Visual interpretation of brain hypometabolism related to neurological long COVID: a French multicentric experience

Abstract

Background: This multicentre study aimed to provide a qualitative and consensual description of brain hypometabolism observed through the visual analysis of ¹⁸F-FDG PET images of patients with suspected neurological long COVID, regarding the previously reported long-COVID hypometabolic pattern involving hypometabolism in the olfactory bulbs and other limbic/paralimbic regions, as well as in the brainstem and cerebellum.

Methods: From the beginning of August 2021 to the end of October 2021, the brain ¹⁸F-FDG PET scans of patients referred for suspected neurological long COVID with positive reverse transcription polymerase chain reaction (RT-PCR) and/or serology tests for SARS-CoV-2 infection were retrospectively reviewed in three French nuclear medicine departments (143 patients; 47.4 years old ± 13.6; 98 women). Experienced nuclear physicians from each department classified brain ¹⁸F-FDG PET scans according to the same visual interpretation analysis as being normal, mildly to moderately (or incompletely) affected, or otherwise severely affected within the previously reported long-COVID hypometabolic pattern.

Results: On the 143 brain ¹⁸F-FDG PET scans performed during this 3-month period, 53% of the scans were visually interpreted as normal, 21% as mildly to moderately or incompletely affected, and 26% as severely affected according to the COVID hypometabolic pattern. On average, PET scans were performed at 10.9 months from symptom onset (± 4.8). Importantly, this specific hypometabolic pattern was similarly identified in the three nuclear medicine departments. Typical illustrative examples are provided to help nuclear physicians interpret long-COVID profiles.

Conclusion: The proposed PET metabolic pattern is easily identified upon visual interpretation in clinical routine for approximately one half of patients with suspected neurological long COVID, requiring special consideration for frontobasal paramedian regions, the brainstem and the cerebellum, and certainly further adapted follow-up and medical care, while the second half of patients have normal brain PET metabolism on average 10.9 months from symptom onset.

Keywords: Brainstem; COVID-19; Cerebellum; FDG; Limbic regions; Long COVID; Olfactory bulb; PET; SARS-CoV-2.

Fig. 1

Typical examples of brain ¹⁸F-FDG PET images of patients with suspected long COVID in the three French nuclear medicine departments, all presenting positive RT-PCR and/or serology tests (cases from Nancy in the upper part, Paris in the middle part and Marseille in the lower part of the figure). Patients included in the left column were those with brain ¹⁸F-FDG PET images identified as normal by the nuclear physician experts (a 44-year-old woman referred 301 days after COVID infection for the persistence of dyspnoea on exertion and tachycardia without any cardio-pulmonary damage in the upper part; a 35-year-old woman referred 113 days after acute COVID for persistent asthenia, headaches, sleep disturbance, polyarthralgia and memory/concentration impairment in the middle part; and a 50-year-old woman with memory complaints, headaches and anosmia 314 days after infection in the lower part). The middle column includes patients who were classified as presenting a mild-to-moderate long-COVID hypometabolic pattern (a 41-year-old man who presented asthenia, dyspnoea on exertion and cognitive disorder 315 days after acute COVID acute infection in the upper part; a 52-year-old woman referred 342 days after COVID infection for cognitive complaints with language and memory difficulties, asthenia, insomnia and muscular weakness in the middle part; and a 55-year-old woman presenting memory complaints, loss of words, headaches and dyspnoea 168 days after the acute stage of the infection in the lower part); and the right column includes patients who were classified as presenting a severe long-COVID hypometabolic pattern (a 37-year-old-woman presenting cognitive impairment, dyspnoea, orthostatic hypotension, hypersomnia and fever at 253 days since symptom onset in the upper part; a 38-year-old-woman referred for brain ¹⁸F-FDG PET 545 days after acute COVID infection, with dysexecutive symptoms, memory difficulties, dizziness, limb paraesthesia, asthenia, myalgia and polyarthralgia in the middle part; and a 20-year-old-woman with persistence of functional symptoms, with asthenia, headaches and memory/concentration impairment 170 days after infection in the lower part). In these patients with a typical severe long-COVID hypometabolic pattern, the brain areas with hypometabolism are identified with arrows: white arrows for the fronto-orbital olfactory regions, red arrows for the other limbic/paralimbic regions, grey arrows for the pons and yellow arrows for the cerebellum