Multiple Sclerosis Flashcards
What is multiple sclerosis? What occurs?
Common, chronic, auto-immune mediated inflammatory disease of the CNS causing demyelination of neurons.
De-myelination consists of damage to the protective myeline sheath that surrounds the neurons and this leads to scarring and secondary neuronal cell loss which results in irreversible neurological damage.
85% of those with MS have what form of MS?
Relapsing - remitting
Is MS more common in men or women?
2-3x more common in women
Mean age of onset for MS
30
Aetiology of MS
Mixture between genetics, environmental triggers and chance
genetic
- more common in femakes
- twin concordance 20-35% in monozygotic twins
- occurs earlier in females compared to males
Environmental
- viral infections: EBV (glandular fever)
- geographic latitude: prevalence increases greater distance north or south of equator (age of immigration impacts risk - before or after puberty)
- sunlight exposure: inverse relationship between MS, sunlight and vit D level
- obesity during adolescence, smoking, gender.
Pathophysiology of MS
- Axons are supported by glial cells - oligodendrocytes are one type of glial cell which are important in the formation of the myelin sheath
- In MS, oligodendrocytes are destroyed, leading to demyelination and axonal loss
- There appears to be activation of myelin-reactive T lymphocytes and disruption of the BBB which allows entry of auto-reactive immune cells
- Within the CNS there is then a pro-inflammatory response and recruitment of further inflammatory cells such as B-lymphocytes, macrophages and microglia
- Microglia (macrophages of the CNS) are critical in cytokine release, phagocytosis and antigen-presentation
- There is a marked immune response including antibody-mediated response with evidence of immunoglobulins - oligoclonal bands in the CSF
- Continued immune response leads to damage to oligodendrocytes and de-myelination and formation of MS-plaques which contain reactive T cells, B cells and macrophages
Classical plaque sites for MS?
Optic nerve - 40%
Spinal cord - 50-75%
Brain steam
Cerebellum
Classification of MS? (3)
- relapsing-remitting MS 85-90% cases
- Episodes of exacerbation in symptoms termed relapses followed by complete periods of remissions
- During early stages, symptoms may completely remit
- As disease progresses, there is likely to remain residual damage with each relapse leading to further deterioration - Primary progressive MS - 10%
- Sustained progression of disease severity from onset
- May have periods where disease is not active or non-progressive but there is no evidence of clinical remission - Secondary progressive
- 50% of patients with RRMS will develop this subtype within 15yrs
- Following RRMS phenotype, disease course changes with gradual, sustained worsening in neurological function
- Relapses may still occur but without remission
Clinical course: as brain and spinal cord atrophies further and further, neuroaxonal degeneration increases and disability increases.
Clinical manifestations of MS
Visual manifestations
- Optic neuritis and eye movement abnormalities commonly affect patients with MS
- Optic neuritis is due to inflammation of the optic nerve - partial or total unilateral visual loss that develops over days
- Visual loss
- Blurred vision
- Pain behind the eyes and on movement
- Scotoma: partial visual field loss
- Poor colour differentiation
- Relative afferent pupillary defect
- Optic nerve swelling seen on fundoscopy
Motor co-ordination manifestations
- weakness and ataxia
- progressive paraparesis (spasticity, reduced power, hyper-reflexia)
Sensory and autonomic manifestations
- Paraesthesia
- pain
- heat sensitivity (Uhthoff phenomenom)
- sexual dysfunction
- bladder and bowel dysfunction (up to 75%)
Cognitive and pychological
- depression & fatigue.
How is MS diagnosed? What supporting tests can we use?
Clinical diagnosis supported by MRI scan to identify abnormality
Supporting investigations
- Oligoclonal bands seen in CSF which are not present in serum (paired CSF from spine and serum sample taken at time of LP)
- 95% patient with MS have oligoclonal bands in CSF
Management of MS
bladder dysfunction, bowel dysfunction, depression, fatigue, gait impairment, pain and spasticity
General care
- Physio, occupational & speech therapy are crucial throughout for non-pharmacological treatments
- Bladder dysfunction: may require anticholinergics such as oxybutynin for detrusor overactivity
- Bowel dysfunction: constipation and incontinence may be present and dietary changes, laxatives and enemas are the cornerstone of treatment
- Depression: duloxetine if co-existing neuropathic pain or fatigue. SSRIs commonly used too
- Fatigue: physical activity and treating co-morbidities such as depression. Modafinil can be tried
- Gait impairment: occupational and physiotherapy essential - walking aids or wheelchair may be needed
- Pain: amitriptyline, gabapentin or pregabalin
- Spasticity: physiotherapy and baclofen. Botulism injections may be used
Management of acute relapses of MS
Corticosteroids
- rule out infection
- steroids: oral methylprednisolone
- gastro-protection (PPIs)
Disease modifying therapies for frequent relapses of MS
Immunotherapy decreases number of relapses and slows disease progression
- interferon beta (modulated immune response)
- natalizumab (stops leucocytes migrating across BBB)
- alemtuzumab (mab to CD52)
- cladribine (cytotoxic effect on B and T lymphocytes)
- stem cell transplant
Prognosis for MS?
Highly variable between patients
- 25% of patients with RRMS develop SPMS within 6yrs of diagnosis and 50% within 15yrs
- Following diagnosis, likelihood of walking unaided after 15yrs is about 60%
- RRMS better prognosis than PPMS
- Protective during pregnancy, increased risk of relapse in postpartum period
Bad prognostic factors for MS?
- male gender
- late age onset
- early motor, cerebellar and sphincter problems
- short inter-attack interval
- high number of early attacks
- significant MRI disease burden at onset
- positive CSF for analysis of OCB
