Impact of Donepezil and Memantine on Behavioral and Psychological Symptoms of Alzheimer Disease: Six-month Open-label Study.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the treatment of moderate AD. OBJECTIVE: To evaluate the effects of donepezil and memantine in relieving BPSD in individuals with moderate AD. METHOD: We conducted a prospective, randomized, 6-month clinical trial involving 85 individuals with moderate AD divided into two groups: group 1 (n = 42) was treated with donepezil; group 2 (n = 43) was treated with memantine. We used the Neuropsychiatric Inventory (NPI) to assess the prevalence and severity of BPSD at baseline and after 6 months of treatment with donepezil or memantine. RESULTS: The two groups' baseline characteristics, including age, sex, mean length of education, and disease duration, were comparable, as were their baseline Mini-Mental State Examination scores. The NPI Total score improved from baseline to month 6 in both groups (P < 0.0001). Analyses of the NPI subdomains revealed that both donepezil treatment and memantine treatment produced statistically significant improvement in all of the NPI domains except euphoria and apathy, for which no improvement was observed after memantine treatment. Both treatments were well tolerated, with mostly mild and transient adverse effects. CONCLUSION: Specific drugs for AD, including donepezil and memantine, may be effective in treating BPSD in individuals with moderate AD, with a favorable safety profile.

DELAYED EFFECT OF VNS ON INTERICTAL EPILEPTIFORM DISCHARGES AND PHARMACORESISTANCE IN A PATIENT WITH REFRACTORY PERINATAL POSTISCHEMIC EPILEPSY.

A 20-year-old female with refractory perinatal postischemic catastrophic epilepsy and frequent daily generalized atonic, tonic, tonic-clonic and focal seizures was hospitalized in the progressive phase of illness. The diagnosis was confirmed by semiology, interictal electroencephalogram (EEG), long-term video EEG monitoring, and brain magnetic resonance imaging. Repeated interictal EEG findings showed generalized spike and slow wave complexes with a 2-3 Hz frequency. Interictal EEG showed evidence of electroclinical epileptic status on several occasions. She was treated with various antiepileptic drugs without improvement. After verification of her incompetence for normal autonomous living, which resulted in very low quality of life, this patient with refractory epilepsy underwent implantation of vagus nerve stimulator (VNS). In this case report, we present delayed effect of VNS on interictal epileptiform discharges and pharmacoresistance.

INCIDENCE OF ACUTE SYMPTOMATIC SEIZURES IN PATIENTS WITH COVID-19: A SINGLE-CENTER STUDY.

The most common neurological symptoms in patients with SARS-CoV-2 infection are headache, myalgia, encephalopathy, dizziness, dysgeusia and anosmia, making more than 90 percent of neurological manifestations of COVID-19. Other neurological manifestations such as stroke, movement disorder symptoms or epileptic seizures are rare but rather devastating, with possible lethal outcome. The primary aim of this study was to estimate the prevalence of acute symptomatic seizures among COVID-19 patients, while secondary aim was to determine their possible etiology. Out of 5382 patients with COVID-19 admitted to Dubrava University Hospital from November 1, 2020 until June 1, 2021, 38 (seizure rate 0.7%) of them had acute symptomatic seizures. Of these 38 patients, 29 (76.3%) had new-onset epileptic seizures and nine (23.7%) patients with previous epilepsy history had breakthrough seizures during COVID-19. Although acute symptomatic seizures are an infrequent complication of COVID-19, seizure risk must be considered in these patients, particularly in the group of patients with a severe course of the disease. Accumulation of proinflammatory cytokines may contribute to the occurrence of seizures in patients with COVID-19, but seizures may also be secondary to primary brain pathology related to COVID-19, such as stroke or encephalitis.

FALSE PHARMACORESISTANCE - A TRUE PROBLEM.

Pharmacoresistant epilepsy poses a great burden to patients, their families, and the whole healthcare system, with numerous social, economic, physical, and psychical consequences. Hence, it is a diagnosis that has to be made only in cases of high certainty, after all potential causes of epilepsy have been evaluated. One of the important causes of pharmacoresistant epilepsy is false pharmacoresistance, an entity that implies a condition in which poor disease control is not a consequence of the biology of the disease itself, antiepileptic drug inefficacy, and/or patient specificity. It is a consequence of human error and strongly depends on the experience of the treating physician, as well as on the attitude of the patient. Despite its 'falseness', this entity is accompanied by real consequences for the patient and his family, and at the same time, it delays appropriate treatment of the actual disease from which the patient is suffering. In order to introduce appropriate treatment and avoid unnecessary and harmful diagnostic procedures, false pharmacoresistance is a condition that has to be ruled out in any patient with difficult-to-treat seizures.

Breast cancer resistance protein polymorphism ABCG2 c.421C>A (rs2231142) moderates the effect of valproate on lamotrigine trough concentrations in adults with epilepsy.

BACKGROUND: Valproate inhibits clearance of lamotrigine and greatly increases its concentrations. We assessed whether this effect was moderated by a polymorphism (ABCG2 c.421C>A) of the breast cancer resistance protein. METHODS: In two consecutive independent studies in adults with epilepsy on lamotrigine monotherapy or cotreated with valproate: (i) Exposure to valproate was considered treatment, (ii) dose-adjusted lamotrigine troughs at steady state were the outcome, and (iii) ABCG2 c.421C>A genotype (wild-type [wt] homozygosity or variant carriage) was the tested moderator. We used entropy balancing (primary analysis) and exact/optimal full matching (secondary analysis) to control for confounding, including polymorphisms (and linked polymorphisms) suggested to affect exposure to lamotrigine (UGT1A4*3 c.142T>G, rs2011425; UGT2B7-161C>T, rs7668258; ABCB1 1236C>T, rs1128503) to generate frequentist and Bayesian estimates of valproate effects (geometric means ratios [GMR]). RESULTS: The two studies yielded consistent results (replicated); hence, we analyzed combined data (total N = 471, 140 treated, 331 controls, 378 ABCG2 c.421C>A wt subjects, 93 variant carriers). Primary analysis: in variant carriers, valproate effect (GMR) on lamotrigine (treated, n = 21 vs. controls, n = 72) was around 60% higher than in wt subjects (treated, n = 119 vs. controls, n = 259)-ratio of GMRs 1.61 (95%CI 1.23-2.11) (frequentist) and 1.63 (95%CrI 1.26-2.10) (Bayes). Similar differences in valproate effects between variant carriers and wt subjects were found in the secondary analysis (valproate troughs up to 364 µmol/L vs. no valproate; or valproate ≥364 µmol/L vs. no valproate). Susceptibility of the estimates to unmeasured confounding was low. CONCLUSION: Data suggest that polymorphism rs2231142 moderates the effect of valproate on exposure to lamotrigine.

The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy.

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy. Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data. Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance. Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.