Transverse myelitis is a focal inflammatory disorder of the spinal cord which may arise due to different etiologies. Transverse myelitis may be idiopathic or related/secondary to other diseases including infections, connective tissue disorders and other autoimmune diseases. It may be also associated with optic neuritis (neuromyelitis optica), which may precede transverse myelitis. In this manuscript we review the pathophysiology of different types of transverse myelitis and neuromyelitis optica and discuss diagnostic criteria for idiopathic transverse myelitis and risk of development of multiple sclerosis after an episode of transverse myelitis. We also discuss treatment options including corticosteroids, immunosuppressives and monoclonal antibodies, plasma exchange and intravenous immunoglobulins.
For patients with relapsingremitting multiple sclerosis (RRMS), there are currently six approved medications that have been shown to alter the natural course of the disease. The approved medications include three beta interferon formulations, glatiramer acetate, natalizumab and mitoxantrone. Treating aggressive forms of RRMS and progressive disease forms of MS still presents a great challenge to neurologists. Intense immunosuppression has long been thought to be the only feasible therapeutic option. In patients with progressive forms of MS, lymphoid tissues have been detected in the central nervous system (CNS) that may play a critical role in perpetuating local inflammation. Agents that are currently approved for patients with MS have no or very limited bioavailability in the brain and spinal cord. In contrast, cyclophosphamide (CYC), an alkylating agent, penetrates the bloodbrain barrier and CNS parenchyma well. However, while CYC has been used in clinical trials and off-label in clinical practice in patients with MS for over three decades, data on its efficacy in very heterogeneous groups of study patients have been conflicting. New myeloablative treatment paradigms with CYC may provide a therapeutic option in patients that do not respond to other agents. In this article we review the scientific rationale that led to the initial clinical trials with CYC. We will also outline the safety, tolerability and efficacy of CYC and provide neurologists with guidelines for its use in patients with MS and other inflammatory disorders of the CNS, including neuromyelitis optica (NMO). Finally, an outlook into relatively novel treatment approaches is provided.
Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease of the CNS that is typically diagnosed in the second or third decade of life. It is generally believed that over the last few decades the life expectancy of patients with adult onset MS (AOMS) has approached that of the general population as a result of better medical and nursing care. Thus, an increasing number of MS patients are entering or have reached senescence. A second group of elderly patients with MS that may be very different in terms of disease pathogenesis are patients with late onset MS (LOMS). The diagnosis in LOMS patients can be challenging because of a large number of age-associated MS differential diagnoses, atypical presentations, a low index of suspicion and the lack of diagnostic criteria specific to this age group. Also, specific problems these patients encounter have only recently become a focus of attention. Changes in renal and hepatic function with age, in addition to the coexistence of medical co-morbidities, require special attention in the management of elderly patients with MS. In this review we outline the characteristics of senescent AOMS and LOMS patients. In addition, we discuss therapeutic strategies in elderly patients with MS based on our knowledge of immunosenescence and age-associated characteristics of this disorder. Given the overall aging of the population, focusing on these two patient groups appears highly relevant.
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