Background. Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the ATXN2 gene. Although classically characterized by progressive cerebellar ataxia and oculomotor abnormalities, increasing evidence indicates that SCA2 is a multisystem disorder with prominent cognitive, behavioral, and psychiatric manifestations. These non-motor symptoms may precede overt motor signs, leading to diagnostic challenges and misdiagnosis as primary psychiatric conditions. Case Presentation. We report the case of a 59-year-old man with a several-year history of progressive behavioral and emotional dysregulation, initially diagnosed as a personality disorder. Prominent features included irritability, impulsivity, disinhibition, hypersexuality, altered eating behavior, and recurrent self-endangering suicidal gestures, with relatively preserved functional autonomy. Neurological examination revealed subtle cerebellar signs. Neuropsychological assessment showed impaired verbal memory with preserved recognition and borderline attentional–executive deficits, consistent with cerebello–frontal dysfunction. Brain magnetic resonance imaging (MRI) demonstrated moderate-to-severe cerebellar and brainstem atrophy, while dopamine transporter SPECT revealed severe bilateral presynaptic dopaminergic denervation. Cerebrospinal fluid biomarkers excluded Alzheimer’s disease. Genetic testing confirmed SCA2 with 38 CAG repeats in ATXN2. Conclusions. This case illustrates an atypical presentation of SCA2 in which behavioral and psychiatric symptoms preceded motor manifestations by several years. Recognition of such presentations is crucial to avoid misdiagnosis, reduce diagnostic delay, and enable timely genetic counselling and multidisciplinary management, reinforcing the concept of SCA2 as a multisystem neurodegenerative disorder.

Background:Telehealth can improve access to care for people living with multiple sclerosis (MS), but information on its acceptance is limited in Switzerland. Objective:This study aimed to determine the proportion of people living with MS willing to accept telehealth as a new default and the factors associated with their acceptance. Methods:We conducted a cross-sectional analysis using survey data from the Swiss Multiple Sclerosis Registry. We defined "telehealth as a default" as a health care model where remote consultations (telephone and/or video calls) are the primary mode of interaction between patients and their physicians, with in-person visits based on clinical necessity. Multivariable logistic regression was performed to evaluate the association between telehealth acceptance and sociodemographic and health-related factors. Telehealth acceptance was described in relation to 3 survey variables that mirrored key constructs from the Non-Adoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) framework. The variables were digital communication preferences, internet use for health provider searches, and experience with telemedicine. Results:Among 427 respondents, 15.5% (66/427) reported a willingness to accept telehealth as their default. In this group, only 21.2% (14/66) had experience using telemedicine. A descriptive analysis of our 3 NASSS-derived key constructs showed that among the 78.5% (335/427) respondents who generally agreed to digital access to health data, only 17.0% (57/335) accepted telehealth as a default. Notably, 30.7% (129/427) of participants stated a wish for support for using devices or the internet. Among those 129 individuals, 17.1% (22/129) were willing to accept telehealth as a default. Of the 89 people with prior telehealth experience, 15.7% (14/89) were willing to accept telehealth. In multivariable analysis, digital communication with health care providers (adjusted odds ratio [aOR] 14.56, 95% CI 6.18-39.04; P<.001), current internet use for health care provider search (aOR 7.78, 95% CI 1.34-45.32; P=.021), and a secondary progressive MS diagnosis (aOR 0.22, 95% CI 0.05-0.72; P=.021) were independently associated with accepting telehealth as a default. Conclusions:Our findings suggest a low acceptance of telehealth as a default among people living with MS in Switzerland. While our 3 postulated NASSS-derived key constructs were not associated with telehealth acceptance, we noted additional behavioral factors, including previous digital communication with health care providers and using the internet to search for health care provider information, which were associated with telehealth acceptance. Moreover, advanced disease states like secondary progressive MS were negatively associated with telehealth acceptance. Thus, telehealth as a default will be most acceptable in people living with MS who already use the internet for their health, and those with less severe disease. Future research should explore provider perspectives and evaluate long-term strategies for the acceptance of telehealth in MS care.

Introduction Bone-derived sclerostin impairs cognitive function in both patients with Alzheimer's disease (AD) and mouse models of AD. For the first time, we explored the correlation of sclerostin with neurocognitive domains in the AD continuum. Methods Sclerostin levels were measured in the cerebrospinal fluid (CSF) of a cohort of individuals with biological evidence of AD pathology, including patients with AD dementia, mild cognitive impairment due to AD (MCI), and subjective memory complaints (SMC). Correlations were examined between sclerostin and domain-specific cognitive scores. Results CSF sclerostin correlated with overall cognitive function, as well as with all cognitive domains impaired in AD. Of note, MCI patients with high CSF sclerostin levels displayed a worse overall and domain-specific neurocognitive performance. Discussion Our results evidenced the negative impact of sclerostin on all the cognitive domains predominantly in prodromal AD, suggesting its potential role as a biomarker of cognitive decline in the early stages of the disease.

Introduction Data on the population-based incidence of primary progressive aphasia (PPA), including all variants and Alzheimer's disease (AD) biomarker profiles, are scarce. Methods We conducted a 4-year, prospective, population-based study in the Salento region of Southern Italy, identifying incident PPA cases through a territory-wide surveillance network. Clinical diagnoses followed consensus criteria; AD pathology was defined by positive CSF or amyloid PET biomarkers. Results We identified 35 incident PPA cases, yielding an overall incidence of 1.14 (95% CI, 0.79-1.59) per 100,000 person-years. Incidence peaked in the early 60s for men and in the late 70s for women. The logopenic variant was most frequent and invariably associated with AD pathology. Approximately 20% of nonfluent and semantic cases, and the majority unclassified cases, also showed AD biomarkers. Discussion These findings provide real-world epidemiological evidence and underscore the need for systematic biomarker assessment in PPA to guide diagnosis, prognosis, and access to emerging therapies.

BACKGROUND:Obstructive Sleep Apnea (OSA) is a common comorbidity in Alzheimer's Disease (AD) and may exacerbate neurodegeneration. This study investigates the association between a novel metric of OSA severity-hypoxic burden (HB)-and measures of AD-related neurodegeneration. METHODS:In this retrospective exploratory study, patients with AD at stage 3 and stage 4 (NIA-AA 2018 criteria), enrolled at a Center for Neurodegenerative Diseases, underwent a complete sleep assessment including polysomnography and 3 T brain Magnetic Resonance Imaging. Correlation analyses were conducted between HB and brain volumes. RESULTS:Twenty-two patients (36.4% males, mean age 69.8 ± 7.5) were enrolled. OSA was diagnosed in 40.9% of patients. HB inversely correlated with left hippocampus (ρ = -0.553, p = 0.02) and left amygdala (ρ = -0.496, p = 0.04) volumes. AD patients with OSA showed significantly reduced left hippocampal volume than those without OSA (p = 0.038). CONCLUSIONS:This study highlights that greater OSA severity, measured by HB, correlates with left hippocampus and amygdala atrophy, suggesting a possible association between chronic hypoxia and neurodegeneration in AD.

Importance:Capturing individual multiple sclerosis (MS) progression is difficult; few studies have evaluated glial fibrillary acidic protein (GFAP) in large longitudinal cohorts with independent validation. Objective:To investigate whether serum GFAP levels and treatment-related changes are associated with future progression independent of relapse activity (PIRA). Design, Setting, and Participants:This was a prospective observational study using 2 large MS cohorts: the Swiss MS Cohort (SMSC; initiated in June 2012; data extraction September 22, 2025) and the Expression, Proteomics, Imaging, Clinical study (EPIC; initiated in July 2004; data extraction February 21, 2024). The study took place at tertiary MS centers (8 for SMSC and 1 for EPIC). A total of 2329 persons with MS from both cohorts with at least 1 available time point with neurofilament light chain (NfL) and GFAP measurements were included (overall 18 629 measurements). Exposures:Clinical data and NfL and GFAP z scores, collected and calculated every 6 or 12 months. Main Outcomes and Measures:Risk of future PIRA, defined as Expanded Disability Status Scale score worsening confirmed after 6 or more months without relapses (in SMSC), or a composite additionally including greater than 20% worsening in the 9-hole peg test or timed 25-ft walk test (in EPIC). Results:The SMSC and EPIC cohorts consisted of 1709 (13 375 samples; median [IQR] follow-up, 6.9 [2.5-10.7] years and age, 40.6 [32.1-50.1] years; 1128 [66.0%] female) and 620 (5254 samples; median [IQR] follow-up, 13.1 [9.4-14.0] years and age, 42.0 [35.0-50.0] years; 432 [69.7%] female) persons with MS, respectively. Consistent with prior work, high NfL was associated with relapse risk within the next year, whereas high GFAP was associated with long-term PIRA risk. In addition, elevated GFAP (z score >1.0 [84th percentile]) was associated with an average 40% higher hazard of short-term PIRA in the subsequent visit interval (SMSC: median [IQR] 346 [190-375] days; hazard ratio [HR], 1.45, 95% CI, 1.21-1.75; P < .001; EPIC: 385 [355-518] days; HR, 1.36; 95% CI, 1.07-1.71; P = .01). GFAP-based cohort enrichment in clinical trials targeting PIRA as an end point could reduce sample size by approximately 20%. Further, in SMSC, every yearly GFAP z score unit reduction during the first 2 years receiving fingolimod or B-cell-depleting therapy was associated with a lower risk of subsequent PIRA (54% risk reduction; HR, 0.46; 95% CI, 0.26-0.84; P = .01 and 67% risk reduction; HR, 0.33; 95% CI, 0.18-0.61; P < .001), respectively. Conclusions and Relevance:In this cohort study, elevated GFAP was associated with a higher risk of PIRA, while treatment-associated reductions were associated with a lower PIRA risk. Together, these results suggest that serum GFAP may serve as a biomarker for personalized risk stratification and treatment monitoring and as a screening tool to reduce cohort size in clinical trials targeting MS progression.

Gamma-frequency transcranial alternating current stimulation (gamma-tACS) is a promising neuromodulatory approach for Alzheimer’s disease (AD), given the central role of gamma-band dysfunctions in AD-related neuropathology and cognitive decline. Although multi-session gamma-tACS has shown beneficial cognitive and electrophysiological effects in AD, its impact in Mild Cognitive Impairment due to AD (MCI-AD), particularly on blood-based biomarkers and gamma entrainment, remains poorly understood. This case series provides preliminary evidence on the feasibility, tolerability, and multidimensional effects of 40 Hz tACS in individuals with biomarker-confirmed MCI-AD. Three participants completed 20 sessions of bilateral temporal gamma-tACS (40 Hz, 2 mA, 60 minutes/day, 5 days/week for 4 weeks). Assessments were conducted at baseline, post-intervention, and at 3-month follow-up. Outcome measures included neuropsychological testing, functional scales, blood biomarkers, resting-state electroencephalography (EEG), and 40 Hz auditory entrainment. Change magnitudes were descriptively estimated using within-subject Hedges’ g. Gamma-tACS was highly feasible and well tolerated, with high adherence and only mild transient side effects. Cognitive outcomes showed overall positive trends, including improvements in global cognition and delayed associative memory. Functional outcomes (i.e., autonomies, cognitive complaints and affective evaluation) were mixed, while blood biomarkers had heterogeneous changes, except for a consistent reduction in the Aβ42/Aβ40 ratio. EEG analyses revealed participant-specific modulations and enhanced offline gamma entrainment. Despite limitations related to sample size and study design, these findings support further investigation of gamma-tACS as an early intervention targeting oscillatory dysfunctions AD-MCI.

Background/Objectives: Chronic psychomotor and cognitive slowing after stroke can persist despite standard rehabilitation, especially in young adults with subcortical injuries. Innovative, integrated interventions are crucial for patients who have reached a plateau in their rehabilitation. We present a case of a 41-year-old male with chronic psychomotor and cognitive slowing following a left lenticulostriate infarction (NIHSS score = 5 at onset), who had plateaued after conventional rehabilitation. Methods: Over 4 weeks the patient underwent 20 sessions of a multimodal approach including high-frequency repetitive transcranial magnetic resonance stimulation over the supplementary motor area and bilateral temporo-parietal junctions and simultaneous computerized cognitive training targeting attention and executive function. Both motor and cognitive assessments, along with quantitative EEG (qEEG) evaluations, were conducted before and after the treatment. Results: At the end of treatment, the patient showed significant clinical improvement: speed and coordination in upper extremities (Finger Tapping Test) increased by 66% (dominant hand) and 74% (non-dominant hand), while finger dexterity (Nine-Hole Peg Test) increased by 25% (dominant hand) and 19% (non-dominant hand). Cognitive scores improved in alertness (58%), visual exploration (25%), and flexibility (24%), while divided attention remained stable. qEEG investigation showed increases in alpha (79%), gamma (33%), and beta (10%) power, with topographic shifts in the stimulated regions. Conclusions: These findings highlight the feasibility of combining targeted rTMS and cognitive training to enhance neuroplasticity in the chronic phase of stroke. Clinical recovery was accompanied by normalized cortical rhythms, suggesting qEEG biomarkers may be useful for tracking treatment response. Multimodal precision neurorehabilitation may offer a path forward for patients with persistent cognitive-motor deficits post-stroke.

In the brain, proNGF, the NGF precursor, is in a homeostatic equilibrium with its processing product, mature NGF. Dysregulation of the NGF/proNGF ratio has been associated with neurodegeneration in Alzheimer's disease (AD), positioning these neurotrophins as promising diagnostic biomarkers. Yet, their clinical validation as biomarkers has been hindered by the lack of analytical methods capable of discriminating and quantifying both isoforms under native conditions. Here, we introduce a dual electrochemical sensor based on Molecularly Imprinted Polymers (MIPs) that enables the simultaneous, selective, and label-free quantification of NGF and proNGF. The sensors were fabricated via electropolymerization of o-phenylenediamine on platinum microelectrodes, yielding highly specific recognition sites for each isoform. The MIP-based platform demonstrates remarkable selectivity, reproducibility, and isoform discrimination, achieving picomolar detection limits even for NGF, which is typically present at low concentration in cerebrospinal fluid (CSF). Validated on clinical CSF samples from AD and control patients, this system successfully quantifies both NGF and proNGF without antibodies or sample denaturation. To the best of our knowledge, this represents the first quantitative and simultaneous detection of NGF and proNGF under native conditions. This technology paves the way toward cost-effective, high-throughput, and point-of-care diagnostics for Alzheimer's and other neurodegenerative diseases.

Background and ObjectivesAccurate biomarkers that reflect disease activity, severity, and molecular pathophysiology in multiple sclerosis (MS) remain an unmet diagnostic need. We compared the performance of the established biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), with emerging candidates in CSF and serum.MethodsWe measured 21 analytes using Olink proximity extension assay technology, NfL and GFAP using Simoa, and soluble triggering receptor expressed on myeloid cells (sTREM2) and neuronal pentraxin 2 (NPTX2) using Fujirebio platforms in paired CSF and serum/plasma samples from 293 participants. The cohort included patients with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS), as well as individuals with inflammatory neurologic disease and symptomatic controls (SCs). CSF and serum biomarker levels were compared across diagnostic groups using multivariable Cox and linear regression models. Associations were assessed using CSF immunoglobulin profiles, time from first to second clinical event, and Expanded Disability Status Scale (EDSS) scores in CIS, as well as the Multiple Sclerosis Severity Score (MSSS) in patients with MS.ResultsEight biomarkers showed consistent differential expression. In CSF, CXCL13, CXCL9, IL-12b, and NfL were elevated in most CIS and MS subgroups compared with SCs. Osteopontin (OPN) levels were increased in RRMS and PPMS subgroups, whereas TNFRSF10A elevations were confined to patients with PPMS. In serum, NfL was elevated across all CIS and MS subgroups, GFAP was increased in RRMS and SPMS subgroups, and myelin oligodendrocyte glycoprotein (MOG) was increased in RRMS and PPMS subgroups. Higher CSF levels of CXCL13, CXCL9, and IL-12b predicted shorter intervals to a second clinical attack and correlated strongly with intrathecal IgM synthesis. Elevated EDSS scores at CIS onset were linked to higher CSF levels of CXCL13, IL-12b, TNFRSF10A, and OPN, and to NfL, GFAP, and MOG in serum. Prediction of future MSSS was limited to GFAP in CSF, whereas in serum, GFAP, MOG, OPN, and CXCL9 were significantly associated.DiscussionCSF CXCL13, CXCL9, and IL-12b are promising biomarkers for predicting relapse activity, while serum GFAP and MOG appear to be consistent candidates for prognosticating disease severity.

In multiple sclerosis (MS) patients under therapy, the increase of serum glial fibrillary acidic protein (sGFAP) concentrations is associated with the course of 'progression in absence of relapse' (PIRA). While serum neurofilament light chain (sNfL) reflects both response as well as insufficient or lack of efficiency of disease-modifying therapies (DMT), the longitudinal course of sGFAP levels as a drug response marker for future PIRA in relation to specific types of DMT is less clear. We aimed to compare the predictive capacity of sGFAP and sNfL for PIRA and relapse activity and the longitudinal course in people with MS (PwMS) treated with fingolimod, based on Z scores derived from normative values. Overall, 420 PwMS under fingolimod treatment with follow-up of 9.1 years (interquartile range: 7.0-11.0) from the Swiss MS Cohort, contributing 2935 longitudinal serum samples, were included. A reference data set for sGFAP established from 4297 healthy controls across three European and North American cohorts was used to calculate Z scores. The longitudinal course and the predictive capacity of biomarkers for time to PIRA and relapse were assessed by Cox proportional hazards and linear mixed-effects models. In controls, sGFAP concentrations were 13.6% higher in females than males and increased exponentially with age. Altogether, 31.0% of PwMS experienced ≥1 PIRA event. Elevated sGFAP Z scores (>0.75) were associated with increased risk of PIRA [hazard ratio (HR): 1.64; 95% confidence interval (CI): 1.16-2.32; P = 0.006], while this was not the case for sNfL. Conversely, elevated sNfL predicted relapses (HR: 1.58; 95% CI: 1.13-2.23; P = 0.008), while sGFAP did not. Both biomarkers decreased under treatment: sGFAP by 0.19 Z score units (ZSU)/10 years (95% CI: -0.27 to -0.11; P < 0.001) and sNfL by 0.16 ZSU/10 years (95% CI: -0.27 to -0.06; P = 0.002). Serum GFAP remained elevated in PwMS with future PIRA events (estimate: 0.29; 95% CI: 0.07-0.50; P = 0.009); no such association was found for sNfL. Serum GFAP and sNfL Z scores provide complementary predictive capacity for PIRA and relapse risk. The decrease of sGFAP under fingolimod is a feature not observed with other types of DMT and may hint to a specific anti-neurodegenerative effect of Sphingosine-1-phosphate-receptor modulators on astrocytes.

Background: Natalizumab (NTZ) is a highly effective disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS), originally administered intravenously (IV). A subcutaneous formulation (SC_NTZ) became available in Switzerland in 2021, offering potential advantages. Objective: To investigate satisfaction and convenience of use of SC_NTZ in MS patients. Design: Swiss, prospective, multicenter study. Methods: Consecutive RRMS patients treated with either ⩽6 (starters) or > 6 (long-term users) SC_NTZ injections completed the Treatment Satisfaction Questionnaire with Medication-II (TSQM-II, higher scores indicating greater satisfaction) and the Patient Satisfaction Questionnaire (PSQ) at baseline (Visit 1, V1). Starters were reassessed at the 9th SC_NTZ dose (Visit 2, V2). Non-parametric tests were applied to compare long-term users with starters at V1, and changes from V1 to V2 in starters. Results: One hundred six patients (73.6% female, median age 39.6 years, prior IV_NTZ 81.1%) were enrolled, including 79 long-term users and 27 starters. At V1, in the overall group the median (IQR) TSQM-II effectiveness, side effects, convenience and global satisfaction scores were 83 (67–100), 100 (92–100), 83 (72–89) and 83 (75–100), respectively. On the PSQ, the most commonly cited benefit was short administration time (80.2%). SC_NTZ treatment “never” affected work attendance in 54/87 (62.1%) employed patients. Seventy-nine percent participants reported spending ⩽1 h for SC_NTZ administration. Nonetheless, 76/86 (88.4%) of switchers from IV_NTZ found opportunities for discussions with healthcare professionals to be “similar”/”improved,” and 78 (90.7%) preferred SC_NTZ. Findings were consistent across subgroups and time points. Conclusion: This real-world, multicenter Swiss study supports SC_NTZ as a well-tolerated, highly accepted, and patient-preferred alternative to IV_NTZ.

Abstract INTRODUCTION Sclerostin, a negative regulator of bone formation, has been involved in memory impairment in Alzheimer's disease (AD) mouse models and is increased in elderly people at risk of AD. Here, we investigated sclerostin's role across the clinical stages of AD. METHODS We evaluated cerebrospinal fluid (CSF) sclerostin levels in patients with dementia due to AD, mild cognitive impairment, and subjective memory complaints, biologically characterized via the amyloid/tau/neurodegeneration classification. Results were correlated with AD biomarkers, amyloid beta (Aβ) 42, phosphorylated tau (p‐tau), and total tau (t‐tau), and clinical parameters of dementia severity. RESULTS CSF sclerostin increased in patients with dementia due to AD and correlated negatively with Aβ42 and positively with p‐tau, t‐tau, and dementia severity. DISCUSSION The association of CSF sclerostin with Aβ42, tau pathology, and dementia severity in the early disease stages is of great clinical relevance for the identification of sclerostin as a promising biomarker in early AD stages.

BACKGROUND AND OBJECTIVES:Accurate biomarkers that reflect disease activity, severity, and molecular pathophysiology in multiple sclerosis (MS) remain an unmet diagnostic need. We compared the performance of the established biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), with emerging candidates in CSF and serum. METHODS:We measured 21 analytes using Olink proximity extension assay technology, NfL and GFAP using Simoa, and soluble triggering receptor expressed on myeloid cells (sTREM2) and neuronal pentraxin 2 (NPTX2) using Fujirebio platforms in paired CSF and serum/plasma samples from 293 participants. The cohort included patients with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS), as well as individuals with inflammatory neurologic disease and symptomatic controls (SCs). CSF and serum biomarker levels were compared across diagnostic groups using multivariable Cox and linear regression models. Associations were assessed using CSF immunoglobulin profiles, time from first to second clinical event, and Expanded Disability Status Scale (EDSS) scores in CIS, as well as the Multiple Sclerosis Severity Score (MSSS) in patients with MS. RESULTS:Eight biomarkers showed consistent differential expression. In CSF, CXCL13, CXCL9, IL-12b, and NfL were elevated in most CIS and MS subgroups compared with SCs. Osteopontin (OPN) levels were increased in RRMS and PPMS subgroups, whereas TNFRSF10A elevations were confined to patients with PPMS. In serum, NfL was elevated across all CIS and MS subgroups, GFAP was increased in RRMS and SPMS subgroups, and myelin oligodendrocyte glycoprotein (MOG) was increased in RRMS and PPMS subgroups. Higher CSF levels of CXCL13, CXCL9, and IL-12b predicted shorter intervals to a second clinical attack and correlated strongly with intrathecal IgM synthesis. Elevated EDSS scores at CIS onset were linked to higher CSF levels of CXCL13, IL-12b, TNFRSF10A, and OPN, and to NfL, GFAP, and MOG in serum. Prediction of future MSSS was limited to GFAP in CSF, whereas in serum, GFAP, MOG, OPN, and CXCL9 were significantly associated. DISCUSSION:CSF CXCL13, CXCL9, and IL-12b are promising biomarkers for predicting relapse activity, while serum GFAP and MOG appear to be consistent candidates for prognosticating disease severity.

BackgroundAlthough cognitive impairment (CI) is common in multiple sclerosis (MS), conventional cognitive rehabilitation is often limited by accessibility and adherence challenges. Telerehabilitation offers an accessible alternative, but its efficacy across different CI severity levels remains unclear. The present prospective, single-center, single-arm interventional study with repeated measures aimed to identify changes in cognitive and psychosocial outcomes following a home-based cognitive telerehabilitation program with weekly synchronous coaching in MS patients with mild versus moderate CI, and to explore whether baseline impairment severity was associated with differences in change over time.MethodsSixty-six MS patients (34 mild CI; 32 moderate CI) completed a 12-week home-based cognitive telerehabilitation program (five sessions/week), supported by weekly Skype coaching. Outcomes were assessed at baseline (T0), post-intervention (T1), and 3-month follow-up (T2). Cognitive and emotional-behavioral functioning were investigated using standardized, validated instruments in the MS population. Changes over time and between-group differences were analyzed using linear models.ResultsAt T1, both groups improved in attention, verbal memory, and subjective cognitive perception (all p < 0.05). Processing speed improved only in mild CI (p < 0.001), whereas executive function improved only in moderate CI (p = 0.007). At T2, mild CI further improved in attention and verbal memory (p = 0.003–0.035), while moderate CI improved only in processing speed (p = 0.006). Emotional-behavioral outcomes improved in both groups at T1 (anxiety p = 0.002; depression p = 0.023; fatigue p < 0.001) and were largely maintained at T2, with no statistically significant between group differences. Mental quality of life improved over time, whereas physical quality of life remained unchanged.ConclusionFollowing the intervention, both groups showed improvements in cognitive and emotional-behavioral outcomes, with larger and more sustained changes in mild CI. These findings should be confirmed in randomized controlled studies.

INTRODUCTION:Temperature sensitivity affects many persons with multiple sclerosis (pwMS). Heat sensitivity describes a temporary symptom worsening in response to heat exposure. Cooling methods may counteract this and improve quality of life, but their real-world awareness and usage are poorly understood. OBJECTIVE:To assess the frequency of temperature sensitivity among pwMS and examine awareness and usage of cooling methods. METHODS:This cross-sectional analysis included 760 participants from the Swiss MS Registry. Data from a survey on temperature sensitivity and cooling methods were analyzed using descriptive statistics and logistic regression to identify factors associated with awareness and usage of cooling methods. RESULTS:Overall, 73.3% of respondents indicated temperature sensitivity, most commonly to heat (48.8%) or heat and cold (18%). Fatigue (70.2%), weakness/muscle weakness (48.7%), and gait issues (38.6%) were the most frequently reported exacerbated symptoms. While 62% were aware of cooling methods, only 44.3% of those who were aware and reported being sensitive to heat or heat and cold used them. The most frequently used cooling methods were cold showers (48.7%), ventilators (46.1%), and cooling cloths (33.8%). Awareness was positively associated with female sex, symptom burden, and temperature sensitivity, and varied regionally. Swiss citizenship was associated with cooling method usage. DISCUSSION:Despite the high frequency of temperature sensitivity, many pwMS do not use cooling methods, even when aware of them. Cooling method usage varies widely, making uniform recommendations challenging. Future studies are needed to survey healthcare professionals to better understand their awareness of heat-related symptom worsening and potential barriers to counselling on cooling methods.

INTRODUCTION AND OBJECTIVE:The introduction of follow-on formulations of glatiramer acetate (GA) has raised questions regarding their equivalence to the originator in real-world practice. This study aimed to evaluate the clinical effectiveness and safety of switching from originator GA to its follow-on product, Copemyl® (CO), in people with multiple sclerosis (MS). METHODS:A multicenter, retrospective observational study was conducted, including patients with MS treated for at least two years with GA followed by at least two years with CO. The primary outcome was the annualized relapse rate (ARR), whereas secondary outcomes included disability progression assessed by the Expanded Disability Status Scale (EDSS), MRI activity, and adverse events (AEs). RESULTS:A total of 138 patients were included. The ARR was very low and comparable across treatments (GA: 0.028; CO: 0.019), with a mean paired difference of -0.009 (95 % CI -0.028 to 0.010; p = 0.38), falling within the predefined equivalence margin. Disability progression over six months occurred in 6.0 % of GA and 7.3 % of CO periods (HR 1.53; 95 % CI 0.74-3.16; p = 0.26). No significant difference was found in MRI activity (52.2 % vs 60.1 %, p = 0.14). Safety profiles were comparable, with mostly mild to moderate AEs; four serious AEs occurred under CO, two of them possibly treatment-related. CONCLUSIONS:Switching from originator GA to CO did not influence clinical outcomes or safety. These findings support the therapeutic equivalence of the two formulations in real-world clinical practice, by supporting previous evidence from randomized trials.

Background Fatigue is a common symptom of multiple sclerosis (MS) and impacts quality of life, yet the role of chrononutrition and sleep in MS management remains underexplored. We aimed to investigate the cross-sectional associations of meal and sleep timing with fatigue in persons with MS (pwMS).Methods We implemented a chrononutrition questionnaire within the Swiss MS Registry to quantify the relationships between meal timing, sleep patterns and fatigue among pwMS.Results In unadjusted analyses of 958 participants (median age 49 years, 73% women), a longer interval between the first and last meals (eating window) was associated with less fatigue (OR per 1 SD change in predictor=0.84, 95% CI 0.75 to 0.94), while later wake-up (OR 1.26, 95% CI 1.12 to 1.43) and first meal (OR 1.28, 95% CI 1.14 to 1.44) were associated with more fatigue. Later weekend versus weekday patterns (‘social jetlag’) across meal and sleep timing were associated with less fatigue.Adjustment for lifestyle factors attenuated most of the relationships, with employment status being the most influential. After adjustment, a larger ‘social jetlag’ in first meal (OR 0.86, 95% CI 0.76 to 0.97) and going to bed later (OR 0.86, 95% CI 0.76 to 0.97) remained associated with less fatigue, while a longer time in bed (OR 1.28, 95% CI 1.12 to 1.46) remained associated with more fatigue.Conclusions Associations of meal and sleep timing with fatigue in pwMS were influenced by lifestyle factors, particularly employment status. After adjustment, eating the first meal later during weekends compared with weekdays, going to bed later and a shorter time in bed were associated with less reported fatigue. The apparent benefits of ‘social jetlag’ on first meal times require confirmation from prospective and interventional studies.

BACKGROUND:Survival estimates for frontotemporal lobar degeneration (FTLD)-related syndromes by incorporating fluid biomarkers are essential to better assess their prognostic value and explore how they might inform long-term outcomes in FTLD. Population-based registries provide valuable data for these predictions. The aim of the present study was to assess whether NfL and GFAP levels correlate with mortality risk in a population-based registry of incident FTLD. METHODS:Incident cases with FTLD-spectrum, occurring between 2018 and 2020, were followed for up to six years. Survival and hazard analysis according to biomarkers levels were conducted. RESULTS:Median survival was 6 years from symptom onset and 3 years from diagnosis. While FTD-ALS phenotype showed significantly shorter survival, no differences were observed among bvFTD, PPAs, and CBS/PSP. Biomarkers were significantly associated with survival. Higher plasma GFAP (HR = 1.006, 95%CIs 1.001-1.012; p = 0.026) and plasma NfL (HR = 1.027, 95%CIs 1.003-1.053; p = 0.025) were associated with increased mortality risk in bvFTD, PPAs, and CBS/PSP. CONCLUSIONS:These results highlight the potential of NfL and GFAP as valuable biomarkers for assessing prognosis in FTLD and underscore the importance of incorporating biomarker analysis into clinical practice for more accurate patient management. Further studies are needed to refine prognostic models for FTLD.