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 ABSTRACT
S U P P L E M E N T AL D I G I T A L
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A VA I L A B L E O N L I N E
CITE AS:
CONTINUUM (MINNEAP MINN)
2018;24(2, SPINAL CORD DISORDERS):
386–406.
Address correspondence to Dr
Tracey A. Cho, Massachusetts
General Hospital, Neurology
Department, 55 Fruit St, Boston,
MA 02114, tracey.cho@post.
harvard.edu.
RELATIONSHIP DISCLOSURE :
Dr Cho has received personal
compensation as a case
M
adjudicator of a safety study for
Optum, Inc, on behalf of Merck
& Co, Inc. Dr Bhattacharyya
has received personal
compensation for serving as a
speaker for the American
Academy of Neurology.
UNLABELED USE OF
PRODUCTS/INVESTIGATIONAL
USE DISCLOSURE :
Drs Cho and Bhattacharyya
discuss the unlabeled/
investigational use of
corticosteroids in the
management of
neurosarcoidosis.
© 2018 American Academy
of Neurology.
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Approach to Myelopathy
By Tracey A. Cho, MD, FAAN; Shamik Bhattacharyya, MD, MS
PURPOSE OF REVIEW: Myelopathy is commonly encountered in clinical practice
and is associated with a large number of causes. This article reviews the
anatomy of the spinal cord and discusses how the clinical findings, time
course, and radiographic patterns can help to identify the causes of
myelopathy.
RECENT FINDINGS: Imaging observations such as MRI “pancake” gadolinium
enhancement pattern with spondylotic myelopathy and subpial
enhancement with neurosarcoidosis have improved diagnostic specificity.
On the other hand, common diseases such as degenerative spine disease
are now recognized as presenting much more variably. Improved imaging
and the identification of genetic markers enhance the specificity of
diagnosis. The improved identification of biomarkers has shown that the
same cause, such as compressive myelopathy, can present more variably
than previously appreciated.
SUMMARY: Spinal cord dysfunction, or myelopathy, remains a clinical
diagnosis, and determining the cause requires integration of clinical,
laboratory, and imaging parameters, none of which have great specificity
individually. Most cases of myelopathy will require further neuroimaging,
and some require CSF analysis for diagnosis. This article presents an
approach to the diagnosis of myelopathy based on excluding compressive
myelopathy initially and then differentiating between acute and subacute
processes and chronic causes.
INTRODUCTION
yelopathy is a term that was coined in the late 1800s to describe
spinal cord dysfunction and still remains a clinical diagnosis.1
Investigations including neuroimaging and laboratory studies
provide supportive evidence or can identify a cause of
myelopathy but are not diagnostic of the syndrome. For
instance, in some patients with disabling human T-cell lymphotropic virus type I
(HTLV-I)–associated myelopathy, conventional imaging techniques remain
entirely normal. Hence, the approach to a patient with suspected myelopathy
begins with a thoughtful analysis of clinical history and neurologic examination.
Distinguishing between a cerebral lesion and myelopathy may not always be
clinically possible early in the disease course.
Myelopathy with similar signs and symptoms can be caused by a variety of
diseases. The time course of development of symptoms and the anatomic pattern
of deficits can suggest possible etiologies but often are not sufficiently specific.
Diagnostic studies help to further narrow the possibilities and are generally
APRIL 2018
sequenced to first exclude diseases requiring urgent treatment, such as epidural KEY POINT
abscess or other causes of compressive myelopathy. Despite extensive
● The spinal cord is
investigations, it is not unusual for the ultimate diagnosis to remain unclear. organized with gray matter
Close clinical follow-up and therapeutic trials may be more illuminating and lead located centrally and white
to a more precise diagnosis. matter located peripherally.

BASIC ANATOMY OF THE SPINAL CORD

The spinal cord is continuous with the brainstem and stretches from the
cervicomedullary junction to the L1-L2 disk interspace as the conus medullaris.
The spinal cord is covered by the leptomeninges and dura, which are surrounded
by the bony structures of the spinal column. The spinal cord is organized into
segments from which emerge 31 paired bilateral ventral and dorsal nerve rootlets
(eight cervical, twelve thoracic, five lumbar, and six sacral/coccygeal). Sensory
nerve roots enter via the dorsal aspect, while motor nerve roots exit from the
ventral aspect of the spinal cord. Ventral and dorsal nerve rootlets combine to
form individual spinal nerves near the intervertebral foramen.
In cross-section, the butterfly-shaped gray matter occupies the center of the
cord, and ascending and descending white matter tracts are located around the
central gray matter (FIGURE 1-1).2 The gray matter contains the bodies of neurons
residing within the spinal cord. The volume of gray matter is largest in the
cervical and lumbar regions, while the white matter volume gradually tapers in
the craniocaudal axis. At the center of the gray matter is the central canal, which
is an ependymal-lined structure filled with CSF that communicates with the
fourth ventricle superiorly. Generally, the central canal is small and, if enlarged,
is called hydromyelia (to be distinguished from syringomyelia, which is also a
fluid-filled cavity in the spinal cord, but is instead lined with glial cells). Apart
from the dorsal and ventral horns, a lateral horn (intermediolateral cell column)
is also visible particularly in the thoracic and upper lumbar segments, containing

FIGURE 1-1
Gray and white matter divisions of the spinal cord.
Reprinted with permission from Cho TA, Continuum (Minneap Minn).2 © 2015 American Academy of Neurology.

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APPROACH TO MYELOPATHY
KEY POINTS
● Spinal cord neuronal
circuitry is key in maintaining
smooth and patterned
movement and mediating
reflexes.
● The dorsal column system
carries ipsilateral vibration
and pressure sensation.
● Spinothalamic lesions
cause contralateral loss of
pain and temperature
sensation.
● The corticospinal tract
carries descending cortical
input from the motor cortex
as well as from the premotor
and parietal regions.
388
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the cell bodies of preganglionic sympathetic neurons. Based on histologic
features at a cross-section, the spinal cord gray matter can be further subdivided
into 10 cell layers called laminae of Rexed.
The spinal cord is a complex structure and much more than a conduit of
tracts and monosynaptic connections. Neurons in the gray matter of the spinal
cord may span multiple segments and form intricate interconnections. To
illustrate the underappreciated complexity of the spinal cord, the motor
pathway is often taught in medical school as a monosynaptic connection
starting at the motor cortex proceeding to the descending corticospinal tract
and then synapsing with motor neurons in the ventral horn of the spinal cord
before exiting via spinal nerves. This model is grossly oversimplified, and, in
reality, the corticospinal tract projects widely to all layers of the spinal cord,
including the dorsal horn, and influences nociceptive, somatosensory,
autonomic, and motor functions probably more through spinal interneurons
than through direct motor neuron connections.3 Among other examples, the
ability to produce patterned motor behavior crucially depends on intraspinal
neuronal circuitry and integration of sensory input and motor output at the
level of the spinal cord.4 As V. Reggie Edgerton, PhD, said, “the spinal cord
functions as part of the brain, not as its servant.”3 For neurologists, the
internal spinal neuronal circuitry is accessed during a standard neurologic
examination. The tendon stretch reflex arc is mediated by activation of
intrafusal muscle fibers located in muscle spindles. This afferent signal results
simultaneously in direct activation of motor neurons for the same muscle and
inactivation of antagonist muscles through projecting connections to
interneurons at other spinal segmental levels. The magnitude of this intrinsic
spinal response is modulated by descending input from the brain, illustrating
the complex relationship between the brain and spinal cord function.
The white matter tracts surrounding the gray matter can be roughly grouped
into three different regions called the dorsal, lateral, and ventral funiculi or
columns (FIGURE 1-1). Each one of the regions carries somatotopically organized
ascending or descending tracts with linked function. Although multiple
ascending and descending tracts exist, for the practicing neurologist, three
separate tracts bear special mention (FIGURE 1-2). The dorsal column system
consists of the fasciculus gracilis (fibers from the lumbosacral regions) and the
fasciculus cuneatus (fibers from the cervicothoracic regions). The dorsal columns
carry ascending ipsilateral proprioceptive, vibratory, and touch-pressure
sensation. The dorsal columns ascend and synapse at the nucleus fasciculus
gracilis and nucleus fasciculus cuneatus, which then project decussating fibers to
form the medial lemniscal system in the brainstem. In contrast to the dorsal
columns, the spinothalamic tract is located in the lateral column and carries pain,
temperature, and touch sensation. The spinothalamic tract consists of
contralateral projections of second-order neurons, which receive afferent input
from the dorsal root ganglion cells. The second-order neurons are located within
the gray matter of the spinal cord and project via the ventral commissure to
the contralateral side after ascending about one level or more. Hence, a lesion
in the right spinothalamic tract within the spinal cord affects pain and
temperature sensation on the left side of the body. Within the spinothalamic
tract, somatotopic organization is present, such that sensory fibers from the arms
are more centrally located compared to the fibers from the legs, which are
located peripherally. Pain and temperature sensation are carried more dorsally
APRIL 2018
FIGURE 1-2
Principal white matter tracts of the spinal cord.
Reprinted with permission from Cho TA, Continuum (Minneap Minn). 2 © 2015 American Academy
of Neurology.

compared to touch sensation. The spinothalamic tract ascends to synapse with

the ventral posterolateral nucleus of the thalamus.
The primary descending tract from the cerebral cortex is the corticospinal tract.
The corticospinal tract is heterogeneous and carries descending input not only
from the primary motor cortex but also from frontal premotor regions and the
parietal cortex.5 At the level of the medulla, the majority of corticospinal tracts
decussate to form the lateral corticospinal tract located in the lateral column of the
spinal cord, while a minority descend without decussating as the ventral
corticospinal tract located in the ventral column. The lateral corticospinal tract
synapses with interneurons and motor neurons in the spinal cord. Although the
ventral corticospinal tract descends uncrossed, the fibers from the ventral
corticospinal tract eventually cross via the ventral commissure leading to mostly
contralateral connections, particularly for limb musculature. Lesions in the
corticospinal tract at the level of the spinal cord generally result in ipsilateral paresis
particularly affecting the flexor muscles of the legs (hip flexion, knee flexion, and
foot dorsiflexion) and extensor muscles of the arms (deltoids, triceps, wrist
extensors, and finger extensors). Increased tone, increased muscle stretch
reflexes, and Babinski signs are present. Some of the signs, such as the Babinski
sign or increase in tone, are not absolute, and part of the clinical spectrum of
signs may be related to disruption or modulation of descending brainstem pathways
such as the reticulospinal tract.6
The arterial supply to the spinal cord (FIGURE 1-3)7 is via the anterior and
posterior spinal arteries. The anterior spinal artery is located in the midline on the
ventral surface of the spinal cord and is formed superiorly by union of bilateral

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APPROACH TO MYELOPATHY

FIGURE 1-3
The arterial supply of the spinal cord is via the anterior spinal artery for the anterior
two-thirds of the cord and via the paired posterior spinal arteries for the posterior one-third
of the cord. Both the anterior spinal artery and posterior spinal artery are re-enforced by
radiculomedullary arteries. The largest such artery to the anterior spinal artery is called the
artery of Adamkiewicz.
Reprinted with permission from Martirosyan NL, et al, J Neurosurg Spine.7 © 2011 Nicholas Theodore, MD.

branches from vertebral arteries in the cervical region. The anterior spinal artery
gradually decreases in caliber as it descends to the thoracic region and is
reinforced by successive radicular arteries (which are segmental arteries
branching from the great vessels such as the aorta and entering through the
intervertebral foramen). Extensive variability occurs in radicular arterial supply
to the anterior spinal artery, and many radicular arteries terminate before
reaching the spinal cord. The radicular arteries that ultimately reach the spinal
cord (radiculomedullary arteries) are more often located on the left side
compared to the right, and, on average, about 10 radiculomedullary arteries
contribute to the anterior spinal artery blood supply.7 The largest
radiculomedullary artery is called the artery of Adamkiewicz, which originates
from the T9 through T12 radicular arteries in 75% of people.8 The anterior spinal
artery supplies the anterior two-thirds of the spinal cord including the ventral
gray matter and anterior portions of the lateral columns (containing the
corticospinal and spinothalamic tracts).
The posterior spinal arteries are paired longitudinal arteries located in the
dorsal aspect of the spinal cord near the entrance of the dorsal roots. The arteries
are formed superiorly from branches of either the vertebral or posterior inferior
cerebellar arteries. The posterior spinal arteries receive blood supply from
posterior branches of radicular arteries, which are more numerous than branches
to the anterior spinal artery.9 The posterior spinal arteries form an anastomotic
network and supply the posterior third of the spinal cord containing the posterior
gray matter and dorsal columns.
Intramedullary veins drain into a plexus of veins surrounding the spinal
cord.10 Veins from the plexus are connected to the medullary veins, which exit
via the segmental veins through the intervertebral foramen. The venous plexus is

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also connected superiorly to the cranial sinuses. Knowledge of the venous KEY POINTS
drainage patterns becomes significant particularly in cases of venous
● Extensive variability
hypertension accompanying arteriovenous fistulas. occurs in the number and
location of radiculomedullary
SYMPTOMS AND SIGNS OF MYELOPATHY arteries supplying the anterior
Despite the small size of the spinal cord, myelopathies present in a variety of spinal artery.
ways depending on the tracts affected and the disease process. Some common
● The largest
signs and symptoms are gait instability/imbalance, stiffness or clumsiness in the radiculomedullary artery is
extremities, weakness in the arms or legs, episodic muscle spasms often causing called the artery of
unintentional extension of legs or cramping in the calves, urinary urgency or Adamkiewicz and is found
hesitancy, bowel incontinence, and phenomenon of a sensory level. This last most frequently, but not
always, between the T9 and
feature of a sensory level is often experienced as an irritating bandlike sensation T12 segments.
at the superior margin of the level (as a patient described it to one of the authors
of this article, “like a sensitive, squeezing belt”) with numbness and paresthesia ● A sensory level is the
below that level. One particularly helpful question for the patient is whether most caudal dermatomal
level on each side in which
water temperature feels the same throughout the body when standing in a warm both light touch and
shower or more on one side of the trunk or abdomen than the other. Someone sharp/dull discrimination
with a thoracic cord lesion may describe relative loss of water temperature are intact.
sensation below the abdomen. A subjective sensory level indicates a possible
● A sensory level is
lesion at that dermatomal level of the spinal cord or above. In other words,
consistent with a lesion in
numbness below the umbilicus may be caused by a lesion at the T10 level (the the spinal cord at that
dermatome corresponding to the umbilicus) or a lesion higher in the spinal cord dermatomal level or at any
such as in the upper thoracic or cervical spinal cord. This is a consequence of the point above.
laminated structure of the spinal cord such that eccentrically located lesions in
● A Babinski sign is a
the cervical spinal cord can cause symptoms in the thoracic segments and below. specific but not sensitive
On neurologic examination, a number of findings suggest myelopathy and sign of corticospinal tract
sometimes a particular localization. Acute spinal cord injury affecting the dysfunction.
corticospinal tract causes flaccid paralysis (sometimes called spinal shock),
● Beevor sign is upward
which evolves over days to the more recognizable corticospinal syndrome of
displacement of the
weakness with increased tone, hyperactive muscle stretch reflexes, Babinski umbilicus when a patient sits
sign, and Hoffmann sign (if involving the cervical spinal cord). Although the up or flexes the neck. The
presence of a Babinski sign indicates corticospinal tract injury, absence of a sign may suggest a
thoracic cord lesion.
Babinski sign does not exclude corticospinal tract dysfunction. In a retrospective
review of patients with cervical spondylotic myelopathy, the prevalence of a
Babinski sign ranged from 10% in mild myelopathy to only about 80% even with
severe myelopathy.11
Another sign associated with myelopathy is the Beevor sign, which refers to
upward displacement of the umbilicus when a patient sits up or raises the head
from a reclining position.12 The Beevor sign arises from relative weakness of
the lower abdominal muscles compared to the upper abdominal muscles and
is associated with a thoracic cord lesion between the T10 and T12 segments
(VIDEO 1-1, links.lww.com/CONT/A208).13,14 The Beevor sign is not specific and
is also seen with other diseases causing lower abdominal weakness such
as facioscapulohumeral muscular dystrophy or amyotrophic lateral sclerosis.
Finally, in contrast to muscle stretch reflexes, which are exaggerated, superficial
reflexes such as the abdominal, cremasteric, or anocutaneous wink reflexes are
absent below the level of spinal cord injury.
The subjective experience of a sensory level can be substantiated objectively
by sensory testing. Although many ways exist to assess a sensory level, the
American Spinal Injury Association (ASIA) recommends testing light touch and

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APPROACH TO MYELOPATHY

sharp/dull discrimination at predefined points in 28 dermatomes bilaterally

(SDC APPENDIX, links.lww.com/CONT/A245).15 The sensory level is the most caudal
level on each side at which both light touch and sharp/dull discrimination are
maintained.16 The level should be present both in the back and in the anterior
trunk for cervical and thoracic lesions. As discussed, the demonstrated sensory
level indicates that the spinal cord has a lesion at that dermatomal level or at any
point in the spinal cord above that level. It is not uncommon for the subjective
sensory level to be higher than the objective sensory level. In some patients, other
sensory modalities can be used to show a level as well. An autonomic level can
occasionally be demonstrated in the back by testing for the wheal-and-flare
reaction by scratching the skin longitudinally in the paraspinal region. In patients
with myelopathy, the flare reaction can be missing below the level of spinal
cord injury, suggestive of autonomic dysfunction below that level. Similar to
sharp/touch discrimination, vibration can also be used to define a sensory level,
although it is less precise because of the spread of vibration to connected bony
structures. Proprioception is often significantly affected in spinal cord disorders
and contributes to imbalance.
Because of the anatomy of the spinal cord, selective injury to the spinal cord
can generate characteristic clinical syndromes diagnostic of myelopathy and
sometimes suggest causes. At the most extreme, the syndrome of complete
cord transection causes bilateral paralysis and loss of sensation of all modalities
below the level of the lesion. These significant injuries can occur with spinal
cord trauma, hemorrhage, myelitis, or any other disorder affecting the entirety
of the spinal cord in an axial plane. A lesion affecting half of the spinal cord
causes a hemicord syndrome also known by the eponym Brown-Séquard
syndrome. The hemicord syndrome causes ipsilateral motor weakness,
ipsilateral vibratory/proprioceptive loss, and contralateral pain/temperature
loss below the level of the lesion. The constellation of these clinical findings
suggests myelopathy but is not specific for a particular disorder. The syndrome
is particularly common in multiple sclerosis, which causes eccentric cord
lesions, but can also occur in most other diseases causing incomplete injury to
the spinal cord, including extrinsic compressive lesions or intramedullary
neoplasms. Notably, in clinical practice, the hemicord syndrome is often
incomplete and affects only the lateral column tracts while sparing the
dorsal column.
The dorsal column syndrome spares strength and pain/temperature sensation
but causes impairment of vibration and proprioceptive sense. If the dorsal
column lesion occurs in the cervical spine, Lhermitte sign can be seen, which is
an electric shock–like sensation running down the back elicited by neck flexion.17
Selective posterior column dysfunction is found in syphilitic spinal cord
disease (tabes dorsalis), posterior spinal artery infarction, multiple sclerosis,
partial cord trauma, and after platinum-based chemotherapy. In syphilitic
disease, involvement of the dorsal root ganglion also occurs, likely accounting for
the shooting pain and diminished reflexes distally. Dorsal column dysfunction
manifesting as transient Lhermitte sign is a feature of early delayed radiation
spinal cord injury.18
A related but separate syndrome is the combination of dorsal column and
corticospinal tract dysfunction generating the so-called posterolateral column
syndrome. This clinical syndrome is marked by bilateral corticospinal tract
pattern weakness below the level of the lesion with decreased vibratory and

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position sense but sparing pain/ KEY POINTS
temperature sensation. This clinical
● The hemicord syndrome,
pattern is commonly found in vitamin B12 also known as Brown-
deficiency, copper deficiency, human Séquard syndrome, causes
immunodeficiency virus (HIV)–associated ipsilateral motor
vacuolar myelopathy, weakness, ipsilateral
vibratory/proprioceptive
adrenomyeloneuropathy, HTLV-
loss, and contralateral
I–associated myelopathy, methotrexate pain/temperature loss
toxicity, and spinal dural arteriovenous below the level of
fistula (FIGURE 1-4). The pattern is not the lesion.
exclusive to these disorders and can be
● The dorsal column
found in other disorders such as syndrome causes
spondylotic myelopathy. FIGURE 1-4 impairment of vibration and
The anterior cord syndrome affects Posterolateral column syndrome proprioception below the
after intrathecal methotrexate. Axial level of the lesion, sparing
bilateral lateral columns and the ventral
T2-weighted MRI of cervical spine strength and pain/
horn, sparing the dorsal columns. Patients showing bilateral hyperintensity in the temperature sensation.
experience weakness and loss of dorsal columns (red arrow) and
pain/temperature sensation below the lateral columns (green arrow). ● Lhermitte sign is an
level of the lesion with relative electric sensation running
down the back elicited by
preservation of vibration/proprioception.
neck flexion, suggestive of a
At the level of the lesion, lower motor neuron pattern weakness may also occur dorsal column lesion in the
from injury to the ventral horn. The anterior cord pattern is most suggestive of an cervical spinal cord.
infarct in the territory of the anterior spinal artery. However, lack of this pattern
does not exclude an anterior spinal artery infarct since many patients with a ● The posterolateral
column syndrome causes
spinal cord infarct have atypical clinical patterns that do not follow traditional bilateral corticospinal tract
vascular territories.19 weakness and vibratory/
The central cord syndrome, as its name suggests, affects the gray matter of the position sense loss below
spinal cord. For small midline central cord lesions, the clinical syndrome is driven the level of the lesion with
sparing of pain/temperature
by interruption of the crossing fibers of the spinothalamic tract near the ventral sensation.
commissure. Consequently, patients experience loss of pain and temperature
sensation in a bandlike distribution generating the so-called suspended sensory ● The anterior cord
level. This clinical pattern is associated with syringomyelia but can also be found syndrome causes
corticospinal tract weakness
with intramedullary tumors or small hemorrhages. If the central cord lesion is
and loss of pain/temperature
larger, then the adjacent ventral horns are also affected, causing not only a sensation below the level of
suspended sensory level, but also lower motor neuron pattern weakness in those the lesion with preservation
myotomes. This pattern can be seen with neuromyelitis optica lesions or with of vibration/proprioception.
spinal cord trauma from hyperextension injuries. Occasionally, non–length-
● In a central cord
dependent small fiber neuropathies can simulate a central cord syndrome in syndrome, loss of pain and
terms of patchy involvement of pain/temperature with preservation of other temperature sensation
sensory modalities. occurs in a bandlike
The anterior horn syndrome (distinguished from the anterior cord syndrome) distribution (suspended
sensory level) often
refers to lower motor neuron degeneration with preservation of all sensory caused by syringomyelia.
modalities. This pattern is found in spinal muscular atrophy, progressive Involvement of the ventral
muscular atrophy (lower motor neuron restricted form of amyotrophic lateral horn and lateral columns
sclerosis), spinal and bulbar muscular atrophy (also known as Kennedy disease), occur with larger lesions.
monomelic amyotrophy, Hirayama disease, and West Nile virus myelitis. HIV
● The anterior horn
infection rarely has been associated with isolated anterior horn syndrome.20 syndrome causes selective
Poliomyelitis is the classic example of anterior horn syndrome, although it is lower motor neuron
rarely encountered today. Patients can still be seen with postpolio syndrome who degeneration with
preserved sensation.
had experienced prior anterior horn syndrome from poliomyelitis.

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APPROACH TO MYELOPATHY

An associated clinical syndrome is the combination of anterior horn syndrome

with corticospinal tract signs. This combination of upper and lower motor
neuron symptoms is most concerning for amyotrophic lateral sclerosis. Other
diseases that can also cause this combination include cervical spondylotic
radiculomyelopathy, adult polyglucosan body disease, and foramen magnum
lesions.21 In contrast to amyotrophic lateral sclerosis, adult polyglucosan body
disease is associated with a high propensity for neurogenic bladder and white
matter lesions on brain MRI. Compressive lesions in the foramen magnum cause
a unique syndrome characterized by sensorimotor symptoms starting in the arm,
progressing to the ipsilateral leg and then to the contralateral leg, and finally
progressing to the contralateral arm. This pattern of progression has also been
called “around the clock” or “U syndrome.”

IMAGING PATTERNS AND CAUSES

Clinical determination of myelopathy is usually followed by spine imaging using
MRI or CT and occasionally also x-ray studies. X-ray can show abnormalities
in the alignment of the vertebral bodies but does not image the spinal cord.
Importantly, x-ray allows for dynamic imaging in flexion and extension views
and can uncover spinal column instability missed on static imaging. Obtaining
flexion and extension x-rays, for example, is especially important in patients
with rheumatoid arthritis who are prone to developing atlantoaxial instability.
CT imaging is more illustrative than x-ray because of cross-sectional imaging and
better spatial resolution. While the spinal cord itself cannot be adequately
evaluated by CT, common bony diseases of the spine such as spondylotic disease
can be seen; the neurologic effects are inferred from the degree of narrowing of
the spinal canal or foramina. Particularly after spinal instrumentation, CT of the
spine accurately shows the position of hardware without the extensive artifact
observed on MRI. CT is also useful in some other instances. In patients with
implanted MRI-incompatible devices such as pacemakers or stimulators, CT
myelography (a procedure in which contrast is injected into intrathecal space)
provides visual distinction between the CSF space and the spinal cord with its
exiting nerve roots. Compressive lesions can be evaluated by CT in this manner.
When concern exists for CSF leak, CT myelography can show dural defects
missed on MRI. Finally, CT imaging is fast, and for a substantial number of
patients with claustrophobia, CT imaging is all that can be obtained.
However, MRI is the preferred imaging modality for the spinal cord. A
number of sequences and protocols have been developed for examining the
spinal cord. The first decision is which segment to image. Generally, it is best to
clinically localize the lesion and image a focused region. Whole-spine imaging
generates averaged images of lower resolution and often requires dedicated
regional imaging (such as of the cervical or thoracic spinal cord). Imaging of the
entire spine is appropriate for oncologic surveillance and for screening for
compressive causes of acute myelopathy. In standard sequences, as in the brain,
T1-weighted images produce hyperintense signal for lipid and blood products.
T2-weighted images produce hyperintense signal for CSF, edema, and gliosis and
are particularly useful for evaluating the spinal cord parenchyma. Lipid is
hyperintense in T2 sequences as well; hence, the short tau inversion recovery
(STIR) is a complementary fat-suppressed sequence that produces hypointense
signal for lipids with preserved hyperintense signal for edema and CSF. IV
gadolinium-based contrast is used to generate T1-weighted postcontrast images

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when a concern for inflammatory or neoplastic lesions is present. Depending on
clinical suspicion, sequences with similar properties to brain imaging, such as
susceptibility-weighted imaging for blood products or diffusion-weighted
imaging for ischemia, can be obtained, although often with more limited
sensitivity compared to brain images.
In contrast to brain imaging, MRI of the
spinal cord often appears to be of lower
quality, even in the most compliant of
patients. The bone encasing the spinal cord
generates some of these artifacts; the
magnetic field in the imaging area is not
uniform since the bone itself causes
magnetic field distortion.22 Substantial
motion artifact is also caused by
respiration, CSF pulsation (FIGURE 1-5),
arterial pulsation (the spinal cord is close
to the great arteries), and swallowing.23
Elevated lipid content is associated with
spatial distortion of the images. Metallic
spinal implants can cause further
inhomogeneity of the magnetic field,
resulting in distorted images. Moreover,
higher field strength in 3T MRI scanners
paradoxically causes some of the artifacts
generated from magnetic field
inhomogeneity and movement to be
exaggerated compared to 1.5T scanners,
negating some of the benefits from higher
magnetic field strength scanning. A
number of techniques have been
developed to compensate for these
numerous causes of artifacts. Some
examples include saturation band
placement to compensate for the
swallowing artifact. MRI spine protocols
often also now include newer gradient
echo sequences (appearing confusingly
under different names such as Multiple
Echo Recombined Gradient Echo
[MERGE] on GE Healthcare scanners,
Multi-Echo Data Image Combination
[MEDIC] on Siemens Corporation
scanners, and Merged Fast Field Echo
[MFFE] on Philips scanners), each of
which promise better detection of
intramedullary lesions with fewer artifacts
compared to conventional T2 imaging
(FIGURE 1-6). 24
Although imaging has assumed a central
role in evaluation of spinal cord disorders,
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KEY POINTS
● X-ray allows for flexion
and extension views to
detect dynamic instability of
vertebral body alignment.
● Whole spine imaging is
appropriate for oncologic
surveillance and for
screening for cord
compression, but generally
it is best to image a
dedicated segment of the
spine based on clinical
localization.
● T2-weighted sequences
are more sensitive than
T1-weighted sequences
for showing spinal cord
parenchymal lesions.
● Spine MRI artifact
sources include patient
motion, respiration, CSF
pulsation, arterial pulsation,
and swallowing, which
degrades the quality of
the images.
FIGURE 1-5
CSF pulsation artifact. Sagittal short
tau inversion recovery (STIR) MRI of
thoracic spine showing CSF pulsation
artifact appearing as an intradural
hypointense lesion (green arrow).
FIGURE 1-6
Axial T2-weighted gradient echo MRI
of cervical spine showing better
definition of the spinal cord
compared to standard T2 sequences
and separation of central gray matter
from surrounding white matter.
395
APPROACH TO MYELOPATHY

it is important to remember that myelopathy is a clinical diagnosis and that,

particularly for chronic causes of myelopathy, MRI of the spinal cord can be
apparently normal despite significant myelopathic clinical findings. Also, small
lesions can be missed on MRI and sometimes detected on repeat imaging.
Limited sensitivity of MRI for spinal cord dysfunction is especially relevant for
cervical spondylotic myelopathy, which is the most common cause of
nontraumatic myelopathy in older adults.25 In a series of 52 patients with
compressive cervical myelopathy, for example, T2 cord hyperintense lesions
were present in only 65% of patients.26 It is a common error to equate lack of cord
signal changes with lack of clinical myelopathy or need for treatment. In fact, in
observational studies, the presence or absence of cord signal changes in cervical
spondylotic disease does not predict response to conservative or surgical
treatment.27 Finally, another limitation of current MRI technology is the
mismatch between clinical classification of a cord syndrome and imaging. For
example, a clinical classification of anterior cord syndrome from spinal cord
ischemia may appear similar to a central cord lesion on MRI. This is likely from
the limited spatial resolution of current MRI techniques of the spinal cord.
When a cord lesion is found, the morphology of the lesion can be helpful in
pointing to the cause. One helpful scheme is to subdivide cord lesions into
longitudinally extensive (spanning more than three vertebral segments) versus
shorter, more discreet lesions. Most causes of longitudinally extensive lesions are
also associated with shorter lesions. Some causes of longitudinally extensive
lesions include inflammatory myelitis (particularly neuromyelitis optica,
neurosarcoidosis, systemic lupus erythematosus, paraneoplastic,
postinfectious/parainfectious, HTLV-I, HIV, varicella-zoster virus, and
syphilis), neoplasm (eg, ependymoma and other gliomas), prior trauma,
nutritional causes (vitamin B12 and copper deficiency), and vascular causes (eg,
spinal cord arteriovenous malformations). Of note, multiple sclerosis typically
causes shorter-segment lesions often placed eccentrically in axial cross-sections
of the spinal cord. This rule is not absolute, and, in rare instances, multiple
sclerosis has been known to cause longitudinally extensive lesions as well.28
Unlike the brain, intramedullary cord metastases are quite rare, affecting less
than an estimated 0.5% of all patients with cancer.29
The finding of a T2-hyperintense cord lesion alone usually does not confer
enough specificity to make a diagnosis. Sometimes, associated radiologic signs
can provide diagnostic clues. For any patient with a cord lesion, the associated
vertebral column should be closely examined not only for compressive causes but
also for bony lesions. In arterial embolism, associated vertebral body infarct can
occur, in addition to the spinal cord infarct, which provides a helpful clue.
Epidural abscess causing spinal cord injury is usually associated with adjacent
diskitis and vertebral osteomyelitis. Because spondylotic disease is quite common
radiographically and can be incidental, occasional uncertainty exists as to
whether a spinal cord lesion is secondary to an inflammatory process or
compressive disease. In these instances, IV gadolinium contrast can differentiate
the causes. For compressive myelopathy, a recently described finding is a
“pancake” pattern of peripheral cord enhancement that is generally not found in
inflammatory lesions (FIGURE 1-7).30
For patients with a clinical diagnosis of myelitis of unclear etiology, brain MRI
should generally be obtained even if no clear signs or symptoms of cerebral
involvement are seen. In multiple sclerosis, which is a common cause of myelitis,

396 APRIL 2018

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the majority of patients presenting with KEY POINTS
myelitis will have brain MRI lesions
● Cervical degenerative
suggestive of the disease. In one series, brain disease can cause
MRI abnormalities were present in 87% of myelopathy without cord
patients initially presenting with myelitis T2 signal.
who were eventually diagnosed with
● There may be a mismatch
multiple sclerosis.31 Brain MRI
between the clinical
abnormalities, however, are not specific myelopathy syndrome and
for multiple sclerosis and also present in pattern of cord T2 signal
diseases such as adrenoleukodystrophy or on imaging.
neuromyelitis optica. Myelitis can be the
● Vertebral body infarct
presenting symptom of sarcoidosis, and can accompany spinal cord
specific gadolinium enhancement patterns infarct, providing a helpful
have been described. Neurosarcoidosis with clue to the diagnosis.
a long-segment cord lesion is likely to have
FIGURE 1-7 ● For myelitis of unclear
persistent enhancement for more than
Peripheral enhancement pattern. etiology, brain MRI may be
2 months and a dorsal subpial enhancement Sagittal postcontrast T1-weighted MRI helpful in providing a
pattern, which are features generally not showing a peripheral pattern of diagnosis even when no
seen in diseases such as neuromyelitis enhancement (green arrow) found in clinical cerebral involvement
cord lesions associated with is apparent.
optica (FIGURE 1-8).32 At other times,
compressive myelopathy. As in this
the neuroimaging of neurosarcoidosis is patient, the enhancement can persist ● In patients with
not specific, and the diagnosis is only shortly after decompression. neurosarcoidosis,
reached after investigation for hilar enhancement can be
lymphadenopathy, which can be entirely persistent over months.
asymptomatic and found only on positron ● Myelopathy from
emission tomography (PET)/CT (CASE 1-1). degenerative disease can
present acutely or with more
SUGGESTED CLINICAL APPROACH chronic symptoms and have
only motor or sensorimotor
TO MYELOPATHIES
findings. Most patients with
Despite its common occurrence, no myelopathy should be
consensus guidelines are available for screened for compressive
evaluation and treatment of myelopathy. lesions.
The authors of this article present their
approach in this section. The authors
typically begin by assessing the chronicity
of the clinical syndrome, with chronic
myelopathies having insidious onset over
the course of many months and
acute/subacute myelopathies having onset FIGURE 1-8
Dorsal subpial enhancement. Axial
usually over the scale of hours to days. postcontrast T1-weighted MRI of
Where to draw the line is certainly unclear myelitis from neurosarcoidosis with
since even chronic diseases become dorsal subpial enhancement pattern
noticeable at some threshold and are often (green arrow).
reported to be of acute onset by the patient.
Careful collateral history is helpful.
For myelopathy of any pace of onset, the first step is to exclude compressive
causes of myelopathy not only because they are the most common causes but also
because myelopathy from degenerative causes can have chronic, subacute, and
acute presentations that are hard to distinguish clinically, with variable clinical
presentation ranging from primarily imbalance to severe involvement of

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APPROACH TO MYELOPATHY

CASE 1-1 A 45-year-old man presented with left abdomen, groin, and lower limb
tingling, splitting the midline, reaching maximal symptoms over 2 days. He
also noted sexual dysfunction. On examination, he had a left T10 sensory
level to pinprick and light touch with increased deep tendon reflexes in
the right lower limb but normal reflexes elsewhere, and his strength was
preserved. MRI of the thoracic and lumbar spine revealed a right T6-T7
T2-hyperintense lesion that enhanced on postcontrast T1-weighted
images (FIGURE 1-9). Brain MRI showed some nonspecific white matter T2
hyperintense foci (not in a pattern typical of multiple sclerosis). CSF
examination revealed normal glucose and protein with 4 white blood
cells/µL (lymphocyte predominant) and no oligoclonal bands; CSF
varicella-zoster virus polymerase chain reaction (PCR) was negative.
Serum neuromyelitis optica IgG, antinuclear antibodies, Ro, La, and
angiotensin-converting enzyme were normal. Human immunodeficiency
virus was nonreactive. Chest x-ray showed mild hilar enlargement, so
positron emission tomography (PET)/CT was obtained and revealed
enlarged PET-avid hilar lymph nodes. Bronchoscopic biopsy revealed
noncaseating granulomas. He was started on prednisone 60 mg/d for
neurosarcoidosis with improvement in his symptoms.

COMMENT This is an example of acute partial hemicord myelitis, as evidenced by the

unilateral involvement of anterolateral tract sensation loss and contralateral
corticospinal tract dysfunction (hyperreflexia). While the CSF revealed only
4 white blood cells/µL, the MRI showing contrast enhancement is supportive
of an inflammatory process. The lack of brain involvement to suggest multiple
sclerosis and the abnormal chest x-ray pointed to the possibility of an unusual
cause, namely neurosarcoidosis.

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FIGURE 1-9
MRI of hemicord syndrome in the patient in CASE 1-1. Sagittal (A) and axial (B) T2-weighted
images show a right T6-T7 lesion causing right-sided hyperreflexia and left-sided decreased
sensation to pinprick. Sagittal (C) and axial (D) postcontrast T1-weighted images demonstrate
homogeneous enhancement of the thoracic cord lesion reaching out to the meningeal surface.

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APPROACH TO MYELOPATHY
KEY POINTS
● For patients with
unilateral symptoms and
no cord lesion, consider
a brain localization.
● Unless from a clear
compressive etiology,
evaluation of acute or
subacute myelopathy
includes a lumbar puncture
and CSF analysis.
● Idiopathic transverse
myelitis generally evolves
over the space of hours.
● Some common
alternative considerations
for myelopathy are
normal-pressure
hydrocephalus and
Parkinson disease.
400
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
sensory and motor systems.33 This is accomplished clinically and via imaging,
preferably by MRI.
For acute and subacute causes of myelopathy, the finding of a normal MRI of
the clinically suspected segment should prompt consideration of alternative
causes. In particular, acute-onset peripheral neuropathies such as Guillain-Barré
syndrome and other non–length-dependent neuropathies, such as ganglionopathy,
can clinically appear similar to myelopathy. Some patients with Guillain-Barré
syndrome also experience truncal sensory symptoms, which sound similar to a
sensory level, but the patient typically does not have a sensory level on examination.
If the syndrome is exclusively unilateral, then a cerebral lesion is more likely
compared to a spinal cord lesion.
If the MRI shows a spinal cord lesion or clinical analysis confirms the
presence of a myelopathy, then the authors generally proceed to a lumbar
puncture testing at a minimum for cell count, protein, glucose, and
immunoglobulin levels/oligoclonal bands. The branch point is between myelitis
and other causes of acute myelopathy, which are primarily vascular in nature.
Proposed diagnostic criteria for idiopathic transverse myelitis developed by the
Transverse Myelitis Consortium Working Group require the onset of bilateral
signs and symptoms with a clearly defined sensory level progressing to nadir
between 4 hours and 21 days, in addition to findings of CSF inflammation
(pleocytosis, elevated IgG index) or gadolinium-enhancing lesion on MRI.34
These are proposed consensus criteria and are useful for trial classification but
sometimes prove to be too restrictive clinically. For example, myelitis can cause
a partial hemicord syndrome, and myelitis certainly does not always cause a
defined sensory level on examination. Nonetheless, this is a good starting point
clinically. TABLE 1-1 shows some causes of acute/subacute myelitis and
suggested evaluation.35,36 For many patients, such as those with multiple
sclerosis, the etiology can remain uncertain initially and emerge on follow-up
with a second neurologic event. A subset of patients with idiopathic myelitis
clearly exists. TABLE 1-2 shows other causes of acute/subacute myelopathy for
patients without evidence of inflammation (ie, no evidence to support
myelitis), many of which are from vascular causes. These can be hard to
diagnose and are often missed. As noted, while an anterior cord syndrome
often corresponds to an anterior spinal artery infarct, other clinical patterns can
also emerge depending on collateral vascular supply. Further complicating
matters, cases have also been described of pathologically proven thrombotic
injury to the spinal cord with CSF pleocytosis.37
In patients with the insidious onset of myelopathy, the list of causes is longer,
including more genetic and neurodegenerative disorders. As with acute and
subacute causes of myelopathy, the authors generally start with an MRI of the
clinically indicated segment (CASE 1-2). While many causes of chronic
myelopathy are not well shown on MRI, absence of lesions should prompt
consideration of other localization. A common consideration is normal-pressure
hydrocephalus, which can start as a hypertonic gait disorder without necessarily
having cognitive alteration or urinary urgency. Some patients with
normal-pressure hydrocephalus can have hyperreflexia in the legs and extensor
plantar responses. Extrapyramidal syndromes such as Parkinson disease with
predominant rigidity and gait disorder without tremor can also masquerade as
myelopathy. These diagnostic conundrums can be especially hard to resolve
since these disorders occur in older adults, who have a high burden of
APRIL 2018
Causes of Acute/Subacute Myelitis and Suggested Evaluation TABLE 1-1

Cause Suggestive Diagnostic Clues

Multiple sclerosis Oligoclonal bands in CSF, suggestive lesions on brain MRI, short-segment cord lesion located
peripherally, history of prior neurologic deficits

Neuromyelitis optica Neuromyelitis optica IgG in serum, lack of oligoclonal bands, long-segment lesion in spinal cord
located centrally, rostral extension into brainstem, history of optic neuritis or brainstem
syndrome

Sarcoidosis Concurrent or prior cranial neuropathy, aseptic meningitis, elevated angiotensin-converting

enzyme level in blood or CSF, persistent enhancement over 2 months or dorsal subpial pattern
of enhancement, hilar lymphadenopathy demonstrated by x-ray and often visible only on CT or
positron emission tomography (PET)/CT

Systemic lupus Positive antinuclear antibodies, anti–double-stranded DNA, anti-Smith or antiphospholipid

erythematosus antibodies in serum; decreased complement levels; history of rash, arthritis, serositis, or renal
or hematologic disorders; some cases from comorbid neuromyelitis optica but can also occur
with negative neuromyelitis optica antibody

Sjögren syndrome Many cases from comorbid neuromyelitis optica but can also occur with negative
neuromyelitis optica antibody, positive anti-Ro/La in serum, sicca syndrome with dry eyes and
dry mouth

Infectious causes
Fever at onset, associated encephalitis, associated rash, CSF white blood cell count of more
than 100 cells/µL; specific infectious studies: serum anti–treponemal antibody (followed by
CSF venereal disease research laboratory test if serum positive), human immunodeficiency
virus, and Lyme antibodies; CSF polymerase chain reaction (PCR) for herpes simplex virus
types 1 and 2, varicella-zoster virus, cytomegalovirus; CSF serology for varicella-zoster virus
(more sensitive than PCR), West Nile virus (most common arbovirus in United States), and other
viruses as indicated (including Epstein-Barr virus and human herpesvirus 6 for
immunocompromised patients); rarer causes as indicated by probable exposure history

Postvaccine History of vaccine preceding myelitis usually by 2 to 4 weeks but ranging from days to
3 months35

Postinfectious/ History of systemic infection preceding or concurrent with myelitis, often associated with
parainfectious positive serology for Mycoplasma, recently associated with Zika virus exposure

Acute disseminated Most commonly a pediatric disease, history of preceding infection or vaccine, accompanying
encephalomyelitis acute onset encephalopathy, MRI brain often with large lesions

Paraneoplastic Positive onconeural antibody often anti-amphiphysin or collapsin response mediator protein-5,
known malignancy but can precede detection, MRI with longitudinal, symmetric lesion but can
be normal36

CSF = cerebrospinal fluid; CT = computed tomography; DNA = deoxyribonucleic acid; IgG = immunoglobulin G; MRI = magnetic resonance
imaging.

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APPROACH TO MYELOPATHY
TABLE 1-2
Cause
Spinal cord infarct
Fibrocartilaginous embolism
Hematomyelia
Nitrous oxide toxicity
Decompression illness
Early delayed radiation
myelopathy
MRI = magnetic resonance imaging.
402
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radiographic cervical spondylotic disease. The authors have encountered
patients in clinical practice with Parkinson disease who underwent cervical
decompression for a question of cervical spondylotic myelopathy without
response. TABLE 1-3 shows a summary of the more common considerations for
chronic myelopathy.
CONCLUSION
Myelopathy is a clinical syndrome of spinal cord dysfunction requiring prompt
recognition and management. Initial focus should be placed on excluding
compressive lesions that can cause permanent impairment unless acted upon
quickly. Based on the timing of onset and localization within the spinal cord,
possible etiologies can be considered, but, in almost all cases, further evaluation
with neuroimaging (usually MRI) and often CSF examination will be necessary
to refine the nature and extent of the process. Because spinal cord dysfunction
can occur in the absence of macroscopic structural changes and be occult on
standard MRI, the clinician must rely on knowledge of spinal cord syndromes
and possible imaging-negative disease processes to consider and treat.
Causes of Acute/Subacute Noninflammatory Myelopathy
Suggestive Diagnostic Clues
History of aortic surgery, severe hypotension, or vascular risk factors such as hypertension,
hyperlipidemia, smoking, and diabetes mellitus; anterior cord syndrome for anterior spinal
artery and posterior cord syndrome for posterior spinal artery; on MRI, diffusion-weighted
imaging can show restricted diffusivity and subacute infarcts can show gadolinium
enhancement; note that isolated spinal cord vasculitis is very rare
Provoking history of minor trauma, exercise, or Valsalva maneuver; full syndrome can evolve
over minutes or hours; affects middle aged men and women with few vascular risk factors
History of myelopathy with onset of severe back pain, susceptibility signal on MRI, vascular
malformation on angiography if underlying arteriovenous malformation, cavernous
malformations may be visible only on MRI
Serum vitamin B12 deficiency, history of nitrous oxide exposure either recreationally or during
anesthesia for surgical procedures, clinical appearance of dorsolateral cord syndrome
History of deep diving or rapid ascent in divers and aviators within the prior 24 hours,
concomitant joint pain or rash and cognitive alteration; ataxia is common; MRI is insensitive and
generally normal
Lhermitte sign, history of radiation in prior 6 months, spontaneous improvement over months,
MRI usually normal
APRIL 2018
 A 75-year-old man presented with a 2-year history of progressive bilateral CASE 1-2
lower limb sensory changes, weakness, and gait problems. He first noted
unsteadiness while golfing 2 years prior, with progressive pain and tingling
in the bilateral lower limbs, with some
difficulty rising from a squatting
position. Prior spinal MRI had shown
multilevel degenerative changes
with some mild signal change in the
T12 cord. On examination, he had
normal upper limb strength and
sensation, with right more than left
lower limb flexor weakness; bilateral
T10 sensory level; relative hyperreflexia
in the lower limbs (1+ upper, 2+ lower)
with upgoing toes; and a spastic gait
with circumduction of the right leg.
Repeat MRI revealed longitudinally
extensive T2 signal change from T5
to L1 with patchy enhancement and
prominent dorsal flow voids
(FIGURE 1-10). Subsequent spinal
magnetic resonance angiography
showed a right T9-T10 tangle of
vessels suggestive of a spinal dural
arteriovenous fistula. He underwent FIGURE 1-10
conventional angiography with Flow voids of the patient in CASE 1-2.
Sagittal T2-weighted MRI shows
embolization with partial success,
thoracic cord T2 hyperintensity and
but ultimately required open surgical flow voids from dilated vessels in the
obliteration. subarachnoid space.

This case typifies the slowly progressive myelopathy seen as a result COMMENT
of a spinal dural arteriovenous fistula, which often goes years before diagnosis.
The venous congestion leads to variable dysfunction but often involves the
lateral cord and may be asymmetric, as in this case. When findings are not
explained by structural compression or a time course suggestive of
myelitis, noninflammatory and chronic etiologies should be considered
(TABLE 1-2 and TABLE 1-3).

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APPROACH TO MYELOPATHY

TABLE 1-3 Causes of Chronic Progressive Myelopathy

Cause Suggestive Diagnostic Clues

Multiple sclerosis Progressive forms of multiple sclerosis particularly in older adults, oligoclonal bands in CSF,
suggestive lesions on MRI of brain, short-segment cord lesion located peripherally, history of
progressive cognitive decline

Nutritional Vitamin B12 deficiency: posterolateral syndrome, macrocytic anemia, low serum vitamin B12,
elevated homocysteine and methylmalonic acid
Copper deficiency: posterolateral syndrome, exposure to excess zinc, peripheral neuropathy,
low serum copper levels
Vitamin E deficiency: spinocerebellar syndrome, retinopathy, low serum α-tocopherol levels

Toxic Exposure to IV or intrathecal methotrexate (produces posterolateral syndrome), cytarabine, and

other possible chemotherapeutic associations including cisplatin and cladribine

Spinal dural arteriovenous Usually in older men with slowly progressive myelopathy; MRI with cord T2 hyperintensity,
fistula peripheral T2 hypointensity, and perimedullary flow voids; spinal angiogram with vascular
malformation

Infectious Human immunodeficiency virus (vacuolar myelopathy appears similar to vitamin B12 deficiency),
human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy, syphilis (causes dorsal
column syndrome with peripheral neuropathy)

Neoplastic More common to have compressive lesions (meningiomas, metastases, or other mass lesions);
intramedullary tumors usually ependymoma (central cord lesion often with associated syrinx,
persistent enhancement on MRI), myxopapillary ependymoma (lumbosacral cord and filum
terminale propensity), or astrocytoma; rare to have intramedullary metastases

Motor neuron disease Selective degeneration of ventral motor neurons including amyotrophic lateral sclerosis (usually
with upper motor neuron findings and sparing bowel/bladder function), Kennedy disease (spinal
and bulbar muscular atrophy), monomelic amyotrophy

Genetic disorders
Hereditary spastic paraplegia: expanding group of disorders causing spastic paraparesis usually
with dorsal column involvement, presence of family history, evaluated by genetic sequencing
Adrenoleukodystrophy: progressive spastic paraparesis with sensory loss, adrenal insufficiency
may not be overt, elevated levels of very long chain fatty acids, ABCD1 mutation analysis
Friedreich ataxia: early prominent sensory ataxia with progressive corticospinal tract weakness
and cerebellar signs, associated with cardiomyopathy and diabetes mellitus, autosomal
recessive disorder with loss of function of frataxin protein
Spinocerebellar ataxia: autosomal dominant disorder with ataxia as core feature with other
neurologic signs and symptoms including myelopathy

Delayed radiation History of more than 45 Gy of radiation particularly with combination chemotherapy, onset
myelopathy months to years after radiation; paraparesis with sensory involvement; MRI in early phase with
T2 hyperintensity, cord swelling, and variable enhancement

CSF = cerebrospinal fluid; IV = intravenous; MRI = magnetic resonance imaging.

404 APRIL 2018

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VIDEO LEGEND
VIDEO 1-1
Beevor sign. Beevor sign arises from relative
weakness of the lower abdominal muscles
compared to the upper abdominal muscles and
is associated with thoracic cord lesions between
the T10 and T12 segments. Beevor sign is not
specific to spinal cord pathology, however, as in
this example of Beevor sign in a patient with
muscular dystrophy. In this video, a 50-year-old
man with facioscapulohumeral muscular dystrophy
lies on his back with his head to the left. When
REFERENCES
1 Power H, Sedgwick LW. The New Sydenham
Society’s lexicon of medicine and the allied
sciences, vol. 4. London, UK: The New Sydenham
Society, 1892.
2 Cho TA. Spinal cord functional anatomy.
Continuum (Minneap Minn) 2015;21(1 Spinal Cord
Disorders):13–35. doi:10.1212/01.
CON.0000461082.25876.4a.
3 Lemon RN. Descending pathways in motor
control. Annu Rev Neurosci 2008;31:195–218. doi:
10.1146/annurev.neuro.31.060407.125547.
4 Arber S. Motor circuits in action: specification,
connectivity, and function. Neuron 2012;74(6):
975–989. doi:10.1016/j.neuron.2012.05.011.
5 Standring S. editor. Spinal cord: internal
organization. In: Gray’s anatomy: the anatomical
basis of clinical practice, 40th ed, vol. 268.
London, UK: Churchill Livingstone, 2008.
6 Bucy PC, Keplinger JE, Siqueira EB. Destruction of
the “pyramidal tract” in man. J Neurosurg 1964;
21:285–298.
7 Martirosyan NL, Feuerstein JS, Theodore N, et al.
Blood supply and vascular reactivity of the spinal
cord under normal and pathological conditions.
J Neurosurg Spine 2011;15(3):238–251. doi:
10.3171/2011.4.SPINE10543.
8 Carmichael SW, Gloviczki P. Anatomy of the
blood supply to the spinal cord: the artery of
Adamkiewicz Revisited. Perspect Vasc Surg
Endovasc Ther 1999;12(1):113–122.
9 Standring S. editor. Spinal cord and spinal
nerves: gross anatomy. In: Gray’s anatomy:
the anatomical basis of clinical practice,
40th ed, vol. 758. London, UK: Churchill
Livingstone, 2008.
10 Gillilan LA. Veins of the spinal cord. Anatomic
details; suggested clinical applications.
Neurology 1970;20(9):860–868. doi:10.1212/
WNL.20.9.860.
11 Houten JK, Noce LA. Clinical correlations of
cervical myelopathy and the Hoffmann sign.
J Neurosurg Spine 2008;9(3):237–242.
CONTINUUMJOURNAL.COM
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
he lifts his head, the asymmetric involvement of his
abdominal musculature causes the umbilicus
to be pulled in the direction of the unaffected
muscles.
links.lww.com/CONT/A208
Reproduced from Statland J, Tawil R, Continuum
(Minneap Minn).13 © 2016 American Academy
of Neurology.
12 Pearce JMS. Beevor’s sign. Eur Neurol 2005;53
(4):208–209. doi:10.1159/000086731.
13 Statland J, Tawil R. Facioscapulohumeral
muscular dystrophy. Continuum (Minneap Minn)
2016;22(6 Muscle and Neuromuscular Junction
Disorders):1916–1931. doi:10.1212/con.
0000000000000399.
14 Mathys J, De Marchis GM. Teaching video
neuroimages: Beevor sign: when the umbilicus is
pointing to neurologic disease. Neurology 2013;
80(2).e20. doi:10.1212/WNL.0b013e31827b90f9.
15 American Spinal Injury Association.
International Standards for Neurological
Classification of Spinal Cord Injury.
asia-spinalinjury.org/wp-content/uploads/
2016/02/International_Stds_Diagram_
Worksheet.pdf. Accessed January 29, 2018.
16 American Spinal Injury Association (ASIA)
International Standards Committee; Kirshblum
SC, Waring W, Biering-Sorensen F, et al.
Reference for the 2011 revision of the
International Standards for Neurological
Classification of Spinal Cord Injury. J Spinal Cord
Med 2011;34(6):547–554. doi:
10.1179/107902611X13186000420242.
17 Gutrecht JA. Lhermitte’s sign. From
observation to eponym. Arch Neurol 1989;
46(5):557–558. doi:10.1001/archneur.
1989.00520410091029.
18 Wong CS, Fehlings MG, Sahgal A. Pathobiology of
radiation myelopathy and strategies to mitigate
injury. Spinal Cord 2015;53(8):574–580. doi:
10.1038/sc.2015.43.
19 Novy J, Carruzzo A, Maeder P, Bogousslavsky J.
Spinal cord ischemia: clinical and imaging
patterns, pathogenesis, and outcomes in
27 patients. Arch Neurol 2006;63(8): 1113–1120.
20 Huang PP, Chin R, Song S, Lasoff S. Lower motor
neuron dysfunction associated with human
immunodeficiency virus infection. Arch Neurol
1993;50(12):1328–1330. doi:10.1001/
archneur.1993.00540120041011.
405
APPROACH TO MYELOPATHY
21 Mochel F, Schiffmann R, Steenweg ME, et al.
Adult polyglucosan body disease: natural history
and key magnetic resonance imaging findings.
Ann Neurol 2012;72(3):433–441. doi:10.1002/
ana.23598.
22 Taber KH, Herrick RC, Weathers SW, et al.Pitfalls
and artifacts encountered in clinical MR imaging
of the spine. Radiographics 1998;18(6):1499–1521.
doi:10.1148/radiographics.18.6.9821197.
23 Krupa K, Bekiesińska-Figatowska M. Artifacts in
magnetic resonance imaging. Pol J Radiol 2015;
80:93–106. doi:10.12659/PJR.892628.
24 Martin N, Malfair D, Zhao Y, et al. Comparison of
MERGE and axial T2-weighted fast spin-echo
sequences for detection of multiple sclerosis
lesions in the cervical spinal cord. AJR Am J
Roentgenol 2012;199(1):157–162. doi:10.2214/
AJR.11.7039.
25 Tavee JO, Levin KH. Myelopathy due to
degenerative and structural spine diseases.
Continuum (Minneap Minn) 2015;21(1 Spinal Cord
Disorders):52–66. doi:10.1212/01.
CON.0000461084.71618.35.
26 Matsumoto M, Toyama Y, Ishikawa M, et al.
Increased signal intensity of the spinal cord on
magnetic resonance images in cervical
compressive myelopathy. Does it predict the
outcome of conservative treatment? Spine
(Phila Pa 1976)2000;25(6):677–682.
27 Kadanka Z, Mares M, Bednarík J, et al. Predictive
factors for mild forms of spondylotic cervical
myelopathy treated conservatively or
surgically. Eur J Neurol 2005;12(1):16–24.
doi:10.1111/j.1468-1331.2004.00947.x.
28 Whittam D, Bhojak M, Das K, Jacob A.
Longitudinally extensive myelitis in MS
mimicking neuromyelitis optica. Neurol
Neuroimmunol Neuroinflamm 2017;4(3):e333.
doi:10.1212/NXI.0000000000000333.
406
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
29 Lee SS, Kim MK, Sym SJ, et al. Intramedullary
spinal cord metastases: a single-institution
experience. J Neurooncol 2007;84(1):85–89.
30 Flanagan EP, Krecke KN, Marsh RW, et al.
Specific pattern of gadolinium enhancement in
spondylotic myelopathy. Ann Neurol 2014;76(1):
54–65. doi:10.1002/ana.24184.
31 Bourre B, Zéphir H, Ongagna JC, et al. Long-term
follow-up of acute partial transverse myelitis.
Arch Neurol 2012;69(3):357–362. doi:10.1001/
archneurol.2011.949.
32 Flanagan EP, Kaufmann TJ, Krecke KN, et al.
Discriminating long myelitis of neuromyelitis
optica from sarcoidosis. Ann Neurol 2016;79(3):
437–447. doi:10.1002/ana.24582.
33 Shedid D, Benzel EC. Cervical spondylosis
anatomy: pathophysiology and biomechanics.
Neurosurgery 2007;60(1 supp1 1):S7–S13. doi:
10.1227/01.NEU.0000215430.86569.C4.
34 Transverse Myelitis Consortium Working Group.
Proposed diagnostic criteria and nosology of acute
transverse myelitis. Neurology 2002;59(4):499–505.
35 Sandson TA, Friedman JH. Spinal cord infarction.
Report of 8 cases and review of the literature.
Medicine (Baltimore) 1989;68(5):282–292.
36 Agmon-Levin N, Kivity S, Szyper-Kravitz M,
Shoenfeld Y. Transverse myelitis and vaccines: a
multi-analysis. Lupus 2009;18(13):1198–1204. doi:
10.1177/0961203309345730.
37 Flanagan EP, McKeon A, Lennon VA, et al.
Paraneoplastic isolated myelopathy: clinical
course and neuroimaging clues. Neurology 2011;
76(24):2089–2095. doi:10.1212/WNL.0b013e31821f468f.
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