Acute Myelopathies

1
Acute Myelopathies

• Darrell Laudate
• 12/4/09 AM Report

2
Overview of Acute Myelopathy

• Spinal cord dysfunction or myelopathy, can occur
  due to a lesion arising within the spinal cord or
  due to compression of the spinal cord originating
  outside of it
• Frequently devastating, often producing
  quadriplegia, paraplegia, and sensory deficits
• Many spinal cord diseases are reversible if
  recognized and treated at an early stage

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Transverse Myelopathy vs. Myelitis

• Transverse Myelopathy refers to clinical
  presentation of severe motor, sensory, and
  autonomic dysfunction (bowel, bladder, and sexual
  abnormalities ) below a spinal cord lesion due to
  any acute/ subacute process affecting the spinal
  cord, compressive or not
• Often associated with back pain
• Transverse Myelitis refers to an inflammatory
  process of the grey and white matter of the
  spinal cord

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Transverse Myelopathies (cont.)

• Localization of the lesion depends upon the level
  of the spinal cord involved and the extent of the
  involvement of the various long tracts. In some
  cases, there is almost total paralysis and
  sensory loss below the level of the lesion,
  others only partial loss
• If cervical area is involved, all four limbs may
  be involved and there is risk of respiratory
  paralysis (segments C3,4,5 to diaphragm)
• Lhermitte's sign an electric shock-like
  sensation down the neck, back, or extremities
  that occurs with bending of the neck
• Lesions of the lower cervical (C2-T1) region will
  cause a combination of upper and lower motor
  neuron signs in the upper limbs, and exclusively
  upper motor neuron signs in the lower limbs.
• A lesion of the thoracic spinal cord (T1-12) will
  produce a spastic paraplegia.
• A lesion of the lower part of the spinal cord
  (L1-S5) often produces a combination of upper and
  lower motor neuron signs in the lower limbs

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Upper vs Lower Motor Neuron Lesions

• Lower motor neuron lesion is a lesion which
  affects nerve fibers traveling from the anterior
  horn of the spinal cord to the relevant
  muscle(s) 
• Associated with areflexia
• leads to flaccid paralysis (paralysis accompanied
  by muscle loss)
• Upper motor neuron lesion is a lesion of the
  neural pathway above the anterior horn cell or
  motor nuclei of the cranial nerves and are marked
  by
• Spasticity, increase in tone in the extensor
  muscles (lower limbs) or flexor muscles (upper
  limbs)
• Clasp-knife response where initial resistance to
  movement is followed by relaxation
• Weakness in the flexors (lower limbs) or
  extensors (upper limbs), but no muscle wasting
• Brisk tendon jerk reflexes
• Babinski or Hoffman sign is present
• increase deep tendon reflex
• Pronator drift
• (Spinal Shock - loss of sensation accompanied by
  motor paralysis with initial loss but gradual
  recovery of reflexes
• Occurs following a spinal cord injury, thus what
  may have looked like a lower motor neuron lesion
  can later reveal itself to be an upper motor
  lesion)

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Important Dermatomal Landmarks

• C2 - posterior half of the skull cap
• C3 - area correlating to a high turtle neck shirt
• C4 - area correlating to a low-collar shirt
• C6 - (radial nerve) 1st digit (thumb)
• C7 - (median nerve) 2nd and 3rd digit
• C8 - (ulnar nerve) 4th and 5th digit, also the
  funny bone
• T4 - nipples.
• T5 - Inframammary fold.
• T6/T7 - xiphoid process.
• T10 - umbilicus (important for early appendicitis
  pain)
• T12 - pubic bone area.
• L1 - inguinal ligament
• L4 - includes the knee caps

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Evaluation of suspected myelopathy

• Imaging is indicated in all patient with
  suspicion for myelopathy
• MRI is generally the most appropriate study as it
  images the spine, paraspinal region, and spinal
  cord also may reveal evidence of intrinsic
  lesions
• most patients with suspected cord compression
  should have total spinal cord imaging
• sole imaging of the lumber spine is often ordered
  with cord compression suspicion, but recall the
  spinal cord ends at L1, thus visualization of the
  spinal cord is not possible with a lumbar MRI
  alone
• lumbar MRI is useful however to exclude cauda
  equina compression (lower extremity weakness and
  sensory and bladder disturbances without upper
  motor neuron signs)
• Exceptions may include pts with upper and lower
  extremity symptoms as cervical localization is
  likely -gt Cervical MRI

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Other Studies

• Lumbar Puncture
• Serologic Studies as clinically indicated
• CT myelogram may be beneficial in patients with
  suspected inflammatory or demyelinative lesions
  of the spinal cord

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Noncompressive Myelopathies

• Vascular
• Arteriovenous malformation
• Antiphospholipid syndrome and other
  hypercoagulable states
• Inflammatory
• Multiple sclerosis
• Neuromyelitis optica (Devics Disease)
• Transverse myelitis (idiopathic)
• Sarcoidosis
• Vasculitis
• Infectious/Postinfectious
• Viral VZV, HSV-1 -2, CMV, HIV, HTLV-I,
  enteroviruses, flaivaviruses
• Bacterial and mycobacterial Borrelia, Listeria,
  syphilis, Mycoplasma pneumoniae
• Parasitic schistosomiasis, toxoplasmosis
• Metabolic
• Vitamin B12 deficiency (subacute combined
  degeneration)
• Copper deficiency

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Compressive Myelopathies

• Cervical spondylosis
• Epidural, intradural, or intramedullary neoplasm
• Epidural abscess
• Epidural hemorrhage/hematoma
• Herniated disc
• Posttraumatic compression by fractured or
  displaced vertebra or hemorrhage
• Clinical criteria alone cannot distinguish spinal
  cord compression and intrinsic cord lesions

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Acute Viral Myelitis

• Two Forms
• Enteroviruses (poliovirus, coxsackie virus, and
  enterovirus 71), Flaviviruses (West Nile virus
  and Japanese encephalitis virus) have been known
  to target the gray matter (Anterior horn cells)
  of the spinal cord, producing acute lower motor
  neuron disease.1
• usually accompanied with fever, headache, and
  meningismus
• produces asymmetrical flaccid weakness with
  reduced or absent reflexes and few sensory
  symptoms or signs
• MRI often shows hyperintensities in the anterior
  horns of the spinal cord on T2-weighted imaging
  Cerebrospinal fluid (CSF) analysis demonstrates a
  moderate pleocytosis
• These features help to distinguish this form of
  viral myelitis from Guillain-Barré syndrome,
  which usually produces symmetric deficits, with
  no MRI abnormalities, and is associated with
  elevated CSF protein levels without pleocytosis.

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Acute Viral Myelitis

• CMV, VZV, HSV I II, HCV, and EBV are associated
  with a second form of viral myelitis has clinical
  and diagnostic test features that are similar to
  transverse myelitis
• Association between the myelitis and the virus is
  not always clear, some may represent
  post-infectious transverse myelitis, others, a
  positive polymerase chain reaction (PCR) test in
  the CSF suggests that the myelitis is directly
  related to the viral infection
• Treated with Herpes zoster, HSV, and EBV myelitis
  are treated with intravenous acyclovir (10 mg/kg
  q8h) or oral valacyclovir (2 gm tid) for 1014
  days CMV with ganciclovir (5 mg/kg IV bid) plus
  foscarnet (60 mg/kg IV tid), or cidofovir (5
  mg/kg per week for 2 weeks).2

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Other Infectious Myelopathies

• HIV
• More of a chronic myelopathy, Often found mostly
  in late stages of AIDS and associated with AIDS
  related dementia in half
• slowly progressive spastic paraparesis is
  accompanied by loss of vibration and position
  sense and urinary frequency, urgency, and
  incontinence
• CSF may show nonspecific protein elevation
• ART may reverse the symptoms3
• Bacterial
• Mycoplasma (acute and post infectious), Listeria
  monocytogenes
• TB
• via secondary cord compression from verterbral
  osteomyelitis, aka Potts disease
• Also via compressive tuberculomas
• Lyme disease
• Cases have been described in which clinical and
  MRI features resembling acute transverse myelitis
  have been attributed to Lyme disease.4
• CSF in these cases typically demonstrates a
  lymphocytic pleocytosis and elevated protein
• Schistosomiasis (in endemic areas)

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Tabes Dorsalis (Locomotor Ataxia)

• Form of tertiary neurosyphilis in which the
  nerves of the dorsal (or posterior) columns
  degenerate
• Loss of sense of position (proprioception),
  vibration, and discriminative touch
• Latency period of 3-20 years
• Cardinal signs of tabes are loss of reflexes in
  the legs impaired position and vibratory sense
  Romberg's sign
• also
• bilateral Argyll Robertson pupils
• fleeting and repetitive lancinating pains,
  primarily in the legs
• Paresthesias/ formincation
• visceral crisis (Bladder disturbances, and acute
  abdominal pain with vomiting
• personality changes, dementia, deafness, visual
• skeletal musculature is hypotonic due to
  destruction of the sensory limb of the spindle
  reflex
• Ataxia of the legs and (tabetic) gait due to loss
  of position sense occurs in half of patients

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Tabes dorsalis (cont.)

• VDRL RPR (nontreponemal tests) may be
  nonreactive in late neurosyphilis
• If suspcion suspicion for neurosyphilis, serum
  FTA-ABS or TPPA (treponemal tests) are preferred
• CSF may be completely normal in tabes dorsalis,
  or may show mild lymphocytic pleocytosis with 10
  to 50 cells/microL and protein concentrations of
  45 to 75 mg/dL.
• Syphilitic meningovascular myelitis can represent
  an earlier form of syphilis infection
• focal inflammation of the meninges can
  secondarily affect the adjacent anterior spinal
  artery thus result in a CVA or spinal cord
  infarction
• Treatment - Penicillin G 3 to 4 million units IV
  every four hours or 24 million units continuous
  IV infusion for 10 to 14 days

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Connective tissue Associated Myelopathies

• SLE
• May be the initial feature but onset is usually
  present with other active lupus signs.
• thought to be due to an arteritis, with resultant
  ischemic necrosis of the spinal cord
• ANA, ds-DNA, anti-Sm, Anti-neuronal (may
  correlate with active CNS lupus)
• Has been associated with antiphospholipid
  antibodies in some studies but not all.5
• Treatment Prednisone (1.5 mg/kg per day),
  plasmapheresis, and cyclophosphamide.6
• Antiphospholipid antibodies a may also benefit
  with warfarin as well as steroids and
  immunosuppressive treatment.7
• Mixed connective tissue disease
• Sjogren's syndrome (antibodies to the Ro/SSA or
  La/SSB)
• Scleroderma (ANA, anti-Scl-70, anti-centromere
  (ACA), anti-RNA polymerase III, and
  anti-beta2-glycoprotein I antibodies)
• Ankylosing spondylitis
• Acute myelopathy will typically occur in the
  setting of fracture of ankylosed spine or
  atlantoaxial-axial subluxation
• cauda equina sydrome rare but associated with
  long standing disease
• Rheumatoid arthritis
• atlantoaxial subluxation, atlantoaxial impaction,
  and/or subaxial subluxation
• Rarely associated with CNS vasculitis and more
  rarely with myelopathy from vasculitis

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Sarcoid

• Neurosarcoidosis
• Typically occur perivascularly, but they can be
  extramedullary or intramedullary, and can involve
  the cauda equina.
• Occurs 5 of Sarcoid patients
• MRI signal abnormalities are not specific
• neurosarcoid lesions can appear similar to
  transverse myelitis or can resemble a tumor
• CSF profile consists of variable lymphocytic
  pleocytosis oligoclonal bands are present in
  one-third of case
• Generally treated with corticosteroids and other
  immunomodulatory agents and can improve

19
B12 Deficiency (subacute combined degeneration of
spinal cord)

• Damage to peripheral nerves caused by
  demyelination and irreversible nerve cell death.
• Symptoms include
• paresthesias in the hands and feet
• loss of vibration and position sensation
• progressive spastic and ataxic weakness
• Loss of reflexes due to an associated peripheral
  neuropathy in a patient who also has Babinski
  signs, is an important diagnostic clue
• Optic atrophy and irritability or other mental
  changes may be prominent in advanced cases
• This myelopathy tends to be diffuse rather than
  focal signs are generally symmetric and reflect
  predominant involvement of the posterior and
  lateral tracts, including Romberg's sign

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B12 deficiency (cont.)

• Usually established  by the presence of decreased
  Vit B12 level
• in the cases of low-normal B12, the presence of
  elevated MMA and homocysteine levels may be
  useful
• Treatment 1mg Cbl IM once daily for 1 week,
  followed by 1 mg IM every week for four weeks
• if the underlying disorder persists, 1 mg every
  month for the remainder of the patient's life.

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Hypocuric Myelopathy (Copper Deficiency)

• Very similar to subacute combined degeneration
• Progressive spasticity, severe gait
  abnormalities including ataxia, and a neuropathy.
  
• Also associated with anemia and neutropenia in
  certain patients
• More common after gastric bypass, also with zinc
  supplementation
• Diagnosis usually confirmed with low levels of
  serum copper are found and often there is also a
  low level of serum ceruloplasmin
• Symptoms are potentially reversible with copper
  supplementation and reversal of underlying cause

22
Multiple Sclerosis

• Most common autoimmune inflammatory demyelinating
  disease of the CNS
• Women of Northern European descent who are of
  child-bearing age.
• Histological examination of active plaques
  reveals perivascular infiltration of lymphocytes
  (predominantly T cells) and macrophages with
  occasional plasma cells. Perivascular and
  interstitial edema may be prominent.

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Multiple Sclerosis (cont.)

• Multiple sclerosis (MS) is a clinical diagnosis.
  There are no clinical findings that are unique to
  this disorder, but some are highly characteristic
  
• Older criteria considered clinical
  characteristics and a number of laboratory
  studies
• these findings were then used to place patients
  in categories ranging from clinically definite to
  laboratory supported definite to clinically
  probable to laboratory supported probable MS
• McDonald criteria focus on a demonstration with
  clinical, laboratory and radiologic data of the
  dissemination of MS lesions in time and space,
  also incorporated specific MRI findings into the
  diagnostic scheme
• A diagnosis cannot be made until other possible
  conditions have been ruled out and there is
  evidence of demyelinating events separated
  anatomically and in time

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Multiple Sclerosis (cont.)

• CSF
• oligoclonal bands using isoelectric focusing is
  the most important diagnostic CSF study when
  determining a diagnosis of MS
• 2/3 will have normal leukocyte count
• gt50cells/microliter occurs only rarely and should
  raise suspicion of alternative etiology
• Will also see elevation of the CSF immunoglobulin
  level relative to other protein components,
  suggesting intrathecal synthesis, generally IgG  
• MRI
• Cerebral or spinal plaques that are ovoid and
  hyperintense on proton density and T2-weighted
  studies, and they are hypointense (if visible at
  all) on T1-weighted images.
• Conventional T2-weighted MRI techniques may
  underestimate MS plaque size and burden,
  Diffusion tensor imaging and MR spectroscopy may
  correct this
• Evoked potentials (EPs) CNS electrical events
  generated by peripheral stimulation of a sensory
  organ)
• Can detect abnormal CNS function that may be
  clinically undetectable or help define the
  anatomical site of the lesion in tracts not
  easily visualized by imaging (e.g., optic nerves,
  dorsal columns).

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Neuromyelitis optica (Devics Disease)

• Autoimmune, inflammatory disorder in which the
  optic nerves and spinal cord are targeted but may
  also affect the brain,
• Resembles multiple sclerosis (MS) as it has
  varying degrees of weakness or paralysis in the
  legs or arms, loss of sensation (including
  blindness), and/or bladder and bowel dysfunction.
• Lesions are different from those observed in MS
  in that the attacks appear to be not mediated by
  the immune system's T cells but rather by
  antibodies called NMO-IgG that target aquaporin 4
  of astrocytes.6
• Acts as a channel for the transport of water
  across the cell membrane
• Found in the processes of the astrocytes that
  surround the blood-brain barrier,
• This blood-brain barrier is weakened in Devic's
  disease, but it is unclear how NMO-IgG immune
  response leads to demyelination
• Criteria Optic neuritis, Myelitis, and one of
  the following
• MRI evidence of a contiguous spinal cord lesion
  three or more segments in length, or
• Seropositivity for NMO-IgG
• Treatment Steroids, Cytoxan, PLEX, /- Rituximab

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Cervical Spondylosis

• Chronic degenerative and hypertraphic changes
  that involve intervertebral disks, vertebral
  bodies, facet joints, and ligaments
• if severe, can result in narrowing of cervical
  spinal canal and cause spinal cord compression
• In many case series, cervical spondylotic
  myelopathy is the most common cause of
  myelopathy, particularly in older adults
• Cervical Spondylotic Myelopathy
• clinical syndrome associated with spondylosis but
  with spinal cord dysfunction
• commonly in pts gt 55y, perhaps most common form
  of myelopathy
• insidious onset of numbness, parathesias in upper
  extremities, spastic or stiff-legged gait that is
  often not associated with pain
• surgical decompression is generally used to treat
  if symptomatic, although there is no evidence
  from RCT proving the efficacy of this therapy7

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Metastatic Disease to Spinal Cord

• Oncologic emergency
• usually requring treatment with corticosteroids
  (usually dexamethasone), and emergent radiation
  therapy or surgery
• indications for decompressive surgery for
  metastatic epidural spinal cord compression
  includes when tissue diagnosis is needed,
  presence of spinal instability, or tumor is known
  to be radioresistant
• One study showed patients who underwent anterior
  decompressive surgical resection of metastatic
  epidural spinal cord compression due to cancer
  had better ambulatory outcomes than with
  radiation therapy alone.8

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Epidural Abscess

• Rare, occurring in only 1 patient per 10,000
  admitted to the hospital.9
• Most common pathogen is Staphylococcus aureus,
  which accounts for about two-thirds of cases 9
• Typically originate via contiguous spread from
  infections of skin and soft tissues or as a
  complication of spinal surgery and other invasive
  procedures, including indwelling epidural
  catheters.
• Expected back and/or radicular pain usually but
  not always accompanied systemic signs of
  infection
• MRI preferred test
• Requires emergent surgical decompression and
  antibiotic therapy are indicated to treat
  epidural abscess

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Spinal Cord Infarction

• Rare compared with CVA
• Most frequently caused by surgical procedures and
  pathologies affecting the aorta
• May also occur in the setting of vascular risk
  factors or aortic disease
• Presents with sudden spinal cord dysfunction that
  typically corresponds to the territory of the
  anterior spinal artery
• Weakness and pinprick loss below the level of the
  infarction but sparing vibration and position
  sense
• No treatment available and prognosis is variable
  and dependent upon severity of presenting deficit

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Dural AVM of Spinal Cord

• Rare cause of ischemic spinal cord dysfunction
• Obstructs venous outflow of the spinal cord
• May progress over months to years
• Surgical obliteration of the fistula can
  potentially reverse this condition

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• Porter et al. Endocrine and reproductive
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• McCormick et al. Cervical Spndylotic myelopathy
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• Patchell et al. Direct decompressive surgical
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