scholarly journals Short segment myelitis as the initial and only manifestation of aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorders

2020 ◽  
Vol 13 ◽  
pp. 175628641989859
Author(s):  
Wei Fang* ◽  
Yang Zheng* ◽  
Fan Yang ◽  
Meng-Ting Cai ◽  
Chun-Hong Shen ◽  
...  
Keyword(s):  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Correct Diagnosis ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Chinese Patients ◽  
Careful Study ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Short Segment ◽  
Spectrum Disorders

Background: Short segment myelitis (SSM, < 3 vertebral segments) is an under-recognized initial manifestation of neuromyelitis optica spectrum disorders (NMOSD). Though infrequent, failure to recognize SSM in patients with NMOSD would lead to incorrect diagnosis and treatment. Therefore, delineation of features of NMOSD-associated SSM is of paramount importance. Objective: Our study aimed to determine the demographic, clinical and radiological features of NMOSD-associated SSM, and compare those with NMOSD-associated longitudinally extensive transverse myelitis (LETM) and multiple sclerosis (MS)-associated SSM, respectively. Methods: Chinese patients presenting initially only with acute myelitis and diagnosed with NMOSD ( n = 46) and MS ( n = 11) were included. Clinical, serological, imaging and disability data were collected. Mann–Whitney U test or two-tailed Fisher’s exact tests were used to analyse the data. Results: Of the 46 enrolled NMOSD patients, 34 (74%) collectively had 38 LETM lesions, while 12 (26%) had 14 SSM lesions. When compared with LETM, NMOSD presenting with SSM were more likely to have a delayed diagnosis and a lower level of disability at nadir during the first attack. T1-weighted imaging hypointensity was more prominent in NMOSD-associated LETM lesions than NMOSD-associated SSM lesions. When compared with MS-associated SSM, NMOSD-associated SSM lesions were more likely to be centrally located, grey matter involving and transversally extensive on axial imaging and spanned no less than 2 vertebral segments on sagittal imaging. Conclusion: These findings suggest that SSM does not preclude the possibility of a NMOSD diagnosis. Testing for serum aquaporin-4 immunoglobulin G (AQP4-IgG) and careful study of lesions on spinal cord magnetic resonance imaging could aid in an earlier and correct diagnosis.

scholarly journals Memantine ameliorates motor impairments and pathologies in a mouse model of neuromyelitis optica spectrum disorders.

2020 ◽  
Author(s):  
Leung-Wah Yick ◽  
Chi-Ho Tang ◽  
Oscar Ka-Fai Ma ◽  
Jason Shing-Cheong Kwan ◽  
Koon Ho CHAN
Keyword(s):  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Neurotrophic Factor ◽  
Water Channel ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Glutamate Excitotoxicity ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Motor Impairments ◽  
Spectrum Disorders

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.

scholarly journals Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders

Spinal Cord ◽  
2018 ◽  
Vol 56 (10) ◽  
pp. 949-954 ◽  
Author(s):  
Edgar Carnero Contentti ◽  
Vanessa Daccach Marques ◽  
Ibis Soto de Castillo ◽  
Verónica Tkachuk ◽  
Amilton Antunes Barreira ◽  
...  
Keyword(s):  
Latin American ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Short Segment ◽  
Spectrum Disorders

scholarly journals A Rare Presentation of Neuromyelitis Optica Spectrum Disorders

2018 ◽  
Vol 11 ◽  
pp. 117954761775268
Author(s):  
Navneet K Singh ◽  
Alexander J Sweidan ◽  
Sarah Strube ◽  
Ignacio Carrillo-Nunez
Keyword(s):  
Neuromyelitis Optica ◽  
Disease Process ◽  
Transverse Myelitis ◽  
Aquaporin 4 ◽  
Treatment Modalities ◽  
High Dose ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Rare Presentation ◽  
Lower Extremity Weakness ◽  
Spectrum Disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are a set of demyelinating disorders that primarily target the optic nerves and the spinal cord. Previously thought to be a subset of multiple sclerosis (MS), now is recognized as a distinct entity. We present a 59-year-old female patient who was admitted for acute upper and lower extremity weakness. The patient had woken up from sleep with sudden onset of weakness. Patient was initially diagnosed with a right hemispheric stroke; however, magnetic resonance imaging of the cervical spine later performed showed abnormal enhancement from C2-C4, representing transverse myelitis. Cerebrospinal fluid was negative for organisms and inflammatory biomarkers. An anti-aquaporin-4 receptor antibody titer was found to be elevated with titers >80 units/mL. The patient was treated with high-dose steroids and plasmapheresis. The NMOSD is a rare entity and, here, we present a rare presentation of the disease. Since its description in 1870, it was confused with MS for years. The advent of anti-aquaporin-4 antibody has been instrumental in differentiating the disease process from MS. This distinction is important, in terms of agents used for treatment and prognostication. The NMOSD is a set of debilitating disease, which requires prompt recognition and appropriate treatment, to avoid the disabling sequelae. Future prospects of the disease include development of novel biological treatment modalities which focus on restoring the loss of immune tolerance which is key to the pathogenesis of the disease.

Utility of aquaporin-4 antibody assay in patients with neuromyelitis optica spectrum disorders

2013 ◽  
Vol 19 (8) ◽  
pp. 1060-1067 ◽  
Author(s):  
Sung-Min Kim ◽  
Patrick Waters ◽  
Mark Woodhall ◽  
Jee-Young Kim ◽  
Jee-Eun Kim ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
Poor Response ◽  
Aquaporin 4 ◽  
Time Interval ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Antibody Assay ◽  
The Poor ◽  
Spectrum Disorders

Objective: Our aim was to evaluate the utility of aquaporin-4 antibodies (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: The clinical and radiological characteristics of 78 patients with NMOSD and 22 with multiple sclerosis (MS), who were tested for AQP4-Ab by a cell-based assay, were assessed. Results: The mean time interval between symptom onset and development of optic neuritis and myelitis was 39.9 months in neuromyelitis optica (NMO). About 40% of patients with limited NMO would have fulfilled the diagnostic criteria for MS in the absence of the antibody assay results. In patients with longitudinally extensive transverse myelitis, positive AQP4-Ab assay results were associated with the poor response to acute steroid treatment and asymptomatic visual evoked potential abnormality. Presence of either painful tonic spasm associated with myelitis or severe disability at onset had high specificity and relatively high sensitivity in differentiating NMOSD with AQP4-Ab from MS. Conclusions: The AQP4-Ab assay can facilitate the early diagnosis of NMO and prevent limited NMO from being misdiagnosed as MS. It can predict the poor response to first-line acute-phase treatment and probably detect the subclinical optic nerve involvement in subgroups of NMOSD. Lastly, it will contribute to the upcoming revision of the current diagnostic criteria for NMO.

Aquaporin-4- und Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierte Optikusneuritis: Diagnose und Therapie

2020 ◽  
Vol 237 (11) ◽  
pp. 1290-1305
Author(s):  
Brigitte Wildemann ◽  
Solveig Horstmann ◽  
Mirjam Korporal-Kuhnke ◽  
Andrea Viehöver ◽  
Sven Jarius
Keyword(s):  
Neuromyelitis Optica ◽  
Optic Neuropathy ◽  
Aquaporin 4 ◽  
Phase Iii ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Interferon Β ◽  
Off Label ◽  
Diagnostik Und Therapie ◽  
Spectrum Disorders ◽  
Diagnose Und Therapie

ZusammenfassungDie Optikusneuritis (ON) ist vielfach die erste Manifestation einer AQP4-Antikörper-vermittelten NMOSD (AQP4: Aquaporin-4, NMOSD: Neuromyelitis-optica-Spektrum-Erkrankung, Engl.: neuromyelitis optica spectrum disorders) oder einer Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierten Enzephalomyelitis (MOG-EM; auch MOG antibody associated disorders, MOGAD). Für beide Erkrankungen wurden in den vergangenen Jahren internationale Diagnosekriterien und Empfehlungen zu Indikation und Methodik der serologischen Testung vorgelegt. Seit Kurzem liegen zudem Ergebnisse aus 4 großen, internationalen Phase-III-Studien zur Behandlung der NMOSD vor. Mit dem den Komplementfaktor C5 blockierenden monoklonalen Antikörper Eculizumab wurde 2019 erstmalig ein Medikament zur Langzeitbehandlung der NMOSD, die bislang vornehmlich Off-Label mit Rituximab, Azathioprin und anderen Immunsuppressiva erfolgt, auf dem europäischen Markt zugelassen. Für die erst vor wenigen Jahren erstbeschriebene MOG-EM stehen inzwischen Daten aus mehreren retrospektiven Studien zur Verfügung, die eine Wirksamkeit von Rituximab und anderen Immunsuppressiva in der Schubprophylaxe auch in dieser Indikation nahelegen. Viele der zur Therapie der MS zugelassenen Medikamente sind entweder unwirksam oder können, wie z. B. Interferon-β, eine Verschlechterung des Krankheitsverlaufes bewirken. Beide Erkrankungen werden im Akutstadium mit hochdosierten Glukokortikoiden und Plasmapherese oder Immunadsorption behandelt. Diese Behandlung sollte möglichst rasch nach Symptombeginn eingeleitet werden. Insbesondere die MOG-EM ist durch eine oft ausgeprägte Steroidabhängigkeit gekennzeichnet, die ein langsames Ausschleichen der Steroidtherapie erfordert, und schließt viele Fälle der bislang meist als „idiopathisch“ klassifizierten „chronic relapsing inflammatory optic neuropathy“ (CRION) ein. Unbehandelt kann sowohl die NMOSD- als auch die MOG-EM-assoziierte ON zu schweren, persistierenden und oft bilateralen Visuseinschränkungen bis hin zur Erblindung führen. Beide Erkrankungen verlaufen meist relapsierend. Neben den Sehnerven sind häufig das Myelon sowie der Hirnstamm und, vor allem bei NMO-Patienten, das Dienzephalon betroffen; supratentorielle Hirnläsionen im kranialen MRT sind, anders als früher gedacht, kein Ausschlusskriterium, sondern häufig. In der vorliegenden Arbeit geben wir einen Überblick über Klinik, Diagnostik und Therapie dieser beiden wichtigen Differenzialdiagnosen der MS-assoziierten und idiopathischen ON.

Sign in / Sign up

Export Citation Format

Share Document