Multiple Sclerosis Flashcards
What is MS?
Acquired, chronic, immune-mediated, inflammatory disease of the CNS (can affect brain, brainstem, + spinal cord)
What do the inflammatory processes in MS cause pathophysiologically?
Areas of demyelination (damage to white matter), gliosis (scarring), + neuronal damage throughout the CNS.
Describe the epidemiology of MS
F > M (3:1)
Age of onset: 20-40y
More common at high latitudes
What causes MS?
UNKNOWN
Acute then chronic inflammation precipitated by abnormal response to environmental triggers in genetically pre-disposed
Immune-mediated damage to myelin sheaths results in impaired axonal conduction.
List 2 risk factors for MS
FH
Female
List 3 types of MS
Relapsing-Remitting (RRMS)
Primary Progressive (PPMS)
Secondary Progressive (SPMS)
Describe RRMS
Most common, 85% have RRMS at onset
Attacks (1-2 months) with almost complete recovery between attacks
Describe SPMS
gradual accumulation of disability after initial relapsing course
2/3 of RRMS progress to SPMS
Describe PPMS
Steady progression + worsening of disease from the onset, without remissions.
~10-15% of MS
Define ‘relapse’ of MS
Onset of new Sx, or worsening of pre-existing Sx.
Attributable to demyelinating disease.
Lasting >24 h
In absence of infection, or any other cause.
After a stable period of at least a month.
What do symptoms depend on in MS?
Site of inflammation
List the 4 most common initial presentations of MS
Optic neuritis
Transverse myelitis
Cerebellar-related Sx
Brainstem syndrome
Describe optic neuritis
Unilateral deterioration of visual acuity + colour vision
Pain behind eye + on eye movement
Other than optic neuritis, what are the possible visual manifestations of MS
Optic atrophy
Uhthoff’s phenomenon
Internuclear ophthalmoplegia
What is Uhthoff’s phenomenon?
Worsening of vision following rise in body temperature
Describe fundoscopy in optic neuritis in MS
Often normal but disc may appear pale or swollen.
May be RAPD
What is transverse myelitis?
focal inflammation within the spinal cord
Sensory Sx (such as paraesthesia) or Motor Sx (such as weakness)
below level of inflammation
Typically develop over hours or days.
How may transverse myelitis manifest?
Tight band sensation around the trunk at level of inflammation
Lhermitte’s phenomena
Urinary Sx: urgency, frequency, retention
Focal muscle weakness + reduced sensation below affected spinal level
Muscle tone initially reduced
What is Lhermitte’s phenomena?
Shock-like sensation radiating down the spine + into limbs induced by neck flexion
Describe cerebellar-related symptoms that may arise in MS
Ataxia
Vertigo
Clumsiness
Dysmetria
Describe how brainstem syndromes may manifest in MS
Ataxia
Eye movement abnormalities
Bulbar muscle problems resulting in dysarthria/ dysphagia
What are 3 sensory symptoms of MS?
Pins + needles
Numbness
Burning
What 6 general signs are seen on examination in MS?
Sensory: Paraesthesia
Motor: Spastic weakness most commonly seen in legs
Cerebellar: Limb ataxia (intention tremor, past-pointing)
Urinary frequency/ incontinence
Sexual dysfunction
Cognitive impairment
What is diagnosis based on in MS?
Finding 2 or more CNS lesions with corresponding Sx, separated in time + space (McDONALD CRITERIA)
Only a consultant neurologist should make a dx of MS.
What is seen on brain MRI in MS?
High signal T2 lesions
Periventricular plaques
Dawson fingers: hyper intense lesions perpendicular to corpus callosum
What is seen on spine MRI in MS?
Demyelinating lesions
esp. in the cervical spinal cord
Gadolinium enhancement shows active lesions
What is seen on CSF evaluation in MS?
Oligoclonal bands (+ not in serum)
Increased intrathecal synthesis of IgG
What investigation can be performed in MS when MRI is contraindicated?
Visual evoked potentials: prolongated of conduction (preserved waveform)
Also can perform auditory + somatosensory (painful) evoked potentials but are less commonly abnormal
Why may LP be performed in MS?
r/o infection/ inflammatory causes
What are 4 motor symptoms of MS?
Limb weakness
Spasms
Stiffness
Heaviness
What are 4 autonomic symptoms of MS?
Urinary urgency
Hesitancy
Incontinence
Impotence
What may be found on visual fielding testing in MS?
Central scotoma (if optic nerve is affected) Scotoma = a blind spot in the normal visual field Field defects (if optic radiations are affected)
What occurs in internuclear ophthalmoplegia?
Nystagmus of abducting eye with absent adduction of the other eye
Indicates lesion of contralateral medial longitudinal fasciculus
What is Clinically Isolated Syndrome?
Single clinical attack of demyelination (does NOT count as MS)
10-50% progress to develop MS
Describe management of acute relapse in MS
PO/ IV Methylprednisolone for 3-5 days
Describe the effect of steroids in acute relapse of MS
Shorten duration of relapse but don’t alter degree of recovery
What are the indications for using disease modifying drugs in MS?
RRMS + 2 relapses in past 2y + able to walk 100m unaided
SPMS + 2 relapses in past 2y + able to walk 10m (aided or unaided)
List 5 disease modifying drugs that can be used in MS
Natalizumab
Ocrelizumab
Fingolimod
Beta-interferon
Glatiramer acetate
Describe management of fatigue in MS once other causes have been excluded
Amantadine (specialist initiated)
Mindfulness training + CBT
Alongside PT, which drugs are used first line for spasticity in MS?
Baclofen
Gabapentin
(diazepam, dantrolene + tizanidine)
Describe management of bladder dysfunction in MS
US to assess bladder emptying
Significant residual volume → intermittent self-catheterisation
No significant residual volume → anticholinergics may reduce frequency
What is Oscillopsia?
What drug can be used to manage this in MS?
Where visual fields appear to oscillate
Gabapentin (2nd: memantine)
What is Natalizumab? What is the MOA?
Recombinant monoclonal antibody
Antagonises alpha-4 beta-1-integrin found on surface of leucocytes
Inhibits migration of leucocytes across the BBB
Which disease modifying drug has the strongest evidence base for preventing relapse in MS? What is the mode of delivery?
Natalizumab
Often given first line
IV
What is Ocrelizumab?
Humanized anti-CD20 monoclonal antibody
High-efficacy, often used first-line
IV
What is Fingolimid?
Sphingosine 1-phosphate (S1P) receptor modulator
Prevents lymphocytes from leaving LNs
PO
Describe use of beta interferon in MS
Not considered to be as effective as alternative disease-modifying drugs
SC / IM
What is Glatiramer acetate?
Immunomodulating drug: acts as an ‘immune decoy’
SC
‘older drug’ with less effectiveness
