Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that preferentially affects the spinal cord and optic nerve. Most patients with NMOSD experience severe relapses that lead to permanent neurologic disability; therefore, limiting frequency and severity of these attacks is the primary goal of disease management. Currently, patients are treated with immunosuppressants. Interleukin-6 (IL-6) is a pleiotropic cytokine that is significantly elevated in the serum and the CSF of patients with NMOSD. IL-6 may have multiple roles in NMOSD pathophysiology by promoting plasmablast survival, stimulating the production of antibodies against aquaporin-4, disrupting blood-brain barrier integrity and functionality, and enhancing proinflammatory T-lymphocyte differentiation and activation. Case series have shown decreased relapse rates following IL-6 receptor (IL-6R) blockade in patients with NMOSD, and 2 recent phase 3 randomized controlled trials confirmed that IL-6R inhibition reduces the risk of relapses in NMOSD. As such, inhibition of IL-6 activity represents a promising emerging therapy for the management of NMOSD manifestations. In this review, we summarize the role of IL-6 in the context of NMOSD.

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The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder

BMC Neurology ◽

10.1186/s12883-021-02198-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhila Maghbooli ◽

Abdorreza Naser Moghadasi ◽

Nasim Rezaeimanesh ◽

Abolfazl Omidifar ◽

Tarlan Varzandi ◽

...

Keyword(s):

Insulin Sensitivity ◽

Neuromyelitis Optica ◽

Serum Levels ◽

Spectrum Disorder ◽

Control Group ◽

Neuromyelitis Optica Spectrum Disorder ◽

Downstream Signaling ◽

Reduce Insulin Sensitivity ◽

Circulating Levels

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. Methods We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. Results Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. Conclusions Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

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Acute-onset severe occipital neuralgia as a manifestation of neuromyelitis optica spectrum disorder relapse: A case series study

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.08.3727 ◽

2017 ◽

Vol 381 ◽

pp. 538-539

Author(s):

Y. Hayashi ◽

A. Koumura ◽

M. Yamada ◽

A. Kimura ◽

T. Shibata ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Case Series ◽

Acute Onset ◽

Spectrum Disorder ◽

Occipital Neuralgia ◽

Neuromyelitis Optica Spectrum Disorder ◽

Case Series Study ◽

Series Study

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Neuromyelitis optica spectrum disorder in a tertiary hospital in the Philippines: a case series

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2019.04.006 ◽

2019 ◽

Vol 31 ◽

pp. 124-130 ◽

Cited By ~ 2

Author(s):

Adrian I. Espiritu ◽

Bryan Vincent Q. Mesina ◽

Athena Angellie DL. Puerto ◽

Nikolai Gil D. Reyes ◽

Ludwig F. Damian ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Case Series ◽

Tertiary Hospital ◽

The Philippines ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder

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Potential Role of High Omega6 to Omega3 Fatty Acids Ratio in Increasing Odds of Neuromyelitis Optica Spectrum Disorder

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2019.11.037 ◽

2020 ◽

Vol 37 ◽

pp. 101562

Author(s):

Nasim Rezaeimanesh ◽

Soodeh Razeghi Jahromi ◽

Abdorreza Naser Moghadasi ◽

Zeinab Ghorbani ◽

Sharareh Eskandarieh ◽

...

Keyword(s):

Fatty Acids ◽

Neuromyelitis Optica ◽

Potential Role ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder

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Disruption of the leptomeningeal blood barrier in neuromyelitis optica spectrum disorder

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000343 ◽

2017 ◽

Vol 4 (4) ◽

pp. e343 ◽

Cited By ~ 30

Author(s):

Nasrin Asgari ◽

Eoin P. Flanagan ◽

Kazuo Fujihara ◽

Ho Jin Kim ◽

Hanne P. Skejoe ◽

...

Keyword(s):

Spinal Cord ◽

Neuromyelitis Optica ◽

Area Postrema ◽

Case Series ◽

Systemic Infection ◽

Median Number ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Retrospective Case ◽

Fluid Attenuated Inversion Recovery

Objective:To describe leptomeningeal blood-barrier impairment reflected by MRI gadolinium-enhanced lesions in patients with aquaporin-4 immunoglobulin G (AQP4-IgG)–positive neuromyelitis optica spectrum disorder (NMOSD).Methods:A retrospective case series of 11 AQP4-IgG–positive NMOSD patients with leptomeningeal enhancement (LME) were collected from 5 centers. External neuroradiologists, blinded to the clinical details, evaluated MRIs.Results:LME was demonstrated on postcontrast T1-weighted and fluid-attenuated inversion recovery images as a sign of leptomeningeal blood-barrier disruption and transient leakage of contrast agent into the subarachnoid space in 11 patients, 6 in the brain and 6 in the spinal cord. The patterns of LME were linear or extensive and were accompanied by periependymal enhancement in 5 cases and intraparenchymal enhancement in all cases. The location of LME in the spinal cord was adjacent to intraparenchymal contrast enhancement with involvement of a median number of 12 (range 5–17) vertebral segments. At the time of LME on MRI, all patients had a clinical attack such as encephalopathy (36%) and/or myelopathy (70%) with median interval between symptom onset and LME of 12 days (range 2–30). LME occurred in association with an initial area postrema attack (44%), signs of systemic infection (33%), or AQP4-IgG in CSF (22%) followed by clinical progression. LME was found at initial clinical presentation in 5 cases and at clinical relapses leading to a diagnosis of NMOSD in 6 cases.Conclusion:This study suggests that altered leptomeningeal blood barrier may be accompanied by intraparenchymal blood-brain barrier breakdown in patients with AQP4-IgG–positive NMOSD during relapses.

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Validation of the Modified Fatigue Impact Scale and the relationships among fatigue, pain and serum interleukin-6 levels in patients with neuromyelitis optica spectrum disorder

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.11.041 ◽

2018 ◽

Vol 385 ◽

pp. 64-68 ◽

Cited By ~ 5

Author(s):

Hiroki Masuda ◽

Masahiro Mori ◽

Akiyuki Uzawa ◽

Tomohiko Uchida ◽

Ryohei Ohtani ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Interleukin 6 ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Impact Scale ◽

Fatigue Impact Scale

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Pediatric Neuromyelitis Optica Spectrum Disorder: Case Series and Literature Review

Life ◽

10.3390/life12010019 ◽

2021 ◽

Vol 12 (1) ◽

pp. 19

Author(s):

Michela Ada Noris Ferilli ◽

Roberto Paparella ◽

Ilaria Morandini ◽

Laura Papetti ◽

Lorenzo Figà Talamanca ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Pediatric Patients ◽

Demyelinating Disease ◽

Area Postrema ◽

Case Series ◽

Myelin Oligodendrocyte Glycoprotein ◽

Spectrum Disorder ◽

Neuromyelitis Optica Spectrum Disorder ◽

Periaqueductal Gray Matter ◽

Aquaporin 4 Antibody

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children.

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