Review Article

Treatment of Acute
Address correspondence
to Dr Benjamin M.
Greenberg, University of
Texas Southwestern,

Transverse Myelitis and Department of Neurology,

5323 Harry Hines Blvd,
Dallas, Texas 75390,

Its Early Complications benjamin.greenberg@

utsouthwestern.edu.
Relationship Disclosure:
Dr Greenberg has
Benjamin M. Greenberg, MD, MHS received honoraria from
EMD Serono, Inc., the
Multiple Sclerosis
Association of America,
ABSTRACT and Teva Neuroscience
Acute transverse myelitis (ATM) has many potential etiologies, but a significant pro- and has consulted for
portion of cases are categorized as idiopathic despite thorough evaluation. Clinical DioGenix, Inc., The
Greater Good Foundation,
presentation of ATM typically includes some combination of motor weakness, sensory and Sanofi-Aventis.
symptoms, and bowel and bladder dysfunction. Prompt recognition, even before a Dr Greenberg receives
final etiologic diagnosis is reached, is critical to initiating early therapeutic intervention equity from DioGenix,
Inc. and grant support
to reduce the harmful effects of inflammation. Acute therapeutic options for ATM from Accelerated
include corticosteroids, plasma exchange, IV immunoglobulin, and chemotherapeutic Cure Project for
agents such as cyclophosphamide. In some instances, combinations of these therapies Multiple Sclerosis and
Guthy-Jackson Charitable
are used. This article examines the therapeutic approach to ATM and its various acute Foundation.
clinical manifestations. Unlabeled Use of
Products/Investigational
Use Disclosure:
Continuum Lifelong Learning Neurol 2011;17(4):733–743.
Dr Greenberg discusses
the unlabeled use of
plasma exchange and
cyclophosphamide in
INTRODUCTION optica (NMO), lupus, or sarcoidosis. transverse myelitis.
The lexicon applied to inflammatory Often, patients and physicians apply the Copyright B 2011,
American Academy of
events within the spinal cord is confusing diagnosis of TM as shorthand for idio- Neurology. All rights
and prone to inaccuracies. Transverse pathic TM, which has led to some reserved.
myelitis (TM) refers to inflammation of confusion within the literature.
the spinal cord, and acute transverse ATM is a medical emergency. Be-
myelitis (ATM) refers to progressive cause clinical deficits can evolve over
inflammation of the spinal cord over hours, therapeutic intervention is
hours or days. No data exist, however, needed to prevent disease progression
to differentiate clinically or biologically and hasten recovery. Before therapies
between TM that develops over 24 hours can be initiated for ATM, the clinical
and TM that develops over 28 days. The manifestations of a myelopathy must
term ‘‘ATM’’ thus includes cases of TM be recognized. Patients with spinal cord
that develop over minutes, hours, days, dysfunction can present with unusual
or even weeks. Defining the event as sensory symptoms or isolated bladder
acute is intended to differentiate the retention. Numerous patients have
syndrome from conditions that cause been discharged from emergency de-
chronic, usually progressive, myelopa- partments with a diagnosis of a urinary
thies that evolve over many months or tract infection after a liter of urine
years. Furthermore, TM can be second- was drained during urinary catheter
ary to systemic conditions or an idio- placement only to return a day later
pathic event without an identifiable paralyzed. With numerous therapeutic
cause. Consequently, some patients with options available, neurologists should
TM will ultimately be diagnosed with educate themselves and their col-
multiple sclerosis (MS), neuromyelitis leagues about the various possible

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 Acute Treatment
presentations of myelopathy so that
prompt recognition leads to prompt
treatment and improved outcomes.
Recognizing the various symptoms of
a myelopathy is the first step. The most
common symptoms include numbness,
weakness, and bladder dysfunction that
develop over hours or days. Once this
syndrome is recognized, the next step is
to determine the cause of spinal cord
dysfunction. Diagnostic approaches to
TM focus on differentiating inflamma-
tory from non-inflammatory disorders of
the spinal cord,1 but the diagnostic cri-
teria for immune-mediated pathologies
lack sensitivity and specificity values be-
cause no comparative standard exists.
Once a compressive lesion has been
ruled out for a patient with myelopathy,
several features can suggest inflamma-
tion. Ultimately, clinical judgment must
be used. In many cases, especially cases
in which the diagnostic evaluation of a
patient is delayed (Figure 1-1), therapy
should be applied empirically. This ar-
FIGURE 1-1 Algorithm for the evaluation of patients with myelopathy. PLEX = plasma exchange.
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ticle reviews these therapeutic options
and how they can be applied to various
patient scenarios.
BIOLOGY OF TRANSVERSE
MYELITIS
No single pathobiological process ex-
plains all cases of TM. Because some
patients have idiopathic TM and some
have TM secondary to systemic condi-
tions (eg, MS, NMO, etc.), there are
distinct pathways that lead to demyelin-
ation, axonal damage, and even anterior
horn cell death. While CSF interleukin
(IL)-6 levels are intricately involved in
idiopathic TM and TM secondary to
NMO, they are remarkably lower in
patients with TM secondary to MS.2,3
Some patients, especially children, have
more significant involvement of ante-
rior horn cells, whereas most adult pa-
tients have pure upper motor neuron
syndromes. In all cases, ATM involves in-
appropriate inflammation within the
spinal cord. Lymphocytes, neutrophils,
August 2011
eosinophils, antibodies, or complement
deposition are involved in every patient
to varying degrees. Therapies for ATM
are directed at inhibiting the inflamma-
tory cascade and giving a patient’s spinal
cord a chance to repair and recover. To
date, no proven interventions will pro-
tect myelin or axons from inflammatory
insults. Thus, the goal of therapy is to
limit damage as quickly as possible.
TM symptoms are mediated by three
levels of pathology (Figure 1-2). First, in-
flammatory infiltrates secrete cytokines
that cause dysfunction within the ner-
vous system. For example, IL-2 has been
shown to cause edema in the spinal cord,
which can create symptoms but not ir-
reversible spinal cord damage.4 Symp-
toms from this process recover quickly
during acute therapy because the cells
are preserved. Second, TM causes de-
myelination that leads to inhibition of
signal propagation and thus neurologic
deficits. These symptoms recover after
inflammation abates and the body is
able to produce new myelin.5,6 Third,
TM can cause axonal damage that com-
pletely interrupts signal transmission. Ir-
reversible injury in TM is likely corre-
lated with the degree of axonal injury, as
seen in animal models of demyelinating
disease.7,8 Little evidence exists to sug-
gest that axons within the CNS can re-
grow and form functionally appropriate
new connections. However, symptoms
from axonal damage improve when the
nervous system develops compensatory
mechanisms. For example, if damage to
the lateral corticospinal tract leads to
weakness of a limb, the anterior cortical
spinal tract can transmit signals that re-
sult in a regain of function over time.9
Multiple cytokines have been impli-
cated in TM, including IL-6 and IL-17. One
study correlated IL-6 levels within the CSF
with functional outcomes of patients and
demonstrated that IL-6 modulated spinal
cord injury in vitro.2 IL-6 production by
astrocytes in patients with TM may be
augmented by peripheral production of

FIGURE 1-2 Multiple pathologic processes lead to clinical symptoms in transverse myelitis.
Reprinted with permission from Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions
of multiple sclerosis. N Engl J Med 1998;338(5):278Y285. Copyright B 1998, Massachusetts Medical Society.

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 Acute Treatment

IL-17.10 Thus, therapeutic interventions as soon as possible after the syndrome

in TM should blunt the activation of
the immune system, limiting cellular
infiltration and spinal cord damage.
THERAPEUTIC OPTIONS FOR
ACUTE TRANSVERSE MYELITIS
Consensus guidelines about ATM ther-
apy have been difficult to develop be-
cause no randomized, double-blind,
controlled treatment trials specifically
focusing on ATM have been reported.
Despite this, a growing body of liter-
ature and experience supports the use
of various treatment options. These
treatment options should be initiated
has been recognized.
Corticosteroids
Numerous case reports and case series
have reported that corticosteroids benefit
patients with TM (Case 1-1).11Y14 Sup-
pression of cytokine production, apo-
ptosis of autoreactive lymphocytes, and
reduction of edema have all been re-
ported.15Y17 Study designs in analogous
clinical situations, such as with inflam-
matory optic neuritis, are instructive for
the therapeutic approach to TM, de-
spite the lack of randomized controlled
clinical trials.

Case 1-1
A 42-year-old woman with no significant past medical history presented to
her primary care physician with 6 days of ascending numbness that began
in her legs and moved up to her waist. She denied changes in bladder
function or walking. Physical examination revealed normal strength and
sensation in the upper extremities. The lower extremities had normal
strength but reduced pain and temperature up to a T10 spinal level. She
was admitted to the hospital, and an emergent spinal cord MRI revealed a
lesion at the T8 vertebral level that enhanced after the administration of
gadolinium. Brain MRI showed numerous nonenhancing T2-weighted
hyperintense lesions scattered throughout the cerebral white matter. A
lumbar puncture revealed eight white blood cells, all of which were
lymphocytes; normal protein and glucose; an elevated immunoglobulin G
index; and positive oligoclonal bands. She was diagnosed as having acute
‘‘partial’’ transverse myelitis with high risk for future development of
confirmed multiple sclerosis (a ‘‘clinically isolated syndrome’’). She was
treated with 1 g of IV methylprednisolone daily for 5 days and was then
placed on an oral 14-day prednisone taper. She improved symptomatically
but continued to have intermittent paresthesia. She met with a
neurologist who explained her relatively high risk of a second clinical or
radiographic event that would confirm a diagnosis of multiple sclerosis.
She elected to initiate immunomodulatory therapy with interferon
beta-1a 3 times a week and did well for the next 3 years.
Comment. This case describes a rather typical case of ‘‘partial’’ transverse
myelitis (meaning that the pathology affects only a part of the transverse
axis of the cord) presenting with isolated sensory changes. Clinically, this
example represents one of the mildest deficits that can occur in transverse
myelitis. Treatment with high-dose IV corticosteroids, often followed by an
oral tapering dose, is usually recommended, although randomized controlled
trials of this strategy for transverse myelitis are lacking. While motor
impairments from transverse myelitis tend to improve after appropriate
therapy, perceived improvement in sensory symptoms is often variable.

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The largest controlled trial of cortico-
steroids in demyelinating disease was
the Optic Neuritis Treatment Trial
(ONTT). In this trial, 457 patients with
optic neuritis were randomly assigned
to one of three treatment arms: IV meth-
ylprednisolone (1 g daily for 3 days)
followed by an 11-day oral steroid
course, oral prednisone (1 mg/kg daily
for 14 days), or oral placebo for 11
days.18 Subjects in each of the treat-
ment arms then underwent an identi-
cal 4-day oral medication taper. The
study was not blinded to route of drug
administration. Outcomes were mea-
sured over 6 months and included
visual acuity, visual field testing, con-
trast vision, color vision, and number
of subsequent demyelinating events.
The results determined that the IV
methylprednisolone treatment arm
had faster clinical recovery and better
visual field results, contrast vision, and
color vision compared with the placebo
arm at 6 months. Patients in the oral
prednisone and placebo arms recov-
ered visual acuity but at a slower rate.
The more sensitive tests for irreversible
axonal damage (visual fields, contrast
sensitivity, and color vision) supported
the use of IV steroids over oral steroids
or no treatment (placebo).18 Although
higher rates of subsequent demyelinat-
ing events were observed in patients
treated with oral prednisone when
compared with the placebo arm (rela-
tive risk 1.79, 95% CI 1.08Y2.95),
continued follow-up of the ONTT
cohort showed that this effect was no
longer detectable.
The active treatment arms of the
ONTT differed in three respects. First,
the administered dose of steroid was
substantially higher in the IV treatment
arm than the oral-only arm. Second, the
route of administration differed for the
first 3 days of treatment. Third, the ad-
ministered steroid differed (methyl-
prednisolone followed by prednisone
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KEY POINT
versus prednisone alone). Because pred- h The Optic Neuritis
nisone and methylprednisolone work Treatment Trial provided
on the same steroid receptor and the excellent evidence that
bioavailability of oral and IV steroids acute attacks of
is the same, the primary difference be- demyelination should be
tween the active treatment arms in the treated with high-dose
ONTT was the dose of steroid used.19 corticosteroids and not
Thus, the ONTT provided excellent evi- low-dose regimens.
dence that acute attacks of demyelin-
ation should be treated with high-dose
corticosteroids rather than low-dose
regimens. Furthermore, a Cochrane Re-
view of therapies for acute exacerba-
tions of MS determined that high-dose
corticosteroids were effective.20
Short-term dosing for acute inflam-
mation carries relatively few risks, but
they should be recognized. Patients
commonly have elevations in blood
glucose, CSF glucose, and blood pres-
sure. Also, patients frequently have
dyspepsia, changes in mood ( both
euphoria and depression), insomnia,
changes in appetite, and, rarely, psy-
chosis. More significant risks include
avascular necrosis or infections, but
these are exceedingly rare. Because
data suggest a role for adjuvant steroid
therapy in bacterial and viral infections
of the CNS, the benefits of empiric
therapy in possible TM outweigh the
risks of dosing an infected patient with
steroids.21,22 Also, because infectious
TM is so rare, clinicians should not feel
obligated to wait for the results of in-
fection workups before dosing ste-
roids. Individual patient characteristics
should be taken into account when mak-
ing these decisions.
IV Immunoglobulin
IV immunoglobulin (IVIg) has been
used in ATM because of its ease of
administration and the literature estab-
lishing its benefit for other neuroinflam-
matory disorders such as Guillain-Barré
syndrome, but no controlled trials of its
use in ATM have been reported. Pub-
lished case series have reported clinical
www.aan.com/continuum 737
 Acute Treatment

KEY POINT
h In a double-blind, sham
treatmentYcontrolled
trial of plasma
exchange in CNS
demyelinating disease,
plasma exchange was
found to have
statistically significant
benefits in terms of
outcome.
improvements in ATM after IVIg ther-
apy.23 In one study of patients with
acute disseminated encephalomyelitis,
only half of the patients treated with
IVIg had a response.24 Of note, this
study initially involved a few patients
with isolated TM, but these patients
were not transitioned to IVIg therapy
because they all had good responses
to corticosteroids.25
One prospective randomized con-
trolled trial of patients with myelitis in
the setting of atopic conditions in Japan
revealed that IVIg lacked efficacy com-
pared with other treatment regimens,
including steroids, plasma exchange
(PLEX), or combination therapies.26
While the underlying atopy could have
affected these results, the data suggest
that IVIg may be inferior to other treat-
ment options in the setting of TM.
The continued use of IVIg is likely
the result of its ease of administration,
safety profile, and high tolerability. A
total of 2 g/kg body weight is usually
administered in five equal consecutive
daily doses. Potential adverse events in-
clude headache, rash, allergic reaction,
anaphylaxis, transmission of blood-
borne pathogens, and nephrotoxicity.
IVIg can also cause an aseptic meningi-
tis syndrome.27 CSF pleocytosis de-
tected on lumbar puncture performed
after IVIg administration can be diffi-
cult to interpret in this setting.
Plasma Exchange or
Plasmapheresis
Therapeutic cleansing of plasma oc-
curs via a variety of processes whose no-
menclature can be confusing. The terms
plasmapheresis and plasma exchange
(PLEX) are often used interchangeably
but are distinctly different procedures.
Apheresis is a process by which blood is
removed from a patient, a portion is sepa-
rated and retained, and the remainder is
transfused back to the patient. Plasma-
pheresis refers to a procedure in which
the plasma is separated from the blood
either by centrifugation or membrane
filtration. PLEX takes plasmapheresis
one step further, separating plasma from
whole blood and infusing a replacement
fluid in equal volume to the plasma that
was removed. This replacement fluid
can be 5% albumin, a mixture of al-
bumin and saline, cryoprecipitate-
poor plasma, or fresh frozen plasma.
With PLEX treatments, red blood cells,
white blood cells, and platelets are re-
turned to the patient along with replace-
ment fluid.
Plasmapheresis and PLEX are thought
to reduce the level of circulating pro-
teins such as antibodies and immune
complexes, thereby reducing inflamma-
tion. Clinical symptoms do not always
correlate with antibody titers, how-
ever,28,29 and the therapeutic benefits
of PLEX are probably also mediated by
antibody-independent mechanisms.
No randomized controlled trials of
PLEX specifically for TM have been re-
ported. In a double-blind, sham treatmentY
controlled trial of PLEX in CNS demye-
linating disease, 22 patients refractory
to steroids were randomized to PLEX
or sham therapy in a crossover design.
PLEX was found to have statistically sig-
nificant outcome benefits.30 A large-
scale retrospective analysis of patients
with TM documented a selective benefit
of PLEX combined with corticosteroid
treatment over isolated corticosteroid
therapy.13 Although this was an uncon-
trolled retrospective analysis, it quanti-
fied the experience seen in a large TM
treatment referral center. For patients
with TM, the evidence substantiating the
usefulness of PLEX therapy is increasing
(Case 1-2).
The most common complications
from PLEX include line-associated
infections, hypotension, allergic reac-
tion, hypocalcemia, and coagulopathy.
Most adverse events are mild or mod-
erate. In one retrospective analysis,

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 KEY POINT

Case 1-2 h In patients with

transverse myelitis
A 26-year-old previously healthy man presented to an emergency
secondary to systemic
department with 3 days of progressive numbness and weakness in his arms
lupus erythematosus
and legs. He reported waking a few days prior with numbness in his legs
or Sjögren syndrome,
that progressed to his arms throughout the day. He noted that the next
cyclophosphamide can
morning he perceived some changes in his walking and difficulty emptying
have an independent
his bladder. On the day of admission, he had significant weakness in his
benefit beyond steroids
legs and arms and required assistance getting into and out of his car.
or plasma exchange.
On examination, he had loss of pain and temperature in his legs and
arms, moderately reduced strength in all lower extremity muscle groups,
and 4-/5 power in the wrists, fingers, and triceps. He was unable to walk.
One liter of urine was drained from his bladder after urinary catheter
insertion. An emergent MRI revealed a lower cervical cord T2 hyperintense
lesion that enhanced after the administration of gadolinium. Brain MRI
was normal. CSF studies revealed 35 white blood cells (87% lymphocytes),
an elevated protein at 62 mg/dL, a negative immunoglobulin G (IgG)
index, and negative oligoclonal bands. Serologic studies, including
antinuclear antigen, neuromyelitis optica IgG, anti-SSA, anti-SSB, and rapid
plasma reagin, were negative. Serum vitamin B12 and copper levels were
normal. Chest CT was normal and without any evidence of mediastinal
adenopathy.
He was started on IV methylprednisolone for 5 days and showed limited
improvement. Plasma exchange (PLEX) was initiated, and by the fourth
exchange he noted improved strength. After the fifth exchange was
completed, he transitioned to inpatient rehabilitation and had complete
return of walking capabilities. Six months after discharge he had normal
motor and bladder functions but continued reduction in sensation
capability.
Comment. This patient experienced a typical idiopathic transverse
myelitis with motor impairment. Patients in this category may derive
benefit from PLEX beyond the effects of steroids. Significant data exist to
support the use of PLEX in patients with motor deficits, especially patients
not responding to steroids.

severe complications occurred in less medication with antiemetics, and use

than 1% of patients.31
Cyclophosphamide
Cyclophosphamide is a prodrug that acts
as an alkylating agent and is metabolized
to its active form in cells with low levels
of aldehyde dehydrogenase. It was orig-
inally created as an antineoplastic agent
but has been used extensively for auto-
immune conditions. In the setting of
acute inflammation, it is typically ad-
ministered as a single pulse dose of
1000 mg/m2 body surface area. Typical
protocols involve prehydration, pre-
of mesna to prevent bladder wall tox-
icity. Adverse events and complications
can include nausea, hair loss, anemia,
hemorrhagic cystitis, and infection.
Literature analyzing the use of cyclo-
phosphamide in the setting of TM is
relatively limited, but there are some
indications with supportive evidence
of efficacy. Specifically, in patients
with TM secondary to systemic lupus
erythematosus or Sjögren syndrome,
cyclophosphamide can have an inde-
pendent benefit beyond steroids or
PLEX (Case 1-3).13,32Y34

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 Acute Treatment

Case 1-3
A 31-year-old woman presented with 2 days of back pain and 6 hours of
progressive weakness and numbness. She was healthy until she developed pain
in her midback on the day prior to admission. She denied any trauma. On the
morning of presentation, she awoke with numbness below the midthoracic
region, and by midday she had difficulty walking. Upon arrival in the emergency
department, she was unable to move either of her legs. She reported a history
of Raynaud phenomenon, joint pain, and a rash on her face that occurred
with exposure to sunlight. Laboratory studies detected proteinuria, positive
serum antinuclear antigen with a homogenous staining pattern (titer 1:1280),
and positive double-stranded DNA antibodies. An emergent spinal MRI
revealed an edematous thoracic cord with T2 signal changes from T6 to T10
and enhancement after gadolinium administration. She was diagnosed
with transverse myelitis secondary to systemic lupus erythematosus (SLE).
Treatment included high-dose IV steroids, with no significant
improvement after five doses. She was then given cyclophosphamide at a
dose of 1000 mg/m2. She steadily improved over 4 weeks and by 3 months
she was walking with a cane.
Comment. This case illustrates the unique biology of lupus-mediated
transverse myelitis. In patients with previously diagnosed SLE or a history
highly suggestive of SLE, consideration should be given for early
intervention with cyclophosphamide.

TREATMENT OF PEDIATRIC to the other, but PLEX should be con-

TRANSVERSE MYELITIS
No prospective studies of pediatric TM
have been reported in the literature.
Case reports, case series, and retrospec-
tive analyses have yielded variable in-
sights and are difficult to compare. Most
of the published studies suggest benefit
of IV steroids, IVIg therapy, or both.35
Most pediatric patients are treated with
a regimen such as 30 mg/kg of IV meth-
ylprednisolone daily for 5 days followed
by an oral prednisone taper. Some
data suggest that early diagnosis may
improve outcomes, presumably via ear-
lier intervention.36 A series of 10 pediat-
ric patients with TM treated with PLEX
at Children’s Hospital in Dallas showed
no complications or clinically significant
adverse events (unpublished data), and
many pediatric patients who failed to
respond to IVIg but had clinical im-
provements after PLEX have been re-
ported.37 Controlled trials of PLEX
versus IVIg are still needed to deter-
mine whether one therapy is superior
sidered in all pediatric patients with
TM if the deficits are profound enough.
MANAGING EARLY
COMPLICATIONS OF
TRANSVERSE MYELITIS
While the initial focus for patients
presenting with myelopathy should be
an accurate diagnosis and early thera-
peutic intervention to limit damage,
neurologists should remain vigilant for
complications that can occur in the set-
ting of ATM (Case 1-4).
Deep Vein Thrombosis and
Pulmonary Embolism
No prospective data are available to re-
liably estimate the rates of deep vein
thrombosis (DVT) or pulmonary embo-
lism in patients with TM. Most of the
literature and treatment guidelines fo-
cus on patients with traumatic spinal
cord injury, as these patients probably
have a higher risk of DVT formation
than patients with TM. Still, for patients

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 KEY POINTS

Case 1-4 h A high level of suspicion

for deep vein
A 28-year-old man was admitted to the hospital with a 3-day history of
thrombosis should be
progressive numbness and weakness in his legs and urinary retention. Over
maintained in all
the first 6 hours of his admission, he progressed to complete flaccid
patients with transverse
paralysis with a T4 sensory level. An MRI of the spinal cord revealed a
myelitis, and prompt
longitudinally extensive T2 hyperintense lesion from T5 to T9 with central
therapy should be
gadolinium enhancement, and his CSF showed a lymphocytic pleocytosis.
initiated if a venous clot
He was initially treated with IV methylprednisolone at a dose of 1 g/d.
is identified.
On day 3 of his admission, the on-call physician was notified about
bradycardia. The patient’s pulse was 40 beats/min. His blood pressure was h Maneuvers that induce
76/42 mm Hg, and he was diaphoretic. He denied any pain but said he felt bradycardia usually
‘‘ill.’’ While being evaluated by the medical staff, the patient developed elicit a sympathetic
asystole. Advanced cardiac life support measures were initiated, but the response that maintains
patient could not be revived. heart rate and blood
Comment. This case illustrates that patients with acute spinal cord pressure. After a spinal
changes (regardless of etiology) may have rapid decline in clinical status. cord injury, these
The differential diagnosis for a patient with myelopathy with reflexes can be blunted,
cardiovascular instability is dependent on the size, location, and severity which can lead to
of the spinal cord lesion. Patients with severe spinal cord damage are cardiovascular instability.
at risk for pulmonary emboli, infections, and autonomic dysreflexia.
Developing a prevention strategy for patients with transverse myelitis is
critical for avoiding life-threatening complications.

with severe motor deficits limiting mobil-
ity, prophylaxis with compression stock-
ings, sequential compression devices,
low-molecular-weight heparin, or un-
fractionated heparin is indicated.38 A
high level of suspicion for DVT should
be maintained in all patients with TM,
and prompt therapy should be initiated
if a venous clot is identified. Anticoagu-
lation therapy should be continued for
6 to 12 months.39
Autonomic Instability
Based on the location of the lesion, pa-
tients with TM may be at risk for dys-
rhythmias, orthostatic hypotension,
and autonomic dysreflexia. Even in
patients with high cervical lesions, para-
sympathetic input to the heart is main-
tained by brainstem nuclei. Maneuvers
that induce bradycardia usually elicit a
sympathetic response that maintains
heart rate and blood pressure. After a
spinal cord injury, however, these re-
flexes can be blunted, which can lead
to cardiovascular instability. For exam-
ple, in patients with cervical spine in-
juries, tracheal suctioning can lead to
bradycardia that may not be effectively
countered by a sympathetic response.
In patients with high thoracic lesions,
procedures or noxious stimuli below
the level of the lesion can lead to in-
stability. These stimuli include consti-
pation, tissue injury (wounds), urinary
catheter manipulation, urinary reten-
tion, and physical examinations. Pa-
tients with autonomic dysreflexia may
experience headaches, sweating, chills,
and tingling.
Some patients with high thoracic
or cervical cord lesions experience or-
thostatic hypotension that may limit
participation in rehabilitation. While try-
ing to regain mobility, patients can be
limited by fluctuations in upright blood
pressure. Severe orthostatic hypoten-
sion can be combated by maintaining
adequate hydration, using compres-
sion stockings, augmenting salt intake,
and administering medications such
as fludrocortisone or midodrine.

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 Acute Treatment
CONCLUSIONS
ATM presents a variety of challenges to
cliniciansVit is rare, may evolve rapidly,
and requires rapid diagnostic evaluation
and emergent therapeutic intervention.
Additionally, life-threatening complica-
tions can arise during the early evolution
of the syndrome. While corticosteroids
remain the mainstay of acute therapy,
data support the use of PLEX or cyclo-
phosphamide in select patient popula-
tions. Controlled trials of these therapies
are needed to improve current treatment
algorithms.
REFERENCES
1. Krishnan C, Kaplin AI, Deshpande DM, et al.
Transverse myelitis: pathogenesis, diagnosis
and treatment. Front Biosci 2004;9:
1483Y1499.
2. Kaplin AI, Deshpande DM, Scott E, et al. IL-6
induces regionally selective spinal cord injury
in patients with the neuroinflammatory
disorder transverse myelitis. J Clin Invest
2005;115(10):2731Y2741.
3. Içöz S, Tüzün E, Kürtüncü M, et al. Enhanced
IL-6 production in aquaporin-4 antibody
positive neuromyelitis optica patients. Int J
Neurosci 2010;120(1):71Y75.
4. Segal JL. Immunoactivation and altered
intercellular communication mediate the
pathophysiology of spinal cord injury.
Pharmacotherapy 2005;25(2):145Y156.
5. Rodriguez M, Miller DJ, Lennon VA.
Immunoglobulins reactive with myelin basic
protein promote CNS remyelination.
Neurology 1996;46(2):538Y545.
6. van Engelen BG, Pavelko KD, Rodriguez M.
Enhancement of central nervous system
remyelination in immune and non-immune
experimental models of demyelination. Mult
Scler 1997;3(2):76Y79.
7. Papadopoulos D, Pham-Dinh D, Reynolds R.
Axon loss is responsible for chronic
neurological deficit following inflammatory
demyelination in the rat. Exp Neurol 2006;
197(2):373Y385.
8. Ure DR, Rodriguez M. Preservation of
neurologic function during inflammatory
demyelination correlates with axon sparing in a
mouse model of multiple sclerosis. Neuroscience
2002;111(2):399Y411.
9. Caramia MD, Palmieri MG, Giacomini P, et al.
Ipsilateral activation of the unaffected motor
742 www.aan.com/continuum
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
cortex in patients with hemiparetic stroke.
Clin Neurophysiol 2000;111(11):1990Y1996.
10. Graber JJ, Allie SR, Mullen KM, et al.
Interleukin-17 in transverse myelitis and
multiple sclerosis. J Neuroimmunol 2008;
196(1Y2):124Y132.
11. Caldas C, Bernicker E, Nogare AD,
Luby JP. Case report: transverse myelitis
associated with Epstein-Barr virus infection.
Am J Med Sci. 1994;307(1):45Y48.
12. Chang CM, Ng HK, Chan YW, et al.
Postinfectious myelitis, encephalitis and
encephalomyelitis. Clin Exp Neurol 1992;29:
250Y262.
13. Greenberg BM, Thomas KP, Krishnan C, et al.
Idiopathic transverse myelitis: corticosteroids,
plasma exchange, or cyclophosphamide.
Neurology 2007;68(19):1614Y1617.
14. Defresne P, Meyer L, Tardieu M, et al.
Efficacy of high dose steroid therapy in
children with severe acute transverse
myelitis. J Neurol Neurosurg Psychiatry 2001;
71(2):272Y274.
15. Morand EF. Corticosteroids in the treatment
of rheumatologic diseases. Curr Opin
Rheumatol 2000;12(3):171Y177.
16. Quante T, Ng YC, Ramsay EE, et al. Am J
Respir Cell Mol Biol. 2008;39(2):208Y217.
17. Rogala B. [Mechanism of action for
corticosteroids]. Wiad Lek 1998;51(suppl 1):
28Y32.
18. Beck RW, Cleary PA, Anderson MM Jr, et al.
A randomized, controlled trial of
corticosteroids in the treatment of acute
optic neuritis. The Optic Neuritis Study
Group. N Engl J Med 1992;326(9):581Y588.
19. Morrow SA, Stoian CA, Dmitrovic J, et al.
The bioavailability of IV methylprednisolone
and oral prednisone in multiple sclerosis.
Neurology 2004;63(6):1079Y1080.
20. Filippini G, Brusaferri F, Sibley WA, et al.
Corticosteroids or ACTH for acute
exacerbations in multiple sclerosis. Cochrane
Database Syst Rev 2000(4):CD001331.
21. Santee JA. Corticosteroids for herpes zoster:
what do they accomplish? Am J Clin
Dermatol 2002;3(8):517Y524.
22. Tunkel AR, Hartman BJ, Kaplan SL, et al.
Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis
2004;39(9):1267Y1284.
23. Marchioni E, Marinou-Aktipi K,
Uggetti C, et al. Effectiveness of intravenous
immunoglobulin treatment in adult patients
with steroid-resistant monophasic or
recurrent acute disseminated
August 2011
 encephalomyelitis. J Neurol 2002;249(1):
100Y104.
24. Ravaglia S, Piccolo G, Ceroni M, et al.
Severe steroid-resistant post-infectious
encephalomyelitis: general features and effects
of IVIg. J Neurol 2007;254(11):1518Y1523.
25. Marchioni E, Ravaglia S, Piccolo G, et al.
Postinfectious inflammatory disorders:
subgroups based on prospective follow-up.
Neurology 2005;65(7):1057Y1065.
26. Murai H, Arahata H, Osoegawa M, et al.
Effect of immunotherapy in myelitis with
atopic diathesis. J Neurol Sci 2004;227(1):
39Y47.
27. Mathy I, Gille M, Van Raemdonck F, et al.
Neurological complications of intravenous
immunoglobulin (IVIg) therapy: an illustrative
case of acute encephalopathy following IVIg
therapy and a review of the literature. Acta
Neurol Belg 1998;98(4):347Y351.
28. Hinson SR, McKeon A, Fryer JP, et al.
Prediction of neuromyelitis optica attack
severity by quantitation of
complement-mediated injury to
aquaporin-4-expressing cells. Arch Neurol.
2009;66(9):1164Y1167.
29. Sakuraba M, Onuki T, Nitta S. Measurement
of antiacetylcholine receptor antibody in
patients with thymoma without myasthenia
gravis complications. Jpn J Thorac Cardiovasc
Surg 2001;49(12):690Y692.
30. Weinshenker BG, O’Brien PC, Petterson TM,
et al. A randomized trial of plasma
exchange in acute central nervous system
inflammatory demyelinating disease. Ann
Neurol 1999;46(6):878Y886.
31. Bramlage CP, Schröder K, Bramlage P, et al.
Predictors of complications in therapeutic
plasma exchange. J Clin Apher 2009;24(6):
225Y231.
Continuum Lifelong Learning Neurol 2011;17(4):733–743
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
32. Ammouri W, Mezalek ZT, Harmouche H, et al.
Myelitis complicating systemic lupus
erythematosus: successfully treated with
corticosteroids and cyclophosphamide.
South Med J 2009;102(7):744Y745.
33. Hirano T, Hagiharai K, Kawai M, et al.
Successful therapy with steroid and
cyclophosphamide pulse for CNS lupus and
lupus myelitis. Nihon Rinsho Meneki Gakkai
Kaishi 2007;30(5):414Y418.
34. Williams CS, Butler E, Román GC. Treatment
of myelopathy in Sjögren syndrome with a
combination of prednisone and
cyclophosphamide. Arch Neurol 2001;58(5):
815Y819.
35. Pohl D. Epidemiology, immunopathogenesis
and management of pediatric central nervous
system inflammatory demyelinating
conditions. Curr Opin Neurol 2008;21(3):
366Y372.
36. Pidcock FS, Krishnan C, Crawford TO, et al.
Acute transverse myelitis in childhood:
center-based analysis of 47 cases. Neurology
2007;68(18):1474Y1480.
37. Khurana DS, Melvin JJ, Kothare SV, et al.
Acute disseminated encephalomyelitis in
children: discordant neurologic and
neuroimaging abnormalities and response
to plasmapheresis. Pediatrics 2005;116(2):
431Y436.
38. Worley S, Short C, Pike J, et al. Dalteparin vs
low-dose unfractionated heparin for
prophylaxis against clinically evident venous
thromboembolism in acute traumatic spinal
cord injury: a retrospective cohort study.
J Spinal Cord Med 2008;31(4):379Y387.
39. Green D. Diagnosis, prevalence, and
management of thromboembolism in
patients with spinal cord injury.
J Spinal Cord Med 2003;26(4):329Y334.
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