Myasthenia Gravis and Multiple Sclerosis

Question 1

Most common disorder of neuromuscular transmission

Answer 1

Myasthenia gravis

Question 2

What is myasthenia gravis?

Answer 2

Autoimmune disorder of the acetylcholine receptors at the NMJ causing weakness and fatiguability of muscles

Question 3

Distribution of myasthenia gravis

Answer 3

20-30s (more females)

60s-80s (more males)

Question 4

Types of myasthenia gravis

Answer 4

Ocular (can progress to next)

Generalized

Question 5

What might play a role in myasthenia gravis?

Answer 5

Thymus (maybe due to similar cells that are on skeletal muscles)-do CT or MRI of chest
Most pts have thymus hyperplasia or thymoma

Question 6

Hallmark of myasthenia gravis

Answer 6

Fluctuating weakness in ocular, bulbar (speech, chewing, swallowing), limb or respiratory muscles

Question 7

Sxs of myasthenia gravis

Answer 7

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

Question 8

Triggers than can worsen myasthenia gravis

Answer 8

Hot temps
Surgery
Emotional stress
Illness
Menstruation, pregnancy, childbirth
Medication

Question 9

Drugs to avoid with myasthenia gravis

Answer 9

Fluoroquinolones
BBs
Hydroxychloroquine (Plaquinil)

Question 10

How to diagnose myasthenia gravis

Answer 10

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

Question 11

Serologic tests for myasthenia gravis

Answer 11

Autoantibodies:
AChR Ab (Ach receptor antibodies)
MuSK Ab (muscle specific kinase antibodies)

Question 12

Edrophonium (Tensilon) Test

Answer 12

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)

Question 13

How to tell generalized MG from ALS

Answer 13

ALS does not have ptosis or diplopia

Question 14

Lambert-Eaton myasthenic syndrome

Answer 14

Reduced Ach release in NMJ
Autoimmune disease often associated with malignancy (SCLC)
Proximal muscle weakness and sxs worse in AM and improve with exercise!!

Question 15

Symptomatic tx for myasthenia gravis

Answer 15

Oral acetylcholinesterase inhibitor (Pyridostigmine/Mestinon) similar to Tensilon so short acting

Question 16

Chronic immunotherapies for myasthenia gravis

Answer 16

Immunomodulating agents (glucocorticoids or azathioprine)

Question 17

Rapid (short acting) immunotherapies for myasthenia gravis

Answer 17

Plasmapheresis/plasma exchange-directly removes AChR antibodies from circulation
IVIG-pooled immunoglobulin from thousands of donors
(can be used as bridge for chronic therapy)

Question 18

Last choice for myasthenia gravis tx

Answer 18

Thymectomy in select pts (remission is possible)

Question 19

Use of pyridostigmine/Mestinon

Answer 19

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)

Question 20

Epidemiology of multiple sclerosis

Answer 20

Usually diagnosed 15-45 YO
More females
Leading cause of permanent disability in young adults

Question 21

What is multiple sclerosis?

Answer 21

Immune mediated attack on axons and myelin sheaths of nerve fibers causing plaques or demyelination and affects nerve transmission

Question 22

Imaging test of choice for MS

Answer 22

MRI with and without contrast of brain (revealing plaques within myelin)

Question 23

Hallmark of MS

Answer 23

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

Question 24

Possible risk factors for MS

Answer 24

Viral infections
Geographic factors related to latitude
Sunlight and Vit D (may be protective)
Genetic susceptibility
Tobaccos

Question 25

Types of MS

Answer 25

Relapsing-remitting disease Secondary progressive Primary progressive Clinically isolated syndrome (1st attack-no prior sxs but now have acute symptomatology)

Question 26

Relapsing-remitting MS

Answer 26

Most common type of MS | Clearly defined relapses with full recovery or some deficit

Question 27

Secondary progressive MS

Answer 27

Initially RRMS with gradual worsening | Usually 10-20 yrs after dx

Question 28

Primary progressive MS

Answer 28

Progressive sx increase from disease onset with no remission

Question 29

What is Uhthoff phenomenon?

Answer 29

Specific to MS-transient worsening due to elevated body temp

Question 30

Typical patient with RRMS

Answer 30

Young adults with episodes (relapses/attacks/exacerbations) of CNS dysfunction Paresthesia Optic neuritis Weakness Sxs develop over hrs-days and resolve wks-mos

Question 31

Most common initial feature of MS

Answer 31

Paresthesia (sensory sxs)

Question 32

What is Lhermitte sign?

Answer 32

MS | Neck flexion causes electrical shock sensation down back/limbs

Question 33

What is the Marcus Gunn Pupil?

Answer 33

Due to optic neuritis with MS: defective pupillary rxn to light (affected pupil does not constrict in response to bright light)

Question 34

Other signs of MS

Answer 34

Cerebellar involvement: nystagmus, incoordination, tremor | UMN signs: hyperreflexia, Babinski, clonus

Question 35

How to diagnose MS

Answer 35

Combo of clinical findings from history and physical and MRI finding (imaging of brain and spinal cord may reveal plaques)

Question 36

What is shown on CSF analysis for MS?

Answer 36

Oligoclonal bands (CNS inflammation) Appearance and pressure are normal Total WBC count are normal (if elevated than consider other causes)

Question 37

Evoked potential studies for MS

Answer 37

Electrical events generated in CNS by peripheral stimulation of a sensory organ Measure time a stimulus takes to reach cerebral cortex

Question 38

What are leukodystrophies?

Answer 38

Rare disease affecting myelin (brain, spinal cord and peripheral nerves)-can be seen on MRI

Question 39

1st line tx for RRMS

Answer 39

Disease-modifying therapy (infusion, injection, oral therapy)

Question 40

Tx for primary and progressive MS

Answer 40

More difficult to treat and fewer option Some benefit with DMT Others can try immune modulating tx (methotrexate, steroids, stem cells transplant, IVIG)

Question 41

Disease modifying therapies for MS

Answer 41

Immune modulating Decrease relapse rate and slower accumulaiotn of MRI brain lesions Lower long term risk of disease progression

Question 42

What must be ruled out before using steroids for MS

Answer 42

Infection

Question 43

First line tx for acute exacerbation of MS

Answer 43

Glucocorticoids (IV methylprednisolone 1000 mg daily x 5 days and short prednisone taper)

Question 44

Other options for acute exacerbation of MS tx

Answer 44

``` ACTH injections (expensive) Plasma exchange or plasmapheresis (if poor response to steroids) ```

Question 45

When to admit with MS

Answer 45

Pt unable to manage at home | Severe relapses

Question 46

Who to refer with MS

Answer 46

All pts with MS should have neurologist (multidisciplinary team)