it a suitable option for patients with focal epilepsy, including a fast onset of action, favorable pharmacokinetic profile with few drug-drug interactions, broad-spectrum activity, and being well tolerated across a range of doses. Brivaracetam is also associated with sustained clinical response and good tolerability in the long term. CONCLUSIONS: These characteristics also make it suitable as an early add-on for the elderly and for patients with post-stroke epilepsy or status epilepticus as highlighted by the present Delphi consensus.

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.

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.

Conversion to Brivaracetam Monotherapy in Clinical Practice: A Retrospective Study.

INTRODUCTION: The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice. METHODS: This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months. Secondary outcomes included the 6- and 12-month rates of seizure freedom. Safety and tolerability outcomes included the frequency and type of adverse events (AEs) and the occurrence of treatment discontinuation due to AEs. RESULTS: A total of 44 participants with a median age of 63.5 (interquartile range 44-73.5) years were included; 17 subjects were seizure free at baseline, and 9 of them switched from levetiracetam because of lack of tolerability. The retention rate of BRV monotherapy was 88.6% (39/44) at 6 months and 83.9% (26/31) at 12 months. The rates of seizure freedom were 72.7% (32/44) in subjects with 6-month follow-up and 58.1% (18/31) in subjects with 12-month follow-up. The median maintenance dosage of BRV monotherapy was 150 (100-200) mg/day at 6 months and 125 (100-200) mg/day in subjects with 12-month follow-up. Adverse events were recorded in 6/44 (13.6%) participants and led to BRV discontinuation in 2/44 (4.5%) cases. The reported AEs were somnolence (n = 3), fatigue (n = 2), and irritability (n = 1); no serious AEs were experienced. In 21/44 (47.7%) participants, BRV monotherapy resulted from the direct switch from levetiracetam. The rates of treatment retention and seizure freedom at 6 and 12 months were higher among people who switched from levetiracetam to BRV monotherapy. CONCLUSION: Brivaracetam may be a valuable treatment of focal seizures in people who converted to monotherapy in a real-life setting.

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.

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.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

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 Cognitive and Behavioural Effects of Perampanel in Children with Neurodevelopmental Disorders: A Systematic Review.

In children and adolescents with epilepsy, neurodevelopmental comorbidities can impair the quality of life more than seizures. The aim of this review was to evaluate the cognitive and behavioural effects of perampanel (PER) in the paediatric population. We performed a systematic search of the literature, selecting studies published in English including children and adolescents with epilepsy treated with PER. Cognitive and behavioural outcomes were assessed through validated neuropsychological standardised scales. Eighteen studies involving 3563 paediatric patients were included. Perampanel did not impair general cognitive functions and visuospatial skills, whereas a slight improvement in verbal memory and a decline in attentional power were detected. In adolescents with refractory epilepsies, high doses and/or rapid titration of PER and an underlying psychiatric disorder were risk factors for developing or worsening psychiatric outcomes such as anger, aggressiveness, and irritability. Data on children and adolescents treated with new antiseizure medications are scant, and neuropsychiatric effects are tricky to be detected during developmental age. According to the currently available evidence, PER showed an overall favourable risk-benefit profile. Pharmacodynamics, co-administration of other antiseizure medications, and family and personal history of neuropsychiatric disorders should be considered before PER treatment.

A real-world comparison among third-generation antiseizure medications: Results from the COMPARE study.

OBJECTIVE: There are few comparative data on the third-generation antiseizure medications (ASMs). We aimed to assess and compare the effectiveness of brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) in people with epilepsy (PWE). Efficacy and tolerability were compared as secondary objectives. METHODS: This multicenter, retrospective study collected data from 22 Italian neurology/epilepsy centers. All adult PWE who started add-on treatment with one of the studied ASMs between January 2018 and October 2021 were included. Retention rate was established as effectiveness measure and described using Kaplan-Meier curves and the best fitting survival model. The responder status and the occurrence of adverse events (AEs) were used to evaluate efficacy and safety, respectively. The odds of AEs and drug efficacy were estimated by two multilevel logistic models. RESULTS: A total of 960 patients (52.92% females, median age = 43 years) met the inclusion criteria. They mainly suffered from structural epilepsy (52.29%) with monthly (46.2%) focal seizures (69.58%). Compared with LCM, all the studied ASMs had a higher dropout risk, statistically significant in the BRV levetiracetam (LEV)-naïve (hazard ratio [HR] = 1.97, 95% confidence interval [CI] = 1.17-3.29) and PER groups (HR = 1.64, 95% CI = 1.06-2.55). Women were at higher risk of discontinuing ESL (HR = 5.33, 95% CI = 1.71-16.61), as well as PER-treated patients with unknown epilepsy etiology versus those with structural etiology (HR = 1.74, 95% CI = 1.05-2.88). BRV with prior LEV therapy showed lower odds of efficacy (odds ratio [OR] = .08, 95% CI = .01-.48) versus LCM, whereas a higher efficacy was observed in women treated with BRV and LEV-naïve (OR = 10.32, 95% CI = 1.55-68.78) versus men. PER (OR = 6.93, 95% CI = 3.32-14.44) and BRV in LEV-naïve patients (OR = 6.80, 95% CI = 2.64-17.52) had a higher chance of AEs than LCM. SIGNIFICANCE: Comparative evidence from real-world studies may help clinicians to tailor treatments according to patients' demographic and clinical characteristics.

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy.

OBJECTIVE: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). METHODS: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. RESULTS: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. SIGNIFICANCE: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.

Post-traumatic decompressive craniectomy: Prognostic factors and long-term follow-up.

Background: Decompressive craniectomy (DC) is still controversial in neurosurgery. According to the most recent trials, DC seems to increase survival in case of refractory intracranial pressure. On the other hand, the risk of postsurgical poor outcomes remain high. The present study aimed to evaluate a series of preoperative factors potentially impacting on long-term follow-up of traumatic brain injury (TBI) patients treated with DC. Methods: We analyzed the first follow-up year of a series of 75 TBI patients treated with DC at our department in five years (2015-2019). Demographic, clinical, and radiological parameters were retrospectively collected from clinical records. Blood examinations were analyzed to calculate the preoperative neutrophil-to-lymphocyte ratio (NLR). Disability rating scale (DRS) was used to classify patients' outcomes (good outcome [G.O.] if DRS ≤11 and poor outcome [P.O.] if DRS ≥12) at 6 and 12 months. Results: At six months follow-up, 25 out of 75 patients had DRS ≤11, while at 12 months, 30 out of 75 patients were included in the G.O. group . Admission Glasgow Coma Scale (GCS) >8 was significantly associated with six months G.O. Increased NLR values and the interval between DC and cranioplasty >3 months were significantly correlated to a P.O. at 6- and 12-month follow-up. Conclusion: Since DC still represents a controversial therapeutic strategy, selecting parameters to help stratify TBI patients' potential outcomes is paramount. GCS at admission, the interval between DC and cranioplasty, and preoperative NLR values seem to correlate with the long-term outcome.