Transcript Transverse Myelitis

Transverse Myelitis
Emily O. Jenkins MD, PGY3
AM Report
12.18.09
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
Idiopathic
Entity
Multifocal CNS
disease
(eg. MS)
Systemic
disease
(eg. SLE)
Spectrum of Neuroimmunologic
Disorders
MUSCLE
SPINAL CORD
PERIPHERAL
NERVE
BRAIN
Polymyositis
Transverse
myelitis
AIDP 1
MS
Dermatomyositis
Tropical spastic
paraparesis
CIDP 2
Paraneoplastic
encephalomyelitis
Myasthenia gravis
Stiff 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
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 TM
Disease
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
recovery
Severe
permanent
disability
Moderate
permanent
disability
Recurrence
• Predictors of recurrence:
▫
▫
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▫
▫
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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