Advertisement

Journal of Clinical Immunology

, Volume 36, Issue 8, pp 793–800 | Cite as

Neurologic Complications of Common Variable Immunodeficiency

  • Jenna Thuc-Uyen NguyenEmail author
  • Ari Green
  • Michael R. Wilson
  • Joseph L. DeRisi
  • Katherine Gundling
Original Article

Abstract

Common variable immunodeficiency is a rare disorder of immunity associated with a myriad of clinical manifestations including recurrent infections, autoimmunity, and malignancy. Though rare, neurologic complications have been described in a small number of case reports and case series of CVID patients. In this article, we present a patient with CVID who suffered significant neurologic morbidity and categorize the reported range of neurologic complications associated with CVID. Our case highlights the complex nature of neurologic manifestations in CVID patients, and our review of the current database suggests that infection and inflammatory neurologic disorders are the cause of most neurologic presentations.

Keywords

Common variable immunodeficiency Neurologic disease Autoimmune 

Notes

Compliance with Ethical Standard

Conflict of Interest

The authors declared that they have no conflict of interest.

Supplementary material

10875_2016_336_MOESM1_ESM.docx (103 kb)
ESM 1 ᅟ(DOCX 102 kb)

References

  1. 1.
    Hermaszewski RA, Webster AD. Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med. 1993;86(1):31–42. 0033-5622 (Print); 0033-5622 (Linking).PubMedGoogle Scholar
  2. 2.
    Wilson MR, Shanbhag NM, Reid MJ, et al. Diagnosing balamuthia mandrillaris encephalitis with metagenomic deep sequencing. Ann Neurol. 2015;78(5):722–30. doi: 10.1002/ana.24499. Epub 2015 Aug 24. (1531-8249 (Electronic); 0364-5134 (Linking)).CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Narula S, LaRosa DF, Kamoun M, et al. Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency and abnormal CD8+ T-cell subset distribution. Ann Allergy Asthma Immunol. 2007;98(5):483–9. 1081-1206 (Print); 1081-1206 (Linking).CrossRefPubMedGoogle Scholar
  4. 4.
    Kurmann R, Weisstanner C, Kardas P, et al. Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine. J Neurovirol. 2015;21(6):694–701. 1538-2443 (Electronic); 1355-0284 (Linking).CrossRefPubMedGoogle Scholar
  5. 5.
    Snyder MD, Storch GA, Clifford DB. Atypical PML leading to a diagnosis of common variable immunodeficiency. Neurology. 2005;64(9):1661 (1526-632X (Electronic); 0028-3878 (Linking)).CrossRefPubMedGoogle Scholar
  6. 6.
    Kurmann R, Weisstanner C, Piotr K, et al. Early progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency syndrome reversed under mirtazapine and mefloquine treatment. Eur J Neurol. 2014;21(Suppl 1 Sp Iss SI):428.Google Scholar
  7. 7.
    Nabavi M, Arshi S, et al. Persistent papilloma and polyoma virus infection in common variable immunodeficiency with progressive multifocal leukoencephalopathy. Ann Allergy Asthma Immunol. 2013;110(2):119–20. doi: 10.1016/j.anai.2012.11.009. Epub 2012 Dec 21. (1534-4436 (Electronic); 1081-1206 (Linking)).CrossRefPubMedGoogle Scholar
  8. 8.
    Scotton PG, Vaglia A, Carniato A, Marchiori GC. Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency. Clin Infect Dis. 1998;26(1):215–6. 1058-4838 (Print); 1058-4838 (Linking).CrossRefPubMedGoogle Scholar
  9. 9.
    Borish L, Ayars AG, Kirkpatrick CH. Common variable immunodeficiency presenting as herpes simplex virus encephalitis. J Allergy Clin Immunol. 2011;127(2):541–3. 1097-6825 (Electronic); 0091-6749 (Linking).CrossRefPubMedGoogle Scholar
  10. 10.
    Jabbari E, Marshall CR, Longhurst H, Sylvester R. Longitudinally extensive transverse myelitis: a rare association with common variable immunodeficiency. Pract Neurol. 2015;15(1):49–52. doi: 10.1136/practneurol-2014-000953. Epub 2014 Oct 21. (1474-7766 (Electronic); 1474-7758 (Linking)).CrossRefPubMedGoogle Scholar
  11. 11.
    Danieli MG, Pettinari L, Marinangeli L, Logullo F. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin. BMJ Case Rep. 2012;8:2012. doi: 10.1136/bcr-01-2012-5637.Google Scholar
  12. 12.
    Akman CI, Patterson MC, Rubinstein A, Herzog R. Limbic encephalitis associated with anti-GAD antibody and common variable immune deficiency. Dev Med Child Neurol. 2009;51(7):563–7. doi: 10.1111/j.1469-8749.2008.03217.x. Epub 2009 Feb 3. (1469-8749 (Electronic); 0012-1622 (Linking)).CrossRefPubMedGoogle Scholar
  13. 13.
    Vella FS, Simone B, Carella A, Schiraldi O, Antonaci S. Acute disseminated encephalomyelitis as first clinical feature in common variable immunodeficiency: a case report. Recenti Prog Med. 2000;91(7-8):365–7.PubMedGoogle Scholar
  14. 14.
    Happe S, Husstedt IW. Successful treatment of acute encephalomyelitis associated with common variable immunodeficiency syndrome (CVID): case report and review of the literature. J Neurol. 2000;247(7):562–5. 0340-5354 (Print); 0340-5354 (Linking).CrossRefPubMedGoogle Scholar
  15. 15.
    Delvecchio M, De Bellis A, De Mattia D, et al. Growth hormone deficiency and antipituitary antibodies in a patient with common variable immunodeficiency. J Endocrinol Invest. 2009;32(8):637–40. doi: 10.3275/6332. Epub 2009 May 26. (1720-8386 (Electronic); 0391-4097 (Linking)).CrossRefPubMedGoogle Scholar
  16. 16.
    Megias MC, Matei AM, Gonzalez Albarran O, Perez Lopez G. Partial central diabetes insipidus in patient with common variable immunodeficiency. BMJ Case Rep. 2012;3:2012. doi: 10.1136/bcr.11.2011.5067.Google Scholar
  17. 17.
    Tovo PA, Lala R, Martino S, et al. Isolated adrenocorticotropic hormone deficiency associated with common variable immunodeficiency. Eur J Pediatr. 1991;150(6):400–2. 0340-6199 (Print); 0340-6199 (Linking).CrossRefPubMedGoogle Scholar
  18. 18.
    Aslam A, Misbah SA, Talbot K, Chapel H. Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency. Clin Immunol. 2004;112(1):24–9. 1521-6616 (Print); 1521-6616 (Linking).CrossRefPubMedGoogle Scholar
  19. 19.
    Yousry TA, Strupp M, Bruning R. Common variable immunodeficiency leading to spinal subacute combined degeneration monitored by MRI. J Neurol Neurosurg Psychiatry. 1998;64(5):663–6. 0022-3050 (Print); 0022-3050 (Linking).CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ziegner UH, Kobayashi RH, Cunningham-Rundles C, et al. Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment. Clin Immunol. 2002;102(1):19–24. 1521-6616 (Print); 1521-6616 (Linking).CrossRefPubMedGoogle Scholar
  21. 21.
    Bonilla FA, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186–205.e1-78. doi: 10.1016/j.jaci.2015.04.049. Epub 2015 Sep 12. (1097-6825 (Electronic); 0091-6749 (Linking)).CrossRefPubMedGoogle Scholar
  22. 22.
    Kaltsonoudis E, Zikou AK, et al. Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study. Arthritis Res Ther. 2014;16(3):R125. doi: 10.1186/ar4582. 1478-6362 (Electronic); 1478-6354 (Linking).CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pfitzmann R, Klupp J, Langrehr JM, et al. Mycophenolatemofetil for immunosuppression after liver transplantation: a follow-up study of 191 patients. Transplantation. 2003;76(1):130–6 (0041-1337 (Print); 0041-1337 (Linking)).CrossRefPubMedGoogle Scholar
  24. 24.
    Ahrens CL, Manno EM. Neurotoxicity of commonly used hepatic drugs. Handb Clin Neurol. 2014;120:675–82. doi: 10.1016/B978-0-7020-4087-0.00046-2. 0072-9752 (Print); 0072-9752 (Linking).CrossRefPubMedGoogle Scholar
  25. 25.
    Lau YL, Levinsky RJ, Morgan G, Strobel S. Dual meningoencephalitis with echovirus type 11 and adenovirus in combined (common variable) immunodeficiency. Pediatr Infect Dis J. 1988;7(12):873–6. 0891-3668 (Print); 0891-3668 (Linking).CrossRefPubMedGoogle Scholar
  26. 26.
    Gloeckel U, Legat G. Common variable immunodeficiency in a 10.5-year-old girl with haemophilus meningitis. Monatsschrift Kinderheilkunde. 1987;135(5):274–6.Google Scholar
  27. 27.
    Cooper CJ, Said S, Quansah R, et al. Pneumococcal meningitis in a young adult female with common variable immunodeficiency. Am J Case Rep. 2013;14:471–5. doi: 10.12659/AJCR.889617. eCollection 2013. (1941-5923 (Electronic); 1941-5923 (Linking)).CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Couch JR, Romyg DA. Histoplasma meningitis with common variable hypogammaglobulinemia. Neurol Neurocir Psiquiatr. 1977;18(2-3 Suppl):403–12. 0028-3851 (Print); 0028-3851 (Linking).PubMedGoogle Scholar
  29. 29.
    Manfredi R, Dentale N, Fortunato L, et al. Severe pneumococcal meningitis heralding a deep hypogammaglobulinaemia related to common variable immunodeficiency, at the age of 27 years. Scand J Infect Dis. 2004;36(10):756–8. 0036-5548 (Print); 0036-5548 (Linking).CrossRefPubMedGoogle Scholar
  30. 30.
    Bakri FG, Bahou YG, Al-Sammarrai FA, et al. Fatal encephalitis due to BK virus in a patient with common variable immunodeficiency: a case report. J Clin Virol. 2013;57(4):363–9. doi: 10.1016/j.jcv.2013.04.016. Epub 2013 Jun 2. (1873-5967 (Electronic); 1386-6532 (Linking)).CrossRefPubMedGoogle Scholar
  31. 31.
    Kralickova P, Mala E, Vokurkova D, et al. Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports. Int Arch Allergy Immunol. 2014;163(1):69–74. doi: 10.1159/000355957. Epub 2013 Nov 16. (1423-0097 (Electronic); 1018-2438 (Linking)).CrossRefPubMedGoogle Scholar
  32. 32.
    Maclennan CA, Dunn G, Wood P, Kumararatne DS, Wood D. Chronic infection with vaccine-derived neurovirulent poliovirus in common variable immunodeficiency and implications for world health. J Allergy Clin Immunol. 2001;107(2):S304–5.Google Scholar
  33. 33.
    Holtkamp M, Okuducu AF, Klingebiel R, Ploner CJ. Cerebral toxoplasmosis in a patient with common variable immunodeficiency. Neurology. 2004;63(11):2192–3. 1526-632X (Electronic); 0028-3878 (Linking).CrossRefPubMedGoogle Scholar
  34. 34.
    Hofmann A, Zaharatos G, Miller M. Case report and review of the literature: Toxoplasma gondii encephalitis in a 40-year-old woman with common variable immunodeficiency and a new diagnosis of large granular lymphocytic leukemia. Can J Infect Dis Med Microbiol. 2008;19(4):309–10. 1712-9532 (Print); 1712-9532 (Linking).PubMedPubMedCentralGoogle Scholar
  35. 35.
    Daugherty WP, Clarke MJ, Cloft HJ, Lanzino GL. Going viral: Fusiform vertebrobasilar and internal carotid aneurysms with varicella angiitis and common variable immunodeficiency. J Neurosurg Pediatr. 2009;4(6):528–31. doi: 10.3171/2009.7.PEDS09107. 1933-0715 (Electronic); 1933-0707 (Linking).CrossRefPubMedGoogle Scholar
  36. 36.
    Alonto AM, DM A, Malani PN. West nile virus meningitis in patient with common variable immunodeficiency. Emerg Infect Dis. 2003;9(10):1353–4. 1080-6040 (Print); 1080-6040 (Linking).CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Sempere AP, Tahoces M, Palao-Duarte S, Garcia-Perez A. Bilateral optic neuritis in a 26-year-old man with common variable immunodeficiency: a case report. J Med Case Rep. 2011;5:319. doi: 10.1186/1752-1947-5-319. 1752-1947 (Electronic); 1752-1947 (Linking).CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kumar N, Hagan JB, et al. Common variable immunodeficiency-associated myelitis: report of treatment with infliximab. J Neurol. 2008;255(11):1821–4. doi: 10.1007/s00415-008-0898-3. Epub 2008 Jul 21. (0340-5354 (Print); 0340-5354 (Linking)).CrossRefPubMedGoogle Scholar
  39. 39.
    Ozdemir O, Okan MS, Kilic SS. Chronic inflammatory demyelinating polyneuropathy in common variable immunodeficiency. Pediatr Neurol. 2012;46(4):260–2. doi: 10.1016/j.pediatrneurol. 2012.02.009. (1873-5150 (Electronic); 0887-8994 (Linking)).CrossRefPubMedGoogle Scholar
  40. 40.
    Mailander V, Gleisner B, Blau IW, Thiel E. Guillain-barre-strohl syndrome unraveled as paraneoplastic syndrome of B-cell acute lymphoblastic leukemia in a patient with preceding common variable immunodeficiency syndrome with evans syndrome. Leuk Lymphoma. 2004;45(1):189–92. 1042-8194 (Print); 1026-8022 (Linking).CrossRefPubMedGoogle Scholar
  41. 41.
    Madaan A, Weiler CR. Intraspinal sarcoidosis and common variable immune deficiency: case report and literature review. J Allergy Clin Immunol. 2003;111(2 Abstract Supplement):S228.CrossRefGoogle Scholar
  42. 42.
    McComish J, Smith A, Blumbergs P, Frasca J, Kupa A. Progressive neurological deterioration in a patient with CVID and granulomatous disease: neuropathological correlation. Allergy (Oxford). 2012;67(Suppl 96 Sp Iss SI):290.Google Scholar
  43. 43.
    Misbah SA, Spickett GP, Esiri MM, et al. Recurrent intra-cranial granulomata presenting as space-occupying lesions in a patient with common variable immunodeficiency. Postgrad Med J. 1992;68(799):359–62. 0032-5473 (Print); 0032-5473 (Linking).CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Dziadzio M, Hortobagyi T, Kidd D, Chee R. Common variable immunodeficiency with coexisting central nervous system sarcoidosis: case report and literature review with implications for diagnosis and pathogenesis. Ideggyogy Sz. 2011;64(11-12):405–8. 0019-1442 (Print); 0019-1442 (Linking).PubMedGoogle Scholar
  45. 45.
    Dolhun R, Sriram S. Neurosarcoidosis presenting as longitudinally extensive transverse myelitis. J Clin Neurosci. 2009;16(4):595–7. doi: 10.1016/j.jocn.2008.06.004. Epub 2009 Feb 5. (0967-5868 (Print); 0967-5868 (Linking)).CrossRefPubMedGoogle Scholar
  46. 46.
    Kondo M, Fukao T, Teramoto T, et al. A common variable immunodeficient patient who developed acute disseminated encephalomyelitis followed by the lennox-gastaut syndrome. Pediatr Allergy Immunol. 2005;16(4):357–60. 0905-6157 (Print); 0905-6157 (Linking).CrossRefPubMedGoogle Scholar
  47. 47.
    Rudge P, Webster AD, Revesz T, et al. Encephalomyelitis in primary hypogammaglobulinaemia. Brain. 1996;119(Pt 1):1–15. 0006-8950 (Print); 0006-8950 (Linking).CrossRefPubMedGoogle Scholar
  48. 48.
    Larner AJ, Webster AD, Thomas DJ. Peripheral neuropathy associated with common variable immunodeficiency. Eur J Neurol. 2000;7(5):573–5. 1351-5101 (Print); 1351-5101 (Linking).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jenna Thuc-Uyen Nguyen
    • 1
    Email author
  • Ari Green
    • 2
    • 3
  • Michael R. Wilson
    • 2
  • Joseph L. DeRisi
    • 4
    • 5
  • Katherine Gundling
    • 1
  1. 1.Division of Allergy and ImmunologyUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of NeurologyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of OphthalmologyUniversity of CaliforniaSan FranciscoUSA
  4. 4.Department of Biochemistry and BiophysicsUniversity of CaliforniaSan FranciscoUSA
  5. 5.Howard Hughes Medical InstituteChevy ChaseUSA

Personalised recommendations