Multiple Sclerosis Population Research Articles

Prevalence, treatment and correlates of depression in multiple sclerosis

BackgroundThe prevalence of depression in Multiple Sclerosis (MS) is often assessed by administering patient reported outcome measures (PROMs) examining depressive symptomatology to population cohorts; a recent review summarised 12 such studies, eight of which used the Hospital Anxiety and Depression Scale-Depression (HADS-D). In clinical practice, depression is diagnosed by an individual structured clinical interview; diagnosis often leads to treatment options including antidepressant medication. It follows that an MS population will include those whose current depressive symptoms meet threshold for depression diagnosis, plus those who previously met diagnostic criteria for depression and have been treated such that depressive symptoms have improved below that threshold. We examined a large MS population to establish a multi-attribute estimate of depression, taking into account probable depression on HADS-D, as well as anti-depressant medication use and co-morbidity data reporting current treatment for depression. We then studied associations with demographic and health status measures and the trajectories of depressive symptoms over time. MethodsParticipants were recruited into the UK-wide Trajectories of Outcome in Neurological Conditions-MS (TONiC-MS) study, with demographic and disease data from clinical records, PROMs collected at intervals of at least 9 months, as well as co-morbidities and medication. Interval level conversions of PROM data followed Rasch analysis. Logistic regression examined associations of demographic characteristics and symptoms with depression. Finally, a group-based trajectory model was applied to those with depression. ResultsBaseline data in 5633 participants showed the prevalence of depression to be 25.3 % (CI: 24.2–26.5). There were significant differences in prevalence by MS subtype: relapsing 23.2 % (CI: 21.8- 24.5), primary progressive 25.8 % (CI: 22.5–29.3), secondary progressive 31.5 % (CI: 29.0–34.0); disability: EDSS 0–4 19.2 % (CI: 17.8–20.6), EDSS ≥4.5 31.9 % (CI: 30.2–33.6); and age: 42–57 years 27.7 % (CI: 26.0–29.3), above or below this range 23.1 % (CI: 21.6–24.7). Fatigue, disability, self-efficacy and self esteem correlated with depression with a large effect size (>0.8) whereas sleep, spasticity pain, vision and bladder had an effect size >0.5. The logistic regression model (N = 4938) correctly classified 80 % with 93 % specificity: risk of depression was increased with disability, fatigue, anxiety, more comorbidities or current smoking. Higher self-efficacy or self esteem and marriage reduced depression. Trajectory analysis of depressive symptoms over 40 months in those with depression (N = 1096) showed three groups: 19.1 % with low symptoms, 49.2 % with greater symptoms between the threshold of possible and probable depression, and 31.7 % with high depressive symptoms. 29.9 % (CI: 27.6–32.3) of depressed subjects were untreated, conversely of those treated, 26.1 % still had a symptom level consistent with a probable case (CI: 23.5–28.9). ConclusionA multi-attribute estimate of depression in MS is essential because using only screening questionnaires, diagnoses or antidepressant medication all under-estimate the true prevalence.Depression affects 25.3 % of those with MS, almost half of those with depression were either untreated or still had symptoms indicating probable depression despite treatment. Services for depression in MS must be pro-active and flexible, recognising the heterogeneity of outcomes and reaching out to those with ongoing symptoms.

Functional gradients reveal cortical hierarchy changes in multiple sclerosis

Functional gradients reveal cortical hierarchy changes in multiple sclerosis

Efficacy and Safety of Two Therapeutic Strategies in a Multiple Sclerosis Population of Afro-Caribbean Descent (P4-6.002)

Efficacy and Safety of Two Therapeutic Strategies in a Multiple Sclerosis Population of Afro-Caribbean Descent (P4-6.002)

NMDA Receptor Antagonist Memantine Ameliorates Experimental Autoimmune Encephalomyelitis in Aged Rats.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes' mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.

Investigating the Prevalence of Comorbidity in Multiple Sclerosis Clinical Trial Populations.

Comorbidity is common in multiple sclerosis (MS) with the most prevalent conditions being depression, anxiety, hypertension, and hyperlipidemia. Limited information regarding the representation of comorbidity status is available from phase III clinical trials in MS leading to concern about the potential underrepresentation of individuals with comorbidity in clinical trials. The objective was to estimate the prevalence of comorbidities in MS clinical trial populations. Individual-level data from multiple sponsors were requested for a 2-stage meta-analysis of phase III clinical trials of MS disease-modifying therapies. To ensure consistency of our approach across trials, we followed the Maelstrom retrospective harmonization guidelines. Chronic comorbidities at clinical trial enrollment recommended by the International Advisory Committee on Clinical Trials in MS were considered (depression, anxiety, hypertension, hyperlipidemia, migraine, diabetes, chronic lung disease). Additional comorbidities were also classified. Classification was based on medical history data. Individual comorbidities were summed and categorized as 0, 1, 2, or ≥3. We report the pooled prevalence (95% confidence interval [95% CI]) of comorbidity. The pooled prevalence and prevalence ratios across age, sex, race, disability level, and treatment were also reported. Heterogeneity was assessed using the I2 statistic. Seventeen trials involving 17,926 participants were included. Fourteen trials enrolled participants with relapsing MS (RMS) while 3 enrolled participants with progressive MS (PMS). The distributions of sex, age, and disability level were generally consistent within RMS and PMS trials. When pooled, almost half of trial participants (46.5%) had ≥1 comorbidity (1: 25.0%, 95% CI 23.0-27.0, I2 = 89.9; 2: 11.4% [9.3-14.0], I2 = 96.3; ≥3: 6.0% [4.2-8.4], I2 = 97.7). Depression (16.45% [12.96-20.88], I2 = 98.3) was the most prevalent comorbidity reported, followed by hypertension (10.16% [8.61-11.98], I2 = 93.2). Heterogeneity was high across trials. Older age and female participants were associated with increased number of comorbidities. Older individuals and male participants had a higher prevalence of hyperlipidemia, while older individuals and female participants had a higher prevalence of depression and anxiety. Individuals with comorbidities are included in clinical trials, although they may still be underrepresented compared with the general MS population. Given the comorbidity prevalence in the trial populations and studies suggesting an association of comorbidities with disease activity, comorbidity may influence outcomes in clinical trials.

Attention Deficit/Hyperactivity Disorder in Children with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurological autoimmune disease; pediatric-onset multiple sclerosis (POMS) represents 5% to 10% of total MS population. Children with POMS may experience attention difficulties due to the disease's impact on the central nervous system. However, little is known regarding Attention Deficit Hyperactivity Disorder (ADHD) in POMS, and its relation to cognitive performance. A retrospective case review was conducted using medical records of 66 children and adolescent patients diagnosed with POMS between 2012 and 2021 in a MS center of a tertiary medical center. All patients had undergone routine clinical neurological examinations and had been assessed for a diagnosis of ADHD by a department pediatric neurologist. In addition, sociodemographic data, disease-related variables, and cognitive performance were collected. Of the 66 patients, 31 (47%) had a diagnosis of ADHD; 29 (44%) had cognitive impairment. Moreover, we identified four different profiles of POMS: those with only ADHD (17, 26%); only cognitive impairment (15, 23%), ADHD and cognitive impairment (14, 21%), and only POMS (20, 30%). A significant difference in disease duration was found among the four profiles [F(3,65) = 8.17, p < .001, η² = 0.29], indicating that patients with ADHD and cognitive impairment were characterized by longer disease duration. ADHD may be prominently involved in POMS, even during the early stages of the disease and early diagnosis is crucial in order to provide appropriate interventions and support.

The Association of miRNA-146a Gene Variation and Multiple Sclerosis in The Iranian Population.

Multiple sclerosis (MS) is a complex human autoimmune-type inflammatory disease of the central nervous system (CNS). MicroRNA-146a (miR-146a) belongs to an endogenous and non-coding RNA family with 18-22 nucleotides long, which modulates the innate and adaptive immune response. Our study aimed to investigate a possible association between rs2910164 and rs2431697 polymorphisms of the miR-146a gene and multiple sclerosis in the Iranian population. A total of 60 MS cases and 100 controls were recruited. Single nucleotide polymorphism (SNP) rs2431697 was genotyped by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SNP rs2910164 was genotyped by using Tetra-primer ARMS-PCR. Statistical Analysis conducted by the chi-squared test utilizing SPSS version 21.0 Software. The Hardy-Weinberg equilibrium assumption was evaluated. The results of the present study suggest the miR-146a gene rs2431697 polymorphism is not associated with multiple sclerosis. However, there is a significant relationship between polymorphism rs2910164 of the miR-146a gene and multiple sclerosis in the population studied (P = 0.012). Our data provide evidence that the miR-146a gene may be involved in creating the susceptibility to MS in the Iranian population.

What Clinical Parameter Strongly Associates White Matter Tract Alterations in a Multiple Sclerosis Population With Voiding Dysfunction? A Prospective Exploratory Study

Purpose: To correlate clinical and urodynamics parameters in patients with multiple sclerosis (MS) presenting lower urinary tract symptoms (LUTS) with both Expanded Disability Status Scale (EDSS) and changes in white matter integrity as seen on diffusion tensor images (DTIs). LUTS worsen throughout MS, as does lesion burden. We investigated which symptoms correlated best with structural changes in the white matter structure. Materials and Methods: Ten adult women &gt;18 years were recruited with stable MS for ≥ 3 months and voiding dysfunction defined as % of post-void residual/bladder volume (%PVR/BV) &gt; 20%. Patients participated in a clinical Urodynamic Study and completed several questionnaires (ie, Hamilton Rating Scale, American Urologic Association Symptom Score, NBS-QoL). DTI images were acquired using a 7-Tesla Siemens MAGNETOM Terra MRI scanner. DTI maps were constructed, and individual patients were coregistered with the International Consortium of Brain Mapping-DTI-81 white matter atlas to extract fractional anisotropy and mean diffusivity (MD). Pearson's correlation test was performed between each white matter tracts (WMT) and clinical parameters and between clinical parameters and the EDSS score as well. P &lt; 0.05 was considered significant. Results: Of the clinical parameters, %PVR/BV obtained from the average of multiple un-instrumented uroflow assessments had significant correlations with the greatest number of WMTs. Furthermore, we observed that in all recorded clinical parameters, %PVR/BV was the only significant parameter correlated with the EDSS score. Conclusion: This study demonstrates that %PVR/BV can be used as an objective parameter to gauge WMT changes and disease progression in patients with MS. Future studies are needed to refine this model.

Editorial Comment: What Clinical Parameter Strongly Associates White Matter Tract Alterations in a Multiple Sclerosis Population with Voiding Dysfunction? A Prospective Pilot Study

Editorial Comment: What Clinical Parameter Strongly Associates White Matter Tract Alterations in a Multiple Sclerosis Population with Voiding Dysfunction? A Prospective Pilot Study

Disease-modifying therapy initiation patterns in multiple sclerosis in three large MS populations.

Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs. To investigate and compare the time to first DMT and its association with sociodemographic and clinical variables after MS diagnosis in three large MS registries. This observational study was conducted using data from the German MS Registry (GMSR), the North American Research Committee on MS Registry (NARCOMS, US data only), and the United Kingdom MS Registry (UKMSR, both self- and clinician-reported). Data from relapsing people with MS (PwMS), with a diagnosis of MS between 2014 and 2019, and available DMT and disability status were pooled using a meta-analytic approach. A total of 5395 PwMS were included in the analysis (GMSR: n = 2658; NARCOMS: n = 447; UKMSR: n = 2290). Kaplan-Meier estimates for the time to first DMT [median months (95% CI)] were 2.0 (1.9-2.0), 3.0 (2-4), and 9.0 (7.7-10.6) for GMSR, NARCOMS, and UKMSR, respectively. Pooled multivariable Cox regression demonstrated shorter time to first DMT for PwMS diagnosed after 2017 [1.65 (1.42-1.92), p < 0.01], and longer time to DMT when a higher-efficacy DMT was selected (0.69 (0.54-0.90), p < 0.0001]. Time to DMT initiation differs across the populations studied, indicating that barriers may exist in early access to DMT, particularly in the United Kingdom. However, a consistent decrease in time to DMT initiation was noted since 2017 across all registries. Further studies are warranted comparing the effects of time to DMT and time to higher-efficacy DMT on long-term outcome.

Comorbidity in the multiple sclerosis and neuromyelitis optica spectrum disorders population: findings from an underserved, low income country, Zambia

Background: Comorbidities are common in multiple sclerosis (MS); little is known in neuromyelitis optica spectrum disorders (NMOSD) or outside high-income regions.Objective: Compare comorbidities in MS/NMOSD patients, Zambia.Methods: Comorbidities were compared for MS/NMOSD patients from Zambia's University Teaching Hospital using logistic regression.Results: Thirty-three were included (MS/NMOSD:17/16); 22 (67 %) females, mean age=35.6-years. Fifteen (46 %) had any comorbidity [MS/NMOSD:11/4], 14 physical (MS/NMOSD:10/4) and 6 psychiatric comorbidity (MS/NMOSD:5/1). Odds of any/any physical comorbidity was higher in MS versus NMOSD (age-adjusted odds ratio[aOR]=6.9;95 %CI:1.4–34.7,p=0.020/aOR=5.6;95 %:1.1–28.0,p=0.037).Conclusions: Physical comorbidity affected >2-in-5 MS/NMOSD patients and psychiatric disorders ∼1-in-5. Odds of any/any physical comorbidity were >five-fold higher in MS versus NMOSD.

A mechanistic insight into sources of error of visual working memory in multiple sclerosis

Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, MGL were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM deficit in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) was responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.

A mechanistic insight into sources of error of visual working memory in multiple sclerosis.

Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). However, recent observations based on the continuous reproduction paradigms have shown that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. Moreover, continuous reproduction paradigms allow for assessing the distribution of error in recalling information, providing new insights into the organization of the WM system. Hence, by utilizing two continuous reproduction paradigms, memory-guided localization (MGL) and analog recall task with sequential presentation, we investigated WM dysfunction in MS. Our results demonstrated an overall increase in recall error and decreased recall precision in MS. While sequential paradigms were better in distinguishing healthy control from relapsing-remitting MS, MGL were more accurate in discriminating MS subtypes (relapsing-remitting from secondary progressive), providing evidence about the underlying mechanisms of WM deficit in progressive states of the disease. Furthermore, computational modeling of the results from the sequential paradigm determined that imprecision in decoding information and swap error (mistakenly reporting the feature of other presented items) was responsible for WM dysfunction in MS. Overall, this study offered a sensitive measure for assessing WM deficit and provided new insight into the organization of the WM system in MS population.

The association between multiple sclerosis and migraine: A meta-analysis.

Multiple sclerosis (MS) is a chronic progressive condition marked by the deterioration of myelin and impairment of neurological function. The global prevalence of MS is approximately 2.2 million. Migraines are common in MS patients, with inconclusive data on their relationship. Our systematic review aimed to assess the prevalence and odds of migraine in pwMS and investigate the potential factors that may influence these associations. Through an extensive search and meticulous study selection, we identified pertinent literature investigating the occurrence and odds of migraines among pwMS. Additionally, we explored the comparative risk of migraines in MS patients compared to healthy controls. Data were extracted, including publication details, diagnostic criteria, and migraine prevalence in MS patients. A total of 35 studies were included, involving 279,620 pwMS and 279,603 healthy controls. The overall prevalence of migraine in pwMS was 0.24 (95% CI: 0.21-0.28). Subgroup analyses and meta-regression were conducted to investigate the potential impact of various factors on the relationship between migraine and MS. These factors included age, duration of MS, study design, and the Expanded Disability Status Scale (EDSS), migraine diagnosis method, study design, publication year of the study, country and continent of the study population. The results of these analyses revealed no significant influence of these factors on the relationship between migraine and MS. The meta-analysis indicated that pwMS had significantly increased odds of having migraine compared to healthy controls (OR=1.96, 95% CI: 1.20-3.20). Sensitivity analyses supported the robustness of the findings. Our study highlights that approximately 24% of pwMS experience migraine. The method of diagnosis significantly affects the reported prevalence, with questionnaires yielding higher rates. Furthermore, pwMS have a 1.96-fold increased odds of having migraine compared to healthy individuals. These findings emphasize the importance of further research and interventions to address the significant burden of migraine in the MS population.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up.

Tremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. To report a large and retrospective study of thalamic DBS in MS tremor. We conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. One hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. We described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

29 Associations Between Social Support and Cognitive Performance Among Persons with MS

Objective: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.Participants and Methods: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).Results: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 &gt; 0.05). None of the social support measures were significantly associated with the verbal memory and verbal fluency/simple attention component scores.Conclusions: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.

"No association between disease modifying treatment and fatigue in multiple sclerosis".

Fatigue affects 60-90% of people with multiple sclerosis (MS). It reduces quality of life and the ability to work. The cause of fatigue in MS remains unknown. Several disease-modifying treatments (DMTs) slow the disease process in relapsing MS by suppressing neuroinflammation. We aimed to investigate if treatment with a DMT is associated with lower rates of fatigue. In this cross-sectional study of the MS population in three counties in Norway, we used the Fatigue Scale for Motor and Cognitive Functions (FSMC) and the Hospital Anxiety and Depression Scale (HADS) to assess patient-reported fatigue, anxiety and depression. Clinical data were retrieved from the electronic patient record system. We categorized DMTs as high-efficacy therapy or moderate-efficacy therapy. High-efficacy drugs included fingolimod, natalizumab, ocrelizumab, rituximab, alemtuzumab, daclizumab, and autologous hematopoietic stem cell transplantation. Moderate-efficacy drugs included interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. We included persons with relapsing MS only. Of 1142 patients, 80% had fatigue. Fifty-six percent of the patients were on DMTs (25% on moderate-efficacy treatment and 30% on high-efficacy treatment), 18% had discontinued treatment and 26% had never received any DMT. Sex, level of disability as measured by the Multiple Sclerosis Severity Score, anxiety and depression were independently associated with fatigue. Moderate-efficacy treatment was associated with less fatigue, but not after adjustment for other variables. There was no association between high-efficacy treatment and fatigue. We found no independent relationship between the use of disease-modifying treatment and fatigue in MS.

Age-related differences in the severity of sexual dysfunction symptoms and psychological distress in individuals with multiple sclerosis.

Sexual dysfunction (SD) is a common symptom for many with multiple sclerosis (MS). However, SD research in general appears to often overlook young adults within their samples, which can be a major issue for better understanding and treatment for the MS population. Few studies have compared age-related differences in distress in response to physical disability. Research has also found that many people diagnosed with MS do not discuss any SD struggles with their providers. The present study hopes to see whether age-related differences exist in the reporting of the levels of primary, secondary, and tertiary SD, as defined by subscale scores of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19), and amount of distress, as defined by the 12-Item Short Form Health Survey (SF-12)'s Mental Component Summary (MCS-12). Additionally, we hope to determine if there are any age-related or sex-related differences in help-seeking behaviors for SD. Study participants were recruited from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Participants completed the MSISQ-19, SF-12, and Patient Determined Disease Steps (PDDS), provided demographic information, and responded if they received medical or psychological treatment for SD. Study participants were 5815 respondents (Mage=51 years, SD=9.63, 75% female, 30% having attained a high school diploma, 35% scoring "advanced disability" on the PDDS). Young adult (19-39 years), middle adult (40-64 years), and mature adult (65-older) were compared on SD. Linear mixed effects modeling revealed that the MSISQ-19 subscale scores were significantly predicted by secondary SD (t=2.48, p<.13). Young adult participants had the lowest primary SD (M=13.87, 95% CI [13.13, 14.61]) when compared to mature adult (M=14.12, 95% CI [13.27, 14.97]) and middle adult participants (M=14.44, 95% CI [14.21, 14.66]), though none were statistically significant. Mature adults had the lowest secondary SD (M=16.50, 95% CI [15.65, 17.35]), a statistically significant difference from the middle adults (M=18.20, 95% CI [17.97, 18.42]) and young adults (M=18.91, 95% CI [18.17, 19.65]). Mature adults had the lowest tertiary symptoms (M=10.12, 95% CI [9.27, 10.96]), followed by young adults (M=12.23, 95% CI [11.48, 12.97]), and middle adults (M=11.65, 95% CI [11.43, 11.88]), though none were statistically significant. Hierarchical multiple regressions found that age had the most significant impact on SD. When SF-12 MCS-12 was added, linear mixed effects did not reveal any statistically significant results between the age groups and SD levels. In contrast, hierarchical multiple regressions found that SF-12 MCS-12 scores had the most significant impact on SD. There were significant age-related and sex-related differences in help-seeking behaviors in those who sought psychological counseling as opposed to medical treatment for SD. Our study has highlighted the importance of clinicians assessing for SD and psychological distress within their patients and to consider potential differences in symptom presentations of age groups to better address their unique needs.

Cancer risk, disease-modifying therapy, and age in multiple sclerosis: A retrospective population-based cohort study

BackgroundLong-term population-based safety studies are needed to investigate cancer outcomes in people with multiple sclerosis (MS) treated with modern disease-modifying therapy (DMT). ObjectivesTo investigate if exposure to DMT increases the risk of invasive cancer in MS. MethodsWe used population-based administrative health data from Alberta, Canada between 2008 and 2018. DMT exposure was defined in two ways: first as exposure to any DMT, and second by DMT type (modulating, sequestering, depleting). Study outcome was time to first diagnosis of invasive cancer. Cancer risk was compared to the general population using standardized incidence ratios (SIRs) and to the unexposed MS cases using hazard ratios (HRs). ResultsThe analysis included 14,313 MS cases: 5,801 (40.5 %) were exposed to DMT. Median (interquartile range) follow-up was 8.4 (4.3, 10.4) years. Compared to the general population, there was no difference in cancer risk for the overall MS population (SIR: 0.94, 95 % confidence interval [CI]: 0.87, 1.02) or the DMT-exposed MS cases (SIR: 0.89; 95 % CI: 0.75, 1.05). Compared to unexposed MS cases, we found an interaction with age for exposure to any DMT (p = 0.001) and modulating DMT (p = 0.001), indicating that a difference in the risk of cancer associated with DMT depends on age. Cancer risk was not associated with exposure to sequestering DMT (HR: 1.28, 95 % CI: 0.78, 2.08) or depleting DMT (HR: 2.29, 95 % CI: 0.86, 6.14). ConclusionsCancer risk for MS patients was similar to the general population. In the MS population, the age-dependent effect of DMT for cancer risk suggests a higher risk of cancer with age 62 or older and a protective effect at younger age. Further investigation is required to clarify whether the interaction between DMT exposure and age is a causal effect.

Multiple sclerosis and bowel symptoms: Frequency and barriers to their management.

The frequency of bowel symptoms (BSs) is still a matter for debate in multiple sclerosis (MS) patients. However, BSs have been shown to cause significant distress. Our study aimed to (i) investigate the frequency of BSs, particularly those that are not managed, (ii) identify potential predictors for help-seeking care for patients with BSs, and (iii) evaluate the ability of the Neurogenic Bowel Dysfunction (NBD) score to screen for BSs. Three hundred sixty-nine MS patients completed a cross-sectional demographic and clinical survey of MS and BSs and their management. BSs were reported by 47.7% of MS patients. Eighty-eight percent of MS patients had a very minor-minor Neurogenic Bowel Disorder (NBD) score and 12% had a moderate-severe NBD score. Forty-one percent of patients did not report their BS to a healthcare provider, mainly because they preferred not to talk about the problem. BS duration was the only significant predictor of help-seeking for BS management. Female sex, visual impairment, a digestive history, and longer MS duration were good predictors of BSs. Patients with BSs (86%) were correctly identified with an NBD score >2. BSs are under-detected in MS populations. This is partially related to non-declaration by patients. Targeting BSs using the NBD score is a good way to increase reporting.