Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content ++ Autoimmune disease where antibodies are produced to the (postsynaptic) acetylcholine (ACh) receptor of neuromuscular junction (NMJ), possibly originating in thymusTen percent of patients have congenital myasthenia with abnormal ACh receptors; cholinesterase inhibitors will be ineffective in these patientsResults in functionally decreased (70–80%) number of postsynaptic receptorsIncidence of about 1:10,000Before age of 40 years, 2F/1M, 40% thymus enlargementAfter age of 40 years, 1F/1M, 20% thymomaMost commonly affects ocular muscles, but can affect any skeletal muscle, including muscles of respirationCharacterized by skeletal muscle weakness that improves with restClinical course often marked by periods of exacerbations and remissionsTreatment:Cholinesterase inhibitors to increase amount of ACh at NMJCorticosteroidsImmunosuppression (mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, and occasionally cyclophosphamide)Plasmapheresis to remove antibodies, IVIgThymectomyPregnancy:Worsening in first 4 months, at delivery, and postpartum (up to 3 weeks)Optimize therapy; immunosuppressants are contraindicatedEpidural for delivery or c/s; avoid high level; consider ropivacaine (less motor block)Breastfeeding OK if well controlledNeonatal myasthenia (antibodies cross placenta) in 20–30%: weak cry, difficulty feeding, occasional respiratory distress; treat with cholinesterase inhibitors, plasmapheresis ++Table Graphic Jump Location|Download (.pdf)|PrintDifferences between Eaton–Lambert Syndrome and Myasthenia GravisSyndromeMyasthenia gravisEaton–Lambert syndromeAssociation with cancerNot associated with cancerUsually small cell lung cancer (SCLC), but also non-SCLC, lymphosarcoma, malignant thymoma, or carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladderClinical manifestations often precede cancer diagnosis by 2–4 yearsPathophysiologyAutoimmune attack directed against the postsynaptic acetylcholine receptor, results in impaired ACh effect at the NMJAutoimmune attack directed against the voltage-gated calcium channels (VGCCs) on the presynaptic motor nerve terminal results in impaired ACh releaseParasympathetic, sympathetic, and enteric neurons are all affectedClinical diagnosisIncreasing weakness with repeated effortImprovement with restIncreasing strength with repeated effortReappearance of tendon reflexes after a period of muscle contraction by the patientEpidemiologyRelatively commonBimodal distribution (see above)Rare (˜400 cases in the United States at any given time)Typically in >60 years old, but has been reported in childrenAutonomic findingsNoneDysautonomia: dryness of the mouth, impotence, difficulty in starting the urinary stream, and constipationTreatment (besides supportive)See belowTreatment of underlying neoplasmCholinesterase inhibitors3,4-DiaminopyridineImmunosuppression with corticosteroids, IVIg, guanidine, aminopyridines, and azathioprine++Table Graphic Jump Location|Download (.pdf)|PrintMain Cholinesterase Inhibitors Used to Treat MGMedicationOnset/durationTypical dosageSide effectsPyridostigmine (Mestinon)PO: 15–30 min/3–4 hPO: 60 mg qidMuscarinic side effects (diarrhea, abdominal cramps, salivation, nausea), treated with atropine/diphenoxylate or loperamideNeostigmine (Prostigmin)PO: 1 h/90 minIM: 30 min/1 hIV: immediate/20 minPO: 15 mgIM: 1.5 mgIV: 0.5 mgSameAmbenonium (Mytelase)PO: 20–30 min/3–8 hPO: 5–25 mg qidSame++Table Graphic Jump Location|Download (.pdf)|PrintSeverity: Osserman–Genkins ClassificationStage IOcular symptoms only (diplopia, ptosis)Stage IIAMild generalized myasthenia with slow progression; ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.