TY - JOUR
T1 - Neurological phenotype of adenosine deaminase 2 deficient patients
T2 - a cohort study
AU - Verschoof, Merelijne A
AU - van Meenen, Laura C C
AU - Andriessen, M Valérie E
AU - Brinkman, Daniëlle M C
AU - Kamphuis, Sylvia
AU - Kuijpers, Taco W
AU - Leavis, Helen L
AU - Legger, G Elizabeth
AU - Mulders-Manders, Catharina M
AU - de Pagter, Anne P J
AU - Rutgers, Abraham
AU - van Well, Gijs T J
AU - Coutinho, Jonathan M
AU - Hak, A Elisabeth
AU - van Montfrans, Joris M
AU - Klouwer, Femke C C
PY - 2024/1
Y1 - 2024/1
N2 - BACKGROUND: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. METHODS: In this cohort study, we included patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands. We analyzed the frequency and recurrence rates of neurological manifestations before and after initiation of TNF-a inhibiting therapy. RESULTS: We included 29 patients with a median age at presentation of 5?years (IQR: 1-17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. TIA/ischemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischemic strokes occurred in 12 patients; one after initiation of TNF-a inhibiting therapy and one while switching between TNF-a inhibitors. None were large-vessel occlusion strokes. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischemic strokes and seldom recurred after initiation of TNF-a inhibiting therapy. CONCLUSIONS: Neurological manifestations, especially TIA/ischemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness among neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischemic stroke without an identified cause should be considered.
AB - BACKGROUND: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. METHODS: In this cohort study, we included patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands. We analyzed the frequency and recurrence rates of neurological manifestations before and after initiation of TNF-a inhibiting therapy. RESULTS: We included 29 patients with a median age at presentation of 5?years (IQR: 1-17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. TIA/ischemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischemic strokes occurred in 12 patients; one after initiation of TNF-a inhibiting therapy and one while switching between TNF-a inhibitors. None were large-vessel occlusion strokes. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischemic strokes and seldom recurred after initiation of TNF-a inhibiting therapy. CONCLUSIONS: Neurological manifestations, especially TIA/ischemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness among neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischemic stroke without an identified cause should be considered.
KW - ADA2 deficiency
KW - pediatric stroke
KW - young stroke
U2 - 10.1111/ene.16043
DO - 10.1111/ene.16043
M3 - Article
SN - 1351-5101
VL - 31
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 1
M1 - 16043
ER -