Accepted Manuscript

Title: Spinal Cord Disorders: Myelopathy

Author: Shamik Bhattacharyya

PII: S0002-9343(18)30282-1
DOI: https://doi.org/10.1016/j.amjmed.2018.03.009
Reference: AJM 14585

To appear in: The American Journal of Medicine

Please cite this article as: Shamik Bhattacharyya, Spinal Cord Disorders: Myelopathy, The
American Journal of Medicine (2018), https://doi.org/10.1016/j.amjmed.2018.03.009.

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Spinal Cord Disorders: Myelopathy

Running header: Myelopathy

Shamik Bhattacharyya, MD, MS

Department of Neurology, Brigham and Women’s Hospital; Harvard Medical School

Contact:
75 Francis Street
Boston, MA 02115
Email: sbhattacharyya3@bwh.harvard.edu
Phone: +1 617-732-7432

All authors had access to the data and a role in writing the manuscript.

Conflict:
The author does not have any relevant conflicts of interest to declare.

Manuscript type: Review

Word Count: 2372

Funding source: None

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Clinical Significance Statement

Myelopathy is a clinical diagnosis based on findings such as sensory level and Lhermitte’s sign,

and workup generally includes imaging with MRI.

The most common cause of nontraumatic paraparesis is cervical degenerative myelopathy which

presents primarily as a progressive gait disorder.

Vitamin B12 deficiency is a common reversible nutritional cause of myelopathy and should be

screened for especially in older adults without a structural etiology.

Abstract

Myelopathy is a clinical diagnosis based on symptoms and physical examination findings.

Laboratories and imaging particularly with MRI can suggest a cause. Compressive myelopathy

from degenerative disease of the vertebral column is the most common cause of myelopathy in

older adults and should be screened for first in most cases. There are many other causes of

myelopathy including infectious, immune mediated, nutritional, vascular, and neoplastic

etiologies.

Key words: Myelopathy; spinal cord; myelitis; spinal cord anatomy

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Introduction

Spinal cord disorder or myelopathy is a common disease that most primary care doctors

encounter. Yet, the variability in symptoms, etiology, and treatment makes myelopathy one of

the more uncomfortable neurologic syndromes. Myelopathy is diagnosed by signs and symptoms

suggestive of spinal cord dysfunction. Imaging and laboratories help point to the cause. We

review here the anatomy of the spinal cord, clinical features of myelopathy, and some common

causes.

Anatomy

The spinal cord is a continuation of the brain and extends from the cranio-cervical junction to the

lumbar spine ending as the conus medullaris most frequently at the L1-2 interspace disc level.

The spinal cord is a segmental structure with pairs of dorsal and ventral nerve rootlets entering

and exiting at each level. The dorsal nerve rootlets bring sensory information to the dorsal horn

while ventral nerve rootlets exit from the ventral horn containing motor nerve fibers. The spinal

rootlets join at the intervertebral foramen to form the spinal nerves (8 cervical, 12 thoracic, 5

lumbar, 5 sacral, and 1 coccygeal nerve – though variations exist). In cross-section, the gray

matter containing neurons are centrally located surrounded by ascending and descending white

matter tracts (Figure 1). The majority of neurons within the spinal cord are interneurons which

integrate the afferent and efferent signals.1

Although there are several white matter tracts in the spinal cord, the major functional

consequences of spinal cord lesions can be explained by three major tracts. The dorsal columns

located in between the two dorsal horns carry ipsilateral pressure and vibration sensation. The

spinothalamic tracts, on the other hand, are in the anterior segment of the spinal cord and relay

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contralateral pain and temperature sensation. The final major white matter tract are the

corticospinal tracts which exerts motor control for ipsilateral muscles. Nerve fibers controlling

leg muscles are located peripherally while those controlling the arms are located centrally

(Figure 1). Hence, extrinsic compression of the cord in the cervical spine may predominantly

cause symptoms in the legs. The other white matter tracts serve many important functions

including maintenance of balance, reflexes, and autonomic control of bladder and bowel

function.

The arterial supply to the spinal cord is from the anterior and posterior spinal arteries. The

anterior spinal artery lies on the ventral surface of the spinal cord and is re-enforced by multiple

radiculomedullary arteries, which are segmental arteries penetrating to the spinal cord mostly

from the aorta. The largest such radiculomedullary artery is the artery of Adamkiewicz present

between T9-T12 vertebral levels in the majority of people.2 The anterior spinal artery provides

blood flow to the anterior two-thirds of the spinal cord containing the ventral horn and most of

the lateral and anterior white matter tracts. The posterior spinal arteries are paired arteries located

posterior to the spinal cord and provide blood flow to the posterior aspects of the spinal cord

containing the dorsal horn and dorsal column. The venous outflow of the spinal cord is through a

surrounding plexus of veins which connect both to segmental veins and to longitudinal channels

continuous with cranial sinuses.

Clinical Features

Partial cord lesions cause a variety of syndromes ranging from primarily sensory to exclusively

motor. Lesions in the spinal cord affecting the descending corticospinal tracts cause the upper

motor neuron syndrome characterized by initial flaccid weakness evolving over days to

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weakness with increased tone, hyperactive muscle stretch reflexes, and presence of Babinski sign

(extension of the big toe with stroking the sole of the foot). This syndrome is not specific for

cord injury (can also be caused by brain lesions), and not all components of the syndrome are

present consistently. The toe can be downgoing (absence of Babinski sign) or tone can only be

mildly elevated despite spinal cord injury causing weakness.

Among other symptoms of myelopathy, the phenomenon of sensory level is described by

patients as numbness below a segment of the body either unilaterally or bilaterally. For example,

a T10 sensory level is experienced as numbness below the level of the umbilicus in the trunk and

legs. Objectively, sensory level can be demonstrated by diminished sensory perception below a

dermatome. The American Spinal Injury Association (ASIA) recommends checking both light

touch and pinprick at dermatomal segments, and a sensory level is defined as the highest level

with preserved light touch and sharp sensation.3 Because of the somatotopic organization of

sensory fibers in the spinal cord, a sensory level indicates a lesion in the spinal cord at that

dermatomal level or any level above. To return to the example of numbness below the umbilicus

(a T10 sensory level), the cord lesion could be present in the thoracic or cervical spinal cord

because a discrete lesion in the cervical spinal cord could affect the ascending fibers from the

thoracic segments without causing any symptoms in the arms. Another sign specific for

myelopathy is Lhermitte’s sign, which is an electric, shock like sensation elicited by neck flexion

usually traveling down the back often extending into the legs.4 This sign is associated with

lesions in the dorsal columns of the cervical spinal cord.

The pattern of neurologic deficits can indicate spinal cord localization. At the most extreme is

spinal cord transection in which there is complete loss of sensation and strength below a

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dermatomal/myotomal level. More frequently encountered is the hemicord syndrome (Brown-

Séquard syndrome) characterized by ipsilateral weakness and vibratory/proprioceptive loss and

contralateral pain/temperature loss (since the spinothalamic tracts are crossed in the spinal cord).

This crossed and dissociated sensory loss is localizing for spinal cord lesion. Other commonly

encountered syndromes include the dorsal column syndrome in which there is selective loss of

vibration/proprioception below a dermatomal level with preservation of other sensory modalities.

A related syndrome is the postero-lateral syndrome in which there is not only decreased

vibratory/proprioceptive loss (posterior cord involvement) but also corticospinal signs below a

segment (lateral column involvement). This syndrome is found in myelopathy from vitamin B12

deficiency, copper deficiency, and HIV associated vacuolar myelopathy.

Imaging

Myelopathy is a clinical diagnosis. Reliance on imaging alone can lead to diagnostic errors. For

example, patients who are paraplegic from HIV associated myelopathy can have only subtle cord

atrophy on imaging. On the other hand, patients with cervical spondylotic disease can have

severe radiographic disease with minimal symptoms. With these caveats in mind, imaging is an

important step in the diagnostic approach to myelopathy. X-ray is useful for investigating bony

fractures and dynamic instability of bony alignment. In rheumatoid arthritis, instability in the C1

and C2 joint can be occult on standard views but become apparent on flexion and extension

views. X-ray also shows post-surgical instrumentation of the spine well. Computed tomography

(CT) of the spine provides cross-sectional views of the bones but does not image the cord or

nerves. CT is used in initial trauma surveys and in patients with contraindication to MRI. In CT

myelogram, contrast is injected intrathecally followed by CT of the spine. The contours of the

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thecal sac, spinal cord and spinal nerves can be imaged with a myelogram when there is concern

for cord or nerve compression or cerebrospinal fluid leak.

MRI is the preferred imaging modality for the spinal cord and can visualize nerve roots, lesions

in the spinal cord, and surrounding bony/soft tissue abnormalities. A common question is which

segment of the spine to image. Whole spine imaging protocols are appropriate for oncologic

surveys and when there is concern for acute cord compression. Whole spine MRI sacrifices

spatial resolution to improve spatial coverage. Small lesions are missed. In other circumstances,

imaging is acquired first for a clinically localized segment and then expanded if no lesions are

found or there is suspicion of a multifocal process. Intravenous gadolinium contrast is used to

characterize neoplastic or inflammatory lesions.

Diseases

Degenerative Cervical Myelopathy

The most common cause of nontraumatic paraparesis and spinal dysfunction in older adults is

degenerative cervical disease.5 With aging, degenerative changes in the cervical spine occur in

the majority of people including dessication and herniation of the intervertebral disc, bone spur

formation, facet joint arthropathy, ligamentous hypertrophy, and subluxation of vertebral bodies.

Most patients have a combination of these factors leading to cervical canal narrowing.

Myelopathy occurs not only from compression of the spinal cord but also from cord stretch

injury and ischemia of the cord microcirculation. Hence, spinal canal narrowing radiographically

does not reliably predict clinical myelopathy. The primary and earliest symptom of degenerative

cervical myelopathy is gait abnormality marked by sense of instability and stiffness in the legs.6

There are often additional complaints of neck pain and decreased dexterity in the hands or

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sensory paresthesias. Bowel or bladder dysfunction is uncommon in early degenerative cervical

myelopathy. The acuity of onset can be variable ranging from insidious over years to more rapid

evolution over days or even hours especially after neck trauma on pre-existing stenosis.

Neurological examination shows a stiff and spastic gait with corticospinal signs along with

atrophy of intrinsic muscles in the hands, which reflects injury to both the descending spinal cord

and exiting spinal nerves.

Almost all patients with myelopathy of unclear origin should first be screened for degenerative

compressive myelopathy. The imaging modality of choice is MRI (Figure 2) though

degenerative changes on MRI are present in the majority of older patients.7 Thus, correlating

symptoms and imaging with certainty is critical. The optimal management of cervical

degenerative myelopathy lacks large randomized trials to guide practice. Most experts agree that

moderate to severe myelopathy or progressive symptoms should be addressed surgically while

mild, stable symptoms could be observed closely depending on patient preferences and other

medical comorbidities.

Myelitis

Myelitis denotes inflammation of the spinal cord. Clinically, myelitis presents with signs and

symptoms of spinal cord dysfunction evolving over the course of hours to days from symptom

onset to nadir. In analysis of different causes of myelopathy, this subacute temporal profile of

symptom onset best discriminated myelitis from other non-inflammatory causes.8 Some

exceptions to this clinical observation are progressive forms of multiple sclerosis, syphilis,

human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) associated

myelopathy in which there can be slow progression of signs and symptoms over the course of

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years. Inflammation of the spinal cord is demonstrated by lumbar puncture showing elevated

cerebrospinal fluid cell count or intrathecal antibody synthesis (presence of oligoclonal bands or

elevated IgG index).9 In active inflammation, there is often enhancement of lesions on MRI with

intravenous gadolinium enhancement.

There are both infectious and immune mediated causes of myelitis. Among infectious causes in

immunocompetent adults, some common etiologies are Lyme, varicella zoster virus, and West

Nile virus. There are many causes of immune mediated causes of myelitis. Multiple sclerosis is a

common cause in the United States. Lesions associated with multiple sclerosis tend to be small

with symptoms improving spontaneously over time and radiologically located eccentrically in

the spinal cord (Figure 3). Patients with first episode of myelitis from multiple sclerosis

frequently have asymptomatic brain lesions uncovered on brain MRI imaging. Longer spinal

cord lesions with more incomplete recovery can be associated with presence of anti-Aquaporin 4

antibody in the serum diagnostic of the disease neuromyelitis optica. When no cause is found,

myelitis is classified as idiopathic, and patients are followed to see if they develop more specific

disease defining features.

Nutritional Myelopathies

Nutritional myelopathies are potentially treatable causes. Vitamin B12 deficiency is most

common in this category and has hematologic effect of macrocytic anemia with hypersegmented

neutrophils and neurologic effects of cognitive dulling, myelopathy, and infrequently optic

neuropathy. The myelopathic syndrome typically consists of sensory paresthesias in the hands,

impaired vibration and proprioceptive sense in the feet, and corticospinal signs in the legs.10

Deficiency in vitamin B12 is most commonly caused from deficiency of intrinsic factor

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production (pernicious anemia) or other gastrointestinal malabsorption diseases. Treatment is

with vitamin B12 supplementation. Abuse of nitrous oxide (used as a propellant commercially)

causes an induced vitamin B12 deficiency. A related disease is copper deficiency which presents

similarly to vitamin B12 deficiency with the addition of peripheral neuropathy.11 Copper

deficiency is associated with intestinal malabsorption or excess ingestion of zinc from

supplements or denture paste. Copper deficiency is diagnosed by testing for serum copper and

ceruloplasmin levels (and for serum zinc when there is suspicion of zinc excess) and treated with

copper supplementation and discontinuing source of excess zinc.

Other

There are many other genetic, neoplastic, vascular, and structural causes of myelopathy.

Myelopathy from genetic causes is grouped under the term hereditary spastic paraplegia with

over 75 different genetic mutations identified. Hereditary spastic paraplegia typically presents as

a slowly progressive spastic paraplegia with sensory impairment and bladder dysfunction.13

Hereditary spastic paraplegia can be isolated to myelopathy or cause other neurologic deficits

such as peripheral neuropathy, ataxia, or cognitive deficits. Treatment is generally supportive.

In comparison to the brain, ischemic stroke of the spinal cord is infrequent and generally occurs

in the context of aortic surgery or other occlusive disease of the arteries branching from the

aorta. Vascular malformations particularly dural arteriovenous fistulas can spontaneously occur

in the spinal cord (mostly in the thoracic spinal cord) and present as slowly progressive

myelopathy predominantly in older men. The disease is diagnosed by spinal angiogram and

treated by correction of the vascular malformation.

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Primary spinal cord tumors are rare compared to metastatic lesions, which typically grow in the

epidural space and cause myelopathy from compression. Ependymomas are the most common

primary neoplasm of the spinal cord in adults and present with a prodromal phase of localized

sensory dyesthesias for months prior to development of other myelopathic signs.14 These tumors

frequently occur in the center of the cord interrupting crossing sensory fibers and generating the

sensory predominant presentation. Treatment is usually with surgical resection. Syringomyelia,

which is a glial lined fluid filled cavity in the spinal cord, also interrupts centrally crossing

sensory fibers and similarly causes sensory dyesthesias with numbness in a band like

distribution. Syringomyelia is distinguished by the presence of fluid filled cavity on imaging and

occurs associated with an ependymoma, prior spinal cord injury, or developmental malformation

(Chiari malformation).15

Conclusion

Spinal cord disorders are recognized clinically by characteristic symptoms such as a sensory

level and findings such as a hemicord syndrome. The pattern of deficits, time course,

laboratories, and imaging all combine to arrive at an etiologic diagnosis.

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15. Milhorat TH. Classification of syringomyelia. Neurosurg Focus. 2000 Mar;15(8):E1

Figure 1: Cross-sectional view of the spinal cord. The central grey matter is surrounded by

descending (red) and ascending (blue) white matter tracts. Although there are many white matter

tracts, the three most clinically relevant ones are the lateral corticospinal tract, dorsal columns,

and spinothalamic tracts. [This work is licensed under a Creative Commons Attribution 2.0

Generic License. The original is attributed to László Tambo, and the image has been modified

further for publication by the author. The original can be found here

(https://commons.wikimedia.org/wiki/File:Spinal_cord_tracts_-_Hu.svg).]

Figure 2: Degenerative cervical spondylotic myelopathy. Sagittal T2 weighted MRI showing

compression of the spinal cord at C3-4 level (white arrow). There is loss of cerebrospinal fluid

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signal (hyperintensity surrounding the cord) at the site of compression. [Original unpublished

image]

Figure 3: Myelitis. A 40 year old woman presented with right leg weakness and left leg

numbness and was found to have a right hemicord lesion – shown in this cervical spine axial

image by the T2 hyperintense lesion indicated by the white arrow. [Original image]

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Figure 2 - Degenerative Disease.jpg

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Figure 3 - Myelitis.jpg

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