Structural Noninfectious Manifestations of the Central Nervous System in Common Variable Immunodeficiency Disorders

Background: Central nervous system (CNS) disease in adult common variable immunodeficiency (CVID) is rare, and therefore diagnostic and therapeutic protocols are lacking.

Objective: To provide clinical information aiming to establish awareness and first experience-based recommendations.

Methods: We reviewed clinical manifestations, genetic and immunological characteristics, diagnostic evaluation, and treatment of patients with CVID with abnormal magnetic resonance imaging (MRI) of the CNS disease in our cohort.

Results: Seventeen patients with CNS manifestation and a previous diagnosis of CVID were identified. Presenting symptoms of the CNS disease included loss of sensory or motoric function, headache, or epilepsy. Contrast-enhancing lesions of the brain or solely the spinal cord were the most common findings on MRI. The prevalence of splenomegaly, lymphadenopathy, interstitial lung disease, and autoimmune cytopenia was significantly increased compared with control CVID patients. In 8 patients, a molecular defect was identified, including mutations in CTLA4, NFKB1, and CECR1. Patients with CVID with CNS involvement generally displayed lymphopenia, skewed CD4⁺ T-cell subsets, and increased proportions of CD21^low B cells in the peripheral blood. CNS involvement usually responded well to high-dose steroids, but regularly required maintenance therapy to prevent relapse.

Conclusion: CNS disease is a severe but rare complication in CVID disorders, particularly affecting patients with other noninfectious disease symptoms. Diagnostic evaluation needs to rule out infectious causes by all means; a genetic evaluation is recommended given the high probability of an underlying monogenic disorder. Possible treatment consists of steroids with yet to be determined optimal maintenance therapy in case of relapse.