Multiple sclerosis natural history, complications and prognosis: Difference between revisions

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* Bowel and bladder dysfunction: [[Bowel]] and [[bladder]] dysfunction is common in [[MS]] patients and accurse in more than 50% of them.<ref name="pmid12515563">{{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=153–66 |date=2003 |pmid=12515563 |doi= |url=}}</ref> [[bladder]] dysfunction can be the result of [[Detrusor hyperactivity|Detrusor overactivity]], Detrusor sphincter dyssynergia, Inefficient [[bladder]] [[contractility]] and Abnormal [[sensation]] and [[bladder]] hypoactivity.<ref name="pmid27116728">{{cite journal |vauthors=Wintner A, Kim MM, Bechis SK, Kreydin EI |title=Voiding Dysfunction in Multiple Sclerosis |journal=Semin Neurol |volume=36 |issue=2 |pages=219–20 |date=April 2016 |pmid=27116728 |doi=10.1055/s-0036-1582255 |url=}}</ref> the most common [[bowel]] problems include [[Constipation]], poor [[defecation]] and [[incontinence]].<ref name="pmid10631634">{{cite journal |vauthors=Hennessey A, Robertson NP, Swingler R, Compston DA |title=Urinary, faecal and sexual dysfunction in patients with multiple sclerosis |journal=J. Neurol. |volume=246 |issue=11 |pages=1027–32 |date=November 1999 |pmid=10631634 |doi= |url=}}</ref>
* Bowel and bladder dysfunction: [[Bowel]] and [[bladder]] dysfunction is common in [[MS]] patients and accurse in more than 50% of them.<ref name="pmid12515563">{{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=153–66 |date=2003 |pmid=12515563 |doi= |url=}}</ref> [[bladder]] dysfunction can be the result of [[Detrusor hyperactivity|Detrusor overactivity]], Detrusor sphincter dyssynergia, Inefficient [[bladder]] [[contractility]] and Abnormal [[sensation]] and [[bladder]] hypoactivity.<ref name="pmid27116728">{{cite journal |vauthors=Wintner A, Kim MM, Bechis SK, Kreydin EI |title=Voiding Dysfunction in Multiple Sclerosis |journal=Semin Neurol |volume=36 |issue=2 |pages=219–20 |date=April 2016 |pmid=27116728 |doi=10.1055/s-0036-1582255 |url=}}</ref> the most common [[bowel]] problems include [[Constipation]], poor [[defecation]] and [[incontinence]].<ref name="pmid10631634">{{cite journal |vauthors=Hennessey A, Robertson NP, Swingler R, Compston DA |title=Urinary, faecal and sexual dysfunction in patients with multiple sclerosis |journal=J. Neurol. |volume=246 |issue=11 |pages=1027–32 |date=November 1999 |pmid=10631634 |doi= |url=}}</ref>


* Cognitive impairment: [[Cognitive disorder|Cognitive disorders]] is common in [[MS]] patients and can even present at early stages of disease. These disorders are in [[attention]], short term memory and information processing. Relapsing-remitting type of [[MS]] seems to have lower [[Cognitive disorder|cognitive problems]].
* Cognitive impairment: [[Cognitive disorder|Cognitive disorders]] is common in [[MS]] patients and can even present at early stages of disease. These disorders are in [[attention]], short term memory and information processing. Relapsing-remitting type of [[MS]] seems to have lower [[Cognitive disorder|cognitive problems]].<ref name="pmid12640060">{{cite journal |vauthors=Achiron A, Barak Y |title=Cognitive impairment in probable multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatry |volume=74 |issue=4 |pages=443–6 |date=April 2003 |pmid=12640060 |pmc=1738365 |doi= |url=}}</ref><ref name="pmid15774439">{{cite journal |vauthors=Deloire MS, Salort E, Bonnet M, Arimone Y, Boudineau M, Amieva H, Barroso B, Ouallet JC, Pachai C, Galliaud E, Petry KG, Dousset V, Fabrigoule C, Brochet B |title=Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatry |volume=76 |issue=4 |pages=519–26 |date=April 2005 |pmid=15774439 |pmc=1739602 |doi=10.1136/jnnp.2004.045872 |url=}}</ref><ref name="pmid2027484">{{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=685–91 |date=May 1991 |pmid=2027484 |doi= |url=}}</ref><ref name="pmid15277630">{{cite journal |vauthors=Huijbregts SC, Kalkers NF, de Sonneville LM, de Groot V, Reuling IE, Polman CH |title=Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS |journal=Neurology |volume=63 |issue=2 |pages=335–9 |date=July 2004 |pmid=15277630 |doi= |url=}}</ref>


* Heat sensitivity: Patients with [[MS]] disease are more sensitive to heat. A slight increase in [[body temperature]] of these patients will lead to worsening of their [[Sign (medicine)|sign]]<nowiki/>s and [[symptom]]<nowiki/>s.
* Heat sensitivity: Patients with [[MS]] disease are more sensitive to heat. A slight increase in [[body temperature]] of these patients will lead to worsening of their [[Sign (medicine)|sign]]<nowiki/>s and [[symptom]]<nowiki/>s.<ref name="pmid7550931">{{cite journal |vauthors=Selhorst JB, Saul RF |title=Uhthoff and his symptom |journal=J Neuroophthalmol |volume=15 |issue=2 |pages=63–9 |date=June 1995 |pmid=7550931 |doi= |url=}}</ref>


* Incoordination: involvement of [[cerebellar]] tracts can cause  Problems in [[Gait]] and balance, poor coordinated actions and [[slurred speech]]. [[Intention tremor]] is present in most of these patients.
* Incoordination: involvement of [[cerebellar]] tracts can cause  Problems in [[Gait]] and balance, poor coordinated actions and [[slurred speech]]. [[Intention tremor]] is present in most of these patients.<ref name="pmid25573524">{{cite journal |vauthors=Rinker JR, Salter AR, Walker H, Amara A, Meador W, Cutter GR |title=Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey |journal=BMJ Open |volume=5 |issue=1 |pages=e006714 |date=January 2015 |pmid=25573524 |pmc=4289717 |doi=10.1136/bmjopen-2014-006714 |url=}}</ref>


* Pain: [[Pain]], a very common [[symptom]] in [[MS]] patients can be either from [[neurogenic]] source leading to burning or ice-cold [[dysesthesias]] or from long immobilization and [[spasm]].
* Pain: [[Pain]], a very common [[symptom]] in [[MS]] patients can be either from [[neurogenic]] source leading to burning or ice-cold [[dysesthesias]] or from long immobilization and [[spasm]].<ref name="pmid26087108">{{cite journal |vauthors=Drulovic J, Basic-Kes V, Grgic S, Vojinovic S, Dincic E, Toncev G, Kezic MG, Kisic-Tepavcevic D, Dujmovic I, Mesaros S, Miletic-Drakulic S, Pekmezovic T |title=The Prevalence of Pain in Adults with Multiple Sclerosis: A Multicenter Cross-Sectional Survey |journal=Pain Med |volume=16 |issue=8 |pages=1597–602 |date=August 2015 |pmid=26087108 |doi=10.1111/pme.12731 |url=}}</ref><ref name="pmid23318126">{{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=632–42 |date=May 2013 |pmid=23318126 |doi=10.1016/j.pain.2012.12.002 |url=}}</ref>


* Sexual dysfunction: [[Sexual dysfunction]] can be due to involvement of [[Motor disorders|motor]] and [[Sensory system|sensory]] pathways or from [[psychological]] problems but either way, it’s a very common [[symptom]]. In women we can see reduced [[libido]] and [[orgasm]], [[dyspareunia]] and decrease [[vaginal]] sensation. Presentations of sexual dysfunction in men are decreased [[libido]] and [[premature ejaculation]], [[erectile dysfunction]] and decreased [[Penis|penile]] sensation.
* Sexual dysfunction: [[Sexual dysfunction]] can be due to involvement of [[Motor disorders|motor]] and [[Sensory system|sensory]] pathways or from [[psychological]] problems but either way, it’s a very common [[symptom]]. In women we can see reduced [[libido]] and [[orgasm]], [[dyspareunia]] and decrease [[vaginal]] sensation. Presentations of sexual dysfunction in men are decreased [[libido]] and [[premature ejaculation]], [[erectile dysfunction]] and decreased [[Penis|penile]] sensation.<ref name="pmid26003254">{{cite journal |vauthors=Lew-Starowicz M, Gianotten WL |title=Sexual dysfunction in patients with multiple sclerosis |journal=Handb Clin Neurol |volume=130 |issue= |pages=357–70 |date=2015 |pmid=26003254 |doi=10.1016/B978-0-444-63247-0.00020-1 |url=}}</ref><ref name="pmid10618700">{{cite journal |vauthors=Zivadinov R, Zorzon M, Bosco A, Bragadin LM, Moretti R, Bonfigli L, Iona LG, Cazzato G |title=Sexual dysfunction in multiple sclerosis: II. Correlation analysis |journal=Mult. Scler. |volume=5 |issue=6 |pages=428–31 |date=December 1999 |pmid=10618700 |doi=10.1177/135245859900500i610 |url=}}</ref>


* Sleep disorders: Many patients with multiple sclerosis suffer from [[sleep disorders]] and daytime [[somnolence]]. This can be the result of so many conditions including [[restless leg syndrome]], [[nocturia]], [[pain]] and medication side effects. Having more cervical lesions lead to experiencing [[restless leg syndrome]] more often.
* Sleep disorders: Many patients with multiple sclerosis suffer from [[sleep disorders]] and daytime [[somnolence]]. This can be the result of so many conditions including [[restless leg syndrome]], [[nocturia]], [[pain]] and medication side effects. Having more cervical lesions lead to experiencing [[restless leg syndrome]] more often.<ref name="pmid17942519">{{cite journal |vauthors=Manconi M, Rocca MA, Ferini-Strambi L, Tortorella P, Agosta F, Comi G, Filippi M |title=Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage |journal=Mult. Scler. |volume=14 |issue=1 |pages=86–93 |date=January 2008 |pmid=17942519 |doi=10.1177/1352458507080734 |url=}}</ref><ref name="pmid8787103">{{cite journal |vauthors=Amarenco G, Kerdraon J, Denys P |title=[Bladder and sphincter disorders in multiple sclerosis. Clinical, urodynamic and neurophysiological study of 225 cases] |language=French |journal=Rev. Neurol. (Paris) |volume=151 |issue=12 |pages=722–30 |date=December 1995 |pmid=8787103 |doi= |url=}}</ref><ref name="pmid23078359">{{cite journal |vauthors=Schürks M, Bussfeld P |title=Multiple sclerosis and restless legs syndrome: a systematic review and meta-analysis |journal=Eur. J. Neurol. |volume=20 |issue=4 |pages=605–15 |date=April 2013 |pmid=23078359 |doi=10.1111/j.1468-1331.2012.03873.x |url=}}</ref>


* vertigo: Benign positional paroxysmal [[vertigo]] is the most common cause of [[vertigo]] in [[MS]] patient. In the course of the disease about 30-50% of patients experience this [[symptom]].
* vertigo: Benign positional paroxysmal [[vertigo]] is the most common cause of [[vertigo]] in [[MS]] patient. In the course of the disease about 30-50% of patients experience this [[symptom]].<ref name="pmid11094117">{{cite journal |vauthors=Frohman EM, Zhang H, Dewey RB, Hawker KS, Racke MK, Frohman TC |title=Vertigo in MS: utility of positional and particle repositioning maneuvers |journal=Neurology |volume=55 |issue=10 |pages=1566–9 |date=November 2000 |pmid=11094117 |doi= |url=}}</ref>


* visual loss: [[Optic neuritis]] is the most common eye involvement and presents as an [[acute]] unilateral eye [[pain]], followed by some degree of [[vision loss]].
* visual loss: [[Optic neuritis]] is the most common eye involvement and presents as an [[acute]] unilateral eye [[pain]], followed by some degree of [[vision loss]].<ref name="pmid16554529">{{cite journal |vauthors=Balcer LJ |title=Clinical practice. Optic neuritis |journal=N. Engl. J. Med. |volume=354 |issue=12 |pages=1273–80 |date=March 2006 |pmid=16554529 |doi=10.1056/NEJMcp053247 |url=}}</ref>


== Prognosis ==
== Prognosis ==

Revision as of 19:47, 1 March 2018

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Overview

Natural History

The symptoms of multiple sclerosis usually develop in the first/ second/ third decade of life, and start with symptoms such as optic neuritis, diplopia, sensory or motor loss, vertigo and balance problems. In young adult eye and sensory problems are prominent while in older patients we see motor problems more often.[1]

Complications

Complications that can develop as a result of mutiple sclerosis are:

  • medication complication: Insufficient blood supply to the bone can cause avascular osteonecrosis. After trauma corticosteroid treatment is the most common cause of AVN.[2][3]
  • Fatigue: Fatigue is seen in almost 80% of MS patient. They commonly feel exhausted and out of energy. We can see fatigue exacerbation before acute attacks in MS and for a while after that.[4]
  • Spasticity: Damage to the upper motor neurons and decrease inhibition of lower motor neurons in MS can increase muscle tone and rigidity in 75% of MS patients.[8]
  • Heat sensitivity: Patients with MS disease are more sensitive to heat. A slight increase in body temperature of these patients will lead to worsening of their signs and symptoms.[16]
  • vertigo: Benign positional paroxysmal vertigo is the most common cause of vertigo in MS patient. In the course of the disease about 30-50% of patients experience this symptom.[25]

Prognosis

there are some factors associated with a particularly poor prognosis among patients with multiple sclerosis but We can’t surly say what is the prognosis of MS patients.[27]

Relapsing versus progressive disease

Progressive form of MS seems to have worse prognosis in comparison to relapsing remitting form of MS. Disabilities start sooner in progressive form[28][29][30] but some studies showed that age of onset is more important in MS disability than the form of the disease.[31][32]

Early symptoms

Some first manifestations of MS disease like bowel and bladder dysfunction, seems to have a worse prognosis.[33]. Another study demonstrated that having so many symptoms at the onset of the disease have a worse prognosis than being monosymptom.[34]

Demographics

Onset of MS in Black Americans is in later age and they are more susceptible of having multifocal signs and symptoms and involvement of optic nerve and spinal cord.[35]

Sex

Women seems to have younger age of onset and so better prognosis than men.[28]

Smoking

Transition of RRMS to SPMS can be accelerated with smoking.[36]

References

  1. ↑ Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC (February 1989). "The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability". Brain. 112 ( Pt 1): 133–46. PMID 2917275.
  2. ↑ Yamamoto T, Irisa T, Sugioka Y, Sueishi K (November 1997). "Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits". Arthritis Rheum. 40 (11): 2055–64. doi:10.1002/1529-0131(199711)40:11&lt;2055::AID-ART19&gt;3.0.CO;2-E. PMID 9365096.
  3. ↑ Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME (October 2002). "Pathogenesis and natural history of osteonecrosis". Semin. Arthritis Rheum. 32 (2): 94–124. PMID 12430099.
  4. ↑ Krupp L (August 2006). "Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease". Mult. Scler. 12 (4): 367–8. doi:10.1191/135248506ms1373ed. PMID 16900749.
  5. ↑ 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 (March 1996). "Depression and multiple sclerosis". Neurology. 46 (3): 628–32. PMID 8618657.
  6. ↑ Sadovnick AD, Eisen K, Ebers GC, Paty DW (August 1991). "Cause of death in patients attending multiple sclerosis clinics". Neurology. 41 (8): 1193–6. PMID 1866003.
  7. ↑ Stenager EN, Stenager E (December 1992). "Suicide and patients with neurologic diseases. Methodologic problems". Arch. Neurol. 49 (12): 1296–303. PMID 1449409.
  8. ↑ Boissy AR, Cohen JA (September 2007). "Multiple sclerosis symptom management". Expert Rev Neurother. 7 (9): 1213–22. doi:10.1586/14737175.7.9.1213. PMID 17868019.
  9. ↑ DasGupta R, Fowler CJ (2003). "Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies". Drugs. 63 (2): 153–66. PMID 12515563.
  10. ↑ Wintner A, Kim MM, Bechis SK, Kreydin EI (April 2016). "Voiding Dysfunction in Multiple Sclerosis". Semin Neurol. 36 (2): 219–20. doi:10.1055/s-0036-1582255. PMID 27116728.
  11. ↑ Hennessey A, Robertson NP, Swingler R, Compston DA (November 1999). "Urinary, faecal and sexual dysfunction in patients with multiple sclerosis". J. Neurol. 246 (11): 1027–32. PMID 10631634.
  12. ↑ Achiron A, Barak Y (April 2003). "Cognitive impairment in probable multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 74 (4): 443–6. PMC 1738365. PMID 12640060.
  13. ↑ Deloire MS, Salort E, Bonnet M, Arimone Y, Boudineau M, Amieva H, Barroso B, Ouallet JC, Pachai C, Galliaud E, Petry KG, Dousset V, Fabrigoule C, Brochet B (April 2005). "Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 76 (4): 519–26. doi:10.1136/jnnp.2004.045872. PMC 1739602. PMID 15774439.
  14. ↑ Rao SM, Leo GJ, Bernardin L, Unverzagt F (May 1991). "Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction". Neurology. 41 (5): 685–91. PMID 2027484.
  15. ↑ Huijbregts SC, Kalkers NF, de Sonneville LM, de Groot V, Reuling IE, Polman CH (July 2004). "Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS". Neurology. 63 (2): 335–9. PMID 15277630.
  16. ↑ Selhorst JB, Saul RF (June 1995). "Uhthoff and his symptom". J Neuroophthalmol. 15 (2): 63–9. PMID 7550931.
  17. ↑ 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.
  18. ↑ Drulovic J, Basic-Kes V, Grgic S, Vojinovic S, Dincic E, Toncev G, Kezic MG, Kisic-Tepavcevic D, Dujmovic I, Mesaros S, Miletic-Drakulic S, Pekmezovic T (August 2015). "The Prevalence of Pain in Adults with Multiple Sclerosis: A Multicenter Cross-Sectional Survey". Pain Med. 16 (8): 1597–602. doi:10.1111/pme.12731. PMID 26087108.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ Zivadinov R, Zorzon M, Bosco A, Bragadin LM, Moretti R, Bonfigli L, Iona LG, Cazzato G (December 1999). "Sexual dysfunction in multiple sclerosis: II. Correlation analysis". Mult. Scler. 5 (6): 428–31. doi:10.1177/135245859900500i610. PMID 10618700.
  22. ↑ Manconi M, Rocca MA, Ferini-Strambi L, Tortorella P, Agosta F, Comi G, Filippi M (January 2008). "Restless legs syndrome is a common finding in multiple sclerosis and correlates with cervical cord damage". Mult. Scler. 14 (1): 86–93. doi:10.1177/1352458507080734. PMID 17942519.
  23. ↑ Amarenco G, Kerdraon J, Denys P (December 1995). "[Bladder and sphincter disorders in multiple sclerosis. Clinical, urodynamic and neurophysiological study of 225 cases]". Rev. Neurol. (Paris) (in French). 151 (12): 722–30. PMID 8787103.
  24. ↑ Schürks M, Bussfeld P (April 2013). "Multiple sclerosis and restless legs syndrome: a systematic review and meta-analysis". Eur. J. Neurol. 20 (4): 605–15. doi:10.1111/j.1468-1331.2012.03873.x. PMID 23078359.
  25. ↑ Frohman EM, Zhang H, Dewey RB, Hawker KS, Racke MK, Frohman TC (November 2000). "Vertigo in MS: utility of positional and particle repositioning maneuvers". Neurology. 55 (10): 1566–9. PMID 11094117.
  26. ↑ Balcer LJ (March 2006). "Clinical practice. Optic neuritis". N. Engl. J. Med. 354 (12): 1273–80. doi:10.1056/NEJMcp053247. PMID 16554529.
  27. ↑ Swanton J, Fernando K, Miller D (2014). "Early prognosis of multiple sclerosis". Handb Clin Neurol. 122: 371–91. doi:10.1016/B978-0-444-52001-2.00015-7. PMID 24507526.
  28. ↑ 28.0 28.1 Weinshenker BG (1994). "Natural history of multiple sclerosis". Ann. Neurol. 36 Suppl: S6–11. PMID 8017890.
  29. ↑ Confavreux C, Vukusic S, Moreau T, Adeleine P (November 2000). "Relapses and progression of disability in multiple sclerosis". N. Engl. J. Med. 343 (20): 1430–8. doi:10.1056/NEJM200011163432001. PMID 11078767.
  30. ↑ Tremlett H, Paty D, Devonshire V (January 2006). "Disability progression in multiple sclerosis is slower than previously reported". Neurology. 66 (2): 172–7. doi:10.1212/01.wnl.0000194259.90286.fe. PMID 16434648.
  31. ↑ Confavreux C, Vukusic S (March 2006). "Age at disability milestones in multiple sclerosis". Brain. 129 (Pt 3): 595–605. doi:10.1093/brain/awh714. PMID 16415309.
  32. ↑ Confavreux C, Vukusic S (March 2006). "Natural history of multiple sclerosis: a unifying concept". Brain. 129 (Pt 3): 606–16. doi:10.1093/brain/awl007. PMID 16415308.
  33. ↑ Langer-Gould A, Popat RA, Huang SM, Cobb K, Fontoura P, Gould MK, Nelson LM (December 2006). "Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review". Arch. Neurol. 63 (12): 1686–91. doi:10.1001/archneur.63.12.1686. PMID 17172607.
  34. ↑ Kremenchutzky M, Rice GP, Baskerville J, Wingerchuk DM, Ebers GC (March 2006). "The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease". Brain. 129 (Pt 3): 584–94. doi:10.1093/brain/awh721. PMID 16401620.
  35. ↑ Cree BA, Khan O, Bourdette D, Goodin DS, Cohen JA, Marrie RA, Glidden D, Weinstock-Guttman B, Reich D, Patterson N, Haines JL, Pericak-Vance M, DeLoa C, Oksenberg JR, Hauser SL (December 2004). "Clinical characteristics of African Americans vs Caucasian Americans with multiple sclerosis". Neurology. 63 (11): 2039–45. PMID 15596747.
  36. ↑ Roudbari SA, Ansar MM, Yousefzad A (July 2013). "Smoking as a risk factor for development of Secondary Progressive Multiple Sclerosis: A study in IRAN, Guilan". J. Neurol. Sci. 330 (1–2): 52–5. doi:10.1016/j.jns.2013.04.003. PMID 23628463.

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