Multiple Sclerosis Phenotypes Research Articles

MicroRNAs in blood and cerebrospinal fluid as diagnostic biomarkers of multiple sclerosis and to monitor disease progression.

Multiple sclerosis is a chronic autoimmune disease of the central nervous system. It is the main cause of non-traumatic neurological disability in young adults. Multiple sclerosis mostly affects people aged 20–50 years; however, it can occur in young children and much older adults. Factors identified in the distribution of MS include age, gender, genetics, environment, and ethnic background. Multiple sclerosis is usually associated with progressive degrees of disability. The disease involves demyelination of axons of the central nervous system and causes brain and spinal cord neuronal loss and atrophy. Diagnosing multiple sclerosis is based on a patient’s medical history including symptoms, physical examination, and various tests such as magnetic resonance imaging, cerebrospinal fluid and blood tests, and electrophysiology. The disease course of multiple sclerosis is not well correlated with the biomarkers presently used in clinical practice. Blood-derived biomarkers that can detect and distinguish the different phenotypes in multiple sclerosis may be advantageous in personalized treatment with disease-modifying drugs and to predict response to treatment. The studies reviewed have shown that the expression levels of a large number of miRNAs in peripheral blood, serum, exosomes isolated from serum, and cerebrospinal fluid are altered in multiple sclerosis and can distinguish the disease phenotypes from each other. Further studies are warranted to independently validate these findings so that individual or pairs of miRNAs in serum or cerebrospinal fluid can be used as potential diagnostic markers for adult and pediatric multiple sclerosis and for monitoring disease progression and response to therapy.

Relationship between MRI perfusion and clinical severity in multiple sclerosis.

Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging (MRI) techniques. Furthermore, MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes, physical disability, and cognitive impairment. However, a review focused on these aspects is still missing. Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings. Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners, with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients. However, only 3T scanners showed a statistically significant distinction. Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found. However, the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.

DEMOGRAPHIC, CLINICAL AND PARACLINICAL CHARACTERISTICS OF A SAMPLE OF EGYPTIAN MULTIPLE SCLEROSIS (MS) PATIENTS ATTENDING MS CLINIC IN AL-AZHAR UNIVERSITY HOSPITALS

Background: Multiple sclerosis is an autoimmune inflammatory demyelinating disorder, affecting people in the most productive period in their lives with more predilection to affect females more than males, many demographic studies of multiple sclerosis had been done in many western countries, in the middle east particularly in Arabic countries multiple sclerosis now being heavily studied in all aspects ofthe disorder after the incidence of multiple sclerosis has been increased. Objective: The aim of this work was to study the clinical and paraclinical characteristics of patients with multiple sclerosis (MS) attending Al-azhar university hospitals, (Al-Hussein and Bab-El-Sherya) along the time of the study (from April 2017 to April 2019) aiming for better management and rehabilitation of Multiple sclerosis patients to improve their quality of life. Patients and Methods: This was a cross sectional descriptive study carried on 400 definite multiple sclerosis patients who were recruited from Al-Azhar university hospitals diagnosed according to revised McDonald's criteria 2017. Results: The current study included 400 MS patients, 113 were males and 287 were females, the main age of disease onset was 28.42±8.48, the motor manifestations was the most common presenting manifestation, followed by optic neuritis then the sensory manifestations, the relapsing remitting phenotype was the commonest phenotype, the family history of MS was positive in 2% in the current study, we observed a statistically significant difference between MS patients as regard MS phenotype and the sex of the patient, age and the total EDSS, first clinical symptoms and the total EDSS, time to 2nd clinical event and the total EDSS and the lesions in the spinal cord and the total EDSS. Conclusion: The first clinical presentation of MS affects the patient EDSS, patients with visual and sensory presentation had commonly lower EDSS, compared to patients with motor presentation had commonly higher EDSS.

Gut microbiota‐dependent CCR9+CD4+ T cells are reduced and altered to an inflammatory phenotype in secondary progressive multiple sclerosis

The risk factors and peripheral immunological changes associated with multiple sclerosis progression to the secondary progressive phase are largely unknown. The present article shows that CCR9+CD4+ T cells, of which frequencies are altered by the gut microbiota and aging, are reduced and their immune regulatory function is altered in secondary progressive multiple sclerosis.

TNFRSF13C/BAFFR P21R and H159Y polymorphisms in multiple sclerosis

Recent studies implicate B cells in multiple sclerosis (MS) pathogenesis, and consequently, several molecules participating in B cell survival and proliferation, including B-cell activating factor (BAFF), have recently been analyzed in MS patients. BAFF mediates its function through binding to three receptors; among them, its interaction with the BAFF receptor (BAFFR) is crucial in mediating its survival function. Interestingly, two common polymorphisms of the TNFRSF13C gene, encoding BAFFR, P21R (rs77874543) and H159Y (rs61756766), have been reported to affect BAFFR assembly and signaling. In order to evaluate the possible contribution of BAFFR in MS pathogenesis and/or phenotype, we analyzed both TNFRSF13C/BAFFR polymorphisms in 486 MS patients in relation to their disease severity, their disability status and the age of disease onset and duration. As control group, we used allele frequencies extracted from the Exome Aggregation Consortium (ExAC) Browser. Interestingly, we found a higher prevalence of the H159Y polymorphism in MS patients, suggesting that enhanced BAFFR-signaling might contribute to the disease pathogenesis.

Combined Cerebrospinal Fluid Neurofilament Light Chain Protein and Chitinase-3 Like-1 Levels in Defining Disease Course and Prognosis in Multiple Sclerosis.

Background: Neurofilament light chain protein (NFL) and chitinase3-like1 (CHI3L1) have gained importance recently as prognostic biomarkers in multiple sclerosis (MS).Objectives: We aimed to investigate NFL and CHI3L1 cerebrospinal fluid (CSF) profiles in multiple sclerosis and the informative and prognostic potential of the individual and combined measures.Methods: CSF NFL and CHI3L1 levels were measured in a cross-sectional cohort of 157 MS patients [99 relapsing-remitting (RRMS), 35 secondary progressive (SPMS), and 23 primary progressive (PPMS)]. Clinical relapse and/or gadolinium-enhanced lesions (GEL) in MRI within 90 days from CSF collection by lumbar puncture (LP) were registered and considered as indicators of disease activity. Longitudinal treatment and disability data were evaluated during medical visits with a median follow-up of 50 months.Results: CSF levels of NFL and CHI3L1 were higher in MS patients compared to non-MS controls. In RRMS and SPMS patients, increased NFL levels were associated with clinical relapse, and gadolinium-enhanced lesions in MRI (p < 0.001), while high CHI3L1 levels were characteristic of progressive disease (p = 0.01). In RRMS patients, CSF NFL, and CHI3L1 levels correlated with each other (r = 0.58), and with IgM-oligoclonal bands (p = 0.02 and p = 0.004, respectively). In addition, CSF CHI3L1 concentration was a predictor for 1-point EDSS worsening {HR = 2.99 [95% CI (1.27, 7.07)]} and progression during follow-up {HR = 18 [95% CI (2.31, 141.3)]}. The pattern of combined measure of biomarkers was useful to discriminate MS phenotypes and to anticipate clinical progression: RRMS more frequently presented high NFL combined with low CHI3L1 levels, compared to SPMS (HR 0.41 [0.18–0.82]), and PPMS (HR 0.46 [0.19–0.87]), while elevation of both biomarkers preceded diagnosis of clinical progression in RRMS patients (log rank = 0.02).Conclusions: Individual measures of CSF NFL and CHI3L1 are biomarkers of disease activity and progression, respectively. The pattern of combined measure discriminates MS phenotypes. It also predicts the subset of RRMS patients that will progress clinically allowing early intervention.

Multiple brain networks support processing speed abilities of patients with multiple sclerosis

ABSTRACTObjectives: Many people affected by multiple sclerosis (MS) experience cognitive impairment, especially decreases in information processing speed (PS). Neural disconnection is thought to represent the neural marker of this symptom, although the role played by alterations of specific functional brain networks still remains unclear. The aim is to investigate and compare patterns of association between PS-demanding cognitive performance and functional connectivity across two MS phenotypes.Methods: Forty patients with relapsing-remitting MS (RRMS) and 25 with secondary progressive MS (SPMS) had neuropsychological and MRI assessments. Multiple regression models were used to investigate the relationship between performance on tests of visuomotor and verbal PS, and on the verbal fluency tests, and functional connectivity of four cognitive networks, i.e. left and right frontoparietal, salience and default-mode, and two control networks, i.e. visual and sensorimotor.Results: Patients with SPMS were older and had longer disease history than patients with RRMS and presented with worse overall clinical conditions: higher disease severity, total lesion volume, and cognitive impairment rates. However, in both patient samples, cognitive performance across tests was negatively correlated with functional connectivity of the salience and default-mode networks, and positively with connectivity of the left frontoparietal network. Only the visuomotor PS scores of the RRMS group were also associated with connectivity of the sensorimotor network.Conclusions: PS-demanding cognitive performance in patients with MS appears mainly associated with strength of functional connectivity of frontal networks involved in the evaluation and manipulation of information, as well as the default mode network. These results are in line with the hypothesis that multiple neural networks are needed to support normal cognitive performance across MS phenotypes. However, different PS measures showed partially different patterns of association with functional connectivity. Therefore, further investigations are needed to clarify the contribution of inter-network communication to specific cognitive deficits due to MS.

Multiple sclerosis: oral health, behaviours and limitations of daily oral hygiene - a questionnaire study.

Neurological deficits and progressing disability in patients with multiple sclerosis (MS) may hamper daily oral hygiene, but their relations with oral problems have not yet been clearly determined. The aim of this study was to identify the most significant dental problems and limitations of daily oral hygiene in Polish patients with MS. 199 patients with diagnosed MS (median age 37 years) treated in the neurological outpatient clinic were interviewed using a paper-based questionnaire. They provided answers on oral health, behaviours and the limitations of their daily oral hygiene. Clinical information regarding symptoms, MS phenotype, relapses, medication and degrees of disability was based on medical records. The most frequent symptoms were dry mouth (43.2%) and bleeding from gums (28.1%). Dry mouth was more frequent in patients with secondary-progressive MS (SPMS) than relapsing-remitting MS (65.4% vs 41.3%, p = 0.023). Patients with bleeding from gums had had MS for a longer duration (median 6 vs 4 years, p = 0.002). Difficulties in daily oral hygiene were more frequent in patients with SPMS (24.0% vs 8.1%; p = 0.016). Greater proportions of patients with muscle weakness of limbs, imbalance or pain brushed their teeth irregularly. Frequent (i.e. at least every six months) visits to the dentist's surgery were uncommon in patients with SPMS (12.0% vs 39.7%, p = 0.010). Dry mouth and bleeding from gums are more frequent in patients with longer lasting and more advanced types of MS. Daily oral hygiene and oral health self-control is limited in patients with MS, mainly due to motor deficits, balance problems and pain, and this becomes worse with disease duration. To minimise the burden of the disease, patients with MS require better education and improvement in their awareness regarding proper oral health control, such as the use of electric toothbrushes. In addition, patients with chronic and progressive disability from multiple sclerosis may benefit from better organised access to dental care.

Additive Effect of Spinal Cord Volume, Diffuse and Focal Cord Pathology on Disability in Multiple Sclerosis.

Introduction: Spinal cord (SC) pathology is strongly associated with disability in multiple sclerosis (MS). We aimed to evaluate the association between focal and diffuse SC abnormalities and spinal cord volume and to assess their contribution to physical disability in MS patients.Methods: This large sample-size cross-sectional study investigated 1,249 patients with heterogeneous MS phenotypes. Upper cervical-cord cross-sectional area (MUCCA) was calculated on an axial 3D-T2w-FatSat sequence acquired at 3T using a novel semiautomatic edge-finding tool. SC images were scored for the presence of sharply demarcated hyperintense areas (focal lesions) and homogenously increased signal intensity (diffuse changes). Patients were dichotomized according EDSS in groups with mild (EDSS up to 3.0) and moderate (EDSS ≥ 3.5) physical disability. Analysis of covariance was used to identify factors associated with dichotomized MUCCA. In binary logistic regression, the SC imaging parameters were entered in blocks to assess their individual contribution to risk of moderate disability. In order to assess the risk of combined SC damage in terms of atrophy and lesional pathology on disability, secondary analysis was carried out where patients were divided into four categories (SC phenotypes) according to median dichotomized MUCCA and presence/absence of focal and/or diffuse changes.Results: MUCCA was strongly associated with total intracranial volume, followed by presence of diffuse SC pathology, and disease duration. Compared to the reference group (normally appearing SC, MUCCA>median), patients with the most severe SC changes (SC affected with focal and/or diffuse lesions, MUCCA<median) had an almost 5-times higher risk of having moderate disability (OR 4.75, 95% CI 3.07–7.49, p < 0.001). Patients with normally appearing SC and MUCCA below the median had a 2-fold increased risk of being in the moderate disability group when compared to the reference patients (OR 2.15, 95% CI 1.26–3.67, p < 0.001). In contrast, patients with MUCCA above the median with SC lesions/diffuse changes did not differ significantly from the reference group.Conclusion: Low cervical SC volume is a strong independent predictor of physical disability in MS patients. The contribution of focal SC lesions and diffuse changes to the worse disability outcomes is limited and present especially in patients with low SC volume.

Nanoparticles for regenerative medicine.

Nanoparticles for regenerative medicine.

Early complement genes are associated with visual system degeneration in multiple sclerosis.

Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms. Though genetic studies have identified variants that are associated with an increased risk of developing multiple sclerosis, no variants have been consistently associated with multiple sclerosis severity. In part, the lack of findings is related to inherent limitations of clinical rating scales; these scales are insensitive to early degenerative changes that underlie disease progression. Optical coherence tomography imaging of the retina and low-contrast letter acuity correlate with and predict clinical and imaging-based outcomes in multiple sclerosis. Therefore, they may serve as sensitive phenotypes to discover genetic predictors of disease course. We conducted a set of genome-wide association studies of longitudinal structural and functional visual pathway phenotypes in multiple sclerosis. First, we assessed genetic predictors of ganglion cell/inner plexiform layer atrophy in a discovery cohort of 374 patients with multiple sclerosis using mixed-effects models adjusting for age, sex, disease duration, optic neuritis and genetic ancestry and using a combination of single-variant and network-based analyses. For candidate variants identified in discovery, we conducted a similar set of analyses of ganglion cell/inner plexiform layer thinning in a replication cohort (n = 376). Second, we assessed genetic predictors of sustained loss of 5-letters in low-contrast letter acuity in discovery (n = 582) using multivariable-adjusted Cox proportional hazards models. We then evaluated candidate variants/pathways in a replication cohort. (n = 253). Results of both studies revealed novel subnetworks highly enriched for connected genes in early complement activation linked to measures of disease severity. Within these networks, C3 was the gene most strongly associated with ganglion cell/inner plexiform layer atrophy (P = 0.004) and C1QA and CR1 were top results in analysis of sustained low-contrast letter acuity loss. Namely, variant rs158772, linked to C1QA, and rs61822967, linked to CR1, were associated with 71% and 40% increases in risk of sustained LCLA loss, respectively, in meta-analysis pooling discovery and replication cohorts (rs158772: hazard ratio: 1.71; 95% confidence interval 1.30-2.25; P = 1.3 × 10-4; rs61822967: hazard ratio: 1.40; 95% confidence interval: 1.16-1.68; P = 4.1 × 10-4). In conclusion, early complement pathway gene variants were consistently associated with structural and functional measures of multiple sclerosis severity. These results from unbiased analyses are strongly supported by several prior reports that mechanistically implicated early complement factors in neurodegeneration.

Trials and therapies in secondary progressive MS, simplified.

The FDA approvals of siponimod and cladribine for secondary progressive multiple sclerosis raise questions about the diagnostic criteria for multiple sclerosis phenotypes and their applicability to clinical trials. A simpler classification for the disease could be the answer.

The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis.

This review provides a brief update of new research findings on the changing epidemiology, disease course, and prognosis of multiple sclerosis (MS). Evidence not only continues to support the female predominance in incidence and prevalence of the disease but also supports an increase in incidence of MS in geographic areas that were previously considered to be low incidence for the disease. An increased interest in population-based registries and databases will provide more valid epidemiological measures and observational studies conducted in well-defined study populations. Such studies are crucial for an accurate description of both changing prognosis of MS and differential characteristics of the various MS phenotypes.

Multiple sclerosis prevalence and incidence in San Vicente del Raspeig, Spain

BackgroundChanges in the demographic epidemiology of multiple sclerosis (MS) may challenge the view of a latitudinal gradient in the distribution of MS. The objective of this study was to assess the incidence and prevalence of MS in addition to information on MS phenotypes and the use of disease modifying therapies (DMTs) in San Vicente del Raspeig in south eastern Spain. MethodsThis was a prospective epidemiological study of MS in San Vicente del Raspeig (population of 57,175 inhabitants based on the 2017 census) from 2005 to 2018. Multiple sources were used to identify MS cases. We considered as prevalent and incident cases all patients who satisfied either the criteria of Poser for clinically or laboratory-supported definite MS, or McDonald criteria. MS phenotypes were defined according to the 2013 revisions. ResultsFor the prevalence data, 64 patients were identified. The non-adjusted prevalence was 111.9 (95% CI: 87.7–142.9) cases per 100,000 inhabitants; the prevalence was 159.3 cases per 100,000 inhabitants for women and 63.6 cases per 100,000 inhabitants for men. The female-to-male ratio was 2.6:1. The age-adjusted prevalence for the European standard population was 107 cases per 100,000 inhabitants. During the study period, the incidence was 5 cases per 100,000 inhabitants per year. Most patients were being treated with DMTs (81.3%). MS was active in at least 12.5% of patients. ConclusionsThe results are consistent with the increased risk of MS in Spain observed over the last three decades, with growing prevalence rates that place the country in the high-risk prevalence zone.

Differential activation of an innate immune signaling pathway in lymphocytes from patients with multiple sclerosis

Abstract Prior work demonstrated that epithelial V-like antigen (EVA), a cell surface adhesion molecule, is expressed in lymphocytes and is necessary for the efficacy of anti-alpha4integrin treatment of experimental autoimmune encephalomyelitis (EAE), a mouse model of human multiple sclerosis (MS). EVA deficiency is associated with a severe clinical phenotype of EAE in the presence or absence of treatment. Recent work demonstrates that EVA, which is encoded by the mpzl2 gene, also regulates expression of the anti-viral oligoadenylate synthase genes, Oas1 and Oas2. Here the EVA signaling pathway was assessed in patients with MS and healthy controls from the UIC Neuroimmunology Biobank. The goal of this initiative is to assess individual variation in innate immune responses that are associated with severe phenotypes of multiple sclerosis (MS) in underrepresented racial and ethnic minority groups. In response to treatment with the Tlr7/8 agonist R848, peripheral blood lymphocytes from MS patients demonstrated an increase in mpzl2 expression that was not observed in healthy controls. In addition, racial and ethnic differences were observed in the expression of Oas1and Oas2 genes. It is hypothesized that differential innate immune activation of these transcriptional pathways are novel biomarkers and modifiers of disease severity in MS. This work was funded by the Evelyn Garcia Research Fund at the University of Illinois College of Medicine, Chicago.

Costs of illness progression for different multiple sclerosis phenotypes: a population-based study in Sweden.

BackgroundLittle is known of how the cost of illness and health-related quality of life changes over time after a diagnosis of multiple sclerosis.ObjectivesThe aim was thus to explore the progression of annual direct and indirect costs and health-related quality of life among people with multiple sclerosis of working ages, following diagnosis with relapsing–remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) or conversion to secondary progressive multiple sclerosis (SPMS) after RRMS.MethodsSwedish nationwide registers were linked to estimate the annual cost of illness in 2006–2013 among people with a registered new multiple sclerosis phenotype, including: direct costs, indirect costs, and health-related quality of life.ResultsDrugs and indirect costs for sick leave were the main cost drivers after diagnosis with RRMS. After conversion to SPMS, the RRMS cost drivers were replaced by indirect costs for disability pension. The main cost driver in newly diagnosed PPMS was indirect costs for sick leave, later replaced by disability pension. Health-related quality of life scores were similar after RRMS and SPMS.ConclusionsAfter initial high indirect costs for sick leave, people with RRMS had higher drug costs compared to people with PPMS. Cost drivers during SPMS initially followed the pattern in the RRMS population, but were replaced by indirect costs for disability pension.

Changes in the Risk of Reaching Multiple Sclerosis Disability Milestones In Recent Decades

Clinicians' experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before. To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden. A nationwide population-based retrospective cohort study. By April 2017, 12 512 patients with available information on demographics, MS phenotype, and date of MS onset and diagnosis were registered in the Swedish MS Registry of which 7331 patients with at least 2 recorded Expanded Disability Status Scale scores (EDSS) and diagnosed between January 1995 and December 2010 were included. No further exclusion criteria were applied. Patients were followed up until December 2016 with a median duration follow-up of 8.5 (interquartile range, 4.7-13.8) years. Statistical analysis began in April 2017. Patients were followed up from MS onset date to the date of sustained EDSS 3.0, 4.0, and 6.0. To handle interval-censored observations, a Weibull model was fit, and the change in the risk of EDSS 3.0, 4.0, and 6.0 over calendar years was estimated and hazard ratios (HRs) with corresponding CIs were calculated. Of 7331 patients, 5196 (70.9%) were women, and the mean (SD) age at diagnosis was 38.3 (11.7) years. Adjusting for sex, number of clinic visits, diagnostic delay, and onset age, a 3% decrease per calendar year of diagnosis for the risk of sustained EDSS 3.0 (HR, 0.97; 95% CI, 0.96-0.97), a 6% decrease for the risk of EDSS 4.0 (HR, 0.94; 95% CI, 0.93-0.95), and a 7% decrease for the risk of EDSS 6.0 (HR, 0.93; 95% CI, 0.91-0.94) among patients with relapsing-onset MS was found. The trends were not significant for patients with progressive-onset MS (EDSS 3.0: HR, 1.01; 95% CI, 0.98-1.03; EDSS 4.0: HR, 1.00; 95% CI, 0.98-1.02; EDSS 6.0: HR, 1.00; 95% CI, 0.98-1.02). Risk of reaching major disability milestones has significantly decreased over the last decade in patients with relapsing-onset MS in Sweden. Several factors could potentially be responsible for this observation. However, given that no change was seen in disability accrual of patients with progressive-onset MS and the absence of efficacious treatment option in this group, increased use of more efficacious disease-modifying treatments could be a possible driver of this change.

Discriminative clinical and neuroimaging features of motor-predominant hereditary diffuse leukoencephalopathy with axonal spheroids and primary progressive multiple sclerosis: A preliminary cross-sectional study

BackgroundHereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant white matter disease, typically characterized by juvenile cognitive decline and frontoparietal white matter lesions. A portion of HDLS patients exhibit preferential motor dysfunctions as their initial symptoms, mimicking multiple sclerosis (MS). However, there is no study comparing this phenotype of HDLS and primary progressive multiple sclerosis (PPMS), which greatly resemble each other. This is the first preliminary study to clarify the clinical and neuroimaging features of motor-predominant HDLS, and compare it with PPMS, using cases whose colony stimulating factor 1 receptor (CSF1R) were sequenced. MethodsClinical and radiological data from Japanese patients at the Department of Neurology, Kyushu University Hospital, Fukuoka, Japan, were evaluated retrospectively and cross-sectionally. Twenty-nine brain and 18 spinal cord magnetic resonance imaging (MRI) scans from four motor-predominant HDLS patients with CSF1R mutations and 15 PPMS patients without CSF1R mutations, were evaluated using an HDLS MRI scoring system. ResultsTwo patients with HDLS were initially diagnosed with MS and received immunotherapy. Clinically, motor-predominant HDLS and PPMS patients resembled each other in onset age and disability. However, motor-predominant HDLS patients had a significantly higher frequency of frontal release signs, lower positivity rates of oligoclonal IgG bands (OCB), and lower IgG index values. Total HDLS MRI scores, total white matter lesions (WMLs), and brain atrophy were similar between the diseases. However, motor-predominant HDLS patients had more marked atrophy of the corpus callosum (CC) body, more WMLs in the deep and subcortical regions of the frontoparietal lobes, fewer WMLs in the occipitotemporal periventricular regions, and more restricted diffusivity lesions on MRI than PPMS patients. There was a stronger association between disease duration and CC index in HDLS, suggesting more rapid progression compared with PPMS. ConclusionsMotor-predominant HDLS has characteristic frequent frontal release signs, normal findings for OCB and the IgG index, severe CC body atrophy, abundant deep and subcortical WMLs in the frontoparietal lobes, subtle occipitotemporal lobe periventricular WMLs, and more restricted diffusivity lesions on MRI. Although the present study was limited by the small number of HDLS cases, we propose that immunotherapy should be avoided in such cases.

Social Mind and Long-Lasting Disease: Focus on Affective and Cognitive Theory of Mind in Multiple Sclerosis.

The role of social cognition, including theory of mind (ToM), in affecting quality of life (QoL) along the course of diseases has been reported. This is a considerable aspect in chronic pathologies, such as multiple sclerosis (MS), in which supporting and maintaining QoL is of crucial importance. We aimed to investigate the relation between ToM, clinical variables and neuropsychological profile in a cohort of adults with long lasting disease, such as different clinical MS phenotypes (Relapsing Remitting -RR- versus Progressive -Pr). In particular, our study focuses on (1) how (affective and cognitive) ToM impairment occurs in different phenotypes, (2) whether MS ToM impairment is secondary to or independent from cognitive deficit and (3) whether ToM deficit impacts QoL. 42 adults with MS (18 M: 24 F, 52.38 ± 10.31 mean age, 21.24 ± 10.94 mean disease duration, 26 RR and 16 Pr) and 26 matched healthy controls (HC) (7 M: 19 F, 51.35 ± 12.42 mean age) were screened with a neuropsychological and ToM battery, assessing both affective and cognitive components. We found statistically significant groups differences in cognitive but not affective ToM, with a lower performance in PrMS than those with a RRMS disease course. Also, significant predictive effects of neuropsychological tests on ToM were identified in MS group. Finally, MS people with different level of affective ToM differed significantly in QoL. ToM deficit in moderately disabled people with MS involves cognitive but not affective ToM components with implications on QoL. It also appears to be related to cognitive performance. As neurological and neurocognitive profiles influence mentalizing in MS, ToM evaluation should be considered for inclusion in clinical screening.

Predicting clinical progression in multiple sclerosis after 6 and 12 years

Background and purposeTo predict disability and cognition in multiple sclerosis (MS) after 6 and 12 years, using early clinical and imaging measures.MethodsA total of 115 patients with MS were selected and followed up after 2 and 6 years, with 79 patients also being followed up after 12 years. Disability was measured using the Expanded Disability Status Scale (EDSS); cognition was measured only at follow‐up using neuropsychological testing. Predictors of interest included EDSS score, baseline brain and lesion volumes and their changes over 2 years, baseline age, clinical phenotype, sex and educational level.ResultsHigher 6‐year EDSS score was predicted by early EDSS score and whole‐brain volume changes and baseline diagnosis of primary progressive MS (adjusted R 2 = 0.56). Predictors for 12‐year EDSS score included larger EDSS score changes and higher T1‐hypointense lesion volumes (adjusted R 2 = 0.38). Year 6 cognition was predicted by primary progressive MS phenotype, lower educational level, male sex and early whole‐brain atrophy (adjusted R 2 = 0.26); year 12 predictors included male sex, lower educational level and higher baseline T1‐hypointense lesion volumes (adjusted R 2 = 0.14).ConclusionsPatients with early signs of neurodegeneration and a progressive disease onset were more prone to develop both disability progression and cognitive dysfunction. Male sex and lower educational level only affected cognitive dysfunction, which remains difficult to predict and probably needs more advanced imaging measures.