Neuromyelitis Optica Spectrum Disorder (NMOSD)


Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an immunological disorder with manifestations similar to those of multiple sclerosis (MS). The lesions that form in NMOSD differ from those in MS in that they specifically affect the optic nerve and spinal cord, whereas MS is more diffuse and peripheral. NMOSD develops when autoantibodies attack the body tissues, specifically targeting a protein called aquaporin-4 (AQP4), which is found predominantly in the optic nerves and spinal cord.1

Etymology

The term neuromyelitis was defined in the Dictionnaire de l’Académie Française in 1836, but it was not widely used at the time. Following the publication of Robley Dunglison’s Medical Lexicon, which explained the etymology of the term (neuro-, “nerve”; myelo-, “marrow” or “spinal cord”; and -itis, “inflammation”), neuromyelitis was again defined in 1848 as “inflammation of the medullary matter of the nerves” in the Dictionary of Medical Science. Subsequent German dictionaries published the term in 1857 and 1863.2

History of NMOSD

In 1894, Eugène Devic (1858-1930) described the characteristics of a new syndrome that he called neuro-myélite optique aiguё, translated from French into English as “acute optic neuromyelitis.” That same year, Devic’s student, Fernand Gault (1873-1936), published his doctoral thesis, De la neuro-myélite optique aiguё, in which he reviewed the medical literature, described the features of the disease that his mentor had defined, and analyzed the pathophysiology. Many of the cited references were based on the works of a German ophthalmologist, Fritz Schanz.2 

Gault and Devic may have overlooked earlier possible cases of NMOSD.  Antoine Portal (1742-1832), first physician to King Louis XVIII, reported the first known account in the Western literature of vision loss in a patient with spinal cord inflammation in the absence of brain pathology. Other possible cases were described in 1844 by an Italian physician, Giovanni Battista Pescetto (1806-1884); in 1850 by a British physician, Christopher Mercer Durrant (1814-1901); and in 1862 by a British neuroanatomist, neuropathologist, and neurologist, Jacob Augustus Lockhart Clarke (1817-1880). Lastly, Thomas Clifford Allbutt, inventor of the clinical thermometer and a proponent of the clinical use of the ophthalmoscope, described a patient with acute myelitis and “a sympathetic eye disorder” in his 1870 lecture, “On the Ophthalmoscopic Signs of Spinal Disease,” although he never specifically used the term neuromyelitis optica.2 

The term acute optic neuromyelitis appeared in 1903 in the British Medical Journal and again in 1904 in the Practical Medicine Series of Year Books. The term neuromyelitis optica is credited to an Austrian psychiatrist, Erwin Stransky, who in 1904 reviewed and critiqued a report by the French pathologist and neurologist Edouard Brissaud, in which he described a case of NMOSD.2 

In 1907, the Turkish physician Peppo Acchioté suggested use of the eponym Devic’s disease or Devic’s syndrome for NMOSD. He also reported another case of bilateral optic neuritis, paraparesis, and sensory impairments.2

In 1935, the German neurologist Erwin Stengel described a series of patients who had neuritis cranialis with brainstem encephalitis, referring to this condition as neuro-encephalitis. One of the patients had optic neuritis, which he described as neuro-encephalitis optica.2 

Another, earlier possible mention of neuro-encephalitis optica was discovered in the second edition of John Abercrombie’s (1780-1844) Pathological and Practical Researches on Diseases of the Brain and Spinal Cord. Manifestations of the disorder included recalcitrant vomiting, relapsing vision loss, intractable hiccups, and spinal pain, all of which are harbingers of myelitis and medulla oblongata involvement.2 

NMOSD in the 20th and 21st Centuries

During the past 120 years, various diagnostic criteria for NMOSD have been proposed. This biggest issue involved the differentiation of NMOSD from MS; the 2 conditions share many clinical characteristics. For a while, it was necessary to base the diagnosis of NMOSD on clinical and radiological findings indicating the presence of lesions on the spinal cord and optic nerves. In NMOSD,  the central regions of the nerves tend to be affected, with lesions rarely reaching the surface, whereas, in MS, the peripheral regions are more often affected.3 

Differentiation between NMOSD and MS became significantly easier after 2004, when researchers discovered a biomarker for NMOSD — pathogenic autoantibodies, or immunoglobulin G antibodies (IgGs), binding at or near the blood-brain barrier.4 In 2005, many of the same researchers discovered that the IgGs specifically attack AQP4 channels (AQP4-IgGs).5 In conjunction with radiological and clinical findings, laboratory results must indicate NMO-IgG seropositivity if NMOSD is to be diagnosed. NMO-IgG negativity indicates a possible diagnosis of MS.2 

However, recent investigations have identified a small subset of patients with symptoms of NMOSD but without AQP4-IgG seropositivity, suggesting that other pathological mechanisms may cause NMOSD symptoms. Because of the possibility that the same disorder may have multiple causes, it has been suggested that the term Devic disease be changed to Devic syndrome, referring to a clinical phenotype manifesting with specific symptoms of optic neuritis and myelitis. These clinical manifestations or phenotypes have recently been shown to be broad in scope; thus, many authors and researchers have proposed use of the term NMOSD spectrum disorder to indicate the variety of clinical manifestations of this disorder.2  

References

  1. Devic’s disease (neuromyelitis optica): symptoms & treatment. Cleveland Clinic. Accessed October 15, 2021.
  2. Jarius S, Wildemann B. The history of neuromyelitis optica. J Neuroinflammation. 2013;10:8. doi:10.1186/1742-2094-10-8
  3. Lalan S, Khan M, Schlakman B, Penman A, Gatlin J, Herndon R. Differentiation of neuromyelitis optica from multiple sclerosis on spinal magnetic resonance imaging. Int J MS Care. 2012;14(4):209-214. doi:10.7224/1537-2073-14.4.209
  4. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112. doi:10.1016/S0140-6736(04)17551-X
  5. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005;202(4):473-477. doi:10.1084/jem.20050304

Reviewed by Kyle Habet, MD, on 10/8/2021.

Reviewed by Kyle Habet, MD, on 10/8/2021.

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