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Multiple sclerosis, susceptibility to(MS)

MedGen UID:
358269
Concept ID:
C1868685
Finding
Synonyms: DISSEMINATED SCLEROSIS; Multiple sclerosis susceptibility
 
Genes (locations): HLA-DQB1 (6p21.32); HLA-DRB1 (6p21.32); PDCD1 (2q37.3)
 
Monarch Initiative: MONDO:0007462
OMIM®: 126200
OMIM® Phenotypic series: PS126200

Definition

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system (CNS) with various degrees of axonal damage. MS affects mainly young adults with predominance for females. The disorder often leads to substantial disability (summary by Bomprezzi et al., 2003). Genetic Heterogeneity of Susceptibility to Multiple Sclerosis Additional MS susceptibility loci include MS2 (612594) on chromosome 10p15, MS3 (612595) on chromosome 5p13, MS4 (612596) on chromosome 1p36, and MS5 (614810), conferred by variation in the TNFRSF1A gene (191190) on chromosome 12p13. [from OMIM]

Additional description

From MedlinePlus Genetics
Multiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord. These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath) and damage to nerve cells. Multiple sclerosis is considered an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.

Multiple sclerosis usually begins in early adulthood, between ages 20 and 40. The symptoms vary widely, and affected individuals can experience one or more effects of nervous system damage. Multiple sclerosis often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. Problems with muscle control are common in people with multiple sclerosis. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms worse.

There are several forms of multiple sclerosis: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. The most common is the relapsing-remitting form, which affects approximately 80 percent of people with multiple sclerosis. Individuals with this form of the condition have periods during which they experience symptoms, called clinical attacks, followed by periods without any symptoms (remission). The triggers of clinical attacks and remissions are unknown. After about 10 years, relapsing-remitting MS usually develops into another form of the disorder called secondary progressive MS. In this form, there are no remissions, and symptoms of the condition continually worsen.

Primary progressive MS is the next most common form, affecting approximately 10 to 20 percent of people with multiple sclerosis. This form is characterized by constant symptoms that worsen over time, with no clinical attacks or remissions. Primary progressive MS typically begins later than the other forms, around age 40.

Progressive relapsing MS is a rare form of multiple sclerosis that initially appears like primary progressive MS, with constant symptoms. However, people with progressive relapsing MS also experience clinical attacks of more severe symptoms.  https://medlineplus.gov/genetics/condition/multiple-sclerosis

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Urinary hesitancy
MedGen UID:
56259
Concept ID:
C0152032
Sign or Symptom
Difficulty in beginning the process of urination.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Emotional lability
MedGen UID:
39319
Concept ID:
C0085633
Mental or Behavioral Dysfunction
Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Incoordination
MedGen UID:
141714
Concept ID:
C0520966
Finding
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Diplopia
MedGen UID:
41600
Concept ID:
C0012569
Disease or Syndrome
Diplopia is a condition in which a single object is perceived as two images, it is also known as double vision.

Professional guidelines

PubMed

Kreft KL, Uzochukwu E, Loveless S, Willis M, Wynford-Thomas R, Harding KE, Holmans P, Lawton M, Tallantyre EC, Robertson NP
Ann Neurol 2024 Mar;95(3):459-470. Epub 2023 Dec 9 doi: 10.1002/ana.26831. PMID: 37974536
Abolfazli R, Samadzadeh S, Sabokbar T, Siroos B, Armaki SA, Aslanbeiki B, Ghelman M, Taheri T, Shakoori A
J Neurol Sci 2014 Oct 15;345(1-2):92-6. Epub 2014 Jul 16 doi: 10.1016/j.jns.2014.07.013. PMID: 25064442
McDonald I
Can J Neurol Sci 2004 Feb;31(1):37-47. doi: 10.1017/s031716710000281x. PMID: 15038469

Curated

UK NICE Guideline NG220, Multiple sclerosis in adults: management, 2022

Recent clinical studies

Etiology

Shams H, Shao X, Santaniello A, Kirkish G, Harroud A, Ma Q, Isobe N; University of California San Francisco MS-EPIC Team, Schaefer CA, McCauley JL, Cree BAC, Didonna A, Baranzini SE, Patsopoulos NA, Hauser SL, Barcellos LF, Henry RG, Oksenberg JR
Brain 2023 Feb 13;146(2):645-656. doi: 10.1093/brain/awac092. PMID: 35253861Free PMC Article
He D, Liu L, Shen D, Zou P, Cui L
Front Immunol 2022;13:867693. Epub 2022 May 10 doi: 10.3389/fimmu.2022.867693. PMID: 35619713Free PMC Article
Vandebergh M, Degryse N, Dubois B, Goris A
J Neurol 2022 Aug;269(8):4565-4574. Epub 2022 Apr 2 doi: 10.1007/s00415-022-11072-4. PMID: 35366084
Khoy K, Mariotte D, Defer G, Petit G, Toutirais O, Le Mauff B
Front Immunol 2020;11:549842. Epub 2020 Sep 24 doi: 10.3389/fimmu.2020.549842. PMID: 33072089Free PMC Article
Compston A, Coles A
Lancet 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X. PMID: 11955556

Diagnosis

Aloisi F, Giovannoni G, Salvetti M
Lancet Neurol 2023 Apr;22(4):338-349. Epub 2023 Feb 7 doi: 10.1016/S1474-4422(22)00471-9. PMID: 36764322
Guerrero BL, Sicotte NL
Front Immunol 2020;11:374. Epub 2020 Mar 20 doi: 10.3389/fimmu.2020.00374. PMID: 32265902Free PMC Article
Axisa PP, Hafler DA
Curr Opin Neurol 2016 Jun;29(3):345-53. doi: 10.1097/WCO.0000000000000319. PMID: 27058221Free PMC Article
Constantinescu CS, Farooqi N, O'Brien K, Gran B
Br J Pharmacol 2011 Oct;164(4):1079-106. doi: 10.1111/j.1476-5381.2011.01302.x. PMID: 21371012Free PMC Article
Compston A, Coles A
Lancet 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X. PMID: 11955556

Therapy

Begemann MJ, Brand BA, Ćurčić-Blake B, Aleman A, Sommer IE
Psychol Med 2020 Nov;50(15):2465-2486. Epub 2020 Oct 19 doi: 10.1017/S0033291720003670. PMID: 33070785Free PMC Article
Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG
Lancet Neurol 2020 Feb;19(2):179-194. Epub 2019 Nov 18 doi: 10.1016/S1474-4422(19)30356-4. PMID: 31753762
Alfredsson L, Olsson T
Cold Spring Harb Perspect Med 2019 Apr 1;9(4) doi: 10.1101/cshperspect.a028944. PMID: 29735578Free PMC Article
Axisa PP, Hafler DA
Curr Opin Neurol 2016 Jun;29(3):345-53. doi: 10.1097/WCO.0000000000000319. PMID: 27058221Free PMC Article
Compston A, Coles A
Lancet 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X. PMID: 11955556

Prognosis

Aloisi F, Giovannoni G, Salvetti M
Lancet Neurol 2023 Apr;22(4):338-349. Epub 2023 Feb 7 doi: 10.1016/S1474-4422(22)00471-9. PMID: 36764322
Kuhlmann T, Moccia M, Coetzee T, Cohen JA, Correale J, Graves J, Marrie RA, Montalban X, Yong VW, Thompson AJ, Reich DS; International Advisory Committee on Clinical Trials in Multiple Sclerosis
Lancet Neurol 2023 Jan;22(1):78-88. Epub 2022 Nov 18 doi: 10.1016/S1474-4422(22)00289-7. PMID: 36410373Free PMC Article
He D, Liu L, Shen D, Zou P, Cui L
Front Immunol 2022;13:867693. Epub 2022 May 10 doi: 10.3389/fimmu.2022.867693. PMID: 35619713Free PMC Article
Ascherio A, Munger KL
Semin Neurol 2016 Apr;36(2):103-14. Epub 2016 Apr 26 doi: 10.1055/s-0036-1579693. PMID: 27116717
Compston A, Coles A
Lancet 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X. PMID: 11955556

Clinical prediction guides

Shams H, Shao X, Santaniello A, Kirkish G, Harroud A, Ma Q, Isobe N; University of California San Francisco MS-EPIC Team, Schaefer CA, McCauley JL, Cree BAC, Didonna A, Baranzini SE, Patsopoulos NA, Hauser SL, Barcellos LF, Henry RG, Oksenberg JR
Brain 2023 Feb 13;146(2):645-656. doi: 10.1093/brain/awac092. PMID: 35253861Free PMC Article
He D, Liu L, Shen D, Zou P, Cui L
Front Immunol 2022;13:867693. Epub 2022 May 10 doi: 10.3389/fimmu.2022.867693. PMID: 35619713Free PMC Article
Vandebergh M, Degryse N, Dubois B, Goris A
J Neurol 2022 Aug;269(8):4565-4574. Epub 2022 Apr 2 doi: 10.1007/s00415-022-11072-4. PMID: 35366084
Montarolo F, Martire S, Perga S, Bertolotto A
Int J Mol Sci 2019 Sep 30;20(19) doi: 10.3390/ijms20194858. PMID: 31574937Free PMC Article
Canto E, Oksenberg JR
Mult Scler 2018 Jan;24(1):75-79. doi: 10.1177/1352458517737371. PMID: 29307290

Recent systematic reviews

Voon CC, Wiltgen T, Wiestler B, Schlaeger S, Mühlau M
Neuroimage Clin 2024;42:103598. Epub 2024 Mar 25 doi: 10.1016/j.nicl.2024.103598. PMID: 38582068Free PMC Article
De Lury AD, Bisulca JA, Lee JS, Altaf MD, Coyle PK, Duong TQ
J Neurol Sci 2023 Oct 15;453:120816. Epub 2023 Sep 29 doi: 10.1016/j.jns.2023.120816. PMID: 37827008
Harirchian MH, Fatehi F, Sarraf P, Honarvar NM, Bitarafan S
Mult Scler Relat Disord 2018 Feb;20:43-47. Epub 2017 Dec 24 doi: 10.1016/j.msard.2017.12.015. PMID: 29291483
Zhang YJ, Zhang L, Chen SY, Yang GJ, Huang XL, Duan Y, Yang LJ, Ye DQ, Wang J
Neurol Sci 2018 Feb;39(2):225-234. Epub 2017 Nov 6 doi: 10.1007/s10072-017-3175-3. PMID: 29110148
Andalib S, Emamhadi M, Yousefzadeh-Chabok S, Salari A, Sigaroudi AE, Vafaee MS
Acta Neurol Belg 2016 Dec;116(4):439-443. Epub 2016 Jul 25 doi: 10.1007/s13760-016-0675-5. PMID: 27457485

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2022
      UK NICE Guideline NG220, Multiple sclerosis in adults: management, 2022

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