Pregnancy planning and outcomes in patients with multiple sclerosis after mitoxantrone therapy: a monocentre assessment.

BACKGROUND AND PURPOSE: Patients with multiple sclerosis (MS) have many pregnancy-related doubts and fears. Careful counselling is thus important. Mitoxantrone (MITO) is used in patients with aggressive MS and may affect reproductive capacity. The aim of this study was to investigate pregnancy planning and outcomes in patients with MS treated with MITO, both before and after the treatment. METHODS: Patients with MS previously treated with MITO were recruited. Clinical, demographic and treatment data were recorded. A questionnaire regarding the planning and outcomes of all pregnancies was administered. Parametric and non-parametric tests were performed using SPSS 22 software. RESULTS: A total of 238 patients (female/male, 158/80) were included; 106 subjects planned a pregnancy before MITO and 40 after MITO. Of these, respectively, 102 (97%) and 35 (85%) resulted in conception, 19 (19%) and 7 (18%) in miscarriage, 6 (6%) and 1 (3%) in abortion and 98 (96%) and 32 (91%) were full-term pregnancies. A total of 96 patients (40%) planned a pregnancy only before MITO (and not after), whereas 30 (13%) planned a pregnancy only after MITO (and not before) (P < 0.01). A total of 103 patients did not plan a pregnancy before MITO and 198 did not plan a pregnancy after MITO. The reasons included lack of interest or a partner, fear of MS and infertility. All of the babies born were healthy until the end of follow-up. CONCLUSIONS: Mitoxantrone does not affect the ability to conceive or pregnancy outcomes. We found no differences in pregnancies, abortions or miscarriages before and after MITO. The tendency to plan pregnancies decreased significantly after MITO. Our findings may be useful for improving the quality of life of patients and the approach taken by neurologists.

Performance in daily activities, cognitive impairment and perception in multiple sclerosis patients and their caregivers.

BACKGROUND: The relationship between cognitive assessment results in multiple sclerosis (MS) and performance in daily activities (DAs) remains unclear. Our study aimed to evaluate the relationship between cognitive functions (CF) measured by tests, performance in DAs, and the perception of CF in patients and their caregivers (CG) in MS. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used to evaluate cognitive status. We created an ad hoc questionnaire (DaQ) to assess performance in DAs not requiring specific motor skills. We used the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to measure each patient self-judgment and caregiver's perception of CF. RESULTS: Forty-nine patients and their caregivers were included in the study. Significant correlations were found between the BICAMS and the DaQ (Symbol Digit Modalities Test (SDMT): r = - 0.48, p < 0.001; California Verbal Learning Test (CVLT): r = - 0.33, p = 0.01; Brief Visual Memory Test (BVMT-R): r = - 0.42; p = 0.002); patients self-judgment (SDMT: r = - 0.38, p = 0.004; CVLT: r = - 0.26, p = 0.03); caregiver perception of patient's CF (SDMT: r = - 0.52, p < 0.001; CVLT: r = - 0.3, p = 0.01; BVMT-R: r = - 0.42, p = 0.002). The difference in perception between the patients and their caregivers was related to patient age (p = 0.001) and severity of cognitive impairment (p = 0.03). CONCLUSIONS: Cognitive assessment results show a significant correlation with performance in daily activities and with patients and, especially, caregiver perception of cognitive impairment. These data support the importance of a routine evaluation of cognitive function in MS that includes an anamnestic evaluation of patients, and, when possible, consideration of the caregiver's point of view.

Combining HLA-DRB1-DQB1 and Mycobacterium Avium Subspecies Paratubercolosis (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

BACKGROUND: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. METHODS: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. RESULTS: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). CONCLUSIONS: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP.

Diagnostic tools for assessment of urinary dysfunction in MS patients without urinary disturbances.

Many guidelines are available for the management of lower urinary tract symptoms (LUTSs) in multiple sclerosis (MS) patients, but no agreement exists on the best approach for subjects without LUTSs. The objective of this study was to evaluate whether LUTSs can be detected in MS patients asymptomatic for urinary dysfunction, comparing three different tools [measure of post-void residual volume (PRV), bladder diary (BD), a focused questionnaire (IPSS)], and whether disability, disease duration and signs of pyramidal involvement are linked to their subclinical presence. 178 MS patients (118 women) have been included (mean age 41.2 years, mean disease duration 11.3 years, mean EDSS 2.2), and tested with the above-mentioned tools. PRV was abnormal in 14 subjects (7.8%), associated to abnormal findings at IPSS in 3 cases, at BD in 2 cases, at both in 1. BD was abnormal in 37 subjects (20.8%), with concomitant abnormal PRV in 2, abnormal IPSS in 10 cases, abnormal IPSS and BD in 1. IPSS was ≥ 9 in 43 subjects (24.1%). At least one test was abnormal in 76 patients (42.7%): 1 in 57 patients (32.0%), 2 in 17 (9.5%), and 3 tests in 2 (1.1%). Patients with at least one abnormal urinary variable, compared to patients without urinary abnormalities, had a more frequent pyramidal involvement (69.5 vs. 16.8%, χ(2) = 48.6, p < 0.00001), a more frequent occurrence of EDSS ≥2 (83.1 vs. 23.5%, χ(2) = 56.9, p < 0.00001), and a longer disease duration (15.7 ± 7.3 vs. 9.1 ± 7.1, t = 5.7, p < 0.00001). Asymptomatic LUTS were frequent but none of the tests used permitted to better identify asymptomatic patients.

Attitude towards physical activity in patients with multiple sclerosis: a cohort study.

Multiple sclerosis (MS) is a long-lasting neurological disease with onset in young adult age. Patients with MS are less active than healthy people, and their sedentary lifestyle might lead to secondary diseases or worsening of symptoms, disability and quality of life. In the study, we evaluated the attitude of physical activity (PA) of a group of MS patients and the differences in practice PA before and after the diagnosis. A randomly recruited group of patients with MS fulfilled a questionnaire about their attitudes towards PA before the onset and after the diagnosis of the disease. Clinical and demographic data were recorded. Out of 118 patients, 37 % practiced PA only before the diagnosis, 9 % only after and 52 % during both periods. After the diagnosis, 64 % of participants noted some negative differences in PA, in particular less physical resistance and worsening of symptoms, and 38 % stopped PA. However, patients referred benefits from PA after diagnosis. Individual exercises rather than group activities were preferred after diagnosis. Only 26 % of patients knew that adapted PA existed and the differences between adapted PA and classic physiotherapy. We observed a reduction in the practice of PA in patients after the diagnosis of MS, in particular for disease-related reasons. Nevertheless, active patients referred benefits from PA. It is important to know the point of view of patients towards developing individualized training programs. In this way, it could be possible to achieve more benefits from PA and reduce the negative effects.

A genetic study of the FMR1 gene in a Sardinian multiple sclerosis population.

Multiple sclerosis (MS) is a complex autoimmune disease originated from the interplay between genetic and environmental factors. An overlap of clinical and neuroradiological parameters has been described between MS and an adult-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). This syndrome is caused by a trinucleotide premutation expansion of a CGG sequence in the 55-200 repeat range, which is located in the fragile-X mental retardation 1 (FMR1) gene. Female premutation carriers have an increased propensity for immune-mediated disorders. Recently, a case of co-occurrence of MS and FXTAS was reported. Assuming that the premutation expansion may play a role in the MS susceptibility, we evaluated its frequency in a cohort of MS patients from Sardinia, an island characterized by a very high frequency of MS. Nuclear DNA was extracted by standard methods, purified with bisulfite treatment and then amplified twice by PCR with specific primers. Microsatellite analysis was performed and emizogotic subjects were sequenced. Clinical data of patients were also collected. Only 1/755 MS patients exhibited the premutation expansion with a heterozygosis pattern (30/58). No pathogenic repeat expansions (>200 repeats) were found in the entire cohort. Repeats labeled as the gray zone (45-60 repeats) were observed in 15/755 patients. No specific clinical features concerning disease course, disease activity, and disability were reported for these patients. Our results do not support a possible role for premutation or gray zone alleles in MS Sardinian patients. Further studies are needed to better understand the relationship between FXTAS and MS.

Progressive multiple sclerosis and mood disorders.

Mood disorders are very common among multiple sclerosis (MS) patients, but their frequency in patients with progressive course (PMS) has not been adequately researched. Our study aimed to determine the frequency of mood disorders among patients with PMS compared with those with relapsing-remitting MS (RMS) and to explore the associations with disability and disease duration. The study included consecutive outpatients affected by MS according the 2010 revised Mc Donald diagnostic criteria. Psychiatric diagnoses were determined according to DSM-IV by psychiatrists using structured interview tools (ANTAS-SCID). Demographic and clinical data of patients were also collected. Disease courses were defined according to the re-examined phenotype descriptions by the Committee and MS Phenotype Group. Intergroup comparisons were performed by Chi-square test, while logistic regression analysis was performed to assess possible factors associated with mood disorders. In total, 240 MS patients (167 women) were enrolled; of these, 18 % (45/240) had PMS. The lifetime DSM-IV major depression diagnosis (MDD) was established in 40 and 23 % of the PMS and RMS patients, respectively. Using logistic regression analysis, the presence of MDD was independent from disease duration and disability and dependent on PMS course (P = 0.02; OR 2.2). Patients with PMS presented with MDD more frequently than those with RMS, independently from disease duration and physical disability. These findings highlight the importance of considering mood disorders, especially MDD, in the management of PMS patients.

Mycobacterium avium subsp. paratuberculosis and multiple sclerosis in Sardinian patients: epidemiology and clinical features.

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) is an infectious factor recently found in association with multiple sclerosis (MS) in Sardinia. OBJECTIVES: The objectives of this study were to confirm this association and evaluate its role in clinical features. METHODS: A total of 436 patients and 264 healthy controls (HCs) were included. We examined the blood of each individual for MAPDNA and MAP2694 antibodies using IS900-specific PCR and ELISA, respectively. Differences in MAP presence between the MS group and HCs were evaluated. In MS patients, we considered: gender, age, age at onset, duration of disease, course, EDSS, therapy, relapse/steroids at study time, and oligoclonal bands (OBs). RESULTS: MAPDNA and MAP2694 antibodies were detected in 68 MS and six HCs (p = 1.14 × 10(-11)), and 123 MS and 10 HCs (p = 2.59 × 10(-23)), respectively. OBs were found with reduced frequency in MAP-positive patients (OR = 0.52; p = 0.02). MAP2694 antibodies were detected more in patients receiving MS treatments (OR = 2.26; p = 0.01), and MAPDNA in subjects on steroids (OR = 2.65; p = 0.02). CONCLUSION: Our study confirmed the association of MAP and MS in Sardinia. The low OB frequency in MAP patients suggests a peripheral role as a trigger in autoimmunity. MAP positivity might be influenced by steroids and MS therapy. Studies in other populations are needed to confirm the role of MAP in MS.

Multidimensional frailty and its association with quality of life and disability: A cross-sectional study in people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) have a high risk of frailty. We aim to evaluate frailty using the Tilburg frailty indicator (TFI), a multidimensional self-reported questionnaire, and to explore its relationship with autonomy, quality of life (QoL), and disability. METHODS: All the patients with MS enrolled completed TFI (frail when TFI score ≥ 5 points), the Groningen Activities Restriction Scale to evaluate autonomy, and the Multiple Sclerosis Impact Scale-29 to evaluate QoL. We collected the Expanded Disability Status Scale (EDSS) score, age and gender. Data were analysed using descriptive analyses, hierarchical multiple regression, and ANCOVA. RESULTS: A total of 208 pwMS (mean age 44 years, SD=11; 75% women; 89.4% relapsing-remitting) were enrolled. The mean TFI total score was 5.7 points (SD=3.0; range 0-14), with the 62.5% of participants exhibiting frailty. After controlling for age and gender, the EDSS score was associated with the total (ß=0.469; R2=0.255; p<0.001) and the physical (ß=0.571; R2=0.349; p<0.001) frailty score, with an explained variance of 25.5% and 34.9%, respectively. No relationships between the EDSS and psychological and social frailty domains were detected. The proportion of frail patients with EDSS ≥ 6.0, EDSS within 3.5-5.5, and EDSS ≤ 3.0 was 91.7%, 83.3%, and 66.0%, respectively. Frail patients exhibited higher autonomy impairment (p = 0.017) and worse QoL (p<0.001). DISCUSSION: We found a high frequency of frail patients with MS. Frailty is more common in patients with higher disability, but it affects also those with low EDSS. In people with MS frailty could be influenced by factors other than disability.

Evolution of teriflunomide use in multiple sclerosis: A real-world experience.

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.

The cohort of the multiple sclerosis center of Cagliari.

We report our experience in long-term treatment of relapsing remitting multiple sclerosis patients with natalizumab (N). In November 2009 we evaluated 141 patients (126 AIFA criterion A, 15 AIFA criterion B). We paid particular attention to the treatment period and the patients follow-up; during the whole therapeutic program, they undergone to clinical and radiological evaluation for every 3 months. The compliance was optimal and we found no significant side effects. 26 patients completed the 24 monthly doses. After 24 months 51% of patients were free from disease activity. We found a reduction in relapses and EDSS, moreover the clinical improvement was also confirmed by radiological examinations. Our results show that the best therapeutic results are achieved by early initiation of treatment.

Event-related potentials and deep grey matter atrophy in multiple sclerosis: Exploring the possible associations with cognition.

BACKGROUND: Event-related potentials (ERPs) have been proposed as a neurophysiological biomarker to capture cognitive dysfunction in multiple sclerosis (MS). Few studies have evaluated the relationships between ERPs and brain atrophy as known marker of structural brain damage related to cognitive impairment (CI). OBJECTIVES: To explore the relationships of brain atrophy, including of the cortex and deep grey matter, with ERP abnormalities and cognitive function, as defined using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). RESULTS: Seventy-eight patients with relapsing-remitting MS were enroled, of which 38 (48.7%) had CI. Independent t-test comparisons of the ERP parameters found a significant difference in P300 wave latency, with a latency of 343.7 ± 32.6 ms in the CI group vs. 320.3 ± 16.5 ms in the cognitively preserved (CP) group (p = 0.001). Significant differences in the MRI measurements, including the cortex (p = 0.02) and deep grey matter structures [thalamus (p = 0.001), amygdala (p = 0.030), and nucleus accumbens (p = 0.004)) were observed, with lower measurements in the CI group. Regression models were also performed to explore the impact of brain volumes on ERP parameters. This showed a relationship between P300 latency and the lower amygdala (p = 0.02) and hippocampus (p = 0.03) volumes, while the amplitude of the P300 was significantly associated with a lower cortex volume (p = 0.01). CONCLUSION: Cortex volume emerged as the most significant predictor of the P300 amplitude. The amygdala and hippocampal volumes were found to influence P300 latency, highlighting the role of deep grey matter atrophy in ERPs for the first time. The combination of structural MRI and neurophysiological techniques, sensitive to diverse aspects of MS pathology, could improve the understanding of CI in MS and its neurodegenerative and inflammatory substrate.

The impact of deep grey matter volume on cognition in multiple sclerosis.

BACKGROUND: Cognitive dysfunctions are very frequent in people living with multiple sclerosis (MS). Several studies have previously indicated grey matter (GM) atrophy as useful predictor of patients' cognitive impairment. However, considerable uncertainty exists about the possible impact of deep grey matter volumes on cognition. This study aimed to evaluate the relationship of the subcortical (sc) GM volumes with the presence and severity of global and selective cognitive impairment in MS. METHODS: A group of MS patients with relapsing remitting course were enrolled. Patients underwent a neuropsychological evaluation by using the Brief Repeatable Battery of Neuropsychological Tests (BRBN) and the Delis-Kaplan Executive Function System Sorting Test (D-KEFST); z scores were estimated and items with z score below 2 standard deviation were considered failed. Thus, brain MRIs images were acquired and measurements of whole brain (WB), white matter (WM), and cortical grey matter (GM) were obtained by SIENAX. After FIRST tool segmentation, volumes of subcortical GM structures were also estimated. RESULTS: The sample included 50 MS patients, of which 16/50 (32%) subjects were cognitively impaired. Multiple regression analyses found a significant association of severity of cognitive impairment, defined as number of failed neuropsychological tests, with lower volumes of cortex (p=0.003), thalamus (p=0.009), caudate (p=0.011), putamen (p=0.020), pallidus (p=0.012) and hippocampus (p=0.045), independently from other MS features. In addition, an association between accumbens volume and D-KEFS ST FSC and D-KEFS ST FSD z scores was observed (p<0.03). CONCLUSIONS: Our results indicated that volumes of several scGM structures, and in particular of thalamus, contribute to determine cognitive dysfunctions in MS, mainly influencing the executive functioning. Further investigations in larger MS cohorts with cognitive impairment are necessary to better understand the structural brain damage underlying this "invisible disability".

Bipolar disorders and deep grey matter in multiple sclerosis: A preliminary quantitative MRI study.

BACKGROUND: Bipolar disorder (BD) is frequently observed in patients affected by multiple sclerosis (MS), presenting a lifetime estimate of around 8%. However, uncertainty exists on the brain damage associated with this psychiatric comorbidity. This study aimed to investigate the effect of brain atrophy, particularly that of the subcortical grey matter (scGM) structures that notoriously regulate the affective functioning, on the co-occurrence of BD in patients with MS. METHODS: A group of patients with MS affected by BD and a control group of patients with MS without any mood/psychiatric disorder, as defined using standardised diagnostic tools (Advanced Neuropsychiatric Tools and Assessment Schedule), were recruited. The patients underwent brain MRI, and the volumes of the whole brain (WB), white matter (WM), and grey matter (GM) were estimated using SIENAX. Thus, the scGM volumes of the putamen, caudate, thalamus, hippocampus, amygdala, nucleus accumbens, and pallidus were estimated using the FIRST tool. RESULTS: The sample included 61 patients with MS, amongst whom 15 (24.6%) had BD. No differences in the WB, WM, and cortical GM volumes were observed between the patients with MS with and without BD. Conversely, the multiple regression analysis revealed a significant association of BD with lower volumes of the putamen (p = 0.032), nucleus accumbens (p = 0.029), and pallidus (p = 0.061; with a trend towards significance), independently from the demographic and MS clinical features. CONCLUSIONS: Our preliminary results indicated that the nucleus accumbens and putamen are smaller in MS patients with BD. Further investigations in larger cohorts of MS patients with affective disorders are necessary to confirm these data and understand the structural brain damage underlying this psychiatric comorbidity.

Assessing the burden of vascular risk factors on brain atrophy in multiple sclerosis: A case- control MRI study.

BACKGROUND: Some studies have indicated the importance of considering the presence of vascular comorbidities as negative prognostic factors for MRI outcomes in multiple sclerosis (MS). This study aimed to evaluate the possible influence of the most frequent vascular risk factors on brain volume in MS, also exploring the burden of their combined effects. METHODS: MS patients with at least one vascular risk factor and a control group of MS patients were enrolled. Patients underwent brain MRI and the volumes of the whole brain (WB), white matter (WM), grey matter (GM), and cortical GM were estimated by SIENAX. Longitudinal atrophy was assessed by SIENA. RESULTS: The sample included 326 MS patients, of these 49 (15%) had diabetes mellitus, 44 (13.4%) hypertension and 50 (15.3%) were active smokers. Multiple regression analyses revealed that diabetes mellitus was associated with significant reductions in WB (p = 0.03), GM and cortical GM (p = 0.01) volumes. Similarly, reduced cortical GM volume was associated with hypertension (p < 0.05). A strong relationship between the co-occurrence of multiple vascular risk factors and lower cortical GM volume (p = 0.007) was also identified. Ninety patients were included in the longitudinal study and a greater annualized brain volume loss was found in those with at least one vascular risk factor than in the control group (-1.05% vs. -0.58%, p = 0.005). CONCLUSIONS: Our results show that the vascular comorbidities affect brain atrophy, indicating that these conditions should be carefully monitored in patients with MS with a focus on limiting brain damage.

Adult brain volume in multiple sclerosis: The impact of paediatric onset.

BACKGROUND: Paediatric onset multiple sclerosis (POMS) is associated with reduced brain and deep grey matter volume in comparison with that in healthy controls and individuals with adult onset multiple sclerosis (AOMS). The aim of our study was to evaluate the impact of POMS on adult brain volume with adjustment for other parameters, such as disease duration. PATIENTS AND METHODS: We recruited 20 POMS and 40 AOMS patients and 20 healthy controls matched for age and sex. All study participants were adults at the time of inclusion in the study. All study subjects underwent brain magnetic resonance imaging (MRI) to evaluate whole brain, white matter, grey matter, cortical, and deep grey matter volumes. Clinical features, such as the Expanded Disability Status Scale (EDSS) score and disease duration, were also assessed. RESULTS: Brain (p = 0.01), grey matter (p = 0.01), and deep grey matter volume (p = 0.03) was significantly lower in POMS patients than in AOMS patients, while no differences were detected in the volume of white matter or cortical grey matter. A multiple linear regression analysis showed a relationship between brain volume (dependent variable) and the independent variables age (p < 0.000) and paediatric onset (p < 0.001), while other independent variables, including disease duration, sex, and disability, were not significantly different among groups. There were significant differences in thalamic volume among POMS and AOMS patients and healthy controls. CONCLUSION: Our data support the previous findings that POMS patients have reduced brain and deep grey matter volume, particularly thalamic volume, compared with sex- and age-matched AOMS patients and healthy controls. These findings appear to be independent of disease duration and other clinical features.

Brain volume in early MS patients with and without IgG oligoclonal bands in CSF.

BACKGROUND: Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. AIM: to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. METHODS: Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. RESULTS: In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. CONCLUSIONS: Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.

Cognition in multiple sclerosis: Between cognitive reserve and brain volume.

BACKGROUND: Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS. OBIECTIVE: To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor. METHODS: 195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool. RESULTS: Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p<0.000) NGV(r=0.31; p<0.000), CGV (r=0.35; p<0.000) and CRI score(r=0.42; p<0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p<0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS. CONCLUSIONS: Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS.

'Timed up and go' and brain atrophy: a preliminary MRI study to assess functional mobility performance in multiple sclerosis.

Motor and cognitive disabilities are related to brain atrophy in multiple sclerosis (MS). 'Timed up and go' (TUG) has been recently tested in MS as functional mobility test, as it is able to evaluate ambulation/coordination-related tasks, as well as cognitive function related to mobility. The objective of this study is to evaluate the relationship between brain volumes and TUG performances. Inclusion criteria were a diagnosis of MS and the ability to walk at least 20 m. TUG was performed using a wearable inertial sensor. Times and velocities of TUG sub-phases were calculated by processing trunk acceleration data. Patients underwent to a brain MRI, and volumes of whole brain, white matter (WM), grey matter (GM), and cortical GM (C) were estimated with SIENAX. Sixty patients were enrolled. Mean age was 41.5 ± 11.6 years and mean EDSS 2.3 ± 1.2. Total TUG duration was correlated to lower WM (ρ = 0.358, p = 0.005) and GM (ρ = 0.309, p = 0.017) volumes. A stronger association with lower GM volume was observed for intermediate (ρ = 0.427, p = 0.001) and final turning (ρ = 0.390, p = 0.002). TUG is a useful tool in a clinical setting as it can not only evaluate patients' disability in terms of impaired functional mobility, but also estimate pathological features, such as grey atrophy.

An unusual infection in MS patient treated with dimethyl fumarate: A case report of omphalitis.

BACKGROUND: Notoriously the treatment of multiple sclerosis (MS) is based on the use of several different drugs, characterized by a diverse mechanism of action, efficacy and safety. Recently, progress has been made towards developing new oral immunotherapies, and dimethyl fumarate is the third oral agent approved for the treatment of relapsing-remitting forms. CASE: A 24-year-old patient, affected by relapsing remitting multiple sclerosis, started treatment in December 2014 with dimethyl fumarate. The common side effects (flushing and gastrointestinal events) of dimethyl fumarate occurred at the beginning of treatment, but resolved after 1 month. Six months later, the patient presented with serious recrudescence of the gastrointestinal event. In addition to this symptom, he had developed acute omphalitis-a very rare infection in adults. CONCLUSION: The pathogenic role of dimethyl fumarate to induce this rare infection was probably related to changes in immunological surveillance as well as to the irritant effect of this agent on the gastrointestinal epithelium. Therefore, post-marketing studies in clinical practice are still needed to provide the necessary long-term safety data.