COVID-19-Associated Amnesia With Bilateral Hippocampal Lesions in an 8-Year-old Boy: A Case Report.

To the Editors: Coronavirus disease-2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In adult and pediatric patients, COVID-19 often affects the cardiovascular, gastrointestinal or neurological systems, aside from the respiratory system. Although memory impairment is known as a neurological complication associated with COVID-19 in adults, no report has described hippocampal legions in such cases. Herein, we report a case of pediatric COVID-19–associated amnesia with bilateral hippocampal abnormality on magnetic resonance imaging (MRI). An 8-year-old boy presented to the emergency department with generalized seizures persisting for 2 minutes. He had no history of seizures. On admission, he was alert and oriented, with 39.6°C body temperature. He was diagnosed with febrile seizures (FS) associated with COVID-19 which was confirmed through positive reverse transcription polymerase chain reaction test for SARS-CoV-2 from a nasopharyngeal swab. Although fever resolved in 2 days, his mother noticed that he had repeated the same questions since his admission. He could not remember what he ate a couple of hours before, suggesting anterograde amnesia. Neurological and cerebrospinal fluid (CSF) examinations showed no abnormalities. Reverse transcription polymerase chain reaction for SARS-CoV-2 in CSF was negative. However, MRI of his brain demonstrated bilateral hippocampal hyperintensities on both fluid-attenuated inversion recovery (Fig. 1) and diffusion-weighted imaging. Thus, methylprednisolone pulse therapy (30 mg/kg/dose) was administered for 3 consecutive days. At the 4th week follow-up, MRI showed less intensity of his hippocampal lesions. He had fully recovered without significant sequelae.FIGURE 1.: Magnetic resonance imaging of the brain. Sagittal (A) and coronal (B) imaging showed hyperintensity in the bilateral hippocampal regions on fluid-attenuated inversion recovery.Various COVID-19–associated neurological manifestations have been reported since the pandemic began. FS and encephalopathy are major causes of hospitalization in children with COVID-19.1 Even in mild cases, memory impairment often persists beyond the acute disease phase.2 Nevertheless, the mechanisms remain poorly understood. The hippocampus stores new memories and spatial memories and transfers them to long-term memories. Our result suggested that anterograde amnesia was attributed to bilateral hippocampal lesions as detected by MRI during the acute phase of COVID-19. This is supported by a recent pathological study which showed neuronal degeneration and decreased neurogenesis of the hippocampus in victims of COVID-19; however, the genome or antigens of SARS-CoV-2 is not tested in their brain specimens.3 To the best of our knowledge, MRI findings in COVID-19–associated amnesia have not been reported, possibly because brain MRI is not commonly performed in children with simple FS with no or mild postictal neurological abnormalities. Additionally, amnesia diagnosis is difficult in young children before language acquisition. SARS-CoV-2 genome was not detected from CSF in our patient; thus, the virus may not have directly affected the neuronal cells of hippocampus. Experimental mice infected with a non-neurotropic influenza show memory deficits associated with elevated hippocampal cytokines production by activated microglia despite lack of viral genome in the hippocampus.4 Similar mechanisms may be involved in the hippocampal damage of our patient. Our patient had rapidly and completely recovered after receiving methylprednisolone pulse therapy. Further investigation is needed to elucidate the mechanism of hippocampal damages and establish therapeutic strategies for COVID-19–associated amnesia in the future. ACKNOWLEDGMENTS We would like to thank Enago (www.enago.jp) for the English language reviews.