Sandbox:JAF
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Multiple sclerosis Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Sandbox:JAF On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D. Julinka Auta Fernandes
Overview
The symptoms of multiple sclerosis (MS) are variable and may involve vision, sensory function, motor function, coordination, cognitive impairment, mood, bowel and bladder function, sexual dysfunction, sleep, and fatigue. Common manifestations include Fatigue, mood problems, spasticity, pain, eye movement problems, visual disturbance, gait and balance impairment, incoordination, cognitive impairment, mood disorders, bowel and bladder dysfunction, sexual dysfunction, sleep disorder, vertigo, and visual loss.[1]
The clinical manifestations of MS vary substantially between individuals and may change over the course of the disease. Assessment should consider the effects of symptoms on physical, cognitive, psychological, social, and occupational functioning, together with factors that may aggravate symptoms or mimic MS-related worsening.[1]
History and Symptoms
History
Clinical history and initial presentation of.
Patients with MS may report previous episodes of focal neurological dysfunction that develop over more than 24 hours, persist for days or weeks, and subsequently improve. Typical presenting features include loss or reduction of vision in 1 eye with painful eye movements, diplopia, sensory disturbance and/or weakness, Lhermitte's sign (an electric shock-like sensation or pain travelling down the spine and sometimes into the limbs when the neck is flexed forward), brainstem or cerebellar symptoms, and progressive difficulties with balance and gait.[1][2]
A typical MS presentation is generally characterized by focal neurological symptoms or signs rather than isolated nonspecific symptoms. Persistent fatigue, depression, dizziness, or vague sensory complaints without other evidence of focal neurological dysfunction should not, by themselves, be considered sufficient to suggest MS.[1]
The diagnosis of MS should use the revised 2024 McDonald criteria. The revised criteria provide a unified diagnostic framework for relapsing and progressive presentations. The optic nerve is recognized as a fifth anatomical location within the central nervous system for demonstrating dissemination in space, in addition to the periventricular, cortical or juxtacortical, infratentorial, and spinal cord regions. When available and appropriate, the central vein sign, paramagnetic rim lesions, and cerebrospinal fluid biomarkers including kappa free light chains may provide supportive diagnostic information. In selected circumstances, the revised criteria allow diagnosis without the traditional requirement for demonstration of dissemination in time.[2]
A clinical attack should represent a typical neurological event attributable to inflammation or demyelination in the central nervous system and should not be better explained by another disorder. The historical requirement that an attack must simply last more than 24 hours should therefore not be used in isolation to establish an MS diagnosis.[2]
Transient worsening of pre-existing neurological symptoms should be distinguished from a new relapse or progression of MS. Symptoms may worsen temporarily in association with increased body temperature, infection, fever, sleep disturbance, pain, medication effects, or other medical conditions. These contributing factors should be assessed before attributing symptom worsening to new inflammatory MS activity.[1]
Risk and epidemiologic history
Patients with MS may have a history or epidemiologic background associated with an increased risk of MS, including:
- Smoking. Cigarette smoking is associated with increased risk of MS and may adversely affect disease progression. Smoking cessation should therefore be encouraged as part of comprehensive MS care.[3]
- A family member with multiple sclerosis disease. Familial occurrence is associated with increased risk of MS, although most people with MS do not have an affected first-degree relative.[4][5]
- female sex. Multiple sclerosis is more common in women than in men, although the magnitude of the sex difference varies between populations and disease phenotypes.[6]
- Low vitamin D status or limited ultraviolet exposure. Observational studies have associated lower vitamin D status and lower sunlight exposure with increased MS risk. These associations do not establish vitamin D deficiency as a sufficient cause of MS.[7][8]
- Ethnic and geographic background. The incidence and prevalence of MS vary among populations and geographic regions. Differences reported between populations should be interpreted in the context of genetic susceptibility, environmental exposures, migration, and changing diagnostic practices.
- Previous Epstein-Barr virus (EBV) infection. EBV infection is strongly associated with subsequent development of MS, but EBV seropositivity or antibody titres alone are not diagnostic of MS.[9]
The previous American Academy of Neurology report concerning the relationship between MS and physical trauma or psychological stress is retired and should not be used as a current guideline for attributing MS onset or worsening to psychological stress or physical trauma.
Common Symptoms
The most common clinical manifestations of MS vary substantially between individuals. Symptoms may occur singly or in combination and may fluctuate over time.
- Fatigue: Fatigue is one of the most frequent and disabling symptoms of multiple sclerosis. It may be persistent or fluctuate during the day and may be worsened by physical or cognitive exertion. Clinicians should assess for potentially treatable contributors to fatigue, including sleep disturbance, pain, spasticity, bladder dysfunction, medication effects, infection, anemia, thyroid disease, anxiety, and depression. Management should be individualized and may include energy-conservation strategies, lifestyle measures, and aerobic, resistance, and balance exercise. Cognitive behavioural approaches may also be considered where appropriate.[1]
- Mood problems: Psychiatric symptoms, particularly depression and anxiety, are clinically important in MS and should be actively assessed. Pseudobulbar affect and emotional lability may also occur. Depression and other psychiatric symptoms should not be regarded as inevitable features of MS. The American Academy of Neurology guideline supports the use of validated assessment instruments for depressive symptoms and pseudobulbar affect and identifies telephone-delivered cognitive behavioural therapy as a possible treatment for depressive symptoms.[10]
- Spasticity: Spasticity may present with involuntary muscle spasms, muscle stiffness, pain, restricted movement, or worsening mobility and upper-limb function. Clinicians should assess for factors that can worsen spasticity, including pressure ulcers, bladder or bowel dysfunction, infection, poor posture or positioning, and pain. Reducing spasticity may sometimes adversely affect useful function such as standing, transfers, or walking and treatment should therefore be individualized.[1]
- Bowel and bladder dysfunction: Bowel and bladder dysfunction are common manifestations of MS. Bladder symptoms may include urgency, frequency, difficulty storing urine, difficulty emptying the bladder, or other lower urinary tract dysfunction. Bowel symptoms may include constipation, difficulty with evacuation, urgency, or incontinence. These symptoms should be assessed during routine comprehensive review, with consideration of infection, medication effects, mobility, fluid intake, and other contributing factors.[1]
- Eye movement abnormalities: Eye movement abnormalities may result from brainstem or cerebellar involvement and may produce diplopia, nystagmus, abnormalities of ocular motility, or oscillopsia. Ocular motor manifestations may occur during an acute neurological presentation.[1]
- Incoordination: Involvement of cerebellar pathways can cause problems with gait, balance, coordinated movement, and speech. Intention tremor may also occur. Mobility and balance impairment should be assessed in relation to weakness, spasticity, sensory impairment, ataxia, fatigue, and other contributing factors.[11][1]
- Pain: Pain in MS may be neuropathic, musculoskeletal, nociceptive, or mixed. Neuropathic pain may include burning, electric-shock-like, or other abnormal sensory pain. Musculoskeletal pain may arise in association with immobility, spasticity, altered posture, weakness, or abnormal movement. The cause of pain should be assessed before treatment is selected.[1][12]
- Sexual dysfunction: Sexual dysfunction may result from neurological impairment, sensory changes, bladder or bowel symptoms, fatigue, medication effects, psychological factors, or combinations of these factors. Manifestations may include reduced libido, impaired genital sensation or orgasm, erectile dysfunction, ejaculation problems, dyspareunia, and other difficulties with sexual function.[13]
- Sleep disorders: Sleep disturbance and daytime somnolence may occur in people with MS. Potential contributors include pain, nocturia, medication effects, restless legs syndrome, mood disorders, and other sleep disorders. Sleep should be assessed because sleep disturbance may worsen fatigue and cognitive symptoms.[1]
- Visual loss: Optic neuritis is an important MS presentation and may cause unilateral visual loss or reduction associated with pain on eye movement. Other visual manifestations may occur depending on the site of central nervous system involvement.[1][2]
Less Common Symptoms
- Heat sensitivity: Increased body temperature may cause transient worsening of pre-existing neurological symptoms in people with MS. This phenomenon, traditionally termed Uhthoff's phenomenon, should be distinguished from a new inflammatory relapse, particularly when symptoms improve after body temperature returns toward baseline.[1]
- Cognitive impairment: Cognitive impairment may occur early in MS and may involve attention, processing speed, executive function, learning, and memory. Cognitive symptoms should be assessed in the context of fatigue, sleep disturbance, mood disorders, and medication effects, which may themselves contribute to cognitive difficulties. Assessment and management should be individualized according to the person's cognitive profile and functional needs.[1]
- Vertigo: Vertigo and dizziness may occur in MS, particularly with brainstem or vestibular pathway involvement. However, nonspecific dizziness alone is not a typical reason to suspect MS, and alternative causes, including common peripheral vestibular disorders, should also be considered.[1]
Other Important Symptoms and Clinical Features
- Mobility and balance impairment: MS may cause gait impairment, falls, impaired balance, ataxia, weakness, spasticity, tremor, and reduced endurance. Mobility problems should be assessed comprehensively, including the contribution of fatigue, sensory impairment, visual impairment, pain, spasticity, and environmental factors. Exercise and rehabilitation should be individualized according to the person's abilities and goals.[1]
- Sensory symptoms: Sensory disturbances may include numbness, tingling, altered temperature or vibration sensation, dysaesthesia, and abnormal sensory pain. Sensory symptoms may occur as part of an acute demyelinating event or as persistent symptoms in established MS.[1][2]
- Motor symptoms and weakness: Weakness may be focal or may contribute to gait impairment, reduced endurance, falls, and difficulty with activities of daily living. Weakness should be considered together with spasticity, fatigue, sensory dysfunction, ataxia, and other neurological deficits when assessing mobility.[1]
- Lhermitte's sign: Lhermitte's sign is an electric-shock-like sensation that may travel down the spine and sometimes into the limbs when the neck is flexed. It may occur with cervical spinal cord involvement in MS but is not specific to MS.[1]
- Speech and swallowing: Dysarthria and other communication difficulties may occur with cerebellar, brainstem, or other neurological involvement. Swallowing difficulties may occur in some people with MS and should be assessed when clinically suspected because they may affect nutrition, hydration, and aspiration risk.[1]
- Emotional lability and pseudobulbar symptoms: Emotional lability, including involuntary laughing or crying that is disproportionate or unrelated to the person's underlying emotional state, may occur in MS. These symptoms should be distinguished from depression, anxiety, or other psychiatric disorders.[10][1]
- Bladder, bowel, and sexual symptoms may interact with fatigue, sleep disturbance, mobility, mood, and quality of life and should therefore be considered together during comprehensive MS assessment.[1]
Disease-modifying therapies (DMTs) are used to reduce MS disease activity and do not eliminate the need for treatment of established symptoms. People with MS may therefore require symptomatic treatment, rehabilitation, and other supportive interventions in addition to DMT.[14]
The American Academy of Neurology guideline on disease-modifying therapies was published in 2018 and reaffirmed in October 2024. It remains an important American evidence-based guideline for disease-modifying treatment but is not used as the principal source for the symptom inventory on this page.[14]
The joint ECTRIMS-EAN guideline remains an important European reference for pharmacological disease-modifying treatment of MS. It addresses treatment selection, response, switching, safety, and special situations including pregnancy. It is primarily a treatment guideline and is therefore cited selectively on this history and symptoms page.[15]
The ECTRIMS/EAN European guidance should be interpreted alongside newer European consensus work where applicable, but disease-modifying treatment selection and detailed pharmacological management are addressed in the dedicated treatment chapter rather than in this history and symptoms chapter.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 "Multiple sclerosis in adults: management (NG220)". National Institute for Health and Care Excellence. June 2022. Retrieved 2026-08-21.
- ↑ 2.0 2.1 2.2 2.3 2.4 Montalban X, Lebrun-Frénay C, Oh J, Arrambide G, Moccia M, Amato MP, Amezcua L, Banwell B, Bar-Or A, Barkhof F, Butzkueven H, Ciccarelli O, Chataway J, Cohen JA, Comi G, Correale J, Deisenhammer F, Filippi M, Fiol J, Freedman MS, Fujihara K, Granziera C, Green AJ, Hartung HP, Hellwig K, Kappos L, Kimbrough D, Killestein J, Lublin F, Marignier R, Marrie RA, Miller A, Otero-Romero S, Ontaneda D, Ramanathan S, Reich DS, Rocca MA, Rovira A, Saidha S, Salter A, Sastre-Garriga J, Saylor D, Solomon AJ, Sormani MP, Stankoff B, Tintore M, Tremlett H, Van der Walt A, Viswanathan S, Wiendl H, Wildemann B, Yamout B, Zaratin P, Calabresi PA, Coetzee T, Thompson AJ (October 2025). "Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria". Lancet Neurol. 24 (10): 850–865. doi:10.1016/S1474-4422(25)00270-4. PMID 40975101 Check
|pmid=value (help). - ↑ Hernán MA, Olek MJ, Ascherio A (July 2001). "Cigarette smoking and incidence of multiple sclerosis". Am. J. Epidemiol. 154 (1): 69–74. PMID 11427406.
- ↑ Robertson NP, Fraser M, Deans J, Clayton D, Walker N, Compston DA (April 1996). "Age-adjusted recurrence risks for relatives of patients with multiple sclerosis". Brain. 119 ( Pt 2): 449–55. PMID 8800940.
- ↑ Sadovnick AD, Baird PA, Ward RH (March 1988). "Multiple sclerosis: updated risks for relatives". Am. J. Med. Genet. 29 (3): 533–41. doi:10.1002/ajmg.1320290310. PMID 3376997.
- ↑ Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC (November 2006). "Sex ratio of multiple sclerosis in Canada: a longitudinal study". Lancet Neurol. 5 (11): 932–6. doi:10.1016/S1474-4422(06)70581-6. PMID 17052660.
- ↑ van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, Butzkueven H, Kilpatrick T (August 2003). "Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study". BMJ. 327 (7410): 316. doi:10.1136/bmj.327.7410.316. PMC 169645. PMID 12907484.
- ↑ Munger KL, Zhang SM, O'Reilly E, Hernán MA, Olek MJ, Willett WC, Ascherio A (January 2004). "Vitamin D intake and incidence of multiple sclerosis". Neurology. 62 (1): 60–5. PMID 14718698.
- ↑ Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A (May 2005). "Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis". JAMA. 293 (20): 2496–500. doi:10.1001/jama.293.20.2496. PMID 15914750.
- ↑ 10.0 10.1 Minden SL, Feinstein A, Kalb RC, Miller D, Mohr DC, Patten SB, Bever CT Jr, Schiffer RB, Gronseth GS, Narayanaswami P (January 2014). "Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology". Neurology. 82 (2): 174–181. doi:10.1212/WNL.0000000000000013. PMID 24376275.
- ↑ Rinker JR, Salter AR, Walker H, Amara A, Meador W, Cutter GR (January 2015). "Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey". BMJ Open. 5 (1): e006714. doi:10.1136/bmjopen-2014-006714. PMC 4289717. PMID 25573524.
- ↑ Foley PL, Vesterinen HM, Laird BJ, Sena ES, Colvin LA, Chandran S, MacLeod MR, Fallon MT (May 2013). "Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis". Pain. 154 (5): 632–42. doi:10.1016/j.pain.2012.12.002. PMID 23318126.
- ↑ Lew-Starowicz M, Gianotten WL (2015). "Sexual dysfunction in patients with multiple sclerosis". Handb Clin Neurol. 130: 357–70. doi:10.1016/B978-0-444-63247-0.00020-1. PMID 26003254.
- ↑ 14.0 14.1 "Practice Guideline Recommendations: Disease-modifying Therapies for Adults with Multiple Sclerosis". American Academy of Neurology. April 2018. Retrieved 2026-08-21.
- ↑ Montalban X, Gold R, Thompson AJ, Otero-Romero S, Amato MP, Chandraratna D, Clanet M, Comi G, Derfuss T, Fazekas F, Hartung HP, Havrdova E, Hemmer B, Kappos L, Liblau R, Lubetzki C, Marcus E, Miller DH, Olsson T, Pilling S, Selmaj K, Siva A, Sorensen PS, Sormani MP, Thalheim C, Wiendl H, Zipp F (February 2018). "ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis". Mult Scler. 24 (2): 96–120. doi:10.1177/1352458517751049.