Multiple sclerosis history and symptoms: Difference between revisions

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{{Template:Multiple sclerosis}}
{{Template:Multiple sclerosis}}
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==Overview==
==Overview==
== History and symptoms ==
The most common [[symptoms]] of multiple sclerosis include: [[Fatigue]], [[mood]] problems, [[spasticity]], [[bowel]], [[bladder]] dysfunction, [[cognitive impairment]], [[Ophthalmoplegia|eye movement problems]], heat sensitivity, [[incoordination]], [[pain]], [[sexual dysfunction]], [[Sleep disorders|sleep disorder]], [[vertigo]], and [[visual loss]].
 
MS can cause a variety of symptoms, including changes in sensation ([[hypoesthesia]]), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance ([[ataxia]]); problems in speech ([[dysarthria]]) or swallowing ([[dysphagia]]), visual problems ([[nystagmus]], [[optic neuritis]], or [[diplopia]]), [[fatigue (medical)|fatigue]] and acute or chronic [[pain and nociception|pain]] syndromes, [[Urinary bladder|bladder]] and [[bowel]] difficulties, [[cognitive]] impairment, or emotional symptomatology (mainly [[clinical depression|depression]]). The main clinical measure of disability progression and severity of the symptoms is the [[Expanded Disability Status Scale]] or EDSS.<ref>{{cite journal |author=Kurtzke JF |title=Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) |journal=Neurology |volume=33 |issue=11 |pages=1444-52|year=1983 |pmid=6685237 |doi=}}</ref>
 
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 based on 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]]) (16%), weakness (13%), [[diplopia|double vision]] (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as [[aphasia]] or [[psychosis]].<ref>{{cite journal |author=Navarro S, Mondéjar-Marín B, Pedrosa-Guerrero A, Pérez-Molina I, Garrido-Robres J, Alvarez-Tejerina A |title=[Aphasia and parietal syndrome as the presenting symptoms of a demyelinating disease with pseudotumoral lesions] |journal=Rev Neurol |volume=41 |issue=10 |pages=601-3|year= |pmid=16288423}}</ref><ref>{{cite journal |author=Jongen P |title=Psychiatric onset of multiple sclerosis |journal=J Neurol Sci |volume=245 |issue=1–2 |pages=59–62 |year=2006 |pmid=16631798}}</ref> Fifteen percent of individuals have multiple symptoms when they first seek medical attention.<ref>Paty D, Studney D, Redekop K, Lublin F. ''MS COSTAR: a computerized patient record adapted for clinical research purposes.'' Ann Neurol 1994;36 Suppl:S134-5. PMID 8017875</ref> For some people the initial MS attack is preceded by [[infection]], [[Physical trauma|trauma]], or strenuous physical effort.
 
=== Bladder ===
 
[[Urinary bladder|Bladder]] problems (See also [[urinary system]] and [[urination]]) appear in 70-80% of MS patients and they have an important effect both in [[hygiene]] habits and social activity.<ref>{{cite journal |author=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 |year=1999 |pmid=10631634}}</ref><ref>{{cite journal |author=Burguera-Hernández JA |title=[Urinary alterations in multiple sclerosis] |language=Spanish; Castilian |journal=Revista de neurologia |volume=30 |issue=10 |pages=989-92|year=2000 |pmid=10919202}}</ref>
 
However bladder problems are usually related with high levels of [[disability]] and pyramidal signs in lower limbs<ref>{{cite journal |author=Betts CD, D'Mellow MT, Fowler CJ |title=Urinary symptoms and the neurological features of bladder dysfunction in multiple sclerosis |journal=J. Neurol. Neurosurg. Psychiatr. |volume=56 |issue=3 |pages=245-50 |year=1993 |pmid=8459239}}</ref>
 
The most common problems are an increase of frequency and urgency ([[Urinary incontinence|incontinence]]) but difficulties to begin urination, hesitation, leaking, retention and sensation of incomplete urination also appear. When there is retention secondary [[urinary infection]]s are common.
 
There are many [[Cerebral cortex|cortical]] and [[subcortical]] structures implicated in [[micturition]].<ref>{{cite journal|author=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= |pages=781-9 |year=2000 |pmid=10734009}}</ref> Accordingly; MS lesions in different [[central nervous system]] structures can cause these kind of symptoms.
 
=== Cognitive ===
 
Cognitive impairments are common. Neuropsychological studies suggest that 40 to 60 percent of patients have cognitive deficits;<ref>{{cite journal |author=Rao S, Leo G, Bernardin L, Unverzagt F |title=Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction |journal=Neurology |volume=41 |issue=5 |pages=685-91 |year=1991 |pmid=2027484}}</ref> with the lowest percentages usually from community-based studies and the highest ones from hospital-based.


Cognitive impairment, sometimes referred to as [[brain fog]], is already present in the beginnings of the disease.<ref>{{cite journal |author= |title=Attention impairment in recently diagnosed multiple sclerosis |journal=Eur J Neurol |volume=5 |issue=1|pages=61-66 |year=1998 |pmid=10210813}}</ref> Even in probable MS (after the first attack but before a second confirmatory one) up to 50% of patients have mild impairment.<ref>{{cite journal |author=Achiron A, Barak Y |title=Cognitive impairment in probable multiple sclerosis |journal=J Neurol Neurosurg Psychiatry |volume=74 |issue=4 |pages=443-6 |year=2003 |pmid=12640060}}</ref>
== History and Symptoms  ==


Some of the most common declines are in recent [[memory]], [[attention]], processing speed, visual-spatial abilities and [[executive functions]].<ref>{{cite journal |author=Bobholz J, Rao S |title=Cognitive dysfunction in multiple sclerosis: a review of recent developments |journal=Curr Opin Neurol |volume=16 |issue=3 |pages=283-8 |year=2003 |pmid=12858063}}</ref> Other cognitive-related symptoms are [[labile affect|emotional instability]], and [[fatigue (physical)|fatigue]], including purely [[neurological fatigue]].
=== History ===
The cognitive impairments in MS are usually mild; and only in 5% of patients can we speak of [[dementia]]. Nevertheless they are related with unemployment and reduced social interactions.<ref>{{cite journal |author=Amato M, Ponziani G, Siracusa G, Sorbi S|title=Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years |journal=Arch Neurol |volume=58|issue=10 |pages=1602-6 |year=2001 |pmid=11594918}}</ref> They are also related with driving difficulties.<ref>{{cite journal|author=Shawaryn M, Schultheis M, Garay E, Deluca J |title=Assessing functional status: exploring the relationship between the multiple sclerosis functional composite and driving |journal=Arch Phys Med Rehabil |volume=83 |issue=8 |pages=1123-9 |year=2002|pmid=12161835}}</ref>
Patients with Multiple sclerosis may have a positive history of:
* [[Smoking (patient information)|Smoking]]<ref name="pmid14581676" /><ref name="pmid11427406">{{cite journal |vauthors=Hernán MA, Olek MJ, Ascherio A |title=Cigarette smoking and incidence of multiple sclerosis |journal=Am. J. Epidemiol. |volume=154 |issue=1 |pages=69–74 |date=July 2001 |pmid=11427406 |doi= |url=}}</ref>


=== Emotional ===
* A family member with [[MS]] disease <ref name="pmid8800940">{{cite journal |vauthors=Robertson NP, Fraser M, Deans J, Clayton D, Walker N, Compston DA |title=Age-adjusted recurrence risks for relatives of patients with multiple sclerosis |journal=Brain |volume=119 ( Pt 2) |issue= |pages=449–55 |date=April 1996 |pmid=8800940 |doi= |url=}}</ref><ref name="pmid3376997">{{cite journal |vauthors=Sadovnick AD, Baird PA, Ward RH |title=Multiple sclerosis: updated risks for relatives |journal=Am. J. Med. Genet. |volume=29 |issue=3 |pages=533–41 |date=March 1988 |pmid=3376997 |doi=10.1002/ajmg.1320290310 |url=}}</ref>


Emotional symptoms are also common and are thought to be both the normal response to having a debilitating disease and the result of damage to specific areas of the cental nervous system that generate and control emotions.
* [[Women|Female gender]]<ref name="pmid17052660">{{cite journal |vauthors=Orton SM, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, Ebers GC |title=Sex ratio of multiple sclerosis in Canada: a longitudinal study |journal=Lancet Neurol |volume=5 |issue=11 |pages=932–6 |date=November 2006 |pmid=17052660 |doi=10.1016/S1474-4422(06)70581-6 |url=}}</ref><ref name="pmid11526384">{{cite journal |vauthors=Whitacre CC |title=Sex differences in autoimmune disease |journal=Nat. Immunol. |volume=2 |issue=9 |pages=777–80 |date=September 2001 |pmid=11526384 |doi=10.1038/ni0901-777 |url=}}</ref>


[[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.<ref>{{cite journal |author=Sadovnick A, Remick R, Allen J, Swartz E, Yee I, Eisen K, Farquhar R, Hashimoto S, Hooge J, Kastrukoff L, Morrison W, Nelson J, Oger J, Paty D |title=Depression and multiple sclerosis |journal=Neurology |volume=46 |issue=3 |pages=628-32 |year=1996 |pmid=8618657}}</ref><ref>{{cite journal|author=Patten S, Beck C, Williams J, Barbui C, Metz L |title=Major depression in multiple sclerosis: a population-based perspective|journal=Neurology |volume=61 |issue=11 |pages=1524-7 |year=2003 |pmid=14663036}}</ref>
* Low [[vitamin D]] level<ref name="pmid12907484">{{cite journal |vauthors=van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, Butzkueven H, Kilpatrick T |title=Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study |journal=BMJ |volume=327 |issue=7410 |pages=316 |date=August 2003 |pmid=12907484 |pmc=169645 |doi=10.1136/bmj.327.7410.316 |url=}}</ref><ref name="pmid14718698">{{cite journal |vauthors=Munger KL, Zhang SM, O'Reilly E, Hernán MA, Olek MJ, Willett WC, Ascherio A |title=Vitamin D intake and incidence of multiple sclerosis |journal=Neurology |volume=62 |issue=1 |pages=60–5 |date=January 2004 |pmid=14718698 |doi= |url=}}</ref>


Other feelings such as [[anger]], [[anxiety]], [[frustration]], and hopelessness also appear frequently, and [[suicide]] is a very real threat since 15% of deaths in MS sufferers are due to this cause.<ref>{{cite journal |author=Sadovnick A, Eisen K, Ebers G, Paty D |title=Cause of death in patients attending multiple sclerosis clinics |journal=Neurology |volume=41 |issue=8 |pages=1193-6|year=1991 |pmid=1866003}}</ref>
* [[stress]]<ref name="pmid10371517">{{cite journal |vauthors=Goodin DS, Ebers GC, Johnson KP, Rodriguez M, Sibley WA, Wolinsky JS |title=The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology |journal=Neurology |volume=52 |issue=9 |pages=1737–45 |date=June 1999 |pmid=10371517 |doi= |url=}}</ref>


=== Fatigue ===
* African Americans, Mexicans, Japanese, Chinese and Filipinos ethnic <ref name="pmid573402" />


[[Fatigue (medical)|Fatigue]] is very common and disabling in MS. At the same time it has a close relationship with depressive symptomatology.<ref name="pmid12814166">{{cite journal |author=Bakshi R |title=Fatigue associated with multiple sclerosis: diagnosis, impact and management |journal=Mult. Scler. |volume=9 |issue=3 |pages=219–27 |year=2003 |pmid=12814166 |doi=}}</ref> When depression is reduced fatigue also tends to improve, so patients should be evaluated for depression before other therapeutic approaches are used.<ref name="pmid12883103">{{cite journal |author=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=542–7 |year=2003|pmid=12883103 |doi=}}</ref>. In a similar way other factors like disturbed sleep, chronic pain, poor nutrition, or even some medications can contribute to fatigue; and therefore medical professionals are encouraged to identify and modify them.<ref name="isbn = 1 86016 182 0">{{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 | date = 2004 | location = Salisbury, Wiltshire | isbn = 1 86016 182 0 }}[http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf Free full text]([[2004-08-13]]). Retrieved on [[2007-10-01]].</ref>
* high titer of [[Epstein Barr virus|EBV]] [[Antibody|antibodies]]<ref name="pmid15210894" /><ref name="pmid15914750">{{cite journal |vauthors=Levin LI, Munger KL, Rubertone MV, Peck CA, Lennette ET, Spiegelman D, Ascherio A |title=Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis |journal=JAMA |volume=293 |issue=20 |pages=2496–500 |date=May 2005 |pmid=15914750 |doi=10.1001/jama.293.20.2496 |url=}}</ref>


=== Mobility restrictions ===
NOTE: [[McDonald criteria]] for a [[MS]] attack is a [[symptom]] cause by [[Demyelination|demyelinating]] event in the[[CNS]], lasting more than 24 hours. There should be no [[fever]] or [[Sign (medicine)|sign]] of [[infection]].<ref name="pmid21387374">{{cite journal |vauthors=Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS |title=Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria |journal=Ann. Neurol. |volume=69 |issue=2 |pages=292–302 |date=February 2011 |pmid=21387374 |pmc=3084507 |doi=10.1002/ana.22366 |url=}}</ref> First common [[Symptom|symptoms]] of MS disease are [[optic neuritis]], [[diplopia]], [[Sensory loss|sensory]] or [[Muscle weakness|motor loss]], [[vertigo]], and [[Balance disorder|balance]] problems. In young adult [[eye]] and [[sensory]] problems are prominent while in older patients we see [[Motor skill|motor]] problems more often.<ref name="pmid2917275">{{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= |pages=133–46 |date=February 1989 |pmid=2917275 |doi= |url=}}</ref>


Restrictions in [[mobility]] (walking, transfers, bed mobility) are common in individuals suffering from multiple sclerosis. Within 10 years after the onset of MS one-third of patients reach a score of 6 on the [[Expanded Disability Status Scale]] (requiring the use of a unilateral walking aid),and by 30 years the proportion increases to 83%. Within 5 years the Expanded Disability Status Score is 6 in 50% of those with the progressive form of MS.<ref>{{cite journal |author=Weinshenker BG, Bass B, Rice GP, ''et al''|title=The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability |journal=Brain|volume=112 ( Pt 1) |issue= |pages=133-46 |year=1989 |pmid=2917275 |doi=}}</ref>
=== Common Symptoms ===
The most common [[symptoms]] of multiple sclerosis include:
* Fatigue: [[Fatigue]] is seen in almost 80% of [[MS]] patients. They commonly feel exhausted and out of [[energy]]. We can see [[fatigue]] exacerbation before acute attacks in MS and for a while after that.<ref name="pmid25700869">{{cite journal |vauthors=Čarnická Z, Kollár B, Šiarnik P, Krížová L, Klobučníková K, Turčáni P |title=Sleep disorders in patients with multiple sclerosis |journal=J Clin Sleep Med |volume=11 |issue=5 |pages=553–7 |date=April 2015 |pmid=25700869 |pmc=4410929 |doi=10.5664/jcsm.4702 |url=}}</ref> The [[etiology]] of this [[symptom]] is poorly understood.<ref name="pmid16900749">{{cite journal |vauthors=Krupp L |title=Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease |journal=Mult. Scler. |volume=12 |issue=4 |pages=367–8 |date=August 2006 |pmid=16900749 |doi=10.1191/135248506ms1373ed |url=}}</ref>


In MS a wide range of impairments may exist which can act either alone or in combination to impact directly on a person's balance, function and mobility. Such impairments include [[fatigue (medical)|fatigue]], [[Muscle weakness|weakness]], hypertonicity, low exercise tolerance, impaired balance, [[ataxia]] and [[tremor]].<ref>{{cite journal |author=Freeman JA |title=Improving mobility and functional independence in persons with multiple sclerosis |journal=J. Neurol. |volume=248 |issue=4 |pages=255-9 |year=2001|pmid=11374088 |doi=}}</ref>
* Mood problems: [[Psychiatric]] disorders, especially [[depression]], is common and can be seen in almost 50% of [[MS]] patients.<ref name="pmid8618657">{{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=628–32 |date=March 1996 |pmid=8618657 |doi= |url=}}</ref> Some studies show higher risk of [[suicide]] in [[MS]] patients.<ref name="pmid1866003">{{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=1193–6 |date=August 1991 |pmid=1866003 |doi= |url=}}</ref><ref name="pmid1449409">{{cite journal |vauthors=Stenager EN, Stenager E |title=Suicide and patients with neurologic diseases. Methodologic problems |journal=Arch. Neurol. |volume=49 |issue=12 |pages=1296–303 |date=December 1992 |pmid=1449409 |doi= |url=}}</ref>


=== Eye symptoms ===
* [[Spasticity]]: Damage to the [[upper motor neurons]] and decrease inhibition of [[lower motor neurons]] in [[MS]] can increase [[muscle tone]] and [[Muscle rigidity|rigidity]] in 75% of [[MS]] patients.<ref name="pmid17868019">{{cite journal |vauthors=Boissy AR, Cohen JA |title=Multiple sclerosis symptom management |journal=Expert Rev Neurother |volume=7 |issue=9 |pages=1213–22 |date=September 2007 |pmid=17868019 |doi=10.1586/14737175.7.9.1213 |url=}}</ref>
{{Main|Optic neuritis}}
Individuals experience rapid onset of [[pain]] in one eye, followed by blurry [[Visual perception|vision]] in part or all of the [[visual field]] of that [[eye]]. [[Inflammation]] of the optic nerve causes loss of vision usually due to the swelling and destruction of the [[myelin]] sheath covering the optic nerve. This condition is called optic neuritis.


The blurred vision usually resolves within ten weeks, but individuals are often left with less vivid [[color vision]] (especially red) in the affected eye.
* Bowel and bladder dysfunction: [[Bowel]] and [[bladder]] dysfunction is common in [[MS]] patients and occurs in more than 50% of patients.<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>


=== Pain ===
* Eye movement abnormalities: From more to less common, eye movement problems include [[Gaze palsy|abnormalities of voluntary gaze]], [[nystagmus]], abnormalities of slow phase [[Eye movement|eye movements]], paroxysmal disorders of [[eye movements]], and isolated ocular motor nerve palsies. These can lead to [[oscillopsia]] or [[diplopia]].<ref name="pmid15664543">{{cite journal |vauthors=Frohman EM, Frohman TC, Zee DS, McColl R, Galetta S |title=The neuro-ophthalmology of multiple sclerosis |journal=Lancet Neurol |volume=4 |issue=2 |pages=111–21 |date=February 2005 |pmid=15664543 |doi=10.1016/S1474-4422(05)00992-0 |url=}}</ref>


[[Pain]] is a common symptom in MS; appearing in 55% of patients at some point of their disease process; specially as time passes.<ref>{{cite journal |author=Stenager E, Knudsen L, Jensen K |title=Acute and chronic pain syndromes in multiple sclerosis. A 5-year follow-up study |journal=Italian journal of neurological sciences |volume=16 |issue=9 |pages=629-32 |year=1995 |pmid=8838789|doi=}}</ref>. It is strong and debilitating and has a profound effect in the [[quality of life]] and [[mental health]] of the sufferer.<ref>{{cite journal |author=Archibald CJ, McGrath PJ, Ritvo PG, ''et al'' |title=Pain prevalence, severity and impact in a clinic sample of multiple sclerosis patients |journal=Pain |volume=58 |issue=1 |pages=89-93 |year=1994 |pmid=7970843 |doi=}}</ref>
* Incoordination: Involvement of [[cerebellar]] tracts can cause problems in [[Gait]] and balance,l 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>
It usually appears 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.<ref>{{cite journal |author=Clanet MG, Brassat D |title=The management of multiple sclerosis patients |journal=Curr. Opin. Neurol. |volume=13 |issue=3 |pages=263-70 |year=2000 |pmid=10871249|doi=}}</ref>
Most frequent pains reported are [[headache]]s (40%), dysesthetic limb pain (19%), back pain (17%), and painful [[spasm]]s (11%).<ref>{{cite journal |author=Pöllmann W, Feneberg W, Erasmus LP |title=[Pain in multiple sclerosis--a still underestimated problem. The 1 year prevalence of pain syndromes, significance and quality of care of multiple sclerosis inpatients]|language=German |journal=Der Nervenarzt |volume=75 |issue=2 |pages=135-40 |year=2004 |pmid=14770283|doi=10.1007/s00115-003-1656-5}}</ref>


[[Acute (medical)|Acute]] pain is mainly due to [[optic neuritis]].<ref>{{cite journal |author=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=225-32 |year=2002 |pmid=12051466 |doi=}}</ref> [[Subacute]] pain is usually secondary to the disease and can be consequence of being too much time in the same position, urinary retention, infected skin ulcers and many others. [[Chronic (medical)|Chronic]] pain is very common and the harder to treat being its most common cause dysesthesias.
* 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>


==== Trigeminal neuralgia ====
* 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 reduced [[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>


[[Trigeminal neuralgia]] or "tic douloureux", is a disorder of the [[trigeminal nerve]] that causes episodes of intense pain in the [[eye]]s, [[lip]]s, [[nose]], [[scalp]], [[forehead]], and [[jaw]]. It affects 1 to 2% of MS patients during their disease.<ref>{{cite journal |author=Brisman R |title=Trigeminal neuralgia and multiple sclerosis |journal=Arch. Neurol. |volume=44|issue=4 |pages=379-81 |year=1987 |pmid=3493757 |doi=}}</ref><ref>{{cite journal |author=Bayer DB, Stenger TG |title=Trigeminal neuralgia: an overview |journal=Oral Surg. Oral Med. Oral Pathol. |volume=48 |issue=5 |pages=393-9 |year=1979 |pmid=226915|doi=}}</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.<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>
The episodes of pain occur paroxysmally, or 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.


==== Dysesthesias ====
* 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>
=== Less Common Symptoms ===
* 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 [[symptoms]]<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>


[[Dysesthesias]] are disagreeable sensations produced by ordinary [[Stimulus (physiology)|stimuli]]. The abnormal sensations are often described as painful feelings such as burning, wetness, itching, electric shock or pins and needles; and are caused by lesions of the peripheral or central sensory pathways.
* 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>


=== Sexual ===
* Vertigo: Benign positional paroxysmal [[vertigo]] is the most common cause of [[vertigo]] in [[MS]] patients. 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>
 
[[Sexual dysfunction]] (SD) is one of many symptoms affecting persons with a diagnosis of [[multiple sclerosis]] (MS) and other neurological disease.  SD in men encompasses both erectile and ejaculatory disorder.  The prevalence of SD in men with MS ranges from 75 to 91% (O'Leary et al., 2007).  [[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 may be affected by neurological conditions such as MS <ref>O'Leary, M., Heyman, R., Erickson, J., Chancellor, M.B.: Premature ejaculation and MS: A Review, Consortium of MS Centers,  http://www.mscare.org, June 2007</ref>
 
=== Spasticity ===
 
[[Spasticity]] is characterised by increased stiffness and slowness in [[Limb (anatomy)|limb]] movement, the development of certain postures, an association with weakness of voluntary [[muscle]] power, and with involuntary and sometimes painful [[spasm]]s of limbs.<ref name="isbn = 1 86016 182 0">{{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 | date = 2004 |location = Salisbury, Wiltshire |  isbn = 1 86016 182 0 }}[http://www.rcplondon.ac.uk/pubs/books/MS/MSfulldocument.pdf Free full text]([[2004-08-13]]). Retrieved on [[2007-10-01]].</ref>
 
=== Transverse myelitis ===
{{Main|Transverse myelitis}}
 
Some MS patients develop rapid onset of [[paresthesia|numbness]], weakness, [[bowel]] or [[Urinary bladder|bladder]] dysfunction, and/or loss of [[motor neuron|muscle]] function, typically in the lower half of the body. This is the result of MS attacking the [[spinal cord]]. The symptoms and signs depend upon the level of the spinal cord 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.
 
=== 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 (human)|gait]].
 
Tremor and ataxia are frequent in MS. They present in 25 to 60% of patients. They can be very disabling and embarrassing, and are difficult to manage.<ref>{{cite journal |author=Koch M, Mostert J, Heersema D, De Keyser J |title=Tremor in multiple sclerosis|journal=J. Neurol. |volume=254 |issue=2 |pages=133-45 |year=2007 |pmid=17318714 |doi=10.1007/s00415-006-0296-7}}</ref> The origin of tremor in MS is difficult to precise but it can be due to a mixture of different factors such as damage to the [[cerebellar]] connections, weakness, [[spasticity]], etc.


[[File:Symptoms of multiple sclerosis.svg.png|500px|none|thumb|https://en.wikipedia.org/wiki/File:Symptoms_of_multiple_sclerosis.svg]]
==References==
==References==
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[[Category:Neurology]]
[[Category:Orthopedics]]
[[Category:Rheumatology]]

Latest revision as of 22:47, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.

Overview

The most common symptoms of multiple sclerosis include: Fatigue, mood problems, spasticity, bowel, bladder dysfunction, cognitive impairment, eye movement problems, heat sensitivity, incoordination, pain, sexual dysfunction, sleep disorder, vertigo, and visual loss.

History and Symptoms 

History

Patients with Multiple sclerosis may have a positive history of:

  • African Americans, Mexicans, Japanese, Chinese and Filipinos ethnic [10]

NOTE: McDonald criteria for a MS attack is a symptom cause by demyelinating event in theCNS, lasting more than 24 hours. There should be no fever or sign of infection.[13] First common symptoms of MS disease are 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.[14]

Common Symptoms

The most common symptoms of multiple sclerosis include:

  • Fatigue: Fatigue is seen in almost 80% of MS patients. They commonly feel exhausted and out of energy. We can see fatigue exacerbation before acute attacks in MS and for a while after that.[15] The etiology of this symptom is poorly understood.[16]

Less Common Symptoms

  • 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 symptomss.[34]
  • Vertigo: Benign positional paroxysmal vertigo is the most common cause of vertigo in MS patients. In the course of the disease, about 30-50% of patients experience this symptom.[39]
https://en.wikipedia.org/wiki/File:Symptoms_of_multiple_sclerosis.svg

References

  1. ↑
  2. ↑ Hernán MA, Olek MJ, Ascherio A (July 2001). "Cigarette smoking and incidence of multiple sclerosis". Am. J. Epidemiol. 154 (1): 69–74. PMID 11427406.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Whitacre CC (September 2001). "Sex differences in autoimmune disease". Nat. Immunol. 2 (9): 777–80. doi:10.1038/ni0901-777. PMID 11526384.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ Goodin DS, Ebers GC, Johnson KP, Rodriguez M, Sibley WA, Wolinsky JS (June 1999). "The relationship of MS to physical trauma and psychological stress: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 52 (9): 1737–45. PMID 10371517.
  10. ↑
  11. ↑
  12. ↑ 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.
  13. ↑ Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (February 2011). "Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria". Ann. Neurol. 69 (2): 292–302. doi:10.1002/ana.22366. PMC 3084507. PMID 21387374.
  14. ↑ 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.
  15. ↑ Čarnická Z, Kollár B, Šiarnik P, Krížová L, Klobučníková K, Turčáni P (April 2015). "Sleep disorders in patients with multiple sclerosis". J Clin Sleep Med. 11 (5): 553–7. doi:10.5664/jcsm.4702. PMC 4410929. PMID 25700869.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ Stenager EN, Stenager E (December 1992). "Suicide and patients with neurologic diseases. Methodologic problems". Arch. Neurol. 49 (12): 1296–303. PMID 1449409.
  20. ↑ 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.
  21. ↑ DasGupta R, Fowler CJ (2003). "Bladder, bowel and sexual dysfunction in multiple sclerosis: management strategies". Drugs. 63 (2): 153–66. PMID 12515563.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ Frohman EM, Frohman TC, Zee DS, McColl R, Galetta S (February 2005). "The neuro-ophthalmology of multiple sclerosis". Lancet Neurol. 4 (2): 111–21. doi:10.1016/S1474-4422(05)00992-0. PMID 15664543.
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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.
  29. ↑ 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.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ 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.
  33. ↑ Balcer LJ (March 2006). "Clinical practice. Optic neuritis". N. Engl. J. Med. 354 (12): 1273–80. doi:10.1056/NEJMcp053247. PMID 16554529.
  34. ↑ Selhorst JB, Saul RF (June 1995). "Uhthoff and his symptom". J Neuroophthalmol. 15 (2): 63–9. PMID 7550931.
  35. ↑ Achiron A, Barak Y (April 2003). "Cognitive impairment in probable multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 74 (4): 443–6. PMC 1738365. PMID 12640060.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.

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