Delayed encephalopathy after COVID-19: A case series of six patients

Abstract

Rationale: Acute encephalopathy is a severe neurological complication of coronavirus disease 2019 (COVID-19). Most cases of acute encephalopathy associated with COVID-19 occur within several weeks of COVID-19 onset. We describe a case series of 6 patients who developed delayed encephalopathy (DE) after COVID-19. Patient concerns and diagnoses: We evaluated patients who recovered from COVID-19 and showed acute disturbance of consciousness or focal neurological deficits without recurrence of pneumonitis. Six patients, 2 females and 4 males, with ages ranging from 65 to 83 years were included. Durations of hospitalization due to COVID-19 were between 25 and 44 days. The severity of COVID-19 was moderate in 5 and severe in 1 patient. Patients were rehospitalized for acute disturbance of consciousness concomitant with postural tremor and, abnormal behavior, hemiplegia, aphasia, or apraxia between 34 and 67 days after the onset of COVID-19. Chest computed tomography showed no exacerbation of pneumonitis. Brain magnetic resonance imaging showed no specific findings except in 1 patient with an acute lacunar infarction. Electroencephalogram demonstrated diffuse slowing in all patients. Repeat electroencephalogram after recovery from encephalopathy demonstrated normal in all patients. One of the 6 patients had cerebrospinal fluid (CSF) pleocytosis. CSF protein levels were elevated in all patients, ranging from 51 to 115 mg/dL. CSF interleukin-6 levels ranged from 2.9 to 10.9 pg/mL. The immunoglobulin index was 0.39 to 0.44. Qlim(alb) < QAlb indicating dysfunction of the blood–brain barrier was observed in all patients. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction of CSF was negative in all patients. Neuronal autoantibodies were absent in serum and CSF. Interventions and outcomes: Immunotherapy including steroid pulses was administered to 3 patients; however, symptoms of encephalopathy resolved within several days in all patients, regardless of treatment with immunotherapy, and their consciousness levels were recovered fully. Notably, postural tremor remained for 2 weeks to 7 months. Lessons: In our patients, DE after COVID-19 was characterized by symptoms of acute encephalopathy accompanied with tremor in the absence of worsening pneumonitis after the fourth week of COVID-19 onset. Our findings indicate blood–brain barrier dysfunction may contribute to the pathogenesis of DE after COVID-19.

COVID-19-associated encephalopathy: connection between neuroinflammation and microbiota-gut-brain axis

“…COVID-19, caused by the SARS-CoV-2 virus, is linked to various neurological complications, including COVID-19 encephalopathy, which is often observed in severe cases, particularly in older patients with acute respiratory distress syndrome and multiple organ failure ( Ellul et al, 2020 ; Abenza Abildúa et al, 2021 ; Garg et al, 2021 ; Pilotto et al, 2021 ; Akimoto et al, 2022 ). The Global COVID-19 Neuro Research Coalition defines COVID-19 encephalopathy as necessitating a COVID-19 diagnosis, temporal correlation with symptoms, exclusion of other diseases, and differentiation between primary brain disease and secondary brain dysfunction related to COVID-19 severity ( Michael et al, 2023 ).…”