Treatment of epilepsy in patients with Alzheimer’s disease

Introduction: Epilepsy is significantly more frequent in AD patients than in age-matched controls, even though the true extent of the phenomenon is not clear yet. Areas covered: In this review, we describe in detail the available data on the pharmacological treatment of epilepsy in patients with AD. We also briefly describe general principles of AEDs use in elderly, as well as the potential cognitive profile of AEDs and safety of concomitant psychotropic drugs in patients with epilepsy and AD. Expertcommentary: As some preclinical data suggest a role of epileptiform discharges in cognitive decline in AD, a prompt diagnosis and treatment of seizures in these patients should be pursued. The few data on the use of AEDs in AD patients suggest that newer AEDs (in particular lamotrigine and levetiracetam) might be good choices. Experimental data even support a potential role of some AEDs in modifying the disease course of AD

Phylogeography of the threatened crayfish (genus Austropotamobius) in Italy: implications for its taxonomy and conservation

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Clinical pathways of epileptic seizures and status epilepticus: results from a survey in Italy

Objective: Patients with seizures or status epilepticus (SE) access the hospital through emergency departments and may be admitted into different wards according to the level of care required. Clinicians with different expertise are in charge of taking critical therapeutic decisions. To date, very few studies have investigated the stage at which these patients are referred to neurologists or epileptologists and how guideline recommendations are applied in clinical practice. Methods: A survey was used to investigate how patients with epileptic seizures or SE are managed in emergency and in subsequent hospital pathways in Italy. Results: One hundred and seventy-seven physicians (mainly neurologists) from all parts of Italy filled in a questionnaire. Less than half of the participants (35%) answered that, in their hospital, patients with epilepsy were managed by epileptologists. The percentages were lower for patients presenting with acute seizures (21%) or SE (16%). Diagnostic, therapeutic, and assistance pathways (PDTA) for patients presenting with seizure(s) or SE were available for both conditions in about 50% of cases, while, in the rest of the hospitals, participants indicated informal agreements (about 25% of cases) or lack of any agreement (about 25% of cases) between clinicians. Professionals more often involved in PDTA were epileptologists/neurologists, emergency physicians, and intensivists. More than half ot the participants (55%) thought that organizational issues are the most important criticalities for such patients and need to be improved (61%). Significance: There is a high variability in hospital clinical pathways for epilepsy in Italy

Adjunctive Cenobamate for Focal-Onset Seizures in Adults: A Systematic Review and Meta-Analysis

Background: Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. This drug can enhance the inactivated state of voltage-gated sodium channels, preferentially inhibiting the persistent component of the sodium channel current, and acts as a positive allosteric modulator of GABAA receptors, binding at a non-benzodiazepine site. Objective: We assessed the efficacy and safety of adjunctive cenobamate for the treatment of focal-onset seizures in adult patients with epilepsy using meta-analytical techniques. Methods: We systematically searched (May, week 4, 2020) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov). There were no date limitations or language restrictions. Randomized, placebo-controlled, single or double-blinded, add-on trials of cenobamate in adult patients with uncontrolled focal-onset seizures were identified. Main outcomes included the proportion of patients with ≥ 50 and 100% reduction in seizure frequency during the maintenance treatment period compared with baseline and the incidence of treatment withdrawal and adverse events (AEs). Risk ratio (RR) with 95% confidence interval (CI) was estimated for each outcome. Results: Two trials were included, overall enrolling 659 patients (442 for the add-on cenobamate group and 217 for the add-on placebo group). Seizure frequency reduction by at least 50% occurred during the maintenance phase in 50.1% of the patients randomized to cenobamate and 23.5% of the placebo-treated participants (RR 2.18, 95% CI 1.67–2.85; p < 0.001). The pooled estimated RR to achieve seizure freedom for the cenobamate group in comparison with placebo was 3.71 (95% CI 1.93–7.14; p < 0.001). Withdrawal from randomized treatment occurred in 16.7 and 11.1% of participants receiving cenobamate and placebo, respectively (RR 1.34, 95% CI 0.85–2.09; p = 0.205). Treatment was discontinued due to AEs in 12.2 and 4.1% of the patients in the active and control arms (RR 2.27, 95% CI 1.08–4.79; p = 0.031). AEs were reported in 76.9 and 66.8% of the patients during treatment with cenobamate and placebo (RR 1.14, 95% CI 1.02–1.26; p = 0.021). The cenobamate-associated AEs included somnolence, dizziness, fatigue, balance disorder, and diplopia. Conclusions: Adjunctive cenobamate in adult patients with uncontrolled focal-onset seizures is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo

Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis

Background: Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels, neurotransmitter transporters, and multiple 7-transmembrane receptors. In contrast to tetra-hydrocannabinol, CBD lacks psychoactive properties, does not produce euphoric or intrusive side effects, and is largely devoid of abuse liability. Objective: The aim of the study was to estimate the efficacy and safety of CBD as adjunctive treatment in patients with epilepsy using meta-analytical techniques. Methods: Randomized, placebo-controlled, single- or double-blinded add-on trials of oral CBD in patients with uncontrolled epilepsy were identified. Main outcomes included the percentage change and the proportion of patients with ≥ 50% reduction in monthly seizure frequency during the treatment period and the incidence of treatment withdrawal and adverse events (AEs). Results: Four trials involving 550 patients with Lennox–Gastaut syndrome (LGS) and Dravet syndrome (DS) were included. The pooled average difference in change in seizure frequency during the treatment period resulted 19.5 [95% confidence interval (CI) 8.1–31.0; p = 0.001] percentage points between the CBD 10 mg and placebo groups and 19.9 (95% CI 11.8–28.1; p < 0.001) percentage points between the CBD 20 mg and placebo arms, in favor of CBD. The reduction in all-types seizure frequency by at least 50% occurred in 37.2% of the patients in the CBD 20 mg group and 21.2% of the placebo-treated participants [risk ratio (RR) 1.76, 95% CI 1.07–2.88; p = 0.025]. Across the trials, drug withdrawal for any reason occurred in 11.1% and 2.6% of participants receiving CBD and placebo, respectively (RR 3.54, 95% CI 1.55–8.12; p = 0.003) [Chi squared = 2.53, degrees of freedom (df) = 3, p = 0.506; I2 = 0.0%]. The RRs to discontinue treatment were 1.45 (95% CI 0.28–7.41; p = 0.657) and 4.20 (95% CI 1.82–9.68; p = 0.001) for CBD at the doses of 10 and 20 mg/kg/day, respectively, in comparison to placebo. Treatment was discontinued due to AEs in 8.9% and 1.8% of patients in the active and control arms, respectively (RR 5.59, 95% CI 1.87–16.73; p = 0.002). The corresponding RRs for CBD at the doses of 10 and 20 mg/kg/day were 1.66 (95% CI 0.22–12.86; p = 0.626) and 6.89 (95% CI 2.28–20.80; p = 0.001). AEs occurred in 87.9% and 72.2% of patients treated with CBD and placebo (RR 1.22, 95% CI 1.11–1.33; p < 0.001). AEs significantly associated with CBD were somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. Conclusions: Adjunctive CBD in patients with LGS or DS experiencing seizures uncontrolled by concomitant anti-epileptic treatment regimens is associated with a greater reduction in seizure frequency and a higher rate of AEs than placebo

Towards ecological flows: status of the benthic macroinvertebrate community during summer low-flow periods in a regulated lowland river

Climate change along with the increasing exploitation of water resources exacerbates low-flow periods, causing detrimental effects on riverine communities. The main mitigation measure currently adopted to counteract hydrological alterations induced by off-stream diversion is the release of minimum flows (MFs), even if within the European Union Water Framework Directive an upgrade towards ecological flows is urgently required to achieve good ecological status (GES). In this study, we investigated the temporal evolution of the benthic macroinvertebrate community in an Italian regulated lowland river (Ticino River) to clarify the ecological effects of summer low flows, and we evaluated the current MFs in the perspective of meeting GES standard. Biomonitoring was carried out for four consecutive years (2019-2022), in a river site immediately below a large off-stream diversion. The four study years were characterized by different streamflow patterns, thus allowing us to compare the temporal trajectories of the community under different flow conditions. Moreover, the interruption of the low-flow periods due to overflow spilled by the upstream dam gave us the opportunity to assess the effects of experimental flow peaks. Contrary to the expectation, the macroinvertebrate assemblage kept almost unvaried across the years, showing great resistance and resilience to hydrological changes. Even in extraordinarily dry 2022, the community composition varied only slightly, with a reduction of mayflies and an increase of mollusks. However, a deterioration of the ecological status below GES standard was recorded that summer, indicating the need for an upgrading of the current MFs. This upgrade would include experimental flow peaks in critical periods, which act as intermediate disturbances, enhancing community richness, diversity, and overall quality, as well as compliance with a threshold of an index specifically developed for the hydrological pressure

A flowsheet-based model approach to reduce water consumption and improve water networks management in the steel sector

Resource consumption is an important topic for steelmaking industry, which is spending significant efforts to reduce its environmental impact and improve its competitiveness. Water is largely exploited in steelworks for indirect and direct cooling, specific surface treatment, and fumes washing and cooling. It is already reused and recycled after restoring its quality through treatments for temperature and/or pollutant reduction. However, sometimes water networks are not optimized due to outdated water treatments, lack of continuous monitoring, and water network management strategies often based on experience without automation. In recent years, new water treatments, simulation, and optimization tools are becoming available, together with a stronger awareness of the importance of online parameters monitoring. Therefore, improvement of water cleaning, reuse, recycling, and consequent reduction of impact related to water exploitation are potentially achievable. The introduction of innovative treatments must be tested before their implementation in steel plants and the exploration of their behavior in different operating conditions is fundamental. The presented work addresses this topic through the application of several models of operational units, developed in OpenModelica environment and aggregated into a plant simulator. The simulator was used in different case studies related to an Italian plant to assess the impact of new filtering technology for reducing suspended solids on the analyzed water networks and test the effects of different operating configurations on the treatment efficiency. The introduction of new filtration technology leads to environmental and economic advantages due to freshwater intake reduction and water management improvemen

A 20-year study of persistence of lower urinary tract symptoms and urinary incontinence in young women treated in childhood

OBJECTIVE: To determine whether urinary incontinence (UI) and lower urinary tract symptoms (LUTS) persist over years, patients treated for UI and LUTS in childhood were re-evaluated in adulthood. MATERIALS AND METHODS: Forty-seven women (cases) treated in childhood for daytime UI/LUTS (group A) and nocturnal enuresis (group B) self-completed (average age: 24.89 ± 3.5 years) the International Consultation on Incontinence Questionnaire for Female with LUTS (ICIQ-FLUTS). ICIQ-FLUTS was self-administered to 111 healthy women (average age: 23 ± 5.1 years) from a nursing school as a control group. Data obtained from ICIQ-FLUTS and quality of life (QoL) score (0-10) were compared (Fisher's exact test) between patients and controls, and between group A (n = 28) and group B (n = 19). RESULTS: Prevalence of LUTS was higher in patients than in controls. The difference between patients and controls was statistically significant (p = 0.0001) for UI (34% vs. 7%) and feeling of incomplete bladder emptying (49% vs. 28%). QoL score was >5 in 59% of patients and 1% of controls (p = 0.0001). No significant differences were found between groups A and B. CONCLUSIONS: UI and LUTS are confirmed in young women who suffered for the same condition in childhood. Longitudinal studies are needed to assess if these symptoms persist or are newly onset

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total