Multiple Sclerosis Flashcards
Briefly describe MS
An immune mediated inflammatory condition. Plaques of demyelination occur in the CNS that are disseminated in space and time (ie occurring at multiple sites and with 30 days between attacks)
Recurrent episodes of demyelination can lead to what?
Degeneration of nerves and permanent deficit
Is MS more common in men or women?
3 times more common in women
Between what age group is it most commonly diagnosed?
20-40
Is MS more common in higher or lower latitudes?
Higher
What is the cause of MS?
Unknown - likely combination of genetic and environmental
Likely abnormal immune response to environmental triggers in genetically predisposed.
Genetic: female, genes encoding for HLA-DR2 (a specific immune molecule)- used to identify and bind to foreign molecules
Environmental: infections, vit d deficiency
What are the 3 main patterns of presentation?
Relapsing and remitting
Secondary progressive
Primary progressive
Which form of MS is most common?
Relapsing and remitting
Accounts for approximately 85%
Describe relapsing and remitting MS
Acute attacks lasting 1-2 months followed by periods of remission.
Symptoms experienced previously may come back, or new symptoms
Describe secondary progressive MS
With time, remission becomes incomplete, so disability accumulates
Signs and symptoms between relapses
Around 65% of people with relapsing remitting disease go on to develop secondary progressive within 15 years
Describe primary progressive disease
Progressive deterioration from onset
More common in elderly
Accounts for 10%
How does MS commonly present?
Usually monosymptomatic - approximately 20% present with unilateral optic neuritis
Corticospinal tract and bladder involvement are common
How does optic neuritis present?
Unilateral
Pain on eye movement
Sudden loss in vision, partial or complete (usually central visual loss)
Sudden blurring or foggy vision
Loss of colour vision - colours appearing washed out, particularly red (red desaturation)
Reduced contrast sensitivity
Transient worsening of vision with increase in body temperature (Uhthoff’s phenomenon)
Pupil afferent defect
What do symptoms worsen with?
Heat e.g hot bath or exercise
What is a common non specific feature of MS
Significant lethargy
What sensory features are seen in MS?
Pins and needles
Numbness
Reduced vibration sense
Trigeminal neuralgia
Patchy sensory loss
What motor symptoms are seen in MS?
Spastic weakness - most commonly in legs
Myelitis
UMN signs predominate - weakness, spasticity, brisk reflexes
What cerebellar signs are seen in MS?
Ataxia - falls
Intention tremor
Scanning speech ie monotonous
Nystagmus
What sexual/GU symptoms are seen?
Erectile dysfunction
Anorgasmia
Urine retention
Incontinence
Constipation
Swallowing disorders
Other than optic neuritis, what other eye pathology is seen?
Diplopia - eyes not moving in a coordinated way
Hemianopia
Pupil defects (RAPD)
Bilateral internuclear opthalmoplegia - a condition affecting movement of eyes that is characteristic of MS. When covering one eye unilateral movements will be normal. But when together, the adducting eye will not move past midline (may affect one or both eyes). Due to a lesion in the medial longitudinal fasciculus - a heavily myelinated tract that connects optic brainstem nuclei on either side of brainstem (so conjugate movement but not unilateral movement is affected)
Is cognitive decline seen in MS?
Yes
Also visuospatial decline
How is MS diagnosed?
Clinically based on McDonald criteria and after alternative diagnosis excluded.
Early diagnosis reduces relapse rates and disability
What investigations should be done?
MRI of brain and spinal cord - demonstrate demyelination plaques. This is sensitive but not specific.
- helps to rule out other causes e.g cord compression
Immunoelectrophoresis of CSF - shows oligoclonal bands of IgG (suggests CNS inflammation)
Visual Evoked Potentials - can detect lesions in visual pathway - patient has EEG probes on skull to measure brain response to visual stimuli (if response delayed, suggests lesion)
- can also do auditory and somatosensory evoked potentials
Lesions in MS typically involve which areas of the brain?
Temporal lobes, brainstem, cerebellum, cervical spinal cord
What are some characteristics of the spinal cord lesions?
Often small, peripherally located, cervical region
Spinal cord lesions uncommon in most other CNS diseases
Lesions are typically juxtacortical and …
Periventricular white matter
What are some poor prognostic signs?
Older age of presentation
Motor signs at onset
Many early relapses
Many MRI lesions
What impact does pregnancy have?
Does not alter rate of progression
Relapses may reduce during pregnancy and increase afterwards for 3-6 months then return to previous rate
What lifestyle advise should be given?
Regular exercise
Stop smoking
Avoid stress
Is there a cure for MS?
No - treatment focuses on reducing frequency and duration of relapses
How do you treat an acute relapse?
High dose steroids - oral or IV methylprednisolone for 5 days to shorten length of acute relapse.
Use sparingly ie less than twice per year.
Does not alter overall prognosis
What drugs can be used for mild/ moderate relapsing disease?
Disease modifying drugs
Beta interferon
Glatiramer acetate
monoclonal antibodies e.g alemtuzumab, natalizumab
These can reduce number of relapses and may have small effect on slowing disease progression (not a cure)
How can spasticity be managed?
Baclofen and gabapentin
Physiotherapy
Cannabis and Botox undergoing investigation
What type of hypersensitivity reaction is MS?
Type IV
What is included in charcot’s neurological triad?
Dysarthria - difficult or unclear speech
Plaques in brainstem interferes with movements such as eating, talking and swallowing
Nystagmus - involuntary rapid eye movements (plaques in nerves of eyes)
Intention tremor - plaques along motor pathway
What colour appears less saturated?
Red
Does optic neuritis usually cause lasting loss of vision?
No - for most people problem in short term and no lasting loss of vision
Usually gets better on its own
How quickly does the visual loss occur in optic neuritis?
Over hours to days
What cells produce myelin?
Oligodendrocytes
What happens when the immune system attacks the protective myelin sheaths?
Communication between neurons breaks down - sensory, motor and cognitive problems
Hay type of hypersensitivity reaction is MS?
Type IV = cell mediated
Myelin specific T cells release cytokines which dilates BBB - allowing more immune cells in. Cytokines attract B Cells and macrophages - B cells make antibodies that mark the myelin sheath proteins. Macrophages use the markers to engulf the oligodendricytes.
Leaves behind areas of scar tissue also called plaques
Early on demyelination occurs, over time = irreversible
What can improve arm tremor and function?
Botulinum toxin type A injections
What percentage develop progressive disability?
80%
Can an MRI differentiate between active and non active lesions?
Active show up as white patches when a contrast fluid containing gadolinium is injected. If the lesion does not light up - likely older
What is Lehrmitte sign?
On voluntary flexing the head, there is an electric shock sensation travelling down spine to limbs
In terms of rehabilitation, what can be done?
Modifications to cars, walking frame, and rails
Treat all infections promptly
Urinary incontinence common in late stage - manage with oxybutynin or self catheterisation
Physio therapy - reduces pain in spasticity
Cannabis - used for symptom relief
Prevent pressure sores
What is reduced contrast sensitivity?
Inability to pick out objects against their backgrounds, particularly if they are similar shade of colour
People who have an acute episode of demyelinating optic neuritis have what percentage risk of going on to develop MS within 10 years?
38%
What signs suggest optic neuritis?
Optic disc swelling
What suggests spinal cord lesion?
Pyramidal tract lesion - spasticity, hyperreflexia, positive Babinski
Involvement of the dorsal spinal column - loss of vibration and fine touch sensation, numbness, paraesthesia
Urinary incontinence
Lhermitte’s sign - electric shock on neck flexion
What suggests brainstem demyelination?
Diplopia - most commonly CNVI affected
INO
Vertigo and nystagmus
Pseudobulbar palsy
How can end stage disease present?
Spastic tetraparesis Ataxia and nystagmus Urinary incontinence Pseudobulbar palsy Dementia
Death often due to uraemia and bronchopneumonia
How can bladder dysfunction be managed?
USS to assess bladder emptying first
If significant residual volume - self catheterisation
If no significant residual volume - anticholinergics may improve frequency e.g oxybutynin
What type of MRI is particular useful for MS?
FLAIR (similar to T2 but CSF signal nullified)
Particularly useful for evaluating structures in CNS inc periventricular areas, sulci and gyri
What is the criteria for giving beta interferon?
2 attacks in last 3 years followed by reasonable recovery
Why is beta interferon useful?
Helps to reduce relapse rate by about 30%
Does not alter long term outcome
What are Dawson’s fingers?
Finger like radial extensions around ventricles on MRI (signifying MS plaques)
What differentials are there?
Other causes of inflammatory demyelination:
Neuromyelitis optica (Devic’s disease)
Acute disseminated encephalomyelitis ADEM
Vasculitis - SLE…
Infections - neurosyphilis, HIV encephalopathy, PML
