To describe and compare the prevalence of psychosocial and psychiatric disorders among veterans with multiple sclerosis (MS) and a propensity-score-matched group of veterans without MS, and to identify sociodemographic and clinical characteristics associated with comorbid psychosocial and psychiatric problems among veterans with MS.

Data were linked and extracted from the Veterans Affairs (VA) Homeless Operations Management and Evaluation System and the Corporate Data Warehouse. The total sample comprised 27,342 veterans in the VA healthcare system between January 1, 2022, and June 30, 2023, who met eligibility criteria for an MS diagnosis (n=13,671) and 1:1 propensity-score-matched sample of veterans who did not have MS (n=13,671). MS diagnosis, substance use disorder (SUD), mental illness, and homelessness were defined using standard ICD-10 codes. Covariates included sex, age, Charlson Comorbidity Index (CCI), and VA service-connected disability rating.

A higher prevalence of mental illness among veterans with MS (33%) was found compared with those without MS (31%). Multivariable logistic regression models indicated MS was negatively associated with diagnoses of alcohol use disorder, stimulant use disorders, posttraumatic stress disorder, and schizophrenia/schizoaffective disorder but positively associated with diagnoses of cannabis use disorder and major depressive disorder. MS was not significantly related to homelessness. Disparities in psychosocial and psychiatric disorders among veterans with MS are described.

This study provides novel insights regarding rates of homelessness, SUD, and mental illnesses among veterans with MS. Interdisciplinary approaches to identification and management of mental illness, SUD, and homelessness among veterans with MS are critically needed.

Pediatric-onset multiple sclerosis (POMS) accounts for approximately 2 to 5% of all individuals with MS and is associated with an increased risk for cognitive impairment. In recent years, neuropsychological screening questionnaires have been increasingly utilized for pediatric populations in multidisciplinary settings. This study examines the clinical utility of the Colorado Learning Difficulties Questionnaire (CLDQ) and Pediatric Perceived Cognitive Functioning (Peds PCF) screening measures for identifying cognitive impairment in persons with POMS during a target neuropsychological evaluation.

Retrospective data was gathered from electronic medical records at a single pediatric hospital.

Forty-nine participants were included (69% female; 43% Hispanic/Latinx; mean age = 16.1 years old, range = 9.9 to 20.6 years old). Correlation analyses demonstrated strong interrelatedness between caregiver ratings on screening measures and performance on traditional neuropsychological measures. Effect sizes were medium across comparisons (CLDQ: Spearman’s rho = −.321 to −.563; PedsPCF: Spearman’s rho = .308 to .444). Exploratory cut-points using receiver operating characteristic analysis and Youden indices are also discussed.

Comparison of scores across caregiver rating questionnaires and on a targeted neuropsychological battery suggests that the screening surveys alone may not be sensitive enough to identify children with cognitive impairments, but ratings may provide qualitatively meaningful information along with neuropsychological testing. This study illustrates how pediatric neuropsychologists can leverage screening tools to focus consultative interviews and effectively triage referrals for evaluation within an academic medical setting.

Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care.

Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied.

Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied.

Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.

Ocrelizumab is an effective anti-CD20 therapy approved for Relapsing Remitting (RRMS) and Primary Progressive Multiple Sclerosis (PPMS). In clinical trials, a proportion of patients developed hypogammaglobulinemia which could contribute to infection risk. This study aimed to identify hypogammaglobulinemia and its risk factors and evaluate potentially associated serious infection risk in a real-world cohort of patients.

All MS patients treated with ocrelizumab in a Quebec City MS clinic from January 2017 to August 2021 were included and detailed patient characteristics were collected by chart review. Levels of immunoglobulins (IgM, IgA and IgG) were assessed prior to each treatment. Serious infection was defined as an infection requiring hospitalization or emergency room treatment. Association between hypogammaglobulinemia and serious infection was analyzed.

A total of 266 patients (average follow-up 2.05 years) were included (87% RRMS). After 6 infusions, 32.8%, 3.5% and 4.2% of patients had at least one IgM, IgA and IgG hypogammaglobulinemia event respectively. Aside from pre-treatment hypogammaglobulinemia, there were no variables associated with on-treatment hypogammaglobulinemia. There was a total of 21 serious infections (3.36 and 12.33 per 100-person-years in RRMS and PPMS). Developing hypogammaglobulinemia during treatment was not associated with serious infection. A regression analysis did not show associations between serious infection and key disease characteristics.

Similar to ocrelizumab extension studies, our cohort demonstrated a significant rate of hypogammaglobulinemia over time, mostly with IgM. No association was found between hypogammaglobulinemia and serious infection.

Multiple sclerosis (MS), an inflammatory autoimmune disease of the central nervous system, is characterized by damage to white matter via myelin degeneration with resulting sclerotic plaques and lesions. Upwards of 70% of people with MS show cognitive changes in multiple domains including verbal memory. Advances in disease-modifying therapies have increased the expected lifespan of people with MS, making aging with MS a critical emerging area of study. Memory declines during normal aging, yet the specific impact of MS on verbal memory in aging is inconclusive and understudied. To address this gap in knowledge, we examined whether MS was associated with verbal learning slope, total learning, delayed recall, and recognition performance in older adults. We further explored whether MS disease severity influenced these memory operations.

Participants included two cohorts: older adults with MS recruited from MS centers and patient registries, and healthy controls recruited from the community. A total of 164 adults age 60 and older without dementia were included in the current study, 79 in the MS group (mean age = 65.05 + 4.72; %female = 62) and 85 in the control group (mean age = 69.53 + 6.65; %female = 65.9). All participants were administered a neuropsychological battery including the Hopkins Verbal Learning Test-Revised (HVLT-R). The Patient Determined Disease Steps (PDDS), a patient-rated score of disability severity in MS comprised of eight steps related to walking ability, was used to operationalize MS severity. Using a median split, the PDDS was dichotomized into low (PDDS = 0-2) versus high (PDDS = 3-5) MS severity groups. Linear regression models were run to examine the effect of group (MS vs. control) and disease severity (PDDS) on four operations from the HVLT-R: learning slope, total learning, delayed recall, and recognition. Statistical analyses adjusted for age, years of education, and sex.

Linear regression models revealed that older adults with MS showed lower total learning compared to healthy controls (β = -.18, p = .03). Learning slope, delayed recall, and recognition did not differ by group (p > .05). Compared to healthy controls, older adults with high MS severity performed worse on total learning (β = -.21; p = .01) and delayed recall (β = -.18; p = .03). Group differences on learning slope and recognition were not significant (p > .05).

The presence of MS was associated with worse total learning. Moreover, high severity of MS was associated with worse total learning and delayed recall in older adults. These results delineate the influence of MS on specific memory operations and emphasize the potential utility of disease severity on cognitive performance in aging.

Depression is common in persons with MS (PwMS), substantially contributing to morbidity and mortality. Depression can dually impact PwMS as both a psychosocial reaction to living with the disease and a neurological effect of it. Cardinal features of depression include reduced ability to seek and experience pleasure, often attributed to dysregulation of the brain's reward system. People with depression exhibit atypical reward processing, as do fatigued PwMS. However, it is unclear whether MS itself affects reward processing, and whether it interacts with depression. The current study explored the associations of depression, MS, and their interaction on reward responsiveness. We hypothesized that depression and MS would independently be associated with poorer reward responsiveness and that they would interact synergistically to impair reward responsiveness.

Forty PwMS and 40 healthy age- and education-matched healthy controls (HC) participated in a computerized switching task with high- and low-reward manipulations. The Chicago Multiscale Depression Inventory (CMDI) Mood subscale measured depressive symptoms. The Behavioral Inhibition/Activation Scales (BIS/BAS) measured self-reported reward responsiveness and behavioral inhibition. Switching task performance was measured as response time (RT) and accuracy. Performance differences between the high- and low-reward conditions represented performance-based reward responsiveness. Linear mixed effects models were used to estimate the associations of MS and depression with reward responsiveness, behavioral inhibition, and task performance.

Depression, but not MS, was associated with higher BIS scores (p=.007). Neither depression nor MS was associated with BAS subscales. On the switching task, participants who reported lower depression responded to reward such that they were slightly faster in the high-reward condition compared to the low-reward condition (p=.07). By contrast, in participants who reported higher depression, there was no effect of reward on response time. Additionally, MS (p=.009) and depression (p=.018) were each associated with slower response times. Regarding accuracy, no effects of reward were observed; however, there was an interaction between MS and depression. Among HC participants, depression was not related to accuracy. In comparison, PwMS who reported higher depression were more accurate than PwMS who reported less depression (p=.043).

Consistent with hypotheses, higher depressive symptoms were associated with increased behavioral inhibition. Depression was not associated with self-reported reward responsiveness, but it was associated with reduced reward responsiveness on a cognitive task. Contrary to hypotheses, MS was not associated with reduced reward responsiveness. Additionally, higher depression and an MS diagnosis were related to slower response time, consistent with prior findings that psychomotor slowing is a hallmark feature of both disorders. Interestingly, we observed a unique behavioral trend in PwMS, such that PwMS with higher depressive symptoms were more accurate than PwMS with lower depressive symptoms, whereas this relationship was not present among HCs. Altogether, depression in both PwMS and cognitively healthy individuals may be associated with blunted reward responsiveness, but MS does not exacerbate this relationship. In fact, PwMS with depression may be more conscientious in their functioning and therefore perform better on cognitive task accuracy. Continued work should examine how reward processing and its underlying mechanisms may differ in depressed PwMS.

Social support is an emerging protective factor against cognitive decline. However, the relationship between social support and cognitive functioning in the multiple sclerosis (MS) population is not well understood. The present study aimed to investigate the associations between different aspects of social support and cognitive performance among persons with MS.

A volunteer sample of 63 persons with MS (% female = 88.9, mean age = 48.16) completed measures assessing perceived levels of social support measured by the Medical Outcomes Study Support Social Survey 5-item short form (MSSS-5), and social network (social network diversity and total size of social network) measured by the Social Network Index (SNI). Cognitive functioning was assessed by a brief virtual examiner-administered neuropsychological test battery (using a teleconferencing platform), including the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test, animal naming, and the Symbol Digit Modalities Test. Participants also completed brief, self-paced, virtual cognitive tests through the testmybrain.org platform, which consisted of digit span and the Trail-Making Test. A principal component analysis (PCA) was carried out to reduce the number of neuropsychological outcomes into fewer dimensions. Multiple linear regressions were conducted to examine the associations between social support measures and cognitive performance. Regression models were adjusted by the levels of depressive symptoms (operationalized by the Chicago Multiscale Depression Inventory or the Hospital Anxiety and Depression Scale) and premorbid functioning (measured by the Test of Premorbid Functioning).

A PCA reduced neuropsychological outcomes into 3 components representing cognitive domains of 1) processing speed/executive functioning, 2) verbal memory, and 3) verbal fluency / simple attention. In the unadjusted models, both perceived social support (i.e., to what extent one receives assistance from their social network) as well as total size of social network (i.e., total number of people one regularly talks to) were significant predictors of the processing speed/executive functioning component score of moderate strength, where F(1, 59) = 11.93, p = .001, β = 0.41 and F(1, 59) = 11.57, p = .001, β = 0.41, respectively. These associations were maintained after adjusting for depressive symptoms and level of premorbid functioning (F(4, 55) = 3.31, p = .003 and F(4, 55) = 3.31, p = .006, respectively). On the other hand, social network diversity (i.e., number of different types of close social relationships one has) was not a significant predictor of the processing speed/executive functioning component score (p > 0.05). None of the social support measures were significantly associated with the verbal memory and verbal fluency/simple attention component scores.

Greater social support (specifically, perceived levels of assistance and total size of social network) is associated with better performance on processing speed/executive functioning measures among persons with MS, independent of effects from depressive symptoms and premorbid functioning. Maintaining a strong social support network may be an important factor in optimizing cognitive health in MS.

Fatigue is common in pediatric-onset multiple sclerosis (POMS), yet causal factors and correlates of fatigue are poorly understood in this population. A 2016 review suggested an association between fatigue and emotional difficulties, sleep disturbance, and reduced quality of life in POMS. Information regarding the potential association between fatigue and cognitive challenges is limited and mixed. Through this systematic review, we searched for relationships between fatigue, cognition, and mental health.

Systematic review methodology and PRISMA guidelines were followed. Five electronic databases were searched: Ovid: Medline, Ovid: EMBASE, Ovid: PsycInfo, Web of Science and CINAHL. Search terms were specific to each database. Reference lists of included studies were also hand-searched. We included empirical studies that were published in English after 2001, included a sample with confirmed diagnoses of POMS using McDonald criteria, and measured fatigue, cognition and clinical factors including mental health outcomes. Cognition had to be assessed using a standardized assessment tool and studies must have examined associations between outcomes of interest either descriptively or by assessing bivariate or multivariate relationships. Covidence was used to complete the screening, extraction, and quality assessment. Two independent researchers (i.e., T.L.F, and/or S.D, and/or M.G) reviewed each paper included in the title and abstract screen and full text review. S.D and M.G completed the extraction and quality assessments. Conflicts at all stages were resolved by the lead author (T.L.F). The University of Adelaide JBI critical appraisal checklist for analytical cross-sectional studies was used to ensure the scientific rigor of each included study. Sample characteristics and measures of fatigue, clinical and cognitive variables were extracted. A narrative synthesis was conducted.

We identified 1025 abstracts through our initial search and retained 119 articles for full text review. One hundred and six of these studies were excluded during the full text review including six studies which did not examine the relationship between the outcomes of interest. Fifty-one additional studies were identified from hand-searching reference lists of included studies, of which 24 were retained for full text review. A total of 15 studies were extracted and analyzed. Overall, a positive relationship was found between fatigue and mental health outcomes (i.e., anxiety and depression), whereas results were mixed regarding the association between fatigue and performance-based measures of cognition as well as fatigue and other clinical characteristics (e.g., disease duration, EDSS, treatment with DMDs, relapse rate, age at disease onset). In some studies, fatigue and executive functioning performance were negatively related; the relationship was less clear in others (e.g., both fatigued and non-fatigued MS patients demonstrated cognitive challenges, an association between fatigue and executive functioning was identified at follow-up but not baseline). Eleven of the 15 included studies (73%) did not identify associations between fatigue and cognition.

While studies are mixed, fatigue in children has been associated with aspects of cognition. Understanding the relationship between fatigue, cognition, and mental health and identifying gaps in the existing literature, have implications for informing interventions for this clinical population.

The objective of the present study is to expand our understanding of visual complaints in people with multiple sclerosis (MS) with the aim of exploring potential rehabilitation approaches for treating visual complaints. Visual complaints are increasingly recognized as a core manifestation of MS. Up to 90% of people with MS report all kinds of visual complaints, such as blurry vision, double vision, being blinded by bright light, a reduced visual field and having trouble with depth perception. Since intact vision is quintessential to many activities of daily life, such as reading or car driving, these complaints affect independent participation to a great extent. The complaints cannot be fully explained by optical neuritis (a common symptom of MS) or other treatable visual or ophthalmological disorders. Moreover, there are no rehabilitation programs available for visual complaints in people with MS. However, the complaints are not yet understood well enough to develop effective rehabilitation strategies to reduce the impact of the visual complaints.

Visual complaints were assessed using the Screening Visual Complaints questionnaire. 68 people with MS with visual complaints, and 37 with hardly any visual complaints received a standard visual function assessment and a neuropsychological assessment. Correlations between the visual complaints, visual functions and cognitive functions were calculated. In addition, correlations were calculated between several visual functions and a composite score of the neuropsychological assessment.

Only some specific visual measures related to visual complaints, with small to moderate effect sizes. While most specific cognitive functions did not show correlations, measures indicative of overall cognitive capacity in people with MS (such as motor speed) consistently correlated with different kinds of visual complaints. Additionally, visual functions that related to visual complaints also correlated with the composite score for cognitive functioning.

Our study serendipitously showed that in developing or composing effective rehabilitation strategies for visual complaints, we should look beyond a person’s visual functioning: first, the overall cognitive capacity should be taken into account. Second, visual functioning and cognitive functioning are closely related. These results indicate that visual complaints may be a result of a general decline of the visual and/or cognitive system as one. When treating these complaints, low vision rehabilitation and neuropsychological rehabilitation strategies may be combined. Strategies should not focus on specific visual or cognitive functions, but at making the visual world more easily accessible, or more easily visible, to reduce the impact on the visual system and cognitive capacity. Strategies could range from applying more contrast in the environment to psycho-education. Future research should focus on developing rehabilitation programs and assessing their effectiveness in people with MS or with other types of non-acquired brain injuries.

Multiple sclerosis (MS) is a persistent neuroinflammatory disease of the central nervous system that affects young adults, and is pathologically characterized by multiple and distributed focal white matter lesions, although they are characteristically located in periventricular regions. Cognitive impairment occurs in all clinical forms of the disease, with great variability and great impact on the quality of life of patients. Recent research indicates that in addition to cognitive and physical deficits, they also have deficits in social cognition, such as Theory of Mind. Although social cognition in patients with multiple sclerosis has begun to be studied in recent years, there is still little knowledge about its impact in the early stages of the disease, when the load of injuries is low and physical disability is not yet present. A series of 7 cases of patients diagnosed with MS in follow-up by the Multiple Sclerosis polyclinic of the Institute of Neurology of the Hospital de Clínicas is presented.

Clinically stable patients with no recent urges and no cognitive complaint were included. They were evaluated with the ACE-R screening test and Theory of Mind tests: Reading the mind in the eyes and Faux Pas tests.

All patients presented normal ACE results, without indicators of cognitive impairment and poor performance in the emotion reading test. In two cases, poor yields in Faux Pas were also found.

Social cognition has a great impact on quality of life, and there are indicators of involvement in early stages of the disease in which other typical cognitive deficits are not yet evident, and may constitute the first indicator of deterioration. The evaluation and early detection of deficits in social cognition could contribute to the treatment and quality of life of patients.

To evaluate changes in neuropsychiatric symptoms among patients with multiple sclerosis (MS) following coronavirus disease of 2019 (COVID-19) infection using the National COVID Cohort Collaborative (N3C). The N3C represents the largest cohort of COVID-19 cases, through the unification of electronic health records from over 60 medical centers.

Out of 5,631,225 COVID-19 confirmed positive patients, we identified a cohort of patients with MS who were diagnosed with COVID-19. Conditions were searched using terms denoting common neuropsychiatric comorbid diagnoses, including anxiety, depression, pain, sleep disorders, fatigue, and cognitive disorders. We examined descriptively the percentages of patients who were newly diagnosed with each comorbid condition after COVID-19 infection. Additionally, we searched for various patient-reported outcome measures in the N3C dataset; only the Patient Health Questionnaire-9 (PHQ-9) had an adequate sample size in our cohort for analysis. To control for variability due to non-COVID-19 factors, we only included PHQ-9 scores that were reported one year before and after COVID-19 infection. A repeated-measures analysis of variance (ANOVA) was conducted to analyze the difference between PHQ-9 scores before and after COVID-19 diagnosis among MS patients.

In our final dataset, there were 40,690 patients who were diagnosed with MS and COVID-19. Among patients without pre-existing anxiety conditions, 9.18% were diagnosed with an anxiety disorder after COVID-19 infection. Among those who did not have a pre-existing cognitive disorder, 1.73% had such diagnoses after COVID-19 infection. Among those without previous depressive disorders, 8.89% were diagnosed with a depressive disorder after COVID-19 infection. Of those without fatigue conditions prior to COVID-19 in their medical records, 8.81% had documented fatigue in their records after contracting COVID-19. Of those without pain conditions in their medical records, 11.37% had documented pain in their records after COVID-19 infection. Finally, among patients without pre-existing sleep disorders, 8.71% were diagnosed with sleep disorders after COVID-19 infection. Regarding PHQ-9 scores, 50 patients had documented scores before their COVID-19 diagnosis and 50 after COVID-19 diagnosis (17 had scores for both before and after COVID-19 diagnosis). There was no significant difference in PHQ-9 scores before and after COVID-19 diagnosis (F(df) = 0.326, p = 0.572; meanbefore = 8.77, meanafter = 9.32).

Approximately 2-11% of MS patients developed new neuropsychiatric conditions after COVID-19 infection, with pain being the most common, followed by anxiety, fatigue, depression, and sleep disorders. Cognitive disorders were the least prevalent new onset neuropsychiatric sequelae of COVID-19 in this cohort. Additionally, there was a non-significant increase in severity of depressive symptoms, as indicated by a 1.36-point increase in PHQ-9 scores. These results suggest that patients with MS who have also been diagnosed with COVID-19 may be at risk for developing newly onset neuropsychiatric symptoms.

Word finding difficulty is a prevalent cognitive symptom in multiple sclerosis (MS). Word finding relies on retrieving concepts and word forms from the long-term store. Neuropsychological assessment of word finding difficulty in persons with MS (pwMS) is typically characterized by semantic errors and decreased speed in naming tests, along with decreased semantic verbal fluency scores. Despite this, there is significant heterogeneity in the detection of verbal fluency deficits across studies in the MS literature. This may be partially due to disease-related heterogeneity and/or low sensitivity of commonly used scoring approaches. We investigate the latter in the present study. Semantic network analysis, derived from graph theory, provides a fine-grained approach to understanding semantic retrieval by utilizing information about the co-occurrence of words produced on semantic verbal fluency tasks. Analysis results in a graphical quantification of the conceptual-lexical store. A preliminary study found that semantic networks from Spanish-speaking pwMS had fewer associative connections and more central connective pathways, which if affected, may lead parts of the network to become inaccessible for retrieval. However, their investigation was limited in the generalizability of their findings, as they excluded pwMS who have cognitive impairment (CI), which represents a significant proportion of pwMS. We sought to investigate network differences in an English-speaking MS sample, without exclusion based on CI, using widely-used metrics of micro-, meso-, and macroscopic structure. We hypothesize the MS network will be less efficiently organized, thus characterized by higher average shortest path length (ASPL), lower clustering coefficient (CC) and lower modularity (Q).

53 persons with MS and 44 neurologically healthy controls (HC) were recruited as a part of an ongoing study (NMSS RG-1907-34364 & RG-1901-33304). As a part of a larger battery, participants were administered the semantic verbal fluency subtest of the Controlled Oral Word Association Test. Responses were analyzed using a network-analysis R suite.

The MS and HC networks were characterized by having similar average shortest path lengths (ASPL MS =2.466, ASPL HC=2.463, F(1,1997)=0.281, p=0.596), indicating they require similar numbers of edges to be traversed to reach other nodes in the network. This suggests similar efficiency of information transfer. Clustering coefficient was not significantly different between the MS and HC networks (CC MS = 0.742, CC HC =0.742, F(1,1997)=0.10, p=0.919), suggesting similar local interconnectivity. The MS network had significantly lower modularity compared to the HC network (Q MS =0.497, Q HC = 0.502, F(1,1997)=16.678, p<0.001). This means that sub-communities of the network were less segregated into densely connected sub-graphs.

Contrary to expectation, ASPL and CC were not significantly different between groups. The absence of finding lower CC was consistent with prior findings. Consistent with our hypothesis, the MS network had lower modularity. This may suggest that pwMS were unable to use categorical clustering to aid in retrieval from the lexicon. Specifically, low modularity coupled with similar CC may suggest the structure of the MS lexicon is characterized by intact clustering on a microscopic scale but less strong organization into distinct clusters on a larger scale.

To test whether adherence to treatment in patients with MS is influenced by cognitive variables (executive functions), personality, and social support.

This is a pilot observational, descriptive, cross-sectional study. 60 patients with Relapsing remitting MS ( 73.33% female; age: 41.41 ±14.00) undergoing medical treatment ( 28 dymethilfumarate, 7 ocrelizumab/ rituximab, 6 fingolimod, 5 interferon, 5 natalizumab, 4 cladribine, 3 teriflunomide, 1 alemtuzumab, 1 glatiramer acetate) underwent a comprehensive multi-component evaluation including : cognition, social support (using the self-reported record of social support scale), personality (using the NEO-FFI questionnaire) and evaluation of treatment adherence using the Morisky Green Levine Medication Adherence Scale Participants were divided into two groups according to their adherence to medical treatment, low vs. high adherence was defined using a cutoff score of 4. Differences between groups were evaluated using Student's t-test with a significance level of p<0.05, the effect size was calculated with Cohen's d test.

Groups did not differ significantly in age, sex, type of treatment, Montreal Cognitive Assesments (MoCA) or neuropsychiatric scales of depression and anxiety. Regardless of treatment type, 63.33% of the patients had high treatment adherence. Significant differences between groups were found in the Global Index of Social Support (p=0.016, Cohen's d= 0.73) and the responsibility factor of the NEO-FFI (p=0.048, Cohen's d= 0.20). Conversely, no significant differences were found in executive functions (p=0.8), Openness (p=0.062), Extraversion (p=0.5), Neuroticism (p=0.4) and Agreeableness (p=0.8).

Social support and the responsibility factor of personality are significantly different between MS patients with high and low adherence to medical treatment. The study of social support and personality may be a key component in improving adherence strategies.

Multiple Sclerosis (MS) affects up to 500,000 adults in the United States, with cognitive impairment present in 45%-65% of people. Studies showed hippocampal atrophy in MS, but the underlying mechanisms remain unknown. Inflammation has been proposed to play a significant role, and associations between systemic inflammatory biomarkers and hippocampal atrophy have been shown in other neurological conditions. However, research exploring serum biomarker and volumetric associations in MS are lacking. Given that conventional imaging methods lack resolution for hippocampal internal architecture (HIA), new protocols were developed. We used the High-Resolution Multiple Image Co-Registration and Averaging (HR-MICRA) method to visualize the HIA subfields. We investigated the relationship between subfield volumes generated from HR-MICRA scans and systemic serum biomarkers in MS.

Patients with MS were recruited (N= 34, mean age= 54.6, 35.3% Black) underwent Magnetic Resonance Imaging (MRI), and serum biomarkers were obtained, specifically chosen for their potential role in MS. Inflammatory biomarkers included; granulocyte colony stimulating factor (G-CSF), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor- a (TNF- a), and growth factors; vascular endothelial growth factor (VEGF); insulin-like growth factor-1 (IGF-1), and brain derived growth factor (BDNF). Imaging was performed in a Siemens Prisma 3T scanner with a 64-channel head coil using the HR-MICRA method. Hippocampal subfields were calculated using the Automated Segmentation of Hippocampal Subfields (ASHS) package. We used the Magdeburg Young Adult 7T Atlas for sub-hippocampal structures and Penn Temporal Lobe Epilepsy T1-MRI Whole Hippocampus ASHS Atlas for general hippocampal structure and segmentation. Pearson's product-moment analyses provided correlations between biomarkers and hippocampal subfield volumes for each cerebral hemisphere. A statistical significance level of p < 0.05 was used for all analyses.

Correlations emerged between left hemisphere Cornu Ammonis (CA) 2 and G-CSF (r = -.384; p = .025); IL-10 (r = -.342; p = .048); VEGF (r = -.371; p= .031); and CA3 with IL-10 (r = -.488, p = .003); G-CSF (r = -.386; p= .024); VEGF (r = -.352; p= .041). Dentate gyrus correlated with MMP-9 (r =.416; p=.014); IL-10 (r = -.365; p =.034). BDNF was correlated with right hemisphere CA1 (r = -.417, p = .014), CA2 (r = -.497; p= .003) and CA3 (r = -.451; p=.007).

In our sample of persons with MS, left hemisphere hippocampal subfield volumes were negatively correlated with inflammatory biomarkers, supporting previous reports linking inflammation to reduced brain volumes in other neurological conditions. In the right hemisphere, we found negative correlations between HIA and BDNF, suggesting a neuroprotective function for BDNF in this neurodegenerative disease. These findings in a representative sample of patients with MS highlight the need for further research exploring the relationship between HIA and systemic serum biomarkers in MS.