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Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.
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Background: Delayed post-hypoxic leukoencephalopathy (DPHL) with associated microbleeds is a clinical entity presenting with cognitive impairment days or weeks after an episode of acute hypoxic brain injury. Case report: We describe a 68-year-old male with SARS-CoV2 infection who had cardiac arrest, required sedation and mechanical ventilation for 17 days, and after sedation was discontinued, he became unresponsive. Brain MRI showed diffuse confluent hyperintense signals in the subcortical white matter and multiple subcortical white matter microhemorrhages. EEG revealed diffuse attenuation of brain electrical activity with isolated polymorphic delta waves in the frontal region without epileptiform activity. Conclusion(s): Clinicians need to be aware that patients with Covid-19 can develop delayed post-hypoxic leukoencephalopathy.Copyright © 2022 The Authors
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Objective Our objective was to evaluate the incidence of seizures, pattern of EEG abnormalities, and localization of abnormal discharges in hospitalized patients with COVID-19. Background The COVID-19 epidemic has revealed significant neurological manifestations including de novo seizures in patients who do not have a prior history of epilepsy or clear epilepsy risk factors. Our center is located in Arizona, which in the early part of January 2021 had more cases per capita than any other place in the world. Design/Methods We performed a retrospective review to observe the electroencephalogram (EEG) patterns of hospitalized adult patients with COVID-19 between March 2020 and February 2021. Results We identified 99 patients who were COVID-19 positive and had EEG testing during the same hospitalization. The most common EEG abnormality was diffuse background slowing, which was seen in 63.6% of patients (n = 63/99), compare to 15.1% of focal background slowing. Epileptiform discharges were seen in 11.1% of patients and seizures were found in 5.1% of patients, as newly diagnosed seizures. When combining all focal abnormalities, the most common location for these abnormalities was in the frontal regions 36.4% (n = 8/22). Even though 21 patients had acute focal neuroradiologic findings, only 5 had correlated EEG abnormalities within the same region. When EEG was obtained with suspected seizures (n = 33), 4 cases (12.1%, n = 4/33) indeed showed ictal pattern compared to 1.6% when seizures was not suspected (p = 0.087). Conclusions Abnormal EEG findings are most commonly found in the frontal lobe among hospitalized patients with acute COVID-19 symptoms. De novo seizures may be seen with COVID-19 infection. Suspicion of seizures should be raised in patients with COVID-19 encephalopathy. The utility of an EEG may help allow us better insight into how and where the COVID infection affects our central nervous system.
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Introduction: Abounding physical and mental exhaustion among the health care workers (HCW) during COVID-19 pandemic rekindled the need to acknowledge the psychological impact of this unprecedented stressful situation on the first-line warriors. The rising stress among the HCW during COVID duties for many months could have long-term effects on their personal and professional life. The situation necessitated presenting a feasible solution which can positively impact mental health. Patanjali's 'Kriya yoga' amalgamates several relaxation techniques, inclusively breath modulation, pranayama, mantra chanting, and asana holding, with a potential for stress management. The effects of 'Kriya Yoga' on EEG and perceived stress among the HCW were investigated. Method(s): Participants were recruited through digital advertisements. Those meeting the eligibility criteria were enrolled in either intervention or control groups. The complete set of 'Kriya yoga' was taught to the subjects in the intervention group by a yoga expert. It included a set of six techniques comprising Breath awareness (Ana pana), Complete breath, Anulom Vilom (Alternate nostril breathing), Om chanting, Gayatri Mantra, and Shavasan (Deep Relaxation). The participants were required to practice it for a period of 6 weeks. Result(s): Data for EEG, electrodermal activity (EDA), perceived stress scale (PSS) scores and depression, anxiety and stress scores were collected at different time points. EEG was quantitatively (QEEG) analyzed for delta, theta, alpha, and beta power over several regions. We found improvement in the DASS-21 and PSS scores at the end of the practice sessions. The mean power for alpha frequency was increased in the frontal, central, and parietal regions, and for delta range was raised over the central and parietal areas. The tonic skin conductance level revealed a reduction in stress among the practitioners. The participants reported a subjective feeling of calmness, well-being, and ease of practice. Conclusion(s): 'Kriya yoga' is an easily deliverable intervention for stress mitigation among the HCW. It leads to relaxation, a decrease in anxiety, and a reduction in perceived stress. The long-term psychophysiological effects of Kriya yoga practice are depicted by the changes in the power of brain waves and EDA. The proposed intervention can be a model for the mental health well-being of the HCW in stressful circumstances. Copyright © 2022
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Objective: NA Background: The etiology of MOGAD post-COVID-19 infection is not well understood and there are limited publications describing cases in pediatric patients. Here we report a case of a 14-year-old male with MOG antibody positive ADEM (Acute Disseminated Encephalomyelitis) and positive COVID-19 PCR. Design/Methods: NA Results: The patient presented to our hospital in December of 2020 with acute onset of ataxia and lower extremity weakness. His exam was pertinent for mild and symmetric weakness in bilateral hip flexors, dysmetria with ataxic gait, as well as bilateral patellar and ankle hyporeflexia. MRI brain showed symmetric areas of T2 signal hyperintensity, predominantly adjacent to the fourth ventricle as well as the peri-insular and frontal regions. MRI of the lumbosacral spine demonstrated T2 signal hyperintensity within the conus medullaris without enhancement. CSF studies revealed an increased white blood cell count of 74 (90% lymphocyte), elevated protein of 51, elevated kappa free light chain (0.12) and positive oligoclonal bands (3). He was also found to be serum anti-MOG antibody positive (1:100) and COVID-19 positive (PCR). He received 1000 mg of intravenous methylprednisolone daily for 5 days and 2 g/kg IVIG. He was subsequently placed on a 6 week taper of oral prednisone. 2 months after his initial presentation, his neurologic symptoms have completely resolved, and he has been asymptomatic since. Repeat MRI brain 4 months later showed improvement in his multifocal supratentorial FLAIR signal abnormalities. Conclusions: Here we describe a case of a 14-year-old male with MOGAD post-COVID-19, with complete resolution of his symptoms after high dose corticosteroid and IVIG treatment.
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Background-Aim: While a frontal dysfunction is reported in post- SARS-CoV-2 with neurological symptoms (neuro-SARS-CoV-2), it is unclear whether this brain vulnerability is long lasting or reversible. The present study evaluated brain dysfunctions-as measured by FDG-PET-in neuro-SARS-CoV-2 over time to provide a better understanding of physiopathology underlying central nervous system involvement. Methods: 26 patients with neuro-SARS-CoV-2 were included. Seven patients were in the acute, the others in the sub-acute and chronic phase, namely, four at 1-month, four at 2-months, four at 3-months, four at 5 months and four at 7-9-months after onset. Patients underwent FDG-PET exams, clinical and cognitive evaluations. One patient was evaluated longitudinally, during the acute phase, and at a 5-months follow-up. Brain metabolism was analysed at the singlesubject and group levels by a comparisons with healthy controls. Correlations between severity/extent of hypometabolism and clinical variables of interest (global cognitive cognition, blood oxygen level saturation, and inflammatory status -C-reactive protein measurements) were also assessed. Results: Patients with acute neuro-SARS-CoV-2 showed the most severe and diffuse cortical hypometabolism, affecting almost all cortical areas. 2-months after the acute infection, a significant decrease in hypometabolism extension emerged, affecting mainly the frontal and temporal cortex. At 5-months after the acute phase, a recovery of cortical hypometabolism was evident, with limited residual clusters in frontal regions. At 7-9-months, no regions with brain hypometabolism were present. The only patient evaluated longitudinally showed a significant brain metabolic improvement from the acute phase (with diffuse cortical hypometabolism) to a 5-months follow-up (brain hypometabolism limited to frontal areas). Of note, the extent and severity of hypometabolism were associated with severe global cognitive dysfunctions, low blood oxygen level saturation, and high inflammatory status in all patients. Conclusions: These findings suggest that cortical functional impairment observed in patients with neuro-SARS-CoV-2 infection is likely to be transient and almost reversible, possibly due to synergistic effects of systemic virus-mediated inflammation sustained by systemic cytokine release and transient hypoxia inducing reversible neural dysfunction and local microglial activation.
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Background-Aim: A 46 years old housewife patient with a bachelor's degree in Law contracted Covid-19 at the end of March 2021. She had a flu-like form with associated asthenia and drowsiness and no lack of sense of smell. It has been resolved in 25 days. Later, she developed progressive immediate memory loss, word-finding issues, motor and thinking slowing down. Methods: CT brain scan appeared as within the norm as well as liver enzymes, TSH, Vitamin B12, Folate and Rapid Plasma Reagine. Anti- ENA DNA ANA HIV TPO TG were negative too. In October, the patient had a further neuropsychological assessment that showed an overall picture characterized by partial orientation to space, working memory disorders, writing and comprehension (of complex tasks) issues, and immediate memory loss (possible sign both of attention span and concentration reduction). The auto-antibodies were assessed in November and they resulted negative. Moreover, the brain MRI scan and EEG (dated at the end of November) were both within the range. CSF neurodegenerative biomarkers and anti-neuronal antibodies appeared in the norm too. Results: Ultimately, in December 2021 she underwent an 18F-FDG PET brain scan and the SPM analysis showed an extensive hypometabolism in the bilateral frontal cortex and bilateral straight gyrus. Spared the cingulate cortex. Conclusions: The patient contracted Covid in March 2021. She developed neurological deterioration identified by FDG-PET. Negative autoantibodies and CSF biomarkers. PET scan was the only exam to define the brain damage in the patient above. Symmetrical bilateral frontal cortex and bilateral straight gyrus hypo-metabolism have been observed, the last one at the direct level of the olfactory bulb. In this area, in patients who died from Covid-19 it has been histologically demonstrated (data to be published) the presence of cellular inclusions named Corpore Amylacea. They would be a small hyaline mass that functions as a waste container that accumulates in the human brain in aging and in neurodegenerative and infectious processes. It is hypothesized to be that it can be involved in a sort of brain cleaning process1. Recently it has been described that they contain some neoepitopes that are recognized by natural IgMs, revealing a possible link between them and the natural immune system2. However, to now in our patient, the only diagnostic tool to evaluate the brain condition has been the 18F-FDG PET.
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SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, are increasingly recognised. Through immunohistochemistry against the SARS-CoV-2 nucleocapsid protein (NP), we aimed to characterise the multisystem viral tropism of SARS-CoV-2. FFPE tissue was obtained from 16 PCR-confirmed post-mortem COVID cases. Of these cases, 10 were full-body, 5 were brain only and 1 was a brain biopsy. Brain regions studied included frontal cortex, medulla, cerebellum, pons and olfactory bulb. Neurological symptoms featured in the cohort included brainstem encephalitis, acute disseminated encephalomyelitis (ADEM) and brain infarction. Immunohistochemistry of digestive system tissues revealed presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE-2 expression, the entry receptor for SARS-CoV-2 and one of the earliest affected cells in Parkinson's disease (PD). Within the brain, staining was widespread in all sampled regions but limited to endothelial cells only (including in the olfactory bulb). Furthermore, in the full-body post-mortem cases, positivity in brain endothelia was restricted to cases exhibiting multiorgan tissue positivity (3/9 cases). The average time from symptom onset to time of death was shorter in positively versus negatively stained postmortem cases (mean = 10.3 days vs mean = 20.3 days, p = 0.0416) suggesting NP detection was confined to the infectious period. Together, our findings provide evidence for enteric nervous system but not brain neuroinvasion of SARS-CoV-2 as well as potential insights into long-term complications of COVID-19 and PD pathogenesis.
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SARS-Cov-2 infection is frequently associated with Nervous System manifestations. However, it is not clear how SARS-CoV-2 can cause neurological dysfunctions and which molecular processes are affected in the brain. In this work, we examined the frontal cortex tissue of patients who died of COVID-19 for the presence of SARS-CoV-2, comparing qRT-PCR with ddPCR. We also investigated the transcriptomic profile of frontal cortex from COVID-19 patients and matched controls by RNA-seq analysis to characterize the transcriptional signature. Our data showed that SARS-CoV-2 could be detected by ddPCR in 8 (88%) of 9 examined samples while by qRT-PCR in one case only (11%). Transcriptomic analysis revealed that 11 genes (10 mRNAs and 1 lncRNA) were differential expressed when frontal cortex of COVID-19 patients were compared to controls. These genes fall into categories including hypoxia, hemoglobin-stabilizing protein, hydrogen peroxide processes. This work demonstrated that the quantity of viral RNA in frontal cortex is minimal and it can be detected only with a very sensitive method (ddPCR). Thus, it is likely that SARS-CoV-2 does not actively infect and replicate in the brain; its topography within encephalic structures remains uncertain. Moreover, COVID-19 may have a role on brain gene expression, since we observed an important downregulation of genes associated to hypoxia inducting factor system (HIF) that may inhibit the capacity of defense system during infection and oxigen deprivation, showing that hypoxia, well known multi organ condition associated to COVID-19, also marked the brain.