transverse myelitis emily o. jenkins md, pgy3 am report 12.18.09

Transverse MyelitisEmily O. Jenkins MD, PGY3AM Report12.18.09

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

Multi-focal CNS

disease (eg. MS)

Systemic disease

(eg. SLE)

Idiopathic Entity

Spectrum of Neuroimmunologic Disorders

MUSCLE SPINAL CORD PERIPHERAL NERVE

BRAIN

Polymyositis Transverse myelitis

AIDP 1 MS

Dermatomyositis

Tropical spastic paraparesis

CIDP 2 Paraneoplastic encephalomyeli

tis

Myasthenia gravis

Stiff person syndrome

Hashimoto’s encephalomyeli

tis

Neuromyelitis optica

Rasmussen’s encephalomyeli

tis

ADEM 3

PANDAS 41. Acute inflammatory demyelinating polyneuropathy 2. Chronic inflammatory demyelinating

polyneuropathy 3. Acute disseminated encephalomyelitis 4. pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

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

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

TM Diagnostic Criteria

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

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

Diseases associated with TMDisease Examples

Bacterial Infections Mycoplasma pneumoniae, Lyme borreliosis, syphilis (tabes dorsalis), tuberculosis

Viral Infections herpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr virus, enteroviruses (poliomyelitis, Coxsackie virus, echovirus), human T-cell, leukemia virus, human immunodeficiency virus, influenza, rabies

Post-Vaccination Rabies, cowpox

Autoimmune diseases SLE, Sjogren’s syndrome, sarcoidosis

Multiple Sclerosis

Paraneoplastic syndromes

Vascular Thrombosis of spinal arteries, vasculitis secondary to heroin abuse, spinal AVM

Distinguishing TM and GBS

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

Pathology

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

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

Full recov-

ery

Moderate per-manent disabil-

ity

Severe permanent disability

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