Development of an integrated conceptual model of multiple sclerosis spasticity

Abstract Purpose Spasticity is common in multiple sclerosis (MS), often leading to functional limitations and disability. We developed a conceptual model of spasticity in MS integrating expert opinion, recent literature, and experiences of clinicians and people with MS spasticity. Methods A conceptual model was developed based on a targeted literature review of articles published between 2014 and 2019, followed by input from clinicians, then input from participants with MS spasticity. Multidisciplinary experts on spasticity provided guidance at each step. Results Key concepts of the integrated spasticity conceptual model included: moderators; triggers; modifiers; treatment; objective manifestations; subjective experience; physical, functional, social, and emotional/psychological impacts; and long-term consequences. Participants with MS spasticity most frequently endorsed spasms, tightness, and pain as descriptors of spasticity. Some participants with MS spasticity had difficulty distinguishing spasticity from other MS symptoms (e.g. muscle weakness). Some triggers, emotional/psychological impacts, and long-term consequences of spasticity reported by participants with MS spasticity were not previously identified in the published literature. Conclusions This conceptual model of spasticity, integrating published literature with the experience of clinicians, people with MS spasticity, and experts, demonstrates the complex, multidimensional nature of MS spasticity. This model may be used to improve clinician–patient dialogue, research, and patient care. IMPLICATIONS FOR REHABILITATION Many people with multiple sclerosis (MS) have spasticity, generally in the lower limbs, but this symptom is complex and multidimensional and therefore difficult to characterize. MS spasticity may be influenced by moderators, triggers, modifiers, and treatment, all of which can affect objective measures and the subjective experience of spasticity. MS spasticity can have physical, functional, social, and emotional/psychological impacts as well as long-term consequences that can affect rehabilitation and ultimately reduce health-related quality of life for people with MS. Given that people with MS may view spasticity differently than their rehabilitation providers, providers should ask patients about their spasticity, including their moderators, triggers, modifiers, experience, impacts, long-term consequences, and effects on quality of life. This conceptual model provides a framework to improve clinician-patient dialogue, research, and rehabilitation for MS spasticity.


Introduction
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of the central nervous system resulting in a variety of symptoms and often leading to functional impairment [1,2].In 2017, it was estimated that there were over 900,000 people with MS (PwMS) in the United States [3].Up to 80% of PwMS experience spasticity, a complex and multidimensional symptom [4].Spasticity is challenging to characterize.Physiologic and environmental variables can trigger spasticity, and PwMS may experience spasticity in various ways [5,6].Published studies that highlight the perspectives of PwMS on spasticity and its impact on health-related quality of life are limited [7].Since input from both PwMS and clinicians is needed to ultimately improve dialogue between PwMS and their healthcare providers, research is needed to better understand how PwMS and clinicians view MS spasticity based on their respective experiences.
The purpose of this study was to develop a conceptual model of MS spasticity that integrates perspectives from recent peerreviewed literature with those of clinicians, people with MS spasticity, and multidisciplinary experts in the field of spasticity from academia and industry.This integrated conceptual model provides a framework for describing and understanding spasticity in PwMS.

Overview of study design
This study used qualitative methods to develop a conceptual model of MS spasticity using a multistep iterative process (Figure 1).Relevant peer-reviewed literature was reviewed to produce an initial conceptual model.Clinician feedback was then used to revise this initial conceptual model and to develop a guide for interviews of PwMS with spasticity.Semi-structured interviews with PwMS and spasticity were conducted to further refine and finalize the conceptual model.At each step, input was provided by the six authors who are experts on spasticity from different disciplines, including neurology, physiatry, and physical therapy (JB, JRS, JMW, FB, MC, and EFF; Figure 1).

Targeted literature review
A targeted literature search of PubMed of English language papers on MS spasticity was performed.Only randomized controlled trials, other interventional studies, observational studies, and review articles were included.Abstracts were included if they were published within the five years prior to when the project was initiated (January 1, 2014 through September 3, 2019).The complete search strategy for this targeted literature review is available in Supplemental Table 1.This resulted in 282 abstracts.Two authors reviewed these abstracts independently for inclusion in the full-text literature review.Abstracts were excluded if they described animal studies, did not mention symptoms or impacts of spasticity, or did not mention spasticity.Of the 282 abstracts retrieved, 29 met these criteria and were reviewed as full-text articles.Of the 29 reviewed articles, only 19 described spasticity in terms of symptoms, impacts, and other concepts of interest and provided insights across MS and other key indications.The spasticity experts were asked to identify additional key references, including seminal papers published outside the screening publication time window and papers referred to by the identified publications.This yielded an additional four articles for a total of 23 articles.Additionally, a desk review of patient organization websites (National Multiple Sclerosis Society [www.nationalmssociety.org])and the Multiple Sclerosis Trust [www.mstrust.org.uk]) was conducted to identify any additional patient-friendly spasticity descriptors and impacts.These were used to develop the initial conceptual model of MS spasticity.

Interviews with MS clinicians
Three clinicians who treat PwMS at different institutions were individually interviewed via telephone using a semi-structured interview guide.Their identities were not disclosed to the sponsor.Each interview lasted approximately one hour.The interviews focused on the key characteristics of spasticity and how, in their experience, PwMS describe symptoms of spasticity.These clinicians also gave feedback on the relevance and completeness of the initial conceptual model based on the literature review.The interviews were audio recorded.These clinician interviews and subsequent discussions with the experts in spasticity were the basis for initial refinements to the conceptual model which was used to develop a semi-structured patient interview guide.

Interviews with people with spasticity due to MS
Twenty partients with clinician-diagnosed MS of any subtype with MS-related spasticity were individually interviewed via telephone using a patient interview guide.Their identities were not disclosed to the sponsor.The interview took approximately 90 min.The interviews focused on the patients' experience of spasticity and its impacts.The interviews were audio recorded and transcribed.confirmation letter from the clinician, or other confirmatory documentation.Potential participants were screened for eligibility prior to the interview.Participants were eligible if they were ≥ 18 years old, could read and write English, were diagnosed with MS of any subtype for ≥ 12 months, and had spasticity due to MS for ≥ 6 months prior to the study as determined by the referring clinician.Exclusion criteria included any comorbid disorder of the central nervous system, a diagnosis of clinically isolated syndrome, or an impairment (e.g.visual) that could interfere with study participation.

Study enrollment
Potential participants were recruited during regularly scheduled patient clinical visits (in person or via telehealth) or by phone.Interested PwMS were invited to contact the recruitment vendor to schedule an interview.Written consent was provided by participants at the time of the interview; participants confirmed consent verbally to be audio recorded.Participants were remunerated for their time.This study received ethics approval from an independent institutional review board (Advarra Pro00045192).

Interviews
The interviews were conducted by four trained research staff with experience in qualitative methods.The semi-structured interview guide was used to draw out the participants' experience of spasticity.Participants were first asked how long they had been diagnosed with MS, what symptoms they typically experienced in relation to spasticity, where those symptoms occurred in their body, and what spasticity meant to them.Additional questions focused on understanding the triggers of spasticity, how long the symptoms lasted, and how daily functioning was affected.Participants were also asked to comment on whether spasticity caused or worsened other symptoms, such as pain, fatigue, or sexual dysfunction.Participants were then asked to describe their spasticity experience and were probed using the key concepts identified in the literature or during the clinician interviews as necessary for further elucidation or clarification.Interviews were continued until saturation was reached.Saturation was defined as the point at which no substantially new themes, descriptions of a concept, or terms were introduced as additional interviews were conducted [8].
After the interviews, participants were asked to complete the following forms and assessments: a sociodemographic and clinical information form, the Patient Determined Disease Steps (PDDS) [9], and Spasticity Numeric Rating Scale (NRS-S).The NRS-S was a single question asking, "On a scale of 0 to 10, please indicate your level of spasticity over the last 24 h, considering 0 as 'no spasticity' and 10 as 'worst possible spasticity'".

Data analysis
The patient participant interview transcripts were reviewed and the content coded for concepts by trained coders.The codes were then entered into a saturation grid to track and tally identified concepts.Content analysis was performed using thematic analysis in ATLAS.ti version 8.0.(ATLAS.ti,Bergmannstraße 68, Berlin, Germany).Demographic and self-reported clinical data were analyzed using descriptive statistics, such as frequencies, means, and percentages.

Interviews with MS clinicians
The clinicians were two physicians and a physical therapist.They had an average of 22 years of experience treating PwMS.They reported PwMS using a wide variety of spasticity descriptors, including stiffness, spasms, muscle contractions, weakness, heaviness, tightness, and cramping.All clinicians described PwMS reporting pain as a part of the spasticity experience.The key revisions of the conceptual model based on the clinician interviews and the input of the multi-disciplinary experts on spasticity were the addition of: the triggers of physical dysfunction (e.g.skin lesions) and other environmental factors (e.g.tight clothing); altered voluntary movement pattern, which is an objective manifestation of spasticity in the final model; both slowness of movement and muscle jerks as subjective experiences in the final model; and the impact of loss of leisure and physical activities as a long-term consequence.Other key revisions include the removal of the descriptors of rigidity, limited range of motion, and orthopedic symptoms and the impact of disability (Table 1, Column 3; Supplemental Table 3).
The quantitative results and representative qualitative quotes from the interviews with PwMS are provided in Table 3.A summary of the concepts identified during this research at each step is listed in Supplemental Table 3.In this table, key changes are noted from each step of the model development.

Final conceptual model
The draft conceptual model based on the targeted literature review was modified by findings from the interviews of clinicians and people with spasticity due to MS and was finalized by the multidisciplinary experts on spasticity (Table 1 Column 4; Figure 2).The final conceptual model describes moderators (variables that affect the presentation of spasticity for PwMS), triggers, modifiers (descriptors of the experience of spasticity), and treatment of spasticity.These affect a range of objective manifestations and subjective experiences of MS spasticity.These subsequently result in physical impacts that can lead to functional limitations, social impacts, and emotional/psychological impacts.The conceptual model then describes the long-term consequences of spasticity, which may ultimately reduce the health-related quality of life of PwMS.
Reduced time with family and friends

Discussion
Spasticity is common in PwMS, although difficult to characterize because it is complex and multidimensional.Our conceptual model, derived from this qualitative study, integrates a targeted literature review, clinician opinions, and insights from people with spasticity due to MS with opinions from experts in the field of MS spasticity, to provide a comprehensive framework to better describe and understand spasticity in PwMS.
The clinicians and multi-disciplinary experts gave us information that further refined the model.Two additional triggers were added: skin lesions and tight clothing.Their feedback also led us to remove rigidity and limited range of motion from the model.The following descriptors of spasticity were added based upon their feedback: weakness, slowness of movement, altered voluntary movement pattern, and muscle jerks.Disability was removed from impacts and consequences.Frustration, loss of mobility, difficulty with transfers, and reduced life expectancy were added to impacts and long-term consequences.
The PwMS confirmed many items, identified some new concepts, and recommended removal of some triggers.Specifically, the new concepts were social impacts of reduced time with family/ friends and embarrassment.They also recommended adding triggers of stress, physical activity (e.g.movement daily activities, exertion, sitting/standing too long) and other environmental factors, and removing triggers of urinary tract infection, full bladder, and sleep.
In addition, spasticity can occur alongside other symptoms of MS [12], making it difficult for PwMS to distinguish between the variety of sensorimotor dysfunctions they experience and spasticity.For instance, a few participants mentioned tremor or numbness as part of their spasticity experience; however, this descriptor was not confirmed in the literature or by the multidisciplinary experts on spasticity as being associated with spasticity.The authors believe that participants were using "tremor" in a nontechnical way to describe an aspect of their experience.For instance, it is possible that they were experiencing clonus, which  Multidisciplinary experts on spasticity were consulted, and some concepts were removed based on their feedback (see supplemental table 3 for more detail).c other Ms symptoms included: increased disability/motor impairment, pain, musculoskeletal symptoms, orthopedic symptoms, urinary and bowel dysfunction, balance disorders, fatigue/deconditioning, weakness, ataxia, sensory abnormalities.d Fatigue and stress were identified in the literature review only as impacts of spasticity.e Physical dysfunction included gastrointestinal problems, such as constipation, and skin lesions.
f Weakness was identified in the literature review only among other Ms symptoms that may influence spasticity.g limited range of motion was identified in the literature review as a descriptor of spasticity.h "transfers" was identified in the literature review as an impact of spasticity.Participants who struggled to walk because of spasticity reported this was due to muscle spasms and cramping in their lower extremities."when your feet want to cramp up, and it can be like in the awkwardest of places, like it can be like the side of my ankle or something and it kind of turns my foot in a little bit, you know, it's hard to straighten out that foot and take a step or put your foot down flat because it just wants to bring it in."Reduced dexterity 15/20 (75%) reported reduced dexterity as a functional impact of spasticity "i can't reach and grasp things like i used to.they will slip out of my hand or my hand will get locked around it where i have to almost pry my fingers off of it." Difficulty with transfers 14/20 (70%) reported difficulty with transfers as a functional impact of spasticity e.g., getting in and out of the bed, the car, the tub, standing up from a seated position, and getting on and off the toilet "oh, sometimes it's just a matter of, you know, i can't get in and out of my bed myself so he'll [help] me and sometimes just do it really.there are times that i've literally just gotten stuck because i can't get off the toilet so he'll help me with that."Reduced swallowing 12/20 (60%) reported reduced swallowing as a functional impact of spasticity "i have noticed it a couple of times.i have gotten choked up.and, um, like my drink actually-i had to spit it back out.and then, um, like as like swallowing certain pills, like i can't get those down.""it feels like muscle cramps in my throat… sometimes it happens when i'm eating.sometimes it happens when i'm swallowing.".:"…suddenlysomething that should have been so enjoyable was so painful and i couldn't move and i said, no, i need to stop now… and there was no being able to finish, no anything.it embarrassed me and made me feel awkward."social impacts Quantitative assessment Qualitative representative quotes Reduced time with family/ friends 14/20 (70%) reported that their spasticity has social impacts 6/14 reported that their spasticity (like pain, slowness of movement, or spasms) kept them from participating in social activities with family and friends) "Um, it limits my ability to participate in social activities.and it also limits my ability in terms of scheduling because there are only certain parts of the day where i'm fairly sure that it's-i'm going to have less impact.so, for example, i don't typically schedule things early in the morning and i don't typically schedule things in the late afternoon or evening." Work limitations 4/20 (20%) were employed at the time of the interview.3/4 (75%) of those who were employed had work limitations due to spasticity one had to modify the type of desk they used in the office and be more conscious of their slow movement while seated.Delegation of tasks to their employees when experiencing spasticity.Falling at work.

emotional/ Psychological impacts
Quantitative assessment Qualitative representative quotes Fear of falling 16/20 (80%) reported a fear of falling "yes, i do.that is a big fear of mine 'cause it, it has happened.Um, yeah.i mean it is-yeah.it's just one of my series of falls can result in injuries and i don't have time to be injured right now." one participant explained the concern that standing up after a fall could be daunting because their legs could stiffen or "lock up."Frustration 14/20 (70%) reported frustration "Just the spasms themselves.they're so frustrating when i can't stop them.if-i wish there was a medication that would-i could take during the day that wouldn't put me to sleep" Depression 13/20 (65%) reported depression "i mean it all over kind of could be depressive period, you know, because it limits your life in so many ways, like grandchildren, playing with your grandkids.""i went through a bad bout of depression… in December because my legs had gotten so bad that [i had] to lie around and everybody was out doing all the fun things."anxiety 13/20 (65%) reported anxiety "yeah.i think that's again when i can't get up from the floor or when i can't get into the car.or here that's a good is a rhythmic movement commonly associated with spasticity.
Weakness (subjective experience), bladder dysfunction (physical impact), and reduced swallowing (functional impact) were included in the conceptual model, as these items were associated with spasticity according to participants and the literature.The conceptual model includes moderators such as MS duration, type of MS, and other MS symptoms to acknowledge that there are external factors, both MS-related and non-related, that may influence the experience of spasticity.
This conceptual model presents pain as a prevalent and complicated component of spasticity; the recent literature [6,28], opinions from clinicians and multidisciplinary experts on spasticity, and participant interviews confirmed pain as a subjective experience, a trigger, a physical impact, and a moderator of MS spasticity.Almost all participants reported pain as part of their spasticity experience.Clearly, understanding the relationship between pain and spasticity is important for optimizing the management of MS spasticity.Some patient participants felt that fatigue, which is one   of the most common and debilitating symptoms of MS [31,32], could be caused by pain (subjective experience and physical impact) and soreness from spasticity.Thus, fatigue was included as both a trigger and physical impact of spasticity.The long-term consequences of spasticity are difficult to assess with traditional clinical research studies, which usually last a maximum of two years; therefore, consequences beyond two years may not be well represented in the literature.However, PwMS described several long-term consequences of spasticity, including contractures, fear of falling, difficulty with transfers, loss of employment, loss of driving ability, loss of independent living, and increased burden of care.Given that PwMS may live decades with spasticity [33], additional research is needed to elucidate the long-term consequences of spasticity in order to develop and implement strategies to minimize their occurrence and improve the quality of life of PwMS.
This study had a number of strengths.Our model included multiple perspectives, including those of clinicians who treat many patients with MS spasticity and the expertise of people with the lived experience in an iterative process to develop this conceptual model of MS spasticity.During the iterative development process, experts from academia and industry further informed the development of the model.Importantly, the interviews with PwMS were repeated until saturation was reached.Another strength is that the project team utilized experts in conceptual models and qualitative research to conduct this project.This model confirms that MS spasticity is complex and multifaceted.The model takes a very complex experience and breaks it down into moderators, triggers, modifiers, and treatment of spasticity as well as describing spasticity (both objective and subjective experiences).In addition, this model describes the impacts and long-term consequences of spasticity that PwMS experience.The most comprehensive scale to date used to assess MS spasticity, the MSSS-88, focuses on the impacts of spasticity in PwMS but does not address moderators, modifiers, treatment, triggers, or long-term consequences of MS spasticity.[34].
The development of this conceptual model is not without limitations.Our initial literature review was not systematic and was time limited.However, this only served as a starting place for the iterative multistep model-building process.Some of the symptoms and consequences of spasticity described in our final model could also be explained by other symptoms of MS (e.g.difficulty moving that a PwMS attributes to spasticity may actually be related to muscle weakness).However, our approach balanced input from PwMS and clinicians to mitigate this limitation.Bias could have been introduced by financial compensation to the PwMS, although it was provided as reimbursement for their time at fair market value, as is standard in clinical research.Finally, all study participants being US based, and the sample of clinicians and PwMS was small.However, the demographics of our sample of 20 people with MS is similar to that of other studies [33,35], and is in line with recent literature on qualitative concept elicitation, which indicates that a sample of 20 people should capture 97% of symptom concepts [36].

Conclusion
Spasticity in PwMS is common, complex, and has a wide range of moderators, triggers, modifiers, treatment, objective manifestations, and subjective experiences.MS spasticity can have impacts that are physical, functional, social, and psychological as well as long-term consequences that can ultimately reduce health-related quality of life.This integrated conceptual model of MS spasticity includes the perspectives of PwMS, clinicians who treat PwMS, and multidisciplinary spasticity experts.The model may have several practical applications at the point of care, including improving clinician-patient dialogue, allowing treatment decisions to be personalized, assisting PwMS to set goals, and facilitating spasticity education.Furthermore, the model may be used to select and validate clinical research endpoints and to inform regulatory decision making.

Figure 1 .
Figure 1.steps in developing the integrated conceptual model of multiple sclerosis spasticity.PwMs = people with multiple sclerosis.

a
two spasticity triggers (infection and menstruation) were not specifically probed in the participant interview and were not mentioned by participants; however, they were endorsed by targeted literature search, clinician interviews and the spasticity expert input and were therefore kept in the final model.b in the model, physical dysfunction includes gastrointestinal problems, such as constipation, and skin lesions.c Muscle tension was included in the final model based upon input received from the clinician interviews and the spasticity experts.

Table 1 .
Multistep process for developing the integrated conceptual model of multiple sclerosis spasticity a .

Table 2 .
Demographic and self-reported clinical characteristics.

Table 3 .
summary of interview information from PwMs.yeah.and i-to say i absolutely love the heat and i am a bikini advocate.Um, but this has been a bit of a stretch for me and that's when i just-it, it really-the heat does warrant how long i can enjoy.i mean there's no boating now.it's i'll watch you from the beach kind of thing.Um, but i definitely, um, think that it does impact me a little bit." "the cold definitely makes [spasticity] so much worse… the heat is not great either…but the cold makes it so much worse.""the quick weather changes is enough to just kind of give me a little kick me down." it just wears down my body overall.so, i mean i'm extremely fatigued.i have to be very careful about how i spend what energy i have.it makes me really fatigued and also, i think maybe since i was using those muscles more or something, they're more, more prone to have spasticity.""When i'm having chronic fatigue, then i have more issues with spasticity.""if i walked up the driveway too many times a day, i would be hunched over [from spasticity]… getting into the house, go lie down, and kick for a minute….thinkthat if it's just not, like i was describing before, if it's something that's just not where it's just a spasm and it doesn't come with very much pain, it goes away quicker.if it's coupled with pain that makes it harder, more intense, then it lasts longer."Um, like i mean so i mentioned intestinal issues.so i recently-they sent me to the eR two separate times because of the pain involved in that.and i mean it just seemed like the pain-like the excruciating pain from my stomach, it seemed to-i don't know.My legs got worse and, you know, it just seemed more miserable.", it hurts, you know, it's like when you get a cramp, it hurts and then it hurts usually if i have one in my calves, sometimes they feel bad.My calves hurt several days after because it's been pushing, it spasms, yeah, i have it like three or four days after, like i've been working out but i haven't.""i'm in pain every single day.i have a pain in my hip, but i experience pain in other areas every single day…the spasticity will make the back pain worse from jerking." "spasms were often described as "twitching," "jerking," "jumping," or "kicking.""Um,to me it's when my muscles twitch and that's what they do.likemy fingers will twitch.My toes will twitch.youcan see in my arms and legs.youcan literally see them to where it looks like, um, it's jumping inside.likemy arm may not actually move, but you can see the muscle, um, twitch in the arm.andthen there's times where you can actually see the arm move, like, like someone is moving it, but it's not me.it-that'swhen it gets really bad."or that's more when like the jerking-like my muscles sit there and like contract and keep going and my leg will start literally like jerking and-or like you can look at the muscle and you can see the muscle twitching and stuff, and that has woken me up.that usually happens during the night when i'm sleeping.""whenmy legs shake, my whole leg shakes.When my arms shake, my whole arm shakes.itjerks, yeah, it's big jerks."slowness of movement 5/20 (25%) reported slowness of movement "or if somebody-you know, your daughter watching you get in the car."Comeon.let'sgo." i just function a lot slower.andagain if that's because i'm stiff or i can't move as quickly as somebody might want me to.that's, that's what causes anxiety, is that external, uh, thing.""youknow, everything is just tight and so i can't, i can't undo my legs so that they will move.Um, i remember other times like walking and then you just stop because i can't-my hip and my upper thigh, thigh are too-so tight that i can't move at like a regular walk and i have of the participants with balance impairment, most believed it was due to spasticity only.

Table 3 .
question.if there's other people around, right.and if i'm stuck on the floor and somebody wants to try to help me get up and i can't figure it out and my leg won't move, Um, it's not, not great and it's not-in those moments, i try not to like drive at night…i get very, very achy and so i try to kind of keep it pretty simple.""yeah, yeah.yeah, it was, i loved driving but you know, when you get to the point you're afraid, you know, what if i kill somebody because i make a bad judgment call.""i can still drive, but i will not drive when i don't feel good.i won't put other people in danger."not worked in over 10 years…the work limitations were not being able to walk up and down stairs…lift more than 10 pounds… stand for more than five minutes… sit for more than 10 min without shifting position… i realize now that it was Ms." Continued.

"
Well, right now i can't walk so yes, and it's not because of weakness or anything, it's because of spasticity that i cannot walk very well, because my knees will not straighten out.""Welli-yeah.iguess that's the whole walking.ijust do thing-everything is slower.Um, i, i don't-i only use-in the house i have a three-wheeled walker, just to try to help me keep my head off the ground."Um,i have always been a really independent person.ihave reached a point because of the fall risk, um, and my fatigue level, um, and my mobility issues, i can't do things like housework.soi can't vacuum.ican't, um, put groceries away.ican't do laundry.thingslike that, i just, i can't do.icannot independently live on my own and that, that is frustrating for me."notes:abbreviations: eR = emergency room; Mss = multiple sclerosis spasticity; Pt = physical therapy; PwMs = people with multiple sclerosis.
Figure 2. integrated conceptual model of multiple sclerosis spasticity.*Variablenotidentified in literature review.†Variablenot identified in clinician interviews.‡Variablenot identified in patient interviews.abbreviations:aDl= activities of daily living; Gi = gastrointestinal; Ms = multiple sclerosis.triggers,Msspasticity -subjective experience, Functional limitations/impacts, social impacts, emotional/Psychological impacts, and long-term Consequences are listed in order of decreasing percentage of patients reporting the variable, as in table3.