1,721,226 research outputs found
New evidence in adjunctive treatment of focal-onset seizures in adults: a critical appraisal
Full text linkAnti-seizure medications (ASMs) represent the pillar of the treatment of epilepsy. The rate of drug-resistant epilepsy remained substantially unchanged over time and there is still the need for new and more effective treatment options. Brivaracetam, cenobamate, eslicarbazepine acetate, lacosamide and perampanel are 'third-generation' ASMs. The aim of this article is to summarize the currently available evidence about the relative efficacy and tolerability of the 'third-generation' ASMs as adjunctive treatment of focal-onset seizures in adults. So far, no randomized controlled study directly compared these ASMs, and their comparative efficacy and tolerability have been indirectly evaluated by one network meta-analysis. Sixteen trials were included in the network meta-analysis. The efficacy endpoints were the rates of seizure response and seizure freedom, defined as ≥ 50% and 100% reduction in baseline monthly seizure frequency. The tolerability endpoints were the rate of patients who developed any treatment emergent adverse events (TEAEs) and any TEAE leading to drug discontinuation. Cenobamate had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction. Brivaracetam and lacosamide had the greatest likelihood to rank as the best-tolerated treatments for the occurrence of any TEAE and TEAE leading to discontinuation. Although network meta-analyses are not substitutes of direct comparisons, they can provide valuable evidence about the hierarchy of interventions. Additional real-world data can be useful complement to characterize the clinical profile and therapeutic potentialities of third-generation ASMs
Cerebral hemodynamics and cognitive performance in carotid artery disease
Full text linkObiettivi: Le connessioni tra malattia aterosclerotica dell’arteria carotide interna (ACI), rivascolarizzazione chirurgica ed abilità cognitive non sono ancora completamente chiarite. L’obiettivo dello studio è stato esplorare la relazione tra emodinamica cerebrale e funzioni neuro-cognitive in pazienti con stenosi severa dell’ACI trattati con endarterectomia carotidea (EAC).
Materiali e metodi: Pazienti con anamnesi di attacco ischemico transitorio nei precedenti 6 mesi e stenosi ipsilaterale di grado severo dell’ACI trattati con EAC sono stati reclutati. La reattività vasomotoria cerebrale (RVC) all’ipercapnia è stata misurata tramite ultrasonografia Doppler transcranica. Le Matrici Colorate Progressive ed il Test della Copia della Figura Complessa, ed i test di Fluenza Verbale fonologica e categoriale sono stati somministrati per valutare le funzioni cognitive degli emisferi cerebrali destro e sinistro, rispettivamente. Emodinamica cerebrale e funzioni cognitive sono state valutate prima e 6 mesi dopo l’intervento di EAC.
Risultati: Centottantatre pazienti sono stati inclusi. L’età media è risultata 73.1 (6.9) anni e 122 (66.7%) erano maschi. Prima dell’EAC, i pazienti hanno mostrato una ridotta RVC dal lato della stenosi dell’ACI e ridotte abilità nei test cognitivi relativi all’emisfero cerebrale ipsilaterale. A 6 mesi dall’EAC, l’emodinamica cerebrale e le funzioni neurocognitive sono risultate significativamente migliorate. La variazione nei risultati ottenuti nei test cognitivi relativi all’emisfero rivascolarizzato è risultata inversamente associata alla RVC pre-operatoria e positivamente associata al miglioramento dell’emodinamica cerebrale.
Conclusioni: Nei pazienti con stenosi severa sintomatica della ACI, le abilità cognitive sono migliorate dopo 6 mesi dell’EAC. Il miglioramento cognitive è risultato essere associato all’incremento della RVC dal lato della correzione chirurgica e predetto dallo stato emodinamico cerebrale pre-operatorio. L’emodinamica cerebrale può essere un determinante indipendente e potenzialmente reversibile della disfunzione cognitiva nella malattia aterosclerotica carotidea.Background and aim: The inter-relationships between atherosclerotic disease of internal carotid artery (ICA), surgical revascularization and cognitive outcome are not fully understood. The aim of this study was to explore the relationship between cerebral hemodynamics and neurocognitive functioning in patients with high-grade ICA stenosis undergoing carotid endarterectomy (CEA).
Materials and methods: Patients with history of transient ischemic attack within the past 6 months and ipsilateral high-grade stenosis of ICA undergoing CEA were prospectively enrolled. Cerebral vasomotor reactivity (CVR) to hypercapnia was measured through transcranial Doppler ultrasonography. Coloured Progressive Matrices plus Complex Figure Copy Test, and phonemic plus categorical Verbal Fluency tests were performed to test cognitive functions of right and left hemispheres, respectively. Cerebral hemodynamics and cognitive functions were assessed before and 6 months after CEA.
Results: One hundred and eighty-three patients were included. The mean age was 73.1 (6.9) years and 122 (66.7%) were males. Before CEA, patients had decreased CVR on the side of ICA stenosis and reduced performance in the cognitive tests exploring the ipsilateral cerebral hemisphere. At 6 months from CEA, cerebral hemodynamics and neurocognitive functioning were significantly improved. The performance change in cognitive tests exploring the revascularized hemisphere was inversely associated with pre-operative ipsilateral CVR and positively associated with the improvement in cerebral hemodynamics.
Conclusions: In patients with symptomatic high-grade ICA stenosis, cognitive performance was enhanced at 6 months since CEA. The cognitive improvement was related to the increase in CVR on the side of stenosis correction and predicted by baseline cerebral hemodynamic status. Cerebral hemodynamics may be an independent and potentially reversible determinant of cognitive dysfunction in severe carotid artery disease
Diagnosing epileptic seizures in patients with Alzheimer's disease and deciding on the appropriate treatment plan
No full textIntroduction: 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
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Cenobamate add-on therapy for drug-resistant focal epilepsy
No full textBackground: 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
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