Acute Transverse Myelitis Param Vidwan March 7, 2008 Morning Report

Know thy terminology Myelopathy: CNS dysfunction due to a lesion (1) within the spinal cord (inflammatory or demyelinating lesions, cord infarction, vitamin B12 deficiency, copper deficiency, etc), OR (2) compression of the cord (epidural tumors, epidural abscess, cervical or thoracic disk). Transverse Myelopathy: clinical presentation of severe motor, sensory, and autonomic dysfunction due to any process affecting spinal cord. Transverse Myelitis: when myelopathy is due to an inflammatory or demyelinating lesion.

Transverse Myelopathy Transverse Myelitis CNS dysfunction due to anything…. Clinical finding suggesting problem at spinal cord level… When transverse myelopathy is due to ‘itis SLE, Scarcoidosis, post-vaccination

Epidemiology “Transverse Myelitis is a rare syndrome with incidence of between 1 and 8 new cases per million people per year.” “ATM in SLE is a very rare manifestation...a prevalence of less than 1% has been estimated, and only about 105 cases are reported in the literature.” Berman M, Feldman S, Alter M, et al. Acute transverse myelitis: incidence and etiologic considerations. Neurology. 31:966–971. Kovacs B, Lafferty TL, Brent LH, et al. Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. Ann Rheum Dis 2000; 59: 120–4.

Pathogenesis of acute transverse myelitis Short Answer: nobody knows. However, some historical clues: Osler in 1892: ‘acute post-infectious polyneuritis’ Molecular Mimicary A characteristic component of human neural tissue is, sialic acid, which is found in neural cell walls. Sialic Acid is also found as a surface antigen on C. jejuni within its lipopolysaccharide outer coat. Antibodies that crossreact with gangliosides from C. jejuni.

Pathogenesis of acute transverse myelitis In 1922, physicians in England and Holland observed o ‘post-vaccinal encephalomyelitis’ after polio vaccination Autoimmune process resulting in ATM. Autopsy evaluation of the spinal cord revealed severe axonal loss with mild demyelination and a mononuclear infiltrate, predominantly T lymphocytes in nerve roots and spinal ganglia

Vidwan’s hypothesis Vasculitis Disruption of BBB Lymphocytic infiltration Vascular occlusion coagulopathy due to: Inflammation +/- APLA Autoimmune Occlusion leads to ischemic necrosis Antineuronal Ab Vasculitis, disruption of BBB. Infiltration of lymphocytes. Vasculitis and APLA increase risk for coagulopathy vascular occlution and ischemic necrosis. Autoimmune (antineuronal antibodies).

Inflammation and Thrombus leads to Demyelination and necrosis Vasculiis Disruption of Blood-Brain barrier Lymphocytic infiltration Peri-vascular inflammation Thrombi Inflammation and Thrombus leads to Demyelination and necrosis …which then causes Radiological and Clinical manifestation Vasculitis, disruption of BBB. Infiltration of lymphocytes. Vasculitis and APLA increase risk for coagulopathy vascular occlution and ischemic necrosis. Autoimmune (antineuronal antibodies).

Diagnosis Systemic lupus erythematosus (SLE) is a systemic disease that can affect any organ system in the body. Central nervous system involvement is reported in 24% to 51% of cases Common CNS manifestations of SLE include: CVA, seizure, psychosis, depression, aseptic meningitis, cognitive dysfunction, and headaches Longitudinal myelitis as an initial manifestation of systemic lupus erythematosus.American Journal of Medical Sciences. 2004 Feb;327(2):105-8. Review

CNS manifestation of SLE by prevalence (least to most) Autonomic Neuropathy, 10% Seizures, 10-20% CVA, 19% Mood disorder Headache,50% Cognitive Decline 80% Stroke 19%, Cognitive decline up to 80%, Headache (migraine or tension) CVA Accelerate atherosclerosis Antiphospholipid Ab Hypertension Psychosis Acute Transverse Myelitis

Presentation of ATM in SLE 50% of patients have motor deficits involving lower extermities “Virtually all” patients have some degree bladder or bowel dysfunction: autonomic symptoms vary from increased urinary urgency, to bowel or bladder incontinence, difficulty to void, incomplete evacuation or bowel constipation” 80 to 94 % have numbness, paraethesia or bandlike dysesthesia. Christensen PB, Wermuth L, Hinge HH, et al. Clinical course and long-term prognosis of acute transverse myelopathy. Acta Neurol Scand. 1990;81:431–435

Idiopathic acute transverse myelitis criteria From:   Kerr: Curr Opin Neurol, Volume 15(3).June 2002.339-347

Differential diagnosis Differential diagnosis of transverse myelopathy in patients with SLE includes: Medullar compression caused by vertebral fractures, Epidural or subdural hematoma, Epidural and/or paraspinal abscess complicating disc space infection, disc herniation, Intra- and extramedullary tumor, Multiple Sclerosis (MS), Infection, Guillain-Barre ssyndrome, Neuromyelitis optica, Acute Disseminated Encephalomyelitis.

Treatment Intravenous (IV) pulse methylprednisolone and cyclophosphamide It is unclear whether plasmapheresis has any additional therapeutic benefit Poor Prognosis: A 1989 review revealed 44 reported cases of SLE ATM. Of these, only 7 (26%) recovered either full or partial neurologic function; others remained static, worsened, or died Kovacs B, Lafferty TL, Brent LH, et al. Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases and review of the literature. Ann Rheum Dis 2000; 59: 120–4. Propper DJ, Bucknall RC. Acute transverse myelopathy complicating systemic lupus erythematosus. Ann Rheum Dis 1989; 48: 512–5.

78yo woman evaluated in ED for worsening of left hemiparesis, which was caused by a stroke 2 years earlier. The stroke involved the right middle cerebral artery territory and was attributed to atrial fibrillation. Initially, she had a very severe left hemiparesis, but gradually improved with 3 months of rehabilliation. At her most recent office evaluation, she had a very mild left central facial palsy, a left pronator drift, and a left foot drop. Today, she awoke and realized that she could not walk due to increased weaknesss, which has now persisted for several hours. Her current medications are warfarin and metoprolol. Vitals: BP: 110/70, HR: 18, Temp: 38.1. Physical Exam: irregularly irregular heart rhythm. Neurological exam reveals normal mental status, normal visual fields, moderate left central facial palsy, and moderate left hemiparesis. INR is 2.3. Chem 7 is normal. CT of brain shows a chronic hypodensity in the right middle cerebral artery territors. Which of the following is the most likely diagnosis? Acute cerebral infarction, due to underlying a.fib Seizure Unmasking of chronic deficit due to infection Hemorrhagic stroke

A 64 yo woman is evaluated in the ED for a 4 day history of progressive leg weakness and numbness and a 1-day history of urinary incontinence. She also had increasingly severe midback pain for the past 2 months. She has a hx of breast cancer diagnosed 2 years ago, treated with surgery and local radiation. Physical exam: normal mental status and cranial nerves. Strength in the arms is normal. Legs are diffusely weak. Sensory exam shows diminished pin sensation from the nipples downward; vibratory sense is severely diminished in the feet. Anal sphincter tone is diminished. Which of the following is the most appropriate diagnostic study at this time? CT of lumbar spine MRI of lumbar spine MRI of entire spine MRI of brain Electromyograpthy and nerve conduction study

32yo woman is hospitalized because of symptoms that began as numbness and tingling in both feet and progressed over few days to include gait instability, hand weakness, diplopia, and dyspnea. The symptoms began 11 days after a viral illness. On admission she has sinus tachycardia, proximal and distal weakness in her upper and lower extermities bilaterally, areflexia, and marked vibratory and position sense loss in the toes and fingers. She cannot walk. Which of the following is the most appropriate treatment? Prednisone Pyridostigmine Plasma exchange Intravenous methylprednisolone.