Desmielinizantes Flashcards
Como fazer o diagnóstico de esclerose múltipla?
2 or more attacks; objective clinical evidence of 2 or more lesions or objective clinical evidence of 1 lesion with reasonable historical evidence of a prior attack
None
2 or more attacks; objective clinical evidence of 1 lesion
Dissemination in space, demonstrated by • ≥1 T2 lesion on MRI in at least two out of four MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord) OR • Await a further clinical attack implicating a different CNS site
1 attack; objective clinical evidence of 2 or more lesions
Dissemination in time, demonstrated by • Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time OR • A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan OR • Await a second clinical attack
1 attack; objective clinical evidence of 1 lesion (clinically isolated syndrome)
Dissemination in space and time, demonstrated by: For dissemination in space • ≥1 T2 lesion in at least two out of four MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord) OR • Await a second clinical attack implicating a different CNS site AND For dissemination in time • Simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time OR • A new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan OR • Await a second clinical attack
Insidious neurologic progression suggestive of MS (PPMS)
One year of disease progression (retrospectively or prospectively determined) PLUS Two out of the three following criteria Evidence for dissemination in space in the brain based on ≥1 T2+ lesions in the MScharacteristic periventricular, juxtacortical, or infratentorial regions Evidence for dissemination in space in the spinal cord based on ≥2 T2+ lesions in the cord Positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index)
Quais os exames obrigatórios na esclerose múltipla?
(1) MRI has revolutionized the diagnosis and management of MS (Fig. 39-3); characteristic abnormalities are found in >95% of patients, although more than 90% of the lesions visualized by MRI are asymptomatic. An increase in vascular permeability from a breakdown of the BBB is detected by leakage of intravenous gadolinium (Gd) into the parenchyma. Such leakage occurs early in the development of an MS lesion and serves as a useful marker of inflammation. Gd enhancement persists for approximately 1 month, and the residual MS plaque remains visible indefinitely as a focal area of hyperintensity (a lesion) on spin-echo (T2-weighted) and protondensity images.
(2) The measurement of oligoclonal banding (OCB) in the CSF also assesses intrathecal production of IgG. OCBs are detected by agarose gel electrophoresis. Two or more OCBs are found in 75–90% of patients with MS. OCBs may be absent at the onset of MS, and in individual patients the number of bands may increase with time. It is important that paired serum samples be studied to exclude a peripheral (i.e., non-CNS) origin of any OCBs detected in the CSF. A mild CSF pleocytosis (>5 cells/μL) is present in ∼25% of cases, usually in young patients with RRMS. A pleocytosis of >75 cells/μL, the presence of polymorphonuclear leukocytes, or a protein concentration >1 g/L (>100 mg/dL) in CSF should raise concern that the patient may not have MS.
(3) The specific tests required to exclude alternative diagnoses will vary with each clinical situation; however, an erythrocyte sedimentation rate, serum B12 level, ANA, and treponemal antibody should probably be obtained in all patients with suspected MS
Qual o prognóstico da esclerose múltipla?
(1) Most patients with clinically evident MS ultimately experience progressive neurologic disability. In older studies, 15 years after onset, only 20% of patients had no functional limitation, and between one-third and one-half progressed to SPMS and required assistance with ambulation; furthermore, 25 years after onset, ∼80% of MS patients reached this level of disability. For unclear reasons, the long-term prognosis for untreated MS appears to have improved in recent years. In addition, the development of disease-modifying therapies for MS also appears to have favorably improved the long-term outlook.
(2) Mortality as a direct consequence of MS is uncommon, although it has been estimated that the 25-year survival is only 85% of expected. Death can occur during an acute MS attack, although this is distinctly rare. More commonly, death occurs as a complication of MS (e.g., pneumonia in a debilitated individual). Death can also result from suicide.
Qual os três principios do tratamento da esclerose múltipla?
Therapy for MS can be divided into several categories: (1) treatment of acute attacks, (2) treatment with disease-modifying agents that reduce the biological activity of MS, and (3) symptomatic therapy
Como avaliar objetivamente a gravidade da esclerose múltipla?
The Expanded Disability Status Score (EDSS) is a useful measure of neurologic impairment in MS (Table 39-5). Most patients with EDSS scores <3.5 have RRMS, walk normally, and are generally not disabled; by contrast, patients with EDSS scores >5.5 have progressive MS (SPMS or PPMS), are gait-impaired, and, typically, are occupationally disabled.
Qual o tratamento do ataque da MS?
(1) When patients experience acute deterioration, it is important to consider whether this change reflects new disease activity or a “pseudoexacerbation” resulting from an increase in ambient temperature, fever, or an infection.
(2) Glucocorticoid treatment is usually administered as intravenous methylprednisolone, 500–1000 mg/d for 3–5 days, either without a taper or followed by a course of oral prednisone beginning at a dose of 60–80 mg/d and gradually tapered over 2 weeks. Orally administered methylprednisolone or dexamethasone (in equivalent dosages) can be substituted for the intravenous portion of the therapy, although GI complications are more common by this route. Outpatient treatment is almost always possible. Side effects of short-term glucocorticoid therapy include fluid retention, potassium loss, weight gain, gastric disturbances, acne, and emotional lability. Concurrent use of a low-salt, potassium-rich diet and avoidance of potassium-wasting diuretics is advisable. Lithium carbonate (300 mg orally bid) may help to manage emotional lability and insomnia associated with glucocorticoid therapy. Patients with a history of peptic ulcer disease may require cimetidine (400 mg bid) or ranitidine (150 mg bid). Proton pump inhibitors such as pantoprazole (40 mg orally bid) may reduce the likelihood of gastritis, especially when large doses are administered orally.
(3) Plasma exchange (5–7 exchanges: 40–60 mL/kg per exchange, every other day for 14 days) may benefit patients with fulminant attacks of demyelination (from MS and other fulminant causes) that are unresponsive to glucocorticoids. However, the cost is high, and conclusive evidence of efficacy is lacking
(4) Physical and occupational therapy can help with mobility and manual dexterity
Quais as opções de DMARD na esclerose múltipla?
even such agents are approved by the U.S. Food and Drug Administration (FDA): (1) IFN-β-1a (Avonex), (2) IFN-β-1a (Rebif), (3) IFN-β-1b (Betaseron), (4) glatiramer acetate (Copaxone), (5) natalizumab (Tysabri), (6) fingolimod (Gilenya), and (7) mitoxantrone (Novantrone).
(1) IFN-β-1a (Avonex), 30 μg, is administered by intramuscular injection once every week. IFN-β-1a (Rebif), 44 μg, is administered by subcutaneous injection three times per week. IFN-β-1b (Betaseron), 250 μg, is administered by subcutaneous injection every other day. Common side effects of IFN-β therapy include flulike symptoms (e.g., fevers, chills, and myalgias) and mild abnormalities on routine laboratory evaluation (e.g., elevated liver function tests or lymphopenia). Approximately 2–10% of IFN-β-1a (Avonex) recipients, 15–25% of IFN-β-1a (Rebif) recipients, and 30–40% of IFN-β-1b (Betaseron) recipients develop neutralizing antibodies to IFN-β, which may disappear over time. Thus, for a patient doing well on therapy, the presence of antibodies should not affect treatment. Conversely, for a patient doing poorly on therapy, alternative treatment should be considered, even if there are no detectable antibodies.
(2) Glatiramer acetate, 20 mg, is administered by subcutaneous injection every day. Injection-site reactions also occur with glatiramer acetate. Initially, these were thought to be less severe than with IFN-β-1b, although two recent head-to-head comparisons of high-dose IFN-β to glatiramer acetate did not bear out this impression. In addition, approximately 15% of patients experience one or more episodes of flushing, chest tightness, dyspnea, palpitations, and anxiety after injection. This systemic reaction is unpredictable, brief (duration <1 h), and tends not to recur. Finally, some patients experience lipoatrophy, which, on occasion, can be disfiguring and require cessation of treatment.
(3) Natalizumab, 300 μg, is administered by IV infusion each month. Treatment with natalizumab is, in general, well tolerated. A small percentage (<10%) of patients experience hypersensitivity reactions (including anaphylaxis) and ∼6% develop neutralizing antibodies to the molecule. The major concern with long-term treatment is the risk of PML. Because the risk is extremely low during the first year of treatment with natalizumab, we currently recommend treatment for periods of 12–18 months only for most patients; after this time, a change to another disease-modifying therapy should be considered. Recently, a blood test to detect antibodies against the PML (JC) virus has shown promise in identifying individuals who are at risk for this complication
(4) Fingolimod, 0.5 mg, is administered orally each day. Treatment with fingolimod is also, in general, well tolerated. Mild abnormalities on routine laboratory evaluation (e.g., elevated liver function tests or lymphopenia) are more common than in controls. Although rarely severe, sometimes discontinuation of the medication is necessary. First-degree heart block and bradycardia can also occur, the latter necessitating the prolonged (6-h) observation of patients receiving their first dose.
(5) Mitoxantrone can be cardiotoxic (e.g., cardiomyopathy, reduced left ventricular ejection fraction, and irreversible congestive heart failure). As a result, a cumulative dose >140 mg/m2 is not recommended. At currently approved doses (12 mg/m2 every 3 months), the maximum duration of therapy can be only 2–3 years. Furthermore, >40% of women will experience amenorrhea, which may be permanent. Finally, there is risk of acute leukemia, and this complication has already been reported in several mitoxantrone-treated MS patients
Quando trocar a DMARD da MS?
Currently, most patients with relapsing forms of MS receive IFN-β or glatiramer acetate as first-line therapy. Although approved for first-line use, the role of fingolimod in this situation has yet to be defined. Regardless of which agent is chosen first, treatment should probably be changed in patients who continue to have frequent attacks or progressive disability Beneficial effects seen in early MS include a reduction in the relapse rate, a reduction in CNS inflammation as measured by MRI, and a prolongation in the time to reach certain disability outcomes.
Qual o tratamento sintomático na MS?
(1) For all patients, it is useful to encourage attention to a healthy lifestyle, including maintaining an optimistic outlook, a healthy diet, and regular exercise as tolerated (swimming is often well tolerated because of the cooling effect of cold water). It is reasonable also to correct vitamin D deficiency with oral vitamin D, and to recommend dietary supplementation with long-chain (omega-3) unsaturated fatty acids (present in oily fish such as salmon) because of their immunomodulatory properties.
(2) Spasticity and spasms may improve with physical therapy, regular exercise, and stretching. Avoidance of triggers (e.g., infections, fecal impactions, bed sores) is extremely important. Effective medications include baclofen (Lioresal) (20–120 mg/d), diazepam (2–40 mg/d), tizanidine (8–32 mg/d), dantrolene (25–400 mg/d), and cyclobenzaprine hydrochloride (10–60 mg/d). For severe spasticity, a baclofen pump (delivering medication directly into the CSF) can provide substantial relief
(3) Weakness can sometimes be improved with the use of potassium channel blockers such as 4-amino pyridine (10–40 mg/d) and 3,4-di-aminopyridine (40–80 mg/d), particularly in the setting where lower extremity weakness interferes with the patient’s ability to ambulate. The FDA has approved 4-amino pyridine (at 20 mg/d), and this can be obtained either as dalfampridine (Ampyra) or, more cheaply, through a compounding pharmacy. The principal concern with the use of these agents is the possibility of inducing seizures at high doses
(4) Ataxia/tremor is often intractable. Clonazepam, 1.5–20 mg/d; Mysoline, 50–250 mg/d; propranolol, 40–200 mg/d; or ondansetron, 8–16 mg/d, may help. Wrist weights occasionally reduce tremor in the arm or hand. Thalamotomy or deep-brain stimulation has been tried with mixed success.
(5) Pain is treated with anticonvulsants (carbamazepine, 100–1000 mg/d; phenytoin, 300–600 mg/d; gabapentin300–3600 mg/d; or pregabalin, 50–300 mg/d), antidepressants (amitriptyline, 25–150 mg/d; nortriptyline, 25–150 mg/d; desipramine, 100–300 mg/d; or venlafaxine, 75–225 mg/d), or antiarrhythmics (mexiletine, 300–900 mg/d). If these approaches fail, patients should be referred to a comprehensive pain management program
(6) Bladder dysfunction management is best guided by urodynamic testing. Evening fluid restriction or frequent voluntary voiding may help detrusor hyperreflexia. If these methods fail, propantheline bromide (10–15 mg/d), oxybutynin (5–15 mg/d), hyoscyamine sulfate (0.5–0.75 mg/d), tolterodine tartrate (2–4 mg/d), or solifenacin (5–10 mg/d) may help. Coadministration of pseudoephedrine (30–60 mg) is sometimes beneficial. Detrusor/sphincter dyssynergia may respond to phenoxybenzamine (10–20 mg/d) or terazosin hydrochloride (1–20 mg/d). Loss of reflex bladder wall contraction may respond to bethanechol (30–150 mg/d). However, both conditions often require catheterization.
(7) Urinary tract infections should be treated promptly. Patients with large postvoid residual urine volumes are predisposed to infections. Prevention by urine acidification (with cranberry juice or vitamin C) inhibits some bacteria. Prophylactic administration of antibiotics is sometimes necessary but may lead to colonization by resistant organisms. Intermittent catheterization may help to prevent recurrent infections.
(8) Treatment of constipation includes high-fiber diets and fluids. Natural or other laxatives may help. Fecal incontinence may respond to a reduction in dietary fiber.
(9) Depression should be treated. Useful drugs include the selective serotonin reuptake inhibitors (fluoxetine, 20–80 mg/d; or sertraline, 50–200 mg/d), the tricyclic antidepressants (amitriptyline, 25–150 mg/d; nortriptyline, 25–150 mg/d; or desipramine, 100–300 mg/d), and the non-tricyclic antidepressants (venlafaxine, 75–225 mg/d).
(10) Fatigue may improve with assistive devices, help in the home, or successful management of spasticity. Patients with frequent nocturia may benefit from anticholinergic medication at bedtime. Primary MS fatigue may respond to amantadine (200 mg/d), methylphenidate (5–25 mg/d), or modafinil (100–400 mg/d).
(11) Cognitive problems may respond to the cholinesterase inhibitor donepezil hydrochloride (10 mg/d).
(12) Paroxysmal symptoms respond dramatically to lowdose anticonvulsants (acetazolamide, 200–600 mg/d; carbamazepine, 50–400 mg/d; phenytoin, 50–300 mg/d; or gabapentin, 600–1800 mg/d).
(13) Heat sensitivity may respond to heat avoidance, airconditioning, or cooling garments.
(14) Sexual dysfunction may be helped by lubricants to aid in genital stimulation and sexual arousal. Management of pain, spasticity, fatigue, and bladder/bowel dysfunction may also help. Sildenafil (50–100 mg), tadalafil (5–20 mg), or vardenafil (5–20 mg) taken 1–2 h before sex are now the standard treatments for maintaining erections
Qual o tratamento da neuromielite optica?
(1) Acute attacks of NMO are usually treated with high-dose glucocorticoids (Solu-Medrol 1–2 g/d for 5–10 days followed by a prednisone taper). Because of the likelihood that NMO is antibody-mediated, plasma exchange (typically 7 qod exchanges of 1.5 plasma volumes) has also been used empirically for acute episodes that fail to respond to glucocorticoids.
(2) Prophylaxis against relapses can be achieved in some patients with one of the following regimens: mycophenolate mofetil (250 mg bid gradually increasing to 1000 mg bid); B cell depletion with anti-CD20 monoclonal antibody (Rituxan); or a combination of glucocorticoids (500 mg IV methylprednisolone daily for 5 days; then oral prednisone 1 mg/kg per day × 2 months, followed by slow taper) plus azathioprine (2 mg/kg per day started on week 3).
Qual do tratamento da ADEM (Encefalomielite disseminada aguda)?
(1) Initial treatment is with high-dose glucocorticoids as for exacerbations of NMO (discussed earlier); depending on the response, treatment may need to be continued for 4–8 weeks.
(2) Patients who fail to respond within a few days may benefit from a course of plasma exchange or intravenous immunoglobulin.
(3) The prognosis reflects the severity of the underlying acute illness. Measles encephalomyelitis is associated with a mortality rate of 5–20%, and most survivors have permanent neurologic sequelae. Children who recover may have persistent seizures and behavioral and learning disorders.
O que difere esclerose múltipla de ADEM?
(1) The diagnosis is easily established when there is a history of recent vaccination or viral exanthematous illness.
(2) The simultaneous onset of disseminated symptoms and signs is common in ADEM and rare in MS. Similarly, meningismus, drowsiness, coma, or seizures suggest ADEM rather than MS.
(3) Unlike MS, in ADEM optic nerve involvement is generally bilateral and transverse myelopathy complete.
(4) MRI findings that favor ADEM include extensive and relatively symmetric white matter abnormalities, basal ganglia or cortical gray matter lesions, and Gd enhancement of all abnormal areas.
(5) By contrast, oligoclonal bands in the CSF are more common in MS
O que diferente a neuromielite optica da esclerose múltipla?
(1) Attacks of ON can be bilateral (rare in MS) or unilateral; myelitis can be severe and transverse (rare in MS) and is typically longitudinally extensive, involving three or more contiguous vertebral segments.
(2) Attacks of ON may be precede or follow an attack of myelitis by days, months, or years, or vice versa. In contrast to MS, progressive symptoms do not occur in NMO.
(3) The brain MRI was classically thought to be normal at the onset of NMO, but recent studies now indicate that asymptomatic lesions sometimes resembling typical MS are common. Lesions involving the hypothalamus, periaqueductal region of the brainstem, or “cloud-like” white matter lesions in the cerebral hemispheres are suggestive of NMO. Brainstem disease can present with nausea and vertigo, and large hemispheral lesions can present as encephalopathy or seizures. Spinal cord MRI typically reveals a focal enhancing region of swelling and cavitation, extending over three or more spinal cord segments and often located in central gray matter structures.
(4) A highly specific autoantibody directed against the water channel protein aquaporin-4 is present in the sera of 60–70% of patients who have a clinical diagnosis of NMO. Seropositive patients have a very high risk for future relapses.
Quais os sinais de alarme para pensar que não se trata de esclerose múltipla?
(1) symptoms are localized exclusively to the posterior fossa, craniocervical junction, or spinal cord; (2) the patient is aged <15 or >60 years; (3) the clinical course is progressive from onset; (4) the patient has never experienced visual, sensory, or bladder symptoms; or (5) laboratory findings (e.g., MRI, CSF, or EPs) are atypical. Similarly, uncommon or rare symptoms in MS (e.g., aphasia, parkinsonism, chorea, isolated dementia, severe muscular atrophy, peripheral neuropathy, episodic loss of consciousness, fever, headache, seizures, or coma) should increase concern about an alternative diagnosis. Diagnosis is also difficult in patients with a rapid or explosive (stroke-like) onset or with mild symptoms and a normal neurologic examination.
