Neurological involvement in patients with primary immunodeficiency

Main Article Content

Hulya Kose
Zuhal Karali
Muhittin Bodur
Sukru Cekic
Sara Sebnem Kilic

Keywords

Cvid, Dgs, Neurologic Abnormalities, Nervous System, Primary Immune Deficiency

Abstract

Introduction: Primary immunodeficiency diseases (PID) are defined by recurrent infections, allergies, autoimmunity, and malignancies. Neurologic symptoms are one of the major components of some immunodeficiency syndromes, such as Ataxia-Telangiectasia (AT), Nijmegen breakage syndrome (NBS), and Purine Nucleoside Phosphorylase (PNP) deficiency, which are considered as the primary involvement. Various pathological mechanisms, DNA repair disorders, metabolic abnormalities, and autoimmune phenomena have also been linked with neurological conditions.


Materials and method: We retrospectively assessed the neurological involvement in 108 patients out of 6000 with PID in this study.


Results: The female/male ratio of the cases was 49/59, and the median age was 13 years (min = 1; max = 60). Neurological problems were detected at a median age of 7 years (min = 0.5; max = 30). Di George Syndrome (DGS) and CVID (common variable immunodeficiency) were the most common diseases in our cohort (n = 31, 30% and n = 30, 27%, respectively). The most frequent outcomes were cognitive delay (n = 63, 58%), epilepsy (n = 25, 23%), and ataxia (n = 20, 18%). Central nervous system involvement was found in 99% of the patients (n = 107), and peripheral nervous system complication was found in only one patient with CVID and chronic inflammatory demyelinating polyneuropathy (CDIP). Cranial MRI was found to be abnormal in 74% (n = 80) of the patients. MRI findings included cerebellar atrophy (n = 33, 34%), white matter lesion (n = 27, 28.4%), cerebral atrophy (n = 21, 22.3%), gray matter lesion (n = 6, 6.3%), hydrocephalus (n = 5, 5,3%), and pituitary gland lesion (n = 3, 3.2%), intracranial hemorrhage (n = 3, 3%), intracranial vasculitis (n = 3, 2.7%), and arterio-venous malformation (n = 1, 0,9%). Primary involvement (a component of the disease) was 60% (n = 65), and secondary (infection or autoimmunity) and tertiary involvements (structural or incidental lesions) contributed 20% (n = 20) each in the patients.


Conclusion: In this study, we describe the various neurologic findings of patients with PID. The neurologic presentation may represent the initial manifestation of certain types of PID. Early diagnosis and treatment are essential to prevent or reduce further neurologic damages.

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References

1. Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022;42(7):1473–1507. 10.1007/s10875-022-01289-3

2. Yildirim M, Ayvaz DC, Konuskan B, Gocmen R, Tezcan I, Topcu M, et al. Neurologic involvement in primary immunodeficiency disorders. J Child Neurol. 2018;33(5):320–8. 10.1177/0883073817754176

3. Özdemir Ö, Okan MS, Kilic SS. Chronic inflammatory demyelinating polyneuropathy in common variable immunodeficiency. Pediatr Neurol. 2012;46(4):260–2. 10.1016/j.pediatrneurol.2012.02.009

4. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21. 10.1111/epi.13709

5. Gothelf D, Schaer M, Eliez S. Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome. Dev Disabil Res Rev. 2008;14(1):59–68. 10.1002/ddrr.9

6. Shprintzen RJ. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008;14(1):3–10. 10.1002/ddrr.2

7. Altmann T, Gennery AR. DNA ligase IV syndrome; a review. Orphanet J Rare Dis. 2016;11(1):1–7. 10.1186/s13023-016-0520-1

8. Dehkordy SF, Aghamohammadi A, Ochs HD, Rezaei N. Primary immunodeficiency diseases associated with neurologic manifestations. J Clin Immunol. 2012;32(1):1–24. 10.1007/s10875-011-9593-8

9. Yavuz H, Chee R. A review on the vascular features of the hyperimmunoglobulin e syndrome. Clin Exp Immunol. 2010;159(3):238–44. 10.1111/j.1365-2249.2009.04044.x

10. Bulut E, Erden A, Karadag O, Oguz KK, Ozen S. Deficiency of adenosine deaminase 2; special focus on central nervous system imaging. J Neuroradiol. 2019;46(3):193–8. 10.1016/j.neurad.2018.05.002

11. Batu ED, Karadag O, Taskiran EZ, Kalyoncu U, Aksentijevich I, Alikasifoglu M, et al. A case series of adenosine deaminase 2-deficient patients emphasizing treatment and genotype-phenotype correlations. J Rheumatol. 2015;42(8):1532–4. 10.3899/jrheum.150024

12. Elbracht M, Mull M, Wagner N, Kuhl C, Abicht A, Kurth I, et al. Stroke as initial manifestation of adenosine deaminase 2 deficiency. Neuropediatrics. 2017;48(2):111–4. 10.1055/s-0036-1597611

13. Sahin S, Adrovic A, Kasapcopur O. A monogenic autoinflammatory disease with fatal vasculitis: Deficiency of adenosine deaminase 2. Curr Opin Rheumatol. 2020;32(1):3–14. 10.1097/BOR.0000000000000669

14. Balkan S, Dora B, Ozbilim G, Acikbas C, Unal A. Progressive multifocal leucoencephalopathy: Clinical, neuroradiological and neuropathological findings. Turkish J Neurol. 2001; 7(1): 95–00.

15. Salzer U, Grimbacher B. TACI deficiency — a complex system out of balance. Curr Opin Immunol. 2021;71:81–8. 10.1016/j.coi.2021.06.004

16. Du SW, Jacobs HM, Arkatkar T, Rawlings DJ, Jackson SW. Integrated B cell, toll-like, and BAFF receptor signals promote autoantibody production by transitional B cells. J Immunol. 2018;201(11):3258–68. 10.4049/jimmunol.1800393

17. Barroeta Seijas AB, Graziani S, Cancrini C, Finocchi A, Ferrari S, Miniero R, et al. The impact of taci mutations: From hypogammaglobulinemia in infancy to autoimmunity in adulthood. Int J Immunopathol Pharmacol. 2012;25(2):407–14. 10.1177/039463201202500210

18. Romberg N, Virdee M, Chamberlain N, Oe T, Schickel JN, Perkins T, et al. TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development. J Allergy Clin Immunol . 2015;136(5):1315–25. 10.1016/j.jaci.2015.05.012

19. Etzioni A, Tonetti M. Leukocyte adhesion deficiency II-From A to almost Z. Immunol Rev. 2000;178:138–47. 10.1034/j.1600-065X.2000.17805.x

20. Faghri S, Tamura D, Kraemer KH, Digiovanna JJ. Trichothiodystrophy: A systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. J Med Genet. 2008;45(10):609–21. 10.1136/jmg.2008.058743