key: cord-0739828-a32on79j authors: Rehmani, Razia; Segan, Scott; Maddika, Srikanth Reddy; Lei, Yadanar Win; Broka, Andrea title: Spectrum of Neurologic & Neuroimaging manifestation of COVID-19 date: 2021-03-03 journal: Brain Behav Immun Health DOI: 10.1016/j.bbih.2021.100238 sha: 9d77e116e788a89f7b1c794b6ce3ce662880cc76 doc_id: 739828 cord_uid: a32on79j OBJECTIVE: Coronavirus Disease 2019 (COVID-19) initially thought to be confined to the respiratory system only, is now known to be a multisystem disease. It is critical to be aware of and timely recognize neurological and neuroradiological manifestations affecting patients with COVID-19, to minimize morbidity and mortality of affected patients. METHODS: We performed a retrospective chart review of patients admitted to our Level 1 trauma and stroke center during the peak of the COVID-19 outbreak in New York from March 1(st) to May 30, 2020, with a positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) who presented mainly with neurological findings and had acute radiological brain changes on Computed Tomography (CT) scan. Patients with known chronic neurological disease processes were excluded from the study. We obtained and reviewed demographics, complete blood count, metabolic panel, D-dimer, inflammatory markers such as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), imaging, and patient’s hospital course. We reviewed the current literature on neuroimaging, pathophysiology, and their clinical correlations on COVID-19. This case series study was approved by our institutional review board. RESULT: A total of 16 patients were selected for our case series. The most common neuroimaging features on CT, were territorial to multifocal ischemic infarcts, followed by a combination of ischemia and acute white matter encephalopathic changes, followed by temporal lobe predominant focal or more generalized encephalopathy with both confluent and non-confluent patterns, isolated cortical or more extensive intracranial hemorrhages and some combination of ischemia or hemorrhage and white matter changes. All our patients had severe acute respiratory distress syndrome (ARDS), most of them had elevated inflammatory markers, and D dimer. CONCLUSION: COVID-19 infection is a multi-organ disease, which can manifest as rapidly progressive neurological disease beyond the more common pulmonary presentation. Early recognition of various neurological findings and neuroimaging patterns in these patients will enable timely diagnosis and rapid treatment to reduce morbidity and mortality. Our retrospective study is limited due to small non-representative sample size, strict selection criteria likely underestimating the true extent of neurological manifestations of COVID-19, mono-modality imaging technique limited to predominantly CT scans and lack of CSF analysis in all except one patient. Multi-institutional, multi-modality, largescale studies are needed with radio-pathological correlation to better understand the complete spectrum of neurologic presentations in COVID-19 patients and study the causal relationship between SARS-CoV-2 and CNS disease process. World health organization (WHO) declared it a pandemic on March 11th, 2020 (1). 55 COVID-19 initially thought to affect only the respiratory system is now known to be a multisystem 56 disease. Symptoms range from mild features such as fever, headache, myalgia, fatigue, cough, and 57 shortness of breath to life-threatening complications such as acute respiratory distress syndrome, acute 58 cardiac injury, and septic shock (2), as well as neurological symptoms from headaches to altered mental 59 status, seizure, focal neurological deficits, neuropathy including hypogeusia and hyposmia as well as in hypokinesis. Hypothermia protocol was not started as the patient was vitally unstable. 24 hours later, the 133 patient had sluggish pupillary reflex with minimal corneal and gag reflexes suggesting brain stem 134 damage. Follow-up repeat head CT done 9 days after the initial exam showed multiple infarcts 135 throughout the supratentorial brain with focal isolated white matter encephalopathy at the left temporal 136 lobe (Figure 2Figure 3) . He continued to be on vasopressor, broad-spectrum antibiotics, and 137 anticoagulation. On day 14 th , the patient had a second cardiac arrest secondary to pulmonary embolism 138 while in DNR status and passed away. middle cerebral artery territory ischemic infarct. In the upcoming days, the patient became vitally 150 unstable, secondary to worsening pneumonia, complicated by septic shock and cardiorespiratory arrest. The patient passed away on day 7 th of hospitalization. home with supportive treatment. On presentation, the patient was obtunded, tachypneic and tachycardic. Work up showed bilateral patchy pulmonary infiltrates and elevated inflammatory markers including 159 elevated d dimer. The lumbar puncture was negative. He was started on empiric antibiotics and 160 anticoagulation. Initial head CT showed multiple hypodensities bilaterally in the supratentorial brain The patient passed away on day 11th. Common neurological presentations in our case series, besides obvious hemiparesis/hemiplegia or 306 stroke-like features, included altered mental status, neuropathy, and seizures. Most of these patients 307 were found to have ischemic strokes with different infarct patterns, from single vascular territory to 308 multiple embolic type infarcts diffusely followed by white matter encephalopathic changes with both 309 confluent as well as non-confluent pattern with most of them involving medial temporal lobes, isolated 310 hemorrhages and the remaining with both white matter changes and ischemia or hemorrhage ( The reported incidence of cerebrovascular accidents is variable ranging from around 0.9% to 8.0% (7- incidence. The latter can be dependent on differences between various populations, criteria used for 321 requesting brain imaging, and the number of critically ill patients who were able to undergo imaging. The etiology of acute cerebrovascular accidents in COVID-19, probably is multifactorial, with 323 preexisting conditions, like hypertension, diabetes, cardiovascular disease, and their severity of disease 324 playing the main part. The exact role of SARS-CoV-2 remains unclear, but it has been documented in 325 autopsy reports that COVID-19 is associated with an increased incidence of thromboembolic events(10). acids, and a two-step attachment mechanism should be further addressed in the future. 361 The second suggested mechanism is via retrograde axonal transport, using several cranial nerves, mostly It has also been reported that COVID-19 is associated with a hyperimmune inflammatory response 372 which incites activation of the coagulation cascade with release of cytokines and chemokines causing 373 vasodilation, edema, and endothelial injury. Notably, a hypercoagulation state is known to be present 374 due to elevated factor VIII, elevated fibrinogen, and hyperviscosity (18) . This is called COVID- J o u r n a l P r e -p r o o f Central nervous 565 system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Neuroimaging and neurologic findings in 568 COVID-19 and other coronavirus infections: A systematic review in 116 patients Early evidence of pronounced brain 572 involvement in fatal COVID-19 outcomes COVID-19-associated 575 hyperviscosity: a link between inflammation and thrombophilia? The Lancet Thromboinflammation and the hypercoagulability of COVID-19 Spontaneous echo contrast in venous 581 ultrasound of severe COVID-19 patients The association of race 589 and COVID-19 mortality-NC-ND license Confluent and non confluent (temporal lobe predominant) white matter hypodenisities +/-ischemia Isolated or non confluent temporal lobe predominant white matter hypodensities only Confluent and non confluent (temporal lobe) white matter hypodensities only rapidly progressive Non confluent (temporal lobe predominant) white matter hypodenisities +/-microhemorrhage Confluent and non confluent white matter hypodensities +/-microhemorrhage Hospitalization 50 15 7 11 2 51 23 7 10 6 15 17 19 9 11 8 Outcome Expired Expired Expired Expired Expired Discharged Expired Discharged Discharged Discharged Discharged Expired Discharged Expired Discharged Discharged Age 78 42 77 64 64 32 68 74 53 72 55 80 61 71 68 90 Sex Female Male Male Male Female Female Female Female Male Male Male Female Male Male Female Female Ethic Background • COVID-19 most commonly affects the respiratory system but is now known to be a multisystem disease.• SARS-COV-2 is shown to have neurotropic/neuroinvasive capabilities which may present with multitude of neurological symptoms such as strokes with motor, sensory, visual and speech deficits, encephalopathy, peripheral neuropathy, seizures, altered mental status, bowel, and bladder incontinence.• Close analysis of clinical neurological presentations along with laboratory parameters inclusive of inflammatory data (CRP/ESR) or coagulation markers (D-dimer levels) when correlated with the observed imaging patterns on computed tomography (CT scans) can steer one towards the most probable diagnosis amidst confounding coexistence of various comorbidities.• -6 key imaging patterns we observed on non-contrast CT scan included most commonly ischemic infarcts followed by combination of both ischemia and white matter encephalopathy, followed by isolated temporal lobe predominant or more generalized encephalopathy, followed by intracranial hemorrhages (ICH) which included both isolated cortical as well as more extensive ICH, followed by combination of ICH and encephalopathy.