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Background: Although apathy has been associated with fronto-striatal dysfunction in several neurological disorders, its clinical and magnetic resonance imaging (MRI) correlates have been poorly investigated in people with multiple sclerosis (PwMS)., Objectives: To evaluate clinical variables and investigate microstructural integrity of fronto-striatal grey matter (GM) and white matter (WM) structures using diffusion tensor imaging (DTI)., Methods: A total of 123 PwMS (age: 40.25 ± 11.5; female: 60.9%; relapsing-remitting multiple sclerosis: 75.6%) were prospectively enrolled and underwent neurological and neuropsychological evaluation, including Expanded Disability Status Scale (EDSS), Apathy Evaluation Scale (AES-S), Hospital Anxiety and Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS) and brain 3T-MRI volumes of whole brain, frontal/prefrontal cortex (PFC) and subcortical regions were calculated. DTI-derived metrics were evaluated in the same GM regions and in connecting WM tracts., Results: Apathetic PwMS (32.5%) showed lower education levels, higher HADS, MFIS scores and WM lesions volume than nonapathetic PwMS. Significant differences in DTI metrics were found in middle frontal, anterior cingulate and superior frontal PFC subregions and in caudate nuclei. Significant alterations were found in the right cingulum and left striatal-frontorbital tracts., Conclusions: Apathy in PwMS is associated with higher levels of physical disability, depression, anxiety and fatigue together with lower educational backgrounds. Microstructural damage within frontal cortex, caudate and fronto-striatal WM bundles is a significant pathological substrate of apathy in multiple sclerosis (MS)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: M.I. received grants from NIH, NMSS and FISM; received fees for consultation from BMS; Janssen, Roche, Genzyme, Merck, Biogen and Novartis. M.C. received personal compensations from Novartis, Sanofi Genzyme and Teva and consulting fees from Zambon. G.B. was supported by a research fellowship FISM – Fondazione Italiana Sclerosi Multipla 2019/BR/016 and financed or co-financed with the ‘5 per mille’ public funding. He received personal fee from Novartis and Roche. C.L. received personal fee from Novartis, Roche, Sanofi, BMS and Janssen. All other authors declare no competing interests.

Dry needling (DN) is a minimally invasive treatment technique widely used by physical therapists to treat myofascial trigger points (MTrP). Even if its safety has been commonly declared and the majority of adverse events are considered mild, serious adverse events cannot be excluded and DN treatments of several trunk muscles can potentially result in pneumothorax. Ultrasound imaging (US) skin-to-rib measurement could ensure the safety of this treatment procedure. Therefore, the aim of this study was to determine the inter-rater reliability of depth measurement of different trunk muscles (i.e., rhomboid, lower trapezius, iliocostalis, and pectoralis major) between an expert and two novice physiotherapists. Skin-to-rib distance of 26 asymptomatic and normal weights subjects was consecutively, independently, and randomly measured for each muscle by the three examiners (1 expert and 2 novice physical therapists) with a handheld US wireless probe. Intraclass correlation coefficient (ICC 3,k ) and standard error of measurement (SEM) were used to assess inter-rater reliability. Inter-rater reliability of skin-to-rib measurements between the three examiners was good to excellent or excellent for every muscle, with an ICC 3,k ranging from 0.92 and 0.98 (95% CI 0.86-0.99). The SEM never exceeded 10% of the skin-to-rib distance. In conclusion, skin-to-rib US measurements of the trunk muscles can be reliably performed by novice physical therapists using a handheld US device. These measures could be used as an innovative and reliable technique to improve the safety of some potential dangerous DN treatments.