Neuromyelitis optica spectrum disorder: pathophysiological approach.

Aim: To review the main pathological findings of Neuromyelitis Optica Spectrum Disorder (NMOSD) associated with the presence of autoantibodies to aquaporin-4 (AQP4) as well as the mechanisms of astrocyte dysfunction and demyelination. Methods: An comprehensive search of the literature in the field was carried out using the database of The National Center for Biotechnology Information from . Systematic searches were performed until July 2022. Results: NMOSD is an inflammatory and demyelinating disease of the central nervous system mainly in the areas of the optic nerves and spinal cord, thus explaining mostly the clinical findings. Other areas affected in NMOSD are the brainstem, hypothalamus, and periventricular regions. Relapses in NMOSD are generally severe and patients only partially recover. NMOSD includes clinical conditions where autoantibodies to aquaporin-4 (AQP4-IgG) of astrocytes are detected as well as similar clinical conditions where such antibodies are not detected. AQP4 are channel-forming integral membrane proteins of which AQ4 isoforms are able to aggregate in supramolecular assemblies termed orthogonal arrays of particles (OAP) and are essential in the regulation of water homeostasis and the adequate modulation of neuronal activity and circuitry. AQP4 assembly in orthogonal arrays of particles is essential for AQP4-IgG pathogenicity since AQP4 autoantibodies bind to OAPs with higher affinity than for AQP4 tetramers. NMOSD has a complex background with prominent roles for genes encoding cytokines and cytokine receptors. AQP4 autoantibodies activate the complement-mediated inflammatory demyelination and the ensuing damage to AQP4 water channels, leading to water influx, necrosis and axonal loss. Conclusions: NMOSD as an astrocytopathy is a nosological entity different from multiple sclerosis with its own serological marker: immunoglobulin G-type autoantibodies against the AQP4 protein which elicits a complement-dependent cytotoxicity and neuroinflammation. Some patients with typical manifestations of NMSOD are AQP4 seronegative and myelin oligodendrocyte glycoprotein positive. Thus, the detection of autoantibodies against AQP4 or other autoantibodies is crucial for the correct treatment of the disease and immunosuppressant therapy is the first choice.

Neuromyelitis optica spectrum disorder in Western Mexico.

BACKGROUND: Neuromyelitis Optica Spectrum Disorders (NMOSD) are a group of inflammatory diseases of the Central Nervous System (CNS) that primarily affect the optic nerve and spinal cord, usually with a severe and relapsing course. Due to the scarce information in non-Caucasian populations, we aimed to describe incidence, prevalence, and main clinical characteristics of NMOSD in a defined region in Mexico. MATERIALS AND METHODS: Descriptive, retrospective analysis of all reported cases of NMOSD attended in the neurology department of the UMAE-HE, CMNO, IMSS, the biggest third level hospital in Western Mexico. We searched the electronic medical records of the hospital for patients with a diagnosis of NMO, and reviewed all cases to confirm if they fulfilled NMOSD 2015 diagnostic criteria. Data were collected through a structured form. We described adjusted incidence and prevalence according to the WHO method, for the IMSS affiliated total population in Jalisco state in 2019. RESULTS: 67 NMOSD patients were included in the analysis of clinical data, with a mean age at onset of symptoms of 36 years ((Rivera et al., 2008-65). Most patients were female (74.6%). 53 patients living in Jalisco by the end of 2019 were included in the analysis of prevalence and incidence. Adjusted prevalence was 0.71/100,000 (95% CI 0.55-0.92), while adjusted incidence was 1.87/1,000,000 person-years (95% CI 1.11-3.16). In the full cohort, the first symptom of NMOSD was optic neuritis in 49.3% of the patients, followed by transverse myelitis (23.9%) and area postrema syndrome (10.4%). 62 patients relapsed in a mean follow-up of 2 years (0-7). 5 patients with less than 6 months of follow up had not relapsed. 55.2% of the patients were AQP4-IgG +, 14.9% AQP4-IgG -, and 29.9% unknown status. CONCLUSIONS: Although NMOSD prevalence is similar to other reports around the world, incidence is higher than in Caucasian populations. We believe that this high incidence is related to an increased awareness of the disease in the era of new NMOSD treatments. Recurrent disease is very frequent in our cohort.