Myelitis (Spinal Cord Inflammation)

Transverse myelitis MRI[1]

Myelitis is infection or inflammation of myelin (the lipoid membrane covering nerve fibers) sensu stricto of the spinal cord resulting, as it were, in disruption of transmission of nerve impulses between the spinal cord and the rest of the body. The signs and symptoms of myelitis depend upon the cause and location of the lesions.


Presentation

The signs and symptoms of myelitis are determined by the causative agent (infectious or immune-mediated), location of the lesions and associated disease(s).  

These are (in alphabetical order):

The onset of symptoms in transverse myelitis (TM) is characterized by sudden neck and back pain, with loss of bladder or bowel control. Sharp pains are common. Poliomyelitis is accompanied by fever, headache, nausea, fatigue, stiffness and pain in the neck, back and extremities.

The duration of illness in TM is from a few hours to several days (acute) or more than 1 to 4 weeks (subacute). Chief complains include localized lower back pain, paresthesias (abnormal sensations of tickling, burning, pricking, or tingling) in the legs, loss of sensorium, and paraparesis. At a later stage, paraplegia may ensue, with urinary bladder and bowel dysfunctions. Some patients may experience muscle spasms, discomfort, headache, fever, anorexia and respiratory problems depending on the location of lesions in the spinal cord

Workup

Diagnosis of TM:

  • In addition to medical history and neurologic examination, magnetic resonance imaging (MRI) of the spinal cord is needed, with or without paramagnetic contrast (with gadolinium) to visualize the lesions and cord swelling. Contrast enhancement can facilitate the observation of inflammation or gross abnormality in the cord. 
  • Spinal tap to obtain a sample of CSF to assess leukocytosis (increased white blood cell counts) as a measure of presence and degree of inflammation.
  • Blood tests to rule out concomitant disorders e.g., HIV infectionsystemic lupus erythematosus,  avitaminosis B12, NMO-IgG in Devic's disease, MS, etc.

In the absence of an identifiable etiologic agent the condition is diagnosed to be idiopathic transverse myelitis (IATM).

Treatment

Early diagnosis and treatment is important. Given the varied nature of myelitis, only after thorough consideration of probable cause and clinical course of each type of myelitis, may one prescribe the following modes of treatment: 

  • Intravenous steroids - high IV dose of methyl-prednisolone for 3-5 days.
  • Plasma exchange or plasmapheresis (PLEX) - for patients not responding to steroid therapy.
  • Immunotherapy - medications that modulate or suppress the immune system.
  • Rehabilitation - radical treatment and long-term management of symptoms.
  • Physical therapy - for long-term recovery and restoration of functionality; it teaches the patient the use of self-help devises.
  • Occupational therapy - to develop the ability to perform daily routinary activities.
  • Psychotherapy - to alleviate anxiety neurosis, sexual dysfunction and to develop coping mechanisms.

Prognosis

Recovery from transverse myelitis is expected within 2 to 12 weeks after the onset of symptoms, or longer; it may extend up to 2 years and beyond in some cases. Otherwise the likelihood for complete recovery is nil without evident clinical improvement within 3 to 6 months. Partial recovery, if at all, may be expected with aggressive physical therapy and rehabilitation. 

In retrospect, with conservative therapy, one third of patients recover sufficiently as to be able to resume certain activities normally such as walking, with improved urinary and bowel functions and minimal paresthesia. A third group may recover partially with residual deficits such as spastic gait, sensory dysfunction, and urinary urgency or incontinence. Refractory patients may remain bedridden or wheelchair-bound and unable to perform normal daily functions. It has been shown that prognosis is poor with rapid onset of symptoms. Nonetheless, radical therapy and long-term rehabilitation should be undertaken. 

Etiology

Causes of myelitis:

  • Bacterial: e.g., Mycobacterium tuberculosis.
  • Viral: e.g., poliovirus (human enterovirus, Family Picornaviridae), HIV (human immunodeficiency virus) can cause chronic myelitis). 
  • Fungal: e.g., Cryptococcus neoformans, Histoplasma capsulatum.
  • Autoimmune conditions: direct attack on nerve cells. 
  • Parasites: e.g., Schistosoma spp., Toxocara canis
  • Vaccination

Epidemiology

In the USA less than 200,000 people are affected by myelitis, hence, it is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health. However, this is not the case particularly in the tropics where infectious diseases are highly prevalent. 

A nationwide outbreak of acute myelitis in children has been reported in the literature [1]. Transverse myelitis (TM) affects all persons regardless  of age, gender, ethnic origin; evidently, with no hereditary predisposition. New cases are seen each year in the high risk groups of 10 to 19 years and 30 to 39 years. The annual incidence of TM in the U.S. is around 1,400; 33,000 Americans have some kind of disability that is associated with TM. Acute transverse myelitis (ATM) is either idiopathic, i.e., of unknown etiology (IATM) or secondary, i.e., associated with a known cause or condition (SATM). IATM is an immune-mediated demyelinating inflammation of the spinal cord. The annual incidence of IATM is estimated between 1 in 1,000,000 and 1 in 250,000 population.

SATM is linked to an infectious disease entity or an autoimmune condition. Other parts of the nervous system may be involved thus, the optic nerves in multiple sclerosis (MS) and neuromyelitis optica (NMO) or Devic's disease, the peripheral nerves in systemic lupus erythematosus (SLE) or anti-Ro/SS-A antibodies in Sjogren's syndrome. Direct attack or invasion of the spinal cord by parasites and microbial pathogens can likewise cause SATM. The incidence of SATM depends on a multiplicity of causes hence it is difficult to come up with a composite estimate. 

Sex distribution
Age distribution

Pathophysiology

The histopathology of acute transverse myelitis (ATM) is confined to the spinal cord. For example, the histology differs from multiple sclerosis. In MS, axons are usually intact and lesions are few and scattered (primary demyelination) whereas in ATM there is extensive demyelination and damage to axons; lesions may be cavitary in severe transverse myelitis.

Necrotizing processes  are involved in addition to inflammation and demyelination as in Devic's disease, acute hemorrhagic leukoencephalitis and progressive necrotizing myelopathy. These diseases differ in their clinical course, histology, serum marker and nature of the lesions. Neuromyelitis optica (NMO), or Devic's disease, is characterized by an immune attack on the optic nerve and spinal cord. Serological tests in 70% of patients with NMO have an IgG antibody called aquaporin-4 (AQP4). In both Devic's disease and TM, lesions are located in the center of the cord with intact sections in subpial areas. Cerebrospinal fluid (CSF) shows elevated protein with transient or absent oligoclonal bands. The spinal cord is swollen in MRI. In a study, antibodies against myelin-associated glycoprotein were found in all cases of Devic's disease [2]. The finding of aquaporin 4 in NMO differentiates cases of optic neuritis and myelitis from multiple sclerosis, heretofore, necessitating a different therapeutic approach [3].

Inflammatory cytokines e.g., IL-6 is increased in CSF in MS and inflammatory neurologic diseases. The elevation can reach 300-fold in cases of idiopathic transverse myelitis versus non-IAMT [4]. 

Prevention

  • To prevent the occurrence of post-vaccinal myelitis forego new vaccination during the acute stage of the disease or when there is a strong index of suspicion of possible myelitis.
  • Prophylactic measures and/or vaccination against influenza in upper respiratory tract infections; supportive treatment with sunlight and vitamin D, eliminate habit of smoking and weight control in MS.
  • Modification of these risk factors is likewise recommended in idiopathic transverse myelitis.

When the prospect of clinical cure appear to outweigh the associated risk of neurological problems arising after vaccination, which is considered very low, the choice of preventive measure should be based on that premise.

Summary

Myelitis is a disorder of the central nervous system (CNS) particularly the spinal cord. There are several types of myelitis each with a different etiology namely:

  • Grey matter - consisting of demyelinated neurons (nerve cells without sheaths), as in poliomyelitis, a viral infection causing muscle weakness and paralysis.
  • White matter - myelinated (with sheaths) neurons, as in leukomyelitis and herpes vrus infection.
  • Transverse myelitis - inflammatory demyelinated nerves on both sides of the spinal cord
  • Meningococcal myelitis - lesions in the meninges (the protective membrane around the brain and spinal cord). 
  • Multiple sclerosis (MS or encephalomyelitis) - damaged nerve coverings in the brain and spine, causing various physical and mental disabilities.
  • Post-vaccinal myelitis - side effects of vaccination.

Patient Information

  • Myelitis is a disease entity which involves inflammation of the spinal cord. Transverse myelitis (TM) means that the inflammation occurs on both sides of the spinal cord. The exact cause of TM is unknown.
  • Inflammation may be due to any of the following i.e., infection with disease-causing organisms, insufficient blood flow through blood vessels in the spinal cord, or to the effect of immune processes which can damage myelin, the membrane covering nerve fibers.  This causes lesions that disrupt the transmission of impulses between the nerves in the spinal cord and the rest of the body.
  • Transverse myelitis may likewise develop as a complication of infectious diseases or as an adverse effect of vaccinations, as in chickenpox and rabies.
  • The duration of symptoms of TM may last for few hours to several weeks starting as a sudden attack of muscle weakness, abnormal sensations in the toes and feet or lower back pain, rapidly progressing to more severe stages, with paralysis, urinary bladder and bowel dysfunctions.
  • Some people may recover fully or partially from TM with little or no residual effects, others may suffer permanent disabilities that prevent them from resuming normal daily living.
  • Demyelination at the thoracic level results into problems with leg movement, bowel and bladder control; these functions are dependent upon signals from the lower regions of the spinal cord.
  • Pain, the chief complain in 50% of TM patients, includes lower back or sharp, shooting sensations in the extremities and around the torso. About 80 percent experience heightened sensitivity to touch and temperature changes, and discomfort or pain (allodynia). 
  • Medical history and thorough neurological examination are important for effective treatment.

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References

  1. CDC. Acute flaccid myelitis: interim considerations for clinical management. Atlanta, GA: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/ncird/downloads/acute-flaccid-myelitis.pdf
  2. Haase CG, Schmidt S. Detection of brain-specific autoantibodies to myelin oligodendrocyte glycoprotein, S100beta and myelin basic protein in patients with Devic’s neuromyelitis optica. Neurosci Lett 2001;307:131-3.
  3. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-12.
  4. Kaplin AI, Deshpande DM, Scott E, et al. IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis. J Clin Invest 2005;115:2731-41.

Media References

  1. Transverse myelitis MRI, CC BY-SA 3.0

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