Signs and symptoms of multiple sclerosis#Fatigue
{{Short description|Neurological signs and symptoms}}
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Multiple sclerosis can cause a variety of symptoms varying significantly in severity and progression among individuals: changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty moving; difficulties with coordination and balance; problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, phosphenes or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly major depression). The main clinical measure in progression of the disability and severity of the symptoms is the Expanded Disability Status Scale or EDSS.{{cite journal | vauthors = Kurtzke JF | title = Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) | journal = Neurology | volume = 33 | issue = 11 | pages = 1444–1452 | date = November 1983 | pmid = 6685237 | doi = 10.1212/WNL.33.11.1444 | author-link = John F. Kurtzke | doi-access = free }}
The initial attacks are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made after further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (20%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis.{{cite journal | vauthors = Navarro S, Mondéjar-Marín B, Pedrosa-Guerrero A, Pérez-Molina I, Garrido-Robres JA, Alvarez-Tejerina A | title = [Aphasia and parietal syndrome as the presenting symptoms of a demyelinating disease with pseudotumoral lesions] | journal = Revista de Neurologia | volume = 41 | issue = 10 | pages = 601–603 | year = 2005 | pmid = 16288423 }}{{cite journal | vauthors = Jongen PJ | title = Psychiatric onset of multiple sclerosis | journal = Journal of the Neurological Sciences | volume = 245 | issue = 1–2 | pages = 59–62 | date = June 2006 | pmid = 16631798 | doi = 10.1016/j.jns.2005.09.014 | s2cid = 33098365 }} Fifteen percent of individuals have multiple symptoms when they first seek medical attention.{{cite journal | vauthors = Paty D, Studney D, Redekop K, Lublin F | title = MS COSTAR: a computerized patient record adapted for clinical research purposes | journal = Annals of Neurology | volume = 36 | issue = Suppl | pages = S134–S135 | year = 1994 | pmid = 8017875 | doi = 10.1002/ana.410360732 | s2cid = 23425667 | author4-link = Fred D. Lublin }}
Fatigue
Fatigue is very common{{Cite web|url=https://mstrust.org.uk/a-z/fatigue|title=Fatigue|website=mstrust.org.uk}} and disabling in MS.{{Cite web|url=https://mstrust.org.uk/a-z/fatigue|title=Fatigue | location = Letchworth Garden City, United Kingdom | publisher = Multiple Sclerosis Trust }}{{cite journal | vauthors = Moore H, Nair KP, Baster K, Middleton R, Paling D, Sharrack B | title = Fatigue in multiple sclerosis: A UK MS-register based study | journal = Multiple Sclerosis and Related Disorders | volume = 64 | page = 103954 | date = August 2022 | pmid = 35716477 | doi = 10.1016/j.msard.2022.103954 }}{{cite journal | vauthors = Hubbard AL, Golla H, Lausberg H | title = What's in a name? That which we call Multiple Sclerosis Fatigue | journal = Multiple Sclerosis | volume = 27 | issue = 7 | pages = 983–988 | date = June 2021 | pmid = 32672087 | pmc = 8142120 | doi = 10.1177/1352458520941481 }} Some 65% of people with MS experience fatigue symptomatology, and of these some 15-40% report fatigue as their most disabling MS symptom.{{cite journal | vauthors = Bakalidou D, Giannopapas V, Giannopoulos S | title = Thoughts on Fatigue in Multiple Sclerosis Patients | journal = Cureus | volume = 15 | issue = 7 | pages = e42146 | date = July 2023 | pmid = 37602098 | pmc = 10438195 | doi = 10.7759/cureus.42146 | doi-access = free }} A 2023 study found that effect on fatigue was the most valued attribute of MS therapy, and that participants would accept six additional relapses in 2 years and a decrease of 7 years in time to disease progression to improve either cognitive or physical fatigue from "quite a bit of difficulty" to "no difficulty."{{cite journal | vauthors = Tervonen T, Fox RJ, Brooks A, Sidorenko T, Boyanova N, Levitan B, Hennessy B, Phillips-Beyer A | title = Treatment preferences in relation to fatigue of patients with relapsing multiple sclerosis: A discrete choice experiment | journal = Multiple Sclerosis Journal: Experimental, Translational and Clinical | volume = 9 | issue = 1 | page = 20552173221150370 | date = 2023 | pmid = 36714174 | pmc = 9880588 | doi = 10.1177/20552173221150370 }}
The pathophysiology and mechanisms causing MS fatigue are not well understood.{{cite journal | vauthors = Manjaly ZM, Harrison NA, Critchley HD, Do CT, Stefanics G, Wenderoth N, Lutterotti A, Müller A, Stephan KE | title = Pathophysiological and cognitive mechanisms of fatigue in multiple sclerosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 90 | issue = 6 | pages = 642–651 | date = June 2019 | pmid = 30683707 | pmc = 6581095 | doi = 10.1136/jnnp-2018-320050 }}{{cite journal | vauthors = Ellison PM, Goodall S, Kennedy N, Dawes H, Clark A, Pomeroy V, Duddy M, Baker MR, Saxton JM | title = Neurostructural and Neurophysiological Correlates of Multiple Sclerosis Physical Fatigue: Systematic Review and Meta-Analysis of Cross-Sectional Studies | journal = Neuropsychology Review | volume = 32 | issue = 3 | pages = 506–519 | date = September 2022 | pmid = 33961198 | pmc = 9381450 | doi = 10.1007/s11065-021-09508-1 }}{{cite journal | vauthors = Newland P, Starkweather A, Sorenson M | title = Central fatigue in multiple sclerosis: a review of the literature | journal = The Journal of Spinal Cord Medicine | volume = 39 | issue = 4 | pages = 386–399 | date = July 2016 | pmid = 27146427 | pmc = 5102292 | doi = 10.1080/10790268.2016.1168587 }}{{cite journal | vauthors = Chen MH, Wylie GR, Sandroff BM, Dacosta-Aguayo R, DeLuca J, Genova HM | title = Neural mechanisms underlying state mental fatigue in multiple sclerosis: a pilot study | journal = Journal of Neurology | volume = 267 | issue = 8 | pages = 2372–2382 | date = August 2020 | pmid = 32350648 | doi = 10.1007/s00415-020-09853-w }}{{Excessive citations inline|date=April 2024}}
MS fatigue can be affected by body heat and this may differentiate MS fatigue from other primary fatigue.{{cite journal | vauthors = Leavitt VM, De Meo E, Riccitelli G, Rocca MA, Comi G, Filippi M, Sumowski JF | title = Elevated body temperature is linked to fatigue in an Italian sample of relapsing-remitting multiple sclerosis patients | journal = Journal of Neurology | volume = 262 | issue = 11 | pages = 2440–2442 | date = November 2015 | pmid = 26223805 | doi = 10.1007/s00415-015-7863-8 }}{{Excessive citations inline|date=April 2024}}
Perceived fatigue and fatigability (loss of strength) are regarded independently.{{cite journal | vauthors = Loy BD, Taylor RL, Fling BW, Horak FB | title = Relationship between perceived fatigue and performance fatigability in people with multiple sclerosis: A systematic review and meta-analysis | journal = Journal of Psychosomatic Research | volume = 100 | pages = 1–7 | date = September 2017 | pmid = 28789787 | pmc = 5875709 | doi = 10.1016/j.jpsychores.2017.06.017 }}{{cite journal | vauthors = Patejdl R, Zettl UK | title = The pathophysiology of motor fatigue and fatigability in multiple sclerosis | journal = Frontiers in Neurology | volume = 13 | page = 891415 | date = 2022 | pmid = 35968278 | pmc = 9363784 | doi = 10.3389/fneur.2022.891415 | doi-access = free }} Primary MS fatigue is sometimes called "lassitude.'{{Cite web|url=https://www.nationalmssociety.org/|title=Empowering people affected by MS to live their best lives|website=National Multiple Sclerosis Society}} MS fatigue may reduce during periods of other MS symptom remission.{{Cite web|url=https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis|title=Fatigue in Patients With Multiple Sclerosis|website=Practical Neurology}}{{cite web |url=https://www.mssociety.org.uk/about-ms/types-of-ms/relapsing-remitting-ms |title=Relapsing remitting MS (RRMS) |website=mssociety.org |access-date=2024-04-23}}
Knowledge of MS fatigue pathophysiology, diagnosis and treatment is very limited.{{Cite journal|title=Overview of the Current Pathophysiology of Fatigue in Multiple Sclerosis, Its Diagnosis and Treatment Options - Review Article|first1=Dalibor|last1=Zimek|first2=Martina|last2=Miklusova|first3=Jan|last3=Mares|date=May 1, 2023|journal=Neuropsychiatric Disease and Treatment|volume=19|pages=2485–2497|doi=10.2147/NDT.S429862|doi-access=free |pmid=38029042|pmc=10674653}}
= Primary vs. secondary =
In some areas it has been proposed that fatigue be separated into primary fatigue, caused directly by a disease process, and secondary fatigue, caused by more general impacts on the person of having a disease (such as disrupted sleep).{{Cite web|url=https://practicalneurology.com/articles/2018-july-aug/fatigue-in-patients-with-multiple-sclerosis|title = Fatigue in Patients with Multiple Sclerosis}}{{cite journal | vauthors = Chalah MA, Riachi N, Ahdab R, Créange A, Lefaucheur JP, Ayache SS | title = Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation | journal = Frontiers in Cellular Neuroscience | volume = 9 | page = 460 | year = 2015 | pmid = 26648845 | pmc = 4663273 | doi = 10.3389/fncel.2015.00460 | doi-access = free }}{{cite journal | vauthors = Gerber LH, Weinstein AA, Mehta R, Younossi ZM | title = Importance of fatigue and its measurement in chronic liver disease | journal = World Journal of Gastroenterology | volume = 25 | issue = 28 | pages = 3669–3683 | date = July 2019 | pmid = 31391765 | pmc = 6676553 | doi = 10.3748/wjg.v25.i28.3669 | doi-access = free }}{{cite journal | vauthors = Hartvig Honoré P |title=Fatigue |journal=European Journal of Hospital Pharmacy |date=June 2013 |volume=20 |issue=3 |pages=147–148 |doi=10.1136/ejhpharm-2013-000309 |s2cid=220171226 |doi-access=free }}{{Excessive citations inline|date=April 2024}}
= Contributory factors to secondary fatigue =
Factors such as disturbed sleep, chronic pain, poor nutrition, or even some medications can all contribute to secondary fatigue and medical professionals are encouraged to identify and modify them.{{cite book | last = The Royal College of Physicians |title = Multiple Sclerosis. National clinical guideline for diagnosis and management in primary and secondary care | publisher = Sarum ColourView Group | year = 2004 | location = Salisbury, Wiltshire | isbn = 978-1-86016-182-7 | url = http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf }}
= Association with depression =
Early 2000s commentary saw a close relationship of secondary fatigue with depressive symptomatology.{{cite journal | vauthors = Bakshi R | title = Fatigue associated with multiple sclerosis: diagnosis, impact and management | journal = Multiple Sclerosis | volume = 9 | issue = 3 | pages = 219–227 | date = June 2003 | pmid = 12814166 | doi = 10.1191/1352458503ms904oa | s2cid = 40931716 }} When depression is reduced fatigue also tends to reduce and it is recommended that patients should be evaluated for depression before other therapeutic approaches are used.{{cite journal | vauthors = Mohr DC, Hart SL, Goldberg A | title = Effects of treatment for depression on fatigue in multiple sclerosis | journal = Psychosomatic Medicine | volume = 65 | issue = 4 | pages = 542–547 | year = 2003 | pmid = 12883103 | doi = 10.1097/01.PSY.0000074757.11682.96 | s2cid = 16239318 | citeseerx = 10.1.1.318.5928 }}
= Correlation with brain changes =
Studies have found MS fatigue correlates, not with lesion volume or brain atrophy, but with damage to NAWM (normal appearing white matter) (which will not show on normal MRI but will show on DTI (diffusion tensor imaging)).{{cite journal | vauthors = Palotai M, Guttmann CR | title = Brain anatomical correlates of fatigue in multiple sclerosis | journal = Multiple Sclerosis | volume = 26 | issue = 7 | pages = 751–764 | date = June 2020 | pmid = 31536461 | doi = 10.1177/1352458519876032 }}{{cite journal | vauthors = Camera V, Mariano R, Messina S, Menke R, Griffanti L, Craner M, Leite MI, Calabrese M, Meletti S, Geraldes R, Palace JA | title = Shared imaging markers of fatigue across multiple sclerosis, aquaporin-4 antibody neuromyelitis optica spectrum disorder and MOG antibody disease | journal = Brain Communications | volume = 5 | issue = 3 | pages = fcad107 | date = 2023 | pmid = 37180990 | pmc = 10171455 | doi = 10.1093/braincomms/fcad107 }}{{cite journal | vauthors = Preziosa P, Rocca MA, Pagani E, Valsasina P, Amato MP, Brichetto G, Bruschi N, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Meani A, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, Filippi M | title = Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis | journal = Journal of Neurology | volume = 270 | issue = 3 | pages = 1543–1563 | date = March 2023 | pmid = 36436069 | doi = 10.1007/s00415-022-11486-0 | hdl-access = free | hdl = 10026.1/20405 | url = https://discovery.ucl.ac.uk/id/eprint/10171992/20/Chataway_JOON-D-22-02550.R1.pdf }}{{cite journal | vauthors = Novo AM, Batista S, Alves C, d'Almeida OC, Marques IB, Macário C, Santana I, Sousa L, Castelo-Branco M, Cunha L | title = The neural basis of fatigue in multiple sclerosis: A multimodal MRI approach | journal = Neurology. Clinical Practice | volume = 8 | issue = 6 | pages = 492–500 | date = December 2018 | pmid = 30588379 | pmc = 6294533 | doi = 10.1212/CPJ.0000000000000545 }}{{cite journal | vauthors = Bisecco A, Caiazzo G, d'Ambrosio A, Sacco R, Bonavita S, Docimo R, Cirillo M, Pagani E, Filippi M, Esposito F, Tedeschi G, Gallo A | title = Fatigue in multiple sclerosis: The contribution of occult white matter damage | journal = Multiple Sclerosis | volume = 22 | issue = 13 | pages = 1676–1684 | date = November 2016 | pmid = 26846989 | doi = 10.1177/1352458516628331 }}{{cite journal | vauthors = Rocca MA, Parisi L, Pagani E, Copetti M, Rodegher M, Colombo B, Comi G, Falini A, Filippi M | title = Regional but not global brain damage contributes to fatigue in multiple sclerosis | journal = Radiology | volume = 273 | issue = 2 | pages = 511–520 | date = November 2014 | pmid = 24927473 | doi = 10.1148/radiol.14140417 }} The correlation becomes unreliable due to ageing in patients aged over 65.{{cite journal | vauthors = Muñoz Maniega S, Chappell FM, Valdés Hernández MC, Armitage PA, Makin SD, Heye AK, Thrippleton MJ, Sakka E, Shuler K, Dennis MS, Wardlaw JM | title = Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 37 | issue = 2 | pages = 644–656 | date = February 2017 | pmid = 26933133 | pmc = 5381455 | doi = 10.1177/0271678X16635657 }}
A 2008 study found MS fatigue correlated with lesion load and brain atrophy.{{cite journal | vauthors = Sepulcre J, Masdeu JC, Goñi J, Arrondo G, Vélez de Mendizábal N, Bejarano B, Villoslada P | title = Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways | journal = Multiple Sclerosis | volume = 15 | issue = 3 | pages = 337–344 | date = March 2009 | pmid = 18987107 | doi = 10.1177/1352458508098373 | s2cid = 2701289 }}
A 2024 study found results suggested that fatigue was not driven by neuroinflammation or neurodegeneration measurable by current structural MRI in early RRMS.{{Cite journal|url=https://academic.oup.com/braincomms/article/6/5/fcae278/7733609|title=Fatigue in early multiple sclerosis: MRI metrics of neuroinflammation, relapse and neurodegeneration|date=October 1, 2024|journal=Brain Communications|volume=6|issue=5|pages=fcae278|via=Silverchair|doi=10.1093/braincomms/fcae278|pmc=11462441 |pmid=39386090 | vauthors = Meijboom R, Foley P, MacDougall NJ, Mina Y, York EN, Kampaite A, Mollison D, Kearns PK, White N, Thrippleton MJ, Murray K, ((del C Valdés Hernández M)), Reich DS, Connick P, Jacobson S, Nair G, Chandran S, Waldman AD }}
=Medications=
Medications used to treat MS fatigue include amantadine,{{cite journal | vauthors = Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C | title = Amantadine for fatigue in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2007 | issue = 1 | pages = CD002818 | date = January 2007 | pmid = 17253480 | pmc = 6991937 | doi = 10.1002/14651858.CD002818.pub2 | veditors = Pucci E }}{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682064.html | title = Amantadine | publisher = US National Library of Medicine | work = Medline | date = April 2003| access-date = 7 October 2007 }} pemoline,{{cite journal | vauthors = Weinshenker BG, Penman M, Bass B, Ebers GC, Rice GP | title = A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis | journal = Neurology | volume = 42 | issue = 8 | pages = 1468–1471 | date = August 1992 | pmid = 1641137 | doi = 10.1212/wnl.42.8.1468 | s2cid = 41990406 }}{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682313.html | title = Pemoline | publisher = US National Library of Medicine | work = Medline | date = January 2006 | access-date = 7 October 2007 }} methylphenidate, and modafinil,{{Cite web |date=2023-09-01 |title=Comparing Treatments for Multiple Sclerosis-Related Fatigue - Evidence Update for Clinicians {{!}} PCORI |url=https://www.pcori.org/evidence-updates/comparing-treatments-multiple-sclerosis-related-fatigue |access-date=2023-11-30 |website=www.pcori.org |language=en}} as well as cognitive behavioral therapy (CBT) and psychological interventions of energy conservation;{{cite journal | vauthors = Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P | title = Randomized controlled trial of an energy conservation course for persons with multiple sclerosis | journal = Multiple Sclerosis | volume = 11 | issue = 5 | pages = 592–601 | date = October 2005 | pmid = 16193899 | doi = 10.1191/1352458505ms1198oa | s2cid = 33902095 }}{{cite journal | vauthors = Matuska K, Mathiowetz V, Finlayson M | title = Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue | journal = The American Journal of Occupational Therapy | volume = 61 | issue = 1 | pages = 62–69 | year = 2007 | pmid = 17302106 | doi = 10.5014/ajot.61.1.62 | doi-access = }} but their effects are limited. For these reasons fatigue is a difficult symptom to manage.
=Technology=
As of 2022 apps were being experimented with in the field of MS fatigue.{{cite journal | vauthors = Pinarello C, Elmers J, Inojosa H, Beste C, Ziemssen T | title = Management of multiple sclerosis fatigue in the digital age: from assessment to treatment | journal = Frontiers in Neuroscience | volume = 17 | page = 1231321 | date = 2023 | pmid = 37869507 | pmc = 10585158 | doi = 10.3389/fnins.2023.1231321 | doi-access = free }}
Bladder and bowel
Bladder problems (See also urinary system and urination) appear in 70–80% of people with multiple sclerosis (MS) and they have an important effect both on hygiene habits and social activity.{{cite journal | vauthors = Hennessey A, Robertson NP, Swingler R, Compston DA | title = Urinary, faecal and sexual dysfunction in patients with multiple sclerosis | journal = Journal of Neurology | volume = 246 | issue = 11 | pages = 1027–1032 | date = November 1999 | pmid = 10631634 | doi = 10.1007/s004150050508 | s2cid = 30179761 }}{{cite journal | vauthors = Burguera-Hernández JA | title = [Urinary alterations in multiple sclerosis] | language = es | journal = Revista de Neurologia | volume = 30 | issue = 10 | pages = 989–992 | year = 2000 | pmid = 10919202 | doi = 10.33588/rn.3010.99371 }}
Bladder problems are usually related with high levels of disability and pyramidal signs in lower limbs.{{cite journal | vauthors = Betts CD, D'Mellow MT, Fowler CJ | title = Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 56 | issue = 3 | pages = 245–250 | date = March 1993 | pmid = 8459239 | pmc = 1014855 | doi = 10.1136/jnnp.56.3.245 }}
The most common problems are an increase in frequency and urgency (incontinence) but difficulties to begin urination, hesitation, leaking, sensation of incomplete urination, and retention also appear. When retention occurs secondary urinary infections are common.
There are many cortical and subcortical structures implicated in urination{{cite journal | vauthors = Nour S, Svarer C, Kristensen JK, Paulson OB, Law I | title = Cerebral activation during micturition in normal men | journal = Brain | volume = 123 ( Pt 4) | issue = 4 | pages = 781–789 | date = April 2000 | pmid = 10734009 | doi = 10.1093/brain/123.4.781 | doi-access = free }} and MS lesions in various central nervous system structures can cause these kinds of symptoms.
Treatment objectives are the alleviation of symptoms of urinary dysfunction, treatment of urinary infections, reduction of complicating factors and the preservation of renal function. Treatments can be classified in two main subtypes: pharmacological and non-pharmacological.
Pharmacological treatments vary greatly depending on the origin or type of dysfunction and some examples of the medications used are:{{cite journal | vauthors = Ayuso-Peralta L, de Andrés C | title = [Symptomatic treatment of multiple sclerosis] | language = es | journal = Revista de Neurologia | volume = 35 | issue = 12 | pages = 1141–1153 | year = 2002 | pmid = 12497297 | doi = 10.33588/rn.3512.2002385 }}
alfuzosin for retention,{{Cite web|url=https://medlineplus.gov/druginfo/meds/a604002.html|title=Alfuzosin| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}
trospium and flavoxate for urgency and incontinency,{{Cite web|url=https://medlineplus.gov/druginfo/meds/a604037.html|title=Trospium| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682706.html|title=Flavoxate| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}
and desmopressin for nocturia.{{cite journal | vauthors = Bosma R, Wynia K, Havlíková E, De Keyser J, Middel B | title = Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis | journal = Acta Neurologica Scandinavica | volume = 112 | issue = 1 | pages = 1–5 | date = July 2005 | pmid = 15932348 | doi = 10.1111/j.1600-0404.2005.00431.x | hdl-access = free | s2cid = 46673620 | hdl = 11370/1eb88003-4dfb-4de1-9aa2-1100972e8666 }}{{cite web | work = MedlinePlus | publisher = U.S. National Library of Medicine | title = Desmopressin
| url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682876.html }}
Non pharmacological treatments involve the use of pelvic floor muscle training, stimulation, biofeedback, pessaries, bladder retraining, and sometimes intermittent catheterization.{{Cite web | vauthors = Dyro FM | date = 8 August 2019 | veditors = Egan RA |url=https://emedicine.medscape.com/article/1159627-overview|title=Urologic Management in Neurologic Disease: Overview, Neuroanatomy of Pelvic Floor, Neurophysiology of Pelvic Floor |via=eMedicine }}{{cite book|last=The National Collaborating Centre for Chronic Conditions (UK)|url=https://www.ncbi.nlm.nih.gov/books/NBK48919/pdf/TOC.pdf |title=Multiple sclerosis: national clinical guideline for diagnosis and management in primary and secondary care|year=2004|publisher=Royal College of Physicians (UK)|location=London|isbn=978-1-86016-182-7|access-date=6 February 2013|pmid=21290636|chapter=Diagnosis and treatment of specific impairments|pages=87–132|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK48911/|series=NICE Clinical Guidelines|volume=8}}
Bowel problems affect around 70% of patients. Around 50% of patients experience constipation and up to 30% experience fecal incontinence. Cause of bowel impairments in MS patients is usually either a reduced gut motility or an impairment in neurological control of defecation. The former is commonly related to immobility or secondary effects from drugs used in the treatment of the disease. Pain or problems with defecation can be helped with a diet change which includes among other changes an increased fluid intake, oral laxatives or suppositories and enemas when habit changes and oral measures are not enough to control the problems.{{cite journal | vauthors = DasGupta R, Fowler CJ | title = Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies | journal = Drugs | volume = 63 | issue = 2 | pages = 153–166 | year = 2003 | pmid = 12515563 | doi = 10.2165/00003495-200363020-00003 | s2cid = 46351374 }}
Cognitive deficits (cog-fog)
=Deficits=
Some of the most common deficits affect recent memory, attention, processing speed, visual-spatial abilities and executive function.{{cite journal | vauthors = Bobholz JA, Rao SM | title = Cognitive dysfunction in multiple sclerosis: a review of recent developments | journal = Current Opinion in Neurology | volume = 16 | issue = 3 | pages = 283–288 | date = June 2003 | pmid = 12858063 | doi = 10.1097/00019052-200306000-00006 }} Symptoms related to cognition include emotional instability and fatigue including neurological fatigue. Cognitive deficits are independent of physical disability and can occur in the absence of neurological dysfunction.{{cite journal | vauthors = Amato MP, Ponziani G, Siracusa G, Sorbi S | title = Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years | journal = Archives of Neurology | volume = 58 | issue = 10 | pages = 1602–1606 | date = October 2001 | pmid = 11594918 | doi = 10.1001/archneur.58.10.1602 | doi-access = }}
=Appraisal=
Reviews have recommended annual appraisal using the Symbol Digit Modalities Test (SDMT) or similarly validated test.{{cite journal | doi=10.1177/1352458518803785 | title=Recommendations for cognitive screening and management in multiple sclerosis care | date=2018 | journal=Multiple Sclerosis Journal | volume=24 | issue=13 | pages=1665–1680 | pmid=30303036 | pmc=6238181 | vauthors = Kalb R, Beier M, Benedict RH, Charvet L, Costello K, Feinstein A, Gingold J, Goverover Y, Halper J, Harris C, Kostich L, Krupp L, Lathi E, Larocca N, Thrower B, Deluca J }}{{cite web | url=https://mymsaa.org/ms-information/symptoms/cognitive/ | title=Cognitive Changes | date=23 December 2015 }}{{cite journal | doi=10.1212/WNL.0000000000004977 | title=Cognition in multiple sclerosis | date=2018 | journal=Neurology | volume=90 | issue=6 | pages=278–288 | vauthors = Sumowski JF, Benedict R, Enzinger C, Filippi M, Geurts JJ, Hamalainen P, Hulst H, Inglese M, Leavitt VM, Rocca MA, Rosti-Otajarvi EM, Rao S | pmid=29343470 | pmc=5818015 }}
=Effects=
Severe cognitive impairment is a major predictor of a low quality of life, unemployment, caregiver distress, and difficulty in driving;{{cite journal | vauthors = Shawaryn MA, Schultheis MT, Garay E, Deluca J | title = Assessing functional status: exploring the relationship between the multiple sclerosis functional composite and driving | journal = Archives of Physical Medicine and Rehabilitation | volume = 83 | issue = 8 | pages = 1123–1129 | date = August 2002 | pmid = 12161835 | doi = 10.1053/apmr.2002.33730 }} limitations in a patient's social and work activities are also correlated with the extent of impairment.
=Prevalence=
Cognitive impairments occur in about 40 to 60 percent of patients with multiple sclerosis,{{cite journal | vauthors = Rao SM, Leo GJ, Bernardin L, Unverzagt F | title = Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction | journal = Neurology | volume = 41 | issue = 5 | pages = 685–691 | date = May 1991 | pmid = 2027484 | doi = 10.1212/wnl.41.5.685 | s2cid = 9962959 }}{{cite journal |doi=10.1016/j.msard.2023.104952 |doi-access=free |title=Managing cognitive impairment and its impact in multiple sclerosis: An Australian multidisciplinary perspective |date=2023 |journal=Multiple Sclerosis and Related Disorders |volume=79 |pmid=37683558 | vauthors = Lechner-Scott J, Agland S, Allan M, Darby D, Diamond K, Merlo D, Van Der Walt A }}
with the lowest percentages usually from community-based studies and the highest ones from hospital-based.
Impairments may be present at the beginning of the disease.{{cite journal | vauthors = Dujardin K, Donze AC, Hautecoeur P | title = Attention impairment in recently diagnosed multiple sclerosis | journal = European Journal of Neurology | volume = 5 | issue = 1 | pages = 61–66 | date = January 1998 | pmid = 10210813 | doi = 10.1046/j.1468-1331.1998.510061.x | s2cid = 33389996 }} Probable multiple sclerosis patients, meaning after a first attack but before a secondary confirmatory one, have up to 50 percent of patients with impairment at onset.{{cite journal | vauthors = Achiron A, Barak Y | title = Cognitive impairment in probable multiple sclerosis | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 74 | issue = 4 | pages = 443–446 | date = April 2003 | pmid = 12640060 | pmc = 1738365 | doi = 10.1136/jnnp.74.4.443 }} Dementia is rare and occurs in only five percent of patients.
=Causation=
Cognitive deficits have been linked to greater lesion load, white matter lesion location, microstructural injury, gray matter lesions, cortical and subcortical gray matter brain atrophy, and discrepant patterns of cerebral activation.
Measures of tissue atrophy are well correlated with, and predict, cognitive dysfunction. Neuropsychological outcomes are highly correlated with linear measures of sub-cortical atrophy. Cognitive impairment is the result of not only tissue damage,{{cite journal | vauthors = Kletenik I, Cohen AL, Glanz BI, Ferguson MA, Tauhid S, Li J, Drew W, Polgar-Turcsanyi M, Palotai M, Siddiqi SH, Marshall GA, Chitnis T, Guttmann CR, Bakshi R, Fox MD | title = Multiple sclerosis lesions that impair memory map to a connected memory circuit | journal = Journal of Neurology | volume = 270 | issue = 11 | pages = 5211–5222 | date = November 2023 | pmid = 37532802 | pmc = 10592111 | doi = 10.1007/s00415-023-11907-8 | s2cid = 260433348 }} but tissue repair and adaptive functional reorganization.{{cite journal | vauthors = Benedict RH, Carone DA, Bakshi R | title = Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis | journal = Journal of Neuroimaging | volume = 14 | issue = 3 Suppl | pages = 36S–45S | date = July 2004 | pmid = 15228758 | doi = 10.1177/1051228404266267 | doi-broken-date = 1 May 2025 }}
=Postulated treatments=
As of 2018 efficacy of possible interventions was low, inconclusive, or preliminary.
Neuropsychological rehabilitation may help to reverse or decrease the cognitive deficits although studies on the issue have been of low quality.{{cite journal | vauthors = Chiaravalloti ND, DeLuca J | title = Cognitive impairment in multiple sclerosis | journal = The Lancet. Neurology | volume = 7 | issue = 12 | pages = 1139–1151 | date = December 2008 | pmid = 19007738 | doi = 10.1016/S1474-4422(08)70259-X | s2cid = 25783642 }} Acetylcholinesterase inhibitors are commonly used to treat Alzheimer's disease related dementia and so are thought to have potential in treating the cognitive deficits in multiple sclerosis. They have been found to be effective in preliminary clinical trials.
= Prevention=
Emotional
Emotional symptoms are also common and are thought to be both a normal response to having a debilitating disease and the result of damage to specific areas of the central nervous system that generate and control emotions.{{citation needed|date=August 2021}}
Clinical depression is the most common neuropsychiatric condition: lifetime depression prevalence rates of 40–50% and 12-month prevalence rates around 20% have been typically reported for samples of people with MS; these figures are considerably higher than those for the general population or for people with other chronic illnesses.{{cite journal | vauthors = Sadovnick AD, Remick RA, Allen J, Swartz E, Yee IM, Eisen K, Farquhar R, Hashimoto SA, Hooge J, Kastrukoff LF, Morrison W, Nelson J, Oger J, Paty DW | title = Depression and multiple sclerosis | journal = Neurology | volume = 46 | issue = 3 | pages = 628–632 | date = March 1996 | pmid = 8618657 | doi = 10.1212/wnl.46.3.628 | s2cid = 33587300 }}{{cite journal | vauthors = Patten SB, Beck CA, Williams JV, Barbui C, Metz LM | title = Major depression in multiple sclerosis: a population-based perspective | journal = Neurology | volume = 61 | issue = 11 | pages = 1524–1527 | date = December 2003 | pmid = 14663036 | doi = 10.1212/01.wnl.0000095964.34294.b4 | s2cid = 1602489 | citeseerx = 10.1.1.581.3646 }} Brain imaging studies trying to relate depression to lesions in certain regions of the brain have met with variable success. On balance the evidence seems to favour an association with neuropathology in the left anterior temporal/parietal regions.{{cite journal | vauthors = Siegert RJ, Abernethy DA | title = Depression in multiple sclerosis: a review | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 76 | issue = 4 | pages = 469–475 | date = April 2005 | pmid = 15774430 | pmc = 1739575 | doi = 10.1136/jnnp.2004.054635 }}
Other feelings such as anger, anxiety, frustration, and hopelessness also appear frequently. Suicide is a possibility, since it accounts for 15% of MS deaths.{{cite journal | vauthors = Sadovnick AD, Eisen K, Ebers GC, Paty DW | title = Cause of death in patients attending multiple sclerosis clinics | journal = Neurology | volume = 41 | issue = 8 | pages = 1193–1196 | date = August 1991 | pmid = 1866003 | doi = 10.1212/wnl.41.8.1193 | s2cid = 31905744 }}
Rarely psychosis may also be featured.Murray ED, Buttner N, Price BH. (2012) Depression and Psychosis in Neurological Practice. In: Neurology in Clinical Practice, 6th Edition. Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds.) Butterworth Heinemann. April 12, 2012. {{ISBN|1-4377-0434-4}} | {{ISBN|978-1-4377-0434-1}}
Internuclear ophthalmoplegia
File:Internuclear ophthalmoplegia.jpg ]]
{{Main|Internuclear ophthalmoplegia}}
Internuclear ophthalmoplegia is a disorder of conjugate lateral gaze. The affected eye shows impairment of adduction. The partner eye diverges from the affected eye during abduction, producing diplopia; during extreme abduction, compensatory nystagmus can be seen in the partner eye. Diplopia means double vision while nystagmus is involuntary eye movement characterized by alternating smooth pursuit in one direction and a saccadic movement in the other direction.{{citation needed|date=August 2021}}
Internuclear ophthalmoplegia occurs when MS affects a part of the brain stem called the medial longitudinal fasciculus, which is responsible for communication between the two eyes by connecting the abducens nucleus of one side to the oculomotor nucleus of the opposite side. This results in the failure of the medial rectus muscle to contract appropriately, so that the eyes do not move equally (called disconjugate gaze).{{citation needed|date=June 2022}}
Different drugs as well as optic compensatory systems and prisms can be used to improve these symptoms.{{cite journal | vauthors = Leigh RJ, Averbuch-Heller L, Tomsak RL, Remler BF, Yaniglos SS, Dell'Osso LF | title = Treatment of abnormal eye movements that impair vision: strategies based on current concepts of physiology and pharmacology | journal = Annals of Neurology | volume = 36 | issue = 2 | pages = 129–141 | date = August 1994 | pmid = 8053648 | doi = 10.1002/ana.410360204 | s2cid = 23670958 }}{{cite journal | vauthors = Starck M, Albrecht H, Pöllmann W, Straube A, Dieterich M | title = Drug therapy for acquired pendular nystagmus in multiple sclerosis | journal = Journal of Neurology | volume = 244 | issue = 1 | pages = 9–16 | date = January 1997 | pmid = 9007739 | doi = 10.1007/PL00007728 | s2cid = 12333107 }}{{cite journal | vauthors = Clanet MG, Brassat D | title = The management of multiple sclerosis patients | journal = Current Opinion in Neurology | volume = 13 | issue = 3 | pages = 263–270 | date = June 2000 | pmid = 10871249 | doi = 10.1097/00019052-200006000-00005 }}{{cite journal | vauthors = Menon GJ, Thaller VT | title = Therapeutic external ophthalmoplegia with bilateral retrobulbar botulinum toxin- an effective treatment for acquired nystagmus with oscillopsia | journal = Eye | volume = 16 | issue = 6 | pages = 804–806 | date = November 2002 | pmid = 12439689 | doi = 10.1038/sj.eye.6700167 | doi-access = free }}
Surgery can also be used in some cases for this problem.{{cite journal | vauthors = Jain S, Proudlock F, Constantinescu CS, Gottlob I | title = Combined pharmacologic and surgical approach to acquired nystagmus due to multiple sclerosis | journal = American Journal of Ophthalmology | volume = 134 | issue = 5 | pages = 780–782 | date = November 2002 | pmid = 12429265 | doi = 10.1016/S0002-9394(02)01629-X }}
Mobility restrictions
File:Animal locomotion. Plate 559 (Boston Public Library) Animation all rows.gif]]
Restrictions in mobility (walking, transfers, bed mobility etc.) are common in individuals with multiple sclerosis. Although this is not something constant it can happen when experiencing a flare up. Within 10 years after the onset of MS one-third of patients reach a score of 6 on the Expanded Disability Status Scale (EDSS), requiring the use of a unilateral walking aid, and by 30 years the proportion increases to 83%. Within five years of onset the EDSS is six in 50% of those with the progressive form of MS.{{cite journal | vauthors = Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC | title = The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability | journal = Brain | volume = 112 ( Pt 1) | issue = 1 | pages = 133–146 | date = February 1989 | pmid = 2917275 | doi = 10.1093/brain/112.1.133 | doi-access = free }}
A wide range of impairments may exist in people with MS, which can act either alone or in combination to impact directly on a person's balance, function and mobility. Such impairments include fatigue, weakness, hypertonicity, low exercise tolerance, impaired balance, ataxia and tremor.{{cite journal | vauthors = Freeman JA | title = Improving mobility and functional independence in persons with multiple sclerosis | journal = Journal of Neurology | volume = 248 | issue = 4 | pages = 255–259 | date = April 2001 | pmid = 11374088 | doi = 10.1007/s004150170198 | s2cid = 12461962 }}
Interventions may be aimed at the individual impairments that reduce mobility or at the level of disability. This second level intervention includes provision, education, and instruction in the use of equipment such as walking aids, wheelchairs, motorized scooters and car adaptations as well as instruction on compensatory strategies to accomplish an activity — for example undertaking safe transfers by pivoting in a flexed posture rather than standing up and stepping around.
Optic neuritis
{{Main|Optic neuritis}}
Up to 50% of patients with MS will develop an episode of optic neuritis and 20% of the time optic neuritis is the presenting sign of MS. The presence of demyelinating white matter lesions on brain MRIs at the time of presentation for optic neuritis is the strongest predictor in developing clinical diagnosis of MS. Almost half of patients with optic neuritis have white matter lesions consistent with multiple sclerosis.
At five year follow-ups the overall risk of developing MS is 30%, with or without MRI lesions. Patients with a normal MRI still develop MS (16%), but at a lower rate compared to those patients with three or more MRI lesions (51%). From the other perspective, however, 44% of patients with any demyelinating lesions on MRI at presentation will not have developed MS ten years later.{{cite journal | vauthors = Beck RW, Trobe JD | title = What we have learned from the Optic Neuritis Treatment Trial | journal = Ophthalmology | volume = 102 | issue = 10 | pages = 1504–1508 | date = October 1995 | pmid = 9097798 | doi = 10.1016/s0161-6420(95)30839-1 }}{{cite journal | vauthors = | title = The 5-year risk of MS after optic neuritis: experience of the optic neuritis treatment trial. 1997 | journal = Neurology | volume = 57 | issue = 12 Suppl 5 | pages = S36–S45 | date = December 2001 | pmid = 11902594 }}
Individuals experience rapid onset of pain in one eye followed by blurry vision in part or all its visual field. Flashes of light (phosphenes) may also be present.{{cite journal | vauthors = Cervetto L, Demontis GC, Gargini C | title = Cellular mechanisms underlying the pharmacological induction of phosphenes | journal = British Journal of Pharmacology | volume = 150 | issue = 4 | pages = 383–390 | date = February 2007 | pmid = 17211458 | pmc = 2189731 | doi = 10.1038/sj.bjp.0706998 }} Inflammation of the optic nerve causes loss of vision most usually by the swelling and destruction of the myelin sheath covering the optic nerve.
The blurred vision usually resolves within 10 weeks but individuals are often left with less vivid color vision, especially red, in the affected eye.{{Citation needed|date=August 2010}}
A systemic intravenous treatment with corticosteroids may quicken the healing of the optic nerve, prevent complete loss of vision and delay the onset of other symptoms.{{Citation needed|date=August 2010}}
= Asymmetry in thickness of RNFL as indicator of optic neuritis in MS =
Asymmetry between the eyes in thickness of RNFL has been proposed as a strong indicator of optic neuritis in MS."An intereye difference of 5–6 μm in RNFL thickness is a robust structural threshold for identifying the presence of a unilateral optic nerve lesion in MS." {{cite journal | vauthors = Nolan RC, Galetta SL, Frohman TC, Frohman EM, Calabresi PA, Castrillo-Viguera C, Cadavid D, Balcer LJ | title = Optimal Intereye Difference Thresholds in Retinal Nerve Fiber Layer Thickness for Predicting a Unilateral Optic Nerve Lesion in Multiple Sclerosis | journal = Journal of Neuro-Ophthalmology | volume = 38 | issue = 4 | pages = 451–458 | date = December 2018 | pmid = 29384802 | doi = 10.1097/WNO.0000000000000629 | pmc = 8845082 }}{{cite journal | vauthors = Jiang H, Delgado S, Wang J | title = Advances in ophthalmic structural and functional measures in multiple sclerosis: do the potential ocular biomarkers meet the unmet needs? | journal = Current Opinion in Neurology | volume = 34 | issue = 1 | pages = 97–107 | date = February 2021 | pmid = 33278142 | pmc = 7856092 | doi = 10.1097/WCO.0000000000000897 }}{{cite journal | vauthors = Nij Bijvank J, Uitdehaag BM, Petzold A | title = Retinal inter-eye difference and atrophy progression in multiple sclerosis diagnostics | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 93 | issue = 2 | pages = 216–219 | date = February 2022 | pmid = 34764152 | pmc = 8785044 | doi = 10.1136/jnnp-2021-327468 }} RNFL data may indicate the pace of future development of the MS.{{cite journal | vauthors = Bsteh G, Hegen H, Altmann P, Auer M, Berek K, Pauli FD, Wurth S, Zinganell A, Rommer P, Deisenhammer F, Leutmezer F, Berger T | title = Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis | journal = Multiple Sclerosis Journal: Experimental, Translational and Clinical | volume = 6 | issue = 4 | page = 2055217320966344 | date = October 19, 2020 | pmid = 33194221 | pmc = 7604994 | doi = 10.1177/2055217320966344 }}{{cite journal | vauthors = Martinez-Lapiscina EH, Arnow S, Wilson JA, Saidha S, Preiningerova JL, Oberwahrenbrock T, Brandt AU, Pablo LE, Guerrieri S, Gonzalez I, Outteryck O, Mueller AK, Albrecht P, Chan W, Lukas S, Balk LJ, Fraser C, Frederiksen JL, Resto J, Frohman T, Cordano C, Zubizarreta I, Andorra M, Sanchez-Dalmau B, Saiz A, Bermel R, Klistorner A, Petzold A, Schippling S, Costello F, Aktas O, Vermersch P, Oreja-Guevara C, Comi G, Leocani L, Garcia-Martin E, Paul F, Havrdova E, Frohman E, Balcer LJ, Green AJ, Calabresi PA, Villoslada P | title = Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study | journal = The Lancet. Neurology | volume = 15 | issue = 6 | pages = 574–584 | date = May 2016 | pmid = 27011339 | doi = 10.1016/S1474-4422(16)00068-5 | url = https://discovery.ucl.ac.uk/id/eprint/1481598/ }}
Pain
Pain is a common symptom in MS. A 2013 study which systematically pooled results from 28 studies (7101 patients) estimated that pain affected 63% of people with MS.{{cite journal | vauthors = Foley PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, MacLeod MR, Fallon MT | title = Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis | journal = Pain | volume = 154 | issue = 5 | pages = 632–642 | date = May 2013 | pmid = 23318126 | doi = 10.1016/j.pain.2012.12.002 | s2cid = 25807525 }} These 28 studies described pain in a large range of different people with MS. The authors found no evidence that pain was more common in people with progressive types of MS, in females compared to males, in people with different levels of disability, or in people who had had MS for different periods of time.
MS pain can be
- neuropathic (nerve) pain directly caused by MS. A lesion in the brain or spinal cord can cause nerves to fire inappropriately. Neuropathic pain is most commonly steady, and described as burning, tight, tingling, nagging, aching, throbbing, or even icy. However neuropathic pain can also be intermittent, and described as shooting, stabbing, or lightning bolt-like. Other unpleasant sensations may also occur.
- musculoskeletal (muscle/bone) pain, caused when muscles, bones, or joints experience decreased mobility, prolonged sitting, spasms, and other improper use and disuse.{{Cite web|url=https://www.va.gov/MS/Veterans/symptoms_of_MS/Successfully_Managing_Pain_in_Multiple_Sclerosis.asp|title=VA.gov | Veterans Affairs|website=www.va.gov}}{{Cite web|url=https://mstrust.org.uk/a-z/pain|title=Pain | MS Trust|first=M. S.|last=Trust|website=mstrust.org.uk}}
MS patients may also be experiencing pain from comorbidity causes.{{Cite journal|title=Comorbidity is associated with pain-related activity limitations in multiple sclerosis|date=September 17, 2015|journal=Multiple Sclerosis and Related Disorders|volume=4|issue=5|pages=470–476|doi=10.1016/j.msard.2015.07.014|pmid=26346797|doi-access=free |author10=CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS) | vauthors = Fiest K, Fisk J, Patten S, Tremlett H, Wolfson C, Warren S, McKay K, Berrigan L, Marrie R }}
Pain can be severe and debilitating, and can have a profound effect on the quality of life and mental health of those affected.{{cite journal | vauthors = Archibald CJ, McGrath PJ, Ritvo PG, Fisk JD, Bhan V, Maxner CE, Murray TJ | title = Pain prevalence, severity and impact in a clinic sample of multiple sclerosis patients | journal = Pain | volume = 58 | issue = 1 | pages = 89–93 | date = July 1994 | pmid = 7970843 | doi = 10.1016/0304-3959(94)90188-0 | s2cid = 25295712 }}
Certain types of pain are thought to sometimes appear after a lesion to the ascending or descending tracts that control the transmission of painful stimulus, such as the anterolateral system, but many other causes are also possible.
The most prevalent types of pain are thought to be headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%) such as the MS Hug,{{Cite web|url=https://masterhealth.care/articles/ms-hug-7-tips-for-relieving-ms-hug-symptoms/|title=MS Hug: 7 Tips for Relieving MS Hug Symptoms|work=MasterHealth |date=November 25, 2022}} painful Lhermitte's phenomenon (16%) and Trigeminal Neuralgia (3%). These authors did not however find enough data to quantify the prevalence of painful optic neuritis.
Acute pain is mainly due to optic neuritis, trigeminal neuralgia, Lhermitte's sign or dysesthesias.{{cite journal | vauthors = Kerns RD, Kassirer M, Otis J | title = Pain in multiple sclerosis: a biopsychosocial perspective | journal = Journal of Rehabilitation Research and Development | volume = 39 | issue = 2 | pages = 225–232 | year = 2002 | pmid = 12051466 }} Subacute pain is usually secondary to the disease and can be a consequence of spending too much time in the same position, urinary retention, or infected skin ulcers. Chronic pain is common and harder to treat.{{Citation needed|date=August 2010}}
=Trigeminal neuralgia=
Trigeminal neuralgia (or "tic douloureux") is a disorder of the trigeminal nerve that causes episodes of intense pain in the eyes, lips, nose, scalp, forehead, and jaw, affecting 2-4% of MS patients. The episodes of pain occur paroxysmally (suddenly) and the patients describe it as trigger area on the face, so sensitive that touching or even air currents can bring an episode of pain. Usually it is successfully treated with anticonvulsants such as
carbamazepine,{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682237.html|title=Carbamazepine| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}
or phenytoin{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682022.html|title=Phenytoin| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}
although others such as gabapentin{{Cite web|url=https://medlineplus.gov/druginfo/meds/a694007.html|title=Gabapentin| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}} can be used.{{cite journal | vauthors = Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL | title = Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis | journal = European Neurology | volume = 44 | issue = 1 | pages = 45–48 | year = 2000 | pmid = 10894995 | doi = 10.1159/000008192 | s2cid = 39508538 | hdl = 11567/301010 }}
When drugs are not effective, surgery may be recommended. Glycerol rhizotomy (surgical injection of glycerol into a nerve) has been studied{{cite journal | vauthors = Kondziolka D, Lunsford LD, Bissonette DJ | title = Long-term results after glycerol rhizotomy for multiple sclerosis-related trigeminal neuralgia | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 21 | issue = 2 | pages = 137–140 | date = May 1994 | pmid = 8087740 | doi = 10.1017/S0317167100049076 | doi-access = free }}
although the beneficial effects and risks in MS patients of the procedures that relieve pressure on the nerve are still under discussion.{{cite journal | vauthors = Athanasiou TC, Patel NK, Renowden SA, Coakham HB | title = Some patients with multiple sclerosis have neurovascular compression causing their trigeminal neuralgia and can be treated effectively with MVD: report of five cases | journal = British Journal of Neurosurgery | volume = 19 | issue = 6 | pages = 463–468 | date = December 2005 | pmid = 16574557 | doi = 10.1080/02688690500495067 | s2cid = 33819410 }}{{cite journal | vauthors = Eldridge PR, Sinha AK, Javadpour M, Littlechild P, Varma TR | title = Microvascular decompression for trigeminal neuralgia in patients with multiple sclerosis | journal = Stereotactic and Functional Neurosurgery | volume = 81 | issue = 1–4 | pages = 57–64 | year = 2003 | pmid = 14742965 | doi = 10.1159/000075105 | s2cid = 39449873 }}
=Lhermitte's sign=
Lhermitte's sign is an electrical sensation that runs down the back and into the limbs and is produced by bending the neck forward. The sign suggests a lesion of the dorsal columns of the cervical cord or of the caudal medulla, correlating significantly with cervical MRI abnormalities.{{cite journal | vauthors = Gutrecht JA, Zamani AA, Slagado ED | title = Anatomic-radiologic basis of Lhermitte's sign in multiple sclerosis | journal = Archives of Neurology | volume = 50 | issue = 8 | pages = 849–851 | date = August 1993 | pmid = 8352672 | doi = 10.1001/archneur.1993.00540080056014 }}
Between 25 and 40% of MS patients report having Lhermitte's sign during the course of their illness.{{cite journal | vauthors = Al-Araji AH, Oger J | title = Reappraisal of Lhermitte's sign in multiple sclerosis | journal = Multiple Sclerosis | volume = 11 | issue = 4 | pages = 398–402 | date = August 2005 | pmid = 16042221 | doi = 10.1191/1352458505ms1177oa | s2cid = 33610136 }}{{cite journal | vauthors = Sandyk R, Dann LC | title = Resolution of Lhermitte's sign in multiple sclerosis by treatment with weak electromagnetic fields | journal = The International Journal of Neuroscience | volume = 81 | issue = 3–4 | pages = 215–224 | date = April 1995 | pmid = 7628912 | doi = 10.3109/00207459509004888 }}{{cite journal | vauthors = Kanchandani R, Howe JG | title = Lhermitte's sign in multiple sclerosis: a clinical survey and review of the literature | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 45 | issue = 4 | pages = 308–312 | date = April 1982 | pmid = 7077340 | pmc = 491365 | doi = 10.1136/jnnp.45.4.308 }} It is not always experienced as painful, but about 16% of people with MS will experience painful Lhermitte's sign.
=Dysesthesias=
Dysesthesias are disagreeable sensations produced by ordinary stimuli. The abnormal sensations are caused by lesions of the peripheral or central sensory pathways, and are described as painful feelings such as burning, wetness, itching, electric shock or pins and needles. Both Lhermitte's sign and painful dysesthesias usually respond well to treatment with carbamazepine, clonazepam or amitriptyline.{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682279.html|title=Clonazepam| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682388.html|title=Amitriptyline| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}{{cite journal | vauthors = Moulin DE, Foley KM, Ebers GC | title = Pain syndromes in multiple sclerosis | journal = Neurology | volume = 38 | issue = 12 | pages = 1830–1834 | date = December 1988 | pmid = 2973568 | doi = 10.1212/wnl.38.12.1830 | s2cid = 647138 }} A related symptom is a pleasant, yet unsettling sensation which has no normal explanation (such as sensation of gentle warmth arising from touch by clothing){{citation needed|date=August 2021}}
Reduced sense of smell
People with Multiple Sclerosis have been found to have reduced sense of smell, including lower olfactory thresholds.{{cite journal | vauthors = Schmidt FA, Maas MB, Geran R, Schmidt C, Kunte H, Ruprecht K, Paul F, Göktas Ö, Harms L | title = Olfactory dysfunction in patients with primary progressive MS | journal = Neurology | volume = 4 | issue = 4 | pages = e369 | date = July 2017 | pmid = 28638852 | pmc = 5471346 | doi = 10.1212/NXI.0000000000000369 | s2cid = 1080966 | doi-access = free }}{{cite web | url=https://ms-uk.org/news/smell-test-might-predict-dmt-affectiveness/ | title=Smell test might predict DMT affectiveness | date=4 April 2022 }}{{cite journal | vauthors = Atalar AÇ, Erdal Y, Tekin B, Yıldız M, Akdoğan Ö, Emre U | title = Olfactory dysfunction in multiple sclerosis | journal = Multiple Sclerosis and Related Disorders | volume = 21 | pages = 92–96 | date = April 2018 | pmid = 29529530 | doi = 10.1016/j.msard.2018.02.032 }}
Sexual
Sexual dysfunction (SD) is one of many symptoms affecting persons with a diagnosis of MS. SD in men encompasses both erectile and ejaculatory disorder. The prevalence of SD in men with MS ranges from 75 to 91%. Erectile dysfunction appears to be the most common form of SD documented in MS. SD may be due to alteration of the ejaculatory reflex which can be affected by neurological conditions such as MS.{{cite report | vauthors = O'Leary M, Heyman R, Erickson J, Chancellor MB | title = Premature Ejaculation and MS: A Review | url = https://cdn.ymaws.com/www.mscare.org/resource/resmgr/Articles/Article0025_PremEjac&MS.pdf | publisher = Consortium of MS Centers | date = June 2007 }} Sexual dysfunction is also prevalent in female MS patients, typically lack of orgasm, probably related to disordered genital sensation.
Spasticity and spasms
File:Animal locomotion. Plate 541 (Boston Public Library).jpg]]
Spasticity is characterised by involuntary muscle movements (spasms), muscle stiffness, pain and restriction with certain movements or positions (causing difficulty in performing some activities), and a change in mobility or upper limb function.{{Cite web|url=https://www.nice.org.uk/guidance/ng220/chapter/Recommendations#ms-symptom-management-and-rehabilitation|title=Recommendations | Multiple sclerosis in adults: management | Guidance | NICE|date=June 22, 2022|website=www.nice.org.uk}}
Spasms{{Cite web|url=https://mstrust.org.uk/a-z/spasticity-and-spasms|title=Spasticity and spasms | MS Trust|first=M. S.|last=Trust|website=mstrust.org.uk}}{{Cite web|url=https://www.mssociety.org.uk/about-ms/signs-and-symptoms/spasms-and-stiffness/understanding-spasms-and-stiffness|title=Understanding MS Spasms and Stiffness | MS Society|website=www.mssociety.org.uk}} affect about 15% of people with MS overall.
A physiotherapist can help to reduce spasticity and avoid the development of contractures with techniques such as passive stretching.{{cite journal | vauthors = Cardini RG, Crippa AC, Cattaneo D | title = Update on multiple sclerosis rehabilitation | journal = Journal of Neurovirology | volume = 6 | issue = Suppl 2 | pages = S179–S185 | date = May 2000 | pmid = 10871810 }} There is evidence, albeit limited, of the clinical effectiveness of THC and CBD extracts,{{cite journal | vauthors = Lakhan SE, Rowland M | title = Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review | journal = BMC Neurology | volume = 9 | page = 59 | date = December 2009 | pmid = 19961570 | pmc = 2793241 | doi = 10.1186/1471-2377-9-59 | doi-access = free }} baclofen,{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682530.html | title = Baclofen oral | publisher = U.S. National Library of Medicine | work = Medline | date = April 2003 | access-date = 17 October 2007 }} dantrolene,{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682576.html | title = Dantrolene oral | publisher = U.S. National Library of Medicine | work = Medline | date = April 2003 | access-date = 17 October 2007 }} diazepam,{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682047.html | title = Diazepam | publisher = U.S. National Library of Medicine | work = Medline | date = April 2003 | access-date = 17 October 2007 }} and tizanidine.{{cite web | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601121.html | title = Tizanidine | publisher = U.S. National Library of Medicine | work = Medline | date = April 2003 | access-date = 17 October 2007 }}.{{cite journal | vauthors = Beard S, Hunn A, Wight J | title = Treatments for spasticity and pain in multiple sclerosis: a systematic review | journal = Health Technology Assessment | volume = 7 | issue = 40 | pages = iii, ix–x, 1–111 | year = 2003 | pmid = 14636486 | doi = 10.3310/hta7400 | doi-access = free }}{{cite journal | vauthors = Paisley S, Beard S, Hunn A, Wight J | title = Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review | journal = Multiple Sclerosis | volume = 8 | issue = 4 | pages = 319–329 | date = August 2002 | pmid = 12166503 | doi = 10.1191/1352458502ms795rr | s2cid = 1641319 }} In the most complicated cases intrathecal injections of baclofen can be used.{{cite journal | vauthors = Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA | title = Long-term intrathecal baclofen therapy in patients with intractable spasticity | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 22 | issue = 3 | pages = 208–217 | date = August 1995 | pmid = 8529173 | doi = 10.1017/S031716710003986X | doi-access = free }} There are also palliative measures like castings, splints or customized seatings.
Speech and swallowing
Speech problems include slurred speech, decreased talking speed, and problems with articulation of sounds (dysarthria).{{Cite web|url=https://mymsaa.org/ms-information/symptoms/speech/|title=Speech Difficulties|first=Hoff|last=Communications|date=December 23, 2015|website=MSAA}} Low tone of voice (dysphonia) may be caused by changes in diaphragm control.{{Cite web|url=https://www.nationalmssociety.org/understanding-ms/what-is-ms/ms-symptoms/speech-problems|title=Empowering people affected by MS to live their best lives|website=National Multiple Sclerosis Society}}{{Cite web|url=https://mstrust.org.uk/a-z/speech-problems|title=Speech problems | MS Trust|first=M. S.|last=Trust|website=mstrust.org.uk}}
A related problem, since it involves similar anatomical structures, is swallowing difficulties (dysphagia).{{cite web|title=The Speech and Swallowing Problems of Multiple Sclerosis|url=http://www.webmd.com/multiple-sclerosis/guide/speech-swallowing?page=2|publisher=Web MD|access-date=25 May 2013|author=Richard Senelick (Reviewer)|date=Aug 2012}}
Transverse myelitis
{{Main|Transverse myelitis}}
Some MS patients develop rapid onset of numbness, weakness, bowel or bladder dysfunction, and/or loss of muscle function, typically in the lower half of the body.{{Citation needed|date=August 2010}} This is the result of MS attacking the spinal cord. The symptoms and signs depend upon the nerve cords involved and the extent of the involvement.
Prognosis for complete recovery is generally poor. Recovery from transverse myelitis usually begins between weeks 2 and 12 following onset and may continue for up to 2 years in some patients and as many as 80% of individuals with transverse myelitis are left with lasting disabilities.{{Citation needed|date=October 2007}}
Though it was considered for many years that traverse myelitis was a normal consequence of MS, since the discovery of anti-AQP4 and anti-MOG biomarkers it is not. Now TM is considered an indicator of neuromyelitis optica, and a red flag against the diagnosis of MS.{{cite journal | vauthors = Asnafi S, Morris PP, Sechi E, Pittock SJ, Weinshenker BG, Palace J, Messina S, Flanagan EP | title = The frequency of longitudinally extensive transverse myelitis in MS: A population-based study | journal = Multiple Sclerosis and Related Disorders | volume = 37 | issue = | page = 101487 | date = January 2020 | pmid = 31707235 | doi = 10.1016/j.msard.2019.101487 }}
Tremor and ataxia
{{Main|Tremor}}
Tremor is an unintentional, somewhat rhythmic, muscle movement involving to-and-fro movements (oscillations) of one or more parts of the body. It is the most common of all involuntary movements and can affect the hands, arms, head, face, vocal cords, trunk, and legs.
Ataxia is an unsteady and clumsy motion of the limbs or torso due to a failure of the gross coordination of muscle movements. People with ataxia experience a failure of muscle control in their arms and legs, resulting in a lack of balance and coordination or a disturbance of gait.
Tremor and ataxia are frequent in MS and present in 25 to 60% of patients. They can be very disabling and embarrassing, and are difficult to manage.{{cite journal | vauthors = Koch M, Mostert J, Heersema D, De Keyser J | title = Tremor in multiple sclerosis | journal = Journal of Neurology | volume = 254 | issue = 2 | pages = 133–145 | date = February 2007 | pmid = 17318714 | pmc = 1915650 | doi = 10.1007/s00415-006-0296-7 }} The origin of tremor in MS is difficult to identify but it can be due to a mixture of different factors such as damage to the cerebellar connections, weakness, spasticity, etc.
Many medications have been proposed to treat tremor; however their efficacy is very limited. Medications that have been reported to provide some relief are isoniazid,{{cite journal | vauthors = Bozek CB, Kastrukoff LF, Wright JM, Perry TL, Larsen TA | title = A controlled trial of isoniazid therapy for action tremor in multiple sclerosis | journal = Journal of Neurology | volume = 234 | issue = 1 | pages = 36–39 | date = January 1987 | pmid = 3546605 | doi = 10.1007/BF00314007 | s2cid = 23597601 }}{{cite journal | vauthors = Duquette P, Pleines J, du Souich P | title = Isoniazid for tremor in multiple sclerosis: a controlled trial | journal = Neurology | volume = 35 | issue = 12 | pages = 1772–1775 | date = December 1985 | pmid = 3906430 | doi = 10.1212/wnl.35.12.1772 | s2cid = 24266989 }}{{cite journal | vauthors = Hallett M, Lindsey JW, Adelstein BD, Riley PO | title = Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis | journal = Neurology | volume = 35 | issue = 9 | pages = 1374–1377 | date = September 1985 | pmid = 3895037 | doi = 10.1212/wnl.35.9.1374 | s2cid = 30254514 }}{{cite web | title = Isoniazid | url = https://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682401.html| publisher = U.S. National Library of Medicine | work = Medline | date = April 2003 | access-date = 17 October 2007 }} carbamazepine, propranolol{{cite journal | vauthors = Koller WC | title = Pharmacologic trials in the treatment of cerebellar tremor | journal = Archives of Neurology | volume = 41 | issue = 3 | pages = 280–281 | date = March 1984 | pmid = 6365047 | doi = 10.1001/archneur.1984.04050150058017 }}{{cite journal | vauthors = Sechi GP, Zuddas M, Piredda M, Agnetti V, Sau G, Piras ML, Tanca S, Rosati G | title = Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up | journal = Neurology | volume = 39 | issue = 8 | pages = 1113–1115 | date = August 1989 | pmid = 2668787 | doi = 10.1212/wnl.39.8.1113 | s2cid = 36050520 }}{{Cite web|url=https://medlineplus.gov/druginfo/meds/a682607.html|title=Propranolol (Cardiovascular)| work = MedlinePlus Drug Information | publisher = U.S. National Library of Medicine}}
and gluthetimide{{cite journal | vauthors = Aisen ML, Holzer M, Rosen M, Dietz M, McDowell F | title = Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury | journal = Archives of Neurology | volume = 48 | issue = 5 | pages = 513–515 | date = May 1991 | pmid = 2021365 | doi = 10.1001/archneur.1991.00530170077023 }} but published evidence of effectiveness is limited.{{cite journal | vauthors = Mills RJ, Yap L, Young CA | title = Treatment for ataxia in multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD005029 | date = January 2007 | pmid = 17253537 | doi = 10.1002/14651858.CD005029.pub2 | veditors = Mills RJ }} Physical therapy is not indicated as a treatment for tremor or ataxia although the use of orthese devices can help. An example is the use of wrist bandages with weights, which can be useful to increase the inertia of movement and therefore reduce tremor.{{cite journal | vauthors = Aisen ML, Arnold A, Baiges I, Maxwell S, Rosen M | title = The effect of mechanical damping loads on disabling action tremor | journal = Neurology | volume = 43 | issue = 7 | pages = 1346–1350 | date = July 1993 | pmid = 8327136 | doi = 10.1212/wnl.43.7.1346 | s2cid = 23433712 }} Daily use objects are also adapted so they are easier to grab and use.
If all these measures fail patients are candidates for thalamus surgery. This kind of surgery can be both a thalamotomy or the implantation of a thalamic stimulator. Complications are frequent (30% in thalamotomy and 10% in deep brain stimulation) and include a worsening of ataxia, dysarthria and hemiparesis. Thalamotomy is a more efficacious surgical treatment for intractable MS tremor though the higher incidence of persistent neurological deficits in patients receiving lesional surgery supports the use of deep brain stimulation as the preferred surgical strategy.{{cite journal | vauthors = Bittar RG, Hyam J, Nandi D, Wang S, Liu X, Joint C, Bain PG, Gregory R, Stein J, Aziz TZ | title = Thalamotomy versus thalamic stimulation for multiple sclerosis tremor | journal = Journal of Clinical Neuroscience | volume = 12 | issue = 6 | pages = 638–642 | date = August 2005 | pmid = 16098758 | doi = 10.1016/j.jocn.2004.09.008 | s2cid = 38770179 }}
Sleep disturbance
Around half of people with MS say they experience disturbed sleep.
Sleep disturbance is not regarded as a primary effect of the MS disease itself. Rather it is regarded as a secondary effect resulting from other factors that are themselves caused or exacerbated by MS, such as spasms, pain, anxiety, depression and high caffeine intake.{{cite web | url=https://mstrust.org.uk/information-support/wellbeing-ms/sleep | title=Sleep and MS | MS Trust }}{{cite web | url=https://www.nationalmssociety.org/managing-ms/living-with-ms/diet-exercise-and-healthy-behaviors/sleep | title=Empowering people affected by MS to live their best lives }}{{cite journal |doi=10.36740/WLek202102115 |url=https://wiadlek.pl/wp-content/uploads/archive/2021/WLek202102115.pdf |title=Sleep Disorders in Relapsing-Remitting Multiple Sclerosis Patients |date=2021 |journal=Wiadomości Lekarskie |volume=74 |issue=2 |pages=257–262 |pmid=33813482 | vauthors = Odintsova TA, Kopchak OO }}{{cite journal |doi=10.1191/135248506ms1320oa |url=https://www.researchgate.net/publication/6886015 |title=Sleep and fatigue in multiple sclerosis |date=2006 |journal=Multiple Sclerosis Journal |volume=12 |issue=4 |pages=481–486 |pmid=16900762 |vauthors = Stanton BR, Barnes F, Silber E }}{{cite journal | url=https://jnnp.bmj.com/content/93/11/1162 | pmid=35896381 | doi=10.1136/jnnp-2022-329227 | title=Poor sleep and multiple sclerosis: Associations with symptoms of multiple sclerosis and quality of life | date=2022 | journal=Journal of Neurology, Neurosurgery & Psychiatry | volume=93 | issue=11 | pages=1162–1165 | vauthors = Laslett LL, Honan C, Turner JA, Dagnew B, Campbell JA, Gill TK, Appleton S, Blizzard L, Taylor BV, Van Der Mei I }}{{cite web | url=https://www.ajmc.com/view/sleep-quality-in-ms-impacted-by-comorbidities-study-finds | title=Sleep Quality in MS Impacted by Comorbidities, Study Finds | date=16 May 2024 }}
MS fatigue has been found to not correlate with sleep duration, but there was some correlation with insomnia and sleep quality.{{cite journal | pmc=10460472 | date=2023 | title=Sleep disturbance and fatigue in multiple sclerosis: A systematic review and meta-analysis | journal=Multiple Sclerosis Journal - Experimental, Translational and Clinical | volume=9 | issue=3 | doi=10.1177/20552173231194352 | pmid=37641617 | vauthors = Patel KS, Dunn KM, Brown A, Opelt B, Hughes AJ, Hughes AJ }} It may be that primary MS fatigue is unaffected by sleep characteristics, but that sleep deprivation correlates with secondary MS fatigue.{{cite journal | doi=10.3389/fneur.2015.00021 | doi-access=free | title=Fatigue in Multiple Sclerosis: A Look at the Role of Poor Sleep | date=2015 | journal=Frontiers in Neurology | volume=6 | pmid=25729378 | vauthors = Strober LB | page=21 | pmc=4325921 }}
CPAP treatment in patients with MS and sleep apnea may reduce fatigue and improve the physical quality of life.{{cite web | url=https://www.neurologylive.com/view/effects-long-term-cpap-therapy-ms-daria-trojan | title=Effects of Long-term CPAP Therapy in Multiple Sclerosis: Daria Trojan, MD, MSC | date=15 November 2023 }}