Impact of natural menopause on multiple sclerosis: a multicentre study.

OBJECTIVE: To study the effect of natural menopause on multiple sclerosis clinical course. METHODS: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status. RESULTS: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059). CONCLUSION: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

Genetic Counseling Dilemmas for a Patient with Sporadic Amyotrophic Lateral Sclerosis, Frontotemporal Degeneration & Parkinson's Disease.

Amyotrophic lateral sclerosis (ALS), frontotemporal degeneration and Parkinson's disease may be different expressions of the same neurodegenerative disease. However, association between ALS and parkinsonism-dementia complex (ALS-PDC) has only rarely been reported apart from the cluster detected in Guam. We report a patient presenting with ALS-PDC in whom pathological mutations/expansions were investigated. No other family members were reported to have any symptoms of a neurological condition. Our case demonstrates that ALS-PDC can occur as a sporadic disorder, even though the coexistence of the three clinical features in one patient suggests a single underlying genetic cause. It is known that genetic testing should be preferentially offered to patients with ALS who have affected first or second-degree relatives. However, this case illustrates the importance of genetic counseling for family members of patients with sporadic ALC-PDC in order to provide education on the low recurrence risk. Here, we dicuss the ethical, psychological and practical consequences for patients and their relatives.

Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study.

BACKGROUND: Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimer's disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. OBJECTIVE: To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). METHODS: Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. RESULTS: Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. CONCLUSIONS: Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.

Isolated theory of mind deficits and risk for frontotemporal dementia: a longitudinal pilot study.

OBJECTIVE: Recent data suggest that theory of mind (ToM) deficits represent an early symptom of the behavioural variant of frontotemporal dementia (bvFTD). However, longitudinal data on the natural history of subjects presenting with isolated ToM deficits are lacking. The aim of the study was to verify if isolated ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD. METHODS: A population of healthy subjects (n=4150, age range: 50-60 years) completed a clinical and neuropsychological evaluation including the Reading the Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we recruited a low-RMET group (n=83) including subjects with RMET scores lower than 2 SDs but an otherwise normal neuropsychological evaluation and a control group. All subjects underwent evaluation at baseline and after 2 years. RESULTS: Subjects in the low-RMET group showed decline in prefrontal functions at follow-up. Moreover, at follow-up 12 subjects in the low-RMET group presented with findings suggestive of bvFTD. Neuropsychological performance was stable in the control group. CONCLUSIONS: Our data suggest that isolated ToM deficits could represent an at-risk situation for the development of future prefrontal dysfunction and bvFTD. ToM evaluation should be included in neuropsychological protocols aimed to evaluate the early phases of dementia.

Assessing the susceptibility to acute respiratory illness COVID-19-related in a cohort of multiple sclerosis patients.

INTRODUCTION: Italy has been the first European country severely affected by the COVID-19 pandemic. OBJECTIVE: To analyze the incidence of the clinical presentations suggestive for COVID-19 infection among patients with Multiple Sclerosis in the province of Lecco, in the North Italy, the closest province capital to Bergamo. To describe the association of demographics, clinical characteristics, and use of DMTs categories with the risk of contracting the disease. METHODS: We telephonically interviewed all the 275 MS patients followed in the MS center. The collected data included recent contact with a patient with COVID-19 diagnosis or a subject with respiratory symptoms and the developing of COVID-19 symptoms or a confirmed diagnosis. RESULTS: 15 out of 275 patients reported symptoms suggestive for COVID-19 infection, only one of them with PCR-confirmed diagnosis. No one of them presented severe symptoms or needed hospitalization. Using a multivariable logistic regression model, the only factor associated with being in the COVID-suspect group was the report of a recent contact with a patient with a COVID-19 diagnosis. CONCLUSIONS: The prevalence of COVID-19 within MS patients seems to resemble the prevalence in general population. The lack of associations with other factors assessed, including DMTs, may reflect a lack of statistical power. Larger population studies are needed to explore the correlation between different disease-modifying therapies and COVID-19 course.

Clinical Application of 2017 McDonald Diagnostic Criteria for Multiple Sclerosis.

BACKGROUND AND PURPOSE: McDonald criteria for multiple sclerosis diagnosis have been revised over the years, diagnostic procedures have been simplified and earlier diagnosis facilitated. The new 2017 revision introduces other important changes, with a further simplification for the diagnosis. Oligoclonal bands reassume a more relevant role in the workup. METHODS: We describe 3 typical cases of patients admitted for clinically isolated syndrome and illustrate how the application of the new criteria can change the diagnostic approach with respect to the previous criteria. RESULTS: In two of the three cases a diagnosis of multiple sclerosis is now possible. CONCLUSIONS: The new 2017 Multiple Sclerosis criteria may have an important impact in clinical practice with an earlier treatment to avoid the risk of disease dissemination. Their application requires a careful assessment to avoid misdiagnosis and mistreatments.

Prevalence and cognitive underpinnings of isolated apathy in young healthy subjects.

BACKGROUND: Apathy is well described in neurodegenerative conditions, however to date there is no evidence of significant isolated apathy in subjects free from other neurological and psychiatric co-morbidites. Identifying isolated apathy in subjects free from neuropsychiatric conditions could contribute to refining current concepts of apathy and reevaluate its nosological classification as an independent clinical syndrome. METHODS: We assessed apathy and perceived quality of life in a group of 2751 adults (age 19-40 years) free from neuropsychiatric or medical conditions. Subjects with and without elevated apathy were compared on measures of depression, self-efficacy, behavioral inhibition, and behavioral activation. RESULTS: Observed prevalence of isolated elevated apathy was 1.45%. Subjects with apathy presented with reduced quality of life and lower behavioral activation compared to apathy-free subjects, while there was no difference between the two groups on measures of depression, self-efficacy, and perceived social skills. LIMITATIONS: The main limitation of this study is the use of self-report questionnaires. CONCLUSIONS: Isolated, ecologically-relevant apathy can be found in adults independently from the presence of subclinical depression or of concurrent medical conditions. Apathy screening should be considered in the evaluation of young non-depressed subjects with reduced perceived quality of life.

Quantitative assessment of finger motor impairment in multiple sclerosis.

OBJECTIVE: To address the disability impact on fine hand motor functions in patients with Multiple Sclerosis (MS) by quantitatively measuring finger opposition movements, with the aim of providing a new "score" integrating current methods for disability assessment. METHODS: 40 MS patients (Expanded Disability Status Scale (EDSS): 0-7) and 80 healthy controls (HC) performed a repetitive finger-to-thumb opposition sequence with their dominant hand at spontaneous and maximal velocity, and uni- and bi-manually metronome-paced. A sensor-engineered glove was used to measure finger motor performance. Twenty-seven HC were tested twice, one month apart, to assess test-retest reliability. RESULTS: The motor parameters showed a good reproducibility in HC and demonstrated significantly worse performance in MS patients with respect to HC. A multivariate model revealed that rate of movement in the spontaneous velocity condition and inter-hand interval (IHI), indicating bimanual coordination, contributed independently to differentiate the two groups. A finger motor impairment score based on these two parameters was able to discriminate HC from MS patients with very low EDSS scores (p<0.001): a significant difference was already evident for patients with EDSS = 0. Further, in the MS group, some motor performance parameters correlated with the clinical scores. In particular, significant correlations were found between IHI and EDSS (r = 0.56; p<0.0001), MS Functional Composite (r = -0.40; p = 0.01), Paced Auditory Serial Addition (r = -0.38; p = 0.02). No motor performance parameter correlated with Timed 25-Foot Walk. CONCLUSIONS: A simple, quantitative, objective method measuring finger motor performance could be used to define a score discriminating healthy controls and MS patients, even with very low disability. This sensitivity might be of crucial importance for monitoring the disease course and the treatment effects in early MS patients, when changes in the EDSS are small or absent.