Brain autopsies of critically ill COVID-19 patients demonstrate heterogeneous profile of acute vascular injury, inflammation and age-linked chronic brain diseases.

BACKGROUND: This study examined neuropathological findings of patients who died following hospitalization in an intensive care unit with SARS-CoV-2. METHODS: Data originate from 20 decedents who underwent brain autopsy followed by ex-vivo imaging and dissection. Systematic neuropathologic examinations were performed to assess histopathologic changes including cerebrovascular disease and tissue injury, neurodegenerative diseases, and inflammatory response. Cerebrospinal fluid (CSF) and fixed tissues were evaluated for the presence of viral RNA and protein. RESULTS: The mean age-at-death was 66.2 years (range: 26-97 years) and 14 were male. The patient's medical history included cardiovascular risk factors or diseases (n = 11, 55%) and dementia (n = 5, 25%). Brain examination revealed a range of acute and chronic pathologies. Acute vascular pathologic changes were common in 16 (80%) subjects and included infarctions (n = 11, 55%) followed by acute hypoxic/ischemic injury (n = 9, 45%) and hemorrhages (n = 7, 35%). These acute pathologic changes were identified in both younger and older groups and those with and without vascular risk factors or diseases. Moderate-to-severe microglial activation were noted in 16 (80%) brains, while moderate-to-severe T lymphocyte accumulation was present in 5 (25%) brains. Encephalitis-like changes included lymphocytic cuffing (n = 6, 30%) and neuronophagia or microglial nodule (most prominent in the brainstem, n = 6, 30%) were also observed. A single brain showed vasculitis-like changes and one other exhibited foci of necrosis with ball-ring hemorrhages reminiscent of acute hemorrhagic leukoencephalopathy changes. Chronic pathologies were identified in only older decedents: 7 brains exhibited neurodegenerative diseases and 8 brains showed vascular disease pathologies. CSF and brain samples did not show evidence of viral RNA or protein. CONCLUSIONS: Acute tissue injuries and microglial activation were the most common abnormalities in COVID-19 brains. Focal evidence of encephalitis-like changes was noted despite the lack of detectable virus. The majority of older subjects showed age-related brain pathologies even in the absence of known neurologic disease. Findings of this study suggest that acute brain injury superimposed on common pre-existing brain disease may put older subjects at higher risk of post-COVID neurologic sequelae.

Acute Hemorrhagic Leukoencephalopathy Triggered by COVID-19 Infection.

Background: This study represents an additional case of a rare entity and complication of COVID-19. Purpose: To further describe COVID's association with acute hemorrhagic leukoencephalopathy (AHL), a variant of acute disseminated encephalomyelitis. Besides, subsequent neuropsychological evaluation is described. Methods: The present case report describes clinical, laboratory, radiological, and electroencephalographic characteristics of AHL triggered by COVID-19, in addition to outcomes in the neuropsychological findings. Results: Radiologic findings of demyelinating lesions in supratentorial white matter permeated by multiple hemorrhagic foci supported the diagnostic of AHL, reinforced by clinical improvement after corticosteroid therapy. Conclusions: There are few similar cases previously reported, and this case highlights the early diagnosis and prompt treatment looking forward to better outcomes in AHL. Further studies are needed to elucidate the involved pathophysiological mechanisms.

Acute Hemorrhagic Leukoencephalopathy: Pathological Features and Cerebrospinal Fluid Cytokine Profiles.

BACKGROUND: Acute hemorrhagic leukoencephalopathy is a rare encephalopathy of unknown etiology, causing fulminant, hemorrhagic central nervous system demyelination with high mortality. It is unclear whether acute hemorrhagic leukoencephalopathy is an entirely distinct entity from acute disseminated encephalomyelitis. PATIENTS AND METHODS: We report two patients with rapidly progressive neurological illness resulting in raised intracranial pressure and coma, with biopsy-proven acute hemorrhagic leukoencephalopathy (perivascular hemorrhages and demyelination, predominantly neutrophil infiltrates). RESULTS: Acute cerebrospinal fluid showed pronounced T cell-associated cytokine elevation (interleukins 6, 8, and 17A) and CCL2 or CCL3, higher than in patients with acute disseminated encephalomyelitis, but no B cell-associated cytokine elevation. CONCLUSION: Improved understanding of the immune process may provide rationale for use of anticytokine biologic agents.

Acute Hemorrhagic Leukoencephalopathy in a Patient with Influenza A and B Coinfection

Acute hemorrhagic leukoencephalopathy is a rare condition associated with the influenza virus, but the role of influenza in this condition has not been clarified. We experienced a patient with influenza A and B virus co-infection who initially presented mild gastrointestinal symptoms and rapidly progressed to coma. Magnetic resonance imaging showed severe brain edema and multiple intracranial hemorrhagic lesions. The patient was treated with oseltamivir and corticosteroid, and her clinical course improved without neurological sequelae.

Acute Hemorrhagic Leukoencephalopathy in a Patient with Influenza A and B Coinfection

Acute hemorrhagic leukoencephalopathy is a rare condition associated with the influenza virus, but the role of influenza in this condition has not been clarified. We experienced a patient with influenza A and B virus co-infection who initially presented mild gastrointestinal symptoms and rapidly progressed to coma. Magnetic resonance imaging showed severe brain edema and multiple intracranial hemorrhagic lesions. The patient was treated with oseltamivir and corticosteroid, and her clinical course improved without neurological sequelae.