Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection, 2024, O’Connor et al.

[SNT Gatchaman]

Macro- and Microstructural White Matter Differences in Neurologic Postacute Sequelae of SARS-CoV-2 Infection
Erin E. O’Connor; Rosangela Salerno-Goncalves; Nikita Rednam; Rory O’Brien; Peter Rock; Andrea R. Levine; Thomas A. Zeffiro

BACKGROUND AND PURPOSE
Neuropsychiatric complications of SARS-CoV-2 infection, also known as neurologic postacute sequelae of SARS-CoV-2 infection (NeuroPASC), affect 10%–60% of infected individuals. There is growing evidence that NeuroPASC is a multi system immune dysregulation disease affecting the brain. The behavioral manifestations of NeuroPASC, such as impaired processing speed, executive function, memory retrieval, and sustained attention, suggest widespread WM involvement. Although previous work has documented WM damage following acute SARS-CoV-2 infection, its involvement in NeuroPASC is less clear. We hypothesized that macrostructural and microstructural WM differences in NeuroPASC participants would accompany cognitive and immune system differences.

MATERIALS AND METHODS
In a cross-sectional study, we screened a total of 159 potential participants and enrolled 72 participants, with 41 asymptomatic controls (NoCOVID) and 31 NeuroPASC participants matched for age, sex, and education. Exclusion criteria included neurologic disorders unrelated to SARS-CoV-2 infection. Assessments included clinical symptom questionnaires, psychometric tests, brain MRI measures, and peripheral cytokine levels. Statistical modeling included separate multivariable regression analyses of GM/WM/CSF volume, WM microstructure, cognitive, and cytokine concentration between-group differences.

RESULTS
NeuroPASC participants had larger cerebral WM volume than NoCOVID controls (β = 0.229; 95% CI: 0.017–0.441; t = 2.16; P = .035). The most pronounced effects were in the prefrontal and anterior temporal WM. NeuroPASC participants also exhibited higher WM mean kurtosis, consistent with ongoing neuroinflammation. NeuroPASC participants had more self-reported symptoms, including headache, and lower performance on measures of attention, concentration, verbal learning, and processing speed. A multivariate profile analysis of the cytokine panel showed different group cytokine profiles (Wald-type-statistic = 44.6, P = .046), with interferon (IFN)-λ1 and IFN-λ2/3 levels higher in the NeuroPASC group.

CONCLUSIONS
NeuroPASC participants reported symptoms of lower concentration, higher fatigue, and impaired cognition compatible with WM syndrome. Psychometric testing confirmed these findings. NeuroPASC participants exhibited larger cerebral WM volume and higher WM mean kurtosis than NoCOVID controls. These findings suggest that immune dysregulation could influence WM properties to produce WM volume increases and consequent cognitive effects and headaches. Further work will be needed to establish mechanistic links among these variables.


Link | PDF (American Journal of Neuroradiology)

 

[SNT Gatchaman]

To increase generalizability, alcohol, marijuana, and nicotine use were permitted. Marijuana use was not permitted on the day of, or day before, participation. Participants were excluded if substance use or substance use disorder was reported in the past 180days. We administered urine drug screens on the testing day.

Other exclusion criteria included 1) pregnancy, 2) claustrophobia, 3) MRI contraindications, 4) neurologic disorders unrelated to SARS-CoV-2 infection including seizure disorders, closed head injuries with loss of consciousness greater than 15 minutes, CNS neoplasm, multiple sclerosis, neurodegenerative disease or stroke, 5) unstable cardiac or pulmonary disease, and 6) chronic fatigue.

 

[rvallee]

They excluded the most common issue found in LC from a LC study?

But they found it anyway. Damn kids these days.

¯\_(ツ)_/¯

 

[SNT Gatchaman]

Possibly that meant the exclusion was a pre-existing diagnosis of ME/CFS, ME, CFS, "chronic fatigue" etc. Or they were drawing a distinction between physical and cognitive fatigue.

Recruitment took place between September 2021 and February 2023. SARS-CoV-2 infected participants were asked about the presence of “cognitive fog” or mental fatigue beginning after SARS-CoV-2 infection.

To determine if cognitive fog or mental fatigue were present, participants were asked during initial screening if they experienced problems with remembering events, concentrating, sustaining mental effort, thinking and focus, slowed conversational responses, or timely word selection and word retrieval. All participants assigned to the NeuroPASC group responded yes to 1 or more of these questions.

After the initial screening, SARS-CoV-2 participants completed structured questionnaires to better characterize their self-reported neurologic and systemic symptoms. We administered the neuroquality of life questions from the NIH Toolbox (NeuroQOL). It included self-reported measures of anxiety, depression, apathy, fatigue, sleep, executive function, and cognition.

It's always confusing when fatigue is so often framed as "neurological".