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1.
Lancet ; 402(10399): 412-424, 2023 07 29.
Article in English | MEDLINE | ID: mdl-37459868

ABSTRACT

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.


Subject(s)
Drug Resistant Epilepsy , Epilepsy , Humans , Adult , Treatment Outcome , Epilepsy/therapy , Epilepsy/drug therapy , Seizures , Drug Resistant Epilepsy/diagnosis , Drug Resistant Epilepsy/therapy , Prognosis
2.
Epilepsia ; 65(4): 1006-1016, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38339985

ABSTRACT

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.


Subject(s)
Alcoholism , Status Epilepticus , Adult , Humans , Aged , Anticonvulsants/therapeutic use , Seizures/epidemiology , Seizures/etiology , Seizures/drug therapy , Status Epilepticus/etiology , Status Epilepticus/complications , Proportional Hazards Models , Kaplan-Meier Estimate
3.
Epilepsia ; 65(3): e27-e34, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38294338

ABSTRACT

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.


Subject(s)
Epilepsy, Generalized , Epilepsy , Pregnancy , Humans , Female , Topiramate/adverse effects , Anticonvulsants/adverse effects , Teratogens/toxicity , Retrospective Studies , Cohort Studies , Fructose/therapeutic use , Epilepsy/drug therapy , Epilepsy, Generalized/drug therapy , Levetiracetam/adverse effects , Immunoglobulin E/therapeutic use
4.
Epilepsia ; 65(2): 456-472, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38052481

ABSTRACT

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.


Subject(s)
Epilepsies, Partial , Epilepsy , Nitriles , Pyridones , Male , Adult , Humans , Female , Anticonvulsants/adverse effects , Epilepsies, Partial/drug therapy , Retrospective Studies , Levetiracetam/therapeutic use , Lacosamide/therapeutic use , Epilepsy/drug therapy , Pyrrolidinones/therapeutic use , Treatment Outcome
5.
Eur J Neurol ; 31(4): e16177, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38258477

ABSTRACT

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.


Subject(s)
Drug Resistant Epilepsy , Status Epilepticus , Adult , Humans , Adolescent , Retrospective Studies , Status Epilepticus/etiology , Seizures/complications , Hospitalization
6.
J Vasc Interv Radiol ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38906244

ABSTRACT

PURPOSE: To summarize identified risk factors, the most common clinical presentations, radiological and neurophysiological features, and proposed pathophysiological mechanisms of contrast medium-induced transient cortical blindness (TCB). METHODS: A systematic search of PubMed, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov was performed. A total of 115 patients from 2 retrospective cohort studies, 10 case series, and 52 case reports were included. RESULTS: The available evidence suggests that TCB can manifest after both invasive and noninvasive contrast-enhanced procedures. The pathophysiology of TCB is unclear; however, the primary mechanism suggested involves the direct neurotoxic effect of the contrast medium. Ionic, nonionic, hyperosmolar, isoosmolar, and even ethiodized oil have been implicated. Imaging findings are nonspecific, and absent in about half of patients. Onset is within 30 minutes in about half of patients and resolves within 1 day in about half of patients, but delayed onset after a day and delayed resolution after a week may occur. Higher contrast medium dosage and its injection solely into the posterior circulation were the only risk factors identified in association with TCB. CONCLUSIONS: TCB is a rare, idiopathic, and typically self-limited condition associated with direct posterior cerebral neurotoxicity of iodinated contrast media, and appears to be dose-dependent.

7.
Epilepsy Behav ; 156: 109827, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759429

ABSTRACT

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.


Subject(s)
Breast Feeding , Epilepsy , Pregnancy Complications , Humans , Female , Pregnancy , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Delivery, Obstetric , Pregnancy Outcome/epidemiology
8.
Epilepsy Behav ; 152: 109660, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38364334

ABSTRACT

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.


Subject(s)
Ischemic Stroke , Stroke , Humans , Neutrophils , Case-Control Studies , Retrospective Studies , Lymphocytes , Stroke/complications , Seizures/complications , Biomarkers
9.
Epilepsy Behav ; 155: 109796, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38643659

ABSTRACT

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.


Subject(s)
Consensus , Delphi Technique , Epilepsies, Partial , Humans , Italy , Epilepsies, Partial/therapy , Patient Reported Outcome Measures
10.
Cochrane Database Syst Rev ; 8: CD014941, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39087564

ABSTRACT

BACKGROUND: Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. OBJECTIVES: To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. SEARCH METHODS: We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. SELECTION CRITERIA: RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. MAIN RESULTS: We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. AUTHORS' CONCLUSIONS: Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.


Subject(s)
Anticonvulsants , Carbamates , Chlorophenols , Drug Resistant Epilepsy , Drug Therapy, Combination , Epilepsies, Partial , Randomized Controlled Trials as Topic , Humans , Anticonvulsants/therapeutic use , Anticonvulsants/adverse effects , Drug Resistant Epilepsy/drug therapy , Epilepsies, Partial/drug therapy , Carbamates/therapeutic use , Carbamates/adverse effects , Chlorophenols/therapeutic use , Chlorophenols/adverse effects , Adult , Bias , Benzyl Compounds/therapeutic use , Benzyl Compounds/adverse effects , Tetrazoles
11.
Neurol Sci ; 45(9): 4519-4527, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38558319

ABSTRACT

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.


Subject(s)
Anticonvulsants , Consensus , Delphi Technique , Epilepsies, Partial , Pyrrolidinones , Humans , Pyrrolidinones/therapeutic use , Pyrrolidinones/administration & dosage , Anticonvulsants/therapeutic use , Anticonvulsants/administration & dosage , Epilepsies, Partial/drug therapy , Drug Therapy, Combination
12.
Epilepsia ; 64(10): e200-e206, 2023 10.
Article in English | MEDLINE | ID: mdl-37597263

ABSTRACT

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.


Subject(s)
Epilepsy , Status Epilepticus , Humans , Status Epilepticus/diagnosis , Status Epilepticus/etiology , Status Epilepticus/drug therapy , Epilepsy/complications , Coma/complications , Sleep Deprivation/complications , Retrospective Studies
13.
Epilepsia ; 64(11): 2922-2933, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38079181

ABSTRACT

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.


Subject(s)
Anticonvulsants , Epilepsies, Partial , Adult , Humans , Anticonvulsants/therapeutic use , Retrospective Studies , Treatment Outcome , Drug Therapy, Combination , Seizures/drug therapy , Seizures/chemically induced , Epilepsies, Partial/drug therapy , Pyrrolidinones/therapeutic use
14.
Epilepsia ; 64(6): e98-e104, 2023 06.
Article in English | MEDLINE | ID: mdl-37000415

ABSTRACT

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox-Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.


Subject(s)
Lennox Gastaut Syndrome , Humans , Lennox Gastaut Syndrome/drug therapy , Retrospective Studies , Anticonvulsants/therapeutic use , Treatment Outcome , Seizures/drug therapy
15.
BMC Neurol ; 23(1): 153, 2023 Apr 14.
Article in English | MEDLINE | ID: mdl-37060045

ABSTRACT

In the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study, the causes of ischemic stroke were identified in 43% of cryptogenic stroke patients monitored with implantable cardiac monitor (ICM), but one-third of these patients had non-cardioembolic causes. These results suggest the need for an early and comprehensive diagnostic work-up before inserting an ICM.


Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Humans , Electrocardiography, Ambulatory/adverse effects , Electrocardiography, Ambulatory/methods , Ischemic Stroke/complications , Stroke/etiology , Electrocardiography , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis
16.
Epilepsy Behav ; 149: 109499, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37972420

ABSTRACT

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.


Subject(s)
Seizures , Valproic Acid , Humans , Valproic Acid/therapeutic use , Levetiracetam/therapeutic use , Systematic Reviews as Topic , Seizures/drug therapy , Seizures/etiology , Seizures/prevention & control , Primary Prevention , Anticonvulsants/therapeutic use
17.
Epilepsy Behav ; 140: 109110, 2023 03.
Article in English | MEDLINE | ID: mdl-36758360

ABSTRACT

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.


Subject(s)
Status Epilepticus , Humans , Reproducibility of Results , Status Epilepticus/therapy , Status Epilepticus/drug therapy , Seizures/complications , Prognosis , Disease Progression
18.
Epilepsy Behav ; 147: 109388, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37625347

ABSTRACT

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.

19.
Epilepsy Behav ; 145: 109292, 2023 08.
Article in English | MEDLINE | ID: mdl-37321160

ABSTRACT

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.


Subject(s)
Epilepsy , Psychiatry , Humans , Neurologists/psychology , Surveys and Questionnaires , Epilepsy/therapy , Epilepsy/etiology , Attitude , Electroencephalography/adverse effects
20.
Neurol Sci ; 44(12): 4313-4322, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37599314

ABSTRACT

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.


Subject(s)
Intracranial Hypertension , Optic Nerve , Papilledema , Pseudotumor Cerebri , Adult , Humans , Intracranial Hypertension/diagnostic imaging , Intracranial Pressure , Optic Nerve/diagnostic imaging , Pseudotumor Cerebri/diagnostic imaging , Ultrasonography
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