Myasthenia Gravis and Multiple Sclerosis Flashcards
Most common disorder of neuromuscular transmission
Myasthenia gravis
What is myasthenia gravis?
Autoimmune disorder of the acetylcholine receptors at the NMJ causing weakness and fatiguability of muscles
Distribution of myasthenia gravis
20-30s (more females)
60s-80s (more males)
Types of myasthenia gravis
Ocular (can progress to next)
Generalized
What might play a role in myasthenia gravis?
Thymus (maybe due to similar cells that are on skeletal muscles)-do CT or MRI of chest
Most pts have thymus hyperplasia or thymoma
Hallmark of myasthenia gravis
Fluctuating weakness in ocular, bulbar (speech, chewing, swallowing), limb or respiratory muscles
Sxs of myasthenia gravis
Fluctuating weakness and fatigue of specific muscle groups (worse at end of day or after exercise)
- ptosis/diplopia
- dysarthria, dysphagia, chewing difficulties
- myasthenic sneer (facial muscle weakness)
- Dropped head syndrome and limb weakness in arms more than legs
- Myasthenic crisis due to resp muscles
Triggers than can worsen myasthenia gravis
Hot temps Surgery Emotional stress Illness Menstruation, pregnancy, childbirth Medication
Drugs to avoid with myasthenia gravis
Fluoroquinolones
BBs
Hydroxychloroquine (Plaquinil)
How to diagnose myasthenia gravis
History and physical
Maintain upward gaze x 1 min (ptosis due to fatigability)
Ice pack test in pt with ptosis should improve sxs
NCS and EMG show decrease response on repetitive nerve stimulation and fatigability
Serologic tests for myasthenia gravis
Autoantibodies: AChR Ab (Ach receptor antibodies) MuSK Ab (muscle specific kinase antibodies)
Edrophonium (Tensilon) Test
Used to be used for myasthenia gravis (prolongs presence of Ach to stimulate limited number of AChR and it shows immediate increase in muscle strength)
How to tell generalized MG from ALS
ALS does not have ptosis or diplopia
Lambert-Eaton myasthenic syndrome
Reduced Ach release in NMJ
Autoimmune disease often associated with malignancy (SCLC)
Proximal muscle weakness and sxs worse in AM and improve with exercise!!
Symptomatic tx for myasthenia gravis
Oral acetylcholinesterase inhibitor (Pyridostigmine/Mestinon) similar to Tensilon so short acting
Chronic immunotherapies for myasthenia gravis
Immunomodulating agents (glucocorticoids or azathioprine)
Rapid (short acting) immunotherapies for myasthenia gravis
Plasmapheresis/plasma exchange-directly removes AChR antibodies from circulation
IVIG-pooled immunoglobulin from thousands of donors
(can be used as bridge for chronic therapy)
Last choice for myasthenia gravis tx
Thymectomy in select pts (remission is possible)
Use of pyridostigmine/Mestinon
Limb and bulbar sxs improve more than the ocular sxs
Allows prolonged effect of Ach strength
Titrate and watch for cholinergic SEs (not great for generalized MG tho)
Epidemiology of multiple sclerosis
Usually diagnosed 15-45 YO
More females
Leading cause of permanent disability in young adults
What is multiple sclerosis?
Immune mediated attack on axons and myelin sheaths of nerve fibers causing plaques or demyelination and affects nerve transmission
Imaging test of choice for MS
MRI with and without contrast of brain (revealing plaques within myelin)
Hallmark of MS
Symptomatic episodes occur months-yrs apart and different anatomic locations (based on clinical findings alone or clinical findings and MRI)
*separation of time and space
Possible risk factors for MS
Viral infections Geographic factors related to latitude Sunlight and Vit D (may be protective) Genetic susceptibility Tobaccos
Types of MS
Relapsing-remitting disease
Secondary progressive
Primary progressive
Clinically isolated syndrome (1st attack-no prior sxs but now have acute symptomatology)
Relapsing-remitting MS
Most common type of MS
Clearly defined relapses with full recovery or some deficit
Secondary progressive MS
Initially RRMS with gradual worsening
Usually 10-20 yrs after dx
Primary progressive MS
Progressive sx increase from disease onset with no remission
What is Uhthoff phenomenon?
Specific to MS-transient worsening due to elevated body temp
Typical patient with RRMS
Young adults with episodes (relapses/attacks/exacerbations) of CNS dysfunction
Paresthesia
Optic neuritis
Weakness
Sxs develop over hrs-days and resolve wks-mos
Most common initial feature of MS
Paresthesia (sensory sxs)
What is Lhermitte sign?
MS
Neck flexion causes electrical shock sensation down back/limbs
What is the Marcus Gunn Pupil?
Due to optic neuritis with MS: defective pupillary rxn to light (affected pupil does not constrict in response to bright light)
Other signs of MS
Cerebellar involvement: nystagmus, incoordination, tremor
UMN signs: hyperreflexia, Babinski, clonus
How to diagnose MS
Combo of clinical findings from history and physical and MRI finding (imaging of brain and spinal cord may reveal plaques)
What is shown on CSF analysis for MS?
Oligoclonal bands (CNS inflammation)
Appearance and pressure are normal
Total WBC count are normal (if elevated than consider other causes)
Evoked potential studies for MS
Electrical events generated in CNS by peripheral stimulation of a sensory organ
Measure time a stimulus takes to reach cerebral cortex
What are leukodystrophies?
Rare disease affecting myelin (brain, spinal cord and peripheral nerves)-can be seen on MRI
1st line tx for RRMS
Disease-modifying therapy (infusion, injection, oral therapy)
Tx for primary and progressive MS
More difficult to treat and fewer option
Some benefit with DMT
Others can try immune modulating tx (methotrexate, steroids, stem cells transplant, IVIG)
Disease modifying therapies for MS
Immune modulating
Decrease relapse rate and slower accumulaiotn of MRI brain lesions
Lower long term risk of disease progression
What must be ruled out before using steroids for MS
Infection
First line tx for acute exacerbation of MS
Glucocorticoids (IV methylprednisolone 1000 mg daily x 5 days and short prednisone taper)
Other options for acute exacerbation of MS tx
ACTH injections (expensive) Plasma exchange or plasmapheresis (if poor response to steroids)
When to admit with MS
Pt unable to manage at home
Severe relapses
Who to refer with MS
All pts with MS should have neurologist (multidisciplinary team)
