II. Definitions

  1. Myelitis
    1. Spinal Cord Inflammation of various causes including Viral Infections, toxins, autoimmune or vascular conditions
    2. Findings include weakness, sensory changes (Paresthesias, numbness), Autonomic Dysfunction (e.g. Urinary Incontinence)
  2. Transverse Myelitis
    1. Spinal cord inflammation of a transverse segment of the cord with demyelination and necrosis
    2. Myelitis findings occur below the segment of spinal cord involvement

III. Epidemiology

  1. No gender or familial predisposition
  2. Incidence (rare): 1.3 to 4.6 per million people
    1. U.S. 1400 new cases per year
  3. Ages: Bimodal distribution
    1. Most common in children and young adults (peak age 10 to 19 years old)
      1. Further bimodal distribution in children (age <3 years and age 5 to 17 years)
      2. Affects 0.2 per 100,000 children per year
      3. Accounts for 20% of acute demyelinating syndrome in children
      4. Associated with Viral Infection or Vaccination in 60% of cases
    2. Second peak at age 30 to 39 years old

IV. Pathophysiology

  1. Spinal cord inflammation due to autoimmune, inflammatory, vascular or infectious causes
    1. Lymphocyte and Monocyte infiltration
    2. Associated with demyelination and axonal injury
  2. Myelitis may be unilateral or bilateral, and may effect only some long tracts but not others
    1. May affect both ascending (sensory) and descending (motor) pathways
    2. The terms Myelitis, Transverse Myelitis and Acute Transverse Myelitis are used interchangeably
    3. The adjective transverse only describes the distribution, but the causes and management are similar

V. Causes: Myelitis

  1. See Acute Flaccid Paralysis
  2. See Acute Flaccid Myelitis
  3. Precautions
    1. Do NOT miss Compressive Neuropathy (e.g. Cauda Equina Syndrome) which is curable with early surgical intervention
  4. Demyelinating Disease (most common cause)
    1. Acute Disseminated Encephalomyelitis (ADEM)
    2. Multiple Sclerosis
    3. Neuromyelitis Optica Spectrum Disorder (NMOSD)
    4. Myelin Oligodendrocyte GlycoproteinAntibody Disease
  5. Autoimmune or Inflammatory Myelitis
    1. Ankylosing Spondylitis
    2. Antiphospholipid Antibody Syndrome
    3. Behcet Disease
    4. Celiac Disease
    5. Graft-vs-host disease
    6. Mixed Connective Tissue Disease (MCTD)
    7. Neurosarcoidosis
    8. Scleroderma
    9. Sjogren Syndrome
    10. Systemic Lupus Erythematosus
  6. Bacterial Myelitis
    1. Bartonella Henselae (Cat Scratch Disease)
    2. Borrelia Burgdorferi (Lyme Disease)
    3. Brucellosis melitensis (Brucellosis)
    4. Campylobacter jejuni (e.g. Acute Diarrhea)
    5. Chlamydia psittaci (Psittacosis)
    6. Chlamydia pneumoniae (Chlamydia Pneumonia)
    7. Coxiella Burnetii (Q Fever)
    8. Legionella pneumonia
    9. Leptospira (Leptospirosis)
    10. Mycobacterium tuberculosis
    11. Orientia Tsutsugamushi (Scrub Typhus)
    12. Salmonella paratyphi B (Paratyphoid)
    13. Streptococcus (Group A and B)
    14. Treponema pallidum (Syphilis)
  7. Viral Myelitis
    1. Coxsackievirus (A and B)
    2. Cytomegalovirus (Mono-Like Illness)
    3. DengueVirus
    4. Echoviruses
    5. Enterovirus (70 and 71)
    6. Epstein-Barr Virus (Mononucleosis)
    7. Hepatitis A Virus
    8. Hepatitis CVirus
    9. Herpes Simplex Virus Type 2 (Genital Herpes)
      1. Elsberg Syndrome is bilateral lumbosacral radiculitis with lower cord Myelitis due to HSV reactivation
    10. HIV Infection (see HIV related Myelitis)
    11. Influenza A Virus (includes H1N1)
    12. Japanese Encephalitis Virus
    13. MeaslesVirus
    14. Mumps Virus
    15. Poliovirus (1, 2, and 3)
    16. St. Louis EncephalitisVirus
    17. Varicella Zoster Virus (Chicken Pox, Shingles)
    18. West Nile Virus
  8. Parasitic Myelitis
    1. Acanthamoeba (Granulomatous Amebic Encephalitis)
    2. Echinococcus Granulosus (Echinococcosis)
    3. Gnathostoma Angiostrongylus (Eosinophilic Meningitis)
    4. Paragonimus westermani fluke (Paragonimiasis)
    5. Schistomosoma (Schistosomiasis)
    6. Taenia solium (Neurocysticercosis)
    7. Toxoplasma gondii (Toxoplasmosis)
    8. Trypanosoma brucei (African trypanosomiasis, African Sleeping Sickness)
  9. Fungal Myelitis
    1. Actinomyces (Actinomycosis)
    2. Aspergillus (Aspergillosis)
    3. Blastomyces (Blastomycosis)
    4. Cryptococcus (Cryptococcosis)
    5. Coccidioides immitis (Coccidioidomycosis, Valley Fever)
  10. Paraneoplastic Conditions (Antibody mediated)
    1. Various antibodies (e.g. ANNA-2, GAD65, NMDAR)
  11. Toxins or Drugs
    1. Poisoning due to Brown Recluse Spider Venom
    2. Heroin abuse
    3. Post-Vaccination Myelitis

VI. Findings: Symptoms and Signs

  1. See Spinal Cord Syndrome
  2. Timing
    1. Onset over hours to days
    2. Progression over days to weeks
  3. Distribution
    1. Myelitis typically affects a full triad of sensory, motor and Autonomic Dysfunction once disease has progressed
      1. However, at onset, findings may be more subtle and the full triad may be absent
    2. Myelitis is typically bilateral but may be unilateral in early or atypical cases (partial Transverse Myelitis)
    3. Myelitis may only cause sensory and motor changes at a few spinal levels (sparing lower cord levels)
    4. Myelitis may effect only some long tracts but not others
  4. Motor weakness
    1. Leg flexors and arm extensors are preferentially affected (pyramidal distribution)
    2. Lower extremity weakness and diminished Muscle tone are frequent initial presenting symptoms
    3. Patients may present with acute flaccid limb weakness and hyporeflexia (Spinal Shock)
      1. Distinguish from Guillain Barre Syndrome
    4. With progression over time, half of patients develop an inability to move their legs
      1. Chronically develop Upper Motor Neuron Deficits (hyperreflexia, positive babinski, increased tone)
  5. Sensory changes
    1. Sensory findings may follow a Dermatomal Distribution
      1. Distinguish from Peripheral Neuropathy or neuropathic pain
    2. Paresthesias
      1. Typically initial sensory symptom
      2. Paresthesias ascend from the feet proximally
    3. Numbness
    4. Pain
  6. Autonomic Dysfunction
    1. Urinary Incontinence
    2. Urine Urgency
    3. Urine Retention
    4. Stool Incontinence
    5. Constipation
    6. Tenesmus
    7. Temperature dysregulation
    8. Hypertension
    9. Sexual Dysfunction
  7. Associated Symptoms
    1. Back pain at or near the level of Myelitis (variably present)

VII. Labs

  1. Cerebrospinal fluid (Lumbar Puncture)
    1. Indicated after structural causes are excluded by neuroimaging
    2. Cerebrospinal fluid (CSF) may be normal in up to 50% of cases (esp. early in course)
    3. CSF Pleocytosis (>5 white cells/uL) is present in a majority of cases
      1. CSF White Blood Cells >100/uL in >50% of cases
    4. CSF IgG Index
      1. Often increased in Transverse Myelitis
    5. Obtain other standard CSF labs (e.g. CSF Protein, CSF Glucose, CSF Culture, CSF viral panel, CSF VRDL, oligoclonal bands)
      1. Exclude alternative diagnoses
  2. Exclude alternative diagnoses
    1. Serum Vitamin B12 Level (and consider methylmalonic acid level)
    2. Thyroid Stimulating Hormone
    3. Syphilis Serology
    4. HIV Test
    5. Consider specific organism testing (e.g. Mycoplasma)
    6. Consider other testing per neurology (e.g. ANA, Neuomyelitis optica Ig)

VIII. Imaging

  1. MRI Spine with gadolinium contrast
    1. Imaging the entire spine (cervical, thoracic and Lumbar Spine) is typically recommended to avoid False Negative testing
      1. At minimum, obtain imaging to include well above the level of involvement
      2. May also obtain combined spine MRIs (e.g. cervico-thoracic MRI or thoracolumbar MRI)
    2. Exclude structural compressive causes (e.g. Epidural Abscess, Epidural Hematoma, acute disc Herniation)
      1. May indicate surgical emergency
    3. May also demonstrate inflammatory cord changes (gadolinium enhancement)
    4. Findings consistent with Transverse Myelitis
      1. T2 weighted images with high intensity signals at lesions
      2. Transverse Myelitis lesions typically span at least 2 Vertebral levels
        1. Multiple Sclerosis related lesions typically span only one level
        2. Neuromyelitis Optica Spectrum Disorder (NMOSD) typically spans 3 or more levels
  2. CT Myelogram
    1. Alternative if MRI contraindicated
  3. MRI Brain
    1. Consider to exclude other demyelinating disease

X. Diagnosis: Idiopathic Acute Transverse Myelitis

  1. Progression to nadir (low point) with 4 hours to 21 days from symptom onset in Acute Transverse Myelitis
    1. Nadir <4 hours from onset suggests acute vascular Myelopathy with ischemia (e.g. Anterior Spinal Artery thrombosis)
    2. Nadir >21 days from onset suggests chronic progressive Myelopathy (e.g. AV fistula, MS)
  2. Sensory, Motor or Autonomic Dysfunction attributable to spinal cord lesion (all 3 are typically present at nadir)
    1. Sensory deficits have a clearly defined level
  3. Findings are bilateral (but may be asymmetric)
  4. Spinal cord inflammation
    1. CSF Pleocytosis or IgG Index elevated or MRI Gadolinium enhancement
    2. Repeat MRI and LP again in 2 to 7 days if inflammation not present on initial testing
  5. Exclusion Criteria
    1. Not due to extra-axial compression on MRI or CT myelography
    2. Spinal radiation in last 10 years
    3. Deficits consistent with alternative diagnosis
      1. Anterior Spinal Artery thrombosis
      2. Spinal cord Arteriovenous Malformation
      3. Demyelinating disease (e.g. Multiple Sclerosis, Optic Neuritis)
      4. Connective Tissue Disorder (e.g. Sarcoidosis, Behcet Disease, Sjogren Syndrome, Systemic Lupus Erythematosus)
      5. CNS Disorders (e.g. HIV, Tertiary Lyme Disease, Neurosyphilis, HTLV1, Viral Encephalitis)

XI. Management

  1. Supportive Care
    1. Admit patients
    2. ABC Management
    3. Keep patient NPO if Dysarthria or Dysphagia
    4. Consider Advanced Airway indications
    5. Significant Urinary Retention may require urine catheterization
  2. Condition specific management
    1. Consult neurology early
    2. Consider infectious disease Consultation if infectious Myelitis is suspected (12% of cases)
  3. High dose Corticosteroids
    1. Consult neurology for indications based on presentation and findings
    2. Methylprednisolone 1000 mg IV daily in divided doses for 3 to 5 days
  4. Plasma exchange
    1. Indications
      1. Corticosteroids contraindicated
        1. Not effective if not Corticosteroid responsive
      2. Life threatening complications (e.g. respiratory compromise)
      3. Consider as adjunctive therapy (per neurology recommendations)
    2. Dosing
      1. Exchange transfusion every other day for 10 to 14 days (total of 5 to 7 exchanges)
  5. Intravenous Immunoglobulin (IVIG)
    1. Indications
      1. Adjunct to Corticosteroids (consult neurology for indications)
    2. Dosing
      1. IVIG 2 g/kg IV for 2 to 5 days
  6. Compressive neureopathy causes of acute Myelitis are surgical emergencies
    1. Emergent Consultation with Spine Surgery or neurosurgery

XII. Prognosis

  1. Idiopathic Transverse Myelitis
    1. Gradual improvement over 3 months (and often further improvement over the next year)
    2. Partial or complete resolution in 50 to 70% of patients
    3. Episodes tend to be monophasic (non-recurring)
  2. Secondary Transverse Myelitis
    1. Variable outcomes depending on cause
    2. Demyelinating disease are at risk of recurrence
      1. Multiple Sclerosis is associated with significant recovery with episodes (full in some cases)
      2. Neuromyelitis Optica Spectrum Disorder (NMOSD) is associated with significant residual deficits
  3. Overall poor prognostic signs
    1. Severe weakness
    2. Hypotonia
    3. Areflexia
    4. Spinal Shock
  4. Pseudoexacerbation (recrudescence)
    1. Neurologic deficits may recur transiently with acute infections or metabolic disturbances
      1. Similar to recrudescence seen after Cerebrovascular Accident
    2. Findings abate with treatment with the acute trigger
    3. Differentiate from recurrence as seen with demyelinating diseases (e.g. MS, NMOSD)

XIV. References

  1. Lindquist and Stephanos in Swadron (2023) EM:Rap 37(3): 4-12
  2. West (2013) Discov Med 16(88):167-77 +PMID: 24099672 [PubMed]

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