Idiopathic Transverse Myelitis – Causes, Symptoms, Treatment - Health

Idiopathic Transverse Myelitis/Myelitis is an acute or subacute rare demyelinating and immune-mediated inflammatory myelopathy disorder of the central nervous system and spinal cord resulting in potentially disabling neurological deficits such as motor weakness and sensory deficits, as well as autonomic dysfunction. It is potentially a devastating disorder with variable outcomes that characterized by a relatively acute onset of motor, sensory, and autonomic dysfunction [rx].

The term “myelitis” covers heterogeneous inflammatory conditions of the spinal cord that are characterized by acute-to-subacute motor, sensory, and autonomic dysfunctions, and may have various causes. Myelitis symptoms are caused by the destruction of ascending or descending pathways or the gray matter of the spinal cord. Patients with myelitis present with various sensory symptoms, with a disturbance in “sensory level” being the most characteristic feature.^[rx^,rx]

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder, which is sometimes called chronic relapsing polyneuropathy, is caused by damage to the myelin sheath (the fatty covering that wraps around and protects nerve fibers) of the peripheral nerves. Although it can occur at any age and in both genders, CIDP is more common in young adults, and in men more so than women. It often presents with symptoms that include tingling or numbness (beginning in the toes and fingers), weakness of the arms and legs, loss of deep tendon reflexes (areflexia), fatigue, and abnormal sensations. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart of that acute disease.

Synonyms


Transverse myelitis Acute transverse myelitis Acute complete transverse myelitis Acute partial transverse myelitis Longitudinally extensive transverse myelitis Idiopathic transverse myelitis Secondary transverse myelitis
ICD-10-CM Code
G37.3	Acute transverse myelitis in demyelinating disease of the central nervous system (Acute transverse myelitis NOS)
TM may also have been coded as:
G04.0	Acute disseminated encephalitis (Encephalitis and Encephalomyelitis: postimmunization)
G04.8	Another encephalitis, myelitis, and encephalomyelitis (Postinfectious encephalitis and encephalomyelitis NOS)
G05.0	Encephalitis, myelitis, or encephalomyelitis in bacterial diseases classified elsewhere
G05.1	Encephalitis, myelitis, or encephalomyelitis in viral diseases classified elsewhere
G05.2	Encephalitis, myelitis, or encephalomyelitis in other infectious and parasitic diseases classified elsewhere
G05.8	Encephalitis, myelitis, or encephalomyelitis in other diseases classified elsewhere
G35	Multiple sclerosis
G36.0	Neuromyelitis Optica (Devic)
G82.2	Paraplegia, unspecified (Paralysis of both lower limbs NOS, Paraplegia [lower] NOS)
G82.5	Tetraplegia, unspecified (Quadriplegia NOS)

Causes of Myelitis

Immune system disorders – appear to play an important role in causing damage to the spinal cord. Such disorders are:
- an aquaporin-4 autoantibody associated neuromyelitis optic. Neuromyelitis Optica is a disorder that affects the eye nerves and spinal cord. Aquaporin-4 is a channel on the cell membrane that lets water enter the cell and helps maintain the chemical balance for processes to take place within the central nervous system. An antibody is a protein that binds to foreign substances that can attack the host organism.
- multiple sclerosis, a disorder in which immune system cells that normally protect us from viruses, bacteria, and unhealthy cells mistakenly attack the protective coating of myelin in the brain, optic nerves, and spinal cord
- the post-infectious or post-vaccine autoimmune phenomenon, in which the body’s immune system mistakenly attacks the body’s own tissue while responding to the infection or, less commonly, a vaccine
- an abnormal immune response to underlying cancer that damages the nervous system; or
- other antibody-mediated conditions that are still being discovered.
Viral infections – including herpes viruses such as varicella-zoster (the virus that causes chickenpox and shingles), herpes simplex, cytomegalovirus, and Epstein-Barr; flaviviruses such as West Nile and Zika; influenza, echovirus, hepatitis B, mumps, measles, and rubella. It is often difficult to know whether a direct viral infection or a post-infectious response causes transverse myelitis.
Bacterial infections – such as syphilis, tuberculosis, actinomyces, pertussis, tetanus, diphtheria, and Lyme disease. Bacterial skin infections, middle-ear infections, campylobacter jejuni gastroenteritis, and mycoplasma bacterial pneumonia have also been associated with the condition.
Fungal infections – in the spinal cord, including aspergillus, Blastomyces, coccidioides, and cryptococcus.
Parasites – including toxoplasmosis, cysticercosis, schistosomiasis, and angtiostrongyloides
Other inflammatory disorders – that can affect the spinal cord, such as sarcoidosis, systemic lupus erythematosus, Sjogren’s syndrome, mixed connective tissue disease, scleroderma, and Bechet’s syndrome.
Vascular disorders – such as arteriovenous malformation, dural arterial-venous fistula, intra-spinal cavernous malformations, or disk embolism.
Dynamic Mechanical Factors – Dynamic stressors refer to the abnormal motion of the cervical spine during flexion or extension, which can contribute to spinal cord injury synergistically with static mechanical factors. Flexion of the cervical spine may lead to compression of the spinal cord against osteophytes bars while extension may lead to compression against the hypertrophied ligamentum flavum [rx, rx, rx].
Lumbar Compression Fracture
Lumbar Degenerative Disk Disease
Lumbar Facet Arthropathy
Lumbar Spondylosis
Mechanical Low Backpain
Rehabilitation for Osteoarthritis
Rheumatoid Arthritis
Spondylodiskitis
Lumbar Compression Fracture
Lumbar Degenerative Disk Disease
Lumbar Facet Arthropathy
Lumbar Spondylosis
Mechanical Low Backpain
Rehabilitation for Osteoarthritis
Rheumatoid Arthritis
Spondylodiskitis

Symptoms of Myelitis

Myelitis may be either acute(developing over hours to several days) or subacute(usually developing over one to four weeks). The segment of the spinal cord at which the damage occurs determines which parts of the body are affected. Damage at one segment will affect function at that level and below. In individuals with transverse myelitis, myelin damage most often occurs in nerves in the upper back.

Four classic features of myelitis are

Weakness of the legs and arms – People with transverse myelitis may have weakness in the legs that progresses rapidly. If the myelitis affects the upper spinal cord it affects the arms as well. Individuals may developparaparesis(partial paralysis of the legs) that may progress to paraplegia(complete paralysis of the legs), requiring the person to use a wheelchair.
Pain – Initial symptoms usually include lower back pain or sharp, shooting sensations that radiate down the legs or arms or around the torso.
Sensory alterations – Transverse myelitis can cause paresthesias(abnormal sensations such as burning, tickling, pricking, numbness, coldness, or tingling) in the legs and sensory loss. Abnormal sensations in the torso and genital region are common.
Bowel and bladder dysfunction – Common symptoms include an increased frequency or urge to use the toilet, incontinence, and constipation.
Muscle spasms – Many individuals also report experiencing muscle spasms, a general feeling of discomfort, headache, fever, and loss of appetite, while some people experience respiratory problems. Other symptoms may include sexual dysfunction and depression and anxiety caused by lifestyle changes, stress, and chronic pain.
Motor symptoms – may vary depending on the level of the spinal cord involved. Upper cervical lesions (C1-C5) may affect all four extremities. Additionally, if the lesion affects the phrenic nerve (C3, C4, C5), it could lead to diaphragmatic dysfunction and respiratory failure.
Lesions in the lower cervical levels (C5-T1) – develop upper and lower motor neuron signs in the upper extremities and exclusive upper motor neuron signs in the lower extremities. Cervical lesions account for approximately 20% of cases.
Lesions in the thoracic region (T1-T12) – may cause both upper and lower motor neuron signs in the lower extremities. The thoracic region is the most commonly affected in TM cases (70%).
Lesions in the lumbosacral regions (L1-S5) – may cause both upper and lower motor neuron signs in the lower extremities. Lumbar lesions account for approximately 10% of cases. Sensory symptoms generally affect the level of the lesion or one of the levels above or below the lesion. Back pain in the corresponding area of the lesion may also be present.[rx]
weakness of the arms and legs,
sensory alterations such as burning, pricking, numbness, or sensory loss,
pain (usually in the lower back or down the legs and arms or around the torso),
and bowel and bladder dysfunction.

Diagnosis of Myelitis

History

Histopathophysiology of transverse myelitis is varied and is related to the underlying etiology. Classically, the majority of cases were characterized by perivascular infiltration, demyelination, and axonal injury by monocytes and lymphocytes at the lesion site.[rx] Heterogeneity, along with both gray and white matter involvement, gives evidence that this is not a pure demyelinating disorder. TM may, in fact, be a mixed inflammatory disorder involving neurons, axons, oligodendrocytes, and myelin. Alternative histopathologic causes of TM have been reported to include molecular mimicry and super antigen-mediated disease associated with autoimmune causes.[rx]

Physical examination

Gait – Examine balance issues or spasticity issues
Reflex examinations for hyperreflexia – Biceps, brachioradialis, patellar, Achilles
Lhermitte sign – Neck flexion causes an electric shock-like (positive exam)
Hoffman sign – Examiner will extend the distal phalanx of the long finger (or flick the end of the digit) then rapidly release this digit- the patient will respond with a reflex flexion of the thumb and/or index finger.
Crossed radial reflex – Extension of both the biceps and wrist following a biceps reflex test
Inverted radial reflex – Extension of both wrist extension and finger flexion following tapping the brachioradialis
Finger escape sign – The patient is unable to hold the ulnar digits in extension and adduction.
Grip test – Failure to repetitive making a tight fist

Provocative Tests in a Spinal Examination

Shoulder Abduction (Relief) sign – Active abduction of symptomatic arm achieved by patient placing their ipsilateral hand on their head. A positive test results in relief (or reduction) of cervical radicular symptoms.
Neck Distraction test – Active distractive force is applied by the examiner while grasping the patient’s head under the occiput and chin. A positive test results in relief (or reduction) of cervical radicular symptoms.
L’hermitte’s sign – Examiner passively flexes patient’s cervical spine. A positive test result is an electric shock-like sensation down the spine or extremities.
Hoffman’s sign – Passive snapping flexion of distal phalanx of patient’s middle finger. A positive test results in flexion-adduction of the ipsilateral thumb and index finger.
Adson’s test – Patient is instructed to inspire with chin elevated, and head rotated to the affected side. A positive test results in obliteration of radial pulse.
The Spurling test – as it was originally described, was performed by passive lateral flexion and compression of the head, though this is no longer considered the proper technique. The test is most commonly defined in the current literature as the passive cervical extension with rotation to the affected side and axial compression. The test is considered positive when radicular pain is reproduced (pain radiates to the shoulder or upper extremity ipsilateral to the direction of head rotation).[rx][rx]

Imaging

To diagnose transverse myelitis, a compressive cord lesion must be excluded first. Exclusion is usually performed by magnetic resonance imaging (MRI). This is followed by a confirmation of inflammation either by a gadolinium-enhanced MRI or lumbar puncture (LP).
A set of diagnostic criteria was developed but is generally reserved for research purposes as not all features are required to make the diagnosis in a clinical setting.[rx]

Diagnostic criteria include

Sensory, motor, or autonomic dysfunction originating from the spinal cord
T2 hyperintense signal changes on MRI
No evidence of a compressive lesion
Bilateral signs/symptoms.
Clearly defined sensory level.
Evidence of inflammatory process demonstrated by gadolinium enhancement on MRI, cerebrospinal fluid (CSF) analysis showing pleocytosis, or elevated immunoglobulin G (IgG) index.
Progression to nadir between 4 hours and 21 days

When considering TM as a possible diagnosis, it is recommended the following investigative analyses be performed:[rx]

Blood tests – may be performed to rule out various disorders, including HIV infection and vitamin B12 deficiency. Blood is tested for the presence of autoantibodies (anti- aquaporin-4, anti-myelin oligodendrocyte) and antibodies associated with cancer (paraneoplastic antibodies). The presence of autoantibodies (proteins produced by cells of the immune system) is linked to autoimmune disorders and point to a definite cause of transverse myelitis.
Laboratory (VDRL) test – oligoclonal bands, immunoglobulin G (IgG) index, and cytology.
Serum anti-aquaporin-4 (APQ-4)-IgG autoantibodies – anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies, B12 level, methylmalonic acid, serum antinuclear antibodies (ANA), Ro/SSA, and La/SSB autoantibodies, syphilis serologies, HIV antibodies, TSH and viral etiology tests as applicable.
Cerebrospinal fluid (CSF) – findings are lymphocytosis (usually less than 100/mm3) and increased protein level (usually 100-120 mg/dl). In 20%-50% of children with definite ATM, CSF analysis shows normal protein levels and white blood cell count [rx,rx,rx,rx]. In isolated ATMs, oligoclonal bands (OCBs) in CSF usually are not detected. However, OCBs are elevated in one-third of LETM patients [rx]. LP for CSF analysis including cell count with differential, protein, glucose, the Venereal Disease Research. If OCBs are detected in CSF, an increased risk of subsequent MS is expected; subsequent MS is expected [rx,rx].
Computed tomography (CT) – The term computed tomography or CT, refers to a computerized x-ray imaging procedure in which a narrow beam of x-rays is aimed at a patient and quickly rotated around the body, producing signals that are processed by the machine’s computer to generate cross-sectional images—or “slices”—of the body.
Gadolinium – enhancement can also distinguish acute cord ischemia, in which the blood-brain barrier is intact (absent enhancement) from non-vascular etiologies which may enhance (intramedullary tumor, etc.). Brain MRI with and without gadolinium contrast to evaluate for evidence of brain lesions. The normal evolution of cord infarction results in an enhancement in the subacute phase, approximately 3 to 4 days after the initial insult.[rx]
Digital subtraction angiography (DSA) – is rarely indicated in ASCI. When clinical features of venous/congestive myelopathy are present, or characteristic MRI findings (dilated vascular flow voids) are suggestive, DSA may be indicated to confirm suspected spinal arteriovenous malformation, fistula, or aneurysm.[rx]
Lumbar Puncture – CSF fluid analysis is generally not helpful in the initial workup of spinal cord ischemia. CSF may variably show elevated protein concentration which is nonspecific.[rx][rx] However, CSF analysis may help diagnose mimic pathologies such as viral myelitis and neuromyelitis optica when there is a high index of suspicion.[rx]
Torg ratio – Compares the diameter of the cervical canal to the width of the cervical body, on the lateral view. Mid-posterior vertebral body to the nearest point on the lamina, divided by the width of the corresponding vertebral body. A ratio lower than 0.8 may indicate congenital stenosis (baseline narrowing).
Brain MRI – with and without contrast for detecting MS or ADEM; CSF analysis for cell count, protein, glucose, OCBs, IgG index, and cytology; serum NMO IgG antibodies (anti-aquaporin-4 IgG); serum B12; methylmalonic acid; human immunodeficiency antibodies; thyroid function test; antiphospholipid antibodies, antinuclear antibodies, rheumatoid factor and anti-dsDNA [rx]. In more than 40% of children, asymptomatic brain MRI lesions are seen and may be a risk factor for developing MS or NMO [rx]. Ophthalmologic consultation for detecting comorbid optic neuritis is recommended for all patients [rx]. Some children with encephalopathy and young children may not have complaints of vision impairments [rx]. Additionally, neurophysiological findings of subclinical optic neuritis may exist [rx].

Additional testing may be performed in the appropriate clinical setting.

Neuro-ophthalmologic evaluation
Paraneoplastic evaluation
Infectious serologic and CSF studies
Nasopharyngeal swab for enteroviral PCR
Serum copper and ceruloplasmin (copper deficiency may mimic TM)
Serum vitamin B12 and vitamin E levels
Spinal angiogram
Prothrombotic evaluation
Salivary gland biopsy

Treatment 0f Myelitis

Treatments are designed to address infections that may cause the disorder, reduce spinal cord inflammation, and manage and alleviate symptoms.

Pharmacological Treatment

Initial treatments and management of the complications of myelitis include

Intravenous corticosteroid drugs – may decrease swelling and inflammation in the spine and reduce immune system activity. Such drugs may include methylprednisolone or dexamethasone. These medications may also be given to reduce subsequent attacks of transverse myelitis in individuals with underlying disorders.
Glucocorticoids – The standard of care and the first-line therapy for the treatment of myelitis is intravenous glucocorticoids. High-dose intravenous glucocorticoids should be initiated as soon as possible. There should not be a delay in treatment while waiting for test results. There are few contraindications to glucocorticoid therapy. Potential regimens would include methylprednisolone or dexamethasone for 3 to 5 days. Further duration of therapy should be directed as the clinical case progresses.
Plasma exchange therapy – (plasmapheresis) may be used for people who don’t respond well to intravenous steroids. Plasmapheresis is a procedure that reduces immune system activity by removing plasma (the fluid in which blood cells and antibodies are suspended) and replacing it with special fluids, thus removing the antibodies and other proteins thought to be causing the inflammatory reaction. Plasma exchange may be efficacious for acute central nervous system demyelinating disease, which fails to respond to glucocorticoid therapy.[rx][rx] Additionally, as knowledge expands regarding TM, immunomodulatory therapy such as cyclophosphamide, mycophenolate, or rituximab might offer benefit in chronic recurrent TM or resistant acute TM.
Intravenous immunoglobulin (IVIG) – is a treatment thought to reset the immune system. IVIG is a highly concentrated injection of antibodies pooled from many healthy donors that bind to the antibodies that may cause the disorder and remove them from circulation.
Pain medicines – that can lessen muscle pain include acetaminophen, ibuprofen, and naproxen. Nerve pain may be treated with certain antidepressant drugs (such as duloxetine), muscle relaxants (such as baclofen, tizanidine, or cyclobenzaprine), and anticonvulsant drugs (such as gabapentin or pregabalin).
Antiviral medications – may help individuals who have a viral infection of the spinal cord.
Medications can treat other symptoms and complications – including incontinence, painful muscle contractions called tonic spasms, stiffness, sexual dysfunction, and depression.
Immunomodulatory or immunosuppressant – medications such as alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-beta, natalizumab, or teriflunomide may be needed. Immunosuppressant treatments are used for neuromyelitis optica spectrum disorder and recurrent episodes of transverse myelitis that are not caused by multiple sclerosis. They are aimed at preventing future myelitis attacks (or attacks at other sites) and include steroid-sparing drugs such as mycophenolate mofetil, azathioprine, and rituximab

Following initial therapy, it is a critical part to keep the person’s body functioning during the recovery period. This may require placing the person on a respirator in the uncommon scenario where breathing is significantly affected.

What research is being done?

The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. NINDS is a component of the National Institutes of Health, the leading supporter of biomedical research in the world.

NINDS researchers are working to better understand how the immune system destroys or attacks the nerve-insulating substance called myelin in autoimmune diseases or disorders. Other work focuses on strategies to repair demyelinated spinal cords, including approaches using cell transplantation. This research may lead to a greater understanding of the mechanisms responsible for damaging myelin and may ultimately provide a means to prevent and treat transverse myelitis.

Glial cell studies – Glia, or neuroglia, are non-neuronal cells (they do not provide electrical impulses) in the nervous system that form myelin and provide support and protection for neurons. Oligodendrocyte progenitor cells (OPCs) are stem cells that generate myelin-producing oligodendrocytes, a type of glial cell. NINDS-funded scientists are studying cellular mechanisms that control the generation and maturation of OPCs to allow remyelination, which could be an effective therapy for transverse myelitis and spinal cord injury. Other NINDS-funded investigators are focusing on mechanisms and interventions designed to increase oligodendrocyte proliferation and remyelination after spinal cord injury.
Astrocytes – are another type of glial cell. The aquaporin-4 IgG antibody binds to astrocytes, which has led to an increased interest in its role in transverse myelitis of neuromyelitis optica spectrum disorder (NMOSD). The antibody appears to cause myelitis in NMOSD by activating other components of the immune system, resulting in injury to the spinal cord. Many studies are trying to better understand the role of astrocytes in autoimmune diseases.
Genetic studies – NINDS-funded scientists hope to develop a better understanding of the molecular control of central nervous system myelination and remyelination by studying the theBrg1(Brahma-related) gene that appears to be involved in oligodendrocyte myelination. The long-term objective of this research is to develop drugs that modulate the activity ofBrg1and other genes to promote myelination and remyelination.
Animal models – NINDS funds research using animal models of spinal cord injury aimed at replacing or regenerating spinal cord nerve cells. The ultimate goals of these studies are to develop interventions for the regeneration or remyelination of spared nerve fibers in humans and to restore function to paralyzed individuals.
Neuroimaging with MRI – Research funded by NINDS aims to develop and implement new MRI techniques to quantitatively assess the relationship between spinal cord pathology and neurological dysfunction in MS. This new approach may assess changes in lesions and myelin in MS and possibly transverse myelitis. Other NIH-funded researchers plan to develop MRI methodologies to non-invasively detect and characterize networks to identify the extent of injury to the spinal cord and to monitor the progression of recovery after injury. These techniques may aid in earlier detection of transverse myelitis and other neurological disorders such as MS.
Brain-machine interfaces and prosthetic devices – Scientists are developing brain-machine interfaces and neural prostheses to help people with spinal cord damage regain functions by bypassing the injury site. These sophisticated electrical and mechanical devices connect with the nervous system to supplement or replace lost motor and sensory function.

References

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