Quantitative susceptibility mapping of the normal-appearing white matter as a potential new marker of disability progression in multiple sclerosis.

OBJECTIVES: To investigate the normal-appearing white matter (NAWM) susceptibility in a cohort of newly diagnosed multiple sclerosis (MS) patients and to evaluate possible correlations between NAWM susceptibility and disability progression. METHODS: Fifty-nine patients with a diagnosis of MS (n = 53) or clinically isolated syndrome (CIS) (n = 6) were recruited and followed up. All participants underwent neurological examination, blood sampling for serum neurofilament light chain (sNfL) level assessment, lumbar puncture for the quantification of cerebrospinal fluid (CSF) ß-amyloid1-42 (Aß) levels, and brain MRI. T2-weighted scans were used to quantify white matter (WM) lesion loads. For each scan, we derived the NAWM volume fraction and the WM lesion volume fraction. Quantitative susceptibility mapping (QSM) of the NAWM was calculated using the susceptibility tensor imaging (STI) suite. Susceptibility maps were computed with the STAR algorithm. RESULTS: Primary progressive patients (n = 9) showed a higher mean susceptibility value in the NAWM than relapsing-remitting (n = 44) and CIS (n = 6) (p = 0.01 and p = 0.02). Patients with a higher susceptibility in the NAWM showed increased sNfL concentration (ρ = 0.38, p = 0.004) and lower CSF Aß levels (ρ = -0.34, p = 0.009). Mean NAWM susceptibility turned out to be a predictor of the expanded disability status scale (EDSS) worsening at follow-up (ß = 0.41, t = 2.66, p = 0.01) and of the MS severity scale (MSSS) (ß = 0.38, t = 2.43, p = 0.019). CONCLUSIONS: QSM in the NAWM seems to predict the EDSS increment over time. This finding might provide evidence on the role of QSM in identifying patients with an increased risk of early disability progression. KEY POINTS: • NAWM-QSM is higher in PPMS patients than in RRMS. • NAWM-QSM seems to be a predictor of EDSS worsening over time. • Patients with higher NAWM-QSM show increased sNfL concentration and lower CSF Aß levels.

Low CSF ß-amyloid levels predict early regional grey matter atrophy in multiple sclerosis.

BACKGROUND AND PURPOSE: Grey matter (GM) atrophy is present from the earliest stages of multiple sclerosis (MS) and occurs largely in a nonrandom manner. However, the biological mechanisms underlying the progression of regional atrophy are still unclear. Aim of this study is to investigate whether amyloid pathology might be involved in determining the pattern of GM atrophy over time. METHODS: Forty-six subjects were recruited: 31 newly diagnosed relapsing-remitting (RR-) MS patients and 15 age- and sex-matched healthy controls (HC). Aß levels were determined in CSF samples from all subjects. All participants underwent brain magnetic resonance imaging (MRI) at baseline, and 23 out of 31 patients at one year follow-up. T1-weighted scans were segmented using the Geodesic Information Flows software. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. RESULTS: CSF Aß concentration was the best predictor of global GM loss over time after age (ß = 0.403; p = 0.024), in particular in the left precuneus (p = 0.045), in the left middle cingulate gyrus (p = 0.009), in the left precentral gyrus (p = 0.021) and in the right angular gyrus (p = 0.029). CONCLUSIONS: CSF Aß levels seem to be crucial in MS early brain volume loss as GM atrophy manifests in regions particularly vulnerable to early Aß deposition.

Cortical markers of cognitive syndromes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) can be associated with a spectrum of cognitive and behavioural symptoms, but the related patterns of focal cortical atrophy in non-demented ALS patients remain largely unknown. We enrolled 48 non-demented ALS patients and 26 healthy controls for a comprehensive neuropsychological assessment and a magnetic resonance exam. Behavioural and cognitive impairment was defined on the basis of a data-driven multi-domain approach in 21 ALS patients. Averaged cortical thickness of 74 bilateral brain regions was used as a measure of cortical atrophy. Cortical thinning in a fronto-parietal network, suggesting a disease-specific pattern of neurodegeneration, was present in all patients, independent of cognitive and behavioural status. Between-group and correlational analyses revealed that inferior frontal, temporal, cingular and insular thinning are markers for cognitive and behavioural deficits, with language impairment mainly related to left temporal pole and insular involvement. These specific correlates support the concept of a spectrum of deficits, with an overlap between the ALS cognitive phenotypes and the syndromes of frontotemporal dementia.