Doenças da junção neuromuscular

Question 1

Quais as três possíveis topografias das doenças da junção neuromuscular?

Answer 1

Presynaptic: Lambert-Eaton myasthenic syndrome, congenital myasthenic syndromes (CMS), botulism, tick paralysis, some drugs, & venoms. Synaptic: CMS of end-plate AChE defi ciency, cholinesterase inhibiting drugs, organophosphates. Postsynaptic: MG, transient neonatal MG, CMS, drugs/venoms.

Question 2

Como é a história e exame fisico da miastenia gravis?

Answer 2

Patient history: Variable or fatiguable weakness, 20% p/w pharyngeal weakness, fatigability or hoarse voice, diplopia (in subtle cases, pts may report blurred vision), orthopnea 2/2 diaphragmatic weakness.

Neurologic exam: Ptosis (usu asymmetric & fatigues w/ upgaze), hypercontracted frontalis to maintain eye opening, fatigability, ophthalmoparesis, bulbar weakness, nl pupillary refl exes, prox limb weakness, tachypnea & shallow respirations, intact sensation, variably depressed refl exes.

Question 3

Quais os subtipos da miastenia gravis?

Answer 3

Classificado conforme anticorpos:

(1) Anti-MuSK: Young F w/ orofacial weakness & early resp weakness.
(2) Ocular: Sx limited to ocular weakness for >2 yr → 90% do not generalize; electrodiagnostic challenge; mono-Rx w/ AChEIs usu suffi cient.
(3) Antibody negative: Classic presentation, neg ab tests (MuSK Ab discovery ↓’d no. in this subgroup), 70% poor response to AChEIs

Question 4

Como fazer a investigação na suspeita de miastenia gravis?

Answer 4

(1) Tensilon test (edrophonium, an AchEI) IV test dose 2 mg, then 3–8 mg at a time up to 10 mg; observe 90 s b/n each dose & 3–5 min after last dose. Follow clinically observable defi cit & only accept unequivocal improvement as (+). Onset 30 s, lasts 5–10 min. Side effects: Salivation, sweating, nausea, cramping, fasciculations, & bradycardia, ↓ BP, resp distress. AMBU bag at bedside, telemetry. Utility: Se 70%–95%, Sp unknown.
(2) Ice test: Put ice pack on closed eye ×3 min–ptosis improves (Se 80%–90%).
(3) EMG/NCS: Repetitive Nerve Stimulation: Low rates of rep stim (2–5 Hz) deplete ACh, → decrement >10% (Se 50%–100% for general MG & 10%–20% for ocular MG). SFEMG: increased jitter or variation in contraction time b/n muscle fi bers (Se 80%– 99%).
(4) Ab testing: (4a) AChR antibodies: Binding Ab: Se 80%–85% in generalized MG; Se 55% in ocular MG; Blocking aAb: + in isolation in ∼1% of MG; Modulating ab: + in 3%–4% MG in isolation, ↑ freq w/ thymoma. (4b) Anti-MuSK (anti-muscle-specifi c tyrosine kinase abs). Prominent orofacial & resp sx at onset; rarely isolated ocular sx. Classic pt 20–30 yo F w/o thymoma. (4c) Striated muscle ab: Se ∼75% for MG w/ thymoma; can be present in older MG pts; utility limited by poor Sp.

Question 5

Qual o prognóstico de um paciente com miastenia gravis?

Answer 5

Prognosis: Early in course, exacerbations are often severe, but w/ Rx remissions lasting many months are common. Max dz severity reached in 2 yr in 66% pts. Spontaneous & durable remission in 10%–15%. On avg, active dz lasts 7 yr followed by 10 yr of relative quiescence, then fi nally “burned out” phase characterized by some degree of fi xed defi cit

Question 6

Como é o manejo da crise miastenica?

Answer 6

# Causes: Dz progression, stressor/illness, withdrawal/↓ in MG Rx, contraindicated medication. 
# Cholinergic crisis (salivation, lacrimation, diarrhea, bradycardia): If pt in crisis, ↓/ hold AChE meds.
#