Doenças da Junção Neuromuscular Flashcards
O que perguntar na história de um paciente com MG?
(1) Diplopia, ptosis, weakness
(2) Weakness in characteristic distribution
(3) Fluctuation and fatigue: worse with repeated activity,
(4) improved by rest
(5) Effects of previous treatments
O que avaliar no exame físico do paciente com MG?
(1) Ptosis, diplopia
(2) Motor power survey: quantitative testing of muscle strength
(3) Forward arm abduction time (5 min)
(6) Vital capacity
(7) Absence of other neurologic signs
O que solicitar de exames laboratoriais para confirmar diagnostico na MG?
(1) Anti-AChR radioimmunoassay: ∼85% positive in generalized MG; 50% in ocular MG; definite diagnosis if positive; negative result does not exclude MG. ∼40% of AChR antibody–negative patients with generalized MG have anti-MuSK antibodies.
(2) Repetitive nerve stimulation: decrement of >15% at 3 Hz: highly probable Single-fiber electromyography: blocking and jitter, with normal fiber density; confirmatory, but not specific
(3) Edrophonium chloride (Tensilon) 2 mg + 8 mg IV; highly probable diagnosis if unequivocally positive
(4) For ocular or cranial MG: exclude intracranial lesions by CT or MRI
Quais exames devemos solicitar em todo doente com MG, além dos exames confirmatorios?
CT or MRI of mediastinum Tests for lupus erythematosus, antinuclear antibody, rheumatoid factor, antithyroid antibodies Thyroid-function tests PPD skin test Chest radiography Fasting blood glucose measurement hemoglobin A1c Pulmonary-function tests Bone densitometry in older patients
Qual o prognóstico da miastenia gravis?
The prognosis has improved strikingly as a result of advances in treatment. Nearly all myasthenic patients can be returned to full productive lives with proper therapy.
Quais os pilares do tratamento da miastenia gravis?
The most useful treatments for MG include (1) anticholinesterase medications, (2) immunosuppressive agents, (3) thymectomy, and (4) plasmapheresis or intravenous immunoglobulin (IVIg).
Como utilizar a medicação anticolinesterasica?
Pyridostigmine is the most widely used anticholinesterase drug. The beneficial action of oral pyridostigmine begins within 15–30 min and lasts for 3–4 h, but individual responses vary. Treatment is begun with a moderate dose, e.g., 30–60 mg three to four times daily. The frequency and amount of the dose should be tailored to the patient’s individual requirements throughout the day. For example, patients with weakness in chewing and swallowing may benefit by taking the medication before meals so that peak strength coincides with mealtimes. Long-acting pyridostigmine may occasionally be useful to get the patient through the night but should not be used for daytime medication because of variable absorption. The maximum useful dose of pyridostigmine rarely exceeds 120 mg every 4–6 h during daytime. Overdosage with anticholinesterase medication may cause increased weakness and other side effects. In some patients, muscarinic side effects of the anticholinesterase medication (diarrhea, abdominal cramps, salivation, nausea) may limit the dose tolerated. Atropine/ diphenoxylate or loperamide is useful for the treatment of gastrointestinal symptoms.
Qual o papel da timectomia na miastenia gravis?
Two separate issues should be distinguished: (1) surgical removal of thymoma, and (2) thymectomy as a treatment for MG. Surgical removal of a thymoma is necessary because of the possibility of local tumor spread, although most thymomas are histologically benign. In the absence of a tumor, the available evidence suggests that up to 85% of patients experience improvement after thymectomy; of these, ∼35% achieve drug-free remission. However, the improvement is typically delayed for months to years. The advantage of thymectomy is that it offers the possibility of long-term benefit, in some cases diminishing or eliminating the need for continuing medical treatment. In view of these potential benefits and of the negligible risk in skilled hands, thymectomy has gained widespread acceptance in the treatment of MG. It is the consensus that thymectomy should be carried out in all patients with generalized MG who are between the ages of puberty and at least 55 years. Whether thymectomy should be recommended in children, in adults >55 years of age, and in patients with weakness limited to the ocular muscles is still a matter of debate. There is also suggestive evidence that patients with MuSK antibody–positive MG may respond less well to thymectomy. Thymectomy must be carried out in a hospital where it is performed regularly and where the staff is experienced in the pre- and postoperative management, anesthesia, and surgical techniques of total thymectomy.
Como usar o corticoide na miasasttenia gravis?i
Glucocorticoids, when used properly, produce improvement in myasthenic weakness in the great majority of patients. To minimize adverse side effects, prednisone should be given in a single dose rather than in divided doses throughout the day. The initial dose should be relatively low (15–25 mg/d) to avoid the early weakening that occurs in about one-third of patients treated initially with a high-dose regimen. The dose is increased stepwise, as tolerated by the patient (usually by 5 mg/d at 2- to 3-day intervals), until there is marked clinical improvement or a dose of 50–60 mg/d is reached. This dose is maintained for 1–3 months and then is gradually modified to an alternate-day regimen over the course of an additional 1–3
months the goal is to reduce the dose on the “off day” to zero or to a minimal level. Generally, patients begin to improve within a few weeks after reaching the maximum dose, and improvement continues to progress for months or years. The prednisone dosage may gradually be reduced, but usually months or years may be needed to determine the minimum effective dose, and close monitoring is required. Few patients are able to do without immunosuppressive agents entirely. Patients on long-term glucocorticoid therapy must be followed carefully to prevent or treat adverse side effects. The most common errors in glucocorticoid treatment of myasthenic patients include (1) insufficient persistence—improvement may be delayed and gradual; (2) tapering the dosage too early, too rapidly, or excessively; and (3) lack of attention to prevention and treatment of side effects.
Quais os outros imunossupressores não corticoide que podem ser usados na miastenia gravis?
(1) Until recently, azathioprine has been the most commonly used immunosuppressive agent for MG because of its relative safety in most patients and long track record. Its therapeutic effect may add to that of glucocorticoids and/or allow the glucocorticoid dose to be reduced. However, up to 10% of patients are unable to tolerate azathioprine because of idiosyncratic reactions consisting of flulike symptoms of fever and malaise, bone marrow suppression, or abnormalities of liver function. An initial dose of 50 mg/d should be used for several days to test for these side effects. If this dose is tolerated, it is increased gradually to about 2–3 mg/kg of total body weight, or until the white blood count falls to 3000 to 4000/μL. The beneficial effect of azathioprine takes 3–6 months to begin and even longer to peak. In patients taking azathioprine, allopurinol should never be used to treat hyperuricemia. Because the two drugs share a common degradation pathway; the result may be severe bone marrow suppression due to increased effects of the azathioprine.
(2) Mycophenolate mofetil has become one of the most widely used drugs in the treatment of MG because of its effectiveness and relative lack of side effects. A dose of 1–1.5 g bid is recommended. Its mechanism of action involves inhibition of purine synthesis by the de novo pathway. Since lymphocytes lack the alternative salvage pathway that is present in all other cells, mycophenolate inhibits proliferation of lymphocytes but not proliferation of other cells. It does not kill or eliminate preexisting autoreactive lymphocytes, and therefore clinical improvement may be delayed for many months to a year, until the preexisting autoreactive lymphocytes die spontaneously. The advantage of mycophenolate lies in its relative lack of adverse side effects, with only occasional production of GI symptoms, rare development of leukopenia, and very small risks of malignancy or PML inherent in all immunosuppressive treatments. Although two published studies did not have positive outcomes, most experts attribute the negative results to flaws in the trial designs, and mycophenolate is widely used for long-term treatment of myasthenic patients.
(3) The calcineurin inhibitors cyclosporine and tacrolimus (FK506) are approximately as effective as azathioprine and are being used increasingly in the management of MG. Their beneficial effect appears more rapidly than that of azathioprine. Either drug may be used alone, but they are usually used as an adjunct to glucocorticoids to permit reduction of the glucocorticoid dose. The usual dose of cyclosporine is 4–5 mg/kg per d, and the average dose of tacrolimus is 0.07–0.1 mg/kg per d, given in two equally divided doses (to minimize side effects). Side effects of these drugs include hypertension and nephrotoxicity, which must be closely monitored. “Trough” blood levels are measured 12 h after the evening dose. The therapeutic range for the trough level of cyclosporine is 150–200 ng/L, and for tacrolimus it is 5–15 ng/L.
Como usar plasmaferese ou imunoglobulina na miastenia gravis?
(1) Plasmapheresis has been used therapeutically in MG. Plasma, which contains the pathogenic antibodies, is mechanically separated from the blood cells, which are returned to the patient. A course of five exchanges (3–4 L per exchange) is generally administered over a 10- to 14-day period. Plasmapheresis produces a short-term reduction in anti-AChR antibodies, with clinical improvement in many patients. It is useful as a temporary expedient in seriously affected patients or to improve the patient’s condition prior to surgery (e.g., thymectomy).
(2) The indications for the use of IVIg are the same as those for plasma exchange: to produce rapid improvement to help the patient through a difficult period of myasthenic weakness or prior to surgery. This treatment has the advantages of not requiring special equipment or large-bore venous access. The usual dose is 2 g/kg, which is typically administered over 5 days (400 mg/kg per d). If tolerated, the total dose of IVIg can be given over a 3- to 4-day period. Improvement occurs in ∼70% of patients, beginning during treatment, or within a week, and continuing for weeks to months. The mecha
nism of action of IVIg is not known; the treatment has no consistent effect on the measurable amount of circulating AChR antibody. Adverse reactions are generally not serious but include headache, fluid overload, and rarely aseptic meningitis or renal failure.
Qual a definição de crise miastenica?
Myasthenic crisis is defined as an exacerbation of weakness sufficient to endanger life; it usually consists of respiratory failure caused by diaphragmatic and intercostal muscle weakness.
Qual o manejo da crise miastenica?
Treatment should be carried out in (1) intensive care units staffed with teams experienced in the management of MG, respiratory insufficiency, infectious disease, and fluid and electrolyte therapy.
(2) The possibility that deterioration could be due to excessive anticholinesterase medication (“cholinergic crisis”) is best excluded by temporarily stopping anticholinesterase drugs.
(3) The most common cause of crisis is intercurrent infection. This should be treated immediately, because the mechanical and immunologic defenses of the patient can be assumed to be compromised. The myasthenic patient with fever and early infection should be treated like other immunocompromised patients with early and effective antibiotic therapy.
(4) Respiratory assistance (preferably noninvasive, using BiPap) and pulmonary physiotherapy are essentials of the treatment program.
(5) As discussed earlier, plasmapheresis or IVIg is frequently helpful in hastening recovery.
Quais drogas devemos evitar na miastenia gravis?
Drugs That May Exacerbate MG
Antibiotics
Aminoglycosides:
e.g., streptomycin, tobramycin, kanamycin
Quinolones:
e.g., ciprofloxacin, levofloxacin, ofloxacin, gatifloxacin Macrolides:
e.g., erythromycin, azithromycin, Nondepolarizing
muscle relaxants for surgery
D-Tubocurarine (curare), pancuronium, vecuronium, atracurium
Beta-blocking agents Propranolol, atenolol, metoprolol
Local anesthetics and related agentes
Procaine, Xylocaine in large amounts Procainamide (for arrhythmias)
Botulinum toxin Botox exacerbates weakness
Quinine derivatives Quinine, quinidine, chloroquine, mefloquine (Lariam)
Magnesium Decreases ACh release
Penicillamine May cause MG
Qual o padrão da eletroneuromiografia nos diagnósticos diferenciais da MG na junção neuromuscular? E como isso muda a conduta?
(1) LEMS: Nerve stimulation produces an initial low-amplitude response and, at low rates of repetitive stimulation (2–3 Hz), decremental responses like those of MG; however, at high rates (50 Hz), or following exercise, incremental responses occur. - The diagnosis of LEMS may signal the presence of a tumor long before it would otherwise be detected, permitting early removal. Treatment of LEMS involves plasmapheresis and immunosuppression, as for MG. 3,4-Diaminopyridine (3,4-DAP) and pyridostigmine may also be symptomatically helpful. 3,4-DAP acts by blocking potassium channels, which results in prolonged depolarization of the motor nerve terminals and thus enhances ACh release. Pyridostigmine prolongs the action of ACh, allowing repeated interactions with AChRs.
(2) Botulism: Nerve stimulation studies reveal findings of presynaptic neuromuscular blockade with reduced compound muscle action potentials (CMAPs) that increase in amplitude following high-frequency repetitive stimulation. - Treatment includes ventilatory support, and aggressive inpatient supportive care (e.g., nutrition, DVT prophylaxis) as needed. Antitoxin should be given as early as possible to be effective
