CNS Complications in Immunodeficiency Syndromes Due to Mutations in Transcription Factors STAT-1 and GATA-2 (S57.003)

Abstract

Objective: To describe CNS complications of immunodeficiency syndromes. Background CNS complications of patients with congenital immunodeficiencies are poorly understood. STAT1 and GATA2 are transcription factors that regulate interferon-mediated immune responses and early hematopoiesis, respectively. STAT1 mutations predispose to infection with nontuberculous mycobacteria (NTM), viruses, or mucocutaneous candida, depending on the location of the effect of the mutation. Deficiencies in GATA2 are associated with recurrent infection with NTM, monocytopenia, and transformation to myelodysplastic syndrome/acute myelogenous leukemia. Design/Methods: Three patients from the Neurology Consult Service at the NIH are described with regards to their immunodeficiency syndromes and their neurological presentations. Results: A 22 year old woman with a STAT1 mutation presented with brain lesions and an intramedullary spinal cord lesion due to disseminated coccidioidomycosis, which was refractory to antifungal therapy. Typically, coccidioidomycosis in the CNS infects the intradural and extramedullary spaces. A 3 year old boy with a STAT1 mutation presented with multiple intracranial aneurysms and subarachnoid hemorrhage. While STAT1 protein defects are associated with abdominal aneurysms in the setting of chronic inflammation, CNS aneurysms are recently recognized with gain of function STAT1 mutations. A 38 year old woman with a GATA2 mutation and myelodysplasia developed three deep vein thromboses in five years, followed by multiple cardioembolic strokes due to culture negative subacute endocarditis. The mechanism for her hypercoagulability, and that of other patients with GATA2monomac deficiency is unknown, but GATA2 regulates endothelial gene expression, as well. Conclusions: Neurological signs and symptoms in patients with recurrent infection should prompt the neurologist to consider primary immunodeficiency syndromes. STAT1 and GATA2 transcription factors may predispose patients to vascular as well as infectious CNS complications. The overlap between chronic infection and inflammatory complications, such as cord edema or an inflammatory-type vasculopathy, presents additional challenges in management, since direct immunosuppression is usually not possible. Disclosure: Dr. Kranick has nothing to disclose. Dr. Holland has nothing to disclose. Dr. Uzel has nothing to disclose. Dr. Nath has nothing to disclose.