Sex Differences in Long-Term Mortality and Functional Outcome After Rehabilitation in Patients With Severe Stroke

Objective: We sought to determine sex differences in outcomes in patients with severe stroke who had been admitted to inpatient rehabilitation. Methods: We studied 1,316 patients aged 18 to 99 (mean 72) classified as case-mix groups 0108, 0109, and 0110 of the Medicare case-mix classification system. These groups encompass the most severe strokes. Three outcomes were analyzed: (1) 3-year mortality from admission to rehabilitation; (2) combined outcome of transfer to acute care or death within 90 days from admission to rehabilitation; (3) functional outcome, including proportional recovery in motor functioning and good functional outcome as defined by achievement of a Functional Independence Measure (FIM)-motor score ≥65 points at discharge. Multivariable regression analyses were used to assess sex-difference in each outcome between women and men. The covariates examined included age, marital status, comorbidities, time from stroke onset to rehabilitation admission <30 days, ischemic stroke, dysphagia, neglect, motor FIM score at admission, and cognitive FIM score at admission. Results: Kaplan-Meier estimated 3-year mortality rate was 20.7% in women and 22.0% in men. The crude hazard ratio (HR) of death for women compared with men was 0.94 (95% CI 0.74–1.20). After adjustment for significant covariates, the HR of 3-year mortality was 0.73 (95% CIs 0.56–0.96; p = 0.025). Comorbidity, including diabetes, anemia, coronary artery disease, atrial fibrillation, and chronic obstructive pulmonary disease, significantly increased mortality risk by 49–88%. The incidence of the combined outcome was 8.3% in women and 8.4% in men. The crude HR of the combined end-point for women compared with men was 1.05 (95% CI 0.72–1.53). After adjustment for significant covariates, the HR was 0.95 (95% CIs 0.65–1.40; p = 0.810). Likewise, no significant difference in proportional recovery or in the rate of achievement of a good functional outcome between women and men was observed. Conclusion: Among patients admitted to inpatient rehabilitation after severe stroke, women and men had comparable crude mortality rates at 3 years. After multivariable adjustment, however, women had lower mortality risk. No sex-differences in the risk of being transferred to acute care or dying within 90 days from admission to rehabilitation or in responsiveness to rehabilitation were observed

A voxel-based morphometry study of disease severity correlates in relapsing–remitting multiple sclerosis

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing–remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing–remitting multiple sclerosis (Expanded Disability Status Scale range 1.0–6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease

Surface-enhanced Raman spectroscopy of tears: Toward a diagnostic tool for neurodegenerative disease identification

Significance: A noninvasive method based on surface-enhanced Raman spectroscopy (SERS) of tears was proposed as a support for diagnosing neurodegenerative pathologies, including different forms of dementia and Alzheimer's disease (AD). In this field, timely and reliable discrimination and diagnosis are critical aspects for choosing a valid medical therapy, and new methods are highly required. Aim: The aim is to evince spectral differences in SERS response of human tears from AD affected, mild cognitive impaired (MCI), and healthy control (Ctr) subjects. Approach: Human tears were characterized by SERS coupled with multivariate data analysis. Thirty-one informed subjects (Ctr, MCI, and AD) were considered. Results: Average SERS spectra from Ctr, MCI, and AD subjects evidenced differences related to lactoferrin and lysozyme protein components. Quantitative changes were also observed by determining the intensity ratio between selected bands. We also constructed a classification model that discriminated among AD, MCI, and Ctr subjects. The model was built using the scores obtained by performing principal component analysis on specific spectral regions (i-PCA). Conclusions: The results are very encouraging with interesting perspectives for medical applications as support of clinical diagnosis and discrimination of AD from other forms of dementia

Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study

Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes. Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models. Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (P.001). In the relapsing-remitting MS group,WMlesion burden proved to be the main contributor to volume loss for all deep gray matter structures (P .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (P .01), coupled with thalamic susceptibility changes (P .05). Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS

Clinical activity after fingolimod cessation: Disease reactivation or rebound?

Background and purpose: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Methods: Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. Results: A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. Conclusions: The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described

The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis.

Synthetic glycopeptides have the potential to detect antibodies in multiple sclerosis (MS). In the present study, we analyzed the antibodies (IgM class, IgG class and IgG subclasses) to the synthetic glycopeptide CSF114(Glc) in the serum of 186 MS patients, 166 blood donors (BDs), 25 patients affected by meningitis/encephalitis, 41 affected by systemic lupus erythematosus (SLE) and 49 affected by rheumatoid arthritis (RA). The IgM antibody level to CSF114(Glc) was significantly increased in MS patients versus BDs (p<0.001) or versus other autoimmune diseases (SLE or RA, p<0.001). The IgG response was restricted to the subclass IgG2. IgM antibodies to CSF114(Glc) were found in 30% of relapsing/remitting MS patients and, at lower levels, in subjects affected by meningitis/encephalitis. The study of antibodies to CSF114(Glc) is a new, potential immunological marker of MS

Lesion load may predict long-term cognitive dysfunction in multiple sclerosis patients.

Magnetic Resonance Imaging (MRI) techniques provided evidences into the understanding of cognitive impairment (CIm) in Multiple Sclerosis (MS).To investigate the role of white matter (WM) and gray matter (GM) in predicting long-term CIm in a cohort of MS patients.303 out of 597 patients participating in a previous multicenter clinical-MRI study were enrolled (49.4% were lost at follow-up). The following MRI parameters, expressed as fraction (f) of intracranial volume, were evaluated: cerebrospinal fluid (CSF-f), WM-f, GM-f and abnormal WM (AWM-f), a measure of lesion load. Nine years later, cognitive status was assessed in 241 patients using the Symbol Digit Modalities Test (SDMT), the Semantically Related Word List Test (SRWL), the Modified Card Sorting Test (MCST), and the Paced Auditory Serial Addition Test (PASAT). In particular, being SRWL a memory test, both immediate recall and delayed recall were evaluated. MCST scoring was calculated based on the number of categories, number of perseverative and non-perseverative errors.AWM-f was predictive of an impaired performance 9 years ahead in SDMT (OR 1.49, CI 1.12–1.97 p = 0.006), PASAT (OR 1.43, CI 1.14–1.80 p = 0.002), SRWL-immediate recall (OR 1.72 CI 1.35–2.20 p<0.001), SRWL-delayed recall (OR 1.61 CI 1.28–2.03 p<0.001), MCST-category (OR 1.52, CI 1.2–1.9 p<0.001), MCST-perseverative error(OR 1.51 CI 1.2–1.9 p = 0.001), MCST-non perseverative error (OR 1.26 CI 1.02–1.55 p = 0.032).In our large MS cohort, focal WM damage appeared to be the most relevant predictor of the long-term cognitive outcome