multiple sclerosis Flashcards
define
Multiple sclerosis is a chronic inflammatory autoimmune disorder of the central nervous system which constitutes the most common cause of neurological disability in young adults.
A chronic inflammatory condition of the CNS characterised by multiple plaques of demyelination disseminated in time and space.
epidemiology
- Lifetime risk UK: 1/1000
- Mean age of onset: 30yr
- F>M = 3:1
Race: common in North America, Australia and northern Europe. Rarer in Black African/Asia
aetiology
- Genetic: HLA-DR2
- Environmental: Early exposure to sunlight/vit. D is important, and vit. D status relates to prevention of MS
- Viral (EBV): infections in genetically susceptible hosts
pathogenesis
- Multiple sclerosis is an autoimmune disease.
- It is proposed that an unknown non-self antigen mimics proteins in myelin. This antigen is presented on the surface of macrophages in combination with class 2 MHC.
- The resulting stimulation of Th1 T helper lymphocytes causes their expression of LFA-1 and VLA-4. These T helper cells may now bind to the cognate adhesion molecules, ICAM-1 and VCAM-1, on vascular endothelial cells. The release of proteases permits the T helper cells to cross the endothelium and enter the central nervous system.
- The destruction of myelin proceeds in three ways:
- TNF-alpha from Th1 lymphocytes
- TNF-alpha, oxygen free radicals, nitric oxide and proteases from activated macrophages
- antibody mediated complement activation
- Multiple sclerosis has classically been considered to be primarily a demyelinating disease. It is clear that neuronal death occurs from the early stages of the disease. It is probably this process of neuronal loss which contributes to the accumulating disability in multiple sclerosis.
Plaques of demyelination are hallmark
disease patterns
- relapsing and remitting: common
- most common form, accounts for around 85% of patients
- acute attacks (e.g. last 1-2 months) followed by periods of remission
- secondary progressive (SPMS)
- describes relapsing-remitting patients who have deteriorated and have developed neurological signs and symptoms between relapses
- around 65% of patients with relapsing-remitting disease go on to develop secondary progressive disease within 15 years of diagnosis
- gait and bladder disorders are generally seen
- primary progressive
- accounts for 10% of patients
- progressive deterioration from onset
- more common in older people
- progressive relapsing
where can demyelination occur?
- Demyelination in white matter of the brain and the S.C = plaques
- Close relationship to the post-capillary venules (peri-venular):
- Periventricular region of the cerebral hemispheres
- Corpus callosum
- Brainstem (including medial longitudinal fasciculus), cerebellum and cerebellar peduncles
- Cervical cord
- Optic nerves
- Myelin destruction – relative sparing of the axon
- An inflammatory infiltrate containing mononuclear cells and lymphocytes is found
Interstitial oedema occurs in acute lesions
s/s
- Relapsing and remitting symptoms: caused by demyelination healing poorly - lesions disseminated in time and space
- Worsen: heat or exercise
- Summary of symptoms (monosymptomatic – exacerbated by heat (e.g. hot bath) or exercise) – TEAM:
- Tingling/numbness: limbs
- Eye: optic neuritis (↓ central vision + pain on eye movement)
- Ataxia, diplopia: other cerebellar/brainstem symptoms
- Motor: usually spastic paraparesis, leg weakness
- Optic Neuritis
- PC: pain on eye movement, rapid ↓ central vision
- o/e: ↓ acuity, ↓ colour vision, white disc, central scotoma,
- RAPD
- INO / ataxic nystagmus / conjugate gaze palsy
- Disruption of MLF connecting CN6 to CN3
- Weak adduction of ipsilateral eye
- Nystagmus of contralateral eye
- Convergence preserved
- Sensory:
- Dysaesthesia
- pins and needles
- ↓ vibration sense
- Trigeminal neuralgia
- Motor:
- Spastic weakness
- Transverse myelitis
- Eye:
- Diplopia, hemianopa
- Optic neuritis → atrophy Visual phenomena (on exercise)
- Bilateral internuclearopthalmoplegia (INO)
- pupil defects
- Cerebellum:
- Trunk and limb ataxia
- Scanning dysarthria
- Falls
- Sexual/GU:
- ED + anorgasmia
- Retention
- Incontinence
- GI:
- Swallowing disorders
- Constipation
- Cognitive/visuospatial decline:
- accidents
- amnesia
- mood changes (no ECT)
- ↓ executive function
ix
nvestigation in multiple sclerosis include:
MRI scanning:
- permits the visualisation of the dissemination of lesions in time and space
- will reliably identify plaques in the cortex, brainstem and spinal cord
- gadolinium enhancement improves sensitivity
CSF:
- permits the detection of intrathecal inflammation
- pleocytosis
- slightly raised protein
- 70% of patients hace a raised IgG - electrophoresis reveals oligoclonal bands in the CSF which are not found on serum electrophoresis
visual evoked potentials:
- permit the demonstration of conduction changes consistent with demyelination
- are of normal amplitude but show an increased latency in patients who have or have had optic neuritis
- measurement of visual evoked potentials is a good way of demonstrating a previous, often subclinical, episode of demyelination in order to make the diagnosis of multiple sclerosis
- auditory brainstem evoked potentials and somatosensory evoked potentials may also be measured
Before referring a person suspected of having MS to a neurologist, exclude alternative diagnoses by performing blood tests including:
- full blood count
- inflammatory markers for example erythrocyte sedimentation rate, C-reactive protein
- liver function tests
- renal function tests
- calcium
- glucose
- thyroid function tests
- vitamin B12
- HIV serology
>>>>>>>>> Do not diagnose MS on the basis of MRI findings alone
mx
Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure.
Acute relapse
High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)
Disease modifying drugs
Beta-interferon has been shown to reduce the relapse rate by up to 30%. Certain criteria have to be met before it is used:
- relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
- secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
- reduces number of relapses and MRI changes, however doesn’t reduce overall disability
Other drugs used in the management of multiple sclerosis include:
- glatiramer acetate: immunomodulating drug - acts as an ‘immune decoy’
- natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier
- fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available
Some specific problems
Fatigue
- once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine
- other options include mindfulness training and CBT
Spasticity
- baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
- physiotherapy is important
- cannabis and botox are undergoing evalulation
Bladder dysfunction
- may take the form of urgency, incontinence, overflow etc
- guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients
- if significant residual volume → intermittent self-catheterisation
- if no significant residual volume → anticholinergics may improve urinary frequency
Oscillopsia (visual fields apper to oscillate)
- gabapentin is first-line
poor prognosis signs
- Poor Prognostic Signs
- Older
- Male
- Motor signs @ onset
- Many relapses early on
- Many MRI lesions
- Axonal loss
good prognosis signs
- Better Prognostic Signs
- Female
- <25
- Sensory signs @ onset
- Long interval betweenrelapses
- Few MRI lesions
- completely recover btw relapses
- RRMS
