Myelitis

General

AKA acute transverse myelitis (ATM).

Difference between Myelitis and Myelopathy

Myelitis	Myelopathy
Both are pathologic conditions of the spinal cord.	Both are pathologic conditions of the spinal cord.
Due to infectious/post-infectious, autoimmune, and idiopathic	Due to compressive, toxic, or metabolic aetiologies

Criteria for idiopathic transverse myelitis

Inclusion Criteria	Exclusion Criteria
Neurologic impairment attributable to the spinal cord	History of radiation to the spine within 10 y
Bilateral signs or symptoms (may be asymmetric)	Anterior spinal artery distribution of deficits
Clearly defined sensory level	Abnormal flow voids on the spinal cord
Exclusion of extra-axial compressive etiology by neuroimaging	Serologic or clinical evidence of systemic autoimmune disease
Evidence of inflammation in the spinal cord (CSF cells or IgG index, or MRI gadolinium enhancement) seen at onset or within 7 d	CNS manifestations of infectious etiology (eg, syphilis, Lyme, HIV, HTLV-1, Mycoplasma)
Progressive worsening to a nadir between 4 h to 21 d after onset	Brain MRI lesions suggestive of MS
ㅤ	History of optic neuritis

CNS, central nervous system; CSF, cerebrospinal fluid; HTLV, Human T-Lymphotropic Virus; Ig, immunoglobulin; MRI, magnetic resonance imaging; MS, multiple sclerosis.
See Transverse Myelitis Consortium Working Group 2002

Subtypes

Myelopathy

A broad, generic term referring to a lesion affecting the spinal cord

Myelitis

Refers to an inflammatory disease of the spinal cord

Transverse myelitis (TM)

Classically describes a pathobiologically heterogeneous syndrome characterized by acute or subacute spinal cord dysfunction resulting in paresis, a sensory level, and autonomic impairment below the level of the lesion

Acute Complete TM (ACTM)

TM causing paresis of the lower and/or upper extremities, sensory dysfunction (characterized by a sensory level), and autonomic impairment below the level of the lesion.
MRI

There is typically a single lesion spanning 1 or 2 vertebral segments;

Axial

There is either full-thickness involvement, or the central portion of the spinal cord is maximally affected.

Acute Partial TM (APTM)

TM causing asymmetric neurologic impairment (localizable to the spinal cord) or deficits attributable to a specific anatomic tract. On MRI, it spans 1 or 2 vertebral segments; there is involvement of a small portion of the spinal cord on axial sections.

Longitudinally-Extensive TM (LETM)

A spinal cord lesion that extends over 3 or more vertebral segments on MRI. On axial sections, it typically involves the center of the cord over more than two-thirds of the spinal cord area.

Secondary TM

TM related to a systemic inflammatory autoimmune disorder (eg, lupus, Sjögren syndrome, sarcoidosis). It is typically an ACTM. Idiopathic TM: TM without any clear etiology despite a thorough investigation. It should meet the criteria listed in Table 8.

Aetiology

Many remain unproven.

Infectious and post-infectious

Primary infectious myelitis

Viral: poliomyelitis, myelitis with viral encephalomyelitis, herpes zoster, rabies
Bacterial: including tuberculoma of spinal cord

Spirochetal: AKA syphilitic myelitis. Causes syphilitic endarteritis

Fungal (aspergillosis, blastomycosis, cryptococcosis)
Parasitic (Echinococcus, cysticercosis, paragonimiasis, schistosomiasis)
Post-infectious: including post-exanthematous, influenza

Posttraumatic
Physical agents

Decompression sickness (dysbarism)
Electrical injury*
Post-irradiation

Paraneoplastic syndrome: lung > prostate/ovary/rectum
Metabolic

Diabetes mellitus*
Pernicious anemia*
Chronic liver disease*

Toxins

Cresyl phosphates*
Intra-arterial contrast agents*
Spinal anaesthetics
Myelographic contrast agents
Following chemonucleolysis

Arachnoiditis
Autoimmune

MS, especially Devic syndrome
Following vaccination (smallpox, rabies)

Collagen vascular disease

Systemic lupus erythematosus
Mixed connective tissue disease

Clinical Presentation

Age of onset ranged 15–55 yrs

66% occurring in 3rd and 4th decade.

35% had a viral-like prodrome.

Symptoms

Symptom	Series A (ATM), n=34	Series B (acute/subacute TM), n=52
Pain (back or radicular)	35%	35%
Muscle weakness	32%	13%
Sensory deficit or paresthesias	26%	46%
Sphincter disturbance	12%	6%

Other S&S: fever and rash.

Presenting level of sensory deficit

Level	%
Cervical	8
High thoracic	36
Low thoracic	32
Lumbar	8

ATM is the presenting symptom of MS (≈ 3–6% of patients with ATM develop MS).

Progression

Usually rapid (66% reaching maximal deficit by 24 hrs)
Interval between first symptom and maximal deficit varies from 2 hrs-14 days.
Symptoms at time of maximal deficit (n=62 with ATM)

Symptom	%
Sensory deficit or paresthesias	100
Muscle weakness	97
Sphincter disturbance (hesitancy, retention, overflow incontinence)	94
Pain in back, abdomen, or limbs	34
Fever	27
Nuchal rigidity	13

Diagnostic criteria by Transverse Myelitis Consortium Working Group

Inclusion criteria

Development of sensory, motor, or autonomic dysfunction attributable to the spinal cord
Bilateral signs and symptoms (though not necessarily symmetric)
Clearly defined sensory level
Exclusion of extra-axial compressive cause by neuroimaging (MRI or myelography; CT is not adequate)
Inflammation within the spinal cord demonstrated by CSF pleocytosis or increased IgG index or gadolinium enhancement
Progression to nadir between 4 hours and 21 days after the onset of symptoms

Exclusion criteria

Radiation to the spine within the last 10 years
Arterial distribution clinical deficit consistent with thrombosis of the anterior spinal artery
Abnormal flow voids on the surface of the spinal cord consistent with AVF

Exclusion criteria for idiopathic ATM

Connective tissue disease
CNS infection
Brain MRI abnormalities suggestive of multiple sclerosis
History of clinically apparent optic neuritis

Evaluation

Imaging should be done to rule out a compressive lesion.

38%: normal during acute phase
62% abnormal during acute phase

Elevated protein (usually > 40mg%) or
Pleocytosis (lymphocytes, PMNs, or both) or both

Variable enlargement of the spinal cord
Variable contrast enhancement patterns (including no enhancement)

40% of cases have no findings on MRI

Remainder, the appearance is variable and non-specific:

There is a large variation in lesion size, however, they most commonly extend for 3-4 spinal segments
Lesions typically occupy greater than two-thirds of the cross-sectional area of the cord 3
There is variable enlargement of the spinal cord

Typical signal characteristics include:

T1: isointense or hypointense
T2: poorly delineated hyperintense signal

“Central dot sign,” an area of high signal on axial T2WI usually centrally located with a small dot of isointense signal in the core of the hyperintensity.

T1 C+ (Gd): variable enhancement patterns (none, diffuse, patchy, peripheral)

Treatment

No treatment has been studied in a randomized controlled trial.

Steroids: not beneficial for some types of myelitis, especially with ASIA A (complete paralysis);

High-dose IV methylprednisolone 3–5 days (doses quoted include 500mg/d, and 1000mg/d).
The decision to introduce additional treatment measures is based on the response to steroids and the MRI appearance after ≈ 5 days of steroids

Plasma exchange (PLEX) for patients that do not respond to steroids within 3–5 days

Other forms of immune suppression may be attempted for failure of above therapies, including: cyclophosphamide (usually under the direction of an oncologist)

Surgical decompression

In cases of focal spinal cord enlargement + fail to respond to immunosuppression

Prognosis

Takes around 1-3 months to recover

55% good recovery

35% poor recovery

10% mortality

62% surviving patients return to ambulation by 3-6 months

Summary of evidence for above data

In 34 patients with ≥5 yrs F/U:

9 patients (26%) had good recovery (ambulate well, mild urinary symptoms, minimal sensory and UMN signs);
9 (26%) had fair recovery (functional gait with some degree of spasticity, urinary urgency, obvious sensory signs, paraparesis);
11 (32%) had poor recovery (paraplegic, absent sphincter control);
5 (15%) died within 4 mos of illness.
18 patients (62% of survivors) became ambulatory (in these cases, all could walk with support by 3–6 mos).

In 59 patients (F/U period unspecified):

22 (37%) had good recovery;
14 (24%) had poor recovery;
3 died in acute stage (respiratory insufficiency in 2, sepsis in 1).
Recovery occurred between 4 weeks and 3 mos after onset (no improvement occurred after 3 mos).

Q&A

What should be considered in a patient who presents less than 48 hours after intrathecal treatment with methotrexate with paraplegia, leg pain, sensory level, and bladder dysfunction?

Answer: Transverse myelitis from a rare idiosyncratic reaction to the intrathecal methotrexate. Also consider a traumatic spinal subdural hematoma from the procedure.