The first presumptive case of COVID-19-associated acute necrotizing hemorrhagic encephalopathy, a rare para-infectious encephalopathy, was reported.
An uncommon complication of influenza and other viral infections, acute necrotizing encephalopathy (ANE) has been related to intracranial cytokine storms. Accumulating evidence suggests a subgroup of patients with severe COVID-19 coronavirus infection may have a .
Radiological features were typical of ANE, showing bilateral thalamic lesions and other symmetric multifocal lesions in white and gray matter with hemorrhages, reported Brent Griffith, MD, of the Henry Ford Health System in Detroit, and coauthors in .
"This case report is particularly important since alteration in level of consciousness is common in patients with COVID-19 associated acute respiratory distress syndrome (ARDS) and is often attributed to hypoxia or multi-organ failure," said Avindra Nath, MD, senior investigator of nervous systems infections at the NIH's National Institute of Neurological Disorders and Stroke, who was not involved with the case.
"MRI of the brain should be considered in these patients to look for the possibility of brain lesions," Nath told ľֱ.
The case involved a female airline worker in her late 50s who presented with a 3-day history of cough, fever, and altered mental status. Her initial work-up was negative for influenza. COVID-19 was diagnosed by detecting SARS-CoV-2, the virus that causes the disease, in a nasopharyngeal swab specimen via real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay.
A traumatic lumbar puncture limited cerebrospinal fluid (CSF) analysis and CSF testing for SARS-CoV-2 could not be performed. CSF bacterial culture showed no growth after 3 days, and tests for herpes simplex virus 1 and 2, varicella zoster virus, and West Nile virus were negative.
Non-contrast head CT images showed symmetric hypoattenuation in the bilateral medial thalami with normal CT angiogram and venogram, reported Griffith and coauthors. MRI demonstrated hemorrhagic rim enhancing lesions in bilateral thalami, medial temporal lobes, and subinsular regions.
The patient was started on intravenous immunoglobulin and high-dose steroids were not used due to concern for respiratory compromise.
Plasmapheresis might be an alternative treatment, but "may not be easily feasible in this setting where patients are in isolation in the ICU," Nath said. "Anti-IL6 and anti-TNF-alpha antibodies are also being considered for treatment of cytokine storm and could potentially be useful for patients with ANE if diagnosed early."
An important distinction needs to be made between ANE and acute disseminated encephalomyelitis (ADEM), which is often post-viral, he added. "In patients with ANE, the CSF may show increased protein but there is no pleocytosis. ADEM has been reported with other coronaviruses such as MERS and HCoV-OC43, and one needs to be on the lookout for the possibility that it may occur with SARS-CoV-2 as well," he noted.
Neurologic complications of COVID-19 are unclear, Nath pointed out in a recent paper.
"Mouse coronaviruses have been shown to from the olfactory pathways to the brainstem and from the lung retrogradely to the lower brainstem," he said. "Anosmia is a very common symptom in COVID-19, suggesting the invasion of the olfactory nerve. However, autopsy studies will be necessary to determine if SARS-CoV-2 is in fact neuroinvasive."
Disclosures
The authors disclosed no conflicts of interest.
Primary Source
Radiology
Poyiadji N, et al "COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features" Radiology 2020; DOI: 10.1148/radiol.2020201187.