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This article reviews the clinical presentation, diagnostic evaluation, and management of immune-mediated myelopathies.The discovery of several neural autoantibodies and their antigenic targets has revolutionized the investigation and treatment of immune-mediated myelopathies. Detection of these serologic biomarkers can support or establish a diagnosis of an autoimmune myelopathy, and, in the case of paraneoplastic syndromes, indicate the likely presence of an underlying malignancy. Distinctive lesion patterns detected on spinal cord or brain MRI narrow the differential diagnosis in patients with acute or subacute inflammatory myelopathies, including those not associated with autoantibody markers.Immune-mediated myelopathies usually present acutely or subacutely and have a broad differential diagnosis. A systematic diagnostic approach using data from the clinical setting and presentation, MRI lesion patterns, CSF data, and autoantibody markers can differentiate these disorders from noninflammatory myelopathies, often with precise disease classification. This, in turn, provides prognostic information, especially whether the disorder is likely to relapse, and facilitates therapeutic decision making. Diagnostic accuracy informs selection of acute immunotherapy aimed at arresting and reversing recent neurologic injury and, when necessary, selection of long-term treatment for prevention of disease progression or relapse.