Multiple Sclerosis & Myasthenia Gravis Flashcards
Define MS
chronic autoimmune disease involving inflammation and destruction of CNS white matter by demyelinating nerve sheaths
What is the epidemiology of MS
- most common demyelinating disease of the CNS
- onset 20-50 with peak at 40s
- 30 year life expectancy
- RF: living far from the equator (low vit D, northern euro descent), W>M, link to EBV
- 5% familial recurrence (hereditary predisposition)
- more likely to have other comorbid autoimmune disorders
Describe the pathophysiology of MS
- autoimmune/inflammatory insult to myelin sheath (B cells)
- inflammatory plaques created disrupting integrity of BBB
- leukocytes enter CNS and cause inflammation cascade (T cells)
- destruction of myelin and gradual neurocognitive decline (macrophages)
What are current therapies for MS focused on
inhibiting T cell and B cell function that takes part in the pathophysiology of MS
What happens to nerve conduction in MS
- nerve impuse unable to traverse the demyelinated portion of an axon efficiently causing it to be slower
Define sclerosis in MS
- pathologic appearance at autopsy
- hard rubbery areas in white matter of brain and spinal cord
- can be any white matter but commonly the periventricular, corpus callosum, optic nerves, dorsal spinal cord
Describe the clinical manifestations of MS
-MC is fatigue
- sensory disturbance
- ataxia
- bladder problems
- visual loss
- spasticity
- gait problems
- Uthoff phenomenon (heat intolerance)
- paresthesia/tingling
- cerebral deficits
- paroxysmal symptoms
What is the most common presenting manifestation of MS
Sensory Symptoms
- paresthesia or hypoesthesia
- starting in one leg and spreading to the other then ascends to pelvis, abdomen, thorax
(characteristic of spinal cord involvement)
What is the second most common manifestation of MS
Motor Symptoms
- limb weakness
- spasticity
- gait disturbance
Describe optic neuritis in MS
- loss of vision evolving over hours/days
- 3rd most common manifestation
- Scotoma; area of blurred vision
- color distinguishing is difficult
- periorbital pain
- diplopia
- demyelinating optic nerve
Describe bilateral internuclear ophthalmoplegia in MS
- failure of eye ADDuction with nystagmus in ABduction
- most common eye movement disorder in MS
Describe the ataxic gait seen in MS
- propulsion
- incoordination
- spasticity
- slapping feet down
- hyperextending knees
- shifting weight to slow body down
Describe the autonomic deficits seen in MS
- urinary difficulties caused by upper motor injury of spinal cord
- susceptible to UTI which can trigger MS flares (immune system stimulated)
Describe the cerebral deficits seen in MS
- memory loss
- personality change
- emotional lability
Describe some of the commonly seen paroxysmal symptoms in MS
Indicative of a relapsing component
- twitching or muscle spasm
- difficulty swallowing
- word finding problems
- shooting pain
- tics of eyelids or lips
- facial or tooth pain
Describe the Uhthoff Phenomenon
temporary worsening of MS syx caused by increased temperature
- usually worsening visual symptoms
- fatigue, pain, balance, weakness, etc
Describe Lhermittes Phenomenon in MS
Sudden brief pain or electrical buzzing sensation, down neck into spine, may spread into arms/legs
- triggers: bending neck forward, coughing, sneezing, etc
- indicates pathology in C-spine
Describe the difference between primary, secondary, and tertiary symptoms of MS
Primary: plaque/axonal damage corresponding to a location in the CNS
Secondary: subsequent conditions from primary plaques
Tertiary: psychosocial effects
Describe the physical exam for MS
- do complete neuro exam
- may see hemi/monoparesis
- ocular abnormalities (blurred, double)
- hyperreflexive +/- clonus
- genital anesthesia
- loss of position/vibration sense
- ataxic gait
- spasticity (LE>UE)
- positive babinski
What are the 4 types of MS
- Clinically isolated syndrome
- relapsing remitting disease
- secondary progressive disease
- primary progressive disease
Describe CIS MS
Clinically Isolated Syndrome
- first episode of neuro syx lasting at least 24hrs
- caused by inflammation or demyelination
- monofocal (single s/s caused by single lesion) or multifocal (multiple s/s caused by lesions in multiple places)
Describe the risk of progression in CIS
- high risk when MRI detects brain lesions
- low risk otherwise
Describe the Macdonald Criteria for diagnosing MS
- evidence of damage in 2+ separate areas of the CNS including the brain, spinal cord optic nerves
AND
-evidence that the damage occurred at different times
AND
-rule out all other diagnoses
Describe imaging for MS
MRI most useful
- gadolinium enhancing lesions can be found in early stages
- sensitive but not specific
- image brain and entire spinal cord (plaques usually dorsal)
What does this show
T1 weighted MRI of brain of someone with MS
Describe
MS lesions seen in each view
image D shows gadolinium enhancing lesion under T1 weighted image with Gd
Describe
MS lesions of the spinal cord
Describe the lumbar puncture findings consistent with MS
- elevated total IgG and IgG ratio
- oligoclonal bands
- proteins indicative of myelin breakdown (oligoproteins)
Describe the 2 major themes of MRI criteria for MS
Dissemination in space (3+)
- one or more T2 lesions in 2 of 4 CNS areas: pariventricular, cortical, infratentorial, spinal cord
Dissemination in time
- Gd enhancing and non Gd at any time
- detectino of new T2 lesion or Gd inhancing lesion compared to baseline scan
Describe evoked potential testing (EEG or EMG) in MS
- measures CNS electric potentials by repetitive stimulation of specific nerves
- looking for delays in potential and conduction blocks
- tests visual pathways and spinal cord dorsal columns
What labs would be helpful in ruling out other disorders in diagnosing MS
- CMP
- lyme titer
- Vit B12
- ANA
- ESR
- HIV ab
- syphilis
Describe Relapsing Remitting MS (RRMS)
most common type
- attacks/relapses followed by complete remission
- can last months to years without new syx
- new episodes are erratic
Describe Secondary Progressive MS (SPMS)
likely the 2nd stage of RRMS
- distinct exacerbations with no remission
- progressive neuro deterioration
- brain atrophy increases
- progression from RRMS to SPMS = 19 years
- men and older pts progress faster
Describe primary progressive MS (PPMS)
least common
- disease progressive from onset with no relapse or remission
- usually later in life
- associated with major spinal cord involvement
- usually present with leg weakness/gait disturbance
What are the factors negatively influencing prognosis
- male gender
- high rate of relapse
- incomplete recovery from first attack
- short remission interval
- symptoms of efferent systems
- older age of onset
- significant disability at 2 and 5 years from onset
- early cerebellar involvement
- involvement of more than one CNS system at time of onset
Describe disease modifying therapy in MS
- immunomodulators ($$$): interferons (Rebiv, Avonex, Plegridy)
- CI in pregnancy and lacttaion
- AEs: elevated LFT, leukopenia, thyroid disease, myalgia, flu-like sx, depression, GI, injection site rxn - off label therapies
Describe the management of MS
Goal is to slow progression and improve QOL, treat exacerbations
- MRI monitoring ever 3 mos after suspicious episode
- corticosteroid therapy to shorten relapse and accelerate recover (prednisone)
- disease modifying therapy started early to minimize axonal damage (anti-CD20 Ab - Ocrevus, Pyrimidine synthesis inhibitor - teriflunomide, Fumarates - Tecfidera)
What are some off-label therapies for MS
- broad spectrum immunosuppressants (cyclophosphamide)
- IVIg
- plasma exchange
Describe the MS relapse protocol
Mild: nonpharm support
Moderate: PO steroids vs 1 IV dose with taper
Severe: hospital, IV methylprednisolone, +/- plasma exchange
Describe the non-pharm treatment of MS
Multidisciplinary
- PT/OT/SLP
- rehab
- psychotheraphy
- complementary/alternative therpies for lifestyle
Describe the symptomatic pharm treatment of MS
-Spasticity: baclofen, tizanidine
-Fatigue: Modafinil
-Neuropathic pain: gabapentin, ASMs
-Bladder: anticholinergic
Describe the Kurtzke Expanded Disability Status Score
Measures the neuro impairment in MS
What may be on your differential list when evaluating for MS
Demyelinating diseases
- guillain barre
Chronic infection
- lyme
- syphilis
- HIV
Psych
Vascular disease
- stroke
- AVM
- vasculitis
Autoimmune
- SLE
- Sjogrens
- Sarcoidosis
Malignancy
Define Myasthenia Gravis
Most common neuromuscular junction disorder
- primary disease of neuromuscular transmission
- weakness d/t autoantibodies against acetylcholine receptors
- usually detected after viral infection
Describe the epidemiology and risk factors of myasthenia gravis
- risk factors: FH 5%, autoimmune disorders, D-penicillamine use in Wilson’s dz, thyroid disorders
- F>M
- onset in F = teens, 20s
- onset in M = 40-50s
Describe the pathophys of MG
- autoantibodies target ACh receptors at NMJ, damage to postsynaptic membrane
- detected after viral infx: measles, EBV, HIV
- small amount associated with thymus dysfunction and T-cell mediated autoantibody production
Describe the clinical presentation of MG
- bilat ocular motor weakness, ptosis, diplopia are the most common initial symptoms
- bulbar symptoms
- generalized muscle weakness in proximal limbs more than legs, trunk, respiratory
- fatigue (hallmark) - onset can be sudden and severe or mild/intermittent over years
Describe a myasthenic crisis
-respiratory muscle weakness producing insufficiency and impending resp failure
- severe bulbar symptoms
- may require mechanical vent
- can be triggered by infection/aspiration, pregnancy, postpartum
Describe the physical exam in MG
- ptosis may worsen with propping of opposite eye or sustained upward gaze (curtain phenomenon)
- snarling expression
- symmetric muscle weakness in proximal limbs (sustained abduction of arms, repeated rising from chair without arms)
- monitor resp function
- Tensilon test
- Ice pack test: 2 mins of icing muscle may improve weakness
Describe the tensilon test used in MG examination
Tensilon (edrophonium) is an acetylcholinesterase inhibitor that is given IV to the pt before they perform muscle movements.
Test is positive if pts strength improves
Less common d/t worsening of syx and cholinergic side effects, and requires cardiac monitoring!
Describe the labs involved in MG examination
-antiacetylcholine receptor antibody blood test: positive in 90% of pts with generalized MG and 50% in ocular MG
- antimuscle specific tyrosine kinase antibody
- other antibody testing
Describe some of the electrodiagnostic studies for MG
- slow repetitive nerve stim: measure action potential of muscle: shows decrease in action potential with first 5 stimuli
- single fiber EMG: variable transmission time called a jitter
What is the hallmark symptom of MG
- fatiguability of muscles
- the more the muscle is used the weaker it will get
What might be on the differential list when evaluating MG
- thyroid ophthalmopathy
- oculopharyngeal muscular dystrophy
- brain stem and motor nerve lesions
- botulism
- ALS
- drug induced MG
Describe the management of MG
Multidisciplinary team
- pharm: cholinesterase inhibitors (Mestinon or Prostigmin), corticosteroids for immunosuppression, IVIg for crisis
- respiratory monitoring
- thickened liquid diet
- avoid meds that can make MG worse: abx, beta blockers, Ca channel blockers, iodine contrast, Li, D-penicillamine (Wilson’s)
Does MG typically present with sensory loss or pain
Nope
