Continued Underutilization of stroke care during the COVID-19 pandemic.

OBJECTIVE: This study aims to investigate the utilization of acute ischemic stroke (AIS) services during the Corona Virus Disease 2019 (COVID-19) pandemic. Based on early observations among healthcare utilization on stroke and other healthcare services, we hypothesized that there would be a persistent significant decline in AIS patients presenting to hospitals as the pandemic has progressed for over a year. METHOD: TriNetX, a large research network, is used to collect real-time electronic medical data. Data on utilization of acute ischemic stroke service was collected for the years 2018, 2019, and 2020 for variables including overall stroke volume and the number of patients that received intravenous tissue plasminogen activator (tPA) and mechanical thrombectomy (MT). RESULT: We found a 13.2-15.4% decrease in total number of AIS patients in 2020 (n 77231) compared with the years 2018 and 2019 (n 88948 and 91270 respectively, p â€‹< â€‹0.001). In the year 2020 Stroke volume was significantly lower in Q4 comparing to Q1 (Q1 vs Q4, p â€‹< â€‹0.01, while there were no significant differences in stroke volume between Quarters 2, 3, and 4 in 2020 (Q2 vs Q3, p â€‹= â€‹0.39, Q2 vs Q4, p â€‹= â€‹0.61, Q3 vs Q4, p â€‹= â€‹0.18). The Proportion of patients receiving tPA in 2020 was significantly lower compared to prior years (5.4% in 2020 vs 6.4% in 2018 and 6.0% in 2019, p â€‹< â€‹0.01), however, the proportion of patients receiving MT was significantly higher in 2020 than in 2018 (0.024 vs 0.022, p â€‹< â€‹0.01). CONCLUSION: Despite significant alteration in practices to optimize healthcare delivery and mitigate the collateral impact of the pandemic on care for other conditions, a persistent decline in AIS volumes remains. Delayed presentation, fear-of-contagion, reallocation, and poor availability of health care resources are potential contributors. Prospective evaluation and further investigation for these trends is needed.

A neuromuscular-based analysis of the open payments program.

INTRODUCTION: In August 2013, the Centers for Medicare and Medicaid Services (CMS) Open Payments Program (OPP) made eligible payment information publicly available. Data about industry payments to neuromuscular neurologists are lacking. METHOD: Financial relationships were investigated between industry and US neuromuscular neurologists from January 2014 through December 2018 using the CMS OPP database. RESULTS: The total annual payments increased more than 6-fold during the study period. The top 10% of physician-beneficiaries collected 80% to 90% of total industry payments except in 2014. In 2018, the most common drugs associated with payments to neuromuscular neurologists were nusinersen, vortioxetine, eteplirsen, alglucosidase alpha, edaravone, and intravenous immunoglobulin. DISCUSSION: A substantial increase in the annual payments to neuromuscular physicians during the study period is likely due to the development of new treatments, including gene therapy.

A review of pathophysiology and neuropsychiatric manifestations of COVID-19.

INTRODUCTION: The outbreak of coronavirus disease 2019 (COVID-19) has become one of the most serious pandemics of the recent times. Since this pandemic began, there have been numerous reports about the COVID-19 involvement of the nervous system. There have been reports of both direct and indirect involvement of the central and peripheral nervous system by the virus. OBJECTIVE: To review the neuropsychiatric manifestations along with corresponding pathophysiologic mechanisms of nervous system involvement by the COVID-19. BACKGROUND: Since the beginning of the disease in humans in the later part of 2019, the coronavirus disease 2019 (COVID-19) pandemic has rapidly spread across the world with over 2,719,000 reported cases in over 200 countries [World Health Organization. Coronavirus disease 2019 (COVID-19) situation report-96.,]. While patients typically present with fever, shortness of breath, sore throat, and cough, neurologic manifestations have been reported, as well. These include the ones with both direct and indirect involvement of the nervous system. The reported manifestations include anosmia, ageusia, central respiratory failure, stroke, acute inflammatory demyelinating polyneuropathy (AIDP), acute necrotizing hemorrhagic encephalopathy, toxic-metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. These data were derived from the published clinical data in various journals and case reports. CONCLUSION: The neurological manifestations of the COVID-19 are varied and the data about this continue to evolve as the pandemic continues to progress.

Immunosuppression in chronic autoimmune neurological disorders during the COVID-19 pandemic.

OBJECTIVE: To study the risk of acquiring Corona Virus Disease 2019 (COVID-19) and its outcomes in patients on immunosuppressive therapy (IST) for chronic autoimmune neuromuscular disorders (aNMD) and multiple sclerosis (MS). METHODS: We used TriNetX, a global health collaborative clinical research platform collecting real-time electronic medical records data, which has one of the largest known global COVID-19 database. We included patients with chronic autoimmune neuromuscular disorders (aNMD) [myasthenia gravis (MG), inflammatory myositis, and chronic inflammatory neuropathies (CIN)] and MS, based on the International Classification of Disease-10 (ICD-10) coding for one year before January 20th, 2020. We examined the use of IST, rate of COVID- 19, hospitalization, intubation, and mortality among the patients with aNMD and MS. RESULTS: A total of 33,451 patients with aNMD and 42,899 patients with MS were included. Among them, 111 (0.33%) patients with aNMD and 115 patients (0.27%) with MS had COVID-19. About one third of them required hospitalization. IST did not appear to have a significant impact on overall infection risk in either group; however, risk of hospitalization for immunosuppressed patients with aNMD was higher (Odds ratio 2.86, p-value 0.011). CONCLUSIONS: IST use does not appear to make patients with aNMD and MS more vulnerable to COVID-19. IST may be continued during the pandemic, as previously suggested by expert opinion guidelines. However, it is important to consider individualizing immunotherapy regimens in some cases. Additional physician reported registry-based data is needed to further confirm these findings.

COVID-19 and stroke, a case series and review of literature.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) cases continue to increase around the World. Typical symptoms include fever and respiratory illness but a constellation of multisystem involvement including central nervous system (CNS) and peripheral nervous system (PNS) have been reported with COVID-19. Acute ischemic strokes (AIS) have also been reported as a complication. METHODOLOGY: We analyzed patient characteristics, clinical outcomes, laboratory results and imaging results of four patients with COVID-19 who had AIS. RESULTS: All four patients were =< 60 years, had hypoxemic respiratory failure secondary to pneumonia, elevated D-dimer and inflammatory markers. CONCLUSION: Ischemic strokes are known complications in patients with severe COVID-19.

Coronavirus Disease 2019 in Patients With Prior Ischemic Stroke.

BACKGROUND: It is uncertain if patients with prior ischemic stroke are vulnerable to coronavirus disease 2019 (COVID-19) and its complications. METHODS: We used TriNetX, a global health collaborative clinical research platform with a large global COVID-19 database. COVID-19 infection was identified with a positive lab value for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related ribonucleic acid (RNA). FINDINGS: A total of 604,258 patients with history of ischemic stroke were identified, of which 891 patients (study cohort) were diagnosed with COVID-19. A control cohort with 32,136 patients diagnosed with COVID-19 after January 20th 2020 without a history of ischemic stroke were identified. A comparison between study cohort and control cohort showed patients with prior history of stroke (study cohort) were older (69.5 vs 47.8; p<0.0001) and had more comorbidities contributing to worse clinical outcomes. After propensity matching for demographic variables and comorbidities, only rate of hospitalization (287 vs 231; p=0.0035) and need for critical care services (85 vs 55; p=0.0082) remained statistically significant while intubation (51 vs 43; p=0.39) and death (119 vs 115; p=0.77) showed trends towards worse outcomes but were not statistically significant.  Interpretation: Patients with history of ischemic stroke tend to be significantly older with several comorbid conditions contributing to worse clinical outcomes after COVID-19, which makes them a vulnerable population.

Spectrum of neuropsychiatric manifestations in COVID-19.

Corona Virus Disease 2019 (COVID-19) emerged in December 2019 from Wuhan, China. It typically presents with mild upper respiratory tract infection symptoms and may have life threatening complications, including acute respiratory distress syndrome, acute stroke, myocardial infarction, kidney failure, shock, and even death. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. We analyzed COVID-19 adult patients in the TriNetX database, which is a global health collaborative clinical research platform collecting real-time electronic medical records data from a network of health care organizations (HCOs) from January 20, 2020 to June 10th, 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headache (3.7%) and sleep disorders (3.4%), Encephalopathy (2.3%), Stroke and transient ischemic attack (TIA) (1.0%) and 0.6% had seizures. Most common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%), while 0.2% patients had suicidal ideation. Early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality.

Treating epilepsy in the setting of medical comorbidities.

OPINION STATEMENT: Treatment of epilepsy in patients with medical comorbidities can be challenging. Comorbidities can affect medical management and quality of life. In this review, we discuss treatment options in patients with epilepsy and medical comorbidities. In our opinion, the best way to manage patients with medical comorbidities and epilepsy is to accurately recognize and diagnose medical comorbidities, and to have adequate knowledge and familiarity with antiepileptic drug (AED) metabolism, dosing, side effects, and drug interactions. We believe the trend should move toward using the newer generation of AEDs given their generally reduced rate of adverse effects and interactions. The primary goal of therapy is seizure freedom without side effects.

Analysis of poly(ADP-Ribose) polymerases in Arabidopsis telomere biology.

Maintaining the length of the telomere tract at chromosome ends is a complex process vital to normal cell division. Telomere length is controlled through the action of telomerase as well as a cadre of telomere-associated proteins that facilitate replication of the chromosome end and protect it from eliciting a DNA damage response. In vertebrates, multiple poly(ADP-ribose) polymerases (PARPs) have been implicated in the regulation of telomere length, telomerase activity and chromosome end protection. Here we investigate the role of PARPs in plant telomere biology. We analyzed Arabidopsis thaliana mutants null for PARP1 and PARP2 as well as plants treated with the PARP competitive inhibitor 3-AB. Plants deficient in PARP were hypersensitive to genotoxic stress, and expression of PARP1 and PARP2 mRNA was elevated in response to MMS or zeocin treatment or by the loss of telomerase. Additionally, PARP1 mRNA was induced in parp2 mutants, and conversely, PARP2 mRNA was induced in parp1 mutants. PARP3 mRNA, by contrast, was elevated in both parp1 and parp2 mutants, but not in seedlings treated with 3-AB or zeocin. PARP mutants and 3-AB treated plants displayed robust telomerase activity, no significant changes in telomere length, and no end-to-end chromosome fusions. Although there remains a possibility that PARPs play a role in Arabidopsis telomere biology, these findings argue that the contribution is a minor one.