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Evaluation of Dalfampridine Extended Release 5 and 10 mg in Multiple Sclerosis

The role of resilience on functional outcomes in multiple sclerosis (MS) has been debated. One theorized pathway is that healthy lifestyle behaviors contribute to better functioning capabilities, which resilient individuals with MS tend to engage in more. This study aimed to explore whether resilience might influence functioning in individuals with MS indirectly through specific lifestyle behaviors.

Participants (N = 64) were individuals with MS who completed measures assessing resilience (Multiple Sclerosis Resiliency Scale; MSRS), lifestyle behaviors (Simple Lifestyle Indicator Questionnaire and Alcohol Use Disorders Identification Test), and functional capabilities (PROMIS Physical Function-Short Form 20a; PROMIS-PF). Mediation models were constructed with the MSRS as the independent variable and significant individual lifestyle behaviors as the mediators, and PROMIS-PF as the dependent variable, with demographics and disease-related factors as covariates.

Physical activity was the only lifestyle behavior associated with functioning capabilities (ρ = 0.43, 

 < .001). Resilience had a significant indirect effect on functioning through physical activity (

 = 0.16; 95% CI, 0.04-0.32). Its corresponding direct effect was not significant (

These findings suggest that resilience indirectly influences functioning through engagement in physical activity. The results highlight the important role of resilience in promoting well-being among individuals with MS.

From the Mandell Center for Multiple Sclerosis, Mount Sinai Rehabilitation Hospital, Trinity Health Of New England, Hartford, CT (ESG, LON, HMD); Department of Rehabilitative Medicine (ESG, LON, HMD) and Department of Medical Science (ESG), Frank H. Netter MD School of Medicine at Quinnipiac University, North Haven, CT; Department of Neurology, University of Connecticut School of Medicine, Farmington, CT (ESG); Multiple Sclerosis Center of Excellence West, Veterans Affairs, Seattle, WA (APT); Rehabilitation Care Service, VA Puget Sound Health Care System, Seattle, WA (APT); Department of Rehabilitation Medicine, University of Washington, Seattle, WA (APT); Ferkauf Graduate School of Psychology, Yeshiva University, Bronx, NY (FWF); and Holy Name Medical Center Multiple Sclerosis Center, Teaneck, NJ (FWF). 

Elizabeth S. Gromisch, PhD, 490 Blue Hills Ave, Hartford, CT 06112; 

: elizabeth.gromisch@trinityhealthofne.org

The authors wish to thank Dotty Wakefield, MS, for coding and management of the REDCap data collection; Albert C. Lo, MD, PhD, for his review of the paper; and Jennifer A. Ruiz, PT, DPT, and Thomas Agresta, MD, MBI, for their input on the initial grant.

The views and opinions expressed in this article reflect those of the authors and do not necessarily reflect those of the United States Department of Veterans Affairs.

 The authors have disclosed no conflicts of interest.

 The study was funded by a BestCare grant from St. Francis Hospital and Medical Center. Dr Gromisch is a Harry Weaver Scholar of the National Multiple Sclerosis Society.

In 2020, it was estimated that 2077 people per month were diagnosed with multiple sclerosis (MS) in the United States.

 Several mechanisms can contribute to MS progression, including inflammation, neurodegeneration, and demyelination.

 Individuals can experience several symptoms, including fatigue, mood changes, and impaired mobility, which may increase in severity with greater disease duration.

 Not only do individuals with MS report having more difficulty completing their daily activities, but they report that several of their symptoms contribute to their limitations.

 Many individuals also report that their diagnosis had a negative impact on their emotional well-being, self-esteem, coping ability, and future outlook.

That said, individuals with MS who are resilient exhibit lower psychological distress,

 describing themselves as “thriv[ing]” and “liv[ing] the best life possible,”

 and they report being able to maintain stability in their well-being.

 Resilience in MS is highly driven by psychological factors (eg, self-efficacy and affect).

 Social support and physical well-being indirectly contribute to resilience through the psychological components, acting as barriers or facilitators.

 As resilience has been associated with better gross motor functioning in MS,

 it has raised the question of whether resilience contributes to functional capabilities.

 However, it has also been suggested that lifestyle behaviors, not resilience itself, are the underlying contributors.

The importance of healthy lifestyle behaviors has been well documented in MS. Physical activity, for example, has been associated with higher health-related quality of life (HRQOL)

 A healthy diet has also been positively associated with HRQOL.

 Conversely, unhealthy behaviors (eg, alcohol misuse and smoking) can have negative effects on MS-related disability.

 Resilient individuals with MS tend to engage in more healthy lifestyle behaviors (ie, more physical activity and healthier diet choices).

 The role of lifestyle behaviors was also recognized as a component of MS-related resilience in the development of the MS Resiliency Scale (MSRS).

It can be conceptualized that resilience 

 influences functional capabilities, with that relationship explained by lifestyle behaviors. Theoretically, as resilient individuals have higher self-efficacy and more effective coping strategies,

 this would contribute to their healthy lifestyle behaviors

 and thus lead to better functional outcomes. The rationale for this pathway is supported by social cognitive theory–based interventions for improving physical activity in MS, which show connections between engagement, self-efficacy, and goal setting.

 Not only is self-efficacy a significant factor in resilience among individuals with MS,

 but goal setting is a component of at least 1 MS-specific resilience-building program.

While there is a theoretical basis for this pathway, it has yet to be tested empirically in a mediation model. Furthermore, it is unknown which specific lifestyle behaviors mediate the relationship between resilience and functional capabilities. Therefore, this study aimed to explore whether resilience might 

 influence functioning in individuals with MS through specific lifestyle behaviors.

This study was a planned secondary analysis of a test-retest reliability investigation of the MSRS.

 Participants were individuals with MS who had agreed to be contacted about research at the Joyce D. and Andrew J. Mandell Center for Comprehensive Multiple Sclerosis Care and Neuroscience Research at Trinity Health Of New England. In addition to an MS diagnosis, eligible individuals were between the ages of 18 and 89 years, able to read and respond to questionnaires in English, and had access to both the internet and a valid email address for the electronic surveys. Data from the first time point (n = 64) were used for these analyses. While the sample size determination was based on the parent study’s primary aim,

 a post hoc power analysis conducted for the present analyses suggested that it could detect a large effect in a linear regression with 7 predictors with 92.5% power and a 5% error rate.

The Trinity Health Of New England Institutional Review Board approved all study procedures and data were collected through the University of Connecticut Health Center-hosted REDCap electronic data capture tools.

 Age, sex, race, MS type, and disease duration were extracted from the parent study. The impacts of fatigue, depression, and anxiety, which can influence the relationship between resilience and functioning,

 were evaluated using their respective items on the SymptoMScreen, a 12-item self-reported assessment.

 Participants rated how much their MS has affected each symptom, using a 7-point Likert scale (

not affected at all to total limitation/I’m unable to do most daily activities

). The individual items have been validated against the Performance Scales (fatigue and depression),

 Patient Health Questionnaire-8 (depression),

 and Generalized Anxiety Disorder-7 (anxiety).

 A composite score was created, which had good internal consistency (α = 0.85); higher scores were indicative of greater symptom impact.

Resilience was measured with the Multiple Sclerosis Resiliency Scale (MSRS),

 an MS-specific multidimensional questionnaire that includes psychological, physical, and social risk and protective factors of resilience. For each item, participants rated their level of agreement (

) using a 4-point Likert scale. To reduce the influence of the Physical Activity and Diet subscale, which taps into some lifestyle behaviors, those 3 items were excluded. The modified 22-item version had good internal consistency (α = 0.88), with higher scores indicating greater resilience.

Physical activity engagement, dietary choices, and tobacco use were assessed with the Simple Lifestyle Indicator Questionnaire (SLIQ)

; alcohol consumption was evaluated using the Alcohol Use Disorders Identification Test (AUDIT-C).

 Both measures have been previously used as self-reported lifestyle behavior measures in MS.

 For smoking, participants were categorized as nonsmokers, current smokers, and previous smokers. Higher scores on the SLIQ Physical Activity and Diet subscales indicated more physical activity engagement and healthier dietary choices, respectively, while higher AUDIT-C scores reflected more negative alcohol-related behaviors.

The Patient-Reported Outcomes Measurement Information System Physical Function-Short Form 20a (PROMIS-PF)

 was used to measure functional abilities. Participants rated how much difficulty they experienced completing different activities of daily living and their health-related physical limitations. Raw scores (range, 20-100) were converted to 

 scores (range, 9.2-62.7) using a conversion table, with higher scores indicating better functioning. A score of 50 (SD = 10) is considered average for the general population.

 In the current sample, the PROMIS-PF had strong internal consistency (α = 0.97) and was highly correlated with the Patient-Determined Disease Steps (PDDS; ρ = –0.83, 

Analyses were conducted with IBM SPSS version 26 and there were no missing values. Bivariate analyses were conducted by examining the relationships between the PROMIS-PF, MSRS, and individual lifestyle behaviors. Spearman correlations (ρ) were used for nonnormally distributed variables (SLIQ Physical Activity and AUDIT-C), Pearson correlations (

) for normally distributed variables (SLIQ Diet and MSRS), and analysis of variance (ANOVA) for categorical variables (SLIQ Smoking). If a significant relationship was observed (

 < .05), mediation analyses were run using the Hayes PROCESS modeling tool,

 with the MSRS as the independent variable, individual lifestyle behaviors as the mediator, and PROMIS-PF as the dependent variable. The modified SymptoMScreen, age, sex, MS type, and disease duration were included as covariates based on the literature.

 The mediation analyses generated a total effect for the MSRS, which is the summation of the direct and indirect effects,

 with the parameter estimates in the total effect model equivalent to a linear regression without the mediators. An indirect effect was considered significant if its confidence interval did not cross 0.

 All assumptions for a linear regression were met.

) were, on average, 50.91 years old (SD = 11.12) and had a disease duration of 13 years (IQR = 15.00). The majority were White (81.3%), women (78.1%), and had relapsing-remitting MS (84.4%). Functional capabilities were positively associated with physical activity (ρ = 0.43, 

 = .003). There was not a significant relationship between functioning and alcohol misuse (ρ = 0.15, 

 = .848). In the mediation model, the total effect of resilience on functioning was nonsignificant (

 = .295). Instead, symptom impact and progressive MS were associated with lower capabilities (

). However, resilience had a significant indirect effect on functional capabilities through physical activity (

 = 0.16; 95% CI, 0.04-0.32), whereas its corresponding direct effect on functioning was nonsignificant. 

Of the lifestyle behaviors examined, only physical activity was associated with functional capabilities. Consistent with previous work,

 mood and fatigue, rather than resilience, had a significant direct effect on functioning. This is also true for a diagnosis of progressive MS, which has also been associated with greater functional limitations.

 However, resilience did have a positive, significant indirect effect, with physical activity explaining its relationship with functioning. This is consistent with the hypothesis that higher resilience would be associated with greater physical activity engagement,

 which in turn would be connected to better functional capabilities.

As part of the comprehensive care model for MS, both pharmacological and nonpharmacological treatments are necessary.

 While some individuals may be predisposed, resilience in response to chronic health conditions can be learned over time via intervention.

 As such, fostering resilience may be an approach to promote physical activity engagement and indirectly improve functional capabilities. Despite the benefits of physical activity,

 many individuals with MS do not meet the recommended 150 minutes per week.

 Several physical activity barriers (eg, limited social support, low confidence, and depression)

 could be addressed through a resilience-building intervention focused on increasing coping strategies and support systems.

 Some programs specifically address physical activity engagement.

 However, while improvements in physical HRQOL have been found,

 to date, no study has included physical activity as an outcome. Future studies should investigate whether resilience-building interventions can be used to improve physical activity engagement and, subsequently, functional outcomes in individuals with MS.

Given their effects on MS-related disability,

 it was unexpected that alcohol misuse and smoking were not related to functioning; however, this may be due to less than 5% of participants being either current smokers (n = 3) or having unhealthy alcohol use (n = 2), defined as a score of 5 or above on the AUDIT-C.

 In addition, participants may have made less healthy dietary choices, reducing the strength of the relationship between diet and functional outcomes. Although there was a positive association between diet and resilience (

 = .049), the average diet score was 7.02 (SD = 2.75). Comparatively, resilient older adults with MS had an average score of 9.86 (SD = 3.40) on the same measure, while those with low resilience had an average score of 8.98 (SD = 3.13).

 As such, the relationship between resilience, lifestyle, and functioning should be reexamined in a larger sample with a greater representation of certain behaviors.

The small sample size should also be taken into consideration when interpreting the results of the mediation, as it was only powered to detect large effects with the number of included variables. As such, the finding that resilience does not have a direct effect on functional capabilities should be interpreted with caution and verified in a larger sample. While the model was theoretically based, the data were cross-sectional; thus, causal conclusions cannot be definitively made. Furthermore, it is likely that some of the relationships examined are bidirectional (eg, lower functional capabilities contributing to decreased physical activity engagement). Functional capabilities were also measured via self-report. Although self-report and performance-based functional measures are correlated,

 there is not a perfect agreement. While the depression and anxiety items of the SymptoMScreen have been validated against traditionally used scales,

 the fatigue item has not been validated against measures such as the Modified Fatigue Impact Scale. In addition, most participants were White and had a relapsing form of MS, limiting the generalizability of the results. Finally, as the SLIQ Physical Activity score was used, a closer examination of the type and level of physical activity could not be done. Future research may examine the specific types of physical activity, confirmed objectively with an accelerometer, and their relationships with resilience and functioning.

Evidence suggests that resilience may indirectly contribute to functional capabilities through physical activity engagement. These findings highlight the important role of resilience in promoting well-being in individuals with MS and potential pathways for increasing activity engagement.

Resilience Indirectly Affects Functional Capabilities Through Physical Activity Engagement in Individuals With Multiple Sclerosis

Until the World Health Organization declared an end to COVID-19 as a global health emergency worldwide in 2023, people with multiple sclerosis (MS) were hesitant to get the COVID-19 vaccine. This study aimed to assess the final vaccination status, attitude, and adverse events related to the COVID-19 vaccine among people with MS in Egypt.

A self-administered survey was offered to people with MS who came to the Alexandria University MS Clinic in Egypt between June 2023 and November 2023.

Of 150 surveys completed, 77% of participants were women. Their median age was 35.5 years (range, 19-59 years); their median disease duration was 4 years. Only 81 (54%) participants received a COVID-19 vaccine. Of that 81, 81.5% received 2 doses. The median fear of COVID-19 score (FCV-19S) was 11, and 15.3% had high levels of fear. Worrying about the worsening effect of the vaccine on MS (69.3%) and about the long-term adverse events (AEs) of the vaccines (63.3%) were the most common causes of fear. The only factor that was significantly related to receiving the vaccine was the FCV-19S score (

 = .049). Among those who received the vaccine, fatigue was the most common AE reported in 48%; 5% had a neurological relapse. No other serious AEs occurred.

In this study, almost half of study participants with MS did not receive a COVID-19 vaccination, mainly due to fear. AEs attributed to the vaccine were mild. Implementing educational programs during future pandemics will be necessary to improve the vaccination rates of people with MS.

From the Department of Neurology (EH, SE-B) and the Department of Community Medicine (EHD), School of Medicine (AD [student]), Alexandria University, Alexandria, Egypt. 

Eman Hamdy, MD, PhD, 17 Champollion Street, Al-Azarrita, Al-Massalah Bab Sharq, Alexandria Governorate, Alexandria, Egypt; 

Even following the US Food and Drug Administration (FDA) approval of the SARS coronavirus 2 (COVID-19) vaccination in 2021,

 acceptance among global citizens varied.

 According to several studies, more than one-third of the population studied did not receive a COVID-19 vaccination despite the critical situation of the pandemic.

 Hesitancy about taking the vaccine was more prevalent among people with chronic illnesses, including those with multiple sclerosis (MS).

Clear guidance about the necessity and urgency of offering COVID-19 vaccines to people with MS was soon released,

 but some members of the MS community continued to have concerns about it.

 People with MS in Egypt had a high rate of vaccine hesitancy—26% at the peak of the pandemic.

 In May 2023, the World Health Organization (WHO) declared an end to COVID-19 as a global health emergency,

 but data about the final vaccination rate in Egypt are scarce. This study aims to uncover the 2023 COVID-19 vaccination status among a cohort of people with MS, their feelings and fears during and then following the pandemic, and any reported adverse events (AEs) from vaccination.

This was a cross-sectional, self-administered survey given to adults with MS seen at the Alexandria University MS Clinic between June 2023 and November 2023. People with relapsing MS (RMS) and progressive MS (PMS) were eligible.

The survey had 6 sections: (1) sociodemographic characteristics; (2) clinical data about the disease (eg, disease duration, phenotype, Patient-Determined Disease Steps [PDDS] score,

 number of relapses in the past year, and disease-modifying therapies [DMTs]); (3) fear of COVID-19 scale (FCV-19S) score

; (4) questions about prior exposure to COVID-19 and commitment to preventive measures; (5) previous vaccinations, DMTs, steroids, and attitudes toward the vaccine; (6) vaccine-related AEs and postvaccination relapses.

All data were analyzed using the IBM SPSS software package, version 20.0. For comparison based on data type, χ

, Monte Carlo, and Fisher exact tests were used.

Ethical approval was obtained from the ethics committee of Alexandria University School of Medicine (IRB no 0012098 [expires October 6, 2025]), which operates according to the International Conference on Harmonization Good Clinical Practice Guideline and applicable local and institutional regulations and guidelines. The ethics committee has a federal-wide assurance from 2010 (FWA no. 00018699 [expires January 21, 2026]).

Of 200 patients invited, 150 (75%) responded to the survey during the study period. The median age of the participants was 35.5 years (range, 19-59). Approximately 77% were women; 47% were highly educated (

). The median disease duration was 4 years (range, 0.019-22), and the median PDSS was 2 (range, 0-7). Approximately 54% (n = 81) received a COVID-19 vaccination (

). Sinopharm, Pfizer, and AstraZeneca vaccines were the most common brands given to 39.2%, 24.1%, and 19%, respectively (Table 1).

The median FCV-19S score was 11 (range, 7-35). Approximately 42.7% of the patients experienced COVID-19 symptoms, and 14.7% had positive COVID-19 tests. Two participants (1.3%) were hospitalized due to COVID-19 infection. The exposure data and commitment to infection control precautions are detailed in Table S2. Of 150 participants, 66 (44%) received 2 doses of COVID-19 and 69 (46%) did not receive any vaccines (Table S3).

Of those who did not receive the vaccine, 65.2% did not want to receive the vaccine at all. The main 2 causes were worries about making their MS worse (69.3%) and being worried about long-term AEs (63.3%) (Table S3).

Of the 81 people with MS who received the vaccine, 20 (24.7%) had a clinical relapse 1 month before vaccination; 16 (19.8%) received corticosteroids during the month before vaccination; and 3 (3.7%) postponed their DMT because of vaccination. They were on dimethyl fumarate, fingolimod, and rituximab. Of note, the only factor significantly related to vaccination state was FCV-19S scores. Two-thirds (65.2%) of patients with a high level of fear did not receive the vaccine vs 67.6% of those with moderate fear and 46.2% of those with low fear (

Fatigue was the most common AE, occurring in 48% of participants in general and in 32% after the second dose (

). Five (≈ 6.2%) people with MS who received the COVID-19 vaccination had a relapse following vaccination. The relapses were confirmed clinically but not radiologically. The details of those who had a relapse are compared with those who did not have a relapse in 

. Of note, relapse occurrence was higher for patients receiving immunosuppressants than for those receiving immunomodulatory DMTs. (All DMTs used were considered immunosuppressants except interferons.) Relapse symptoms are depicted in 

. Imbalance was the most common neurological symptom reported (18%). This was followed by weakness (15%), gait problems (15%), visual disturbances (14%), urinary or bowel symptoms (14%), and sensory symptoms (9%) (Figure 1B).

Although the COVID-19 pandemic is no longer a health emergency, it was essential to investigate vaccine hesitancy among the Egyptian people with MS to help develop regulations and educational programs for the future. We found that approximately only half of the Egyptian people with MS surveyed received the COVID-19 vaccine, mainly due to fear of potential AEs or a negative impact on their MS. In this cohort, 5% had an MS relapse, but no other serious AEs were reported.

Compared to the WHO's 70% vaccination target,

 the vaccination status among Egyptian people with MS is inadequate, especially taking into consideration that 27.3% of those who received the vaccine were forced to do so for work- or travel-related reasons. These numbers are similar to those reported by Ghanem et al,

 who studied 289 people with MS from Cairo and found a hesitancy rate of 26.3%. However, in their study of 160 Egyptian people with MS, Gad et al

 reported a vaccination rate of 40.6%. Although the vaccination rate was low among people with MS in Egypt (either in our study or in previous Egyptian studies

), the rate is slightly higher than that noted among the general Egyptian population, where about 49% (of 18,107 individuals interviewed) were vaccinated.

 This higher rate among people with MS may be due to better education from their neurologists or their perception that they are more vulnerable than people who do not have MS. Vaccination rates among people with other neurological disorders were similar, including immune-mediated diseases (59.2%)

 and other diseases such as cerebrovascular disorders (41.6%),

 People with MS in Egypt were more likely to receive a COVID-19 vaccination than those with stroke or epilepsy, but less likely to receive it compared to those with headache. Regardless, the vaccination rate in Egypt, whether among the general population or among patients with various neurological disorders, is low compared to the WHO target.

The vaccination numbers from Egypt are significantly lower than what has been reported in the literature. For instance, in a 2022 systematic review and meta-analysis of 5983 people with MS mainly from the United States, the United Kingdom, Ireland, Iran, and China, only 2% of people with MS were unwilling to receive COVID-19 vaccines.

 In a study of 4955 people with MS from the North American Research Committee on Multiple Sclerosis (NARCOMS), 84.1% received a COVID-19 vaccine.

 Similarly, of 193 people with MS in Germany, 84.5% and 78.2% received first and second COVID-19 vaccine doses, respectively.

 Data from 2 Australian health care services in 2021 showed a vaccination rate of 82.9% among 281 people with MS.

 The differences noted are likely due to fear and poor knowledge about the vaccine safety, efficacy, and potential AEs.

The case is different in other countries in the Middle East and North Africa (MENA) region. A cross-sectional study of 3041 people with MS from MENA reported a 60.2% willingness rate to receive a COVID-19 vaccine booster.

 Alroughani et al, in a study from Kuwait of 647 people with MS, reported a 59.28% vaccination rate.

 Felemban et al reported that 89.02% of 173 people with MS in Saudi Arabia received the vaccine.

 The only region where the vaccination rate was lower than our study was South Africa, with 17.5% of 394 people with MS receiving the COVID-19 vaccine.

 Although the rate was low, approximately 60.2% had a positive attitude toward vaccination. Here again it seems that the Egyptian population might need specific education as well as detailed studies to investigate what is engendering such a negative attitude toward vaccination.

Fear of vaccination was similar in our study to what has been reported in the literature. In the NARCOMS cohort, the reasons for not getting the COVID-19 vaccine were fear of potential AEs (47.7%), possible lack of efficacy (13.7%), and uncertainty about need for the vaccine (17.1%).

 And, unlike with our cohort, many factors were significantly correlated to receiving the vaccine, including older age, higher socioeconomic status, physical activity level, and DMT.

 Similarly, age, level of education, Expanded Disability Status Scale score, disease duration, depression, psychological status, and DMT use affected reception of COVID-19 vaccination.

 In a German study, concern about potential AEs was the most common reason to not get the vaccine (82.1%) followed by believing the vaccine was not adequately tested (64.3%).

 In an Australian study in 2021, young age and short disease duration (ie, 5 years or less) were the main factors determining the vaccination status.

 In Saudi Arabia, the main determinant for getting the COVID-19 vaccine was education level (

 In a Malawi study, the lack of knowledge about COVID-19 vaccination benefits and importance was the main factor in people choosing to not get the vaccine.

Vaccine AEs in our cohort were mild, with fatigue being the most commonly reported symptom by approximately half of the sample. The relapse rate following vaccination was 6.2%. Patients who had a relapse following vaccination were similar to those who did not experience a relapse except that they were on immunosuppressants. This might be attributed to the vulnerability of the host immune system increasing the risk of vaccine-induced inflammatory response and promoting a relapse. In an Egyptian cohort, the relapse rate following vaccination was 7.7%, and the prevalence of vaccine-related AEs was 33%, mainly in the form of injection-related reactions and general constitutional symptoms.

 In Western countries, the prevalence of AEs related to COVID-19 was 52.8%

 In the Kuwait cohort, 1.31% had relapses following vaccination.

Taken together, it is clear that the COVID-19 vaccination rate among people in Egypt with MS is poor. This is similar to the population in Egypt in general, but inadequate compared with international standards. Although the reported reason for poor vaccination is worry about the potential negative impact of the vaccine on their MS and their general health, in this study, the vaccine did not have any major negative impact on the MS disease or the general condition of the Egyptian cohort. Local educational programs about the importance and safety of vaccination should be provided for this vulnerable population. Further studies are also needed to investigate other potential causes of fear of vaccination among this population.

The main strength of this study is that it concerns people with MS in Egypt, a country with a large population but limited publications on this topic, and it is the first (to the best of our knowledge) to assess final vaccination status. The main limitation of the study is that it was performed after the peak of the COVID-19 pandemic. Still, the study's aim was to present the final vaccination state of a vulnerable group of the population and to demonstrate how excessive concerns over vaccine risks affect COVID-19 vaccine uptake.

More than half of the study cohort of people in Egypt with MS did not receive a COVID-19 vaccine mainly due to fear about its potential negative consequences on their MS disease progression; however, all vaccine-related AEs were mild. These findings emphasize the importance of implementing awareness and education programs for patients with chronic diseases in future pandemics.

Final COVID-19 Vaccination Status, Attitude, and Adverse Events Among People With Multiple Sclerosis: A Cross-Sectional Study From Egypt

 People with multiple sclerosis (MS) often experience psychiatric symptoms, such as anxiety and depression, that impact disease progression and quality of life. Cognitive impairment, particularly in processing speed and episodic memory, is common in MS. There are several studies studying the relationship between anxiety and cognition in the population with MS. This study reviews that literature.

This bibliographic review covers publications in Spanish and English from January 2006 to June 2022. It focuses on quantitative investigations of the relationship between anxiety symptoms and cognitive variables in people with MS.

A majority of studies found an association between anxiety and cognition in people with MS. Anxiety significantly affects information processing speed, learning, memory, attention, working memory, and verbal fluency in people with MS. However, some studies find no association. The impact of depressive symptoms and the bidirectional relationship between anxiety and cognition are highlighted.

Anxiety in people with MS is associated with cognitive impairment. Further research is needed to understand the mechanisms and establish causal relationships between anxiety and cognition in this population.

From the Demyelinating Diseases Working Group (CUEM), Neurology Division, Ramos Mejía Hospital, Buenos Aires, Argentina (RMS, NC, ALM, RA, MBE); and the Research Institute in Psychology, School of Psychology, Buenos Aires University, Buenos Aires, Argentina (NC, MBE). 

 María Bárbara Eizaguirre, JD, Perón 3051, La Matanza, Buenos Aires, Argentina. ZC: 1754; 

We extend our gratitude to the authors of the studies included in this review, whose work has greatly enriched our understanding of the subject.

Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. It is the most common cause of neurologic disability in young adults.

 Psychiatric manifestations, such as symptoms of anxiety and depression, are prevalent in people with MS and are associated with disease progression and a poorer quality of life.

 Although these manifestations are present in up to 60% of people with MS, they are often not adequately treated.

 In contrast, the prevalence of cognitive impairment in adults with MS ranges from 34% to 65% and symptoms vary according to the course of the disease.

 Cognitive impairment is also a neglected but common symptom with a profound effect on essential activities of daily living. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains.

MS can be described as a pathology with an uncertain outcome: a chronic, unpredictable neurological disorder with recurrent relapses (the most common form of MS, the relapsing-remitting MS phenotype) that seem to occur at random; it carries the risk of eventual progression to a chronic progressive disease after years or decades of stability. Therefore, it is quite possible that the unpredictable nature of this disease, particularly with regard to relapses and the potential for future progression and disability, causes anxiety.

Clinical anxiety is defined as an intermittent or persistent feeling of apprehension or fear that can be associated with physical symptoms, including tachycardia, sweating, palpitations, dizziness, and autonomic gastrointestinal symptoms.

Enrique J. Carrazana, MD

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