Myasthenia Gravis for the Internist
Neurologic disorder characterized by muscle weakness worsened by muscled use and improved w/ rest
Epidemiology: women in 20s-30s, men >60
Pathogenesis: auto-Ab’s vs. acetylcholine receptor (80-90% of cases), muscle specific receptor tyrosine kinase Ab’s
Cardinal feature: degree of weakness worsens w/ exercise of affected muscles, improves w/ rest
Eye muscles: ptosis, diplopia (extraocular eye muscle involvement)
Bulbar muscles: facial muscle weakness (smiling), weakness of palate and tongue, difficulty chewing, difficulty swallowing, choking
Limb and trunk muscles: usually proximal muscles
i. Inducible ptosis by sustained upward gaze
ii. Fatigue of upper extremities after outstretched arms
iii. Breath count – deep inspiration followed by counting out quickly during expiration (<20 ≈ FVC<1)
iv. Weakness w/ neck flexion (and extension): 4/5 or less is concerning
i. IV injection of Edrophonium chloride (acetylcholinesterase inhibitor)
EMG studies, repetitive nerve stimulation
Patient history - # intubations, bipap, common myasthenia triggers (ex infection, medication, noncompliance), myasthenia manifestations specific for that particular patient
Breath count (<20 is concerning) – compare to baseline
Low FVC (<=1 or compared to baseline) Æ measure ABG if you don’t think they need intubation in next 20 min.
Intubate if necessary (FVC much lower than baseline, esp if <1, use of accessory muscles, concerning ABG)
*Note: low FVC (or breath count) can be result of poor effort – always look at patient, assess overall clinical status, and remember that FVCs may vary according to how tired the patient is (time of day) and when they got their last dose of Ach-i
Pyridostigmine (mestinon) – acetylcholinesterase inhibitor
i. Muscarinic side effects – abdominal cramping, diarrhea, fasciculations, weakness (distinguish from weakness
precautions, consider nocturnal BIPAP (for tenuous patients)
i. Azathioprine, Cyclosporine, Mycophenolate (cellcept), Plasmapheresis, IVIg
ii. Steroids may initially worsen myasthenia, so start in hospital
Elective intubation for respiratory depression (esp w/ FVC <1) –> admit to NCCU (or MICU, if NCCU full)
Drugs to avoid in myasthenia Drugs that impair N-M transmission and may increase weakness Antibiotics
Aminoglycosides: tobramycin, gentamycin, netilmicin, neomycin, streptomycin, kanamycin Fluoroquinolones: ciprofloxacin, norfloxacin, ofloxacin, gatifloxacin Tetracyclines clindamycin Sulfonamides Penicillins – considered safe, though anecdotes of ampicillin causing resp depression Macrolides: azithromycin, clarithromycin Ritonavir
-avoid magnesium containing drugs in renal failure
Drugs implicated as potentially harmful in myasthenia gravis patients based on either anecdotal case reports or in-vitro microelectrode studies Beta blockers
propanolol, oxprenolol, timolol, practolol, atenolol, labetalol, metoprolol, nadolol
lithium, phenothiazines, amitriptyline, imipramine, amphetamines, haldol
TL'AZT'EN NATION GUIDELINES for RESEARCH IN TL'AZT'EN TERRITORY 1. Purpose These guidelines have been developed to help ensure that, in all research sponsored and supported by the Tl'azt'en Chief and Council, appropriate respect is given to culture, language, knowledge and values of the Tl'azt'enne, and to the standards used by Tl'azt'enne to legitimate knowledge. These guidelines repr
Note: before using this routine, please read the Users’ Note for your implementation to check the interpretation of bold italicised terms andother implementation-dependent details. D01GCF calculates an approximation to a definite integral in up to 20 dimensions, using the Korobov–Conroy number theoretic method. SUBROUTINE D01GCF(NDIM, FUNCTN, REGION, NPTS, VK, NRAND, ITRANS, RES,This routin