This course includes the more common and important causes of nontraumatic spinal cord disorders including risk factors, clinical presentation, diagnosis, treatment and prognostic outcomes.
Upon completion of this course, the participant will be able to:
Spinal cord injury (SCI) occurs commonly. The incidence of traumatic SCI in the United States is about 40 million individuals per year, with approximately 250,000 living survivors of traumatic SCI as of July 2005.1 The prevalence of nontraumatic SCI is unknown, but it is estimated to be three to four times greater than traumatic SCI.2 SCI produces a wide variety of changes in systemic physiology that can lead to a number of complications, which rival the neurologic deficits in their impact on function and quality of life.
Medical complications after SCI are both common and severe. In the Model Spinal Cord Injury Systems Database, rehospitalizations occurred in 55% of patients in the first year after SCI and continued at a stable rate of about 37% per year over the next 20 years.3 Genitourinary and respiratory complications and pressure ulcers were the most common reasons for rehospitalization. Increased patient age and severity of the spinal cord lesion also impacted on the risk of complications requiring rehospitalization.
Pathologies that affect the spinal cord are diverse. In addition to trauma, nontraumatic common etiologies of myelopathy include inflammatory diseases, infections, vascular diseases, toxic-metabolic disorders, inherited-degenerative conditions, neoplasms and a plethora of others. The relative incidence of each of these entities depends in large part upon the clinical setting. In a regional neuroscience center in the United Kingdom, the most common cause of spastic paraparesis or quadriparesis among 585 patients was cervical spondylotic myelopathy (24%), followed by tumor (16%), multiple sclerosis (18%), and motor neuron disease (4%).4
This course will review some of the more common and important causes of nontraumatic spinal cord disorders including risk factors, clinical presentation, diagnosis, treatment and prognostic outcomes.
Life expectancy is reduced among survivors of SCI. Mortality rates are highest in the first year. For patients surviving at least one year after traumatic SCI, life expectancy is approximately 90% of normal.1,5,6 Variables which impact negatively on survival rate are higher neurologic level and severity of the injury as well as older age at the time of SCI.
The most common causes of death after traumatic SCI are diseases of the respiratory system followed by cardiovascular events.1,5 Prior to 1972, urinary complications were the leading cause of death. The risk of suicide is also increased among patients with SCI.6
Amyotrophy: a painful condition with wasting and weakness of muscle.
Demyelination: destruction, removal, or loss of the myelin sheath of a nerve or nerves.
Myelopathy: any functional disturbance or pathological change in the spinal cord. When due to trauma, it is known as acute spinal cord injury. When inflammatory, it is known as myelitis. A disease that is vascular in nature is known as vascular myelopathy.
Myeloradiculopathy: a disease of the spinal cord and spinal nerve roots.
Radiculopathy: a disorder of the spinal nerve roots.
Vacuolar myelopathy: a heterogeneous group of conditions characterized by spinal cord degeneration.
Upper Motor Neuron Signs include:
Lower Motor Neuron Signs include:
Paraparesis: a partial paralysis of the lower extremities.
Quadriparesis: weakness of both arms and both legs.
Ipsilateral: located on or affecting the same side of the body.
Contralateral: pertaining to, situated on, or affecting the opposite side.
Decussate: to cross.
Myotome versus dermatome: Like a dermatome, a myotome is a zone in the body that is served by one spinal nerve root. A dermatome is a zone in which sensory nerves travel on their way back to the central nervous system with sensory information. Myotomes are zones where motor nerves travel as they fulfill their responsibilities of signaling muscles to contract.
Transection: a cross section; division by cutting transversely.
Transverse: extending from side to side; situated at right angles to the long axis.
There are 31 spinal cord segments, each with a pair of ventral (anterior) and dorsal (posterior) spinal nerve roots, which mediate motor and sensory function, respectively. The ventral and dorsal nerve roots combine on each side to form the spinal nerves as they exit from the vertebral column through the neuroforamina.
The spinal cord is divided longitudinally into four regions:
The spinal cord extends from the base of the skull and terminates near the lower margin of the first lumbar vertebral body (L1). Below that level, the spinal canal contains the lumbar, sacral, and coccygeal spinal nerve roots that comprise the cauda equina.
Because the spinal cord is shorter than the vertebral column, vertebral and spinal cord segmental levels are not necessarily the same.
Figure 2
Longitudinal Organization of Spinal Cord, Spinal Nerves, and Vertebrae
The first cervical vertebra (the atlas) and the second cervical vertebra (the axis), upon which the atlas pivots, support the head at the atlanto-occiput junction. The interface between the first and second vertebra is called the atlanto-axis junction.
Cervical spinal segments innervate the skin and musculature of the upper extremity and diaphragm:Figure 3
Nerve Roots and Peripheral Nerves Corresponding to the Principle Movements of the Upper Extremity
Figure 4
The thoracic vertebral segments are defined by those that have an attached rib. The spinal roots form the intercostal nerves that run along the inferior rib margin and innervate the associated dermatomes, as well as, the intercostal abdominal wall musculature. These muscles are the primary muscles of expiration. The thoracic cord also contains the sympathetic nerves that innervate the heart and abdominal organs.
The lumbosacral spinal cord contains the segments that innervate the muscles and dermatomes of the lower extremity, as well as, the buttocks and anal regions. Sacral nerve roots S3 through S5 originate in the narrow terminal part of the cord, called the conus medullaris.
Sacral nerve roots also provide parasympathetic innervation of pelvic and abdominal organs. Lumbar nerve roots L1 and L2 contain sympathetic innervation of some pelvic and abdominal organs.
Figure 5
Nerve Roots and Peripheral Nerves Corresponding to the Principle Movements of the Lower Extremity
In adults, the spinal cord ends at the level of the first or second lumbar vertebral bodies. The filum terminale, a thin connective tissue filament that descends from the conus medullaris with the spinal nerve roots, is connected to the third, fourth, and fifth sacral vertebrae. Its terminal part is fused to the periosteum at the base of the coccygeal bone.
Pathology at the T12 and L1 vertebral level affects the lumbar cord. Injuries to L2 frequently damage the conus medullaris. Injuries below L2 usually involve the cauda equina and represent injuries to spinal roots rather than to the spinal cord.
The spinal cord contains the gray matter, the butterfly-shaped central region, and the surrounding white matter tracts. The spinal cord gray matter, which contains the neuronal cell bodies, is made up of the dorsal and ventral horns, each divided into several laminae.7, 8
Dorsal Horn
The dorsal horn is the entry point of sensory information into the central nervous system (CNS). It is divided into six layers or laminae that process sensory information. More than a relay station for the transmission of sensory information, the dorsal horn also modulates pain transmission through spinal and supraspinal regulatory circuits.
Three major categories of sensory input that are important to the clinical examination of spinal cord pathology include:
Ventral Horn
The dorsal horn is the entry point of sensory information into the central nervous system (CNS). It is divided into six layers or laminae that process sensory information. More than a relay station for the transmission of sensory information, the dorsal horn also modulates pain transmission through spinal and supraspinal regulatory circuits.
Three major categories of sensory input that are important to the clinical examination of spinal cord pathology include:
White matter tracts
The major white matter tracts of clinical importance in the assessment of spinal cord disease include:
Other descending tracts include:
Other ascending tracts include:
Autonomic fibers of hypothalamic and brainstem origin descend in the lateral aspect of the spinal cord but not in a well-defined tract. These synapse with cell bodies in the intermediolateral columns of the central gray matter of the spinal cord. Sympathetic fibers exit between T1 and L2, and parasympathetic fibers exit between S2 and S4.
The sympathetic neurons lie in the lateral horn of the central gray matter at spinal levels T1-L3. The preganglionic fibers exit via the ventral root, spinal nerve, and ventral ramus to reach the paravertebral ganglion. Many will synapse at the paravertebral ganglion; others pass through it to terminate on postganglionic neurons (e.g., coeliac, superior mesenteric, and inferior mesenteric ganglia) more proximate to their end organ.
Parasympathetic neurons originate in the sacral spinal cord and exit the spinal cord with other afferents to the ventral ramus. After leaving the ventral ramus, they may subsequently join with sympathetic nerves to reach the viscera. These preganglionic fibers then synapse with a diffuse network of terminal ganglion cells that affect organs in the pelvis.
Autonomic dysfunction is an important determinant of site, extent, and severity of spinal cord pathology. Many autonomic functions can be affected by spinal cord pathology, but for clinical evaluation, the most useful symptoms relate to bladder control.
Autonomic bladder control is primarily parasympathetic and is unaffected by isolated injury to the sympathetic fibers. Voluntary bladder control is under somatomotor control, mediated by motor fibers originating from the anterior horn cells at levels S2-S4. A spinal cord lesion that interrupts descending motor and autonomic tracts above the S2 level produces an "automatic bladder" that cannot be emptied voluntarily, but empties reflexly when expanded to a certain degree, the so-called neurogenic bladder.13-16 Loss of descending inhibition of segmental reflex control leads to urinary urgency and incontinence. Injury to S2-S4 spinal levels interrupts the bladder reflex circuit. The bladder becomes flaccid and fills beyond capacity with overflow incontinence.
Other autonomic functions are disturbed by spinal cord pathology. The effects of spinal cord injury on the colon and rectum are similar to those of the bladder. Spinal cord transections interrupt voluntary control of the external sphincter and produce constipation. Sacral lesions cause a loss of the anal reflex and rectal incontinence. Impotence can result from spinal cord lesions at any level. Spinal cord injuries can also affect cardiovascular function, most dramatically with lesions above T6 which can produce a phenomenon of autonomic dysreflexia.
A single anterior and two posterior spinal arteries supply the spinal cord (Figure 8). The anterior spinal artery supplies the anterior two-thirds of the cord.17-21 The posterior spinal arteries primarily supply the dorsal columns. The anterior and posterior spinal arteries arise from the vertebral arteries in the neck and descend from the base of the skull. Various radicular arteries branch off the thoracic and abdominal aorta to provide additional blood supply to the spinal arteries. The largest and most consistently present of these radicular branches is the great ventral radicular artery or the artery of Adamkiewicz, which supplies the anterior spinal artery.22 This artery enters the spinal cord anywhere between T5 and L1 (usually between T9 and T12).
In most individuals, the anterior spinal artery passes uninterrupted along the entire length of the spinal cord. In others, it is discontinuous, usually in its midthoracic segment, making these individuals more susceptible to vascular injury. The primary watershed area of the spinal cord in most individuals is in the midthoracic region.
A spinal cord lesion may be suspected when there are bilateral motor and sensory signs or symptoms that do not involve the head or face.
As well as longitudinal localization within the spinal cord, it can also be helpful to distinguish specific areas of functional loss with a spinal cord level (or across spinal cord levels for nonsegmental pathologies). Some disorders affecting the spinal cord preferentially affect different structures, and therefore careful testing of all spinal cord functions, including motor, reflex, and all sensory modalities, and sphincter function is important for clinical localization.
Several distinct spinal cord syndromes are recognized. These are useful for the clinical evaluation, as they often correspond to distinct pathologies. These are summarized in Table 1 and are further discussed below.
| Syndrome | Clinical Manifestations | Causes |
|---|---|---|
| Segmental (Transection) Syndrome | Loss of all sensory modalities, weakness below affected level; bladder dysfunction | Trauma, spinal cord hemorrhage, epidural or intramedullary abscess, transverse myelitis, epidural metastasis |
Dorsal (Posterior) Cord Syndrome | Loss of proprioception, vibratory sensation, variable weakness; bladder dysfunction | Tabes dorsalis, Friedreich ataxia, subacute combined degeneration, AIDS myelopathy, epidural and extramedullary metastases, cervical spondylotic myelopathy, multiple sclerosis, atlantoaxial subluxation |
Ventral Cord (Anterior Spinal Artery) Syndrome | Loss of pain and temperature sensation, weakness; bladder dysfunction | Spinal cord infarction, intervertebral disc herniation, radiation myelopathy, HTLV-1 |
Brown Sequard (Hemi-Cord) Syndrome | Ipsilateral weakness and loss of proprioception; contralateral loss of pain and temperature sensation | Knife or bullet injuries, multiple sclerosis, spinal cord tumors, disc herniation, infarction, infection |
Pure Motor Syndrome | Weakness without sensory disturbance | Poliomyelitis, post-polio syndrome, primary lateral sclerosis, amyotrophic lateral sclerosis, HTLV-1, hereditary spastic paraplegia, lathyrism, progressive muscular atrophy, electric shock-induced myelopathy |
Conus Medullaris Syndrome | Bladder and rectal dysfunction; saddle anesthesia | Disc herniation, spinal fractures, tumors |
Cauda Equina Syndrome | Asymmetric multiradicular pain, leg weakness, and sensory loss; bladder dysfunction | Intervertebral disc herniation, epidural abscess, epidural tumor, intradural extramedullary tumor, lumbar spine spondylosis, spinal arachnoiditis, chronic inflammatory demyelinating polyneuropathy, sarcoidosis, carcinomatous meningitis, cytomegalovirus, herpes simplex virus, herpes zoster virus, Epstein Barr virus, Lyme disease, mycoplasma, and tuberculosis |
Pathologies that affect all functions of the spinal cord at one or more levels produce a segmental syndrome. Loss of function may be total or incomplete. A total cord transection syndrome results from the cessation of function in all ascending and descending spinal cord pathways and results in the loss of all types of sensation and loss of movement below the level of the lesion. Less profound injuries produce a similar pattern of deficits, which are less severe, i.e., weakness rather than paralysis and decreased sensation rather than anesthesia.
Acute transection can cause spinal shock, with a flaccid paralysis, urinary retention, and diminished tendon reflexes. Acute transection is usually temporary, and increased tone, spasticity, and hyperreflexia will usually supervene in days or weeks after the event.
Transverse injuries above C3 involve cessation of respiration and are often fatal if acute. Cervical cord lesions that spare the phrenic nerve but impair intercostal nerve function can produce respiratory insufficiency. Lesions above the L2 cord level will cause impotence and spastic paralysis of the bladder. There is loss of voluntary control of the bladder, which will empty automatically by reflex action.
Causes of segmental syndrome include acute myelopathies, such as traumatic injury and spinal cord hemorrhage. Epidural or intramedullary abscess, tumors, and transverse myelitis may have a more subacute presentation.
Dorsal cord syndrome results from the bilateral involvement of the dorsal columns, the corticospinal tracts, and descending central autonomic tracts to bladder control centers in the sacral cord (Figure 9). Dorsal column symptoms include gait ataxia and paresthesias. Corticospinal tract dysfunction produces weakness that, if acute, is accompanied by muscle flaccidity and hyporeflexia and, if chronic, by muscle hypertonia and hyperreflexia. Extensor plantar responses and urinary incontinence may be present.
Causes of a dorsal cord syndrome include multiple sclerosis (more typically the primary progressive form), AIDS myelopathy, tabes dorsalis, Friedreich ataxia, subacute combined degeneration, vascular malformations, epidural and intradural extramedullary tumors, cervical spondylotic myelopathy, and atlantoaxial subluxation.
Ventral cord or anterior spinal artery syndrome usually includes tracts in the anterior two-thirds of the spinal cord, which include the corticospinal tracts, the spinothalamic tracts, and descending autonomic tracts to the sacral centers for bladder control. Corticospinal tract involvements produce weakness and reflex changes. A spinothalamic tract deficit produces the bilateral loss of pain and temperature sensation. Tactile, position, and vibratory sensation are normal. Urinary incontinence is usually present.
The causes of a ventral cord syndrome include spinal cord infarction, intervertebral disc herniation, radiation myelopathy, and HTLV-1.
A lateral hemisection syndrome, also known as the Brown–Sequard syndrome, involves the dorsal column, corticospinal tract, and spinothalamic tract unilaterally. This condition produces weakness, loss of vibration and proprioception ipsilateral to the lesion, and loss of pain and temperature on the opposite side. The unilateral involvement of descending autonomic fibers does not produce bladder symptoms. While there are many causes of this syndrome, knife or bullet injuries and demyelination (such as occurs in multiple sclerosis) are the most common. Rarer causes include spinal cord tumors, disc herniation, infarction, and infections.
The central cord syndrome is characterized by loss of pain and temperature sensation in the distribution of one or several adjacent dermatomes at the site of the spinal cord lesion caused by the disruption of crossing spinothalamic fibers in the ventral commissure. Dermatomes above and below the level of the lesion have normal pain and temperature sensation, creating the so-called "suspended sensory level." Vibration and proprioception are often spared.
As a central lesion enlarges, it may encroach on the medial aspect of the corticospinal tracts or on the anterior horn gray matter, producing weakness in the analgesic areas. Fibers mediating the deep tendon reflexes are interrupted as they pass from the dorsal to the ventral horn, thus causing tendon reflex loss in the analgesic areas. There are usually no bladder symptoms.
The classic causes of a central cord syndrome are slow-growing lesions such as syringomyelia or intramedullary tumor. However, central cord syndrome is most frequently the result of a hyperextension injury in individuals with long-standing cervical spondylosis. This form of central cord syndrome is characterized by disproportionately greater motor impairment in upper compared with lower extremities, bladder dysfunction, and a variable degree of sensory loss below the level of injury.26-28Clinicians frequently provide treatment to clients that have experienced a non-traumatic spinal cord injury. As Healthcare professionals understanding common, non-traumatic causes of myelopathy including inflammatory diseases, infections, vascular diseases, toxic-metabolic disorders, inherited-degenerative conditions, and neoplasms will positively affect the ability to proficiently assess, prepare a plan of care, implement the plan and evaluate its outcomes and explain deficits to other healthcare professionals. The below scenario demonstrates how increased awareness of non-traumatic spinal cord injury can improve outcomes for clients. A 60-year-old female client is referred from an Urgent Care Center, Workman’s Compensation physician, for Outpatient Occupational Therapy to evaluate and treat the client with right shoulder pain, secondary to work-related upper extremity strain. During the initial evaluation, the client indicates that she works for a local airline. She is the manager of the baggage claim department, specifically the area where lost baggage is stored until the owner is located and comes in for a pickup. She has been a manager for five years but has worked in the same department for 10 years. On this particular day, she was filling in for another agent, when she needed to place a small boarding bag on a top shelf. The client reports that when she raised the bag up over her head, she felt “electrical shock like” sensations down her back. Further investigation reveals that she experienced this same sensation about two weeks ago when washing her hair. Client states that she feels that her right arm is getting weak and impacting her ability to fasten a bra, wash her hair, as well as her ability to function optimally at her job. Physical exam included ROM of both UE’s, which is WNLs. Strength assessment of BUE’s that indicates clients:
Each of these assessments indicates the client has a significant loss of strength in the RUE. Sensory exam indicated the client presents with:
Each of these assessments indicates the client has impaired motor and sensory function along the C 6-7 myotome/dermatome. The client is scheduled for Occupational Therapy, 3x a week x 2 weeks. The treatment plan includes Therapeutic Ex-strengthening program. Self-Care Training-use of compensatory strategies to don/doff bra and wash hair and patient education. Therapeutic Activities- including functional task practice and task modification. The above evaluation is faxed to the MD, with a follow-up phone call. During the phone call, the OT expressed concerns and advised the MD of findings of the exam with emphasis on the assessment results that are inconsistent with a strain, including; complaints of shock like sensations when extending head (+ Lhermitte’s sign), strength loss of RUE, and loss of sensation along the C6-7 myotome/dermatome. The OT suspects the client has been misdiagnosed or presents with multiple diagnoses. Following the MD’s review, it is determined that the client has a probable cervical spondylosis, a form of central cord syndrome, as well as a shoulder strain. |
A pure motor syndrome produces weakness without sensory loss or bladder involvement. This condition may involve only the upper motor neurons, producing hyperreflexia and extensor plantar responses, or only the lower motor neuron bilaterally, producing muscle atrophy and fasciculations. Other disorders involve both the upper and lower motor neurons and produce mixed signs.
The causes of a pure motor syndrome include chronic myelopathies such as HTLV-I myelopathy, hereditary spastic paraplegia, primary lateral sclerosis, amyotrophic lateral sclerosis, progressive muscular atrophy, post-polio syndrome, and electric shock-induced myelopathy.
Lesions at vertebral level L2 often affect the conus medullaris. There is early and prominent sphincter dysfunction with flaccid paralysis of the bladder and rectum, impotence, and saddle (S3-S5) anesthesia. Leg muscle weakness may be mild if the lesion is very restricted and spares both the lumbar cord and the adjacent sacral and lumbar nerve roots.
Causes include disc herniation, spinal fracture, and tumors.13,29
Though not a spinal cord syndrome, cauda equina syndrome is considered here because its location within the spinal canal subjects it to many of the same disease processes that cause myelopathy. The syndrome is caused by the loss of functions of two or more of the 18 nerve roots constituting the cauda equina. Deficits usually affect both legs but are often asymmetric.
Symptoms include30-32:
Many etiologies can cause a cauda equina syndrome, including intervertebral disc herniation, epidural abscess, epidural tumor, intradural extramedullary tumor, lumbar spine spondylosis, and a number of inflammatory conditions including spinal arachnoiditis, chronic inflammatory demyelinating polyneuropathy, and sarcoidosis.29,33-38 The cauda equina can also be the primary site of involvement in carcinomatous meningitis and a number of infections (e.g., cytomegalovirus, herpes simplex virus, herpes zoster virus, Epstein Barr virus, Lyme disease, mycoplasma, and tuberculosis).
This well-described sign describes electric shock-like sensations that run down the back and/or limbs during flexion of the neck. This condition generally occurs with pathologies involving the cervical spinal cord but is not specific to etiology, occurring in patients with cervical spondylotic myelopathy,39 multiple sclerosis, radiation myelopathy, and vitamin B12 deficiency, among others. It can also occur with cervical nerve root pathology.
The differential diagnosis of myelopathy is wide, but can be significantly narrowed by the clinical syndrome (Table 1 above). Other features in the examination and history also limit the differential diagnosis and tailor the diagnostic work-up. Clinical features of some of the more common causes of myelopathy are outlined in Table 2.
| Age | Course | Clinical Features | Diagnosis | |
|---|---|---|---|---|
Cervical spondylotic myelopathy | Usually >60 years | Progressive or stepwise course | Moderate-severe cases demonstrate gait and leg spasticity and amyotrophy of hand or arms | MRI cervical spine |
Transverse myelitis | Children, young adults | Subacute | Segmental cord syndrome | MRI and CSF |
| Viral myelitis | Any age | Acute-subacute | Pure motor syndrome or Segmental cord syndrome | MRI and CSF |
| Epidural abscess | Any age | Subacute; may worsen abruptly | Segmental cord syndrome | MRI |
| Infarction | Usually >60 years | Abrupt onset | Anterior cord syndrome | MRI with diffusion weighted sequences |
Vascular malformation | >40 years (dural fistula) 20's (intramedullary AVM) | Acute and/or stepwise | Radicuomyelopathy | MRI, spinal angiography |
Subacute combined degeneration | Any age | Slowly progressive | Dorsal cord syndrome | Vitamin B12 levels |
Radiation | Any age | Slowly progressive; beginning 6-12 months after radiation therapy | Segmental cord syndrome or Ventral cord syndrome | MRI, clinical history |
Syringomyelia | Children, young adults | Slowly progressive | Central cord syndrome | MRI |
Epidural metastasis | Usually >50 years | Subacute, may worsen abruptly | Segmental cord syndrome | MRI |
Intramedullary tumor | Young adults | Slowly progressive | Central cord syndrome | MRI with gadolinium enhancement |
ALS | Usually >60 years | Progressive | Pure motor syndrome | Electromyography |
*MRI: magnetic resonance imaging; CSF: cerebrospinal fluid; AVM: arteriovenous malformation; ALS: amyotrophic lateral sclerosis.
For patients with a clinical syndrome that suggests a localized process within the spinal cord (e.g., transection syndrome, central cord syndrome, ventral cord syndrome, etc.), an imaging study, usually magnetic resonance imaging (MRI), of the relevant section of the spinal cord is usually required.25,40 Administration of gadolinium contrast is often helpful. When an infectious or inflammatory disorder is suspected, CSF examination may be helpful. The role of positron emission tomography in evaluating patients with myelopathy is under investigation. It appears to be particularly sensitive to neoplastic disease.41
In general, the pace at which spinal cord deficits appear dictates the urgency of the neurologic evaluation. Even when the deficits are not severe, acute myelopathic signs need to be evaluated urgently because neurologic deterioration can occur abruptly, and the clinical deficit at the time of intervention often dictates the chances of recovery. This is true particularly for compressive etiologies such as spinal cord metastases and epidural spinal abscess.
TM is a segmental spinal cord injury caused by acute inflammation.42-44 The inflammation of TM is generally restricted to one or two segments, usually in the thoracic cord. TM is uncommon, with an approximate incidence of between one to five cases per million population annually.45
Most cases of TM are idiopathic and presumably result from an autoimmune process. Up to half of these patients have a preceding infection.46-48 TM can also occur in multiple sclerosis (MS) and can be the presenting demyelinating event.49 Neuromyelitis optica or Devic's disease is a disorder related to MS, in which demyelinating events are limited to the optic nerve and spinal cord.
Indicative Signs and Symptoms | Suggested Evaluation |
|---|---|
Infectious Etiology | |
Fever | CSF Gram stain and bacterial culture |
Meningismus | CSF PCR: HSV-1, HSV-2, HHV-6, VZV, CMV, EBV, enteroviruses |
Rash | CSF viral culture |
Concurrent systemic infection | CSF acid-fast bacilli smear and tuberculous culture |
Recurrent genital infection | CSF anti-Borrelia burgdorferi antibodies |
Symptoms of zoster radiculopathy | CSF VDRL |
Adenopathy | CSF India ink and fungal culture |
Residence in area endemic for parasitic infections | Chest radiograph |
Lymphadenopathy | Serology for antibodies to HIV, HSV, VZV, HTLV-1, B. burgdorferi |
Serology for hepatitis A, B, C, and Mycoplasma | |
Consider serology for parasites | |
Blood cultures | |
Systemic Inflammatory Disease (Vasculitis, Collagen Vascular Diseases, Mixed Connective Tissue Disease) | |
| Rash | Serum ACE |
| Oral or genital ulcers | Auto-antibodies: ANA, ds-DNA, Ro/SSA, La/SSB, Sm, RNP |
| Adenopathy | Complement levels |
| Livedo reticularis | Urinalysis with microscopic analysis for hematuria |
| Serositis | Lip/salivary gland biopsy |
| Photosensitivity | Chest CT with intravenous contrast |
| Inflammatory arthritis | Schirmer test |
| Erythema nodosum | Chest radiograph |
| Xerostomia | Gallium scan |
| Keratitis | Antiphospholipid antiodies (anticardiolipin antibodies, Russel viper venom time, partial thromboplastin time) |
Conjunctivitis | |
Contractures or thickening of skin | |
Anemia/leukopenia/thrombocytopenia | |
Raynaud phenomenon | |
History of arterial and venous thrombosis | |
Multiple Sclerosis | |
Previous demyelination event | Brain MRI |
Incomplete deficit clinically with MRI abnormality ≤2 spinal segments and <50 percent of cord diameter | Evoked potentials |
CSF oligoclonal bands and IgG index | |
Neuromyelitis Optica (Devic's Disease) | |
Optic neuritis | Evoked potentials |
Clinical deficit with MRI abnormality ≥3 spinal segments | Brain MRI (usually negative) |
NMO-IgG testing | |
Idiopathic Transverse Myelitis | |
No clinical or paraclinical features suggestive of another diagnostic category | Evoked potentials |
Electromyography/nerve conduction velocity | |
*ACE: angiotensin-converting enzyme; ANA: anti-nuclear antibodies; CMV: cytomegalovirus; CSF: cerebrospinal fluid; EBV: Epstein-Barr virus; HHV: human herpes virus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; HTLV-1: human T-cell lymphotropic virus 1; IgG: immunoglobulin G; NMO-IgG: neuromyelitis optica IgG autoantibody; VDRL: Venereal Disease Research Laboratory; VZV: varicella zoster virus.*ACE: angiotensin-converting enzyme; ANA: anti-nuclear antibodies; CMV: cytomegalovirus; CSF: cerebrospinal fluid; EBV: Epstein-Barr virus; HHV: human herpes virus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; HTLV-1: human T-cell lymphotropic virus 1; IgG: immunoglobulin G; NMO-IgG: neuromyelitis optica IgG autoantibody; VDRL: Venereal Disease Research Laboratory; VZV: varicella zoster virus.
Modified with permission from: Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002; 59:499. Copyright © 2002 Lippincott Williams & Wilkins.Modified with permission from: Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002; 59:499. Copyright © 2002 Lippincott Williams & Wilkins.
The granulomatous inflammation of sarcoidosis can affect the spinal cord and produce an acute or subacute segmental myelopathy.46,69-71 The lesions can be extramedullary or intramedullary and can involve the cauda equine, as well as, the cord.
The granulomatous inflammation of sarcoidosis can affect the spinal cord and produce an acute or subacute segmental myelopathy.46,69-71 The lesions can be extramedullary or intramedullary and can involve the cauda equine, as well as, the cord.
A number of distinct paraneoplastic syndromes involving the spinal cord has been described. These rare syndromes include:
Spinal epidural abscess is a rare disease, occurring in only one patient per 10,000 requiring hospital admission.75 The most common pathogen is Staphylococcus aureus, which accounts for about two-thirds of cases.75 Damage to the spinal cord can be caused by direct compression of neural elements or arterial blood supply, thrombosis and thrombophlebitis of nearby veins, focal vasculitis, and/or bacterial toxins and mediators of inflammation.
Viral invasion of the anterior horn cells occurs as part of an acute viral illness. Two distinct syndromes of spinal cord involvement are associated with acute viral disease.
The virus targets the gray matter of the spinal cord, producing acute lower motor neuron disease.77
A second form of viral myelitis has clinical and diagnostic test features that are similar to transverse myelitis. The association between the myelitis and the virus is not always clear. In some cases, these may represent a post infectious transverse myelitis. In others, a positive polymerase chain reaction (PCR) test in the CSF suggests that the myelitis is directly related to the viral infection.
HIV infection produces a vacuolar myelopathy, which is found in up to half of patients with AIDS at autopsy.76,90 The pathogenesis of vacuolar myelopathy is unknown but may be related to abnormal transmethylation mechanisms induced by the virus and/or cytokines. Pathological descriptions include demyelination of the dorsal columns and the dorsal half of the lateral columns, with prominent vacuoles within the myelin sheaths. This pathologic appearance is similar to the changes seen in the subacute combined degeneration of the cord.
Clinical manifestations occur when the pathology is advanced, and only about one-fourth of patients demonstrating vacuolar myelopathy at autopsy have symptoms during life.91
Human T-cell lymphotropic virus type I (HTLV-1) causes a progressive neurologic disease, which is called either HTLV-1-associated myelopathy (HAM) or tropical spastic paraparesis (TSP).94,95 Pathologic studies demonstrate inflammation of the lateral corticospinal, spinocerebellar, and spinothalamic tracts, with relative sparing of the posterior columns.96
This disorder is endemic in southern Japan, the Caribbean, South America, the Melanesian islands, Papua New Guinea, the Middle East, and central and southern Africa, with seroprevalences as high as 30% in southern Japan.97-99 In contrast, it is quite rare in the United States and Europe. It is more common in women than men.
Syphilitic meningomyelitis and meningovascular myelitis represent an earlier form of syphilis infection in which focal inflammation of the meninges secondarily affects the adjacent spinal cord thus presenting as a subacute progressive myelopathy101 and/or affects the anterior spinal artery where the clinical presentation may be one of a spinal cord infarction. Tabes dorsalis is a form of tertiary neurosyphilis in which the dorsal or posterior columns of the spinal cord are primarily affected.
Tuberculosis can produce a myelopathy by different mechanisms. Infection of the vertebral body leads to tuberculous spondylitis or Pott's disease, which can lead to secondary cord compression. Tuberculomas within the intramedullary, intradural, and extradural space can also produce myelopathy. 102,103
The parasites Schistosoma mansoni and Schistosoma haematobium typically infect the spinal cord. The lower thoracic region of the spinal cord is most frequently involved, followed by the lumbar and sacral regions. Spinal cord involvement can lead to permanent paralysis. Cysticercosis (i.e., infection caused by eggs of the pork tapeworm) has been reported to cause a cyst within the spinal cord.104
Bacterial meningitis may be complicated by a myelopathy due to formation of an epidural abscess, myelitis, or vasculitic infarction.107-109
Lyme disease rarely affects the spinal cord. However, cases have been described in which clinical and MRI features resembling acute transverse myelitis have been attributed to Lyme disease. 110,111 CSF in these cases typically demonstrates a lymphocytic pleocytosis and elevated protein.
Infarction of the spinal cord is rare compared with cerebral infarction.
Clinical Presentation is consistent with the functional loss within the anterior spinal artery territory and include:
Less than half of patients show substantial motor recovery following spinal cord infarction.112,121
Vascular malformations of the spinal cord are classified into types according to their location and vascular pathology. 122,123
Dural arteriovenous fistula is the most common type, making up about 70% of all lesions.124 These exist on the dural surface, and drain intradurally by retrograde flow through a single medullary vein to the anterior or posterior median vein, resulting in engorgement of the coronal venous plexus.
Intramedullary spinal arteriovenous malformations (AVMs)135,136 are supplied by medullary arteries and drain through medullary veins.
Spinal epidural hematoma can complicate procedures that involve a spinal dural puncture, usually in patients with thrombocytopenia or bleeding diathesis, including anticoagulant therapy.138 This rarely occurs spontaneously.
Deficiency in vitamin B12 (cyanocobalamin) leads to degeneration of the dorsal and lateral white matter of the spinal cord.
Nitrous oxide abuse can also lead to subacute combined degeneration, by inactivation of vitamin B12.148-151
A syndrome similar to the subacute combined degeneration of vitamin B12 deficiency can occur with acquired copper deficiency.
Result of gastrointestinal surgery
Excessive zinc ingestion (e.g., overuse of denture cream).152-154
Treatment can prevent progression
Myelopathy is a serious complication of radiation therapy to the spinal cord.155,156 White matter tracts in the lateral aspects of the cord are preferentially affected.157,158
Two distinct Clinical Presentations are described:
High voltage electrical injury can be associated with a variety of neurologic complications, including spinal cord injury. Direct heat and electrical injury to neural elements, as well as, a delayed microvascular disease are proposed mechanisms.
Progressive myelopathy is a rare neurologic complication of chronic liver disease with portal hypertension.166-169 Neuropathological studies have demonstrated demyelination of the lateral corticospinal tracts with various degrees of axonal loss.168
Impairment of spinal cord function can be a manifestation of decompression sickness, a complication of deep sea diving.171-175 Gaseous occlusion of venous plexus within the spinal cord is one postulated mechanism of injury.
Two disorders of spastic paraparesis have been described, which occur in association with increased dietary intake of food plants with neurotoxic potential, as occurs in certain geographic regions during times of famine.176,177 Pathologic studies have demonstrated a loss of myelinated fibers in the corticospinal and spinocerebellar tracts. The toxin appears to be the neuroexcitatory amino acid, beta-N-oxalylaminoalanine.
Neurolathyrism is associated with prolonged consumption of the grass or chickling pea (Lathyrus sativus).178
Konzo is a disorder characterized by acute spastic paraparesis or quadriparesis. It is linked to high exposure to cyanogenic compounds in diets containing insufficiently processed bitter cassava (Manihot esculenta).179,180 This disorder is less well characterized than lathyrism, and it may reflect a disorder of intracranial rather than intraspinal motor pathways.
Both benign and malignant tumors can produce a myelopathy as a result of external compression or intramedullary growth.
The most common syndrome is that of extradural spinal cord compression, as produced by metastases to the extradural space.
Intramedullary spinal cord tumors are typically primary CNS tumors (ependymoma, astrocytoma). Metastases are less likely.183,184
Myelopathy can also occur as a complication of radiation therapy, as a complication of intrathecal chemotherapy, particularly methotrexate and cytarabine and as a paraneoplastic syndrome.
ALS is a neurodegenerative disorder that produces progressive weakness, usually with mixed upper and motor neuron signs.186,187
Unusual variants of ALS with atypical symptoms can present a diagnostic challenge. Primary lateral sclerosis is a rare variant of ALS with primarily upper motor neuron features.188
HSP is a large group of inherited neurologic disorders, in which the prominent feature is a progressive spastic paraparesis.194 HSP is classified according to the mode of inheritance, the genetic locus when known, and whether the spastic paraplegia syndrome occurs alone or is accompanied by additional neurologic or systemic abnormalities ("pure" versus "complicated").195-199 There have been no recent epidemiological studies, but previously the incidence has been reported to be between 1 in 10,000 and 1 in 100,000.
Genetically diverse, with at least 28 genetic loci for HSP identified, the final common pathway for these disorders is a degeneration of the corticospinal tracts.195 Inheritance is usually autosomal dominant, but recessive and X-linked variants (e.g., Pelizaeus-Merzbacher disease) are known.
Adrenomyeloneuropathy, a variant of Adrenoleukodystrophy, an x-linked recessive disorder.
Friedreich ataxia is an autosomal recessive degenerative disorder of uncertain pathogenesis that typically presents in adolescence.203 The neuropathologic changes in Friedreich ataxia include degeneration of the posterior columns and the spinocerebellar tracts of the spinal cord and loss of the larger sensory cells of the dorsal root ganglia.
Syringomyelia is a fluid-filled, gliosis-lined cavity within the spinal cord. Most lesions are between C2 and T9. They can, however, descend further down or extend upward into the brainstem (syringobulbia). A syrinx can represent a focal dilation of the central canal, or it may lie separately, within the spinal cord parenchyma.205
In many case series, cervical spondylotic myelopathy is the most common cause of myelopathy, particularly in older adults.4 Degenerative changes in the vertebral bodies, discs, and connecting ligaments encroach on the cervical canal, producing a progressive myelopathy.211
OPLL is a condition of abnormal calcification of the posterior longitudinal ligament, usually in the cervical spine.213-218 Its pathogenesis is not known.
A syndrome of acute low back pain followed by progressive lower extremity numbness and weakness without apparent trauma has been described in at least 26 patients while surfing.220-225
Disorders that affect the spinal cord often target specific structural and functional anatomic regions, producing distinct clinical syndromes. The spinal cord syndromes are summarized in the table (Table 1 above). The clinical syndrome along with other features in the examination and history usually significantly limits the differential diagnosis and tailors the diagnostic work-up (Table 2 above).
Pathologies that affect the spinal cord are diverse. In addition to trauma, common nontraumatic etiologies of myelopathy include inflammatory diseases, infections, vascular diseases, toxic-metabolic disorders, inherited-degenerative conditions, neoplasms and a plethora of others. The neurologic examination will characterize the deficits as to the spinal cord syndrome. The spinal cord syndrome along with the clinical setting and course of presentation with the findings of a neuroimaging study (usually magnetic resonance imaging) will identify the likely pathogenesis in most cases.
