About Acute Transverse Myelitis

Acute transverse myelitis (ATM) is a group of disorders characterized by focal inflammation of the spinal cord and resultant neural injury. ATM may be an isolated entity or may occur in the context of multifocal or even multisystemic disease. It is clear that the pathologic substrate-injury and dysfunction of neural cells within the spinal cord- may be caused by a variety of immunologic mechanisms. For example, in ATM associated with systemic disease (i.e. systemic lupus erythematosus or sarcoidosis), a vasculitic or granulomatous process can often be identified. In idiopathic ATM, there is an intraparenchymal and/or perivascular cellular influx into the spinal cord resulting in breakdown of the blood-brain barrier and variable demyelination and neuronal injury. There are several critical questions that must be answered before we truly understand ATM:

   1) what are the various triggers for the inflammatory process that induces neural injury in the        spinal cord;
   2) what are the cellular and humoral factors that induce this neural injury and
   3) is there a way to modulate the inflammatory response in order to improve patient outcome.

Although much remains to be elucidated about the causes of ATM, tantalizing clues as to potential immunopathogenic mechanisms in ATM and related inflammatory disorders of the spinal cord have recently emerged. It is the purpose of this review to illustrate recent discoveries that shed light on this topic, relying when necessary on data from related diseases such as acute disseminated encephalomyelitis (ADEM), Guillain-Barre syndrome (GBS) and Neuromyelitis Optica (NMO). Developing further understanding of how the immune system induces neural injury will depend upon confirmation and extension of these findings and will require multicenter collaborative efforts.

Introduction

Acute transverse myelitis (ATM) is group of poorly understood inflammatory disorders resulting in neural injury to the spinal cord. It is unclear what are the triggers and effector mechanisms resulting in neural injury, though tantalizing clues have emerged. ATM exists on a continuum of neuroinflammatory disorders that also includes Guillain-Barre syndrome (GBS), multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM) and Neuromyelitis Optica (NMO). Each of these disorders differs in the spatial and temporal restriction of inflammation within the nervous system. However, clinical and pathologic studies support the notion that there are many common features of the inflammation and neural injury. In the current review, we will examine recent evidence that shed light on the immunopathogenesis of ATM and, where applicable, related neuroinflammatory disorders. These studies point to a variety of humoral and cellular immune derangements that potentially result in neuronal injury and demyelination. Further advances in understanding the immunopathogenesis of ATM will require controlled studies with epidemiologic and clinical-pathologic correlation. It is only then that we will be able to establish rational intervention strategies designed to improve the outcome of patients with ATM.

History of ATM

Several cases of "acute myelitis" were described in 1882, and pathologic analysis revealed that some were due to vascular lesions and others to acute inflammation [1,2] . In 1922 and 1923, physicians in England and Holland became aware of a rare complication of smallpox vaccination: inflammation of the spinal cord and brain [3] . Given the term post-vaccinal encephalomyelitis, over 200 cases were reported in those two years alone. Pathologic analyses of fatal cases revealed inflammatory cells and demyelination." In 1928, it was first postulated that many cases of acute myelitis are "post-infectious rather than infectious in cause" since for many patients, the "fever had fallen and the rash had begun to fade" when the myelitis symptoms began [4-] . It was proposed, therefore, that the myelitis was an "allergic" response to a virus rather than the virus itself that caused the spinal cord damage. It was in 1948 that the term "acute transverse myelitis" was utilized in reporting a case of fulminant inflammatory myelopathy complicating pneumonia [5] .

Diagnosis of ATM

Acute transverse myelitis (ATM) is an inflammatory process affecting a restricted area of the spinal cord. It is characterized clinically by acutely or subacutely developing symptoms and signs of neurological dysfunction in motor, sensory and autonomic nerves and nerve tracts of the spinal cord. There is often a clearly defined rostral border of sensory dysfunction and a spinal MRI and lumbar puncture shows evidence of acute inflammation. When the maximal level of deficit is reached, approximately 50% of patients have lost all movements of their legs, virtually all patients have some degree of bladder dysfunction, and 80-94% of patients have numbness, paresthesias or band like dysesthesias [6-8,9-,10,11] . Autonomic symptoms consist variably of increased urinary urgency, bowel or bladder incontinence, difficulty voiding, or bowel constipation [12] . This information does not constitute medical advice for any individual. As specific cases may vary from the general information presented here, 180 Medical advises readers to consult a qualified medical or other professional on an individual basis.

This article was written by Douglas A. Kerr, MD/PhDa and Harold Ayetey, BSc Hons (Lond)b aDepartment of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD bGuy's, King's and St. Thomas' School of Medicine, University of London, London, UK. Dr. Douglas A. Kerr, MD/PhD Assistant Professor, Department of Neurology, Johns Hopkins Hospital, Pathology 627 C 600 N. Wolfe Street, Baltimore, MD 21287-6965 Tel: (410) 502 7099 Fax: (410) 502 6736 Email: dkerr@jhmi.edu. This information does not constitute medical advice for any individual. As specific cases may vary from the general information presented here, 180 Medical advises readers to consult a qualified medical or other professional on an individual basis.

If you would like more information on Transverse Myelitis, please visit the Transverse Myelitis Association's website at: http://www.myelitis.org.