Patient 1
A 45 year-old man in good condition was affected by COVID in March 2020. He was admitted to hospital due to dyspnea and hypoxia and received oxygen therapy for 7 days. After discharge he complained of cognitive disorders with memory problems, slowness of ideation, general fatigue, anxiety, and depression without anosmia. In October 2020, the neurological examination and the brain MRI were considered normal. Neuropsychological assessment displayed mildly affected episodic memory and a deficit of executive functions. The FDG PET scan showed diffuse abnormal hypometabolic regions.
Patient 2
A 44 year-old woman suffered from a COVID infection in April 2021 with fever , cough, myalgias and anosmia. The PCR test was positive. The acute phase resolves in two weeks but was immediately followed by attention and memory complaints. Neurological exam and cerebral MRI were normal. Cognitive tests showed a mild attention deficit. Brain FDG PET revealed mainly hypometabolic areas of the cingulum , precuneus and parietal cortex.
Patient 3
A 43 year-old woman had COVID in May 2020 with cough, fever, and fatigue for 7 days without anosmia. PCR test was positive. The acute symptoms progressively weaned off but in August 2020 she complained of general fatigue, walking and memory problems and speech deficit. In November, brain and spinal cord MRIs were normal as well as the electromyogram. In January 2021, neuropsychological tests showed abnormal episodic memory and executive functions. The FDG PET scan shows quite diffuse hypometabolic areas.
Patient 4
A 74 year-old- man with hypertension was admitted in March 2021 for COVID and received oxygen therapy. He was discharged and continue oxygen therapy for two weeks at home. One month later he progressively suffered from cognitive deficit including memory and attention problems. Neurological exam was normal and brain MRI revealed mild cortical atrophy and moderate leukopathy classified Fazekas II. Neuropsychological evaluation revealed executive and attention deficits. FDG PET showed hypometabolic areas of the cingulate cortex and frontal cortex.
Patients 5
A 74 year-old- man with type 2 diabetes was admitted in April 2020 for a few days for COVID and received oxygen therapy. He was discharged after 7 days . He progressively complained of attention problems for 18 months. In October 2021 neurological exam and brain MRI were normal. Neuropsychological tests showed episodic visual memory and executive deficits. FDG PET showed hypometabolic areas of the posterior cingulate cortex, occipital cortex and precuneus
Patient 6
A 28 year old woman suffered from a mild form of COVID in August 2020. PCR test was positive. Three months later , she complained of memory and concentration disturbances. Brain MRI was normal and cognitive tests revealed attention and executive deficits. FDG PET showed hypometabolic areas of the precuneus and cingulate cortex.
Methods
All patients gave their informed consents for the inclusion in this standard of care study and the protocol was approved by the Ethics Committee of Paris Bichat Hospital University of Paris Cité.
Neuropsychological evaluations included MMSE scores for global cognition and Frontal Assessment Battery for executive functions (FAB) (7)
Only patients with neurological Long COVID , cognitive complaints and abnormal initial PET scans revealing hypometabolic areas were included. All patients had cognitive rehabilitation during the period of 12 months. The second PET was performed about 12 months after the first PET.
A quantitative ROI-based analysis using Cortex ID suite (GE Healthcare), a fully automated spatial normalization applied to brain PET data, was carried out. A set of 26 VOIs of particular interest in neurodegenerative diseases and based on functional anatomy give individual maps of cortical hypometabolism, according to the ICBM152 Atlas. Results were automatically compared with those of a set of 294 healthy controls matched for age and sex. The results are expressed as Z-scores, i.e., the difference divided by the standard deviation. Hypometabolic regions with more than two standard deviations are shown in Figure 1
FDG PET scan and cognitive Results (Figure 1,Table 1)
In patient 1, the new FDG PET carried out after 15 months showed a visible reduction of hypometabolic areas detected in the cingulate cortex , the precuneus and parietotemporal cortex. Cognitive tests showed improvement for the MMSE and FAB
In patient 2, the new FDG PET performed after 12 months revealed persistent hypometabolic areas mainly in the cingulate cortex whereas hypometabolic zones were reduced in the frontal cortex. The first and second neuropsychological evaluations were normal for MMSE and FAB
In patient 3, the new FDG PET scan carried out after 12 months displayed clear reductions of hypometabolic regions in the cingulate cortex , and parieto-occipital cortex. At the opposite the neuropsychological assessment revealed exacerbated deficits for MMSE and FAB
In patient 4, FDG PET performed after13 months showed a reduction of hypometabolic regions of the cingulate and frontal cortices. Cognitive evaluation revealed improvement of the FAB
In patient 5, the second FDG PET scan was realized after 10 months and displayed a clear diminution of hypometabolic regions. MMSE and frontal battery test were rather unchanged.
In patient 6, the second FDG PET scan was realized after 12 months showed a clear diminution of hypometabolic regions. MMSE was stable and FAB return to normal