Publication:

Navigating secondary loss of response: breakthrough midbrain ischemia in deficiency of adenosine deaminase 2: a case report

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic autoinflammatory vasculopathy that may present in childhood with lacunar infarcts in deep perforator territories. Tumor necrosis factor-alpha (TNF-alpha) inhibitors have changed the outlook for stroke-predominant disease, but ischemic events can still occur during treatment. An 8-year-old girl with recurrent brainstem and deep gray matter lacunar infarcts had normal magnetic resonance angiography and negative autoimmune and antiphospholipid testing. Genetic analysis confirmed a homozygous pathogenic ADA2 variant. She received infliximab 100 mg intravenously every two months with aspirin, but after five doses developed a new right paramedian superior midbrain infarct. Infliximab was stopped and subcutaneous adalimumab 40 mg every two weeks was started. After 18 doses of adalimumab, she has had no further cerebrovascular events. TNF-alpha blockade markedly reduces stroke risk in DADA2, but it does not abolish it. In this child, switching from infliximab to adalimumab was followed by neurological stability. For a vasculitis-predominant patient without hematologic failure, an intra-class switch is a practical option to consider before hematopoietic cell transplantation, with continued neurologic surveillance.