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Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions

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Abstract

Background

The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear.

Objectives

Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions.

Methods

We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed.

Results

Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD.

Discussion

Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.

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Abbreviations

AHLE:

Acute haemorrhagic leukoencephalitis

AQP4:

Aquaporin-4

AIIDL:

Atypical idiopathic inflammatory demyelinating lesion

CNS:

Central nervous system

DWI:

Diffusion-weighted imaging

FLAIR:

Fluid attenuated inversion recovery

GFAP:

Glial fibrillary acid protein

IgG:

Immunoglobulin G

LFB:

Luxol fast blue

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

NMO:

Neuromyelitis optica

NMOSD:

Neuromyelitis optica spectrum disorders

ON:

Optic neuritis

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Author information

Authors and Affiliations

  1. Department of Neurology, Multiple Sclerosis Center, Montpellier University Hospital, 80 rue Augustin Fliche, 34295, Montpellier, Cedex 05, France

    Xavier Ayrignac, Clarisse Carra-Dalliere, Mahmoud Charif & Pierre Labauge

  2. The Institute for Neurosciences of Montpellier, Inserm UMR1051, Saint Eloi Hospital, University of Montpellier, Montpellier, France

    Xavier Ayrignac

  3. Department of Pathology, Montpellier University Hospital, Montpellier, France

    Valérie Rigau

  4. Department of Pathology, Strasbourg University Hospital, Strasbourg, France

    Benoit Lhermitte

  5. Department of Immunology, Montpellier University Hospital, Montpellier, France

    Thierry Vincent

  6. Department of Neuroradiology, Montpellier University Hospital, Montpellier, France

    Nicolas Menjot de Champfleur

  7. Department of Neurology and Clinical Investigation Center, Strasbourg University Hospital, Strasbourg, France

    Nicolas Collongues & Jérôme de Seze

  8. Department of Radiology, Strasbourg University Hospital, Strasbourg, France

    Sonia Hebbadj & Stéphane Kremer

  9. Department of Neurology, Colmar Hospital, Colmar, France

    Guido Ahle

  10. Department of Pathology, Colmar Hospital, Colmar, France

    Hélène Oesterlé

  11. Department of Radiology, Centre hospitalier Lyon-Sud, hospices civils de Lyon, Lyon, France

    François Cotton

  12. Department of Neurology, Hôpital Neurologique Pierre Wertheimer Hospices Civils de Lyon, Lyon, France

    Françoise Durand-Dubief, Romain Marignier & Sandra Vukusic

  13. Department of Neurology, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Frédéric Taithe

  14. Department of Neurology, Nice University Hospital, Nice, France

    Mikael Cohen

  15. Department of Neurology, Tours University Hospital, Tours, France

    Anne-Marie Guennoc

  16. Department of Neurology, Rennes University Hospital, Rennes, France

    Anne Kerbrat & Gilles Edan

  17. Department of Neuroradiology, Rennes University Hospital, Rennes, France

    Béatrice Carsin-Nicol

  18. Department of Neurology, Perpignan Hospital, Perpignan, France

    Thibaut Allou & Denis Sablot

  19. Department of Neurology, Nimes University Hospital, Nîmes, France

    Eric Thouvenot

  20. Department of Neurology, Bordeaux University Hospital, Bordeaux, France

    Aurélie Ruet

  21. Department of Neurology, Limoges University Hospital, Limoges, France

    Laurent Magy

  22. Department of Neuroradiology, Limoges University Hospital, Limoges, France

    Marie-Paule Boncoeur-Martel

Authors
  1. Xavier Ayrignac
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  2. Valérie Rigau
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  3. Benoit Lhermitte
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  4. Thierry Vincent
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  5. Nicolas Menjot de Champfleur
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  6. Clarisse Carra-Dalliere
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  7. Mahmoud Charif
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  8. Nicolas Collongues
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  9. Jérôme de Seze
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  10. Sonia Hebbadj
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  18. Mikael Cohen
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  20. Anne Kerbrat
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  27. Laurent Magy
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  28. Marie-Paule Boncoeur-Martel
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  29. Pierre Labauge
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  30. Stéphane Kremer
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Contributions

XA: study concept and design, acquisition of data, analysis and interpretation, and writing. VR: laboratory analysis, critical revision of the manuscript for important intellectual content. BL: laboratory analysis, critical revision of the manuscript for important intellectual content. TV: laboratory analysis, critical revision of the manuscript for important intellectual content. NMdeC: acquisition of data, critical revision of the manuscript for important intellectual content. CC-D: acquisition of data, critical revision of the manuscript for important intellectual content. MC: acquisition of data, critical revision of the manuscript for important intellectual content. NC: acquisition of data, critical revision of the manuscript for important intellectual content. JdeS: acquisition of data, critical revision of the manuscript for important intellectual content. SH: acquisition of data, critical revision of the manuscript for important intellectual content. GA: acquisition of data, critical revision of the manuscript for important intellectual content. HO: acquisition of data, critical revision of the manuscript for important intellectual content. FC: acquisition of data, critical revision of the manuscript for important intellectual content. FD-D: acquisition of data, critical revision of the manuscript for important intellectual content. RM: acquisition of data, critical revision of the manuscript for important intellectual content. FT: acquisition of data, critical revision of the manuscript for important intellectual content. MC: acquisition of data, critical revision of the manuscript for important intellectual content. A-MG: acquisition of data, critical revision of the manuscript for important intellectual content. AK: acquisition of data, critical revision of the manuscript for important intellectual content. GE: acquisition of data, critical revision of the manuscript for important intellectual content. BC-N, TA: acquisition of data, critical revision of the manuscript for important intellectual content. DS: acquisition of data, critical revision of the manuscript for important intellectual content. ET: acquisition of data, critical revision of the manuscript for important intellectual content. AR: acquisition of data, critical revision of the manuscript for important intellectual content. LM: acquisition of data, critical revision of the manuscript for important intellectual content. M-P, B-M: acquisition of data, critical revision of the manuscript for important intellectual content. PL: study concept and design, acquisition of data, critical revision of the manuscript for important intellectual content. SK: study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content.

Corresponding author

Correspondence to Xavier Ayrignac.

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Conflicts of interest

Xavier Ayrignac has received consulting and lecturing fees, travel grants and research support from Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, and Teva Pharma. Valérie Rigau reports no disclosure relevant to this manuscript. Benoit Lhermitte reports no disclosure relevant to this manuscript. Thierry Vincent reports no disclosure relevant to this manuscript. Nicolas Menjot de Champfleur reports no disclosure relevant to this manuscript. Clarisse Carra-Dalliere reports no disclosure relevant to this manuscript. Mahmoud Charif reports no disclosure relevant to this manuscript. Nicolas Collongues reports no disclosure relevant to this manuscript. Jérôme de Seze reports no disclosure relevant to this manuscript. Sonia Hebbadj reports no disclosure relevant to this manuscript. Guido Ahle reports no disclosure relevant to this manuscript. Hélène Oesterlé reports no disclosure relevant to this manuscript. François Cotton reports no disclosure relevant to this manuscript. Françoise Durand-Dubief reports no disclosure relevant to this manuscript. Romain Marignier serves on scientific advisory board for MedImmune and has received funding for travel and honoraria from Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme and Teva. Frédéric Taithe reports no disclosure relevant to this manuscript. Mikael Cohen reports no disclosure relevant to this manuscript. Anne-Marie Guennoc reports no disclosure relevant to this manuscript. Anne Kerbrat reports no disclosure relevant to this manuscript. Gilles Edan reports no disclosure relevant to this manuscript. Béatrice Carsin-Nicol reports no disclosure relevant to this manuscript. Thibaut Allou reports no disclosure relevant to this manuscript. Denis Sablot reports no disclosure relevant to this manuscript. Eric Thouvenot reports no disclosure relevant to this manuscript. Aurélie Ruet or her institution received research grants and/or consulting fees from Novartis, Biogen, Merck-Serono, Bayer Healthcare, Roche, Teva, and Genzyme unrelated to the submitted work. Laurent Magy has received Honoraria, housing and consultancies from CSL Behring, Biogen, Teva Pharma, Octapharma, Pharnext, Sanofi Genzyme, Novartis. Marie-Paule Boncoeur-Martel reports no disclosure relevant to this manuscript. Pierre Labauge reports no disclosure relevant to this manuscript. Stéphane Kremer reports no disclosure relevant to this manuscript.

Ethics approval

The study was approved by Montpellier University Hospital Ethical Committee (Q-2017-03-02) and was registered on ClinicalTrial.gov (NCT03121105).

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Ayrignac, X., Rigau, V., Lhermitte, B. et al. Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions. J Neurol 266, 1743–1755 (2019). https://doi.org/10.1007/s00415-019-09328-7

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