MULTIPLE SCLEROSIS DR. SIKANDER ALI

26-12-2013

Definition Multiple Sclerosis is a relapsing/remitting

disorder, consists of plaques of demyelination (and axon loss) at sites throughout the CNS (but not peripheral nerves).

Pathogenesis Pathogenesis involves focal disruption of the

blood brain barrier and associated T cell mediated immune response and myelin damage, the trigger however is unknown.

Epidemiology It is commoner in temperate areas, rare in

Africa and Asia. Mean age of onset is 30 yrs, female to male ratio is 3:1

Presentation is usually monosymptomatic: unilateral optic

neuritis (pain on eye movement and rapid deterioration in central vision); numbness or tingling in the limbs; leg weakness or brainstem or cerebellar symptoms such as diplopia or ataxia. Less often there may be more than 1 symptom. Symptoms may worsen with heat (eg a hot bath) or exercise.

Progression

Initially demyelination may be followed by full recovery, but with time remissions are incomplete so disability accumulates. Prolonged demyelination causes axonal loss and clinically progressive symptoms, while some patients experience no progressive disablement at all.

Varieties of MS Four general categories:• Relapsing-remitting MS(RRMS) is characterized by recurrent

attacks of neurologic dysfunction usually with or without recovery, between attacks, no progression of neurologic impairment is noted. Accounts for 85% of new-onset MS cases.

• Secondary progressive MS(SPMS) always initially presents as RRMS but evolves to be gradually progressive. The majority of RRMS eventually evolves into SPMS.

• Primary progressive MS(PPMS) is characterized by gradual progression of disability from onset without discrete attacks; 15% of new-onset MS cases.

• Progressive-relapsing MS(PRMS) is a rare form that begins with a primary progressive course, but later superimposed relapses occur.

Clinical FeaturesSensory:

Motor:

Cord:

Dysaesthesia (abnormal sensation like pins and needles, vibration, burning or crawling) and trigeminal neuralgia

Spastic weakness, hyper reflexia

Transverse myelitis (Loss of motor, sensory, autonomic, reflex, and sphincter function below the level of a lesion), bowel dysfunction,urinary urgency or retention, anorgasmia and erectile dysfunction.

Ocular:

Cerebellum:

Diplopia, hemianopia, optic neuritis,

nystagmus in the abducting eye on lateral gaze. Pupillary defects (Efferent, afferent or relative afferent) and visual phenomenon (Uhthoff's phenomenon: vision worsens on exercise, eating a hot meal, or in hot baths)

Truncal or limb ataxia, intention tremor, dysarthria, scanning (monotonous) speech, falls

GIT:

Cognitive:

Other:

Swallowing disorders, constipation.

Cognitive and visuospatial decline is a big cause of unemployment, accidents and isolation

Fatigue, depression, mania, odd laughter

Diagnosis

Diagnosis is clinical! as no test is pathognomonic. It requires demonstration of lesions disseminated in time and space; and patient’s neurologic condition could not better be attributed to another disease.

McDonald criteria is often used to diagnose MS but it accord too much weight to MRI.

Clinical presentation

Additional data needed

2 or more attacks with 2 or more objective clinical lesions

None; clinical evidence will do; imaging evidence desirable; must conform to MS

2 or more attacks with 1 objective clinical lesion

Typical disseminated lesions on MRI or +ve CSF and MRI lesions consistent with MS or 2nd attack at a new site

1 attack with 2 or more objective clinical lesions

Dissemination in time, shown by MRI or 2nd clinical attack

1 attack with 1 objective clinical lesion (monosymptomatic attack)

Dissemination in space:*MRI or +ve CSF if MRI lesions consistent with MS*and dissemination in time shown by MRI or 2nd clinical attack

Continued…

Clinical presentation

Additional data needed

Insidious neurological progression suggestive of MS (primary progressive MS)

+ve CSF and dissemination in space, ie: MRI evidence of T2 brain lesions or 2 or more cord lesions or 4-8 brain and 1 cord lesion or +ve (VEP) with 4-8 MRI lesions or +ve VEP + <4 brain lesions + 1 cord lesion and dissemination in time seen on MRI or continued progression for 1yr

Attacks: These must last >1h, eg motor weakness etcTime between attacks: 30 days

MRI findings in MSA. Axial first-echo image from T2-weighted sequence demonstrates multiple bright signal abnormalities in white matter, typical for MS.

B. Sagittal T2-weighted FLAIR image in which the high signal of CSF has been suppressed. CSF appears dark, while areas of brain edema or demyelination appear high in signal as shown here in the corpus callosum (arrows). Lesions in the anterior corpus callosum are frequent in MS and rare in vascular disease

MRI findings in MSLeft. Sagittal T2-weighted fast spin echo image of the thoracic spine demonstrates a fusiform high-signal-intensity lesion in the mid thoracic spinal cord. Right. Sagittal T1-weighted image obtained after the intravenous administration of gadolinium DPTA reveals focal areas of blood-brain barrier disruption, identified as high-signal-intensity regions (arrows)

MRI findings in MS

Treatment

Methylprednisolone: 1g/24h IV/PO for 3d shortens relapses; use sparingly, It does not alter the overall prognosis.

Interferon (IFN-1B and IFN-1a): Decreases relapses by ~30% in active RRMS, they also decrease lesion accumulation on MRI. Their power to decrease disability is modest, as is their role in secondary and primary progressive (SP & PP) MS.

Glatiramer: is a similar alternative to IFN.

Azathioprine: may be as effective as interferons for RRMS and is 20X cheeper.

Monoclonal Antibodies: Alemtuzumab and Natalizumab, acts against T-cells and are considered 2nd line agents in RRMS.

Mitoxantrone (doxorubicin analogue): helps in 2dry progressive MS

Other: for spasticity: baclofen, diazepam, dantrolene and tizanidine can be used. For urgency and frequency oxybutynin my prove useful.

There is no good, safe preventive treatment for those with primary progressive MS

CLINICAL VARIANTS OF MSNeuromyelitis optica(NMO) also known as

Devic’s syndrome consists of separate attacks of acute optic neuritis (bilateral or unilateral) and myelitis. In contrast to MS, the brain MRI is typically, but not always, normal. A focal enhancing region of swelling and cavitation, extending over three or more spinal cord segments, is typically seen on spinal MRI. Acute attacks are usually treated with high-dose glucocorticoids as for MS exacerbations.

CLINICAL VARIANTS OF MSAcute MS(Marburg’s variant) is a fulminant

demyelinating process that progresses to death within 1–2 years. No controlled trials of therapy exist, high dose glucocorticoids, plasma exchange, and cyclophosphamide have been tried, with uncertain benefit.

DifferentialsAcute disseminated encephalomyelitis (ADEM)Antiphospholipid antibody syndromeBehçet’s diseaseHuman immunodeficiency virus (HIV) infection Ischemic optic neuropathy (arteritic and nonarteritic)Neoplasms (e.g., lymphoma, glioma, meningioma)Systemic lupus erythematosus and related collagen

vascular disordersVascular malformations (especially spinal dural AV fistulas)Vitamin B12deficiencyVasculitis (primary CNS or other).

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