Original article
Aquaporin 4 distribution in the brain and its relevance for the radiological appearance of neuromyelitis optica spectrum disease

https://doi.org/10.1016/j.neurad.2019.03.015Get rights and content

Abstract

Background and purpose

To determine the precise incidence of lesions at sites of high Aquaporin-4 expression (hAQP4) and their possible association with known neuromyelitis optica spectrum disease (NMOSD) lesions patterns.

Materials and methods

A retrospective analysis of brain and, when available, spinal cord MRI scans of 54 NMOSD patients recruited among the French NMOSD cohort was performed. Brain lesions were annotated as MS-like, non-specific, or evocative of NMOSD. The topography of hAQP4 was reassessed by human brain atlas. The incidence of lesions in hAQP4 and their association with lesions evocative of NMOSD was estimated.

Results

Among those included (41/54 female, mean age: 45 years) 47/54 (87%) presented brain lesions. Twenty-six/47 (55%) had lesions in hAQP4. Thirty-two/54 patients (60%) had lesions considered evocative of NMOSD. The majority of them also presented lesions in hAQP4 (65%, 21/32). Patients with lesions in hAQP4 and lesions evocative of NMOSD demonstrated more extensive myelitis compared to the other patients (7 [6–10] versus 4 [3–5] vertebral segments, P = 0.009).

Conclusion

The coexistence of lesions evocative of NMOSD and in hAQP4 is associated with significantly more extensive myelitis, and might have pathophysiological and clinical significance.

Introduction

Brain lesions in neuromyelitis optica (NMO) have been widely described [1], [2]. Their clinical and radiological presentation can be similar to that of multiple sclerosis (MS). Differentiating them is important, as patients with NMO require long-term immunosuppression, and some treatments for MS can worsen NMO [1].

Following the discovery of the anti-AQP4 autoantibody; the term NMO spectrum diseases (NMOSD) has been coined [1], [2], [3], [4], [5]. An international study group has defined new consensus criteria [6] and widened the brain radiological spectrum of NMOSD, based on the findings of previous single center studies with a wide variety of inclusion criteria [2], [7], [8], [9], [10]. Studies have also pointed to cerebral lesions at sites of high AQP4 expression (hAQP4), such as periependymal regions [2], [7], [9], [10], [13]. However, gene expression studies of human describe additional hAQP4 [11], [12]. The targeted analysis of hAQP4 might highlight new diagnostic features, especially when associated with other typical NMOSD lesions.

The purpose of this study was to determine the prevalence of lesions in hAQP4, and their possible association with other typical NMOSD lesion patterns as previously described.

Section snippets

Patients and methods

Approval from an ethical standards committee was received and informed consent was given by all participants.

Patients

Eighty-three patients were included by 13 NOMADMUS-associated departments. Twenty-five were excluded because they did not have the required MRI-sequences, and 4 because of intercurrent brain diseases.

The median age of the 54-retained-patients was 45 years (Interquartile range, IQR: [8–74]): 41 women (median: 44 [8–74] years) and 13 men (46 [37–68] years). The median disease duration from first clinical presentation to the brain MRI was 21 months (IQR = [0–384] months). Fifty-three patients (98%)

Discussion

The primary findings of our study were the identification of distinct patterns of cerebral lesion distribution in NMOSD patients:

  • patients with a typical pattern with both lesions evocative of NMOSD and lesions at sites of hAQP4;

  • patients with neither type of these lesions.

Given the co-clustering of this new patient classification with the extent of myelitis, the corresponding lesion distribution patterns might have pathophysiological significance, and should be compared with the distribution of

Conclusions

In conclusion, we showed a heterogeneous prevalence of lesions among hAQP4. We revealed that the co-existence of at least one lesion evocative of NMOSD and one in hAQP4 was associated with more extensive myelitis, and might have particular pathophysiological relevance. The consideration of this association might increase the diagnostic specificity of the recently revised diagnostic criteria for NMOSD.

Disclosure of interest

R.A., C.R.G.G., J.C.P., F.R., and M.P. declare that they have no competing interest.

S.V. receives consulting and lecture fees, travel grants and research support from Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma.

R.M. serves on scientific advisory board for MedImmune and received funding for travel and honoraria from Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme and Teva.

F.C. serves on scientific advisory board for Biogen Idec, and

Acknowledgment

The authors are grateful to the NOMADMUS study group, the imaging group of OFSEP and the COPIL of OFSEP for their help to the elaboration of the study and the management of the data set. Salem Hannoun (CREATIS-LRMN/CNRS UMR 5220–INSERM U630) and Philip Robinson (Université Lyon 1), edited the manuscript for non-intellectual content.

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