BACKGROUND AND PURPOSE: MR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations. MATERIALS AND METHODS: Twenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM. RESULTS: The orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions. CONCLUSIONS: NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.

The recent SARS-CoV-2 pandemic and related vaccines have raised several issues. Among them, the potential role of the viral infection (COVID-19) or anti-SARS-CoV-2 vaccines as causal factors of dysimmune CNS disorders, as well as the safety and efficacy of vaccines in patients affected by such diseases and on immune-active treatments have been analyzed. The aim is to better understand the relationship between SARS-CoV-2 infection/vaccines with dysimmune CNS diseases by describing 12 cases of multiple sclerosis/myelitis onset or reactivation after exposure to SARS-CoV-2 infection/vaccines and reviewing all published case reports or case series in which MS onset or reactivation was temporally associated with either COVID-19 (8 case reports, 3 case series) or anti-SARS-CoV-2 vaccines (13 case reports, 6 case series). All the cases share a temporal association between viral/vaccine exposure and symptoms onset. This finding, together with direct or immune-based mechanisms described both during COVID-19 and MS, claims in favor of a role for SARS-CoV-2 infection/vaccines in unmasking dysimmune CNS disorders. The most common clinical presentations involve the optic nerve, brainstem and spinal cord. The preferential tropism of the virus together with the presence of some host-related genetic/immune factors might predispose to the involvement of specific CNS districts.

Artery-to-artery embolization from vulnerable intracranial nonstenosing atherosclerotic plaques (vNSPs) has been proposed as a major contributor to embolic stroke of undetermined source (ESUS). Vessel wall MRI (VWMRI) offers the potential to identify culprit vNSPs, yet prospective studies in ESUS populations are lacking. This study aimed to assess the role of vNSPs in single-territory ESUS and to evaluate the utility of intracranial VWMRI in the diagnostic workup. Consecutive patients admitted to the Stroke Unit of the IRCCS Mondino Foundation (Pavia, Italy) with a confirmed ESUS diagnosis after a complete etiologic workup were prospectively enrolled in the study. Patients with multiterritorial ischemic lesions, complicated aortic arch atherosclerosis, or a probable patent foramen ovale-associated stroke were excluded. Intracranial VWMRI at 3-T was performed within 1 month of the index event. Atherosclerotic lesions were considered culprit if demonstrating postcontrast enhancement on T1-weighted images and a location consistent with ischemic lesions' distribution. Quantitative radiologic features of vNSPs were also analyzed. A total of 80 patients (mean age 65.6 years, 34 [42.5%] women) were included. VWMRI identified a potentially culprit vNSP in 23 of 80 patients (28.8%, 95% CI 20-39.5). Patients with symptomatic vNSPs were older (72.7 vs 62.8 years, p = 0.002) and more frequently current (43.5 vs 35.1%) or former (30.4 vs 8.8%) smokers (p = 0.014). In a multivariable logistic regression model including major risk factors of intracranial atherosclerosis (age, smoking, hypertension, diabetes, and dyslipidemia), both age (adjusted odds ratio [aOR] 1.12, 95% CI 1.05-1.22, p = 0.002) and smoking status (active smokers: aOR 7.99, 95% CI 1.81-47.8, p = 0.011; former smokers: aOR 8.79, 95% CI 1.73-55.0, p = 0.012) were significantly associated with symptomatic vNSP. Intracranial vNSPs may represent a significant underlying cause of single-territory ESUS, and VWMRI could provide an added value in the diagnostic workup of these patients. Older age and smoking exposure were found to be independently associated with the presence of culprit intracranial vNSPs. Further studies are needed to confirm our findings because of the relatively small and monocentric cohort. This study provides Class IV evidence that VWMRI improves the identification of culprit vNSPs in patients with ESUS.

Background and Purpose: Early detection of peripheral nerve damage in patients with hereditary transthyretin amyloidosis (ATTRv) has become essential for the prompt initiation of effective, recently approved therapies. In our study, we propose a new variable echo time (vTE) MRI sequence as a non‐invasive method to detect nerve injury in ATTRv patients and to establish a novel potential imaging marker of neuropathy that correlates with disease severity and abnormal results of NCS.Methods: In this cohort study, twenty patients with clinically confirmed ATTRv polyneuropathy (PNP) and twenty‐one healthy volunteers underwent 3 T MRI. vTE was performed on the right thigh to include the proximal tract of the sciatic nerve. The cross‐sectional area of the whole sciatic nerve, inner epineurium, and endoneurial fascicles was segmented, and the corresponding pseudo‐T2* was extrapolated from the two acquired echoes of the vTE.Results: Significantly higher fascicles pT2* (p = < 0.001), total cross‐sectional area (CSA: p = 0.017) and fascicular area (p = < 0.001) were found in the ATTRv group compared to healthy controls. Fascicles pT2* also correlated with previously validated clinical outcome measures such as Polyneuropathy Disability Scoring System (PND score p = < 0. 001), Neuropathy Impairment Score (NIS p = 0.030) and NIS items related to the lower limbs, and with nerve conduction parameters, demonstrating the ability to discriminate ATTRv patients with different degrees of PNP from HC.Conclusion: In conclusion, the vTE sequence provides novel and reliable imaging markers capable of detecting early nerve microstructural changes related to disease onset and severity.