Creutzfeldt-Jakob Disease with Initial Typical Parkinsonism Precipitated by COVID-19? A Case Report (preprint)

Background Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease caused by the accumulation of PrPSc. While COVID-19-induced sporadic CJD (sCJD) with parkinsonism as the initial symptom is extremely uncommon, this report aims to raise awareness of sCJD cases that present with parkinsonism that are not associated with genetic mutations or pathological α-synuclein (α-Syn) accumulation. Case presentation This report presents the case of a 72-year-old man with probable sporadic Creutzfeldt-Jakob disease (sCJD) who initially showed symptoms of parkinsonism, which worsened rapidly after contracting COVID-19. Despite a history of responsive tremor and bradykinesia, his condition deteriorated following the viral infection, leading to rapid consciousness decline and diffuse myoclonus. Diagnostic tests, including brain MRI, cerebrospinal fluid analysis, and EEG, pointed towards prion disease. PrPSc, a marker for CJD, was detected in both the cerebrospinal fluid and skin samples using RT-QuIC, further confirming the diagnosis. Notably, skin analysis revealed PrPSc but no pathological α-synuclein deposits, ruling out typical Parkinson's disease.  Conclussion This case underscores the importance of considering sCJD in patients with parkinsonism, especially if they experience sudden neuropsychiatric symptoms, especially if they do not exhibit pathological α-Syn accumulation or have genetic mutations.

Pattern of self-reported adverse events related to COVID-19 vaccines in Saudi Arabia: A nationwide study.

Background: Vaccination against coronavirus disease 2019 (COVID-19) is the most effective way to end the pandemic. Any development of adverse events (AEs) from various vaccines should be reported. We therefore aimed to explore major and minor AEs among vaccinated individuals in Saudi Arabia. Methods: This is a nationwide report based on the Saudi Arabian Ministry of Health (MOH) registry. It included those who received COVID-19 vaccines from 17th December 2020 to 31st December 2021. The study included spontaneous self-reported adverse effects to COVID-19 vaccines where the study participants used a governmental mobile app (Sehhaty) to report their AEs following vaccination using a checklist option that included a selection of side-effects. The primary outcome was to determine AEs reported within 14 days of vaccination which included injection site itching, pain, reaction, redness, swelling, anxiety, dizziness, fever, headache, hoarseness, itchiness, loss of consciousness, nausea, heartburn, sleep disruption, fatigue, seizures, anaphylaxis, shortness of breath, wheezing, swelling of lips, face, and throat, loss of consciousness, and admissions into the intensive care unit (ICU). Results: The study included a total number of 28,031 individuals who reported 71,480 adverse events (AEs); which were further classified into minor and major adverse events including ICU admissions post vaccination. Of the reported AEs, 38,309 (53. 6%) side-effects were reported following Pfizer-BioNTech, 32,223 (45%) following Oxford-AstraZeneca, and 948 (1.3%) following Moderna. The following reported AEs were statistically significant between the different vaccine types: shortness of breath\difficulty of breathing, dizziness, fever above 39°C, headache, hoarseness, injection site reactions, itchiness, nausea, sleep disruption, fatigue, wheezing, swelling of lips/face and\or throat, and loss of consciousness (p-value < 0.05). Fever and seizure were the only statistically significant AEs amongst the number of vaccine doses received (p-value < 0.05). Ten ICU admissions were reported in the 14 days observation period post-COVID-19 vaccination with the following diagnoses: acute myocardial infarction, pneumonia, atherosclerosis, acute respiratory failure, intracranial hemorrhage, grand mal seizure, Guillain-Barré syndrome, abnormal blood gas levels, and septic shock. Conclusion: This study demonstrated that the most prevalent SARS-CoV-2 vaccine side-effects among adults in Saudi Arabia were mild in nature. This information will help reduce vaccine hesitancy and encourage further mass vaccination to combat the COVID-19 pandemic, especially as booster doses are now available. Further studies are warranted to obtain a better understanding of the association between risk factors and the experiencing of side-effects post vaccination.

Prevalence of hypertension and possible risk factors of hypertension unawareness among individuals aged 30-75 years from two Panamanian provinces: Results from population-based cross-sectional studies, 2010 and 2019.

BACKGROUND: Recent estimates of hypertension in Panama remain unknown. We aim to describe the variation in prevalence and unawareness of hypertension in two Panamanian provinces using two different cross-sectional population-based studies and to investigate risk factors associated with hypertension unawareness. METHODS: Data were derived from a sub-national study conducted in the provinces of Panama and Colon (PREFREC-2010 [2,733 participants]) and from a nationally representative study (ENSPA-2019), in which we restricted our analyses to the same provinces (4,653 participants). Individuals aged 30-75 years who had (a) self-reported history of hypertension or (b) blood pressure (BP) ≥140/90mmHg or (c) a combination or both were classified as hypertensive. Participants with BP≥140/90mmHg who denied a history of hypertension were considered unaware of the condition. Multivariable logistic regression models were used to estimate the association between risk factors and unawareness, expressed as odds ratios (OR) and 95% confidence interval (CI). FINDINGS: In 2010, the prevalence and unawareness of hypertension in men were 51.6% (95% CI: 45.7-57.5) and 32.3% (25.4-40.1), respectively, and in women 46.0% (42.1-49.9) and 16.1% (12.6-20.4), respectively. In 2019, the prevalence and unawareness of hypertension in men were 46.5% (42.1-51.0) and 52.3% (45.9-58.6), and in women 42.1% (39.6-44.7) and 33.3% (29.8-37.0). Men (2010 and 2019), age <50 years (2010 and 2019), having no/primary education (2010), and living in a non-urban region (2019) were positively associated with hypertension unawareness, whereas obesity (2010), physical inactivity (2010), family history of hypertension (2019), and BP assessment in the year before study enrollment (2010 and 2019) were inversely associated with hypertension unawareness. INTERPRETATION: Benefits of a decrease in the prevalence of hypertension are being undermined by an increase in hypertension unawareness. Actions should be encouraged to strengthen the implementation of the existing healthcare program for cardiovascular risk factor control.

Hemiplegic Migraine as Cause For Motor Vehicle Collision: A Case Report (preprint)

Introduction: Hemiplegic migraine (HM) is a rare, heterogenous form of migraine characterized by unilateral weakness. This motor aura can present with reversible visual, sensory, and language deficits. HM can be difficult to diagnose due to overlapping presentation with other complex conditions such as multiple sclerosis, seizure disorders, and transient ischemic attack (TIA). Case Presentation: We describe a case of a 40 year old with asymptomatic COVID-19 infection who presented after a motor vehicle collision caused by HM consistent with left sided weakness and loss of consciousness. Conclusions: To date, this is the first description of a patient with known complex migraines to have a motor vehicle collision as a result of HM. The risk of HM-associated neurologic symptoms while driving poses a significant public safety concern. We suggest driving restrictions be considered in patients with HM when migraine aura is present. This case presents support to examine active infection with SARS-CoV-2 as a trigger for HM.

Diabetic ketoacidosis as a complication of methanol poisoning; a case report.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a complication of diabetes presenting with high anion gap metabolic acidosis. Methanol poisoning, on the other hand, is a toxicology emergency which presents with the same feature. We present a case of methanol poisoning who presented with DKA. CASE PRESENTATION: A 28-year-old male was referred to us with blurred vision and loss of consciousness three days after ingestion of 1.5 L of an unknown mixture of bootleg alcoholic beverage. He had history of insulin-dependent diabetes and had neglected his insulin shots on the day prior to hospital admission due to progressive loss of consciousness. Vital signs were normal and venous blood gas analysis showed severe metabolic acidosis and a methanol level of 10.2 mg/dL. After eight hours of hemodialysis, he remained unresponsive. Diabetic ketoacidosis was suspected due to positive urine ketone and blood sugar of 411 mg/dL. Insulin infusion was initiated which was followed by full awakening and extubation. He was discharged completely symptom-free after 4 weeks. CONCLUSIONS: Diabetic ketoacidosis and methanol poisoning can happen simultaneously in a diabetic patient. Given the analogous high anion gap metabolic acidosis, physicians should pay particular attention to examination of the diabetic patients. Meticulous evaluation for both conditions is highly recommended.

New-Onset Transient Global Amnesia: A Clinical Challenge in an Air Medical Transportation Pilot With a History of Coronavirus Disease 2019.

A 43-year-old male Bell 214C helicopter pilot presented to the emergency ward with flu-like syndrome. His nasopharyngeal severe acute respiratory syndrome coronavirus 2 real-time polymerase chain reaction test was positive, and a chest computed tomographic scan confirmed coronavirus disease 2019 pneumonia. He was admitted, received treatment, was discharged, and returned to flying. During the mission debrief, copilots who had flown with him reported that he experienced episodes of in-flight dizziness and blacked out. They occurred briefly during the cruise and hovering flight, perhaps for a few seconds of disorientation and unconsciousness. Rapid identification of the copilot and control of the helicopter prevented any incident or accident. Afterward, he explained the sudden onset and unexpected brief periods of loss of consciousness after a headache. The flight safety office referred him to the aviation medical center for further investigations. The cardiovascular, neurologic, laboratory, and toxicologic assessments were inconclusive with the approach to sudden-onset transient loss of consciousness. The only abnormal finding was hippocampus lesions on brain magnetic resonance imaging (MRI). Because of the possible diagnosis of transient global amnesia, the aviation medical examiner suspended him from flight duties until complete recovery and the absence of any probable complications.

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia.

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following. METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6). RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following  was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

Correlation between bispectral index value and modified Glasgow Coma Scale score in dogs with altered level of consciousness.

OBJECTIVE: This study aims to identify the correlation between bispectral index (BIS) value and modified Glasgow Coma Scale (MGCS) score in dogs with altered level of consciousness (ALOC). DESIGN: This prospective, observational, clinical study was conducted from February 2016 to March 2017, and follow-up was conducted until the death of dogs or their discharge from the hospital. SETTING: This study was performed at the Small Animal Teaching Hospital. ANIMALS: A total of 31 client-owned dogs (males, 20; females, 11) with ALOC and MGCS score <18 with no restrictions for age, breed, sex, and body weight were included. Dogs that received neuromuscular blocking agents before MGCS score evaluation were excluded. INTERVENTIONS: BIS values were measured using the Covidien BIS Loc 2 Channel OEM module and a pediatric 4 sensor with a bifrontal application pattern. MEASUREMENTS AND MAIN RESULTS: Minimal databases of initial neurological assessment, blood profiles, and chest and skull radiographs were developed. In addition, MGCS scores and BIS values were recorded. The mean BIS values for mild, moderate, and severe brain injuries were 89.14 ± 6.52, 77.21 ± 9.82, and 50.58 ± 27.04, respectively. Correlation analysis revealed a significantly positive relationship between BIS values and MGCS scores (r = 0.75; P < 0.001). CONCLUSIONS: The significant correlation observed between MGCS scores and BIS values in dogs with ALOC demonstrated the usefulness of BIS as an alternative to MGCS for monitoring consciousness in patients with ALOC caused by traumatic brain injury, encephalitis, etc.

Neurological, neuropsychiatric and psychiatric symptoms during COVID-19 infection and after recovery: a systematic review of observational studies (preprint)

Background The SARS-CoV-2 virus causes a wide spectrum of disease severity. Initial manifestations include fever, dry cough, and constitutional symptoms, which may progress to respiratory disease. There may also be neurological and psychiatric manifestations, involving both the central and peripheral nervous system. Methods We performed a literature search of the databases PubMed, EMBASE, The Cochrane Library and Web of Science for observational studies reporting neurological, psychiatric, and neuropsychiatric effects of COVID-19. This was followed by a narrative synthesis to summarise the data and discuss neuropsychiatric associations, symptom severity, management, and recovery. Findings The most frequently reported neurological symptoms were ageusia, hyposmia/anosmia, dizziness, headache, and loss of consciousness. Statistically significant relationships were noted between Asian ethnicity and peripheral neuropathy (p=0.0001) and neuro-syndromic symptoms (p=0.001). ITU admission was found to have a statistically significant relationship with male sex (p=0.024). Depression and anxiety were also identified both during and after infection. The most frequent treatments used were intravenous immunoglobulins, followed by antibiotics, antivirals, and hydroxychloroquine; with mean treatment duration of 6 days. Interpretation Various neuropsychiatric symptoms have been associated with COVID-19 infection. More studies are required to further our knowledge in the management of neurological and psychiatric symptoms during and after COVID-19 infection

Factors Associated With Mortality in Hospitalized Cardiovascular Disease Patients Infected With COVID-19 (preprint)

Background: To reduce mortality in hospitalized patients with COVID-19 and cardiovascular disease (CVD), it is necessary to understand the relationship between patient’s symptoms, risk factors, and comorbidities with their mortality rate.Method: To the best of our knowledge, this paper is the first which takes into account the determinants like risk factors, symptoms and comorbidities leading to mortality in CVD patients who are hospitalized with COVID-19. This study was conducted on 6600 hospitalized patients with CVD and COVID-19 recruited between January 2020 and January 2021 in Iran. All patients were diagnosed with previous history of CVD like angina, myocardial infarction, heart failure, cardiomyopathy, abnormal heart rhythms, and congenital heart disease before they were hospitalized for COVID-19. We collected data on patient’s signs and symptoms, clinical and paraclinical examinations, and any underlying comorbidities. t-test was used to determine the significant difference between the two deceased and alive groups. In addition, the relation between pairs of symptoms and pairs of comorbidities has been determined via correlation computation.Findings: Our findings suggest that signs and symptoms such as fever, cough, myalgia, chest pain, chills, abdominal pain, nausea, vomiting, diarrhea, and anorexia had no impact on patients' mortality. There was a significant correlation between COVID-19 cardiovascular patients’ mortality rate and symptoms such as headache, Loss of consciousness (LOC), oxygen saturation less than 93%, and need for mechanical ventilation. We observed no relationship in cardiac cases between mortality and comorbidities such as diabetes, cancer, pulmonary diseases, renal diseases, hematologic disorders, neurological diseases, and hypertension. The only risk factor that has impact on patients’ mortality was age. Other risk factors such as smoking status or addiction had no impact.Interpretation: Our results might help physicians identify early symptoms, comorbidities, and risk factors related to mortality in cardiovascular disease patients hospitalized for COVID-19.Funding Information: There is no funding.Declaration of Interests: The authors declare that there is no conflict of interest.Ethics Approval Statement: The study was approved by the Semnan Hospital Ethics Committee. All the patients completed written consent form before their enrolment in the data collection procedure.

Invasive airway "Intubation" in COVID-19 patients: statistics, causes and recommendations (preprint)

Background: Severe COVID-19 disease could induce acute respiratory distress which is characterized by tachypnea, hypoxia, and dyspnea. Intubation and mechanical ventilation are a strategic treatment of COVID-19 distress or hypoxia. Methods: We searched PubMed, Embase, and Scopus databases through April 1, 2021, to identify relevant randomized control trials, observational studies, and case series. Results: 24 studies were included in this review. Studies were conducted in the USA, China, Spain, South Korea, Italy, Iran, and Brazil. Most patients were intubated in the intensive care unit. Rapid sequence induction was mostly used for intubation. ROX index might be utilized for the predictor of the necessity of intubation in COVID-19 patients. According to the previous studies the rate of intubation reported 5 to 88%. It was revealed that 1.4 - 44.5% of patients might be extubated. Yet obesity and age (elderly) are the only risk factors of delayed or difficult extubation. Discussion and conclusion: Acute respiratory distress in COVID-19 patients could require endotracheal intubation and mechanical ventilation. Severe respiratory distress, loss of consciousness, and hypoxia were the most important reasons for intubation. Also, increased levels of ferritin, d-dimer, and lipase in common with hypoxia are correlated with intubation and ICU admission Mortality following intubation is reported to be 15 to 36%. Awake-prone positioning in comparison to high-flow nasal oxygen therapy did not reduce the risk of intubation and mechanical ventilation. There was no association between intubation timing and mortality of infected patients. noninvasive ventilation may have survival benefits. Keywords: Intubation, COVID-19, critical care, respiratory disease, infectious disease, hypoxia, airway management.

Impact of COVID-19 on the Central Nervous System: Are Spontaneous Intracranial Haemorrhage and Aseptic Meningitis Extrapulmonary Manifestations of COVID-19? (preprint)

Background:The coronavirus pandemic that started in December 2019 is mainly related to respiratory symptoms. Clinical presentations have been reported, but so far, no definitive therapy has been established. Intracranial haemorrhage has been observed in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but the clinical, imaging, and pathophysiological features of intracranial bleeding during coronavirus disease 2019 (COVID-19) infection remain poorly characterized. The occurrence of spontaneous intracranial haemorrhage complicated with aseptic meningitis secondary to COVID-19 is extremely rare.Case presentation:A 19-month-old fever, and shortness of breath was admitted to our intensive care unit on an emergency basis. Two weeks later, the patient developed a generalized convulsion with deterioration of consciousness. A computed tomography scan of the brain revealed a bifrontal intracerebral  haemorrhage compressing the anterior horns of both lateral ventricles of the brain with a massive intraventricular haemorrhage causing hydrocephalus. Emergency ventriculostomy was performed, and a nasal swab for SARSCoV-2 was positive. Cerebrospinal fluid analysis and culture were negative for microorganisms, and analysis revealed features of aseptic meningitis.Conclusions:The possible occurrence of spontaneous intracranial haemorrhage and aseptic meningitis should be kept in mind by physicians, especially when treating critically ill young children with COVID-19. Early recognition Conclusions: The possible occurrence of spontaneous intracranial haemorrhage and aseptic meningitis should be kept in mind by physicians, especially when treating critically ill young children with COVID- 19. Early recognition of central nervous system involvement may be key to providing a better prognosis.

Trends in reasons for emergency calls during the COVID-19 crisis in the department of Gironde, France using automatic classification. (preprint)

Objectives During periods such as the COVID-19 crisis, there is a need for responsive public health surveillance indicators related to the epidemic and to preventative measures such as lockdown. The automatic classification of the content of calls to emergency medical communication centers could provide relevant and responsive indicators. Methods We retrieved all 796,209 free-text call reports from the emergency medical communication center of the Gironde department, France, between 2018 and 2020. We trained a natural language processing neural network model with a mixed unsupervised/supervised method to classify all reasons for calls in 2020. Validation and parameter adjustment were performed using a sample of 20,000 manually-coded free-text reports. Results The number of daily calls for flu-like symptoms began to increase from February 21, 2020 and reached an unprecedented level by February 28, 2020 and peaked on March 14, 2020, 3 days before lockdown. It was strongly correlated with daily emergency room admissions, with a delay of 14 days. Calls for chest pain, stress, but also those mentioning dyspnea, ageusia and anosmia peaked 12 days later. Calls for malaises with loss of consciousness, non-voluntary injuries and alcohol intoxications sharply decreased, starting one month before lockdown. Discussion This example of the COVID-19 crisis shows how the availability of reliable and unbiased surveillance platforms can be useful for a timely and relevant monitoring of all events with public health consequences. The use of an automatic classification system using artificial intelligence makes it possible to free itself from the context that could influence a human coder, especially in a crisis situation. Conclusion The content of calls to emergency medical communication centers is an efficient epidemiological surveillance data source that provides insights into the societal upheavals induced by a health crisis.

COVID-19-Associated Encephalitis: Systematic Review of Case ReportsFindings on Cytokine-Immune-Mediated Inflammation as an Underlying Mechanism (preprint)

Background : Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily attacks the respiratory system resulting to a disease called coronavirus disease 19 (COVID-19), several studies also reported the involvement of the central nervous system along the course of the disease, one of which manifest as encephalitis. This study aims to determine the clinical profile, laboratory, and imaging results of encephalitis associated with COVID-19.Methods : Three databases namely, PubMed / Medline, Embase, and Scopus were systematically used in the search for this literature, in order to gather case reports and case series related to COVID-19-associated encephalitis published from January 1, 2019 to July 20, 2020.Result: There were 24 studies with 33 cases included in this review. The most reported neurological symptoms were disorientation / confusion (72.72%), decreased consciousness (54.54%), and seizures (27.27%). The laboratory examination showed an increase in the levels of C-reactive protein (48.48%), lactate dehydrogenase (30.3%), and lymphophenia (27.27%). The brain imaging examination did not show any pathological findings in half of the cases (51.51%). EEG (electroencephalography) showed a generalized decrease in 45.45% of the cases. The CSF analysis showed an increase in the levels of protein (42.42%) and lymphocytosis (24.24%). Positive cerebrospinal fluid polymerase chain reaction (PCR) was only found in 3 cases, while the most widely used pharmacological agent was hyroxychloroquine (48.48%). Intravenous steroids were given in 8 cases, while immunotherapy such as plasmapheresis and intravenous immunoglobulin were given in 10 cases. Fifteen patients were reported to be discharged from the hospital in stable conditions, while four mortality cases were recorded. Conclusion: The clinical, laboratory, and imaging findings in this review supported the hypothesis that the process of cytokine-immune mediated inflammation was the cause of cerebral damage in COVID-19-associated encephalitis, rather than direct invasion. However, due to the limited availabile facilities in this study, further research and examination are needed to confirm the hypothesis 

Daily Low Dose of Erythropoietin in Neuroinflammation; EPO Might Be Hazardous in COVID-19 (preprint)

Neuroinflammation, defined as inflammatory reactions mediated by cytokines, chemokines, reactive oxygen species, and secondary messengers in the central nervous system (CNS) including the brain and spinal cord is the basis of many neurological disorders. Recently, erythropoietin (EPO) has been considered and studied as a modulator of neuroinflammation. On this article minireview of pathophysiology of neuroinflammation and the neuroprotective effects of EPO is discussed and a case of subacute huge subdural hematoma with double mydriasis operated urgently, treated with low daily dose (vs high dose once or twice a month in the literature) of EPO and recovered fully and discharged home with good consciousness is reported. In addition, the probable unfavorable outcome of erythropoietin administration in patients with neuroinflammation in COVID-19 is considered.