Sexual dysfunction in multiple sclerosis: The impact of different MSISQ-19 cut-offs on prevalence and associated risk factors.

BACKGROUND: Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. OBJECTIVE: To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. METHODS: After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. RESULTS: Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). CONCLUSION: Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies.

Towards predicting shear-banding instabilities in lipid monolayers.

Langmuir monolayers are advantageous systems used to investigate how lipid membranes get involved in the physiology of many living structures, such as collapse phenomena in alveolar structures. Much work focuses on characterizing the pressure-bearing capacity of Langmuir films, expressed in the form of isotherm curves. These show that monolayers experience different phases during compression with an according evolution of their mechanical response, incurring into instability events when a critical stress threshold is overcome. Although well-known state equations, which establish an inverse relationship between surface pressure and area change, are able to properly describe monolayer behaviour during liquid expanded phase, the modelling of their nonlinear behaviour in the subsequent condensed region is still an open issue. In this regard, most efforts are addressed to explain out-of-plane collapse by modelling buckling and wrinkling mainly resorting to linearly elastic plate theory. However, some experiments on Langmuir monolayers also show in-plane instability phenomena leading to the formation of the so-called shear bands and, to date, no theoretical description of the onset of shear banding bifurcation in monolayers has been yet provided. For this reason, by adopting a macroscopic description, we here study material stability of the lipid monolayers and exploit an incremental approach to find the conditions that kindle shear bands. In particular, by starting from the widely assumed hypothesis that monolayers behave elastically in the solid-like region, in this work a hyperfoam hyperelastic potential is introduced as a new constitutive strategy to trace back the nonlinear response of monolayer response during densification. In this way, the obtained mechanical properties together with the adopted strain energy are successfully employed to reproduce the onset of shear banding exhibited by some lipid systems under different chemical and thermal conditions.

A Combined Radiomics and Machine Learning Approach to Overcome the Clinicoradiologic Paradox in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging explains only a fraction of the clinical outcome variance in multiple sclerosis. We aimed to evaluate machine learning models for disability prediction on the basis of radiomic, volumetric, and connectivity features derived from routine brain MR images. MATERIALS AND METHODS: In this retrospective cross-sectional study, 3T brain MR imaging studies of patients with multiple sclerosis, including 3D T1-weighted and T2-weighted FLAIR sequences, were selected from 2 institutions. T1-weighted images were processed to obtain volume, connectivity score (inferred from the T2 lesion location), and texture features for an atlas-based set of GM regions. The site 1 cohort was randomly split into training (n = 400) and test (n = 100) sets, while the site 2 cohort (n = 104) constituted the external test set. After feature selection of clinicodemographic and MR imaging-derived variables, different machine learning algorithms predicting disability as measured with the Expanded Disability Status Scale were trained and cross-validated on the training cohort and evaluated on the test sets. The effect of different algorithms on model performance was tested using the 1-way repeated-measures ANOVA. RESULTS: The selection procedure identified the 9 most informative variables, including age and secondary-progressive course and a subset of radiomic features extracted from the prefrontal cortex, subcortical GM, and cerebellum. The machine learning models predicted disability with high accuracy (r approaching 0.80) and excellent intra- and intersite generalizability (r ≥ 0.73). The machine learning algorithm had no relevant effect on the performance. CONCLUSIONS: The multidimensional analysis of brain MR images, including radiomic features and clinicodemographic data, is highly informative of the clinical status of patients with multiple sclerosis, representing a promising approach to bridge the gap between conventional imaging and disability.

Clinical effects of preemptive intra-articular lidocaine, dexmedetomidine and lidocaine-dexmedetomidine administration in dogs undergoing arthroscopy.

This study investigated the perioperative effects of preemptive intra-articular lidocaine (L group), dexmedetomidine (D group) and lidocaine-dexmedetomidine (LD group) in dogs. Physiological variables were intraoperatively recorded at 5 min intervals starting from baseline (5 min before intra-articular injection). If nociception occurred, IV fentanyl was administered. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale. Twenty-four dogs (eight in each group) were included in this prospective, randomized, masked clinical study. In the LD group, systolic arterial pressure significantly increased at T10 (P = 0.027), T15 (P = 0.021) and T20 (P = 0.022), compared with baseline. In the D and LD groups, mean arterial pressure significantly increased at T10 (P = 0.022; 0.024), T15 (P = 0.024; 0.09) and T20 (P = 0.019; 0.021), compared with baseline and diastolic arterial pressure significantly increased at T10 (P = 0.026; 0.047), T15 (P = 0.021; 0.023), T20 (P = 0.011; 0.012) and T25 (P = 0.019; 0.027), compared with baseline. In the LD group, heart rate significantly decreased at T5 (P = 0.031), T10 (P = 0.026) and T15 (P = 0.034), compared with baseline. Atrioventricular blocks appeared more frequently in the LD group than in L and D groups (P = 0.002). Group L received more fentanyl than the D and LD groups (P = 0.03). No differences in postoperative pain score were detected (P = 0.121). These findings suggested systemic absorption of intra-articular dexmedetomidine. Intra-articular lidocaine-dexmedetomidine was associated with a greater incidence of atrioventricular blocks. Intra-articular dexmedetomidine, alone and combined with lidocaine, provided better intraoperative analgesia than lidocaine in dogs undergoing arthroscopy, although the 12 h postoperative analgesic effect of the three treatments was similar.

Temporin G, an amphibian antimicrobial peptide against influenza and parainfluenza respiratory viruses: Insights into biological activity and mechanism of action.

Treatment of respiratory viral infections remains a global health concern, mainly due to the inefficacy of available drugs. Therefore, the discovery of novel antiviral compounds is needed; in this context, antimicrobial peptides (AMPs) like temporins hold great promise. Here, we discovered that the harmless temporin G (TG) significantly inhibited the early life-cycle phases of influenza virus. The in vitro hemagglutinating test revealed the existence of TG interaction with the viral hemagglutinin (HA) protein. Furthermore, the hemolysis inhibition assay and the molecular docking studies confirmed a TG/HA complex formation at the level of the conserved hydrophobic stem groove of HA. Remarkably, these findings highlight the ability of TG to block the conformational rearrangements of HA2 subunit, which are essential for the viral envelope fusion with intracellular endocytic vesicles, thereby neutralizing the virus entry into the host cell. In comparison, in the case of parainfluenza virus, which penetrates host cells upon a membrane-fusion process, addition of TG to infected cells provoked ~1.2 log reduction of viral titer released in the supernatant. Nevertheless, at the same condition, an immunofluorescent assay showed that the expression of viral hemagglutinin/neuraminidase protein was not significantly reduced. This suggested a peptide-mediated block of some late steps of viral replication and therefore the impairment of the extracellular release of viral particles. Overall, our results are the first demonstration of the ability of an AMP to interfere with the replication of respiratory viruses with a different mechanism of cell entry and will open a new avenue for the development of novel therapeutic approaches against a large variety of respiratory viruses, including the recent SARS-CoV2.

Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) was effective and safe in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. METHODS: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. RESULTS: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0-8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18-0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p = <0.001, CI 1.51-2.73) and previous DMTs status: de-escalating from second-line therapies was associated to higher risk of relapsing (IRR = 1.8, p < 0.001, CI 1.39-2.31). At multivariable Cox proportional hazard model, only age of onset was related with rate or relapses, with younger age being protective (HR 0.96, p = 0,02). EDSS remained stable in 88% of patients. Disease duration was associated with higher rate of NEDA-3 failure, that was instead maintained in 65% of patients at 24 months. 109 patients (22%) discontinued therapy after a mean of 1.1 ±+ 0.7 years. Reasons for DMF discontinuation over time were lack of efficacy (50%), safety issues (30%), tolerability (7%), poor compliance (7%), and pregnancy (4%). Higher pre-treatment EDSS was associated with DMF discontinuation (p = 0.009). Only 33 patients dropped out due to safety reasons (7%), the most frequent safety issues driving to drop out being lymphopenia, liver/pancreatic enzymes increase, gatrointestinal severe tolerability issues. We recorded 95 cases (24%) of lymphopenia: 60 grade I (13%), 31 grade II (7%) and 4 grade III (1%). CONCLUSIONS: We confirm that DMF shows a good efficacy in both naïve patients and patients switching from other first-line DMTs, especially in patients with early onset of disease. Higher baseline EDSS was a risk factor for discontinuing DMF therapy, while shorter disease duration was protective for both EDSS progression and NEDA-3 status maintenance.

Olfactory function and cognition in relapsing-remitting and secondary-progressive multiple sclerosis.

BACKGROUND: Both cognition and olfaction are impaired in multiple sclerosis (MS). However, little is known about the relationship between smell identification ability and measures of cognitive function in this disease. OBJECTIVE: To assess olfactory function in MS and to evaluate its relationship with cognitive and physical disability. METHODS: Fifty-five MS patients and 20 healthy controls (HCs) were tested. The University of Pennsylvania smell identification test (UPSIT) was administered to assess olfactory function. Cognitive function was tested using the symbol digit modalities test (SDMT), California verbal learning test-II (CVLT II), brief visuospatial memory test (BVMT), paced auditory serial addition test (PASAT), and controlled oral word association test (COWAT). Fatigue and depressive symptoms were evaluated using the Modified Fatigue Impact Scale and the Beck Depression Inventory II, respectively. RESULTS: MS patients had lower UPSIT scores than those of the HCs (28.76 ±â€¯5.48 vs 31.7 ±â€¯2.18, p = 0.02), with secondary-progressive and cognitively impaired MS patients showing the greatest impairment. Scores on the SDMT, CVLTII, BVMT and COWAT were related to the olfactory test scores. CONCLUSION: We confirm that olfactory function is impaired in MS, particularly in progressive phenotypes, and show, for the first time, that such dysfunction is related to a broad range of cognitive measures. Our data suggest that olfactory dysfunction might be considered as an indirect measure of MS severity. Longitudinal studies are needed to confirm this possibility.

Retinal vascular density in multiple sclerosis: a 1-year follow-up.

BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1-year prospective study to estimate VD variations over time and possible clinical correlates. METHODS: A total of 50 patients with MS underwent spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up. Mixed-effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes. RESULTS: We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081-2.214; P = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow-up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Growth and in vivo stresses traced through tumor mechanics enriched with predator-prey cells dynamics.

Mechanical stress accumulating during growth in solid tumors plays a crucial role in the tumor mechanobiology. Stresses arise as a consequence of the spatially inhomogeneous tissue growth due to the different activity of healthy and cancer cells inhabiting the various districts of the tissue, an additional piling up effect, induced by stress transferring across the scales, contributing to determine the total stress occurring at the macroscopic level. The spatially inhomogeneous growth rates accompany nonuniform and time-propagating stress profiles, which constitute mechanical barriers to nutrient transport and influence the intratumoral interstitial flow, in this way deciding the starved/feeded regions, with direct aftereffects on necrosis, angiogenesis, cancer aggressiveness and overall tumor mass size. Despite their ascertained role in tumor mechanobiology, stresses cannot be directly appraised neither from overall tumor size nor through standard non-invasive measurements. To date, the sole way for qualitatively revealing their presence within solid tumors is ex vivo, by engraving the excised masses and then observing opening between the cut edges. Therefore, to contribute to unveil stresses and their implications in tumors, it is first proposed a multiscale model where Volterra-Lotka (predator/prey-like) equations describing the interspecific (environment-mediated) competitions among healthy and cancer cells are coupled with equations of nonlinear poroelasticity. Then, an experimental study on mice injected subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2 and MDA.MB231) was conducted to provide experimental evidences that gave qualitative and some new quantitative confirmations of the theoretical model predictions.

A longitudinal real-life comparison study of natalizumab and fingolimod.

BACKGROUND: Different retrospective studies compared natalizumab and fingolimod in relapsing-remitting multiple sclerosis (RRMS), with conflicting results. We aimed to explore the prescriptive attitude and the clinical outcome of the two therapies. METHODS: We retrospectively included all RRMS patients treated with natalizumab (n=101) or fingolimod (n=78) as their first second-line therapy with at least 24-month follow-up. Demographic and clinical features were recorded to calculate the propensity score (PS). Outcomes of interest were annualized relapse rate (ARR), risk of relapse, and change in the EDSS RESULTS: At baseline, natalizumab patients were younger and had a shorter disease duration, a higher number of relapse in 1 year (1yR) and 2 years (2yR) and overall (ARR-PT) pretherapy, compared to fingolimod patients. On therapy, the proportion of relapsing patients and the mean RR were similar in the two groups. However, the change in the ARR was higher in natalizumab than in fingolimod group (P<.002), but, using PS as a covariate, it was comparable (P=.960). Similarly, the change in EDSS was significantly different for the two groups (P<.004), but not after adjusting for the PS (P=.321). CONCLUSION: We observed a comparable efficacy on ARR reduction and on EDSS progression with natalizumab and fingolimod correcting through PS, suggesting that the efficacy difference observed before correction might derive from the clinical attitude in prescribing natalizumab in more active MS patients in real life.

Upper motor neuron evaluation in multiple sclerosis patients treated with Sativex®.

BACKGROUND: Spasticity in multiple sclerosis (MS) results from an imbalance of inputs from descending pathways to the spinal motor circuits, as well as from a damage of the corticospinal tract (CST). OBJECTIVES: To assess CST impairment in MS patients with and without spasticity and to evaluate its evolution under Sativex® treatment. METHODS: Ten MS patients with spasticity ("cases") underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological (central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and after 12 months. We selected 20 MS patients without spasticity as control group at baseline. RESULTS: At baseline, cases showed a lower CST FA (0.492±0.045 vs 0.543±0.047; P=.01) and a higher CMCT (P=.001) compared to the control group. No correlations were found between clinical, electrophysiological, and MRI features. After 12 months, cases showed a decrease in non-prevalent degree of impairment (PDI) side FA (0.502±0.023 vs 0.516±0.033; P=.01) without differences for electrophysiological features compared to baseline. Treatment with Sativex® resulted in a reduction of NRS for spasticity (P=.01). CONCLUSIONS: We confirm the presence of CST impairment in MS patients with spasticity. We did not identify structural/electrophysiological correlates that could explain Sativex® clinical effect.

Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon ß-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

BACKGROUND AND PURPOSE: Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon ß (IFN-ß) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. METHODS: Clinical and demographic features of CIS patients were collected before the start of IFN-ß-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. RESULTS: Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P < 0.001) and GH levels (P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. CONCLUSIONS: Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression.

Grey:white matter ratio at diagnosis and the risk of 10-year multiple sclerosis progression.

BACKGROUND AND PURPOSE: Grey matter (GM) and white matter (WM) are both affected in multiple sclerosis (MS). WM is predominantly involved in inflammatory demyelination of relapsing-remitting MS (RRMS), whereas GM is predominantly involved in neurodegenerative processes of secondary progressive MS. Thus, we investigated the ratio between GM and WM volumes in predicting MS evolution. METHODS: The present 10-year retrospective cohort study included 149 patients with newly-diagnosed RRMS, undergoing magnetic resonance imaging for segmentation and brain volumetry. The ratio between GM and normal-appearing WM (NAWM) volumes was calculated for each subject. Outcome measures of interest were Expanded Disability Status Scale (EDSS) progression, reaching EDSS 4.0 and conversion to secondary progressive (SP) MS. RESULTS: During a period of 10.6 ± 2.4 years, a median 1.5 EDSS progression was observed (range 0-5.5), 54 subjects (36.2%) reached EDSS 4.0 and 30 subjects (20.1%) converted to SP. With ordinal logistic regression models, EDSS progression was associated with GM:NAWM ratio (coefficient, -2.918; 95% CI, -4.739-1.097). With Cox regression models, subjects with higher GM:NAWM ratio at diagnosis had a 90% lower rate of reaching EDSS 4.0 (hazard ratio, 0.111; 95% CI, 0.020-0.609) and of converting to secondary progressive MS (hazard ratio, 0.017; 95% CI, 0.001-0.203) compared with subjects with lower GM:NAWM ratio. CONCLUSIONS: The GM:NAWM ratio is a predictor of disability progression and of SP conversion in subjects with newly diagnosed RRMS, suggesting that GM and NAWM are variably affected in relation to disease evolution from the early phases of MS.

Multimodal evoked potentials follow up in multiple sclerosis patients under fingolimod therapy.

BACKGROUND: Clinical trials have shown the therapeutic effect of fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RR-MS), but its influence on nervous conduction assessed by evoked potentials (EPs) has not been previously investigated. METHODS: EP data of 20 patients examined 12months prior to initiation of fingolimod (t=-1), at treatment initiation (t=0) and 1year later (t=+1) were compared. Each EP (VEP, MEP, SEP) and EP sum score, a global evoked potential score as the sum score of the each EP score was evaluated and correlated with Expanded Disability Status Scale (EDSS). RESULTS: During pre-treatment period (1year) EDSS worsened while one year after fingolimod treatment EDSS remained stable. From t-1 to t0 VEP, SEP, MEP and EP sum score worsened while from t0 to t+1 VEP, SEP and EP sum score improved, and MEP score remain stable. VEP and SEP were related to EDSS at baseline (t=-1), while MEP and total EP sum score were related to EDSS at all time points. CONCLUSION: Fingolimod is able to improve visual and somatosensory evoked potential in RR-MS patients even if clinical disability scale remains stable. VEP and SEP could give eloquent information on pathway underweighted in EDSS. EPs are useful to evaluate fingolimod effects in clinical practice.

Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis.

Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses.

Quality of life and cognitive functions in early onset multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the CNS occurring in young adults and even in children in 5% of cases. Lower quality of life (QoL) and cognitive impairment (CI) (40-54%) have been reported in early-onset MS (EO-MS) patients. OBJECTIVE: To assess QoL and cognitive function in EO-MS and their relationship, also considering demographic and clinical variables. METHODS: Paediatric Quality of life inventory Version 4.0 for patients aged 13-18 and 19-25 years, Beck Depression Inventory II (BDI II) and the Rao Brief Repeatable Battery were performed in EO-MS patients (onset age ≤25years). EDSS and MSSS were performed at same time. After testing for normal distribution, group comparisons were performed through the two-tailed Student's t test, one-way analysis of variance (ANOVA) and linear or logistic regression when appropriate. The Bonferroni correction for multiple testing was used when appropriate. RESULTS: 59 patients were included (mean age: 20 ± 3.6; Female sex 52.54%). 34 patients had a paediatric onset (<18 years) while 20 patients had a juvenile onset (18 < age < 25 years) of disease. 5 patients were excluded for missing data. HR-QoL was higher in paediatric than juvenile MS patients (p = 0.02), and it was inversely related to EDSS (p = 0.0005) and Multiple Sclerosis Severity score (MSSS) (p = 0.0001). Sixtyone % of patients showed a CI at BRB. No association was found between CI and any socio-demographic and clinical data. HR-QoL total score was not related to CI status nor to any domain-specific cognitive function score, even considering BDI as possible bias. CI was related to social, physical functioning score and EDSS (p = 0.01) at a logistic regression backward stepwise estimation. CONCLUSION: HR-QoL resulted to be better in paediatric than juvenile MS onset patients and was inversely related to rapidity of disability accumulation, while cognitive impairment was influenced by physical disability and poor social involvement (school, education …). Social participation, affective relations and psychological flexibility could have a protective function on CI.

Lymphocytosis as a response biomarker of natalizumab therapeutic efficacy in multiple sclerosis.

BACKGROUND: Natalizumab is an effective therapy in relapsing-remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood-brain barrier (BBB) and induces lymphocytosis. OBJECTIVES: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. MATERIALS AND METHODS: We enrolled 50 relapsing-remitting (RR) and progressive-relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. RESULTS: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations (p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse (p=0.03). CONCLUSIONS: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL.

Anatomical and functional retinal changes in multiple sclerosis.

AIMS: The aims of this study was to report anatomical changes of the ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thickness, and macular volume in patients with multiple sclerosis (MS). We also investigated the correlation between anatomical and functional changes in terms of visual acuity and macular sensitivity investigated and visual fields. METHODS: Prospective comparative study included 105 eyes of 53 consecutive patients. The patients were divided into two groups: group A included 56 eyes of 28 patients with diagnosis of MS; group B involved 49 eyes of 25 healthy patients. The examination included Goldmann tonometry, biomicroscopic and fundus oculi examination, retinography, GCC examination, circumpapillary RNFL (cpRNFL), and macular volume. The functional test included measurement of best-corrected visual acuity (BCVA), visual field, and MP. RESULTS: MS group showed a significant reduced GCC, cpRNFL, macular volume, BCVA, visual field, and macular sensitivity compared with the control group (P<0.001). This reduction was more representative (P<0.001) in patients with MS complicated by optic neuritis (ON). We found in the MS group a strong correlation between GCC thickness and macular volume (r(2)=0.59, P<0.001) and also between GCC and RNFL thickness (r(2)=0.48, P<0.001). There was also a correlation between macular sensitivity and macular volume reduction (r(2)=0.25, P<0.001) and also between RNFL and macular volume (r(2)=0.43, P<0.001). CONCLUSIONS: The significant statistical evidence and the strong correlation between anatomical and functional parameters support the use of OCT and MP in the evaluation, treatment, and follow-up of patients diagnosed with MS.

The Framingham cardiovascular risk score in multiple sclerosis.

BACKGROUND AND PURPOSE: Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10-year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS-related outcomes. METHODS: Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10-year likelihood of cardiovascular events. RESULTS: In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing-remitting MS (P < 0.001). Linear regression analysis showed a direct relationship between FR and Expanded Disability Status Scale (P < 0.001) and MS Severity Scale (P < 0.001). CONCLUSION: The FR, evaluating the global cardiovascular health by the interaction amongst different risk factors, relates to MS disability, severity and course.