Early putamen hypertrophy and ongoing hippocampus atrophy predict cognitive performance in the first ten years of relapsing-remitting multiple sclerosis

Background The first years of relapsing-remitting multiple sclerosis (RRMS) constitute the most vulnerable phase for the progression of cognitive impairment (CImp), due to a gradual decrease of compensatory mechanisms. In the first 10 years of RRMS, the temporal volumetric changes of deep gray matter structures must be clarified, since they could constitute reliable cognitive biomarkers for diagnostic, prognostic, and therapeutic purposes. Methods Forty-five cognitively asymptomatic patients with RRMS lasting 64\u200910 years, and with a brain MRI performed in a year from the neuropsychological evaluation (Te-MRI), were included. They performed the Brief International Cognitive Assessment battery for MS. Thirty-one brain MRIs performed in the year of diagnosis (Td-MRI) and 13 brain MRIs of age- and sex-matched healthy controls (HCs) were also included in the study. The relationships between clinical features, cognitive performances, and Te- and Td-MRI volumes were statistically analyzed. Results Cognitively preserved (CP) patients had significantly increased Td-L-putamen (P\u2009=\u20090.035) and Td-R-putamen volume (P\u2009=\u20090.027) with respect to cognitively impaired (CI) ones. CI patients had significantly reduced Te-L-hippocampus (P\u2009=\u20090.019) and Te-R-hippocampus volume (P\u2009=\u20090.042) compared, respectively, with Td-L-hippocampus and Td-R-hippocampus volume. Td-L-putamen volume (P\u2009=\u20090.011) and Te-L-hippocampus volume (P\u2009=\u20090.023) were independent predictors of the Symbol Digit Modalities Test score in all patients (r2\u2009=\u20090.31, F\u2009=\u20096.175, P\u2009=\u20090.001). Conclusion In the first years of RRMS, putamen hypertrophy and hippocampus atrophy could represent promising indices of cognitive performance and reserve, and become potentially useful tools for diagnostic, prognostic, and therapeutic purposes

Fatigue in Multiple Sclerosis: a resting-state EEG microstate study

Fatigue affects approximately 80% of people with Multiple Sclerosis (PwMS) and can impact several domains of daily life. However, the neural underpinnings of fatigue in MS are still not completely clear. The aim of our study was to investigate the spontaneous large-scale networks functioning associated with fatigue in PwMS using the EEG microstate approach with a spectral decomposition. Forty-three relapsing-remitting MS patients and twenty-four healthy controls (HCs) were recruited. All participants underwent an administration of Modified Fatigue Impact scale (MFIS) and a 15-min resting-state high-density EEG recording. We compared the microstates of healthy subjects, fatigued (F-MS) and non-fatigued (nF-MS) patients with MS; correlations with clinical and behavioral fatigue scores were also analyzed. Microstates analysis showed six templates across groups and frequencies. We found that in the F-MS emerged a significant decrease of microstate F, associated to the salience network, in the broadband and in the beta band. Moreover, the microstate B, associated to the visual network, showed a significant increase in fatigued patients than healthy subjects in broadband and beta bands. The multiple linear regression showed that the high cognitive fatigue was predicted by both an increase and decrease, respectively, in delta band microstate B and beta band microstate F. On the other hand, higher physical fatigue was predicted with lower occurrence microstate F in beta band. The current findings suggest that in MS the higher level of fatigue might be related to a maladaptive functioning of the salience and visual network

Treatment of Fatigue in Multiple Sclerosis Patients: A Neurocognitive Approach

The objective of the study was to treat fatigue in patients with multiple sclerosis (MS) by a neurocognitive rehabilitation program aimed at improving motor planning by using motor imagery (MI). Twenty patients with clinically definite MS complaining of fatigue were treated for five weeks with exercises of neurocognitive rehabilitation twice a week. Patients were evaluated by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MSQoL54, Expanded Disability Status Scale (EDSS), and MS Functional Composite (MSFC). After treatment, a decrease in fatigue was detected with both FSS (P = 0.0001) and MFIS (P = 0.0001). MSFC (P = 0.035) and MSQoL54 (P = 0.002) scores improved compared to baseline. At six-month followup, the improvement was confirmed for fatigue (FSS, P = 0.0001; MFIS P = 0.01) and for the physical subscale of MSQoL54 (P = 0.049). No differences in disability scales were found. These results show that neurocognitive rehabilitation, based on MI, could be a strategy to treat fatigue in MS patients

Cerebrospinal fluid cytokine expression profile in multiple sclerosis and chronic inflammatory demyelinating polyneuropathy

Background: Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system. Methods: CSF samples from 49 patients with multiple sclerosis (MS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP. Results: Our results showed differences in CSF cytokine levels in MS and CIDP, in particular IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1 and SCGF- were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups. Conclusions: Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune disease

Neutropenia complicating anti-CD20 treatment in patients with multiple sclerosis: A retrospective case series and a systematic review of reported cases

Neutropenia is an infrequent complication of treatment with CD20 depleting agents and may be require the administration of granulocyte-colony stimulating factors (G-CSF), which have been associated with an increased relapse risk in patients with multiple sclerosis (PwMS). The management of this side effect is still matter of debate

The use of antidepressant medication before and after the diagnosis of amyotrophic lateral sclerosis: A population-based cohort study

Background: The prevalent use of antidepressants (ATDs) in patients with Amyotrophic Lateral Sclerosis (ALS) varies across cross-sectional and clinic-based published studies. This population-based cohort study assesses the real-world prevalence of the use of ATDs, its trajectory and the association of incident use with clinical characteristics. Methods: All patients with incident ALS in the Friuli Venezia Giulia region, Italy, from 2002 to 2009, were identified through multiple sources including health databases. Diagnosis was validated through clinical documentation review. ATDs prescriptions from 2000 to 2011 were obtained from regional database. The trajectory was estimated through generalized estimating equations for repeated measures logistic regression and the Hazard ratio (HR) of initiating ATDs through multivariate proportional hazard Cox regression. Results: In this cohort of 261 ALS cases, age-, sex-adjusted prevalence of the use of ATDs was 37.3%, higher than in general population. The trajectory increased by 16% in 1-year period across diagnosis. Age 6467 years at diagnosis (HR 1.28, 95% CI 0.84-1.95) and bulbar onset (1.43, 95% CI 0.90-2.26) were positively associated with initiating ATDs after diagnosis. Conclusions: More than one-third of patients used ATDs. Depression may occur more frequently than previously reported. Depression may precede motor alterations and be related to both ALS diagnosis and progressio