Transverse Myelitis – Causes, Symptoms, Diagnosis, Treatment

Transverse myelitis

Transverse myelitis (TM) is a neurological disorder caused by inflammation of the spinal cord. Attacks of inflammation can damage or destroy myelin, the fatty insulating substance that covers nerve cell fibers and send impulses from the brain to the nervous system in the whole body. The spinal cord also carries sensory information back to the brain. The term myelitis refers to inflammation of the spinal cord; transverse refers to the pattern of changes in sensation—there is often a band-like sensation across the trunk of the body, with sensory changes below. This causes scars that interrupt communication between the nerves in the spinal cord and the rest of the body.

Transverse myelitis (TM) is a pathogenetically heterogeneous focal inflammatory disorder of the spinal cord characterized by acute or subacute development of motor weakness, sensory impairment, and autonomic dysfunction. [rx] MRI of the spinal cord reveals a focal hyperintense lesion and cerebrospinal fluid usually shows pleocytosis. The causes of TM are heterogeneous, but partial TM (asymmetric, short cord lesions) is associated with multiple sclerosis, whereas longitudinally extensive lesions are associated with neuromyelitis optica spectrum disorders. [rx][rx] [rx]

Transverse myelitis can affect people of any age, gender, or race. It does not appear to be genetic or run in families. The disorder typically occurs between ages 10 and 19 years and 30 and 39 years.

Transverse Myelitis

Types of Transverse Myelitis

  • Ascending Myelitis
  • Brown-Sequard Syndrome
  • Concussion Myelitis
  • Foix-Alajouanine Myelitis
  • Funicular Myelitis
  • Subacute Necrotizing Myelitis
  • Systemic Myelitis

Pathophysiology

This demyelination arises idiopathically following infections or due to multiple sclerosis. One major theory posits that immune-mediated inflammation is present as the result of exposure to a viral antigen. The diarrhea-causing bacteria Campylobacter jejuni is also a reported cause of transverse myelitis. The lesions are inflammatory and involve the spinal cord typically on both sides. With acute transverse myelitis, the onset is sudden and progresses rapidly in hours and days. The lesions can be present anywhere in the spinal cord, though they are usually restricted to only a small portion.

Causes of Transverse Myelitis 

https://rxharun.com/Transverse Myelitis 

The exact cause of transverse myelitis and extensive damage to nerve fibers of the spinal cord is unknown in many cases.  Cases in which a cause cannot be identified are called idiopathic.  However, looking for a cause is important, as some will change treatment decisions.

A number of conditions appear to cause transverse myelitis, including:

  • Immune system disorders.  These disorders appear to play an important role in causing damage to the spinal cord.  Such disorders are:
    • an aquaporin-4 autoantibody associated neuromyelitis optica
    • multiple sclerosis
    • 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 –  It is often difficult to know whether a direct viral infection or a post-infectious response to the infection causes transverse myelitis. Associated viruses include 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, pertussis, tetanus, diphtheria, measles, and rubella.
  • Bacterial infections  – Such as syphilis, tuberculosis, actinomyces, 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, intraspinal cavernous malformations, or disk embolism.
  • Multiple sclerosis  – Is a disorder in which the immune system destroys myelin surrounding nerves in your spinal cord and brain. Transverse myelitis can be the first sign of multiple sclerosis or represent a relapse. Transverse myelitis as a sign of multiple sclerosis usually causes symptoms on only one side of your body.
  • Neuromyelitis Optica (Devic’s disease)  – Is a condition that causes inflammation and myelin loss around the spinal cord and the nerve in your eye that transmits information to your brain. Transverse myelitis associated with neuromyelitis optica usually affects both sides of your body.

Symptoms of Transverse Myelitis 

There are disturbances in sensory nerves and motor nerves and dysfunction of the autonomic nervous system at the level of the lesion or below. Therefore, the signs and symptoms depend on the area of the spine involved

Transverse Myelitis 

  • Cervical – If the upper cervical cord is involved, all four limbs may be involved and there is a risk of respiratory paralysis (cervical nerve segments C3, 4, 5 innervate the abdominal diaphragm). Lesions of the lower cervical (C5–T1) region will cause a combination of upper and lower motor neuron signs in the upper limbs and exclusively upper motor neuron signs in the lower limbs. Cervical lesions account for about 20% of cases.
  • Thoracic – A lesion of the thoracic spinal cord (T1–12) will produce upper motor neuron signs in the lower limbs, presenting as spastic diplegia. This is the most common location of the lesion, and therefore most individuals will have weakness of the lower limbs.
  • Lumbar – A lesion of the lower part of the spinal cord (L1–S5) often produces a combination of upper and lower motor neuron signs in the lower limbs. Lumbar lesions account for about 10% of cases.

Transverse Myelitis 

Other early symptoms can include:

  • Pain –  Transverse myelitis pain may begin suddenly in your lower back. Sharp pain may shoot down your legs or arms or around your chest or abdomen. Pain symptoms vary based on the part of your spinal cord that’s affected.
  • Abnormal sensations – Some people with transverse myelitis report sensations of numbness, tingling, coldness, or burning. Some are especially sensitive to the light touch of clothing or to extreme heat or cold. You may feel as if something is tightly wrapping the skin of your chest, abdomen, or legs.
  • Weakness in your arms or legs –  Some people notice that they’re stumbling or dragging one foot, or heaviness in the legs. Others may develop severe weakness or even total paralysis.
  • Sensitivity to touch (allodynia) — experienced by as many as 80 percent of people; a sensitivity in which clothing or a light touch with a finger causes significant discomfort or pain.
  • 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. 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.
  • Weakness – in the arms or legs (paraparesis)
  • Sensory symptoms (paresthesias) such as numbness, tingling, burning, tickling, or prickling in the legs, feet, or toes.
  • Heightened sensitivity to changes in temperature or to extreme heat or cold.
    Muscle weakness
  • Muscle and/or joint pain
  • Breathing or swallowing difficulties
  • Increased sensitivity to cold temperatures
  • Difficulty in sleeping
  • A decline in the ability to perform basic daily activities.
  • Fatigue.

Diagnosis of Transverse Myelitis

In 2002 the Transverse Myelitis Consortium Working Group proposed the following diagnostic criteria for idiopathic acute transverse myelitis:

Inclusion criteria

  • Motor, sensory or autonomic dysfunction attributable to spinal cord
  • Signs and symptoms on both sides of the body (not necessarily symmetrical)
  • Clearly defined the sensory level
  • Signs of inflammation (pleocytosis of the cerebrospinal fluid, or elevated immunoglobulin G, or evidence of inflammation on gadolinium-enhanced (MRI) Magnetic resonance imaging)
  • The peak of this condition can occur anytime between 4 hours to 21 days after onset.Transverse Myelitis 

Exclusion criteria

  • Irradiation of the spine (e.g., radiotherapy) in the last 10 years
  • Evidence of thrombosis of the anterior spinal artery
  • Evidence of extra-axial compression on neuroimaging
  • Evidence of arteriovenous malformation (abnormal flow voids on surface of spine)
  • Evidence of connective tissue disease, e.g. sarcoidosis, Behçet’s disease, Sjögren’s syndrome, systemic lupus erythematosus or mixed connective tissue disease
  • Evidence of optic neuritis (diagnostic of neuromyelitis optica
  • Evidence of infection (syphilis, Lyme disease, Human immunodeficiency virus, Human T-lymphotropic virus 1, mycoplasma, Herpes simplex virus, Varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, Human herpesvirus 6 or enteroviruses)
  • Evidence of multiple sclerosis (abnormalities detected on MRI and presence of oligoclonal antibodies in cerebrospinal fluid(CSF))
  • Blood tests – may be performed to rule out various disorders such as HIV infection, vitamin B12 deficiency, and many others.  Blood is tested for the presence of autoantibodies (anti- aquaporin-4, anti-myelin oligodendrocyte) and a host of antibodies associated with cancer (paraneoplastic antibodies) that may be found in people with transverse myelitis.
  • Lumbar puncture – (also called a spinal tap) uses a needle to remove a small sample of the cerebrospinal fluid that surrounds the brain and spinal cord.  In some people with transverse myelitis, the cerebrospinal fluid contains more protein than usual and an increased number of white blood cells (leukocytes) that help the body fight infections.
  • Computerized tomography (CT) scan – uses powerful magnets or radio waves to make a detailed image, while a CT scan puts several X-rays together for a more complete picture than one X-ray alone.
  • Magnetic resonance imaging(MRI) – produces a cross-sectional view or three-dimensional image of tissues, including the brain and spinal cord. A spinal MRI will almost always confirm the presence of a lesion within the spinal cord, whereas a brain MRI may provide clues to other underlying causes, especially MS. In some instances, computed tomography (CT) may be used to detect inflammation.

Transverse Myelitis 

Treatment of Transverse Myelitis

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

Initial treatments and management of the complications of transverse myelitis

  • Intravenous corticosteroid drugs – may decrease swelling and inflammation in the spine and reduce immune system activity.  Such drugs may include methylprednisolone or dexamethasone (usually administered for 3 to 7 days and sometimes followed by a tapering off period).  These medications may also be given to reduce subsequent attacks of transverse myelitis in individuals with underlying disorders.
  • 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.
  • 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 those 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.
  • Maintaining strong bones – People with transverse myelitis are at an increased risk of developing osteoporosis because of limited activity. Talk to your doctor about calcium and vitamin D supplements to improve bone health. Weight-bearing exercises, if possible, will also strengthen bones.
  • Preventing bowel problems – If you have bowel problems caused by transverse myelitis, eat a fiber-rich diet and drink plenty of fluids to help prevent constipation.
  • 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.

Following initial therapy, it is a critical part to keep the person’s body functioning while hoping for either complete or partial spontaneous recovery of the nervous system.

Management of Neuromyelitis Optica

Medication Use Typical dose Evidence
  • High dose IV methylprednisolone
 Acute 1 gm IV daily for 5 days with or without a taper Observational studies
  • Plasma exchange
 Acute as a rescue therapy 5 exchanges (each exchange 250 ml) over 5-10 days Randomized trials in TM patients
  • Rituximab
 Maintenance 1 gm (or 375 mg/m2) IV every 1-2 weeks for 2-4 weeks then redoes based on CD19 count (typically every 6-8 month) for ≤ 2 years Several open label and retrospective clinical trials
  • Azathioprine
 Maintenance 2 mg/kg PO divided BID (typically 100 mg BID) for ≤2 years Observational studies
  • Mycophenolate
 Maintenance 1-3 gm PO daily divided BID or TID for ≤2 years Retrospective trial
  • Methotrexate
 Maintenance 5-15 mg PO weekly for ≤2 years Open label trial
  • Mitoxantrone
 Maintenance 12 mg/m2 every 3 months (maximum dose 140 mg/m2) Open-label trial
  • Cyclophosphamide
 Maintenance 0.5-1.5 mg/m2 (typically 1 gm) IV every month until absolute lymphocyte count<1000/mm3 (typically 6 cycles) or immunoablative dose of 200 mg/kg divided over 4 days Open-label trial
  • IVIG
 Maintenance 2 gm/kg induction followed by 0.4-0.5 gm/kg every month Case series

Prevention of future transverse myelitis 

  • Most transverse myelitis only occurs once (called monophasic).  In some cases, chronic (long-term) treatment with medications to modify the immune system response is needed.  Examples of underlying disorders that may require long-term treatment include multiple sclerosis and neuromyelitis optica.
  • Treatment of MS with immunomodulatory or immunosuppressant medications may be considered when it is the cause of myelitis.   These medications include alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-beta, natalizumab, and teriflunomide, among others.

Immunosuppressants

  • 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.

Rehabilitative and long-term therapy

Many forms of long-term rehabilitative therapy are available for people who have disabilities resulting from transverse myelitis.  Strength and functioning may improve with rehabilitative services, even years after the initial episode.  Rehabilitative therapy teaches people strategies for carrying out activities in new ways in order to overcome, circumvent, or compensate for permanent disabilities.  Although rehabilitation cannot reverse the physical damage resulting from transverse myelitis, it can help people, even those with severe paralysis, become as functionally independent as possible and attain the best possible quality of life.

Common neurological deficits resulting from transverse myelitis include severe weakness, spasticity, or paralysis; incontinence, and chronic pain.  In some cases these may be permanent.  Such deficits can substantially interfere with a person’s ability to carry out everyday activities such as bathing, dressing, and performing household tasks.   Individuals with lasting neurological defects from transverse myelitis typically consult with a range of rehabilitation specialists, who may include physiatrists (physicians specializing in physical medicine and rehabilitation), physical therapists, occupational therapists, vocational therapists, and mental health care professionals.

  • Physical therapy – Can help retain muscle strength and flexibility, improve coordination, reduce spasticity, regain greater control over bladder and bowel function, and increase joint movement.  It also can help to reduce the likelihood of pressure sores developing in immobilized areas.  Individuals are also taught to use assistive devices such as wheelchairs, canes, or braces as effectively as possible.
  • Occupational therapy – Teaches people new ways to maintain or rebuild their independence by participating in meaningful, self-directed, everyday tasks such as bathing and dressing.  Therapists teach people how to function at the highest level possible, by developing coping strategies, suggesting changes in their homes to improve safety (such as installing grab bars in bathrooms), and changing obstacles in their environment that interfere with normal activity.
  • Vocational therapy –  Involves offering instructions to help people develop and promote work skills, identify potential employers, and assist in job searches.  Vocational therapists act as mediators between employees and employers to secure reasonable workplace accommodations.
  • Psychotherapy – For people living with permanent includes strategies and tools to deal with stress and a wide range of emotions and behaviors.

Supportive therapy and acute rehabilitation

Supportive therapy for individual symptoms such as respiratory distress, pain, and urinary retention may be added to the treatment regimen as required.

  • Respiratory failure – in a minority of patients with cervical TM, the lesion extends into the medulla and may cause neurogenic respiratory failure. Close observation of respiratory parameters, including measurement of maximal respiratory pressures and forced vital capacity, and involvement of a skilled critical care team are recommended in cases of ascending cervical myelitis.
  • Neuropathic pain – may be acute or chronic. Acute pain can be treated with narcotic analgesics, gabapentin, or carbamazepine. Chronic pain often responds to anticonvulsants or tricyclic antidepressant drugs.
  • Acute urinary retention – may be managed by bladder catheterization. Residual neurogenic bladder symptoms may include urge incontinence, retention, or a mixed disorder, each of which requires specific treatment.
  • DVT prevention – immobilized patients are at increased risk. Extrapolation of data from general medical and orthopedic surgery patients indicates that subcutaneous heparin or enoxaparin plus use of lower extremity compression stockings or devices reduces the risk of DVT.

Acute rehabilitation consists of passive and active therapy to maintain range of motion of limbs; reduce spasticity, spasms, and risk of contractures; and reduce the risk of decubitus ulceration.

Herbal/Ayurvedic/Home Treatment

  • Omega-three fatty acids help reduce inflammation from any cause and very effective in a dose of 5-7 grams daily in acute attacks.
  • Turmeric is very effective in the treatment of spinal cord inflammation use 1-2 grams daily in milk. In allopathic medications, steroids and IVIg are both effective and there is a huge role of antibiotics and antiviral.
  • If the organism is unknown then use a Tens unit, Hulda Clark zapper, or silver colloid. Hydrogen peroxide is an alternative experimentally used in the treatment. Finally are old cases of untreated transverse myelitis please consider stem cell transplant. At cidpusa.org we have had great success with doxycycline in the treatment of transverse myelitis.
  • A patient has treated with ganciclovir and cytomegalovirus (CMV) hyperimmune globulin. He gradually improved and recovered completely within 4 weeks. This case suggests that ganciclovir and CMV hyperimmune globulin appear to be effective for the treatment of EBV-induced transverse myelitis in immunocompromised patients following BMT. (Bone Marrow Transplant)

Homeopathic Remedies

  • Ledum Pal– Pain along the entire course of the nerve and pain increased by movement and better by rest. Better by placing the limb in ice-cold water.
  • Agaricus– Weakness and trembling with stiffness all over. Itching of toes and feet feels frozen. Cramps in soles of the feet and spasmodic contraction of the arms.
  • Tarantula Hisp– Sensation of insects crawling under the skin, extreme restless of the limbs with a desire to move constantly, which partially relieves all the complaints.

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 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 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

Transverse Myelitis