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28.02.2014

Ms disease course, treating atrial fibrillation with pacemaker - Within Minutes

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Neuromyelitis optica (NMO), or Devic's disease, is an uncommon demyelinating disorder, but common mimic of MS.2 NMO manifests as recurrent optic neuritis and longitudinally extensive transverse myelitis, typically extending over three or more vertebral segments. Early in the disease course, MS involves recurrent bouts of CNS inflammation that results in damage to both the myelin sheath surrounding axons as well as the axons themselves.
Historically, MS was classified as an inflammatory disease targeting white matter, with diagnostics and therapeutics focused on this region of pathology. An important implication of this hypothesis is that the accumulation of irreversible tissue damage limits the potential for benefit from disease-modifying immunomodulatory therapy as the disease progresses and becomes a degenerative process.
After the acute relapse is treated, consideration should turn to DMT, which primarily targets the early inflammatory phase of disease.
In randomized, placebo-controlled trials, all of these medications were shown to decrease the rate of clinical relapses by about 30%, decrease the severity of the relapses, and have beneficial effects on measures of disease activity on MRI.13a€“16 All of the platform medications are generally well or moderately tolerated, and 15 to 20 years of accumulated data and clinical experience suggest strong long-term safety.
Broadly speaking, it is appropriate to consider switching DMT for two reasons: breakthrough disease and intolerable adverse effects. Mitoxantrone (Novantrone) is a chemotherapy medication with demonstrated efficacy in very active relapsing and progressive MS.34 Administration is via IV infusion every 3 months, although a monthly induction course is sometimes used in patients with very active disease. Pregnancy does not seem to have any detrimental effects on the overall disease course of MS.
The effect of vaccines on MS has been studied very carefully, and there appears to be no adverse effect of vaccines on the course of disease.41 Vaccines can be given safely in MS and should be administered when clinically indicated.
A relatively specific antibodya€”the NMO antibodya€”has been identified and recognizes the aquaporin-4 water channel in astrocyte foot processes located adjacent to capillary walls.3,4 NMO is a clinically aggressive disease with associated marked disability. On average, patients have clinical relapses every 1 to 2 years during the relapsing-remitting phase of the disease.
To be maximally effective, disease-modifying therapy (DMT) should be started early in the relapsing-remitting phase and before permanent disability develops. MRI is typically obtained at the time of diagnosis to both exclude other diagnoses and stage the severity of disease.


The current goals of management of RRMS involve the treatment of acute relapses, prevention of new disease activity, and management of symptoms that affect the quality of life. Current therapies target the immune dysfunction in MS and resultant neural tissue damage with the goal of preventing or at least reducing the long-term risk of clinically significant disease. There is no formal consensus on the optimal approach to either defining or managing breakthrough disease, although it is commonly encountered in the clinical setting. The Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and MS Council for Clinical Practice Guidelines have made recommendations regarding these therapies.35 Methotrexate, azathioprine, and cyclosporine were each found to be possibly effective (type C recommendation) in altering the course of disease, but cyclosporine was found to have an unacceptable risk-benefit ratio. Identification and treatment of these symptoms should be considered throughout the disease course (Table 3). Although there are clearly patients in whom the disease remains benign, it is very difficult to predict which patients will eventually follow this course.
Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Update on reproductive safety of current and emerging disease-modifying therapies for multiple sclerosis. Nonetheless, oligodendrocyte progenitor cells capable of remyelinating axons have been observed even in white matter plaques from patients with chronic MS (Figure 2).8 This observation suggests that the potential for remyelination persists even very late in the disease course, which is an encouraging indicator for possible therapeutic targets at this late stage of disease. The key to successful treatment of MS is to slow the inflammatory process early in the disease. Breakthrough disease is generally defined as continued clinical or radiographic evidence of MS-related inflammatory disease activity despite being on an established DMT. In their review, pulse cyclophosphamide treatment did not alter the course of MS (type B recommendation), although a more recent clinical trial showed reduced relapses and MRI lesions in patients treated with cyclophosphamide.36 Given the 10 FDA-approved therapies for relapsing MS and relatively weak evidence supporting the efficacy of immunosuppressant therapies, they are not used frequently in the treatment of MS. Pregnancy during MS is associated with a decreased incidence of relapses, but there is a rebound in relapse frequency postpartum.39 Relapses during pregnancy can be treated with short courses of high-dose corticosteroids if needed, though it is preferable to clinically monitor mild relapses since some adverse effects to glucocorticoids have been described. Therapies that slow progression of disease are available; therefore, early diagnosis and treatment are important in limiting the impact of this potentially devastating disease.


Relapsing-remitting MS (RRMS) is the most common form of the disease, where symptoms appear for several days to weeks, after which they usually resolve spontaneously. Although the underlying pathogenesis of MS still remains poorly understood, remarkable progress has been made in the development of drug therapies that inhibit disease activity.
It is likely that the accumulation of irreversible tissue damage limits the potential for benefit from DMT as the disease progresses. Continued clinical relapses or new MRI lesions, particularly after 6 months of treatment with an established DMT, often constitutes breakthrough disease activity. Early studies reported a relatively quick progression from disease onset to walking with a cane, with a median time of about 15 years.
Using available options, including the advent of newer more effective drugs, there is the potential to achieve a disease-free status, characterized by the prevention of clinical relapses and disability progression and absence of new lesions on MRI.
The severity of relapses, their subsequent recovery, and the number and size of new or active MRI lesions all contribute to defining when patients are considered to have breakthrough disease activity.
Relapses can be seen during the early stages of SPMS, but are uncommon as the disease further progresses.
It is thought that at this point the disease has become primarily a degenerative process with neurologic deterioration independent of ongoing inflammation, although superimposed inflammation can continue to cause additional injury.
Continued surveillance of clinical and radiographic measures of disease activity is crucial during treatment, and it is generally recommended that patients are followed every 3 to 12 months with repeat brain MRI every 6 to 12 months, depending on the patient's baseline disease status and DMT of choice. Likewise, in PPMS, early studies reported short median time from disease onset to cane of less than 10 years, whereas more current studies show that median time is closer to 15 years.37 The advent of effective immunomodulating therapy for relapsing MS may in part explain the transition to MS having a better long-term prognosis. If breastfeeding is pursued, cranial MRI 2 months after delivery for disease surveillance is appropriate.



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