Long-term neuroimaging follow-up of COVID-19-related leukoencephalopathy.

More than a year after the start of the COVID-19 pandemic, long-term neurological manifestations of COVID-19 are increasingly being reported. The long-term sequelae of COVID-19-related leukoencephalopathy, however, remain unclear. Here, we present long-term neuroimaging follow-up in two cases of COVID-19-related leukoencephalopathy. The two cases demonstrate the utility of brain MRI for evaluating neurologic symptoms in critically ill patients with COVID-19, for diagnosis of underlying neural injury and prognostication of future recovery. The presence of leukoencephalopathy may result in chronic neurologic manifestations and may represent a poor prognosticator of neurologic recovery. The presence of leukoencephalomalacia on follow-up neuroimaging is potentially an indicator of irreversible white matter damage, which may be associated with more severe chronic deficits.

COVID-19-related diffuse leukoencephalopathy with microbleeds and persistent coma: a case report with good clinical outcome.

A 60-year-old patient presented with respiratory distress, after recently being tested COVID-19 positive and was mechanically ventilated for 15 days. After cessation of sedation, he remained in deep comatose state, without any reaction on pain stimuli (Glasgow Coma Score 3). MRI of the brain showed diffuse leukoencephalopathy and multiple (>50) microbleeds. Diffuse COVID-19-associated leukoencephalopathy with microhaemorrhages is associated with a poor prognosis. However, 3 months later, our patient showed a remarkable recovery and was able to walk independently. This case report shows COVID-related leukoencephalopathy and intracerebral microbleeds, even with persistent comatose state, may have a favourable clinical outcome and prolonged treatment should be considered in individual cases.

Lesson of the month: Severe leukoencephalopathy by SARS-CoV-2.

Neurological manifestations associated with SARS-CoV-2 infection as well as its pathogenesis are insufficiently explained. We present two cases of severe COVID-19 who required hospitalisation in the intensive care unit with persistently depressed mental status and severe leukoencephalopathy. We discuss the clinical and radiological findings and also propose the possible pathogenesis involved.

Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of individuals worldwide. Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection. Patients were confirmed by microbiological/serological testing, or on chest CT semiology. Available data on co-morbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed. A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes. A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis. In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease. Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%). Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi). Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type. Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004). Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%). In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas. Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis. The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043). Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality. We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Clinical, Imaging, and Lab Correlates of Severe COVID-19 Leukoencephalopathy.

BACKGROUND AND PURPOSE: Patients infected with the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) can develop a spectrum of neurological disorders, including a leukoencephalopathy of variable severity. Our aim was to characterize imaging, lab, and clinical correlates of severe coronavirus disease 2019 (COVID-19) leukoencephalopathy, which may provide insight into the SARS-CoV-2 pathophysiology. MATERIALS AND METHODS: Twenty-seven consecutive patients positive for SARS-CoV-2 who had brain MR imaging following intensive care unit admission were included. Seven (7/27, 26%) developed an unusual pattern of "leukoencephalopathy with reduced diffusivity" on diffusion-weighted MR imaging. The remaining patients did not exhibit this pattern. Clinical and laboratory indices, as well as neuroimaging findings, were compared between groups. RESULTS: The reduced-diffusivity group had a significantly higher body mass index (36 versus 28 kg/m2, P < .01). Patients with reduced diffusivity trended toward more frequent acute renal failure (7/7, 100% versus 9/20, 45%; P = .06) and lower estimated glomerular filtration rate values (49 versus 85 mL/min; P = .06) at the time of MRI. Patients with reduced diffusivity also showed lesser mean values of the lowest hemoglobin levels (8.1 versus 10.2 g/dL, P < .05) and higher serum sodium levels (147 versus 139 mmol/L, P = .04) within 24 hours before MR imaging. The reduced-diffusivity group showed a striking and highly reproducible distribution of confluent, predominantly symmetric, supratentorial, and middle cerebellar peduncular white matter lesions (P < .001). CONCLUSIONS: Our findings highlight notable correlations between severe COVID-19 leukoencephalopathy with reduced diffusivity and obesity, acute renal failure, mild hypernatremia, anemia, and an unusual brain MR imaging white matter lesion distribution pattern. Together, these observations may shed light on possible SARS-CoV-2 pathophysiologic mechanisms associated with leukoencephalopathy, including borderzone ischemic changes, electrolyte transport disturbances, and silent hypoxia in the setting of the known cytokine storm syndrome that accompanies severe COVID-19.

Brain MR Spectroscopic Findings in 3 Consecutive Patients with COVID-19: Preliminary Observations.

Brain multivoxel MR spectroscopic imaging was performed in 3 consecutive patients with coronavirus disease 2019 (COVID-19). These included 1 patient with COVID-19-associated necrotizing leukoencephalopathy, another patient who had a recent pulseless electrical activity cardiac arrest with subtle white matter changes, and a patient without frank encephalopathy or a recent severe hypoxic episode. The MR spectroscopic imaging findings were compared with those of 2 patients with white matter pathology not related to Severe Acute Respiratory Syndrome coronavirus 2 infection and a healthy control subject. The NAA reduction, choline elevation, and glutamate/glutamine elevation found in the patient with COVID-19-associated necrotizing leukoencephalopathy and, to a lesser degree, the patient with COVID-19 postcardiac arrest, follow a similar pattern as seen with the patient with delayed posthypoxic leukoencephalopathy. Lactate elevation was most pronounced in the patient with COVID-19 necrotizing leukoencephalopathy.

Serial Imaging of Virus-Associated Necrotizing Disseminated Acute Leukoencephalopathy (VANDAL) in COVID-19.

BACKGROUND AND PURPOSE: Various patterns of leukoencephalopathy have been described in coronavirus disease 2019 (COVID-19). In this article, we aimed to describe the clinical and imaging features of acute disseminated leukoencephalopathy in critically ill patients with COVID-19 and the imaging evolution during a short-term follow-up. MATERIALS AND METHODS: We identified and reviewed the clinical data, laboratory results, imaging findings, and outcomes for 8 critically ill patients with COVID-19 with acute disseminated leukoencephalopathy. RESULTS: All patients demonstrated multiple areas of white matter changes in both cerebral hemispheres; 87.5% (7/8) of patients had a posterior predilection. Four patients (50%) had short-term follow-up imaging within a median of 17 days after the first MR imaging; they developed brain atrophy, and their white matter lesions evolved into necrotizing cystic cavitations. All (8/8) patients had inflammatory cytokine release syndrome as demonstrated by elevated interleukin-6, D-dimer, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and ferritin levels. Most (7/8; 87.5%) patients were on prolonged ventilator support (median, 44.5 days; interquartile range, 20.5 days). These patients had poor functional outcomes (6/8 [75%] patients were discharged with mRS 5) and high mortality (2/8, 25%). CONCLUSIONS: Critically ill patients with COVID-19 can develop acute disseminated leukoencephalopathy that evolves into cystic degeneration of white matter lesions with brain atrophy during a short period, which we dubbed virus-associated necrotizing disseminated acute leukoencephalopathy. This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.

Diffuse necrotising leukoencephalopathy with microhaemorrhages in a patient with severe COVID-19 disease.

A wide range of neurological complications of coronavirus disease 2019 (COVID-19) is increasingly recognised. Although the majority of these remain ischaemic and haemorrhagic events, various disorders are being reported. In particular, several cases of diffuse acute leukoencephalopathy have been observed in critically ill patients with COVID-19 disease. We report the case of a 59-year-old man with multiple comorbidities and severe COVID-19 pneumonia who developed a diffuse leukoencephalopathy with microhaemorrhages and extensive associated white matter necrosis. Although this is the first documented case of extensive COVID-19-associated white matter necrosis, we highlight the relatively constant features of this injury similar to previously reported cases, including symmetrical involvement of the supratentorial white matter, sparing of the peripheral subcortical regions except in the precentral gyri, frequently associated microhaemorrhages, relative sparing of the deep gray matter structures and infratentorial structures, and lack of enhancement.

Unusual Brain MRI Pattern in 2 Patients with COVID-19 Acute Respiratory Distress Syndrome.

We report the cases of 2 patients hospitalized in our intensive care unit with confirmed coronavirus disease 2019 infection in whom brain MR imaging showed an unusual DWI pattern with nodular and ring-shaped lesions involving the periventricular and deep white matter. We discuss the possible reasons for these findings and their relationship to the infection.

Cerebral Microbleeds and Leukoencephalopathy in Critically Ill Patients With COVID-19.

BACKGROUND AND PURPOSE: We conducted this study to investigate the prevalence and distribution of cerebral microbleeds and leukoencephalopathy in hospitalized patients with coronavirus disease 2019 (COVID-19) and correlate with clinical, laboratory, and functional outcomes. METHODS: We performed a retrospective chart review of 4131 COVID-19 positive adult patients who were admitted to 3 tertiary care hospitals of an academic medical center at the epicenter of the COVID-19 pandemic in New York City from March 1, 2020, to May 10, 2020, to identify patients who had magnetic resonance imaging (MRI) of the brain. We evaluated the MRIs in detail, and identified a subset of patients with leukoencephalopathy and/or cerebral microbleeds. We compared clinical, laboratory, and functional outcomes for these patients to patients who had a brain MRI that did not show these findings. RESULTS: Of 115 patients who had an MRI of the brain performed, 35 (30.4%) patients had leukoencephalopathy and/or cerebral microbleeds. Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days; P<0.001), were clinically sicker at the time of brain MRI (median GCS 6 versus 14; P<0.001), and had higher peak D-dimer levels (8018±6677 versus 3183±3482; P<0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2; P=0.03), higher peak international normalized ratio (2.2 versus 1.57; P<0.001) values when compared with patients who had a brain MRI that did not show these findings. They required longer ventilator support (34.6 versus 9.1 days; P<0.001) and were more likely to have moderate and severe acute respiratory distress syndrome score (88.6% versus 23.8%, P<0.001). These patients had longer hospitalizations (42.1 versus 20.9 days; P<0.001), overall worse functional status on discharge (mRS 5 versus 4; P=0.001), and higher mortality (20% versus 9%; P=0.144). CONCLUSIONS: The presence of leukoencephalopathy and/or cerebral microbleeds is associated with a critical illness, increased mortality, and worse functional outcome in patients with COVID-19.

Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review.

OBJECTIVE: This systematic review aimed to synthesize early data on typology and topography of brain abnormalities in adults with COVID-19 in acute/subacute phase. METHODS: We performed systematic literature search via PubMed, Google Scholar and ScienceDirect on articles published between January 1 and July 05, 2020, using the following strategy and key words: ((covid[Title/Abstract]) OR (sars-cov-2[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND (brain[Title/Abstract]). A total of 286 non-duplicate matches were screened for original contributions reporting brain imaging data related to SARS-Cov-2 presentation in adults. RESULTS: The selection criteria were met by 26 articles (including 21 case reports, and 5 cohort studies). The data analysis in a total of 361 patients revealed that brain abnormalities were noted in 124/361 (34%) reviewed cases. Neurologic symptoms were the primary reason for referral for neuroimaging across the studies. Modalities included CT (-angiogram, -perfusion, -venogram), EEG, MRI (-angiogram, functional), and PET. The most frequently reported brain abnormalities were brain white matter (WM) hyperintensities on MRI 66/124 (53% affected cases) and hypodensities on CT (additional 23% affected cases), followed by microhemorrhages, hemorrhages and infarcts, while other types were found in <5% affected cases. WM abnormalities were most frequently noted in bilateral anterior and posterior cerebral WM (50% affected cases). CONCLUSION: About a third of acute/subacute COVID-19 patients referred for neuroimaging show brain abnormalities suggestive of COVID-19-related etiology. The predominant neuroimaging features were diffuse cerebral WM hypodensities / hyperintensities attributable to leukoencephalopathy, leukoaraiosis or rarefield WM.

Leukoencephalopathy Associated with Severe COVID-19 Infection: Sequela of Hypoxemia?

There is increasing evidence to suggest that complications of coronavirus disease 2019 (COVID-19) infection are not only limited to the pulmonary system but can also involve the central nervous system. Here, we report 6 critically ill patients with COVID-19 infection and neuroimaging findings of leukoencephalopathy. While these findings are nonspecific, we postulate that they may be a delayed response to the profound hypoxemia the patients experienced due to the infection. No abnormal enhancement, hemorrhage, or perfusion abnormalities were noted on MR imaging. In addition, Severe Acute Respiratory Syndrome coronavirus 2 was not detected in the CSF collected from the 2 patients who underwent lumbar puncture. Recognition of COVID-19-related leukoencephalopathy is important for appropriate clinical management, disposition, and prognosis.