Multiple sclerosis (N) Flashcards
Define MS.
Chronic, inflammatory demyelinating disease of the CNS characterised by the presence of episodic neurological dysfunction in at least two areas of the CNS (brain, SC and optic nerves) separated in time and space
What does MS result in?
Discrete plaques of demyelination and axonal degeneration in the brain and spinal cord
What response is involved in MS?
T-cell mediated immune response
What is a specific condition the features have to fulfil to be classed as MS?
Separation in time and space - lesions in the CNS must have occurred in at least 2 different places and at least 2 different times
Two episodes of neurological dysfunction that are separated in time and space
What are the different forms of MS? (5)
- relapsing-remitting MS
- primary progressive MS
- secondary progressive MS
- clinically isolated syndrome
- Marburg variant
What is relapsing-remitting MS like?
- most common (85%)
- acute attacks (last 1-2 months) with complete recovery in between attacks
What is primary progressive MS like?
- 10% of patients
- progressive deterioration from onset - no relapsing/remitting, straight progressive, steady accumulation of disability
What is secondary progressive MS like?
- progressive accumulation of disability AFTER initial relapsing-remitting course
- relapsing-remitting patients who have deteriorated and developed neurological signs between relapses
- 65% progress from relapsing-remitting –> secondary progression
What is clinically isolated syndrome (MS) like?
- single clinical attack of demyelination
- attack itself does not count as MS
- 10-50% progress to MS
What is Marburg variant (MS) like?
Severe fulminant variation of MS –> advanced disability or death within weeks
Which demographics is MS most common in? (3)
Most common is young, white female
- female
- 20-40 years old
- white
What are the causes of MS? (2)
- genetic predisposition
- environmental factors e.g. low vitamin D, smoking, EBV
What is the earliest manifestation of MS? (1+6)
Optic neuritis (inflammation of the optic nerve) - earliest and most common presentation
- unilateral, impaired vision
- colour blindness
- rapid loss of central vision
- pain on eye movement
- RAPD - both pupils appear dilated when eye illuminated in swinging torch test
- central scotoma
What is another visual phenomenon that may be seen in MS?
(Apart from optic neuritis)
Intranuclear ophthalmoplegia - lesion of the medial longitudinal fasciculus, blocking connection between contralateral CN6 nucleus and ipsilateral CN3 nucleus, affecting horizontal gaze
–> nystagmus of the abducting eye with absent adduction of the other (ipsilateral) eye
(or isolated nystagmus)
What would a right intranuclear ophthalmoplegia look like (MS)?
Right eye unable to adduct, and nystagmus will occur in left eye simultaneously i.e. when it is abducting
What types of symptoms might we see in MS? (6)
- visual
- sensory
- motor
- cerebellar
- autonomic
- others - psychological/cognitive
What are some visual symptoms of MS? (5)
- optic neuritis (initial and most common) - vision loss, pain
- intranuclear ophthalmoplegia (contralateral medial longitudinal fasciculus lesion) = lateral horizontal gaze
- spastic paraparesis - papillitis, transverse myelitis
- acute paraparesis - visual loss, neuromyelitis optica
- Uhtoff’s phemomenon - worsening of vision following rise in body temperature
What are some sensory symptoms of MS? (5)
- paraesthesia, pins and needles, numbness
- burning
- odd sensation of patch of wetness/burning
- hemibody sensory loss or tingling
- Lhermitte’s sign - paraesthesia in limbs on neck flexion
What are some motor symptoms of MS? (4)
- limb weakness - after walking, leg cramping
- spasms
- stiffness
- heaviness
What are some cerebellar symptoms of MS? (6)
- trunk and limb ataxia + ataxic gait
- intention tremor
- scanning speech
- falls
- dysdiadochokinesia
- tremor
What are some autonomic symptoms seen in MS? (2)
- urinary urgency/frequency/hesitation
- impotence / ED
Urinary incontinence often first sign
What specific signs might be seen in MS? (3)
- Lhermitte’s sign - paraesthesia in limbs on neck flexion
- Uhtoff’s sign - worsening of neurological Sx (eyesight) as body gets overheated
- Hoffman’s sign - flicking/pressure on nail bed causes twitching of thumb/fingers
What visual signs might you see on examination in MS? (3)
- RAPD
- central scotoma (if optic nerve affected)
- field defects (if optic radiation affected)
What UMN signs might you see in MS? (3)
- positive Babinski’s sign
- spasticity (common in legs)
- hyperreflexia
What are some risk factors for MS? (7)
- female sex
- Fx of MS
- Northern latitude
- genetic factors
- vitamin D deficiency
- smoking
- EBV
What are the first-line investigations for MS?
MRI brain and spinal cord with gadolinium contrast
What do we see in MS on MRI brain with contrast?
Hyperintensities in periventricular white matter (white) - periventricular plaques
Dawson fingers: often seen on FLAIR images - hyperintense lesions perpendicular to the corpus callosum
High signal T2 lesions
What do we see in MS on MRI spinal cord with contrast?
Demyelinating lesion in SC, hyperintensities (white)
How can we see separation of time and space in MS in MRI?
Lesions with varying degrees of contrast enhancement and restricted diffusion indicating active/recent demyelination
What more invasive investigation can we do for MS?
Lumbar puncture –> CSF analysis:
- unmatched oligoclonal bands
- elevated IgG antibodies
What would evoked potentials be like in MS?
Visual, auditory and somatosensory evoked potentials may show delayed conduction velocity (but well-preserved waveform)
How would visually evoked potential results be affected in MS?
Optic neuritis –> demyelination of optic nerve –> slower conduction along nerve –> visual evoked potential will take longer to travel along axon = delayed conduction velocity
What are some differential diagnoses for MS? (9)
- myelopathy due to cervical spondylosis
- fibromyalgia - generalised weakness and non-specific fatigue
- sleep disorders
- Sjogren syndrome - dry eyes and mouth
- vitamin B12 deficiency
- ischaemic stroke
- peripheral neuropathy
- amyotrophic lateral sclerosis - UMN&LMN (atrophy and fasciculations), no visual changes
- GBS - loss of reflexes, motor Sx, CSF shows cytoalbumin dissociation
What is the diagnostic criteria for MS?
McDonald criteria - diagnosis is based on the finding of two or more CNS lesions on MRI with corresponding symptoms, separated in time and space
How do we approach treatment of MS? (3)
- treatment of acute attack
- prevention of future attacks - reduce triggers, use disease-modifying therapies
- symptomatic treatment of neurological deficits e.g. spasticity, pain, fatigue, bladder dysfunction
What is the 1st and 2nd line management for an acute exacerbation of MS?
- 1st line: IV methylprednisolone (high-dose glucocorticoid) for 5d
- 2nd line: plasma exchange
How do we treat relapsing MS?
Immunomodulators (beta-interferon) or natalizumab
What are typical indications for disease-modifying drugs in MS?
- relapsing-remitting disease + 2 relapses in past 2y + able to walk 100m unaided
- secondary progressive disease + 2 relapses in past 2y + able to walk 10m aided/unaided
What are some drug options for reducing risk of relapse in MS? (5)
- natalizumab (recombinant monoclonal antibody –> a4b1 integrin) - often 1st line
- ocrelizumab (anti-CD20 monoclonal AB) - often 1st line
- fingolimod (S1P receptor modulator)
- beta-interferon (not as effective)
- glatiramer acetate (not as effective)
How do we manage primary progressive MS?
Ocrelizumab if early stage
What is the 1st and 2nd line management for secondary progressive MS?
- 1st line: methylprednisolone OR siponimod
- 2nd line: cladribine
How do we manage spasticity in MS?
Baclofen or gabapentin
How do we manage sensory symptoms (pain and paraesthesia) in MS?
Low-dose anticonvulsant or antidepressant –> gabapentin, pregabalin, carbamazepine, duloxetine, amitriptyline
How do we manage fatigue in MS?
Once other problems (e.g. anaemia, thyroid or depression) have been excluded, NICE recommend a trial of amantadine
Mindfulness training, CBT
How do we manage bladder dysfunction in MS?
- US to assess bladder emptying - anticholinergics may worsen Sx in some patients
- if significant residual volume –> intermittent self-catheterisation
- if no significant residual volume –> anticholinergics may improve urinary frequency
- frequency: oxybutynin, reduce caffeine
How do we manage oscillopsia (visual fields appear to oscillate) in MS?
Gabapentin is 1st line
How do we manage tremor in MS?
Propranolol
What are some complications of MS? (7)
- UTIs
- osteoporosis
- depression
- visual impairment
- erectile dysfunction
- cognitive impairment
- impaired mobility
Describe the prognosis of MS.
High relapse rate in first two years after MS onset
