COVID-19-associated necrotizing encephalopathy presenting without active respiratory symptoms: a case report with histopathology

Abstract

Acute necrotizing encephalopathy (ANE) is a rare complication of coronavirus disease 2019 (COVID-19) secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The condition is typically diagnosed based on characteristic neuroimaging findings in the context of active viral respiratory symptoms. We present a rare case of COVID-19-associated ANE presenting with expressive aphasia and encephalopathy in the absence of active respiratory symptoms. Initial evaluation revealed bilateral thalamic lesions and a mild neutrophilic-predominant pleocytosis on cerebrospinal fluid analysis, the latter of which has not been described in previously published cases. Presence of these atypical features prompted extensive diagnostic evaluation. Metagenomic next-generation sequencing on cerebrospinal fluid did not detect the presence of pathogenic nucleic acids. Thalamic biopsy revealed perivascular neutrophilic inflammation suggestive of small vessel vasculitis with surrounding hemorrhage and necrosis. Ultimately, the diagnosis was made following detection of SARS-CoV-2 serologies and after exclusion of alternative etiologies. The patient was successfully treated with a short course of high-dose methylprednisolone with favorable outcome.

Analysis of risk factors for seizures and short-term reoccurrence of seizures in febrile children with SARS-CoV-2 infection: an observational study

“…In addition, 2 patients were de nitively diagnosed with acute necrotizing encephalopathy (ANE), a rare and severe encephalopathy usually triggered by a viral infection.The clinical presentation, imaging, and laboratory ndings of these 2 patients met the diagnostic criteria for ANE, namely seizures, impaired consciousness, and imaging manifestations of symmetrical thalamic and multisite lesions.It is worth discussing the other patient in this study. This patient presented with seizures and impaired consciousness, and MRI of the head suggested abnormal signal shadows in the bilateral thalamus, internal capsule, and cerebral hemispheres; such clinical presentation and imaging ndings led the physician to consider necrotizing encephalopathy, but cerebrospinal uid examination in this patient suggested slightly elevated white blood cells, which was inconsistent with the previous diagnostic criteria for ANE.However, a recent study reported a case of COVID-19 infection with typical clinical and imaging manifestations of ANE, but the patient's cerebrospinal uid examination suggested leukocytosis, and the patient was nally diagnosed with ANE anyway after pathological examination of the thalamus and metagenomic next-generation sequencing (mNGS) of the cerebrospinal uid [14].The prognosis of all three patients considered for ANE in this study was poor, with one patient dying, one patient left with motor dysfunction, and one patient whose guardian ultimately chose to abandon treatment due to little hope of cure. Therefore, in patients who develop seizures after COVID-19 infection, physicians need to be alert to the possibility of secondary necrotizing encephalopathy in the children, especially those who develop persistent impairment of consciousness.…”

An eye to the future: Acute and long‐term neuro‐ophthalmological and neurological complications of COVID‐19

“…Cases include a patient with bilateral thalamic lesions that subsequently responded to corticosteroids with a thalamic biopsy demonstrating perivascular neutrophilic infiltration, haemorrhage and necrosis. 5 A second case had lesions consistent with acute disseminated encephalomyelitis on autopsy, a monophasic demyelinating CNS disease often seen in the setting of infections. 6 CNS inflammatory changes were identified in two studies examining the brain transcriptome using single-cell RNA sequencing in autopsy samples of persons who died with severe COVID-19, one with eight patients 7 and one with five patients 8 compared to controls.…”

“…Pathological CNS studies in COVID‐19 have demonstrated cellular changes comparable to those seen in immune mediated encephalitides. Cases include a patient with bilateral thalamic lesions that subsequently responded to corticosteroids with a thalamic biopsy demonstrating perivascular neutrophilic infiltration, haemorrhage and necrosis 5 . A second case had lesions consistent with acute disseminated encephalomyelitis on autopsy, a monophasic demyelinating CNS disease often seen in the setting of infections 6 …”

Neurologic Complications of COVID-19

“…Motor and sensory examinations were normal within the limits of her encephalopathy. MRI of her brain without and with contrast revealed fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in bilateral thalami with associated T1 postcontrast rim enhancement and evidence of hemorrhagic foci within the lesions on susceptibility-weighted imaging (SWI) ( figure 11-1 59 ) . CSF analysis revealed 14 white blood cells per mm 3 (91% neutrophils), protein of 54 mg/dL, and glucose of 73 mg/dL (serum, 131 mg/dL).…”

“…Extensive infectious workup was unrevealing except for positive COVID-19 real-time polymerase chain reaction (PCR) and positive COVID-19 antinucleocapsid antibodies. Because of concern for possible neoplasm, she underwent right thalamic biopsy, which revealed neutrophilic-predominant perivascular inflammation ( figure 11-2 59 ) . She was diagnosed with acute necrotizing encephalitis triggered by systemic infection with SARS-CoV-2 and treated with 5 days of IV methylprednisolone.…”