Immune Mechanism of Epileptogenesis and Related Therapeutic Strategies.

Immunologic and neuroinflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources, it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. For this reason, we performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways involved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

COVID-19 prevalence and mortality in people with epilepsy: A nation-wide multicenter study.

BACKGROUND: To assess the prevalence, severity, and mortality of COVID-19 in people with epilepsy (PWE) and evaluate seizure control in PWE during and after COVID-19. METHODS: Retrospective, observational, multicenter study conducted in 14 hospitals. Medical records of randomly selected PWE followed at neurology outpatient clinics were reviewed. Proportion of PWE with a positive test for SARS-CoV-2 during 2020 was calculated. Risk factors associated with COVID-19 and its morbimortality were evaluated. RESULTS: 2751 PWE were included, mean age 48.8 years (18-99), 72.4% had focal epilepsy, and 35% were drug-refractory. COVID-19 prevalence in PWE was 5.53%, while in the Spanish population was 4.26%. Proportion of admissions to hospital, ICU, and deaths in PWE were 17.1%, 2%, and 4.61% of COVID-19 cases, while in Spanish population were 10.81%, 0.95%, and 2.57%, respectively. A severe form of COVID-19 occurred in 11.8%; dyslipidemia, institutionalization at long-term care facilities, intellectual disability, and older age were associated risk factors. Older age, hypertension, dyslipidemia, cardiac disease, and institutionalization were associated with mortality from COVID-19. Seizure control was stable in 90.1% of PWE during acute COVID-19, while 8.6% reported an increase in seizure frequency. During post-COVID-19 follow-up, 4.6% reported seizure control worsening. CONCLUSIONS: COVID-19 was moderately prevalent in PWE. One out of 5 patients required medical attention and 4.6% died due to COVID-19. Older age, dyslipidemia, institutionalization, and intellectual disability were significant risk factors associated with severe COVID-19. Seizure control remained stable during COVID-19 and throughout long-term follow-up in most PWE who contracted the infection.

Incidence and case fatality rate of COVID-19 in patients with active epilepsy.

OBJECTIVE: This article estimates the incidence and fatality of coronavirus disease 2019 (COVID-19) and identifies potential risk factors for fatality in patients with active epilepsy. METHODS: This is a cross-sectional observational study of patients with active epilepsy and COVID-19. A control group was used to compare the cumulative incidence and case-fatality rate (CFR). The main outcomes of the study were cumulative incidence, defined as number of patients with active epilepsy and COVID-19 admitted to an emergency department divided by the total number of patients with epilepsy at risk, and CFR based on the number of deaths during the enrollment period. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with active epilepsy. RESULTS: Of the 1,537 patients who fulfilled the inclusion criteria, 21 (1.3%) had active epilepsy. The cumulative incidence (95% confidence interval [CI]) of COVID-19 in patients with epilepsy was higher (1.2% [0.6-2.4]) compared to the population without epilepsy (0.5% [0.5-0.5]). In reverse transcription PCR-positive patients, there were no significant differences in CFR in patients with active epilepsy compared to patients without epilepsy (33.3% vs 8.3%; p = 0.266). Of the 21 patients with active epilepsy, 5 (23%) died. In multivariate analysis, the factor associated with fatality in patients with active epilepsy was hypertension (odds ratio [OR] 2.8 [95% CI 1.3-21.6]). In another model, age (OR 1.0 [95% CI 1.0-1.1]) and epilepsy (OR 5.1 [95% CI 1.3-24.0]) were associated with fatality during hospitalization. CONCLUSION: COVID-19 cumulative incidence was higher in patients with active epilepsy. Epilepsy was associated with fatality during hospitalization. Hypertension was associated with fatality in patients with epilepsy.

Incidence and case fatality rate of COVID-19 in patients with inflammatory articular diseases.

OBJECTIVE: To describe the incidence and fatality of coronavirus disease 2019 (COVID-19) and identify risk factors to fatality in patients with inflammatory articular diseases (IAD). METHODS: This is a cross-sectional observational study of IAD patients and COVID-19 with controls matched for age, sex, and RT-PCR. A control group was used to compare the cumulative incidence (CI) and case fatality rate (CFR). The main outcomes of the study were CI and CFR. Other variables included comorbidities, treatments, and characteristics of the COVID-19. Multiple logistic regression analysis was performed to investigate risk factors for fatality in patients with IAD. RESULTS: Of the 1537 patients who fulfilled the inclusion criteria, 23/1537 (1.49%) had IAD 13 (0.8%) had rheumatoid arthritis (RA), 5 psoriatic arthritis (PsA) (0.3%) and 5 axial spondyloarthritis (0.3%). There were no significant differences in CI of COVID-19 and CFR in patients with IAD compared with COVID-19 patients without IAD. In RT-PCR positive patients, the CI of COVID-19 in PsA and AS was higher. Of the 23 IAD patients, 2 RA patients (8.6%) died. The patients did no show characteristics of the COVID-19 disease different from the population. In multivariate analysis, the factor associated with fatality in patients with IAD was older age (OR [95% CI], 1.1 [1.0-1.2]). CONCLUSION: COVID-19 CI, fatality rate and other features do not seem to be increased in IAD patients. Older age was associated with fatality in patients with IAD.