19/11/2011

Transverse
Myelitis

Tun Paksi Sareharto

Terminology
Myelopathy: CNS dysfunction due to a lesion
(1) within the spinal cord (inflammatory or demyelinating lesions, cord
infarction, vitamin B12 deficiency, copper deficiency, etc), OR
(2) compression of the cord (epidural tumors, epidural abscess, cervical or
thoracic disk).

Transverse Myelopathy: clinical presentation of severe motor, sensory, and

autonomic dysfunction due to any process affecting spinal cord.

Transverse Myelitis (TM) : when myelopathy is due to an

inflammatory or demyelinating lesion.

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CNS dysfunction due

Myelopathy to anything….

Transverse Clinical finding

suggesting problem
Myelopathy at spinal cord level…

When transverse
Transverse myelopathy is due to
Myelitis ‘itis

• Acute demyelinating disorder of the spinal cord

• = Necrotic myelopathies progressive
• as part of a multi-focal CNS disease (e.g. MS),
• multisystem disease (e.g. systemic lupus erythematosus),
or as
• an isolated, idiopathic entity.
• A focal inflammatory disorder of the spinal cord,
resulting in motor, sensory, and autonomic dysfunction.
• Rapidly progressive weakness in the lower extremities
with sphincter dysfunction and loss of sensation.

Transverse myelitis

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Epidemiology

“Transverse Myelitis is a rare syndrome with incidence of

between 1 and 8 new cases per million people per year.”

Mean age at onset is 9 years

Berman M, Feldman S, Alter M, et al. Acute transverse myelitis: incidence and etiologic
considerations. Neurology. 31:966–971.

• Preceded by viral illness (usually Respiratory tract

Infection)
viral-induced cell-mediated autoimmune
response
• Viral illness: morbili, parotitis, herpes zoster, echovirus,
hepatitis B, etc.

Etiology

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Pathogenesis of acute transverse myelitis

Short Answer: nobody knows. However, some historical clues:

Osler in 1892: ‘acute post-infectious polyneuritis’

Molecular Mimicary

A characteristic component of human neural tissue is, sialic acid,

which is found in neural cell walls. Sialic Acid is also found as a
surface antigen on C. jejuni within its lipopolysaccharide outer coat.
Antibodies that crossreact with gangliosides from C. jejuni.

Pathogenesis of acute transverse myelitis

In 1922, physicians in England and Holland observed o ‘post-vaccinal

encephalomyelitis’ after polio vaccination

Autoimmune process resulting in TM.

Autopsy evaluation of the spinal cord revealed severe axonal loss

with mild demyelination and a mononuclear infiltrate,
predominantly T lymphocytes in nerve roots and spinal ganglia

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• Autoimmune-induced:
• vasculitis
a. spinalis anterior obstructed
inadequate
blood supply to the spinal cord
necrosis on
thoracolumbar spinal cord
• Spinal cord broken
necrotic, neural element replaced by
an inflammatory cell (cellular infiltrate)
• Changes can be transverse (extending over several spinal
segments)
• Evolves in hours or days

Pathology

Hypothesis

Vascular
• Disruption of occlusion • Occlusion leads
BBB to ischemic
• Lymphocytic • coagulopathy due necrosis
infiltration to: • Antineuronal Ab
• Inflammation +/-
APLA
(antiphospholipid
antibodies)
Vasculitis Autoimmune

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Vasculitis
• Disruption of Blood-Brain barrier
• Lymphocytic infiltration

Peri-vascular inflammation

Thrombi

Inflammation and Thrombus leads to Demyelination and necrosis

…which then causes Radiological and Clinical manifestation

• Symptoms could appear simultaneously with infection triggers

or after symptoms of primary infection healed
• Initially the loss of the pain in the limb
area, abdomen, and back of the body, then immediately
followed by paraparesis
• Sensory disturbances and paralysis occurs very rapidly, maxim
al deficit is attained within 2-3 days, ascenderen,
the lower limb first and then the upper limb
• The lesion usually at thoracic, demarcated by the sensory loss
• Usually symmetric, but it could asymmetric leg weakness
• Paralysis initially flaccid, later became spastic: physiological ref
lexes increases and be found clonus

this process occurs after the end of the second week
• Tendon reflexes may be increased or reduced

Clinical Features

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• When the maximal level of deficit is reached, approximately 50% of

patients have lost all movements of their legs, virtually all patients
have some degree of bladder dysfunction, and 80-94% of patients
have numbness, paresthesias or band like dysesthesias.
• Autonomic symptoms consist variably of increased urinary urgency,
bowel or bladder incontinence, difficulty or inability to void,
incomplete evacuation or bowel constipation and sexual
dysfunction.
• 86% had sphincter muscle disturbances: urine retention,
impaired pain and temperature sensation
• Proprioceptive function is still good (because posterior column not
impaired), sometimes got a stiff neck symptoms
• Diagnostic and classification scheme which has defined TM as either
idiopathic or associated with a known inflammatory disease (i.e.
multiple sclerosis, systemic lupus erythematosus, Sjogren’s
syndrome, or neurosarcoidosis)
• Recovery begins after 6 days, may be incomplete

Presentation of TM

50% of patients have motor deficits involving lower extermities

“Virtually all” patients have some degree bladder or bowel dysfunction: autonomic
symptoms vary from increased urinary urgency, to bowel or bladder incontinence, difficulty
to void, incomplete evacuation or bowel constipation”

80 to 94 % have numbness, paraethesia or bandlike dysesthesia.

Christensen PB, Wermuth L, Hinge HH, et al. Clinical course and long-term prognosis of acute transverse myelopathy. Acta Neurol Scand.
1990;81:431–435

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Idiopathic Acute Transverse Myelitis Criteria

Inclusion criteria

1) Development of sensory, motor or autonomic dysfunction attributable to the spinal cord

2) Bilateral signs or symptoms (although not necessarily symmetric)
3) Clearly-defined sensory level
4) Exclusion of extra-axial compressive etiology by neuroimaging (MRI or myelography; CT of spine not adequate)
5) Inflammation within the spinal cord demonstrated by CSF pleocytosis or elevated IgG index or gadolinium enhancement. If none
of the inflammatory criteria is met at symptom onset, repeat MRI and LP evaluation between 2 and 7 days after symptom onset
meets criteria
6) Progression to nadir between 4 h and 21 days after the onset of symptoms (if patient awakens with symptoms, symptoms must
become more pronounced from point of awakening)
Exclusion criteria

1) History of previous radiation to the spine within the past 10 years

2) Clear arterial distribution clinical deficit consistent with thrombosis of the anterior spinal artery
3) Abnormal flow voids on the surface of the spinal cord consistent with AVM
4) Serological or clinical evidence of connective tissue disease (sarcoidosis, Behcet's disease, Sjogren's syndrome, SLE, mixed
connective tissue disorder, etc.)
5) CNS manifestations of syphilis, Lyme disease, HIV, HTLV-1, mycoplasma, other viral infection (e.g. HSV-1, HSV-2, VZV, EBV,
CMV, HHV-6, enteroviruses)
a) Brain MRI abnormalities suggestive of MS
b) History of clinically apparent optic neuritis
AVM, Arteriovenous malformation; CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed
tomography; EBV, Epstein-Barr virus; HHV, human herpesvirus; HSV, herpes simplex virus; HTLV, human T cell leukemia virus; LP,
lumbar puncture; MRI, magnetic resonance imaging; MS, multiple sclerosis; SLE, systemic lupus erythematosus. "Do not exclude
disease-associated acute transverse myelitis.

From: Kerr: Curr Opin Neurol, Volume 15(3).June 2002.339-347

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• LCS: pleiositosis, peningkatan kadar protein

• CT Myelografi: pembengkakan medula spinalis
• MRI of the spine:
• to exclude acute cord compression
• shows swelling at the level of myelitis
• Cranial MRI
to exclude more widespread disease
• Vision should be checked daily (possibility of Devic
disease)

Pemeriksaan penunjang

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Differential diagnosis
Differential diagnosis of transverse myelopathy includes:

Medullar compression caused by vertebral fractures,

Epidural or subdural hematoma,
Epidural and/or paraspinal abscess complicating disc space
infection,
Disc herniation,
Intra- and extramedullary tumor,
Multiple Sclerosis (MS),
Infection,
Guillain-Barre Syndrome,
Neuromyelitis optica,
Acute Disseminated Encephalomyelitis.

Characteristics TM GBS Distinguishing Feature

Motor findings Paraparesis or Ascending weakness TM: if UE involvement, often as severe
quadriparesis LE>UE in the early as LE; often no UE involvement
stages GBS: There usually is UE involvement
and it is less severe than LE involvement
early in the disease
Sensory findings Usually can diagnosis a Ascending sensory TM: sensory level usually identified.
spinal cord level loss LE>UE in the Often no arm involvement
early stages GBS: no sensory level, usually UE less
affected than LE early in the disease
Autonomic Early loss of bowel and Autonomic TM: urinary urgency or retention early
findings bladder control dysfunction of the and prominent; CV instability only in
cardiovascular (CV) severe cases higher than T6.
System GBS: urinary urgency or retention less
common; CV instability is more common
Cranial nerve None EOM palsies or facial GBS: cranial neuropathies are more
findings weakness common than in TM

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Characteristics TM GBS Distinguishing Feature

Electrophysiologic EMG/NCV findings may EMG/NCV findings The lack of peripheral nerve
findings be normal or may confined to the PNS: abnormalities in a patient with
implicate the spinal cord: motor and/or sensory progressive weakness and sensory loss
Prolonged central nerve conduction should suggest evaluation of the spinal
conduction on velocity reduced, cord for pathology
somatosensory evoked distal latencies Conversely, patients with suspected TM
potential (SEP) latencies prolonged; conduction but equivocal clinical, lab or radiologic
or missing SEP in block; reduced H findings may warrant peripheral nerve
conjunction with normal reflex usually present examination
sensory nerve action
potentials
MRI findings Usually a focal area of Normal MRI abnormalities may be helpful in
increased T2 signal with diagnosing a patient who is suspected of
or without gadolinium having GBS from TM
Enhancement
CSF Usually, CSF pleocytosis Usually, elevated CSF pleocytosis and elevated IgG index
and/or increased IgG protein in the absence may be helpful in diagnosing a patient
index of CSF pleocytosis who is suspected of having GBS from
TM

• High-dose corticosteroids intra venous are generally

used, followed by prednisone tapering doses
(controversial)
• Supportive therapy: Physiotherapy

Management

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Treatment

Intravenous (IV) pulse methylprednisolone and

cyclophosphamide

It is unclear whether plasmapheresis and immunoglobulin

iv have any additional therapeutic benefit

Kovacs B, Lafferty TL, Brent LH, et al. Transverse myelopathy in systemic lupus erythematosus: an analysis of 14 cases
and review of the literature. Ann Rheum Dis 2000; 59: 120–4.

• Patients with TM should be offered immunomodulatory

treatment such as steroids and plasmapheresis though
there is no consensus as to the most appropriate strategy
yet.
• Most TM patients have monophasic disease, while up to
20% will have recurrent inflammatory episodes within
the spinal cord (JHTMC case series, 11, 12).

• Most children with ATM improve with high doses of

methylprednisolone.
• If this medication does not work, there are other
treatments that can be tried (plasmapheresis or
intravenous immunoglobulin therapy)

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• 50-60% make a full recovery, 10% have no recovery, 15-

40% recover incompletely
• Especially have a sensory disturbance
• Healing occurs gradually after 1 month course of the
disease
• Fully recovered after 6 months

Prognosis

• TM is a clinical syndrome caused by focal inflammation of the spinal cord.

• Many cases are post infectious and are thought to be due to a transient
abnormality in the immune system that results in injury to a focal area of the
spinal cord.
• Recent studies have emphasized the need to classify TM according to whether
there is evidence of systemic disease or multifocal CNS disease.
• The importance of this may be that distinct treatment strategies are offered to
patients with distinct forms of TM.
• Though the causes of TM remain unknown, recent advances have suggested
specific cytokine derangements that likely contribute to sustained disability.
• Patients are often left with sustained disability due to injury of motor, sensory or
autonomic neurons within the spinal cord.
• Future research will attempt to define triggers for the immune system
derangements, effector mechanisms that propagate the abnormal immune
response and cellular injury pathways initiated by the inflammatory response
within the spinal cord. Ultimately, this may allow us to identify patients at risk
for developing TM, specifically treat the injurious aspects of the immune
response, and/or offer neuroprotective treatments which minimize the neural
injury that occurs in response to the inflammation.

Summary

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• Fenichel GM. Paraplegia and quadriplegia. In: Fenichel

GM. Clinical pediatric neurology, a signs and symptoms
approach, 4th ed. Philadelphia: WB Saunders; 2001. p.
257-72.
• Tjipta Bahtera. Penyakit autoimun dan pascainfeksi
susunan saraf. Dalam: Soetomenggolo TS, Ismael S. Buku
ajar neurologi anak. Jakarta: BP IDAI; 1999. p. 432-44.
• Infections. In: Gaskill SJ, Marlin AE. Handbook of
pediatric neurology and neurosurgery. New York: Little,
Brown and Company; 1993. p. 193-207.

References

Thank you

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