Imbalanced Brain Neurochemicals in Long COVID and ME/CFS: A Preliminary Study Using MRI.

PURPOSE: Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures. METHODS: Magnetic resonance spectroscopy data were acquired with a 3T Prisma magnetic resonance imaging scanner (Siemens Healthcare, Erlangen, Germany). We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n = 17), ME/CFS (n = 17), and healthy controls (n = 10) using Osprey software. The statistical analyses were performed using SPSS version 29 (IBM, Armonk, NY). Age and sex were included as nuisance covariates. RESULTS: Glutamate levels were significantly higher in patients with long COVID (P = .02) and ME/CFS (P = .017) than in healthy controls. No significant difference was found between the 2 patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (P = .012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS. CONCLUSION: Our study identified significantly elevated glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the 2 patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

BIANCA-MS: An optimized tool for automated multiple sclerosis lesion segmentation.

In this work we present BIANCA-MS, a novel tool for brain white matter lesion segmentation in multiple sclerosis (MS), able to generalize across both the wide spectrum of MRI acquisition protocols and the heterogeneity of manually labeled data. BIANCA-MS is based on the original version of BIANCA and implements two innovative elements: a harmonized setting, tested under different MRI protocols, which avoids the need to further tune algorithm parameters to each dataset; and a cleaning step developed to improve consistency in automated and manual segmentations, thus reducing unwanted variability in output segmentations and validation data. BIANCA-MS was tested on three datasets, acquired with different MRI protocols. First, we compared BIANCA-MS to other widely used tools. Second, we tested how BIANCA-MS performs in separate datasets. Finally, we evaluated BIANCA-MS performance on a pooled dataset where all MRI data were merged. We calculated the overlap using the DICE spatial similarity index (SI) as well as the number of false positive/negative clusters (nFPC/nFNC) in comparison to the manual masks processed with the cleaning step. BIANCA-MS clearly outperformed other available tools in both high- and low-resolution images and provided comparable performance across different scanning protocols, sets of modalities and image resolutions. BIANCA-MS performance on the pooled dataset (SI: 0.72 ± 0.25, nFPC: 13 ± 11, nFNC: 4 ± 8) were comparable to those achieved on each individual dataset (median across datasets SI: 0.72 ± 0.28, nFPC: 14 ± 11, nFNC: 4 ± 8). Our findings suggest that BIANCA-MS is a robust and accurate approach for automated MS lesion segmentation.

Reduction in grey matter atrophy in patients with relapsing multiple sclerosis following treatment with cladribine tablets.

BACKGROUND AND PURPOSE: Measures of atrophy in the whole brain can be used to reliably assess treatment effect in clinical trials of patients with multiple sclerosis (MS). Trials assessing the effect of treatment on grey matter (GM) and white matter (WM) atrophy are very informative, but hindered by technical limitations. This study aimed to measure GM and WM volume changes, using a robust longitudinal method, in patients with relapsing MS randomized to cladribine tablets 3.5 mg/kg or placebo in the CLARITY study. METHODS: We analysed T1-weighted magnetic resonance sequences using SIENA-XL, from 0 to 6 months (cladribine, n = 267; placebo, n = 265) and 6 to 24 months (cladribine, n = 184; placebo, n = 186). Mean percentage GM and WM volume changes (PGMVC and PWMVC) were compared using a mixed-effect model. RESULTS: More GM and WM volume loss was found in patients taking cladribine versus those taking placebo in the first 6 months of treatment (PGMVC: cladribine: -0.53 vs. placebo: -0.25 [p = 0.045]; PWMVC: cladribine: -0.49 vs. placebo: -0.34 [p = 0.137]), probably due to pseudoatrophy. However, over the period 6 to 24 months, GM volume loss was significantly lower in patients on cladribine than in those on placebo (PGMVC: cladribine: -0.90 vs. placebo: -1.27 [p = 0.026]). In this period, volume changes in WM were similar in the two treatment arms (p = 0.52). CONCLUSIONS: After a short period of pseudoatrophy, treatment with cladribine 3.5 mg/kg significantly reduced GM atrophy in comparison with placebo. This supports the relevance of GM damage in MS and may have important implications for physical and cognitive disability progression.

Subcortical and default mode network connectivity is impaired in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic condition with core symptoms of fatigue and cognitive dysfunction, suggesting a key role for the central nervous system in the pathophysiology of this disease. Several studies have reported altered functional connectivity (FC) related to motor and cognitive deficits in ME/CFS patients. In this study, we compared functional connectivity differences between 31 ME/CFS and 15 healthy controls (HCs) using 7 Tesla MRI. Functional scans were acquired during a cognitive Stroop color-word task, and blood oxygen level-dependent (BOLD) time series were computed for 27 regions of interest (ROIs) in the cerebellum, brainstem, and salience and default mode networks. A region-based comparison detected reduced FC between the pontine nucleus and cerebellum vermis IX (p = 0.027) for ME/CFS patients compared to HCs. Our ROI-to-voxel analysis found significant impairment of FC within the ponto-cerebellar regions in ME/CFS. Correlation analyses of connectivity with clinical scores in ME/CFS patients detected associations between FC and 'duration of illness' and 'memory scores' in salience network hubs and cerebellum vermis and between FC and 'respiratory rate' within the medulla and the default mode network FC. This novel investigation is the first to report the extensive involvement of aberrant ponto-cerebellar connections consistent with ME/CFS symptomatology. This highlights the involvement of the brainstem and the cerebellum in the pathomechanism of ME/CFS.