Multiple Sclerosis Flashcards
Define Multiple Sclerosis.
Chronic cell-mediated AI demyelinating disease characterised by the presence of episodic neurological dysfunction in at least two areas of the CNS (brain, spinal cord, and optic nerves) separated in time and space.
What are the two phenotypes of MS?
- Relapsing-remitting disease (most common - 85%)- includes clinically isolated acute attacks lasting 1-2months, followed by remission
- Progressive disease
- Primary progressive (10%)- progressive accumulation of disability from onset. More common if older.
- Secondary progressive - 65% progress to this in 15yrs from an initial relapsing course. Progressive accumulation of disability.
Who is most affected by MS?
White women (3:1, F:M)
Aged 20-40yrs (occasionally diagnosed in 60-70’s where pt have been asymptomatic for many years)
More common in higher latitudes (x5 more common than in tropics)
What are the risk factors for MS?
- Female sex
- Northern latitude
- Genetic factors
- Smoking Vit D deficiency
- AI disease
- EBV
What is the aetiology of MS?
- Environmental and genetic susceptibility (x20-40 risk in first degree relatives, 30% MZ twin concordance, 2% DZ twin concordance)
- EBV may be linked to MS but other viruses have not proved to be causative.
Infection or postnatal hormonal changes may trigger relapses. as well as surgery or stressful life events (although controversial)
Which part of the CNS is involved in MS?
CNS white matter
Demyelination of axons causes distal and retrograde degeneration over time.
What is the pathophysiology of MS?
Unknown - no specific antibody linked. Can be said to have 2 distinct but overlapping phases: inflammatory and degenerative:
- Inflammatory - lymphocytes with ecephalitogenic potential become activated and enter CNS by binding to endothelial cells, releasing MMPs and crossing the BBB. This causes a further influx of inflammatory cells which produce cytokines, attract macrophages and cause demyelination.
- Degenerative - involves axonal degeneration and loss. There is destabilisation of the axonal membrane potential which causes distal and retrograde degeneration over time.
What is the difference in pathophysiology of relapsing-remitting and progressive MS?
Relapsing-remitting MS shows the most inflammatory activity, followed by early secondary progressive MS.
Primary progressive MS is thought to be a primarily degenerative process, although some patients do have relapses and/or enhancing lesions. All currently-approved disease-modifying therapies in MS are most active against inflammation.
What are the most common presentation of MS? (2)
- Optic neuritis - usually lasting over 48hrs with no fever or other illness shows a demyelinating episode of MS
- Transverse myelitis - usually asymmetrical with patches of odd sensation like wetness/tingling
What are the signs and symptoms of MS?
- Fatigue
- Visual disturbance in one eye - like looking through petroleum jelly. May have pain moving eye and discriminating colours especially red.
- Sensory disturbance- patches of wetness, burning, hemibody sensory loss/tingling, banding pattern with spinal cord lesions
- Lhermitte’s sign
- Foot dragging/slapping after walking several miles
- Leg cramping
- Fatigue
- Urinary frequency
- Bowel dysfunction - constipation common
- Spasticity/increased tone (UMN)
- Increased reflexes (UMN) - clonus at ankles, often symmetrical
- Imbalance/incoordination
- Pale optic disc/non-correctable visual loss - optic neuritis
- Incorrect Ishihara answers
- Abnormal eye movements
What abnormal eye movements may be present in MS?
Internuclear ophthalmoplegia (nystagmus of the abducting eye with absent adduction of the other eye)
or isolated nystagmus may be present.
Which colour do people with MS have trouble seeing?
Red - seen as a ligher orange due to damage to the optic nerve
What is Lhermitte’s sign?
Electric shock-like sensations extending down the cervical spine radiating to the limbs - commonly seen in MS
Which type of neuralgia might you also get with S?
Trigeminal
What investigations would you do for MS?
Careful neurological history and examination; confirmed by MRI and CSF
- MRI- brain - sagittal FLAIR images show non-specific white matter changes but must monitor for progression to diagnose MS
- MRI spinal cord - demyelinating lesions particularly in cervical region
- FBC, metabolic panel, TSH, vit B12 - should be normal
- CSF evaluation - oligoclonal bands and elevated CSF IgG with increased IgG synthesis in 80% of MS cases
What are 3 causes of optic neuritis?
- MS
- Diabetes
- Syphilis
What are the clinical features of optic neuritis?
- Unilateral decreased visual acuity over hours/days
- Poor colour discrimination
- “Red saturation”
- RAPD
- Central scotoma
What is the management of optic neuritis?
high dose steroids
What is the prognosis with optic neuritis?
Recover within 4-6 weeks with steroids
If optic neuritis alone, but MRI shows >3 white matter lesions → 50% risk of MS in 5yrs
Which disorders are commonly seen in secondary progressive MS disease?
Gait and bladder disorders commonly seen
Which disorders are commonly seen in secondary progressive MS disease?
Gait and bladder disorders commonly seen
What are the signs of MS on MRI?
- high signal T2 lesions
- periventricular plaques
- Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum
What is seen in CSF in MS?
- oligoclonal bands (and not in serum)
- increased intrathecal synthesis of IgG
What are the visual evoked potentials like in MS?
- delayed, but well preserved waveform
What is shown on this MRI?
MRI showing multiple white matter plaques penpendicular to the corpus callosum giving the appearance of Dawson fingers
NB: The corpus callosum is a large bundle of more than 200 million myelinated nerve fibers that connect the two brain hemispheres
What is shown on this MRI?
Widespread periventricular, juxtacortical, post fossa and upper cervical cord high T2 regions
Difference in the lesions with varying degrees of contrast enhancement and restricted diffusion indicating active/recent demyelination
What is the goal of management of MS?
Reduce frequency and duration of relapses
No cure
What is the management of acute relapses of MS? What is the goal?
High dose IV/oral methylprednisolone 5 days = goal is to shorted length of relapse; will not alter degree of recovery (ie. may not return to baseline)
What disease-modifying drugs are available for MS?
Natalizumab (mAb alpha1-beta1 integrin antagonist) - IV
Fingolimod (sphingosine 1-phosphate (S1P) receptor modulator) - PO
Beta interferon (not as effective) - SC/IM
Glatiramer acetate (given with beta interferon) - SC
What are the indications for DMDs in MS?
Relapsing-remitting AND 2 relapses in last 2yrs AND unable to walk 100m unaided
OR
Secondary progressive AND 2 relapses in last 2yrs AND able to walk 10m (aided or unaided)
Which DMD for MS has the strongest evidence?
Natalizumab - often used first line
Works by inhibiting migration of leukocytes across the endothelium of BBB
What is used to manage … in MS?
- Fatigue
- Spasticity
- Bladder dysfunction
- Oscillopsia
Fatigue - amantadine (if other causes ruled out)
Spasticity - baclofen and gabapentin
Bladder dysfunction - check type with USS, then anticholinergics or self-catheterisation
Oscillopsia - gabapentin
What is oscillopsia?
Visual fields appear to oscillate
What is being researched for management of spasticity in MS?
Cannabis and botox
How is MS managed?
- Lifestyle modification and non-pharamcological therapy - regular exercise and good sleep hygiene
- Methyprednisolone - 1000mg IV OD for 3 days in an acute relapse
- Plasma exchange - with severe or rapidly progressing disability
- Immunomodulators
- Low dose anticonvulsants - for sensory symptoms
- Medical therapy e.g. propanolol for tremor
etc
