Predicted Expenditure for Prescription Drugs for Multiple Sclerosis in the Italian Market Between 2023 and 2028: Results of the Oracle Project.

INTRODUCTION: Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. METHODS: A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020-2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. RESULTS: The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. CONCLUSION: Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.

Cladribine effects on patient-reported outcomes and their clinical and biometric correlates in highly active relapsing multiple sclerosis at first switch: the observational, multicenter, prospective, phase IV CLADFIT-MS study.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients' lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29). Secondary objectives will include self-assessed psychological impact of highly active MS in daily life and general health after the switch to cladribine tablets as well as changes in cognitive function, anxiety, and depression symptoms. Additional PRO measures will include the Hospital Anxiety and Depression Scale (HADS), the EuroQoL 5-Dimension 5-Level (EQ-5D-5L), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI:MS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). Wearable devices will acquire activity data (step counts, walking speed, time asleep, and energy expenditure). Additional clinical, radiological, and laboratory data will be collected when available during routine management. The findings will complement data from controlled trials by providing insight from daily clinical practice into the effect of cladribine tablets on the patient's experience and self-assessed impact of treatment on daily life.

Telerehabilitation and onsite rehabilitation effectively improve quality of life, fatigue, balance, and cognition in people with multiple sclerosis: an interventional study.

Background: Telerehabilitation (TR) offers a valuable opportunity to improve access to care and has shown results comparable to onsite rehabilitation (SR) across different conditions. The present study aimed to explore the efficacy of TR and SR in improving clinically meaningful outcomes in people with multiple sclerosis (pwMS). Materials and methods: Subjects enrolled in the study were assigned to one of two treatment arms: a 6-week TR intervention or a 6-week onsite rehabilitation (SR) intervention. Pre-and post-intervention evaluation included assessment of global wellbeing using the Multiple Sclerosis Quality of Life-54 scale (QoL), fatigue using the Fatigue Severity Status scale (FSS), cognitive status using the Symbol Digit Modalities Test (SDMT), and balance dysfunction using the Berg Balance Scale (BBS). Group-level and single-subject improvements were considered as outcome measures, with QoL as the primary endpoint. To determine significant group changes over time for the entire pwMS cohort, a paired t-test was applied to the overall QoL score, focusing on both physical and mental composites. An independent sample t-test was used to assess differences in baseline and follow-up performance, as well as changes over time between the intervention groups (TR and SR). This same analysis was repeated for the other clinical domains (FSS, BBS, and SDMT). The minimal clinically important difference (MCID) according to treatment group (TR vs. SR) was explored using logistic regression. Additionally, a multiple linear regression model was applied to evaluate the impact of baseline clinical-demographic features on the observed post-intervention modifications. Results: A total of 51 subjects completed the study (37 women, mean age 46.3 ± 9.8, median Expanded Disability Status Scale 3.5, min. 2, max. 6.5). The entire sample benefited from the rehabilitation treatment, with significant improvements observed at both the group and individual levels across all measured domains for both intervention groups (TR vs. SR). Quality of life improved significantly (p = 0.005), as did fatigue and balance (both p < 0.001), and cognition (p = 0.003). Conclusions: Both SR and TR approaches effectively improved the perception of fatigue, cognitive performance, balance, and quality of life in a population of MS patients with moderate disability.

Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod.

BACKGROUND: Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment. OBJECTIVES: to compare the efficacy of natalizumab versus fingolimod in POMS. METHODS: This is an observational longitudinal multicentre study including natalizumab- and fingolimod-treated POMS patients (N-POMS and F-POMS, respectively). We collected Annual Relapse Rate (ARR), Expanded Disability Status Scale (EDSS), Symbol Digit Modality Test (SDMT), and MRI activity at baseline (T0), 12-18 months (T1), and last available observation (T2). RESULTS: We enrolled 57 N-POMS and 27 F-POMS patients from six Italian MS Centres. At T0, N-POMS patients showed higher ARR (p = 0.03), higher EDSS (p = 0.003) and lower SDMT (p = 0.04) at baseline compared with F-POMS. Between T0 and T1 ARR improved for both N-POMS and F-POMS (p < 0.001), while EDSS (p < 0.001) and SDMT (p = 0.03) improved only for N-POMS. At T2 (66.1 ± 55.4 months) we collected data from 42 out of 57 N-POMS patients showing no further ARR decrease. CONCLUSION: Both natalizumab and fingolimod showed high and sustained efficacy in controlling relapses and natalizumab also associated to a disability decrease in POMS. This latter effect might be partly mediated by the high inflammatory activity at baseline in N-POMS.

Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients. METHODS: The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24 months: (1) no new/enlarging T2-hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs). RESULTS: At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod. DISCUSSION: By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.

Ocrelizumab and ofatumumab comparison: an Italian real-world propensity score matched study.

BACKGROUND: The management of Multiple Sclerosis (MS) has undergone transformative evolution with the introduction of high-efficacy disease-modifying therapies (DMTs), specifically anti-CD20 monoclonal antibodies, such as ocrelizumab (OCR) and ofatumumab (OFA). MATERIALS AND METHODS: This is an independent retrospective cohort study in Relapsing MS (RMS) patients followed at eight Italian MS centers who initiated treatment with OCR or OFA in the participating centers and with at least 12 months on therapy. A generalized linear regression model inverse probability of treatment weight (IPTW) PS-adjusted was performed to evaluate the relationship between annualized relapse rate (ARR) and treatment groups. No evidence of disease activity-NEDA-3 at 12-month score was also collected. Safety profile of the investigated DMTs was recorded. RESULTS: A total cohort of 396 RMS patients fulfilled the required criteria and were enrolled in the study. Out of them, 216 had a prescription of OCR and 180 of OFA. The mean follow-up was 13.2 ± 1.9 months. The estimated means for ARR did not show differences between the two groups, 0.059 for patients on OCR and 0.038 for patients on OFA (p = 0.185). The generalized regression model IPTW PS-adjusted did not reveal differences between patients on OCR and OFA (ExpBOFA 0.974, 95%CI 934-1.015, p = 0.207). NEDA-3 at 12 months was experienced by 199(92.1%) patients on OCR and 170(94.4%) patients on OFA (p = 0.368). Generally, both therapies exhibit good tolerability. CONCLUSIONS: The treatment with OCR and OFA resulted in comparable control of disease activity with good safety profile. Our results need further validation in larger multicentre studies with long-term follow-up.

ChatGPT vs. neurologists: a cross-sectional study investigating preference, satisfaction ratings and perceived empathy in responses among people living with multiple sclerosis.

BACKGROUND: ChatGPT is an open-source natural language processing software that replies to users' queries. We conducted a cross-sectional study to assess people living with Multiple Sclerosis' (PwMS) preferences, satisfaction, and empathy toward two alternate responses to four frequently-asked questions, one authored by a group of neurologists, the other by ChatGPT. METHODS: An online form was sent through digital communication platforms. PwMS were blind to the author of each response and were asked to express their preference for each alternate response to the four questions. The overall satisfaction was assessed using a Likert scale (1-5); the Consultation and Relational Empathy scale was employed to assess perceived empathy. RESULTS: We included 1133 PwMS (age, 45.26 ± 11.50 years; females, 68.49%). ChatGPT's responses showed significantly higher empathy scores (Coeff = 1.38; 95% CI = 0.65, 2.11; p > z < 0.01), when compared with neurologists' responses. No association was found between ChatGPT' responses and mean satisfaction (Coeff = 0.03; 95% CI = - 0.01, 0.07; p = 0.157). College graduate, when compared with high school education responder, had significantly lower likelihood to prefer ChatGPT response (IRR = 0.87; 95% CI = 0.79, 0.95; p < 0.01). CONCLUSIONS: ChatGPT-authored responses provided higher empathy than neurologists. Although AI holds potential, physicians should prepare to interact with increasingly digitized patients and guide them on responsible AI use. Future development should consider tailoring AIs' responses to individual characteristics. Within the progressive digitalization of the population, ChatGPT could emerge as a helpful support in healthcare management rather than an alternative.

Identifying definite patterns of unmet needs in patients with multiple sclerosis using unsupervised machine learning.

INTRODUCTION: People with multiple sclerosis (PwMS) exhibit a spectrum of needs that extend beyond solely disease-related determinants. Investigating unmet needs from the patient perspective may address daily difficulties and optimize care. Our aim was to identify patterns of unmet needs among PwMS and their determinants. METHODS: We conducted a cross-sectional multicentre study. Data were collected through an anonymous, self-administered online form. To cluster PwMS according to their main unmet needs, we performed agglomerative hierarchical clustering algorithm. Principal component analysis (PCA) was applied to visualize cluster distribution. Pairwise comparisons were used to evaluate demographics and clinical distribution among clusters. RESULTS: Out of 1764 mailed questionnaires, we received 690 responses. Access to primary care was the main contributor to the overall unmet need burden. Four patterns were identified: cluster C1, 'information-seekers with few unmet needs'; cluster C2, 'high unmet needs'; cluster C3, 'socially and assistance-dependent'; cluster C4, 'self-sufficient with few unmet needs'. PCA identified two main components in determining the patterns: the 'public sphere' (access to information and care) and the 'private sphere' (need for assistance and social life). Older age, lower education, longer disease duration and higher disability characterized clusters with more unmet needs in the private sphere. However, demographic and clinical factors failed in explaining the four identified patterns. CONCLUSION: Our study identified four unmet need patterns among PwMS, emphasizing the importance of personalized care. While clinical and demographic factors provide some insight, additional variables warrant further investigation to fully understand unmet needs in PwMS.

Neuromuscular Electrical Stimulation Does Not Influence Spinal Excitability in Multiple Sclerosis Patients.

(1) Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, under three experimental conditions involving the ankle planta flexor muscles: (1) passive NMES (pNMES); (2) NMES superimposed onto isometric voluntary contraction (NMES+); and (3) isometric voluntary contraction (ISO). (2) Methods: In total, 20 MS patients (MS) and 20 healthy individuals as the control group (CG) took part in a single experimental session. Under each condition, participants performed 15 repetitions of 6 s at 20% of maximal voluntary isometric contraction, with 6 s of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. (3) Results: In MS, H-reflex amplitude did not change under any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased under NMES+ (p = 0.01), decreased under pNMES (p < 0.000) and was unaltered under ISO (p = 0.829). (4) Conclusions: The different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Perspectives on Neuromyelitis Optica Spectrum Disorders, the Narrative Medicine contribution to care.

BACKGROUND: This research aimed to investigate the experience of Neuromyelitis Optica Spectrum Disorders (NMOSD) by integrating the perspectives of patients, caregivers and clinicians through narrative-based medicine to provide new insights to improve care relationships. METHODS: The research was conducted in the second half of 2022 and involved six Italian centres treating NMOSD and targeted adult patients, their caregivers and healthcare providers to collect the three points of view of living with or caring for this rare disease, still difficult to treat despite the pharmacological options. Narratives followed a structured outline according to the time: yesterday-today-tomorrow, to capture all disease phases. RESULTS: Twenty-five patients diagnosed with NMOSD, ten caregivers and 13 healthcare providers participated in the research. Patients reported symptoms limiting their daily activities and strongly impacting their social dimension. We noticed improvements across disease duration, whilst the persistence of limitations was recurrent in patients with longer diagnoses. Caregivers' narratives mainly share experiences of their daily life changes, the burden of the caregiving role and the solutions identified, if any. Healthcare providers defined their role as a guide. CONCLUSION: Limitations in activities are prominent in the lives of people with NMOSD, along with fatigue. Family members are the weakest link in the chain and need information and support. Healthcare professionals are attentive to the helping dimension.

Relapse-associated worsening in a real-life multiple sclerosis cohort: the role of age and pyramidal phenotype.

BACKGROUND AND PURPOSE: The overall disability in patients with relapsing-remitting multiple sclerosis is likely to be partly rather than entirely attributed to relapse. MATERIALS AND METHODS: The aim was to investigate the determinants of recovery from first relapse and relapse-associated worsening (RAW) in relapsing-remitting multiple sclerosis patients from the Italian MS Registry during a 5-year epoch from the beginning of first-line disease-modifying therapy. To determine recovery, the functional system (FS) score was used to calculate the difference between the score on the date of maximum improvement and the score before the onset of relapse. Incomplete recovery was defined as a combination of partial (1 point in one FS) and poor recovery (2 points in one FS or 1 point in two FSs or any other higher combination). RAW was indicated by a confirmed disability accumulation measured by the Expanded Disability Status Scale score confirmed 6 months after the first relapse. RESULTS: A total of 767 patients had at least one relapse within 5 years of therapy. Of these patients, 57.8% experienced incomplete recovery. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.007) and pyramidal phenotype were associated with incomplete recovery (OR = 2.1, 95% CI 1.41-3.14; p < 0.001). RAW was recorded in 179 (23.3%) patients. Age (OR = 1.02, 95% CI 1.01-1.04; p = 0.029) and pyramidal phenotype (OR = 1.84, 95% CI 1.18-2.88; p = 0.007) were the strongest predictors in the multivariable model. CONCLUSIONS: Age and pyramidal phenotype were the strongest determinants of RAW in early disease epochs.

Assessment of the treating physicians' first-hand experience with handling and satisfaction of ofatumumab therapy: findings from the PERITIA survey conducted in Europe.

BACKGROUND: Real-world evidence on experience and satisfaction of ofatumumab as a treatment option for relapsing multiple sclerosis (RMS) is limited. OBJECTIVE: To present cumulative responses from a questionnaire related to first-hand experience of treating physicians on handling and convenience of ofatumumab therapy along with concerns related to COVID-19. METHODS: PERITIA was a multicentre survey conducted to collect responses from the ASCLEPIOS I/II trial investigators from Europe via an online questionnaire. RESULTS: Forty-six physicians (Germany, n = 14; Spain, n = 12; Portugal, n = 10; Italy, n = 10) completed the survey. Overall, 43% of the physicians considered the benefit-risk ratio of ofatumumab as very good. Over 93% were in favour of ofatumumab self-administration at home and the majority (83%) believed it to be completely true that self-administration of ofatumumab eases the burden for patients in terms of time. All investigators would like to potentially use anti-CD20 therapy as a long-term strategy. Even during the COVID-19 pandemic, physicians were in favour of a self-administration of MS therapy at home over other anti-CD20 therapy infusions. CONCLUSION: European neurologists who were part of this survey considered the benefit-risk-ratio of ofatumumab as favourable and the monthly self-administered subcutaneous injections offering convenience for patients in the clinical practice.

Sexual Dysfunction in People with Multiple Sclerosis: The Role of Disease Severity, Illness Perception, and Depression.

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS.

Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis.

OBJECTIVE: Assessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >-30 days and ≤90 days from conception (SHORT_EXP), and describing newborns' outcomes. METHODS: Maternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis. RESULTS: 170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001-0.09)) compared with NO_EXP (n=31, 0.43 (0.21-0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30-0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05-0.24)) compared with SHORT_EXP (0.30 (0.17-0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns' weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population. CONCLUSIONS: Our findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns' outcomes.

Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study.

INTRODUCTION: Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. METHODS: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. RESULTS: Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1-2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04-3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1-4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997-0.999, p = 0.01). CONCLUSION: In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices.

Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?

Secondary progressive multiple sclerosis (SPMS) subtype is retrospectively diagnosed, and biomarkers of the SPMS are not available. We aimed to identify possible neurophysiological markers exploring grey matter structures that could be used in clinical practice to better identify SPMS. Fifty-five people with MS and 31 healthy controls underwent a transcranial magnetic stimulation protocol to test intracortical interneuron excitability in the primary motor cortex and somatosensory temporal discrimination threshold (STDT) to test sensory function encoded in cortical and deep grey matter nuclei. A logistic regression model was used to identify a combined neurophysiological index associated with the SP subtype. We observed that short intracortical inhibition (SICI) and STDT were the only variables that differentiated the RR from the SP subtype. The logistic regression model provided a formula to compute the probability of a subject being assigned to an SP subtype based on age and combined SICI and STDT values. While only STDT correlated with disability level at baseline evaluation, both SICI and STDT were associated with disability at follow-up. SICI and STDT abnormalities reflect age-dependent grey matter neurodegenerative processes that likely play a role in SPMS pathophysiology and may represent easily accessible neurophysiological biomarkers for the SPMS subtype.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

Alopecia Universalis Occurring after Alemtuzumab Treatment for Multiple Sclerosis. A Two-Year Follow-Up of Two Patients.

Alopecia Universalis (AU) is the most severe form of Alopecia Areata and is caused by cytotoxic T-cells reacting with follicular autoantigens, producing complete loss of scalp and body hair. Alemtuzumab is a highly efficacious monoclonal antibody used in the treatment of Multiple Sclerosis (MS), but it causes secondary autoimmunity in up to 40% of patients. Many factors are believed to contribute to this process, but pathogenic mechanisms are not well clear. To date, three cases of AU after treatment with Alemtuzumab have been reported. In this paper we report the cases of two patients who developed AU 12 months after the second cycle of Alemtuzumab, with a review of the literature. One year after the end of the second cycle, two female patients in their thirties experienced complete hair loss. The first case was temporally associated with a significant drop in vitamin D (VD) levels. The second case was accompanied by joint swelling. Both patients had thyroid alterations and showed no hair regrowth after a 2-year follow-up. AU must be considered among the secondary autoimmune manifestations of Alemtuzumab treatment. We emphasize the need for appropriate patient screening and thorough clinical surveillance for factors predisposing patients to secondary autoimmunity.

Physical Exercise Moderates the Effects of Disability on Depression in People with Multiple Sclerosis during the COVID-19 Outbreak.

Physical disability impacts psychosocial wellbeing in people with multiple sclerosis. However, the role of physical activity in this context is still debated. By taking advantage of a previous survey, conducted online from 22 April to 7 May 2020, we performed a post-hoc analysis with the aim to assess the associations between disability, physical exercise, and mental health in multiple sclerosis. We retrieved the following data: (i) sociodemographic information, (ii) changes in lifestyle (including exercise), (iii) physical disability, as measured with the Patient-Determined Disease Steps scale, and (iv) anxiety feelings and depressive symptoms assessed via the items included in the Quality of Life in Neurological Disorders measurement system. Examination of the interaction plot showed that the effect of disability on depression, but not on anxious symptoms, was significant for all levels of physical exercise (low: b = 1.22, 95% C.I. 0.85, 1.58, p < 0.001; moderate: b = 0.95, 95% C.I. 0.66, 1.24, p < 0.001; and high: b = 0.68, 95% C.I. 0.24, 1.13, p = 0.003). Based on these data, we can conclude that disability significantly impacted depression during the COVID-19 pandemic, with physical activity playing a moderating role. Our results suggest that favoring exercise in multiple sclerosis (MS) would ameliorate psychological wellbeing regardless of the level of physical disability.