Acute COVID-19 Infection Associated With Necrotizing Disseminated Acute Leukoencephalopathy and Brain Microhemorrhages in a Pediatric Patient.

We present a case of a 14-year-old, previously healthy female, admitted with acute coronavirus disease 2019 infection and new-onset seizures secondary to virus-associated necrotizing disseminated acute leukoencephalopathy. Her symptoms resolved completely with intravenous immunoglobulin and steroids. Pathophysiology and prognosis of neurologic manifestations of coronavirus disease 2019 remain unclear.

Coronavirus Disease (COVID-19)-Related Disseminated Leukoencephalopathy: A Retrospective Study of Findings on Brain MRI.

Among 2820 inpatients with coronavirus disease (COVID-19), 59 (2.1%) underwent brain MRI. Of them, six (10.2%) had MRI findings suspicious for COVID-19-related disseminated leukoencephalopathy (CRDL), which is characterized by extensive confluent or multifocal white matter lesions (with characteristics and locations atypical for other causes), microhemorrhages, diffusion restriction, and enhancement. CRDL is an uncommon but important differential consideration in patients with neurologic manifestations of COVID-19.

A practical approach to adult-onset white matter diseases, with illustrative cases.

AIM: To evaluate five illustrative cases and perform a literature review to identify and describe a working approach to adult-onset white matter diseases (WMD). STATE OF THE ART: Inherited WMD are a group of disorders often seen in childhood. In adulthood, progressive WMDs are rare, apart from the common nonspecific causes of hypertension and other cerebrovascular diseases. The pattern of WMDs on neuroimaging can be an important clue to the final diagnosis. Due to the adoption of a combined clinical-imaging-laboratory approach, WMD is becoming better recognised, in addition to the rapidly evolving field of genomics in this area. CLINICAL IMPLICATIONS: While paediatric WMDs have a well-defined and literature-based clinical-laboratory approach to diagnosis, adult-onset WMDs remain an important, pathologically diverse, radiographic phenotype, with different and distinct neuropathologies among the various subtypes of WMD. Adult-onset WMDs comprise a wide collection of both acquired and inherited aetiologies. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neurological complications are emerging, we are as yet unaware of it causing WMD outside of post-anoxic changes. It is important to recognise WMD as a potentially undefined acquired or genetic syndrome, even when extensive full genome testing reveals variants of unknown significance. FUTURE DIRECTIONS: We propose a combined clinical-imaging-laboratory approach to WMD and continued exploration of acquired and genetic factors. Adult-onset WMD, even given this approach, can be challenging because hypertension is often comorbid. Therefore, we propose that undiagnosed patients with WMD be entered into multicentre National Organisation for Rare Diseases registries to help researchers worldwide make new discoveries that will hopefully translate into future cures.

Covert Subclinical Neurocognitive Sequelae During the Rehabilitation Course of Severe Coronavirus Disease 2019.

ABSTRACT: Apart from respiratory symptoms, encephalopathy and a range of central nervous system complications have been described in coronavirus disease 2019. However, there is a lack of published literature on the rehabilitative course and functional outcomes of severe coronavirus disease 2019 with encephalopathy. In addition, the presence of subclinical neurocognitive sequelae during postacute rehabilitation has not been described and may be underrecognized by rehabilitation providers. We report the rehabilitative course of a middle-aged male patient with severe coronavirus disease 2019 who required intensive care and mechanical ventilation. During postacute inpatient rehabilitation for severe intensive care unit-related weakness, an abnormal cognitive screen prompted brain magnetic resonance imaging, which revealed destructive leukoencephalopathy. Subsequently, detailed psychometric evaluation revealed significant impairments in the domains of processing speed and executive function. After 40 days of intensive inpatient rehabilitation, he was discharged home with independent function. This report highlights the need for an increased awareness of covert subclinical neurocognitive sequelae, the role of comprehensive rehabilitation, and value of routine cognitive screening therein and describes the neurocognitive features in severe COVID-19.

COVID-19-related diffuse posthypoxic leukoencephalopathy and microbleeds masquerades as acute necrotizing encephalopathy.

BACKGROUND: The complications of coronavirus disease 2019 (COVID-19), the clinical entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are not limited to the respiratory system. Leukoencephalopathy with microbleeds is increasingly seen in patients with COVID-19. New information is needed to delineate better the clinical implications of this infectious disease. CASE REPORT: A 46-year-old man with confirmed SARS-CoV-2 infection was admitted to the intensive care unit (ICU) with severe COVID-19. After transfer to the general wards, the patient was noted drowsy, disorientated, with slow thinking and speech. A brain MRI showed bilateral symmetrical hyperintense lesions in the deep and subcortical whiter matter, involving the splenium of the corpus callosum, as well as multiple microhemorrhages implicating the splenium and subcortical white matter. No contrast-enhanced lesions were observed in brain CT or MRI. CSF analysis showed no abnormalities, including a negative rtRT-PCR for SARS-CoV-2. An outpatient follow-up visit showed near-complete clinical recovery and resolution of the hyperintense lesions on MRI, without microbleeds change. CONCLUSION: We present the case of a survivor of severe COVID-19 who presented diffuse posthypoxic leukoencephalopathy, and microbleeds masquerading as acute necrotizing encephalopathy. We postulate that this kind of cerebral vasogenic edema with microbleeds could be the consequence of hypoxia, inflammation, the prothrombotic state and medical interventions such as mechanical ventilation and anticoagulation.

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.

Imaging Features of Acute Encephalopathy in Patients with COVID-19: A Case Series.

Coronavirus disease 2019 was declared a global pandemic by the World Health Organization on March 11, 2020. There is a scarcity of data on coronavirus disease 2019-related brain imaging features. We present 5 cases that illustrate varying imaging presentations of acute encephalopathy in patients with coronavirus disease 2019. MR features include leukoencephalopathy, diffusion restriction that involves the GM and WM, microhemorrhages, and leptomeningitis. We believe it is important for radiologists to be familiar with the neuroradiologic imaging spectrum of acute encephalopathy in the coronavirus disease 2019 population.

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.