Neuromyelitis optica spectrum disorder
[1][4] The signs and symptoms of NMOSD depend on the neurologic structures the disease affects, and, to some extent, the antibodies involved.
[1][4][2][7][8][9] The myelitis can be transverse, affecting an entire cross-section of the spinal cord, and showing bilateral symptoms.
[4] Lesions in the brain stem or upper cervical spinal cord can cause respiratory insufficiency.
Lesions in the area postrema of the medulla oblongata can cause vomiting or hiccups, as well as pain and tonic spasms.
[21] The astrocytes surround the blood–brain barrier (BBB), a system responsible for preventing substances in the blood from entering the brain.
For antibodies from the blood to reach astrocytes in the central nervous system (CNS), they must cross the BBB, the mechanism of which is not completely known.
[22] There is broad consensus that AQP4/NMO-IgG initially enters the brain via BBB-deficient sites such as the area postrema, where there is access to cerebrospinal fluid (CSF).
[1] NMOSD brain lesions, as seen under a microscope, show IgG, Immunoglobulin M (IgM), inflammatory cells, and complement deposits around blood vessels.
[1] AQP4-IgG is a member of the IgG1 immunoglobulin family, which is an activator of the complement system, which seems to play an integral part in the autoimmune response.
[1] MOG-IgG-positive NMOSD brain lesions, as seen under a microscopic, show demyelination with preservation of oligodendrocytes and axons, presence of inflammatory cells, and IgG and complement deposits.
[34] If AQP4-IgG is undetected, or its status is unknown, two core clinical criteria, each with supportive MRI findings, along with the ruling out of alternative diagnoses, are needed for an NMOSD diagnosis.
In addition oligoclonal bands in the CSF as well as white matter lesions on brain MRIs are uncommon in NMO, but occur in over 90% of MS patients.
[51] Tumefactive demyelinating lesions in NMO are not usual, but they have been reported to appear in several cases mistakenly treated with interferon beta.
[53] Since the discovery of the AQP4 autoantibody, it has been found that it appears also in patients with NMO-like symptoms that do not fulfill the clinical requirements to be diagnosed with NMO (recurrent and simultaneous optic nerve and spinal cord inflammation).
[54] The term neuromyelitis optica spectrum disorders (NMOSD) has been designed to allow incorporation of cases associated with non-AQP4 biomarkers.
[55] Some authors propose to use the name "autoimmune aquaporin-4 channelopathy" for these diseases,[15] while others prefer a more generic term "AQP4-astrocytopathy", which also includes deficiencies of AQP4 with a non-autoimmune origin.
[1] Traditionally, attacks have been treated with short courses (3–5 days) of high dosage intravenous corticosteroids, such as methylprednisolone IV (Solu-Medrol).
[1][59] However, there is no high-level evidence for steroids affecting long-term outcomes; this treatment strategy was borrowed from that for similar diseases (idiopathic optic neuritis and multiple sclerosis).
However, at least 85% of patients have a relapsing form of the disease with repeated attacks of transverse myelitis and/or optic neuritis.
In patients with the monophasic form, the transverse myelitis and optic neuritis occur simultaneously or within days of each other.
[71] Unlike MS, NMO rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission.
In some patients (33% in one study), transverse myelitis in the cervical spinal cord resulted in respiratory failure and subsequent death.
[18] A retrospective study found that prevalence of neuromyelitis optica spectrum disorders was 1.5% among a random sample of neurological patients, with a MS:NMOSD ratio of 42:7.
In the indigenous populations of tropical and subtropical regions, MS is rare; but when it appears, it often takes the form of OSMS.
[citation needed] First reports on an association of spinal cord with optic nerve disorders date back to the late 18th and early 19th century.
[74][75] However, only an 1870 report by Sir Thomas Clifford Allbutt created sustained interest on the part of neurologists and ophthalmologists in this rare syndrome.
[76] In 1894, Eugène Devic and his PhD student Fernand Gault described 16 patients who had lost vision in one or both eyes and within weeks developed severe spastic weakness of the limbs, loss of sensation, and often of bladder control.
[74][77][78] In 2002, Mayo Clinic researchers identified a humoral mechanism, targeting a perivascular protein, as the culprit of NMO,[26] and in 2004 an unknown specific autoantibody was found.
[79] In 2005 they identified the aquaporin 4 protein as the target of the disease, and developed the first in-house test to aid in the diagnosis of NMO by detection of an antibody, AQP4-IgG, in the blood.
[19] The first quantitative ELISA (enzyme-linked immunosorbent assay) kits were soon developed,[80] However, serum AQP4-IgG titer only moderately reflects disease activity, severity, or neurological prognosis.
