Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders

Palace, Jacqueline; Lin, Dan; Zeng, Donglin; Majed, Masoud; Elsone, Liene; Hamid, Shahd; Messina, Silvia; Misu, Tatsuro; Sagen, Jessica; Whittam, Daniel; Tokura, Y.; Leite, Maria Isabel; Weinshenker, Brian G.; Cabre, Philippe; Jacob, Anu; Nakashima, Ichiro; Fujihara, Kazuo; Pittock, Sean J.

doi:10.1093/brain/awz054

Cited by 154 publications

(175 citation statements)

References 38 publications

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“…The implications of this report are limited by the fact that this is a single case. Although we did not find any other cases in the literature of mirror-image lesions reported in association with AQP4 positive NMOSD, a recent international study supported the tendency of sequential NMO relapses to have similar localizing features (13). One reason why we may be the first to report this phenomenon is that it is difficult to discern mirror-image lesions in NMOSD in locations other than the brain.…”

Section: Discussioncontrasting

confidence: 63%

Mirror-Image Lesions in Sequential Relapses of AQP4-Positive Neuromyelitis Optica Spectrum Disorder

2020

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A 25 year-old Nigerian woman with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) presented with a 6 week history of nausea, vomiting, and refractory hiccups; as well as progressive lower extremity sensory loss, weakness, saddle anesthesia, and urinary incontinence. She had experienced her first NMOSD relapse seven years prior with bilateral lower extremity weakness and area postrema syndrome. After pulse steroids and plasma exchange she made a complete neurologic recovery and was started on azathioprine. An initial aquaporin-4 (AQP4) antibody ELISA test was positive, but three subsequent tests were negative and repeat MRI brain showed resolution of T2/FLAIR signal abnormalities with the exception of a right thalamic lesion and a left medullary lesion. Azathioprine was discontinued after 1 year and she was lost to follow-up. With her second relapse, she had new lesions in her left thalamus and right medulla-a mirror image of the thalamic and medullary lesions associated with her first relapse. In addition, an MRI spine demonstrated a new longitudinally extensive transverse myelitis from T7 to L1 with edematous expansion of the cord. Her serum AQP4 antibody test using a cell-based assay was strongly positive. NMOSD lesions are typically associated with brain regions with high density of the AQP4 channel. These areas include optic nerves, hypothalamus, and the diencephalic and brainstem tissues that surround the cerebral aqueduct and third and fourth ventricles. Previous studies have demonstrated that those with relapsing NMOSD have a predilection for recurrence in the same neuroanatomical region as their first episode. We hypothesize, using data from prior pathologic and epidemiologic studies, that mirror image lesions, where the same anatomic sites are affected on the contralateral side of the brain or spinal cord, may appear in subsequent attacks due to (i) areas of high remaining AQP4 density and/or (ii) local compromise of astrocyte or blood-brain barrier (BBB) function that persists after the initial inciting attack.

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Section: Discussioncontrasting

confidence: 63%

Mirror-Image Lesions in Sequential Relapses of AQP4-Positive Neuromyelitis Optica Spectrum Disorder

2020

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“…A recent report also evaluated the usefulness of previous attacks for predicting the future clinical course. 12 Although the report did not conclude on the importance of selecting patients with a recent high disease activity for clinical trials, the data suggested that the relapse rate in the following 2 years may be affected by the number of attacks in the past 2 years. Considered together with the results of this study that the relapse rates are significantly different between during the "clustered" and "nonclustered" intermittent periods, allocating the patients without taking the present disease activity into consideration in clinical trials may cause biases in the achieved results.…”

Section: Discussionmentioning

confidence: 96%

Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence

Akaishi

Nakashima

Takahashi

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveThe aim of this study was to elucidate the characteristics of clinical attacks in neuromyelitis optica spectrum disorders (NMOSDs) with positive serum anti-aquaporin-4 antibody. Both the timing and sequential pattern of clinical types were analyzed.MethodsA total of 69 patients with NMOSD were enrolled in this study, all of whom were treated at a single university hospital. All data regarding the clinical attacks (including types and date) together with other clinical information were collected.ResultsAnalysis of clinical attacks from the enrolled patients showed that there were 2 distributional patterns of attack occurrence in each patient: (1) “clustered” occurrences, which occurred within 12 months from the previous attack, and (2) “nonclustered” intermittent occurrences, which occurred ≥12 months after the previous attack. These occurrences were regardless of the duration from the onset. During the “clustered” period, clinical attacks were more likely to show a similar clinical manifestation, such as optic neuritis or myelitis. After entering the “nonclustered” intermittent period, the relapses were of random clinical type, regardless of the previous clinical manifestation.ConclusionsPatients with NMOSD showed mixed periods of “clustered” occurrence with frequent attacks presenting with similar manifestations and “nonclustered” intermittent periods with sparse relapses. Approximately half of the relapses occurred during the “clustered” period within 12 months of the last clinical attack. Clinicians should pay special attention to whether the patients are presently in the “clustered” or “nonclustered” period to decide optimal relapse-preventive strategies.

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“…For example, Neuromyelitis optica (including AQP4-IgG-positive) is an inflammatory disorder that is characterized by recurrent episodes of optic neuritis. While the involvement of specific cell types in activating these episodes remains unknown, the variability of the clinical manifestations according to the racial group, age of onset, the number of episodes (Palace et al 2019) reflect phenotype diversity that might be governed by an individual ASE-V genomic makeup. Moreover, a recent GWAS that tested the intensity and pattern of mosquito bite revealed predisposition of alleles that are in association with T-cell regulation (Jones et al 2017).…”

Section: Ase Genes Signify a Risk For A Broad Spectrum Of Immunologicmentioning

confidence: 99%

Allele Specific Expression in Human – Genomic Makeup and Phenotypic Implications

Wainer-Katsir

Linial

2019

Preprint

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The allele-specific expression phenomenon refers to unbalanced expression from the two parental alleles in a tissue of a diploid organism. AlleleDB is a high-quality resource that reports on about 30,000 ASE variants (ASE-V) from hundreds of human samples. In this study, we present the genomic characteristics and phenotypic implications of ASE. We identified tens of segments with extreme density of ASE-V, many of them are located at the major histocompatibility complex (MHC) locus. Notably, at a resolution of 100 nucleotides, the likelihood of ASE-V increases with the density of polymorphic sites. Another dominant trend of ASE is a strong bias of the expression to the major allele. This observation relies on the known allele frequencies in the healthy human population. Overlap of ASE-V and GWAS associations was calculated for 48 phenotypes from the UK-Biobank. ASE-V were significantly associated with a risk for inflammation (e.g. asthma), autoimmunity (e.g., rheumatoid arthritis, multiple sclerosis, and type 1 diabetes) and several blood cell traits (e.g., red cell distribution width). At the level of the ASE-genes, we seek association with all traits and conditions reported in the GWAS catalog. The statistical significance of ASE-genes to GWAS catalog reveals association with the susceptibility to virus infection, autoimmunity, inflammation, allergies, blood cancer and more. We postulate that ASE determines phenotype diversity between individuals and the risk for a variety of immune-related conditions.

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Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders

Cited by 154 publications

References 38 publications

Mirror-Image Lesions in Sequential Relapses of AQP4-Positive Neuromyelitis Optica Spectrum Disorder

Mirror-Image Lesions in Sequential Relapses of AQP4-Positive Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence

Allele Specific Expression in Human – Genomic Makeup and Phenotypic Implications

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