Aim The aim of this paper is to describe the clinical features of COVID‐19‐related encephalopathy and their metabolic correlates using brain 2‐desoxy‐2‐fluoro‐D‐glucose (FDG)‐positron‐emission tomography (PET)/computed tomography (CT) imaging. Background and purpose A variety of neurological manifestations have been reported in association with COVID‐19. COVID‐19‐related encephalopathy has seldom been reported and studied. Methods We report four cases of COVID‐19‐related encephalopathy. The diagnosis was made in patients with confirmed COVID‐19 who presented with new‐onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2‐desoxy‐2‐fluoro‐D‐glucose (FDG)‐positron‐emission tomography (PET)/computed tomography (CT) (FDG‐PET/CT). Results The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID‐19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS‐CoV‐2 RT‐PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG‐PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. Conclusions Despite varied clinical presentations, all patients presented with a consistent FDG‐PET pattern, which may reflect an immune mechanism.

Purpose Little is known about the neuronal substrates of neuropsychiatric symptoms associated with COVID-19 and their evolution during the course of the disease. We aimed at describing the longitudinal brain metabolic pattern in COVID-19related encephalopathy using 18F-FDG-PET/CT. Methods Seven patients with variable clinical presentations of COVID-19-related encephalopathy were explored thrice with brain 18F-FDG-PET/CT, once in the acute phase, 1 month later and 6 months after COVID-19 onset. PET images were analysed with voxel-wise and regions-of-interest approaches in comparison with 32 healthy controls. Results Patients' neurological manifestations during acute encephalopathy were heterogeneous. However, all of them presented with predominant cognitive and behavioural frontal disorders. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. MRI revealed no specific abnormalities for most of the subjects. All patients had a consistent pattern of hypometabolism in a widespread cerebral network including the frontal cortex, anterior cingulate, insula and caudate nucleus. Six months after COVID-19 onset, the majority of patients clinically had improved but cognitive and emotional disorders of varying severity remained with attention/executive disabilities and anxio-depressive symptoms, and lasting prefrontal, insular and subcortical 18F-FDG-PET/CT abnormalities. Conclusion The implication of this widespread network could be the neural substrate of clinical features observed in patients with COVID-19, such as frontal lobe syndrome, emotional disturbances and deregulation of respiratory failure perception. This study suggests that this network remains mildly to severely impaired 6 months after disease onset.

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Objective: To evaluate Bacille Calmette-Guérin (BCG) effects after clinically isolated syndromes (CIS).Methods: In a double-blind, placebo-controlled trial, participants were randomly assigned to receive BCG or placebo and monitored monthly with brain MRI (6 scans). Both groups then entered a preplanned phase with IM interferon-b-1a for 12 months. From month 18 onward, the patients took the disease-modifying therapies (DMTs) that their neurologist considered indicated in an open-label extension phase lasting up to 60 months.Results: Of 82 randomized subjects, 73 completed the study (33 vaccinated and 40 placebo). Conclusions: Early BCG may benefit CIS and affect its long-term course.Classification of evidence: BCG, as compared to placebo, was associated with significantly reduced development of gadolinium-enhancing lesions in people with CIS for a 6-month period before starting immunomodulating therapy (Class I evidence). Neurology ® 2014;82:41-48 GLOSSARY BCG 5 Bacille Calmette-Guérin; CDMS 5 clinically definite multiple sclerosis; CI 5 confidence interval; CIS 5 clinically isolated syndrome; CSE 5 conventional spin-echo; DMT 5 disease-modifying therapy; EDSS 5 Expanded Disability Status Scale; Gd 5 gadolinium; IFN 5 interferon; MS 5 multiple sclerosis; RR 5 relative risk; T1W 5 T1-weighted; T2W 5 T2-weighted; TE 5 echo time; TR 5 repetition time.The majority of multiple sclerosis (MS) cases start with a first demyelinating episode (usually referred to as clinically isolated syndrome [CIS]) that is generally reversible. Approximately half of these cases convert to clinically definite MS (CDMS) within 2 years of the diagnosis and have substantial risk of disability, while about 10% of people with CIS remain free of further neurologic events, even in the presence of MRI compatible with MS.

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