A comparison between spinal cord infarction and neuromyelitis optica spectrum disorders: Clinical and MRI studies

Abstract Background: Neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) autoimmune inflammatory demyelinating diseases characterized by recurrent episodes of acute optic neuritis and transverse myelitis. Aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies, which target the water channel aquaporin-4 (AQP4) on astrocytic membrane, are pathogenic in NMOSD. Glutamate excitotoxicity, which is triggered by internalization of AQP4-glutamate transporter complex after AQP4-IgG binding to astrocytes, is involved in early NMOSD pathophysiologies. We studied the effects of memantine, a N-methyl-D-aspartate (NMDA) receptor antagonist, on motor impairments and spinal cord pathologies in mice which received human AQP4-IgG. Methods: Purified IgG from AQP4-IgG-seropositive NMOSD patients were passively transferred to adult C57BL/6 mice with disrupted blood-brain barrier. Memantine was administered by oral gavage. Motor impairments of the mice were assessed by beam walking test. Spinal cords of the mice were assessed by immunofluorescence and ELISA. Results: Oral administration of memantine ameliorated the motor impairments induced by AQP4-IgG, no matter the treatment was initiated before (preventive) or after (therapeutic) disease flare. Memantine profoundly reduced AQP4 and astrocyte loss, and attenuated demyelination and axonal loss in the spinal cord of mice which had received AQP4-IgG. The protective effects of memantine were associated with inhibition of apoptosis and suppression of neuroinflammation, with decrease in microglia activation and neutrophil infiltration and reduction of increase in levels of proinflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). In addition, memantine elevated growth factors including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) in the spinal cord. Conclusions: Our findings support that glutamate excitotoxicity and neuroinflammation plays important roles in complement-independent pathophysiology during early development of NMOSD lesions, and highlight the potential of oral memantine as a therapeutic agent in NMOSD acute attacks.

Download Full-text

Spinal Cord Atrophy in Neuromyelitis Optica Spectrum Disorders Is Spatially Related to Cord Lesions and Disability

Radiology ◽

10.1148/radiol.2020192664 ◽

2020 ◽

Vol 297 (1) ◽

pp. 154-163

Author(s):

Laura Cacciaguerra ◽

Paola Valsasina ◽

Sarlota Mesaros ◽

Vittorio Martinelli ◽

Jelena Drulovic ◽

...

Keyword(s):

Spinal Cord ◽

Neuromyelitis Optica ◽

Neuromyelitis Optica Spectrum Disorders ◽

Spinal Cord Atrophy ◽

Spectrum Disorders

Download Full-text

Lymphocyte Subsets Are Associated with Disease Status in Neuromyelitis Optica Spectrum Disorders

NeuroImmunoModulation ◽

10.1159/000520745 ◽

2021 ◽

pp. 1-10

Author(s):

Hong Yang ◽

Wei Liu ◽

Yi-Fan Wu ◽

De-Sheng Zhu ◽

Xia-Feng Shen ◽

...

Keyword(s):

Spinal Cord ◽

B Cells ◽

Neuromyelitis Optica ◽

Peripheral Blood ◽

Lymphocyte Subsets ◽

Disease Status ◽

Neuromyelitis Optica Spectrum Disorders ◽

Spinal Cord Lesions ◽

Cross Sectional ◽

Spectrum Disorders

Objective: At present, studies on lymphocytes are mostly conducted on CD19+ B cells and CD27+ B cells in neuromyelitis optica spectrum disorders (NMOSDs), but the exact changes in lymphocyte subsets (CD19+ B cells, CD3+ T cells, CD4+ Th cells, CD8+ Ts cells, the CD4+/CD8+ ratio, and NK [CD56+ CD16] cells) have rarely been studied. This study aimed to assess lymphocyte subset changes in patients with NMOSD. Methods: We performed a cross-sectional study of consecutive patients with acute NMOSD (n = 41), chronic NMOSD (n = 21), and healthy individuals (n = 44). Peripheral blood samples were obtained upon admission, and lymphocyte subsets were analyzed by flow cytometry. Levels of lymphocyte subsets among 3 groups were compared and its correlation with the length of spinal cord lesions was analyzed. Results: The levels of peripheral blood CD19+ B cells were significantly higher in patients with acute and chronic NMOSD than in healthy controls (HCs) (17.91 ± 8.7%, 13.08 ± 7.562%, and 12.48 ± 3.575%, respectively; p < 0.001) and were positively correlated with the length of spinal cord lesions in acute NMOSD (r = 0.433, p < 0.05). The peripheral blood CD4+/CD8+ ratio was significantly lower in patients with acute NMOSD and chronic NMOSD than in HCs (1.497 ± 0.6387, 1.33 ± 0.5574, and 1.753 ± 0.659, respectively; p < 0.05), and the levels of peripheral blood NK (CD56+ CD16) cells were significantly lower in patients with acute and chronic NMOSD than in HCs (13.6 ± 10.13, 11.11 ± 7.057, and 14.7 [interquartile range = 9.28], respectively; p < 0.01). Conclusions: The levels of certain subsets of peripheral blood lymphocytes are associated with disease status in NMOSD.

Download Full-text

Neuromyelitis Optica Spectrum Disorders

Neuroimmunology ◽

10.1093/med/9780190050801.003.0006 ◽

2019 ◽

pp. 109-129

Author(s):

A. Sebastian López-Chiriboga ◽

Brian G. Weinshenker

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Neuromyelitis Optica ◽

Inflammatory Diseases ◽

Treatment Options ◽

Neuromyelitis Optica Spectrum Disorders ◽

Future Prospects ◽

Mortality And Morbidity ◽

The Central Nervous System ◽

Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory diseases of the central nervous system, traditionally diagnosed in patients with inflammatory attacks restricted to the optic nerves and spinal cord. The chapter considers the epidemiology, pathophysiology and immunopathogenesis of NMOSD. The clinical presentation and radiographic features are reviewed and the prognosis of patients with NMOSD is considered. The mortality and morbidity of untreated NMOSD is much greater than those of MS. Treatment options are summarized and finally future prospects of research are considered.

Download Full-text

HLA genotype-clinical phenotype correlations in multiple sclerosis and neuromyelitis optica spectrum disorders based on Japan MS/NMOSD Biobank data

Scientific Reports ◽

10.1038/s41598-020-79833-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mitsuru Watanabe ◽

Yuri Nakamura ◽

Shinya Sato ◽

Masaaki Niino ◽

Hikoaki Fukaura ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Optic Neuritis ◽

Neuromyelitis Optica ◽

Clinical Phenotype ◽

Multivariable Analysis ◽

Neuromyelitis Optica Spectrum Disorders ◽

Onset Age ◽

High Tendency ◽

Spectrum Disorders

AbstractHLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype–phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype–phenotype correlations are unclear in NMOSD.

Download Full-text

Short segment myelitis as a first manifestation of neuromyelitis optica spectrum disorders

Multiple Sclerosis Journal ◽

10.1177/1352458516687043 ◽

2017 ◽

Vol 23 (3) ◽

pp. 413-419 ◽

Cited By ~ 26

Author(s):

So-Young Huh ◽

Su-Hyun Kim ◽

Jae-Won Hyun ◽

In Hye Jeong ◽

Min Su Park ◽

...

Keyword(s):

Spinal Cord ◽

Neuromyelitis Optica ◽

Transverse Myelitis ◽

Neuromyelitis Optica Spectrum Disorders ◽

Mri Findings ◽

Initial Manifestation ◽

Short Transverse ◽

Imaging Characteristics ◽

Referral Hospitals ◽

Spectrum Disorders

Background: Some patients with neuromyelitis optica spectrum disorders (NMOSD) present with spinal cord lesions extending fewer than three vertebral segments (short transverse myelitis, STM), hindering an early diagnosis. Objective: We investigated the frequency and imaging characteristics of STM lesions in patients presenting with myelitis as an initial manifestation of NMOSD. Methods: Patients seen at three referral hospitals in Korea between June 2005 and March 2015 who met the following inclusion criteria were recruited for review: seropositivity for aquaporin-4 antibody, initial presentation with myelitis and spinal cord magnetic resonance imaging (MRI) performed within 1 month of initial myelitis onset. Results: Of the 76 enrolled patients, 65 (85.5%) collectively had 69 longitudinally extensive transverse myelitis lesions, while the remaining 11 (14.5%) had a total of 15 STM lesions. Of the 15 STM lesions, 5 spanned 2.5 vertebral segments, 6 were continuous over two segments, 3 showed a length of 1.5 segments and 1 was confined to a single segment. On axial imaging, all of the STM lesions involved the central grey matter. Conclusion: These MRI findings suggested that STM does not preclude the possibility of an NMOSD diagnosis.

Download Full-text