COVID-19 presenting as stroke.

OBJECTIVE: Acute stroke remains a medical emergency even during the COVID-19 pandemic. Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations. Here we present a series of four patients with COVID-19 that presented with acute stroke. METHODS: We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection. All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study. Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study. Retrospective patient data were obtained from electronic medical records. Informed consent was obtained. RESULTS: We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection. We elucidate the clinical characteristics, imaging findings, and the clinical course. CONCLUSIONS: Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke. Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should dawn appropriate personal protective equipment in every suspected patient. Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection.

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.

Industry payments to hospitalist physicians: a 5-year analysis of the Open Payments programme from 2014 to 2018.

We analysed Open Payments programme data (https://openpaymentsdata.cms.gov) on industry-to-physician payments to hospitalists for the years 2014 to 2018. Payments to hospitalists increased by 106.5% from 2014 to 2018 with food and beverage (38.5%) and compensation for services other than consulting (24.3%) being the highest-paid categories. Industry payment to hospitalists was highly skewed with top 10 hospitalists receiving more than 30% of the total payments during the study period. The most common drugs associated with payments were anticoagulant medications (apixaban and rivaroxaban). Industry seems to be spending a significant amount of money to increase awareness of medications among hospitalists. Identification of these trends and potential motives of industry spending is critical to address any potential physician bias.

Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA.

Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders characterized by abnormal iron deposition in the basal ganglia. We report that de novo mutations in WDR45, a gene located at Xp11.23 and encoding a beta-propeller scaffold protein with a putative role in autophagy, cause a distinctive NBIA phenotype. The clinical features include early-onset global developmental delay and further neurological deterioration (parkinsonism, dystonia, and dementia developing by early adulthood). Brain MRI revealed evidence of iron deposition in the substantia nigra and globus pallidus. Males and females are phenotypically similar, an observation that might be explained by somatic mosaicism in surviving males and germline or somatic mutations in females, as well as skewing of X chromosome inactivation. This clinically recognizable disorder is among the more common forms of NBIA, and we suggest that it be named accordingly as beta-propeller protein-associated neurodegeneration.

ß-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

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.

Trends in Demographics of Neurology House Staff in the United States.

Background The lack of an adequate number of neurologists is a worldwide problem. As populations age, the prevalence of neurological disorders will likely increase, thereby increasing the demand for neurologists. In addition to the growing demand, inadequate diversity in the neurology healthcare workforce still exists. The purpose of this study is to examine the demographic characteristics of neurology residents and fellows. Methodology This cross-sectional study used data from the following publicly available databases: Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and the United States Census Bureau. Trends (from 2007 to 2018) in demographic characteristics were assessed using the slope and the associated p-value of a simple linear regression model, with the year as the independent variable. All p-values of <0.05 were considered significant. Results From 2007 through 2018, the percentage of US medical school graduates in neurology residency decreased from 58% to 55% (slope = -0.25; p = 0.0004), while the percentage of international medical graduates (IMGs) decreased from 36% to 32% (slope = -0.29; p = 0.0141) and doctor of osteopathy (DO) graduates increased from 6% to 13% (slope = 0.58; p < 0.0001). Although the percentage of female neurology residents increased from 39.5% in 2007 to 43.1% in 2018 (slope = 0.03; p = 0.8659), female physicians were underrepresented in vascular neurology fellowship (34% in 2018). Collectively, the percentage of underrepresented minorities in neurology residencies was low and increased only slightly over time (from 8% in 2011 to 9% in 2018; slope = 0.17; p = 0.0788). In 2018, the proportion of underrepresented minorities was smaller in neurology fellowships (5.5% neurophysiology, 12.5% epilepsy, 10.4% neuromuscular, and 12.4% vascular) compared to the population as a whole (31.3%). Conclusions IMGs still play an important role in filling a significant portion of the neurology residencies and fellowships. DO graduates have slowly increased in neurology residencies and fellowships. Members of several racial/ethnic minority groups and women are underrepresented in neurology house staff and efforts need to be taken to increase diversity.

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.

Multiple Intracranial Tuberculomas with an Intra-medullary Spinal Cord Tuberculoma in a Pediatric Patient.

Central nervous system (CNS) tuberculosis (TB), caused by Mycobacterium tuberculosis (MT), is a severe form of TB, which presents as meningitis, cerebritis, abscesses, spinal tuberculous arachnoiditis, and rarely tuberculomas. CNS TB is prevalent in the underdeveloped or developing world and is common in malnourished, alcoholics, children, young adults, immunocompromised, and cancer patients. Intracranial tuberculomas (ICT) can present with symptoms and signs of focal neurological deficits with or without systemic manifestations. ICT is the least common presentation of CNS TB. Medical management with anti-TB drugs and steroids is the mainstay of treatment, while surgical intervention is usually reserved for refractory cases. Here, we present the case of a 10-year-old Indian American girl with headaches, diplopia, fever, and neck pain diagnosed with ICT and intramedullary spinal cord tuberculoma.

Corona Virus Disease 2019 (COVID-19) Presenting as Acute ST Elevation Myocardial Infarction.

Patients with Covid-19 disease commonly present with symptoms related to respiratory illness, and less commonly they develop cardiovascular complications either on presentation or during the course of the disease. The mortality/morbidity is high in these patients with cardiovascular involvement. Acute ST-elevation myocardial infarction (STEMI) is a medical emergency which needs immediate coronary re-perfusion for better patient outcomes. Here we present a patient who presented to the emergency room with acute STEMI and later tested positive for COVID-19. She was successfully treated with coronary revascularization and stent placement, and remains on the ventilator to date as she quickly developed acute respiratory distress syndrome. We need more research in Covid-19 patients with cardiovascular involvement for early diagnosis, prevention of exposure to health care workers and effective treatment.

Isolated Area Postrema Syndrome Presenting as Intractable Nausea and Vomiting.

Neuromyelitis optica (NMO) is a disease of central nervous system, characterized by demyelination and axonal damage mostly involving optic nerves and spinal cord. Usually these patients present with symptoms related to optic neuritis or myelitis with a typical relapsing course. Some patients present with less common symptoms involving brain stem like nausea and vomiting, especially those involving area postrema (AP) located in dorsal medulla. International panel for NMO diagnosis revised criteria in 2015 and came up with a unifying term NMO spectrum disorders (NMOSD) instead of NMO. Patients with NMO having AP involvement are grouped under area postrema syndrome (APS). Usually patients with AP symptoms also have neurological symptoms upon presentation. Here we present a rare case of an NMO who presented with isolated APS with no other neurological symptoms.

Severe Respiratory Alkalosis in Acute Ischemic Stroke: A Rare Presentation.

Respiratory alkalosis is a rare but severe complication of acute ischemic stroke (AIS). In ischemic stroke, respiratory alkalosis results from hyperventilation due to the effect of stroke on the respiratory center. We report a case of a young male who presented with acute encephalopathy. Work-up revealed ischemic infarcts in the bilateral cerebellar and left posterior cerebral artery territory. Arterial blood gas (ABG) showed severe respiratory alkalosis with a pH of 7.72. Alkalosis resolved with mechanical ventilation. Such a high pH associated with AIS has not been reported in the medical literature so far. The index case highlights the severity of respiratory alkalosis that can be caused by an AIS. We conclude that early diagnosis and management of severe respiratory alkalosis is crucial for survival and recovery.

New Delhi Metallo-beta-lactamase-producing Enterobacter Cloacae - A Rare Multidrug Resistance Strain in a Caucasian Woman.

New Delhi metallo-beta-lactamase (NDM-1) is a novel metallo-beta-lactamase (MBL) gene carried by some Enterobacteriaceae that induces resistance to most of the antibiotics. First described in a Swedish patient hospitalized in India with an infection due to Klebsiella pneumoniae. NDM-1 makes bacteria resistant to a broad range of beta-lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic-resistant bacterial infections. Most of these carbapenem resistant Enterobacteriaceae (CRE) are increasingly recognized in hospital settings and post-acute care settings like long-term acute care settings. Percentage of CRE infections is increasing in the United States of America, and invasive infections with CRE carry high mortality rates and limited treatment options. We here present a rare case of elderly Caucasian woman with CRE cellulitis of both legs with no travel history.

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.

A Five-Year Analysis of Industry Payments to Sleep Neurologists From 2014 Through 2018.

Background and objectives  Sleep medicine has been one of the fastest-growing medical fields in recent years. The industry plays a big role in developing new medications and devices for both diagnosis and treatment of sleep-related problems. We analyzed payments made by industry to physicians from 2014 through 2018 based on the Open Payments Program data. Methods Centers for Medicare and Medicaid Services Open Payment Program and American Board of Psychiatry and Neurology databases were explored to elicit financial relationships between industry and sleep neurologists. Results Payments made by industry to sleep neurologists have been steadily increasing from 2014 through 2018. Approximately 16% to 22% of sleep certified neurologists received payments from industry during the study period. Interestingly, the payments made to the top 10% of the sleep physicians contributed approximately 85% to 96% of the total payments. The top two categories to which the highest payments were made were compensation for services and royalty and/or licensing fees. Silenor® (doxepin), Xyrem® (sodium oxybate), Aptiom® (eslicarbazepine acetate), Belsomra® (suvorexant), and Fycompa® (perampanel) were most of the drugs, which made the highest payments, that got approved by the Food and Drug Administration in the last decade. Conclusions  It seems that the industry is spending significant amounts of money in educating the physicians and in marketing the newer drugs. This analysis of the data on payments from industry is very useful in identifying any potential conflicts of interest from physicians. Further analyses are needed to study the trends of physician practice behavior and decision making.

Trends of Industry Payments in Neurology Subspecialties.

Background Open Payments is a national disclosure program to promote transparency by the public disclosure of financial relationships between the pharmaceutical and medical device industries and physicians. Objective To explore payments from the industry to physicians in various neurology subspecialties. Methods Open Payments Program (OPP) data (https://openpaymentsdata.cms.gov) on industry-to-physician payments for the years 2014-2018 were extracted for general neurology, neuromuscular, neurophysiology, and vascular neurology. The data were then analyzed to explore trends in payments for various subspecialties and to identify the possible factors underlying these trends. Results Overall, industry-to-physician payments for neurology subspecialties increased by 16% from 2014 to 2018. The introduction of newer drugs in a subspecialty was likely the driving factor for higher industry payments. Nearly half of the total industry-to-physician payments were for the subspecialty of multiple sclerosis (MS)/Neuroimmunology; this coincided with Aubagio and Copaxone being the top two medications associated with the highest industry payments in 2014, Aubagio, and Lemtrada in 2018. A significant increase in spending percentages for headache, neuromuscular disorders, and movement disorders was observed while a relative decrease in the payments for MS/neuroimmunology and epilepsy was identified; these trends coincide with the introduction of new drugs such as Aimovig, Neuplazid, Nusinersen, and Austedo for headache, neuromuscular and movement disorders. Conclusions From 2014 to 2018, the total industry-to-physician payments for neurology subspecialties increased while the distribution of industry-to-physician payments for various neurology subspecialties showed notable changes. The introduction of newer medications in a subspecialty coincided with higher industry payments. Identification of these trends and potential motives of the industry spending is critical to address any potential physician bias in prescribing medications.