2. Transverse Myelitis Emily O. Jenkins MD, PGY3 AM Report 12.18.09

3. Transverse Myelitis (TM) Immune-mediated process results in neural injury to the spinal cord Varying degrees of weakness, sensory alterations and autonomic dysfunction Up to half of idiopathic cases will have a preceding respiratory or gastrointestinal illness

4. Spectrum of Neuroimmunologic Disorders MUSCLESPINAL CORDPERIPHERAL NERVE BRAIN PolymyositisTransverse myelitis AIDP 1 MS DermatomyositisTropical spastic paraparesis CIDP 2 Paraneoplastic encephalomyelitis Myasthenia gravisStiff person syndrome Hashimoto’s encephalomyelitis Neuromyelitis optica Rasmussen’s encephalomyelitis ADEM 3 PANDAS 4 1.Acute inflammatory demyelinating polyneuropathy 2. Chronic inflammatory demyelinating polyneuropathy 3. Acute disseminated encephalomyelitis 4. pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

5. TM: Incidence Rare: Estimated between 1 and 8 cases per million people per year 1400 new cases reported in US each year Affects individuals of all ages with a bimodal peak between ages 10-19 and 30-39

6. Presentation 50% will lose all movement in legs Nearly all have some degree of bladder dysfunction 80-94% have numbness, paresthesias, or band-like dysethesias Autonomic symptoms may include: urgency, incontinence, difficulty or inability to void, incomplete evacuation of bowel and/or bladder, sexual dysfunction 80% of patients reach clinical nadir within 10 days of symptom onset Thoracic spinal cord most typically involved in adults, cervical spinal cord in children

7. TM Diagnostic Criteria

8. Alternative diagnostic considerations B12 deficiency: slowly progressive weakness, sensory ataxia, paresthesias Radiation myelopathy Hepatic myelopathy: rare neurologic complication of chronic liver disease with portal hypertension Decompression sickness: complication of deep sea diving Neurolathyrism: prolonged consumption of grass or chickling pea; slowly developing paraparesis with paresthesias; no treatment Konzo: acute spastic paraparesis from high exposure to cyanogenic compounds in diets containing insufficiently processed bitter cassava

9. Etiology Acquired alteration in the innate or acquired immune system Cellular injury and dysfunction Infectious trigger: infectious agent triggers breakdown of immune tolerance for self-antigens TM and ADEM: Superantigen-mediated activation of T lymphocytes Suspected that multiple immune system components contribute to observed dysfunction including T and B lymphocytes, macrophages, and NK cells Mechanism of injury also probably involves multiple pathways including T lymphocyte killing of neural cells, cytokine injury, activation of toxic microglial pathways, immune-complex deposition, and apoptosis

10. Diseases associated with TM DiseaseExamples Bacterial InfectionsMycoplasma pneumoniae, Lyme borreliosis, syphilis (tabes dorsalis), tuberculosis Viral Infectionsherpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses (poliomyelitis, Coxsackie virus, echovirus), human T-cell, leukemia virus, human immunodeficiency virus, influenza, rabies Post-VaccinationRabies, cowpox Autoimmune diseasesSLE, Sjogren’s syndrome, sarcoidosis Multiple Sclerosis Paraneoplastic syndromes VascularThrombosis of spinal arteries, vasculitis secondary to heroin abuse, spinal AVM

11. Distinguishing TM and GBS

12. TM and MS TM can be the presenting feature of MS Patients ultimately diagnosed with MS are more likely to have: ▫ asymmetric clinical findings ▫ predominant sensory symptoms with relative motor sparing ▫MRI findings extending over fewer than two spinal segments ▫ abnormal brain MRI ▫oligoclonal bands

13. Pathology

14. Treatment No consensus guidelines Mainstays include: ▫ corticosteroids: no randomized trials ▫ plasmapheresis: moderate to severe cases, or those who do not respond to steroids after 3-5 days ▫Pulse dose IV cyclophosphamide ▫CSF filtration therapy: spinal fluid is filtered for inflammatory factors (not available in US) For severe, refractory cases: 2 year course of azothioprine, methotrexate, mycophenolate, or oral cyclophosphamide

15. Prognosis Most will have monophasic disease Up to 20% will have recurrent inflammatory episodes within the spinal cord Significant recovery is unlikely if no improvement by 3 months

16. Recurrence Predictors of recurrence: ▫Multifocal lesions within the spinal cord ▫Demyelinating brain lesions ▫CSF oligoclonal bands ▫Mixed connective tissue disorder ▫SS-A antibodies ▫Persistently high IL-6 levels in CSF: thought to lead to high NO production and subsequent neural injury Predictors of poor outcome: ▫Initial complaint of back pain ▫Rapid progression to maximal symptoms within hours of onset ▫Spinal shock ▫14-3-3 protein, a marker of neuronal injury, in CSF during acute phase