Cerebral involvement in common variable immunodeficiency: Case series and review of literature

Objectives: Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and often recurrent infections. Paradoxically, 8-22% of patients develop granulomatous disease. Granulomata have been described in the lungs, skin, liver, spleen, kidneys, eyes, lymph nodes and intestines. Data about central nervous system (CNS) disease in CVID are extremely rare. We aimed to describe a case series and systematic review of CNS involvement in CVID to understand different features and patterns of the disease. Methods: We searched all the English Pubmed database between 1950 and 2014 using the Key Words 'CVID', 'granulomata', 'brain', 'sarcoidosis', and 'sarcoid-like syndrome'. Only 15 patients were reported. We combined our experience with 4 additional cases from Cleveland Clinic between 2009 and 2014. Demographics, clinical features, laboratory and imaging findings, treatment and follow-up were extracted for the 19 patients and summarized descriptively. Results: Female gender and Caucasian race represented 63.2% (12/19), and 80% of the patients. The mean age of CVID diagnosis was 24 years; mean age when CNS disease was diagnosed was 21.5 years. 68.4% (13/19) had granulomas involving >2 organs, 31.6% (6/19) had CNS granulomas only. Associated granulomatous diseases occurred in lungs (72.7%), lymph nodes (27.2%), spleen (27.2%), eyes (18.1%), liver (18.1%), parotids (9%), and skin (9%). Symptoms of CNS involvement included seizures (31.6%), headaches (21%), vision loss (15.7%), decreased cognition (10.5%), focal weakness (5.2%), nystagmus (5.2%), ataxia (5.2%), coma (5.2%) and polyuria and polydypsia (5.2%). Brain mass was the most common radiologic finding (70%) followed by leptomeningeal enhancement, non specific white matter lesions, and absence of normal signal of the neurohypophysis (10%).Brain pathology findings included granulomatous disease in 83.3%, vasculitis without granulomas in 8.3%, and lymphocytic infiltrates of the meninges with diffuse non caseating granulomas in 8.3%.Cerebrospinal fluid analysis revealed elevated total proteins with/or without lymphocytic pleocytosis in 80%. Treatment included steroid, IVIG, Anti-TNF, rituximab methotrexate, cyclosporine, azathioprine, and cyclophosphamide. Conclusion: CNS disease is a rare challenging complication of CVID. Female gender, Caucasian race and lung involvement appear to be associated with brain involvement. Although immunoglobulin and steroids remain the first line treatment, other immunosuppressive agents have shown some promise with regards to recurrent relapsing presentations.