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.
N1 - Publisher Copyright: © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PY - 2024/1
Y1 - 2024/1
N2 - Background and purpose: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. Methods: In this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF-α) inhibiting therapy were analyzed. Results: Twenty-nine patients were included with a median age at presentation of 5 years (interquartile range 1–17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF-α inhibiting therapy and one whilst switching between TNF-α inhibitors. None was large-vessel occlusion stroke. 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/ischaemic strokes and seldom recurred after initiation of TNF-α inhibiting therapy. Conclusions: Neurological manifestations, especially TIA/ischaemic 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 amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischaemic stroke without an identified cause should be considered.
AB - Background and purpose: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischaemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported. Methods: In this cohort study, patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands were included. The frequency and recurrence rates of neurological manifestations before and after initiation of tumor necrosis factor α (TNF-α) inhibiting therapy were analyzed. Results: Twenty-nine patients were included with a median age at presentation of 5 years (interquartile range 1–17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. Transient ischaemic attack (TIA)/ischaemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischaemic strokes occurred in 12 patients, one after initiation of TNF-α inhibiting therapy and one whilst switching between TNF-α inhibitors. None was large-vessel occlusion stroke. 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/ischaemic strokes and seldom recurred after initiation of TNF-α inhibiting therapy. Conclusions: Neurological manifestations, especially TIA/ischaemic 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 amongst neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischaemic stroke without an identified cause should be considered.
KW - ADA2 deficiency
KW - pediatric stroke
KW - young stroke
UR - http://www.scopus.com/inward/record.url?scp=85169157209&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/ene.16043
DO - https://doi.org/10.1111/ene.16043
M3 - Article
C2 - 37584090
SN - 1351-5101
VL - 31
JO - European journal of neurology
JF - European journal of neurology
IS - 1
M1 - e16043
ER -