Neurology Tute 3 Multiple Sclerosis Chronic inflammatory disease of the CNS Multiple plaques of demyelination within the brain

ain and spinal cord disseminated sclerosis plaques are disseminated in time and space

18/2/2011

Epidemiology Prevalence varies widely, directly proportional to distance of residence from the equator o Increasing prevalence with distance from the equator o ? Dietary factors as a cause of this geographical distribution Aetiology and pathogenesis Inflammatory process in white matter of brain and spinal cord Mediated by CD 4 T cells Initial inflammatory demyelinating event primes autoreactive cellular and humoral immune responses against myelin Antibody-mediated demyelination develops early in MS There is familial association first-degree relatives are at increased risk of developing MS Not a transmittable disease Pathology Cardinal feature = plaques of demyelination (2-10mm in size) Distinct CNS sites affected = optiv nerves, periventricular region, brainstem and its cerebellar connections, cervical spinal cord (corticospinal tracts and posterior columns) Acute relapses due to conduction block caused by focal inflammatory demyelination Remission occurs as inflammation subsides and remyelination If damage is severe, destruction of the axon can occur and this is permanent Plaques not seen in myelin sheaths of peripheral nerves Clinical features Onset 20-45 y.o. (rare before puberty or >60 years) F>M Optic neuropathy o Blurring of vision in one eye o Develops over hours or days o Severity is variable rarely complete blindness o Mild ocular pain

o o o o

Recovery typically within 2 months Disc swelling if demyelination plaque is in the nerve head No ophthalmoscopic abnormalities if plaque is behind the disc Vision gets worse during fever, hot weather, after exercise Typical presentation: o Sudden diplopia o Vertigo with nystagmus o No tinnitus or deafness

Brainstem demyelination o Diplopia o Vertigo o Facial numbness/weakness o Dysarthria/dysphagia o If corticospinal tracts involved pyramidal signs in limbs

Spinal cord lesions o Spastic paraparesis developing over days or weeks due to plaque in cervical or thoracic cord difficulty walking and lower limb numbness. o Urinary symptoms Unusual presenatations o Epilepsy o Trigeminal neuralgia o Tonic spasms o Organic psychosis End-stage MS o Severe disability spastic tetraparesis, ataxia, optic atrophy, nystagmus, brainstem signs, psuedobulbar palsy, urinary incontinence o Dementia o Death from uraemia or bronchopneumonia

Course and diagnosis MS has relapsing and remitting course o Remission may last for several or more years o Length is unpredictable o Mechanism of remission and relapse is unknown Following isolated event that could possibly be MS, it is often unclear (even after MRI) if MS is the cause. Dx MS: pattern on disease, imaging appearance of subsequent lesions Differential diagnosis course of MS is pretty distinctive, not many other disease have remit/relapse course Thromboembolism typically causes symptoms with rapid onset (not gradual, like in MS) Other degenerative conditions (eg. Freidreichs ataxia) CNS sarcoidosis, SLE, Behcets syndrome may mimic relapsing MS Adrenoleucodystrophy progressive paraparesis identical to chronic progressive MS Investigations MRI of brain and spinal cord o Multiple plaques periventricular region, corpus callosum, cerebellar peduncles, juxtacortical posterior fossa, brainstem, cervical cord o Lesions appear elliptical in shape with discrete borders and lack of mass effect o Plaques cannot really be seen with CT Testing vision for optic neuropathy Management Lifestyle Decisions have to be made about plans for future as this is a progressive, potentially disabling disease with no cure Link to MS societies, support groups Therapies Nothing has really been shown to improve long-term outcome, but some things may help to reduce frequency and severity of relapses Acute relapses short course of steroids (eg. Prednisolone) can help to reduce severity Preventing relapse and disability Beta-interferon reduces relapse rate in some patients and prevents and increase in lesions on MRI. Expensive. Immunosuppresants slight benefits? Glatiramer acetate an immunomodulator. Similar to beta-interferon. Natalizumab monoclonal antibody which inhibits migration of leucocytes to CNS. Useful in severe, relapsing remitting MS that is unresponsive to other treatments. Muscle relaxants, injected botulinum helpful in spasticity Cannibis for painful spasms Rehab OTs Practical advice for work, walking aids, wheelchairs, car conversions, house alterations Support for psychological issues eg. Depression Treat infections Physiotherapy - reduce pain and discomfort of spasticity Prevent pressure sores