Journal of Clinical Immunology

, Volume 39, Issue 2, pp 171–181 | Cite as

Neurological Involvement in Childhood Evans Syndrome

  • Thomas PincezEmail author
  • Bénédicte Neven
  • Hubert Ducou Le Pointe
  • Pascale Varlet
  • Helder Fernandes
  • Albane Gareton
  • Guy Leverger
  • Thierry Leblanc
  • Hervé Chambost
  • Gérard Michel
  • Marlène Pasquet
  • Frédéric Millot
  • Olivier Hermine
  • Alexis Mathian
  • Marie Hully
  • Hélène Zephir
  • Mohamed Hamidou
  • Jean-Marc Durand
  • Yves Perel
  • Judith Landman-Parker
  • Fréderic Rieux-Laucat
  • Nathalie Aladjidi
Original Article



Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients.


OBS’CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed.


On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6–15.8). Neurological symptoms appeared with a median delay of 6 years (2.5–18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2).


Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.


Autoimmune cytopenia Evans syndrome primary immunodeficiency CTLA deficiency neurological disorder lymphoproliferation 


Authorship contributions.

TP, BN, JLP, FRL, and NA designed the research, analyzed the data, and participated in writing the paper. HDLP reviewed the MRI. PV and AG reviewed the pathology samples. HF was the data manager and performed the statistical analyses. FRL performed the biology molecular analyses. BN, JLP, NA, GL, TL, HC, GM, MP, FM, OH, AM, MHu, HZ, MHa, JMD, and YP were in charge of the patients and participated in data and blood sample collection. All authors critically read the manuscript, approved the final version, and agreed to be accountable for all aspects of the work.


The clinical database OBS’CEREVANCE was funded by the GIS-Institut des Maladies Rares (INSERM); the French Ministry of Health (Rare Disease Plan, PHRC 2005); the Association Bordelaise pour l’Avancement des Sciences Pédiatriques (ABASP) research charity; the Association pour la Recherche et les Maladies Hématologiques de l’Enfant (RMHE) research charity; and the AFSE and O-CYTO patient associations.

Compliance with Ethical Standards

Disclosure of Conflicts of Interest

TP has received a funding support from LFB biomedicaments to attend the 2017 European Hematology Association Annual Meeting. The authors declare that they have no other conflict of interest.

Supplementary material

10875_2019_594_MOESM1_ESM.pdf (2.6 mb)
Figure S1 Radiological evolution of the lesions. Each patient’s ID is the upper number and the MRI sequence is the lower statement (T1 gado: T1-weighted sequence post gadolinium injection, FLAIR: T2-weighted sequence fluid-attenuated inversion recovery). The delay after manifestation’s onset is under each figure. (PDF 2642 kb)
10875_2019_594_MOESM2_ESM.xlsx (306 kb)
Table S1 Complementary exams at neurological involvement (XLSX 305 kb)
10875_2019_594_MOESM3_ESM.xlsx (9 kb)
Table S2 Pathology findings (XLSX 9 kb)
10875_2019_594_MOESM4_ESM.xlsx (12 kb)
Table S3 Non-neurological organ involvement (XLSX 12 kb)
10875_2019_594_MOESM5_ESM.xlsx (491 kb)
Table S4 Immunobiology (XLSX 491 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Thomas Pincez
    • 1
    • 2
    Email author
  • Bénédicte Neven
    • 3
  • Hubert Ducou Le Pointe
    • 4
  • Pascale Varlet
    • 5
  • Helder Fernandes
    • 6
    • 7
  • Albane Gareton
    • 5
  • Guy Leverger
    • 1
  • Thierry Leblanc
    • 8
  • Hervé Chambost
    • 9
  • Gérard Michel
    • 9
  • Marlène Pasquet
    • 10
  • Frédéric Millot
    • 11
  • Olivier Hermine
    • 12
  • Alexis Mathian
    • 13
  • Marie Hully
    • 14
  • Hélène Zephir
    • 15
  • Mohamed Hamidou
    • 16
  • Jean-Marc Durand
    • 17
  • Yves Perel
    • 6
    • 7
    • 18
  • Judith Landman-Parker
    • 1
  • Fréderic Rieux-Laucat
    • 19
  • Nathalie Aladjidi
    • 6
    • 7
    • 18
  1. 1.Department of Onco-HematologyAPHP–Trousseau HospitalParisFrance
  2. 2.Department of Pediatric Hematology-OncologySainte-Justine University Hospital, Montreal UniversityQuébecCanada
  3. 3.Pediatric Hematology-Immunology DepartmentAPHP–Necker-Enfants Malades HospitalParisFrance
  4. 4.Pediatric Radiology departmentAPHP–Trousseau HospitalParisFrance
  5. 5.Neuropathology DepartmentSainte-Anne HospitalParisFrance
  6. 6.Centre de Référence National des Cytopénies Autoimmunes de l’Enfant (CEREVANCE)University Hospital of BordeauxBordeauxFrance
  7. 7.CIC 1401, INSERM CICPUniversity Hospital of BordeauxBordeauxFrance
  8. 8.Department of HematologyAPHP–Robert Debré HospitalParisFrance
  9. 9.Department of Pediatric HematologyUniversity Hospital Timone EnfantsMarseilleFrance
  10. 10.Hôpital des EnfantsUniversity Hospital of ToulouseToulouseFrance
  11. 11.Department of Pediatric HematologyUniversity Hospital of PoitiersPoitiersFrance
  12. 12.Department of HematologyAPHP–Necker-Enfants Malades HospitalParisFrance
  13. 13.Department of Internal Medicine 2APHP–Pitié-Salpêtrière HospitalParisFrance
  14. 14.Department of NeurologyAPHP–Necker-Enfants Malades HospitalParisFrance
  15. 15.Clinique Neurologique, Pôle des Neurosciences et de l’Appareil LocomoteurLille UniversityLilleFrance
  16. 16.Department of Internal MedicineUniversity Hospital of NantesNantesFrance
  17. 17.Department of Internal MedicineUniversity Hospital Timone EnfantsParisFrance
  18. 18.Department of Pediatric HematologyUniversity Hospital of BordeauxBordeauxFrance
  19. 19.Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institute, INSERM UMR-S1163Paris Descartes UniversityParisFrance

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