Multiple Sclerosis

Wikis > Neurology > Demyelinating Diseases > Multiple Sclerosis

Chronic disabling relapsing and remitting progressive inflammatory demyelinating disease of the CNS with a variable and unpredictable course. Commonest cause of neurological disability in young adults (most commonly diagnosed between ages of 20 and 45) - third most common cause of disability of working age adults. Wide spectrum of medical, psychological and social problems associated with MS.

Prevalence in UK is 50-80/100 000 and in Asia is 4/100 000. Incidence is higher in temperate climates which may hold clues to the aetiology – incidence increases further away one moves from the equator. Migration to an area of higher risk before age of 15  assume risk for that region. M:F ratio of 1:1.5-2 (M blacks. Mean age of onset is 30 years – can occasionally start in children.

Aetiology:
Unknown – autoimmune reaction, most likely an environmental trigger in genetically susceptible person (20x more common in first degree relatives). Some association with HLA A3, B7, Dw2, DR2, DR15 - environmental agent is most likely viral (eg Epstein-Barr virus, influenza, measles, herpes simplex) . (Early 19th century theory was it was due to suppression of sweat)

Pathogenesis:
Characteristic is autoimmune mediated multiple demyelination lesions of white matter in CNS (peripheral NS is usually spared) – more common in optic nerve, spinal cord and periventricular areas. Lymphocytes and monocytes pass through blood-brain barrier  penetrate white matter  recognise myelin derived antigens  inflammatory process  destruction of the oligodendyte-myelin unit by macrophages  destroy myelin and damages axons, though axon is relatively preserved initially – lesions are called ‘plaques’ (these are the pathological hallmarks of the disease). Neurological dysfunction occurs due to a combination of the demyelination and axonal damage.

Clinical features:
Wide spectrum of signs, symptoms and course - depends on the location and severity of the pathological lesion(s). Typically, a young adult that trips or legs feel heavy. Most follow an initial variable relapsing and remitting course, usually with full recovery  later remissions do not lead to full recovery.

Presenting features:
Onset in 85-90% is single symptom (depends on location of demyelination), but on careful history, there is usually a variable period of easy fatigue and low energy – optic neuritis (in 20%; usually starts as pain in eye, double vision or blurred vision; may get loss of visual acuity in one eye); diplopia (from involvement of 4th or 6th cranial nerve); sensory disturbance of the limbs (especially proprioception, parathesia, numbness or ‘leg feels heavy’; numbness may start in foot); weakness in one arm or leg (monoparesis); or weakness of both legs (paraparesis); ataxia (especially uncharacteristic tripping and incoordination of limbs – indicates cerebellar lesion); Lhermitte’s sign (sudden electric shock like sensation shooting down spine into arms or legs when patient flexes neck - thought to indicate posterior column plaques); urinary urgency and incontinence (from spinal cord involvement); severe fatigue (common disabling symptom).

Diagnosis is a generally a clinical one – confidence in diagnosis is often described as definite, probable or possible. No specific laboratory test – spinal fluid abnormalities may show autoimmune abnormalities. Evoked potentials (measure of conduction through CNS) show slowed conduction in areas of demyelination. MRI scan is sensitive in showing typical lesions and can show evidence of dissemination of lesions in both time and space.

Clinical criteria for diagnosis :
1) Clinically definite requires all of:
• <60 years of age • history or signs of deficits in two or more anatomical sites in CNS • On CNS examination abnormal signs are present which indicate white matter involvement • CNS involvement in one of two patterns • relapsing and remitting (two or more episodes lasting >24hrs and >1 month apart)
• Progressive (slow and/or stepwise progression over at least 6 months)
• No other explanation for symptoms
2) Clinically probable:
• relapsing and remitting symptoms with one neurological sign commonly associated with MS
• single episode with partial or complete recovery, with signs of multifocal white matter disease and no other explanation
3) Clinically possible:
• relapsing and remitting symptoms without documented or objective signs to establish more than one anatomical site of CNS involvement
• no other explanation.

The above distinction of definite, probable or possible has recently been recommended as no longer suitable by an International Panel . They recommend diagnosis based on clinical presentation and additional paraclinical studies (CSF analysis and MRI).

Diagnostic criteria :
Clinical Presentation Addition data needed for MS diagnosis
Two or more attacks; objective clinical evidence of 2 or more lesions seperated in time and not necessarily seperated in space None needed, but would be expected to be abnormal if done.
Two or more attacks; objective clinical evidence of one lesion Dissemination in space, demonstrated by MRI; or two or more MRI-detected lesions consistent with MS plus positive CSF; or await further clinical attack implicating a different site
One attack; objective clinical evidence of two or more lesions Dissemination in time, demonstrated by MRI of second lesion; or second clinical attack
One attack; objective clinical evidence of 1 lesion (monosymptomatic presentation; clinically isolated syndrome) Dissemination in space by MRI; or two or more MRI detected lesions consistent with MRI plus positive CSF and dissemination in time, demonstrated by MRI; or second clinical attack
Insidious neurological progression suggestive of MS Positive CSF and dissemination in space, demonstrated by (1) nine or more T2 lesions in brain or (2) 2 or more lesions in spinal cord or (3) 4-8 brain plus one spinal cord lesion or abnormal VEP associated with 4-8 lesions; or with fewer than 4 brain lesions plus one spinal cord lesion demonstrated by MRI and dissemination time demonstrated by MRI or continued progression for 1 year

Differential diagnosis – SLE; polyarteritis nodosa; Sjogrens syndrome; Behcet’s disease; Lyme disease; HIV; sarcoidosis; Vitamin B12 deficiency; spinocerebellar disorder; encephalomyelitis; leukodystrophies; multifocal leuckoencephalopathy

Features of established multiple sclerosis:
• motor and sensory – spinal cord involvement  lower limb symptoms are common (heaviness, weakness, stiffness, gait problems, failure of limb to respond to ‘commands’); strength is decreased, tone increased, reflexes exaggerated (hyperreflexia), clonus, positive Babinski’s reflex, sensory loss, Lhermittes’ sign, proprioception deficits
• optic – optic neuritis (40%)  blurring or darkening of vision, decreased colour perception, pain on eye movement; isolated cases of optic neuritis may be a forme fruste of MS
• cerebellar and brainstem (50%) – action/intention tremor, cerebellar gait disorder, dysarthric (syllabic) speech, diplopia, nystagmus, trigeminal neuralgia, hearing loss, olfactory abnormalities
• genitourinary – urinary retention, urgency, frequency, stress or overflow incontinence, sexual problems
• cognitive and emotional – in up to 50% - subcortical dementia, memory lapses, apraxia, aphasia, changed executive function, depression
• pain – in up to 50%; neurogenic in origin; dysaethetic limb pain is most common – usually burning in nature and may be due to spinal cord involvement
• fatigue – more common during attacks of MS; cause of fatigue is unknown; very disabling symptom
• impaired mobility from lower limb muscle weakness and spasticity (can be painful)
• a number of complications develop secondarily to the neurological dysfunction (eg infections, depression, contractures (from spasticity), pressure sores)

Symptoms can be aggravated by slight rise in temperature (eg fever, bathing, exercise, environmental) – even as little as 0.5 degree.

Involvement of the foot:
Cold feet are common (may only be the patients perception or may actually feel cold); weakness (foot drop); sensory symptoms; ankle oedema

Gait analysis has shown that those with MS have a shorter stride length, slower walking rates, higher cadence than those without MS. Also found were lower excursions for knee and ankle joints with less vertical lift of centre of gravity and a greater truck lean. Walker et al (2000) showed declines in velocity and cadence parameters over an 18 month period in 18 patients with multiple sclerosis. Base of gait in those with MS appears to be wider, presumably for increased stability.

Course/Prognosis:
Usually a relapsing and remitting course – but very unpredictable. MRI’s are being used with increased frequency to provide prognostic information. Most attacks generally/usually develop over a period of a few days to a few weeks, then remain stable for up to a few weeks, then gradually resolve (often incomplete resolution). Usually average one attack every 12-18 months. Generally estimated that the chance of walking unaided at 15yrs from onset is 50%.

Types of clinical courses (may be different variants of multiple sclerosis):
relapsing-remitting (most typical; episodes of acute worsening with recovery and a stable course between relapses; usually have full recovery during remission or mild residual deficits)
primary progressive (gradual, nearly continuous neurologic deterioration from the onset; occurs in about 10%; usually in those who are older at onset)
secondary progressive (usually starts off as relapsing-remitting course, then progresses; gradual neurologic deterioration with or without mild remissions and/or acute relapses).
progressive relapsing (gradual neurologic deterioration from the onset of symptoms, but with subsequent relapses).

Signs indicative of good prognosis :
1. Early age of onset (first symptoms <40yrs) 2. Sensory symptoms at onset (as opposed to motor symptoms) 3. Pattern of exacerbation and remission (as opposed to chronic progression) 4. Female (females have better prognosis than males)Factors associated with a poorer prognosis: Male; older age at onset; motor signs at onset; short intervals between initial attacks; incomplete remissions; early disability; larger numbers of lesions on MRIManagement: • multidisciplinary due range of clinical manifestation and impact on lifestyle • patient education and counselling (diagnosis has major psychological impact  use of self help organisations) • physiotherapy and occupational therapy to assist in maintaining function • good nutrition; regular sleep and exercise; avoid activities that may lead to overheating • depression management (SSRI’s; counselling; antidepressants) • disease modifying therapy – anti-inflammatory drugs (corticosteroids is ‘mainstay’ of management  shortens exacerbations, but prolonged use does not alter long term outcome); immunomodulating drugs (beta-interferon  decreases exacerbation and may affect disease progression – shown to reduce number of relapses by 30%; much is unknown about optimal timing of treatment, doses, frequency and mechanism of action) (glatiramer acetate – immunologically similar to myelin – has been shown to reduce relapse rate); immunosuppressives (eg azathioprine, methotrexate  moderate efficacy) • symptomatic therapy – rest (physical and emotional); pain (clonazepam; tricyclic antidepressants; analgesic creams); spasticity management (physiotherapy, baclofen, diazepam, clonazepam, botulinum toxin, chemical neurectomy); fatigue (rest; physiotherapy; occupational therapy for reorganisation of workplace; amantadine; modafinil; calcium antagonists); tremor (clonazepam, baclofen); bladder dysfunction (timed voiding, fluid restriction, catheterisation, propantheline, amitriptyline, imiparmine); physiotherapy (gait retraining, spasticity management, range of motion exercises, psychological support) • rocker shoes help gait ; AFO’s for foot drop and spasticity reduction • hyperbaric oxygen is used, but is unprovenExternal Links:
Gait impairment in multiple sclerosis (Podiatry Arena)
Multiple Sclerosis: Back to Basics (Podiatry Arena)
Foot disorders in multiple sclerosis (Podiatry Arena)
Multiple Sclerosis (Podiatry Arena)

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