1. Acute Transverse Myelitis
Param Vidwan
March 7, 2008 Morning Report

2. 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.

3. 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

4. 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.

5. 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.

6. 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

7. 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).

8. 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).

9. 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 Feb;327(2): Review

10. 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

11. 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

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

13. 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.

15. 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.

17. 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: 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 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

18. 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

19. 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.