Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody

Multiple sclerosis (MS) in Asian populations is often characterized by the selective involvement of the optic nerve (ON) and spinal cord (SP) (OSMS) in contrast to classic MS (CMS), where frequent lesions are observed in the cerebrum, cerebellum or brainstem. In Western countries, inflammatory demyelinating disease preferentially involving the ON and SP is called neuromyelitis optica (NMO). Recently, Lennon et al. discovered that NMO-IgG, shown to bind to aquaporin 4 (AQP4), could be a specific marker of NMO and also of Japanese OSMS whose clinical features were identical to NMO having long spinal cord lesions extending over three vertebral segments (LCL). To examine this antibody in larger populations of Japanese OSMS patients in order to know its epidemiological and clinical spectra, we established an immunohistochemical detection system for the anti-AQP4 antibody (AQP4-Ab) using the AQP4-transfected human embryonic kidney cell line (HEK-293) and confirmed AQP4-Ab positivity together with the immunohistochemical staining pattern of NMO-IgG in approximately 60% of Japanese OSMS patients with LCL. Patients with OSMS without LCL and those with CMS were negative for this antibody. Our results accorded with those of Lennon et al. suggest that Japanese OSMS with LCL may have an underlying pathogenesis in common with NMO. Multiple Sclerosis 2007; 13: 850—855. http://msj.sagepub.com

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The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis

Multiple Sclerosis International ◽

10.1155/2017/1359761 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

S. Abdullah ◽

W. F. Wong ◽

C. T. Tan

Keyword(s):

Spinal Cord ◽

Transverse Myelitis ◽

Tertiary Hospital ◽

Demyelinating Diseases ◽

Aquaporin 4 ◽

Spinal Cord Lesions ◽

Clinical Presentations ◽

Disability Status ◽

Aquaporin 4 Antibody ◽

Aqp4 Antibody

Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients’ clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p<0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p<0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p=0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p=0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p=0.005; 4.07 versus 2.51, p=0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS.

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MRI of the Entire Spinal Cord—Worth the While or Waste of Time? A Retrospective Study of 74 Patients with Multiple Sclerosis

Diagnostics ◽

10.3390/diagnostics11081424 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1424

Author(s):

Esben Nyborg Poulsen ◽

Anna Olsson ◽

Stefan Gustavsen ◽

Annika Reynberg Langkilde ◽

Annette Bang Oturai ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Cervical Spinal Cord ◽

Brain Mri ◽

Anatomical Location ◽

Spinal Cord Lesions ◽

Chi Square ◽

Exact Test ◽

Mcdonald Criteria ◽

Chi Square Test

Spinal cord lesions are included in the diagnosis of multiple sclerosis (MS), yet spinal cord MRI is not mandatory for diagnosis according to the latest revisions of the McDonald Criteria. We investigated the distribution of spinal cord lesions in MS patients and examined how it influences the fulfillment of the 2017 McDonald Criteria. Seventy-four patients with relapsing-remitting MS were examined with brain and entire spinal cord MRI. Sixty-five patients received contrast. The number and anatomical location of MS lesions were assessed along with the Expanded Disability Status Scale (EDSS). A Chi-square test, Fischer’s exact test, and one-sided McNemar’s test were used to test distributions. MS lesions were distributed throughout the spinal cord. Diagnosis of dissemination in space (DIS) was increased from 58/74 (78.4%) to 67/74 (90.5%) when adding cervical spinal cord MRI to brain MRI alone (p = 0.004). Diagnosis of dissemination in time (DIT) was not significantly increased when adding entire spinal cord MRI to brain MRI alone (p = 0.04). There was no association between the number of spinal cord lesions and the EDSS score (p = 0.71). MS lesions are present throughout the spinal cord, and spinal cord MRI may play an important role in the diagnosis and follow-up of MS patients.

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Cortical oscillopsia without nystagmus, an isolated symptom of neuromyelitis optica spectrum disorder with anti-aquaporin 4 antibody

Multiple Sclerosis Journal ◽

10.1177/1352458511414149 ◽

2011 ◽

Vol 18 (2) ◽

pp. 244-247 ◽

Cited By ~ 8

Author(s):

Sung-Min Kim ◽

Ji-Soo Kim ◽

Young Eun Heo ◽

Hye-Ran Yang ◽

Kyung Seok Park

Keyword(s):

Spinal Cord ◽

Neuromyelitis Optica ◽

Spectrum Disorder ◽

Aquaporin 4 ◽

Neuromyelitis Optica Spectrum Disorder ◽

Ocular Manifestation ◽

Initial Manifestation ◽

Ocular Symptoms ◽

Head Tremor ◽

Aquaporin 4 Antibody

Neuromyelitis optica (NMO), mainly affecting optic nerve and spinal cord, can also manifest diverse ocular symptoms due to brain abnormalities. We present a cortical oscillopsia without nystagmus or head tremor in a patient with neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin 4 antibody. This rare ocular manifestation, which is easily underestimated owing to absence of the typical nystagmus, can be an initial manifestation of NMOSD.

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The Prevalence of Long Spinal Cord Lesions and Anti-Aquaporin 4 Antibodies in Neuromyelitis Optica Patients in Taiwan

European Neurology ◽

10.1159/000322740 ◽

2011 ◽

Vol 65 (2) ◽

pp. 99-104 ◽

Cited By ~ 9

Author(s):

Kai-Chen Wang ◽

Ching-Piao Tsai ◽

Chao-Lin Lee ◽

Shao-Yuan Chen ◽

Shyi-Jou Chen

Keyword(s):

Spinal Cord ◽

Neuromyelitis Optica ◽

Aquaporin 4 ◽

Spinal Cord Lesions

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Multiple Sclerosis Of The Spinal Cord: Is Gadolinium Irreplaceable In Assessing Lesion Activity?

Acta Medica Marisiensis ◽

10.2478/amma-2013-0037 ◽

2013 ◽

Vol 59 (3) ◽

pp. 158-161

Author(s):

Constantina Andrada Treabă ◽

M Buruian ◽

Rodica Bălașa ◽

Maria Daniela Podeanu ◽

I P Simu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Magnetic Resonance ◽

Contrast Enhancement ◽

Signs And Symptoms ◽

Magnetic Resonance Images ◽

Type I ◽

Focal Lesions ◽

Spinal Cord Lesions ◽

Active Lesion

Abstract Purpose: To evaluate the relationship between the T2 patterns of spinal cord multiple sclerosis lesions and their contrast uptake. Material and method: We retrospectively reviewed the appearance of spinal cord lesions in 29 patients (with relapsing-remitting multiple sclerosis) who had signs and symptoms of myelopathy on neurologic examination and at least one active lesion visualized on magnetic resonance examinations performed between 2004 and 2011. We correlated the T2 patterns of lesions with contrast enhancement and calculated sensitivity and specificity in predicting gadolinium enhancement. Results: Only focal patterns consisting of a lesion’s center homogenously brighter than its periphery on T2-weighed images (type I) correlated significantly with the presence of contrast enhancement (p = 0.004). Sensitivity was 0.307 and specificity 0.929. In contrast, enhancement was not significantly related to uniformly hyperintense T2 focal lesions (type II) or diffuse (type III) pattern defined as poorly delineated areas of multiple small, confluent, subtle hyperintense T2 lesions (p > 0.5 for both). Conclusions: We believe that information about the activity of multiple sclerosis spinal cord lesions in patients with myelopathy may be extracted not only from contrast enhanced, but also from non-enhanced magnetic resonance images.

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3D PSIR MRI at 3 Tesla improves detection of spinal cord lesions in multiple sclerosis

Journal of Neurology ◽

10.1007/s00415-019-09591-8 ◽

2019 ◽

Vol 267 (2) ◽

pp. 406-414 ◽

Cited By ~ 5

Author(s):

S. Mirafzal ◽

A. Goujon ◽

R. Deschamps ◽

K. Zuber ◽

J. C. Sadik ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

3 Tesla ◽

Spinal Cord Lesions

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Impact of Astrocyte Depletion upon Inflammation and Demyelination in a Murine Animal Model of Multiple Sclerosis

International Journal of Molecular Sciences ◽

10.3390/ijms20163922 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3922 ◽

Cited By ~ 7

Author(s):

Allnoch ◽

Baumgärtner ◽

Hansmann

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Calcium Binding ◽

Performance Test ◽

Intraperitoneal Administration ◽

Clinical Signs ◽

Aquaporin 4 ◽

Thoracic Spinal Cord ◽

Thoracic Spinal ◽

The Impact

Astrocytes play a key role in demyelinating diseases, like multiple sclerosis (MS), although many of their functions remain unknown. The aim of this study was to investigate the impact of astrocyte depletion upon de- and remyelination, inflammation, axonal damage, and virus distribution in Theiler`s murine encephalomyelitis (TME). Groups of two to six glial fibrillary acidic protein (GFAP)-thymidine-kinase transgenic SJL mice and SJL wildtype mice were infected with TME virus (TMEV) or mock (vehicle only). Astrocyte depletion was induced by the intraperitoneal administration of ganciclovir during the early and late phase of TME. The animals were clinically investigated while using a scoring system and a rotarod performance test. Necropsies were performed at 46 and 77 days post infection. Cervical and thoracic spinal cord segments were investigated using hematoxylin and eosin (H&E), luxol fast blue-cresyl violet (LFB), immunohistochemistry targeting Amigo2, aquaporin 4, CD3, CD34, GFAP, ionized calcium-binding adapter molecule 1 (Iba1), myelin basic protein (MBP), non-phosphorylated neurofilaments (np-NF), periaxin, S100A10, TMEV, and immunoelectron microscopy. The astrocyte depleted mice showed a deterioration of clinical signs, a downregulation and disorganization of aquaporin 4 in perivascular astrocytes accompanied by vascular leakage. Furthermore, astrocyte depleted mice showed reduced inflammation and lower numbers of TMEV positive cells in the spinal cord. The present study indicates that astrocyte depletion in virus triggered CNS diseases contributes to a deterioration of clinical signs that are mediated by a dysfunction of perivascular astrocytes.

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