Lecture 7: Myesthenia Gravis, GBS, Myopathic disorders

Question 1

Myesthenia Gravis: essentials of Dx

Answer 1

• fluctuating weakness of commonly used voluntary muscles, producing ax’s such as diplopia, ptosis, and difficulty swallowing
• activity increases weakness
• short acting anticholinesterases transiently improve the weakness

Question 2

Myesthenia Gravis: general considerations

Answer 2

• occurs in all ages, sometimes in association with thymic tumor, thyrotoxicosis, RA or SLE
• most common in young women with HLA-DR3
• sx’s are due to ABs binding to Ach receptors so that Ach action is blocked

Question 3

MG: signs/sx’s

Answer 3

• present with ptosis, diplopia ,difficulty chewing, swallowing, resp difficulties, limb weakness or combo of these
• weakness: localized or generalized
• most likely to be affected: ocular, masticatory, facial or pharyngeal muscles

Question 4

MG: Phys exam

Answer 4

• sustained activity of muscles increases weakness, which improves after brief rest
• NO reflex changes

Question 5

MG: Dx

Answer 5

• Tensilon test: administer tensilon ( which prevents breakdown of Ach), if ptosis gets better than is MG
• single fiber EMG
• Antibody measurement: AchR, MUSL

Question 6

MG: Tx

Answer 6

Neostigmine and pyridostigmine = anti cholinesterase drugs

• immunosuppressant drugs
• thymectomy
• immunomodulation: PE or IVIg

Question 7

Drugs that can worsen MG

Answer 7

• BB
• Corticosteroids
• Ca channel blockers
• aminogylcosides
• Magnesium
• curariform drugs

Question 8

Guillain-Barre Syndrome (GBS): essentials of dx

Answer 8

• acute or subacute progressive polyradiculoneuropathy
• weakness is more severe than sensory disturbances
• acute dystautonomia may be life threatening

Question 9

GBS: General considerations

Answer 9

• acute or subacute polyradiculoneuropathy sometimes follows infective illness, inoculations, or surgical procedures
• associated with preceding Campylobacteri jejuni enteritis
• probably has immunologic basis but mechanism is unclear

Question 10

GBS: Epidemiology

Answer 10

• incidence: 1-4/100,000
• any age, peak in 4th decade; males > females
• 60-70% with antecedent infxn: C. Jejuni
• other causes: surgery, lymphos, lupus,

Question 11

GBS: Signs/sx (AIDP)

Answer 11

AIDP= acute idiopathic demyelinating polyneuropathy

• LOSS OF DTRs
• paresthesias in feet then ascending
• weakness beginning distally then ascending
• can have other patterns: like onset in eye, face with descending pattern; or onset in hands and arms with descending and ascending pattern
• autonomic disturbances are common: tachycardia, cardiac irregularities, hypo/hyper-tension, facial flushing, sweating, pulm dysfxn, impaired sphincter control

Question 12

GBS: Lab findings

Answer 12

• CSF: high protein

- nerve conduction studies: abnormal sensory condution (arm > leg); abnormal motor nerve conduction

Question 13

GBS therapies

Answer 13

• IV Ig, PE

- supportive: PT, OT, swallow, dysautonomnia, skin, nutrition, vent. monitoring, support

Question 14

GBS: prognosis

Answer 14

• 50% left with residual near signs: loss of reflexes, mild sensory loss, abnormal nerve conduction
• 10% have significant neuro deficit
• 5% mortality rate

Question 15

GBS Variants: AMSAN/AMAN

Answer 15

AMSAN= acute motor and sensory axonal neuropathy
AMAN = acute motor axonal neuropathy
-caused by ABs to gangliosides on axon membrane
-similar to AIDP (clinical picture similar)
-pathophys: axon loss

Question 16

GBS variant: Miller fisher syndrome

Answer 16

• this has ataxia, areflexia and opthalmoplegia

- also associated with anti-GQ1b ABs

Question 17

Lambert-Eaton Syndrome : essentials of dx

Answer 17

• variable weakness, typically improving with activity
• a hx of malignant dz may be present
• dysautonomic sx’s may also be present

Question 18

Lambert-Eaton: gen considerations

Answer 18

• may be associated with small cell carcinoma and occasionally with certain autoimmune dz.’s
• defective release of Ach caused by voltage gated Ca channel ABs–> leads to weakness, especially of PROXIMAL muscles of limbs
• unlike MG: power increases with sustained contraction

Question 19

Lambert Eaton dx

Answer 19

-confirmed with electrophysiogically: muscle response to stimulation of its motor nerves increases if the nerve is stimulated repetitively at high rates

Question 20

Lambert Eaton tx

Answer 20

• Plasma exchange and immunosuppressive therapy

- symptomatic therapy: K channel antagonists

Question 21

Duschend Type MD

Answer 21

• X linked recessive
• onset = 1-5 y/o
• Distribution= pelvic, then shoulder girdle; later is reap muscles and limbs
• rapid progression, mortality within 15 yrs of onset
• intellectual retardation is common
• increase in serum creatinine kinase

Question 22

Becker type MD

Answer 22

• X linked recessive
• onset = 5-25 yrs old
• pelvic then shoulder girdle weakness
• slow progression, may have normal life span
• dystrophin levels normal with increased serum CrK

Question 23

Myotonic type MD

Answer 23

• autosomal dominant
• any age, usually 20-40 y/o
• face, neck and limb weakness
• slow progression
• other features: cataracts, frontal baldness, testicular atrophy, DM, cardiac abnormalities, intellectual changes