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.

Age exacerbates SARS-CoV-2-induced blood-brain barrier leakage and neuropsychiatric dysfunction (preprint)

Persistent cognitive impairment and neuropsychiatric disorders are prevalent sequelae of SARS-CoV-2-induced COVID-19 in middle-aged adults. To model age-related neurological vulnerability to COVID-19, we induced respiratory SARS-CoV-2 MA10 infections by nasal inoculation in young (2 months) and middle-aged (12 months) mice. We hypothesized that aging and SARS-CoV-2 synergistically damage the blood-brain barrier (BBB). Indeed, the combined action of aging and SARS-CoV-2 infection caused more fibrinogen leakage, T cell infiltration, and neuroinflammation in middle-aged SARS-CoV-2-infected mice than in similarly inoculated young adults. Mechanistically, SARS-CoV-2 exacerbated age-related increases in Caveolin-1 BBB transcellular permeability and loss of Wnt/β-catenin ligands, with no apparent changes in tight junction proteins. Finally, SARS-CoV-2 infection induced age-dependent neuropsychiatric abnormalities including bradykinesia and obsessive-compulsive-like behavior. These observations indicate that cerebrovascular aging, including loss of Wnt suppression of Caveolin-1, heightens vulnerability to SARS-CoV-2-induced neuroinflammation and neuropsychiatric sequalae. Our work suggests that modulation of Wnt signaling or its downstream effectors at the BBB could be potential interventional strategies for Long COVID. Highlights To our knowledge, we have for the first time used a small animal model to experimentally test the impact of age on SARS-CoV-2 neuropathology. Aged mice were uniquely vulnerable to neuropsychiatric signs after SARS-CoV-2 infection Middle-age increased gliosis, cerebrovascular inflammation, BBB permeability, and T cell infiltration in SARS-CoV-2 infected mice BBB permeability was related to loss of Wnt7a suppression of Caveolin-1

Severe COVID-19 pneumonia associated with transient complete heart block and myocarditis: A case report (preprint)

A 70-year-old male presented with complaints of fever for 10 days; associated with dry cough for one week, gradually progressive shortness of breath for five days, and non-radiating chest pain for three days. Chest examination revealed bilateral basal crepitation, and cardiac examination showed muffled first heart sound with soft systolic murmur at apex. All severity markers of COVID-19 were elevated. Twelve lead electrocardiography (ECG) showed complete heart block. Troponin-I test was negative. High resolution computed tomography (HRCT) thorax showed extensive bilateral multifocal patchy and confluent areas of ground-glass opacities distributed along with peripheral subpleural and peribronchovascular regions with interlobular septal thickening suggestive of viral pneumonia .He was started on high flow oxygen, parenteral corticosteroids, and anticoagulants with antibiotics coverage. Injection Isoprenaline infusion was started for heart block, but the patient developed atrial flutter-fibrillation with premature ventricular complexes. The patient clinically improved and was discharged on the 11th day of admission. On follow up after 2 weeks, repeat ECG showed atrial fibrillation, and 2D Echocardiography revealed global hypokinesia, severe mitral regurgitation with left ventricular systolic dysfunction (ejection fraction of 28%), and dilated left ventricle and atrium. He was planned for coronary angiography after one month. High clinical suspicion, early diagnosis, and prompt treatment with corticosteroids can yield a favorable outcome. Follow up is necessary to rule out long term complications like viral cardiomyopathy.

Normal coronary myocardial infarction due to COVID-19: A case series (preprint)

Background: : The prevalence of cardiovascular complications in COVID-19 infection varied in different studies. One of these complications is myocardial infarction. A disturbance of the blood supply can lead to myocardial infarction by clot formation in the arteries. However, no evidence of significant coronary stenosis has been found in more than 50% of patients with COVID-19 and ST elevation.Case Presentation: 38 and 49 years old men (patients 1,2) were admitted to our hospital with the complaint of typical chest pain and COVID-19 symptoms. The real-Time Polymerase Chain Reaction (RT-PCR) test confirmed COVID-19 in both. Patient 1 represented inferior posterior ST-Elevation Myocardial Infarction (STEMI) in his electrocardiogram (ECG). Also, patient 2 has ST-elevation in high lateral and septal leads (I, AVL, V1, V2) and ST-segment depression in AVR and inferior leads (III, AVF). Their troponin was positive. The vital signs were normal in both of them. Patient 2 just had a history of aortic valve replacement (AVR) 5 years ago. However, Patient 1 had no medical history. Transthoracic Echocardiography (TTE) data demonstrated some disturbances in patient 1 Severe hypokinesia of Inferior, Posterior, Lateral, and Septal walls. However, TTE data were unremarkable for patient 2. We prescribed recommended medications for them. Therefore, their ECG changes were corrected, and his condition improved. In addition, Coronary angiography was done that demonstrated patent and normal coronary arteries in both of them.Conclusion : COVID-19 infection can cause normal coronary arteries myocardial infarction with probable two mechanisms prolonged vasospasm or intraluminal coronary thrombogenesis.

INFLUENCE OF NOVEL CORONAVIRUS DISEASE (COVID-19) ON PARKINSONS DISEASE: SYSTEMATIC REVIEW (preprint)

Background: The novel Coronavirus (COVID 19) infection has affected the population with various medical issues including the underlying neurological comorbidities such as Parkinson disease. COVID 19 is found to bind with the host angiotensin-converting enzyme 2 (ACE2) receptors for viral entry. ACE2 receptors are normally expressed in various body surfaces as well as in the neurons and glial cells where they act as an entry port to SARS-CoV-2 infection to invade the central nervous system (CNS). ACE2 are also highly expressed in dopamine neurons which might worsen the outcome in terms of motor symptoms in PD with the treatment course. It may lead to an indirect response via immune-mediated cytokine storms and propagate through CNS leading to damage. Parkinsons disease has also been noticed due to certain post viral infections apart from COVID-19 such as, HSV, Influenza virus A, Measles virus, Cytomegalovirus and Mumps (Olsen et al, 2018). We aim to provide a thorough review on neurological outcomes and impact of COVID-19 in Parkinson disease. Methods: A systematic review was conducted to analyze the impact of COVID 19 in patients with Parkinson disease (> 21 yo). Systematic literature search was done using PubMed, Science Direct, Google Scholar and Cochrane databases. PRISMA guidelines were followed summarized in Fig. 3 for study acquisition. Results: Of the Parkinsons patients that were tested positive for SARS-CoV 2, worsening of motor symptoms were reported along with other COVID 19 symptoms (Fig. 4 and 5). These symptoms include bradykinesia, tremors, gait disturbances, delirium and dementia and severe spasms of arms and legs. Encephalopathy was also one of the main symptoms presented in two of the studies. Increased mortality rates were identified for those who were hospitalized due to COVID-19 and PD when compared to other patients. Conclusion: Parkinsons disease may experience substantial worsening of motor and non motor symptoms during COVID 19. Due to the novelty of the virus, studies were reported from recent years and further extensive studies are needed to explore more about the disease severity and neurological outcomes when compared to other non-PD patients. Authors identify this as a limitation for this paper. Additional studies are needed to understand the role of ACE2 in increasing vulnerability to viruses and role of ACE inhibitors as treatment modality.

Treatment of unexplained coma and hypokinetic-rigid syndrome in a patient with COVID-19.

The COVID-19 pandemic has dealt a devastating blow to healthcare systems globally. Approximately 3.2% of patients infected with COVID-19 require invasive ventilation during the course of the illness. Within this population, 25% of patients are affected with neurological manifestations. Among those who are affected by severe neurological manifestations, some may have acute cerebrovascular complications (5%), impaired consciousness (15%) or exhibit skeletal muscle hypokinesis (20%). The cause of the severe cognitive impairment and hypokinesis is unknown at this time. Potential causes include COVID-19 viral encephalopathy, toxic metabolic encephalopathy, post-intensive care unit syndrome and cerebrovascular pathology. We present a case of a 60 year old patient who sustained a prolonged hospitalization with COVID-19, had a cerebrovascular event and developed a persistent unexplained encephalopathy along with a hypokinetic state. He was treated successfully with modafinil and carbidopa/levodopa showing clinical improvement within 3-7 days and ultimately was able to successfully discharge home.

Cardiac Dysfunction in Critically Ill patients with COVID-19 – A Multicentre Observational Study (preprint)

Introduction: The importance of cardiac dysfunction in critically ill patients with COVID-19 is not well studied. The aim of the study was to assess the incidence, clinical risk factors, and prognosis of cardiac dysfunction in critical illness caused by COVID-19, and to evaluate if cardiac biomarkers can detect this condition.Methods: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 hours from admission to the ICU and again after four to seven days. Cardiac biomarkers and clinical data were collected at the time of echocardiography. Cardiac dysfunction was defined as either left ventricular (LV) dysfunction (having an ejection fraction < 50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (having a tricuspid annular plane systolic excursion (TAPSE) < 17mm or a moderate/severe RV dysfunction assessed visually).Results: We included 132 patients of whom 94 (71%) were included prospectively. The vast majority were intubated (n=127). At the time of admission to ICU, 35 (27%) patients had cardiac dysfunction and 7 patients (5%) had cardiac dysfunction detected later in the ICU-period. LV dysfunction was found in 18 patients and RV dysfunction in 17 patients, 7 patients had both RV and LV dysfunction. Noradrenaline > 0.20µg/kg/min was the only clinical variable associated with a higher risk of cardiac dysfunction. RV dysfunction was associated with an increased risk of death in a risk-adjusted model (OR 3.98, p = 0.013). Troponin and N-terminal pro b-type natriuretic peptide (NTproBNP) had moderate values in detecting cardiac dysfunction (AUC 0.729 and AUC 0.744, respectively). A combination of troponin < 1.44 times the upper reference limit and NTproBNP < 857ng/L had 85% probability of excluding cardiac dysfunction.Conclusions: Cardiac dysfunction is common in critically ill patients with COVID-19. Although not easily detected with clinical variables, cardiac biomarkers might be helpful. RV dysfunction is associated with an increased risk of death, these patients might benefit from further investigation or treatments. Trial registration: Registered on 24 Aug 2020 at Clinicaltrials.gov; registration number NCT04524234.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.