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May 2023; 10 (3) Research ArticleOpen Access

Neurologic Manifestations of Common Variable Immunodeficiency

Impact on Quality of Life

Bruno Ivo De Almeida, Tammy L. Smith, Alen Delic, Lawanda Esquibel, Jonathan Galli, Leah Millsap, M. Mateo Paz Soldán, View ORCID ProfileMelissa M. Cortez, John Rose, View ORCID ProfileJohn E. Greenlee, Adi V. Gundlapalli, Harry R. Hill, Ka-Ho Wong, View ORCID ProfileStacey L. Clardy
First published February 16, 2023, DOI: https://doi.org/10.1212/NXI.0000000000200088
Bruno Ivo De Almeida
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Tammy L. Smith
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Alen Delic
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Lawanda Esquibel
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Jonathan Galli
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Leah Millsap
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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M. Mateo Paz Soldán
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Melissa M. Cortez
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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John Rose
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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John E. Greenlee
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Adi V. Gundlapalli
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Harry R. Hill
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Ka-Ho Wong
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Stacey L. Clardy
From the Université de Bordeaux (B.I.D.A.), U de Biologie, France; Department of Neurology (B.I.D.A., T.L.S., A.D., L.E., J.G., M.M.P.S., M.M.C., J.R., J.E.G., K.-H.W., S.L.C.), University of Utah School of Medicine, Salt Lake City; George E. Wahlen Department of Veterans Affairs Medical Center (T.L.S., J.G., M.M.P.S., J.R., J.E.G., S.L.C.), Salt Lake City, UT; University of Utah School of Medicine (L.M.); Department of Internal Medicine, (A.V.G.), University of Utah School of Medicine; and Divisions of Immunology and Infectious Disease (H.R.H.), Departments of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, Salt Lake City.
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Citation
Neurologic Manifestations of Common Variable Immunodeficiency
Impact on Quality of Life
Bruno Ivo De Almeida, Tammy L. Smith, Alen Delic, Lawanda Esquibel, Jonathan Galli, Leah Millsap, M. Mateo Paz Soldán, Melissa M. Cortez, John Rose, John E. Greenlee, Adi V. Gundlapalli, Harry R. Hill, Ka-Ho Wong, Stacey L. Clardy
Neurol Neuroimmunol Neuroinflamm May 2023, 10 (3) e200088; DOI: 10.1212/NXI.0000000000200088

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Abstract

Background and Objectives Common variable immunodeficiency is a systemic disease and not solely a disease of humoral immunity. Neurologic symptoms associated with common variable immunodeficiency are underrecognized and warrant further study. This work aimed to characterize the neurologic symptoms reported by people living with common variable immunodeficiency.

Methods We conducted a single academic medical center study of neurologic symptoms reported by adults previously diagnosed with common variable immunodeficiency. We used a survey of common neurologic symptoms to determine the prevalence of these symptoms in a population with common variable immunodeficiency and further assessed these patient-reported symptoms with validated questionnaires and compared symptom burden with other neurologic conditions.

Results A volunteer sample of adults (aged 18 years or older) previously diagnosed with common variable immunodeficiency at the University of Utah Clinical Immunology/Immune Deficiency Clinic who were able to read and comprehend English and willing and able to answer survey-based questions were recruited. Of 148 eligible participants identified, 80 responded and 78 completed the surveys. The mean age of respondents was 51.3 years (range 20–78 years); 73.1% female and 94.8% White. Patients with common variable immunodeficiency reported many common neurologic symptoms (mean 14.6, SD 5.9, range 1–25), with sleep issues, fatigue, and headache reported by more than 85%. Validated questionnaires addressing specific neurologic symptoms supported these results. T-scores on Neuro QoL questionnaires for sleep (mean 56.4, SD 10.4) and fatigue (mean 54.1, SD 11) were higher, indicating more dysfunction, than in the reference clinical population (p < 0.005). The Neuro QoL questionnaire for cognitive function showed a lower T-score (mean 44.8, SD 11.1) than that in the reference general population (p < 0.005), indicating worse function in this domain.

Discussion Among survey respondents, there is a marked burden of neurologic symptoms. Given the impact of neurologic symptoms on health-related quality-of-life measures, clinicians should screen patients with common variable immunodeficiency for the presence of these symptoms and offer referral to neurologists and/or symptomatic treatment when indicated. Frequently prescribed neurologic medications may also affect the immune system, and neurologists should consider screening patients for immune deficiency before prescribing them.

Glossary

CVID=
common variable immunodeficiency;
HRQL=
health-related quality of life;
ICD=
International Classification of Diseases;
MIDAS=
Migraine Disability Assessment;
OABSS=
Overactive Bladder Symptom Score;
USIDNET=
United States Immunodeficiency Network

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Submitted and externally peer reviewed. The handling editor was Editor Josep O. Dalmau, MD, PhD, FAAN.

  • Received May 23, 2022.
  • Accepted in final form December 1, 2022.
  • Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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