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Effects of Sensory Interventions on Fatigue in People With Multiple Sclerosis: A Systematic Review

Vaccine literacy (VL) is an individual's ability to obtain, understand, and use information related to vaccines to make informed health decisions. This concept is strongly correlated with vaccine hesitancy, which is common among people with multiple sclerosis (MS). The study aims to assess VL in people with MS.

A cross-sectional study was conducted from April 2023 to September 2023 at the MS Policlinic of Bari. A structured questionnaire of 10 questions from the European Health Literacy Survey Consortium covered vaccination behavior, beliefs, trust, and perceived risks, and 4 questions from the Health Literacy Population Survey 2019-2021 Vaccine (HLS19-VAC) tool covered access, understanding, evaluation, and application of vaccination information.

There were 157 respondents (mean age, 34.77 years; 86.4% women; 90.4% with relapsing-remitting MS). Fewer than half (41.4%) had a high school diploma, 73.9% were employed, and 93% were satisfied with nursing care. The HLS19-VAC questionnaire results revealed high vaccination adherence (99%) but mixed beliefs about vaccine safety and efficacy. Trust in vaccines was generally high, though VL scores were lower. Significant correlations were found between VL and education level.

Findings from this study reveal high vaccination adherence and trust among people with MS, but VL remains low, leading to misconceptions and hesitancy. Interventions tailored to age and education level offered by health care providers, especially MS nurses, are essential to improve VL and reduce vaccine hesitancy.

The authors thank Dr Agnese Renna for data collection.

 All authors declare no conflicts of interest.

Vaccine literacy (VL) refers to obtaining, understanding, and effectively using vaccine-related information to make informed health care decisions.

 This includes evaluating information sources, understanding vaccine risks and benefits, and accessing health care services to receive vaccines.

 High levels of VL encourage proactive health behaviors essential for enhancing individual and public health outcomes. Notably, VL directly affects vaccination rates within communities.

 For individuals with chronic diseases such as multiple sclerosis (MS), VL plays a critical role due to their increased vulnerability to infections.

 However, despite widespread immunization programs, vaccine hesitancy remains a significant barrier among the general population

 Vaccine hesitancy is characterized by a delay in vaccination or a refusal to receive a vaccination despite available services.

 The World Health Organization identifies vaccine hesitancy as a top global health threat, highlighting the importance of addressing VL to combat this issue.

Low VL is linked to reduced adherence to preventive measures, including vaccination, due to the complexity of medical information as well as the decision-making processes.

 Technological advancements and expanded access to information have increased the need for reliable medical guidance, especially among individuals with chronic diseases.

 In MS, undervaccination is often due to misinformation, concerns about vaccine interactions with treatments, and false contraindications.

 As MS disease-modifying therapies (DMTs) suppress immune responses, people with MS are at increased risk of infections, making vaccination crucial despite any potential concerns.

 Despite the well-documented benefits of vaccination, hesitancy remains a significant issue among people with MS: Findings from studies indicate that 10% to 20% of them are hesitant to receive a vaccination, often due to knowledge gaps and insufficient promotion by health care workers.

 In Italy, these rates are even higher, with influenza vaccination hesitancy reaching 41.8%.

 This reluctance poses a challenge, as vaccination is particularly crucial for people with MS who may face heightened risks from infections. However, initiatives aimed at promoting vaccination in this population have had limited success.

 The lack of impact underscores the need for more effective strategies, which could include tailored education campaigns and improved communication between health care providers and patients. One promising avenue involves assessing VL levels among people with MS.

Understanding VL, especially in the most vulnerable groups, can provide valuable insights into the barriers faced and inform the development of targeted interventions to address these obstacles.

 By identifying and addressing specific gaps in knowledge and perceptions, health care systems can implement more effective strategies to encourage vaccination among people with MS. Nurses, who are often in close contact with people with MS, are uniquely positioned to assess and enhance VL, playing a critical role in supporting informed decision-making.

 Despite this potential, the extent to which VL has been specifically assessed and addressed in the MS population remains largely unexplored. Current evidence reveals a significant gap in understanding how vaccination-related knowledge, attitudes, and perceptions influence decision-making among people with MS. Although findings from studies have highlighted high levels of vaccine hesitancy in this group,

 little is known about the specific informational needs or misconceptions that contribute to this reluctance. For instance, concerns about vaccine safety, particularly regarding potential interactions with DMTs, may play a role, but data in this area are scarce. Similarly, the influence of health care providers, including nurses, on vaccination behavior has not been thoroughly investigated in the context of people with MS.

Addressing these knowledge gaps is essential, as people with MS often require tailored educational approaches that account for their unique medical conditions and psychological needs. Nurses, given their trusted and frequent interactions with patients, are well suited to assess VL levels and identify barriers to vaccination. By doing so, they can implement targeted interventions to dispel misconceptions, empower patients with accurate information, and ultimately support informed decision-making. No studies have specifically evaluated VL in people with MS, highlighting an urgent need for research to guide effective vaccination promotion strategies. Understanding VL levels in this population could significantly improve vaccination coverage and reduce infection rates, particularly among those undergoing immunosuppressive therapies.

 The development of interventions based on VL assessments could play a pivotal role in overcoming vaccine hesitancy, improving health outcomes, and enhancing the overall care of people with MS. The goal of this study was to assess the VL level in people with MS and examine its correlation with key sociodemographic and clinical variables.

A cross-sectional monocenter study was conducted between April 2023 and September 2023 at MS Center, University of Bari, Bari, Italy. We used the STrengthering the Reporting of OBservational Studies in Epidemiology guidelines.

 The sample size calculation was based on the data analyses performed (Mann-Whitney 

 value of .05 and a power of 0.80, it was expected to be at least 132 participants.

Patients were recruited based on a purposive sampling strategy, ensuring that all participants met the following inclusion criteria: diagnosis of MS, optimal cognitive abilities, and patient consent to the treatment of their personal data for participation in the experimental study. Exclusion criteria were lack of confirmed MS diagnosis or presence of other demyelinating diseases; severe psychiatric disorders, cognitive impairment, or comorbidities that would interfere with the study; recent experimental vaccination treatments or changes in DMTs in the past 3 to 6 months; pregnancy, breastfeeding, or substance abuse; and an inability to provide informed consent or comply with study requirements. For the data collection, a research nurse administered a structured questionnaire to patients during their routine visits at the Bari MS center. All the participant responses were entered directly into a computer platform with a specific form for data entry. The clinical and demographic data relevant to our study were extracted from the Italian Multiple Sclerosis Register (IMSR).

This study was conducted following the ethical principles of the Declaration of Helsinki and used clinical data from patients extracted from the IMSR (

). It received approval from the ethical committee of the Azienda Ospedaliera Universitaria Policlinico di Bari (Study REGISTRO SM001). Written informed consent was obtained from all participants prior to their inclusion in the study in accordance with ethical guidelines and institutional requirements.

All variables were collected from the IMSR database, including sociodemographic (sex, age, education) and clinical data (patient comorbidities, MS phenotype, age of onset, disease duration, ongoing DMTs, and Expanded Disability Status Scale [EDSS] scores). A multiple-choice questionnaire of 5 sections with 10 questions each was used to collect data about vaccine determinants. Derived from the European Health Literacy Survey Consortium, it asked about respondents’ (1) vaccination behavior over the past 5 years, (2) vaccine beliefs, (3) trust in vaccines, and (4) perceived risks of vaccination. The last component of the questionnaire was the HLS19-Vaccination (HLS19-VAC), a 4-question test to assess VL in the general population. The Italian version of HLS19-VAC was validated in an Italian study and in 11 other countries on large cohorts of patients using different data collection methods.

 The test evaluates 4 aspects of the management of vaccine information, with an item for each point regarding immunization information: access/obtain, comprehend, evaluate/judge, and apply/utilize. Respondents choose from a 4-point Likert scale of 

 (1). The HLS19-VAC score is calculated as a percentage of items answered as 

 and can thus be 0, 25, 50, 75, or 100. High scores correlate with high VL.

 At the beginning of the questionnaire, 2 items designed to investigate patient satisfaction with nursing care were included.

Clinical and demographic characteristics were calculated as mean (SD) for continuous variables and as frequencies (proportions) for categorical. The association of some variables (sex, education, age, EDSS, and VL score) was evaluated by Kruskal-Wallis test, Mann-Whitney 

 test, and Spearman ρ. Analysis was performed using IBM SPSS, with a statistical significance level set at a 

A total of 157 people diagnosed with MS were enrolled in the study and completed the questionnaire. Of these, 90.4% had relapsing-remitting MS, 86.4% were women, mean age was 34.77 (± 9.55) years, 54.1% were aged 30 to 49 years, and 40.1% held a bachelor's degree. Most patients were employed (73.9%) and received their diagnosis between the ages of 10 and 29 years (65.6%). The median EDSS score was 2 (IQR, 2-3). The most prescribed DMTs were dimethyl fumarate (23.6%) and natalizumab (17.2%). Additionally, 93% of participants reported being satisfied with nursing care and 82.8% felt comfortable discussing vaccination with their MS nurses (

Regarding vaccination behavior, 99% of participants or their family members had received vaccinations within the past 5 years. Opinions on vaccine beliefs were mixed: A total of 36% disagreed with the notion that vaccines weaken the immune system, whereas 33% agreed. Similarly, 43% rejected the idea that vaccines cause the diseases they aim to prevent whereas 27% agreed and 30% were undecided. A significant majority (83.5%) agreed or strongly agreed that vaccinations were important to protect themselves and their families, whereas 75.8% believed vaccines were safe and 80.3% found them effective. Furthermore, 75.8% considered vaccination compatible with their religious beliefs and 86.6% believed it plays a crucial role in preventing the spread of serious diseases. Finally, 63.1% of respondents perceived a high or very high risk of developing a disease if unvaccinated (

The median (IQR) score of VL was 75 (range, 50-100). The majority of respondents (70.0%) found it easy or very easy to locate vaccination information for themselves and their families. More than half of the participants (55.4%) found it easy or very easy to understand why they and their families need to be vaccinated. A significant portion (67.5%) considered it easy or very easy to understand which vaccinations their families require. An equal proportion (70.0%) found it easy or very easy to decide whether to receive the influenza vaccine (

VL and Associations With Gender, Education, Age, and EDSS 

 test was used to compare the VL scores between male and female participants. The results indicated no significant difference in VL scores between the 2 groups: The mean rank for women (n = 134) was 79.04, and it was 78.74 for men (n = 23). The Mann-Whitney 

 value was 1.535, with a Wilcoxon W of 1.811 and a 

 value was .975. The Kruskal-Wallis test was used to assess differences in VL scores among 3 age groups: 18 to 29 years (n = 56), 30 to 49 years (n = 85), and 50 to 70 years (n = 16). The mean ranks for these groups were 72.75, 79.47, and 98.38, respectively. The results indicated no statistically significant differences between the age groups (H = 4.252; 

 = .119). The relationship between education level and VL scores shows that the mean ranks across different education levels were middle school at 53.35, high school at 74.03, bachelor's degree at 89.01, and postgraduate at 80.63. The test results indicated a significant difference between the groups (H = 8.550; 

). Spearman ρ correlation analysis between the VL score and EDSS score shows a correlation coefficient of 0.049, indicating a weak and nonsignificant correlation (

This study provides a comprehensive overview of VL, beliefs, and behaviors among people with MS, offering valuable insights into their attitudes toward vaccination and the factors influencing their decision-making processes.

Vaccination Behavior, Beliefs, Trust, Perceived Risks, and VL 

The results of the HLS19-VAC questionnaire highlight a generally positive attitude toward 

 among the participants. The majority reported that they or a family member had been vaccinated in the past 5 years, indicating a high level of adherence to vaccination recommendations.

 This suggests a good baseline acceptance of vaccines, which can be attributed to the significant information and awareness campaigns conducted in response to the COVID-19 pandemic. However, 

 shows a more complex scenario. A substantial proportion of patients in the study have misconceptions regarding the safety and effectiveness of vaccines. A notable percentage of participants believe that vaccines can weaken the immune system, cause the diseases they are meant to protect against, or produce severe adverse effects. These misconceptions can undermine vaccine confidence and may be a barrier to achieving higher vaccination rates in people with MS. Burian and colleagues

 highlighted that concerns about vaccines are widespread among people with MS and necessitate targeted education, especially for those with more severe psychopathological symptoms (anxiety or depression) and those who are generally skeptical of vaccination. Public health campaigns and health care providers (eg, MS nurses) should focus on spreading accurate information about the safety and efficacy of vaccines to address these concerns.

 score was high, indicating that despite some misconceptions, there is strong overall trust in the importance, safety, and effectiveness of vaccines. This trust is crucial for maintaining high vaccination coverage and suggests that efforts to improve VL are likely to have a positive impact.

 of contracting infectious diseases for people with MS who were not vaccinated is high, which aligns with the high trust in vaccines. This perception is an important motivator for vaccination, as individuals who recognize the risks of not vaccinating are more likely to seek out vaccines for themselves and their families. This ease of access and comprehension is critical for informed decision-making and suggests that current communication strategies are effective. However, there is still room for improvement, particularly in making information even more accessible and understandable to address any remaining confusion. 

 had a problematic overall score among the sample, despite results revealing that participants generally find it easy to access and understand information about vaccinations. However, there is more difficulty in understanding the underlying reasons for vaccination. This suggests that although logistical aspects are clear, there is a need for better education on the importance of vaccinations.

The relationships between VL and the sociodemographic and clinical variables provide relevant insights. There is no significant difference in VL scores between male and female participants. This suggests that gender does not significantly influence VL in this sample, which is consistent with findings from other studies showing that VL remains generally stable across genders in many populations.

 No significant differences in VL scores were observed between the 3 age groups (18-29, 30-49, and 50-70 years), although the oldest age group (50-70 years) showed a slightly higher mean rank. This finding suggests that age, in this study population, is not a critical factor influencing VL, which is somewhat unexpected, as findings from previous studies have often indicated lower VL among older populations.

 The lack of statistical significance might reflect the high level of regular health care interactions across age groups, which could mitigate age-related differences in VL. Our study population consists primarily of patients who have regular contact with health care providers due to the high percentage of participants receiving intravenous medication. This regular contact allows them to benefit from educational interventions provided by MS nurses, which are fundamental in building the nurse-patient trust relationship.

 Findings from other studies suggest that lower VL is common among younger people with MS, particularly those without regular contact with health care professionals.

In contrast, educational level was found to have a significant effect on VL scores. Participants with a bachelor's degree had the highest mean ranks, followed by those with postgraduate education, and those with a middle school education had the lowest ranks. This outcome is consistent with existing literature, which consistently highlights the impact of educational attainment on health literacy, including VL.

 Previous evidence shows that individuals with lower education tend to have lower health literacy skills compared with those with higher education.

 Individuals with higher education levels are likely to have better tools for accessing, understanding, and applying health-related information, including information about vaccination.

Tasks that other patients may find relatively simple, such as scheduling vaccinations or understanding vaccine recommendations, can be challenging for people with MS and lower VL to manage,

 so improving VL for this population is essential to enhance their understanding and trust in vaccinations and to reduce the influence of potentially dangerous misinformation. This underscores the need for targeted educational interventions, such as those by MS nurses, to address specific informational needs and concerns.

 The lack of a significant correlation between VL and EDSS score suggests that physical disability did not have a meaningful impact on VL for our study participants. This finding implies that cognitive or educational interventions aimed at improving VL can be effectively applied across different levels of disability without the need for significant adaptation.

This study offers valuable insights into VL and attitudes among people with MS. Educational level plays a crucial role in shaping VL, as higher levels of education are often associated with a better understanding of health information. Therefore, tailoring educational interventions to individuals with lower educational backgrounds is essential to improving VL and vaccine confidence. Regular visits to MS centers can significantly enhance VL. These visits provide patients with frequent opportunities to engage with health care professionals, particularly nurses, who play a key role in educating them and addressing any concerns about vaccinations. This ongoing interaction helps reinforce patients’ understanding of and trust in vaccines.

Our sample size is relatively small, and the study is monocentric, which may limit the generalizability of the findings. In addition, the reliance on self-reported data could introduce bias and the cross-sectional design prevents the assessment of changes over time. Future research should focus on the inclusion of a larger and more diverse population as well as adopt longitudinal approaches to gain a better understanding of VL trends. Finally, the phrasing of the vaccination behavior questions (“Have any of your family members, including you and your children, undergone a vaccination in the past 5 years?” and “Have you, your children, or someone in your family had any vaccinations in the last 5 years?” [

]) could introduce ambiguity, as respondents might answer “yes” even if only their children were vaccinated. This may have contributed to the high reported adherence level despite mixed beliefs about vaccines. Additionally, the questionnaire did not specify the type of vaccine, which could have influenced responses due to varying levels of trust in specific vaccines.

Improving VL is crucial for people with MS to make informed health decisions. Although our study findings highlight a high level of trust in vaccines, they also reveal significant gaps in VL, contributing to misconceptions and vaccine hesitancy. Lower educational attainment, in particular, is associated with inadequate vaccine knowledge and, consequently, lower VL. This at-risk population should be the target of tailored educational interventions, ideally provided by specialized MS nurses, to promote greater vaccine acceptance and improve VL. Future studies should further explore the impact of specific educational strategies on improving VL in people with MS, particularly among those with lower educational levels. Research could also investigate the long-term effects of regular health care interactions, such as those with MS nurses, on sustaining improved VL.

Assessment of Vaccine Literacy in People Affected by Multiple Sclerosis: A Cross-Sectional Study From Italy

 To access the article and evaluation online, go to 

 The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, and other health care providers involved in the management of patients with multiple sclerosis (MS).

Identify the longitudinal patterns of olfactory dysfunction seen in various stages of multiple sclerosis disease course, as described in recent literature to better recognize olfaction as a dynamic, dependent variable of neurodegeneration that correlates with inflammation and clinical markers and may have a future role in recognizing and monitoring disease activity.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Intellisphere, LLC. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This activity was planned by and for the health care team, and learners will receive .5 Interprofessional Continuing Education (IPCE) credit for learning and change.

 The CMSC designates this journal-based activity for a maximum of .5 

. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

 The CMSC designates this enduring material for .5 contact hour of nursing continuing professional development (NCPD) (none in the area of pharmacology).

 It is the policy of the Consortium of Multiple Sclerosis Centers to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated.

, have disclosed no relevant financial relationships. Author 

 has a patent pending for olfactory testing and training methods (AROMA, Affordable Rapid Olfaction Measurement Array). There is no product available for commercial sale. Authors 

Sharon G. Lynch, MD; Lauren L. Todd, BS; Ram Sivakumar, BS; Jennifer H. Diebolt, MD;

 have disclosed no relevant financial relationships.

, CMSC, and Intellisphere, LLC who are in a position to influence content have disclosed no relevant financial relationships. 

 CMSC continuing education director, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships.

Release Date: May 1, 2023; valid for credit through: May 1, 2024.

(1) Review the continuing education information, including learning objectives and author disclosures.

(3) Complete the evaluation, which is available at 

Statements of Credit are awarded upon successful completion of the evaluation. There is no fee to participate in this activity.

 This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Intel-lisphere, LLC do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Intellisphere, LLC.

 Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.

Although studies regarding multiple sclerosis (MS) and olfactory dysfunction (OD) have been previously described and summarized, there is not a sole review of longitudinal studies regarding the matter. This review examines the existing literature investigating MS and its effect on olfaction. In addition, the role of OD in the diagnosis and prognosis of MS is explored.

A scoping review of the literature was performed covering longitudinal studies investigating MS and OD. Systematic searches of PubMed, Google Scholar, Web of Science, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, AgeLine, and MEDLINE were performed using terms that encompassed MS and olfaction. The aim of this review was to build on the existing literature by summarizing only findings that were demonstrated longitudinally.

Of 6938 articles identified from the search, 9 met the inclusion criteria: longitudinal observation of relapsing-remitting or progressive MS. Olfaction was measured and scored using various testing arrays, and these scores were then correlated with a multitude of clinical markers. Across all studies, patients with MS demonstrated increased OD. Longitudinally, 2 contrasting patterns were identified: (1) clinical markers of acute inflammation correlated with an increased odor threshold and (2) clinical markers of neurodegeneration, or progression of disease, correlated with a decreased ability to discriminate and identify odors.

These studies suggest that olfaction is a dynamic, dependent variable of neurodegeneration, correlating with inflammation and clinical markers. This opens the door for future exploration of olfaction’s relationship with MS diagnosis, characterization, and therapeutic response.

 Dr Villwock has a patent pending for olfactory testing and training methods (AROMA, Affordable Rapid Olfaction Measurement Array). The other authors declare no conflicts of interest.

 This manuscript was previously presented as a poster at the Consortium of Multiple Sclerosis Centers Annual Meeting; October 25 to 28, 2021; Orlando, Florida.

Multiple sclerosis (MS) is an autoimmune, neurologic, degenerative disease that is associated with olfactory dysfunction (OD).

 Many sources have investigated the connection between olfaction and MS using metrics such as the University of Pennsylvania Smell Identification Test (UPSIT)

 and the Connecticut Chemosensory Clinical Research Center olfactory test

 to better understand the extent of the deficit. Studies usually compare olfaction in patients with MS vs controls or between patients with MS with different disease durations. Although these studies do connect MS and OD, most do so only via cross-sectional methods. Because MS is a disease with multiple progressive patterns—relapsing-remitting (RRMS), primary progressive, and secondary progressive

—the level of OD can be drastically different over time. For example, patients with early-stage MS can have minimal to no loss of olfactory identification or discrimination.

 Identifying studies that use longitudinal methods of tracking olfaction will not only provide more clarity about the progression of OD but may also reveal a connection between the pattern of OD and various MS biomarkers, such as plaque burden. There may also be a place for olfaction in disease detection and surveillance. Olfactory testing is simple, inexpensive, and can be performed during a normal clinic visit.

 Olfactory monitoring in patients with MS could serve as a useful marker for early intervention, tracking progression, and response to therapy.

This scoping review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. As a scoping review, it was not eligible for registration on PROSPERO, an international prospective register of systematic reviews. The purpose of this scoping review was to evaluate the current literature base rather than to collect and analyze the data from these sources.

Studies were eligible if they were longitudinal in design with the primary discussion involving OD and diagnosis of MS (

Data extraction was performed by 2 authors (L.L.T., R.S.) using the databases and search terms listed in 

. A shared EndNote database was used to manage the citations. All disagreements were discussed between the 2 authors to arrive at a consensus. Data collected included author, year, journal, title, abstract. After the citations were filtered, they received a full-text review.

The initial search identified 6938 published manuscripts. After duplicates were removed, 5170 manuscripts remained. After titles and abstracts were reviewed, 9 studies met the inclusion criteria and underwent full-text review. The 9 studies observed patients with MS at varying stages over a longitudinal time frame, from 24 weeks to 10 years. Olfactory function was measured in 6 studies using the Sniffin’ Sticks protocol, in 1 study using the UPSIT, and in 1 study using the Brief Smell Identification Test. A ninth study monitored brain activity during olfaction to measure function. Specific study qualities are listed in 

. Note that of the 9 selected studies, the 5 authored by Bsteh included patients from a single study group.

Many of the studies correlated these results with clinical markers such as Expanded Disability Status Scale score, serum neurofilament light chain (sNfL) level, disease duration, and death, which are presented in 

 exhibited lower scores in all measures of olfaction/olfactory function (threshold, discrimination, and identification) at every point compared with controls. The difference between discrimination (−0.5; IQR, −1.0, 0.0; 

 = .43) and identification (−1.0; IQR, −1.5, −0.5; 

 = .002) scores from baseline to year 3 showed significant decay. Threshold scores did not decline with increased duration of disease. The evolution of scores between patients and controls is presented in the 

Two studies used neurologic imaging to investigate olfaction.

 In both instances, olfaction was consistently impaired in patients with a more severe degree of change on imaging. Specific findings are listed in 

. Of note, threshold scores were not affected by changes seen on MRI.

Brain activity relating to olfaction was measured using evoked potentials (olfactory event-related potentials [OERPs]) in individuals with disease vs controls.

, a blunted degree of brain activity at baseline was predictive of a higher number of relapses and furthered disability in those with RRMS. Only 1 group of patients with RRMS had stable, albeit decreased, levels of olfaction over the course of 3 years.

Two studies of individuals with only RRMS looked at markers of acute inflammation, presence of acute relapse, and increased retinal inner nuclear layer thickness to track disease activity against olfaction.

 Both inflammatory markers dynamically correlated with threshold score (

Another clinical marker—sNfL level, a marker of axonal injury—measured higher in individuals with RRMS than in controls. Those with a sustained increase in sNfL measurements displayed a significantly steeper decline in discrimination and identification scores from baseline.

Only 1 study investigated olfaction in people with progressive MS using degree of disability and length of life.

 A more severe loss of olfaction correlated with increased disability over time, as measured using the Multiple Sclerosis Severity Score and the Age-Related Multiple Sclerosis Severity Score. Impaired baseline olfaction scores were also correlated with higher rates of death in those with progressive MS after 10 years (

This scoping review sought to identify, review, and interpret the emerging literature on the longitudinal implications of MS on olfaction. A previous meta-analysis described the association between MS and OD with a pooled prevalence of 27.2%.

 Although beneficial, cross-sectional studies are limited to illustrating a snapshot of olfaction in an unstable disease course. A need for larger, longitudinal studies to delineate this relationship led to a recent increase in prospective studies. This review included 9 studies, with 8 occurring in the past 5 years, that measured olfaction in people with MS at multiple points in time.

Two main patterns were identified from the literature: (1) Clinical markers of short-term inflammation, as measured by the presence of relapse and thickened retinal nerve fiber layer, correlated most with an increased odor threshold in people with MS and, in contrast, (2) clinical markers of neurodegeneration, or axonal injury as measured by the sNfL level, correlated most with a decreased ability to discriminate and identify odors. Table 1 summarizes these findings.

Odor threshold has been used in multiple validated olfactory tests, such as Sniffin’ Sticks.

 To test threshold, butanol is presented to subjects at varying dilutions, with higher scores indicating identification at lower concentrations. The relationship between decreased odor threshold scores and increased inflammatory processes in people with acute, early-stage MS has been demonstrated in cross-sectional research.

 A similar correlation was supported in the selected longitudinal studies

; however, the longitudinal findings suggest that threshold may play a more fluid role in early disease. The decline and subsequent improvement of threshold scores mirrored that of acute relapse with gradual incomplete recovery. Other clinical markers of relapse and inflammation, such as development of plaques on MRI and inner nuclear layer thickness, also correlated with the threshold’s fluctuation.

 Because odor threshold seems to follow the relapsing and remitting nature of disease symptoms, it could potentially be used to monitor occurrence of relapse.

Akin to odor threshold, discrimination and identification are commonly used in olfactory testing, with identification, such as the UPSIT,

 being included by most testing arrays used in the selected studies. Cross-sectionally, lower discrimination and identification scores have been correlated with lower Expanded Disability Status Scale and quality of life scores, as well as higher plaque burden.

 By viewing these qualities of olfaction longitudinally, the reviewed studies demonstrated a correlation between disease progression and decreased discrimination and identification scores. Disease progression was denoted in the reviewed studies through gray matter atrophy and a sustained increase in sNfL level, indicating axonal injury.

Discrimination and identification are important components in what has previously been described as an odor object. Odor objects are created in the piriform cortex through its direct communication with the olfactory bulb. These objects are unique and allow the brain to both identify and discriminate between specific odors.

 Coincidentally, the piriform cortex lies between the insula and the amygdala, areas where increased demyelination in people with MS is often noted.

This finding suggests that, unlike threshold, decreased discrimination and identification are more permanent changes and may relate to lasting neuronal damage. In addition, the presence of lowered discrimination and identification scores at baseline was associated with worse outcomes at study conclusion, including increased frequency of relapse, greater disability, and a higher risk ratio of death in those with more progressive disease. Discrimination and identification scores may correlate with these biomarkers due to the possible association between odor discrimination and identification and the presence of demyelination in the piriform cortex’s adjacent structures. Future research should investigate this relationship further.

With the predictive value of these scores, there is potential clinical benefit to the early measurement of discrimination, identification, and absence of OERP. In the study by Comi et al,

 patients with a neurologic event and clinical and MRI evidence suggesting the presence of MS were administered interferon beta within 3 months. Early administration of interferon beta correlated with lower rates of acute relapse, decreased plaque burden, and longer time before clinically definite disease.

 The olfaction tests used to measure discrimination, identification, and OERP could serve as an additional test alongside clinical symptoms and MRI to identify those at risk for future disease who could benefit from early treatment. In addition, they could be used to help signal evidence of new breakthrough disease that might require treatment change. These tests have the advantage of being simple, inexpensive, and able to be performed in the course of a normal clinic visit, and their results could help inform the need for more complex or expensive testing.

Note there was not an association between MS course and decline in threshold, discrimination, or identification scores in the 2017 study by Uecker et al.

 These results may have differed from the other studies secondary to a smaller sample size with a lower mean ± SD relapse rate of 0.3 ± 0.5 across 3 years. By mainly observing those with stable disease, they may have been less likely to observe the olfactory changes that we hypothesize to correlate with inflammatory activity and neurodegeneration.

The findings from the studies included in this review reinforce previous findings demonstrated in cross-sectional studies; however, these findings also build on the existing literature and demonstrate longitudinal olfactory patterns in the MS disease process. Although each study bore different results, 2 main patterns were apparent when comparing the data of all studies: (1) Clinical markers of acute inflammation correlated most with an increased odor threshold in people with MS and (2) clinical markers of neurodegeneration, or axonal loss, correlated most with a decreased ability to discriminate and identify odors. These findings suggest that there is a potential clinical benefit to using olfaction in the diagnostic and prognostic journey of this fluctuating, expensive, and challenging disease. Future research of olfaction alongside well-known clinical markers is needed to further understand the patterns discussed in this review and to identify and use olfactory testing as an important clinical marker in people with MS.

Longitudinal Olfactory Patterns in Multiple Sclerosis: A Scoping Review and Implication for Use in Management of Disease

 The target audience for this activity is physicians, advanced practice clinicians, nursing professionals, mental health professionals, social workers, and other health care providers involved in the treatment of people with multiple sclerosis (MS).

1. Describe the role of social support on health overall and the relevant ways that the support of a confidant was found to affect the health of women with MS.

2. Incorporate a simple screening question about the presence
of social support into the evaluation of women with MS, particularly those who are not exhibiting expected responses to care.

In support of improving patient care, this activity has been planned and implemented by the Consortium of Multiple Sclerosis Centers (CMSC) and Intellisphere, LLC. The CMSC is jointly accredited by the Accreditation Council for Continuing Medical Education, the Accreditation Council for Pharmacy Education, and the American Nurses Credentialing Center, to provide continuing education for the health care team.

This activity was planned by and for the health care team, and learners will receive .5 Interprofessional Continuing Education credit for learning and change.

™. Physicians should claim only the credit commensurate with the extent of their participation in the activity

 The CMSC designates this enduring material for .5 contact hour of nursing continuing professional development (none in the area of pharmacology).

 As a Jointly Accredited Organization, the CMSC is approved to offer social work continuing education by the Association of Social Work Boards Approved Continuing Education program. Organizations, not individual courses, are approved under this program. Regulatory boards are the final authority on courses accepted for continuing education credit. Social workers completing this course receive .5 general continuing education credits.

It is the policy of the Consortium of Multiple Sclerosis Centers to mitigate all relevant financial disclosures from planners, faculty, and other persons that can affect the content of this CE activity. For this activity, all relevant disclosures have been mitigated.

, has served as physician planner for this activity. He has disclosed no relevant financial relationships. 

, has disclosed no relevant financial relationships. Authors 

, have disclosed no relevant financial relationships.

, CMSC, and Intellisphere, LLC who are in a position to influence content have disclosed no relevant financial relationships.

, CMSC continuing education director, has served as a planner and reviewer for this activity. She has disclosed no relevant financial relationships.

Release Date: May 1, 2025; Valid for Credit Through: May 1, 2027

This educational activity may contain discussion of published and/or investigational uses of agents that are not approved by the FDA. The CMSC and Intellisphere, LLC do not recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the CMSC or Intellisphere, LLC.

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any medications, diagnostic procedures, or treatments discussed in this publication should not be used by clinicians or other health care professionals without first evaluating their patients’ conditions, considering possible contraindications or risks, reviewing any applicable manufacturer’s product information, and comparing any therapeutic approach with the recommendations of other authorities.

Social support plays a significant role in maintaining one's health and well-being. A perceived or objective lack of close friendships can indicate loneliness and/or limited social support. The present study aimed to examine the impact of having a close friend on the overall health and psychological well-being (PWB) of women with multiple sclerosis (MS).

A prospective national study examining factors associated with unemployment in MS enrolled 160 women. As part of an online survey, participants were asked whether they had someone they could confide in. Group comparisons on measures of health, PWB, quality of life (QOL), social support, and marital/partner satisfaction were made between those who said 

. Regression analyses were also conducted to determine the role of having a confidant and other lifestyle factors related to health, PWB, and QOL.

Approximately 19% of participants reported not having a confidant. These individuals reported worse perceived general, physical, and mental health and more severe depression, anxiety, fatigue, sleep disturbance, and pain. They also reported lower levels of PWB, life satisfaction, social support, and marital/partner satisfaction. Regression analyses revealed that having a confidant was a significant predictor of physical and mental health, PWB, and QOL, even when considering other lifestyle factors.

Results suggest that the simple question 

? may be an important indicator of individuals’ health and well-being. Practitioners should routinely assess patients’ socialization and discuss the importance of social networks and communal activity.

 This work was funded by the National Institutes of Health (NCMRR K23HD069494) and the Robert E. Leet and Clara Guthrie Patterson Trust.

 These findings were presented at the 2023 annual meeting of the National Academy of Neuropsychology, which took place October 25-28 in Philadelphia, PA.

Social connectedness is purported to be a protective or promoting factor of health.

 The relative risks associated with a lack of social integration or social support are as great, if not greater than, as the risks associated with smoking, alcohol use, obesity, and cardiovascular disease (CVD).

 For instance, in 1988, House et al suggested that the evidence supporting social relationships on health was stronger than the role of Type A behavior on CVD and approximated the risk of smoking.

 Two decades later, Holt-Lunstad et al found social support and integration to have large effects in predicting mortality than smoking, alcohol consumption, physical activity, obesity, and CVD risk.

Fatemeh Motaharinezhad, PhD (OT)

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