Neurological phenotype of ADA2 deficient patients: a cohort study

Merelijne A Verschoof; Laura C C van Meenen; M. Valérie E. Andriessen; Daniëlle M C Brinkman; Sylvia Kamphuis; Taco W Kuijpers; Helen L Leavis; G. Elizabeth Legger; Catharina M Mulders-Manders; Anne P J de Pagter; Abraham Rutgers; Gijs T J van Well; Jonathan M Coutinho; A Elisabeth Hak; Joris M van Montfrans; Femke C C Klouwer

doi:10.1111/ene.16043

Neurological phenotype of ADA2 deficient patients: a cohort study

Merelijne A Verschoof, Laura C C van Meenen, M. Valérie E. Andriessen, Daniëlle M C Brinkman, Sylvia Kamphuis, Taco W Kuijpers, Helen L Leavis, G. Elizabeth Legger, Catharina M Mulders-Manders, Anne P J de Pagter, Abraham Rutgers, Gijs T J van Well, Jonathan M Coutinho, A Elisabeth Hak, Joris M van Montfrans, Femke C C Klouwer^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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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-α 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-α inhibiting therapy and one while switching between TNF-α 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-α 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.

Originele taal-2	English
Artikelnummer	e16043
Aantal pagina's	9
Tijdschrift	European Journal of Neurology
Volume	31
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1111/ene.16043
Status	Published - jan.-2024

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10.1111/ene.16043Licentie: CC BY-NC

Neurological phenotype of adenosine deaminase 2 deficient patientsFinal publisher's version, 604 KBLicentie: CC BY-NC

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Verschoof, M. A., van Meenen, L. C. C., Andriessen, M. V. E., Brinkman, D. M. C., Kamphuis, S., Kuijpers, T. W., Leavis, H. L., Legger, G. E., Mulders-Manders, C. M., de Pagter, A. P. J., Rutgers, A., van Well, G. T. J., Coutinho, J. M., Hak, A. E., van Montfrans, J. M., & Klouwer, F. C. C. (2024). Neurological phenotype of ADA2 deficient patients: a cohort study. European Journal of Neurology, 31(1), Artikel e16043. https://doi.org/10.1111/ene.16043

@article{21ef085b919544dfa7f45c459c821a1a,

title = "Neurological phenotype of ADA2 deficient patients: a cohort study",

abstract = "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-α 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-α inhibiting therapy and one while switching between TNF-α 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-α 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.",

author = "Verschoof, {Merelijne A} and {van Meenen}, {Laura C C} and Andriessen, {M. Val{\'e}rie E.} and Brinkman, {Dani{\"e}lle M C} and Sylvia Kamphuis and Kuijpers, {Taco W} and Leavis, {Helen L} and Legger, {G. Elizabeth} and Mulders-Manders, {Catharina M} and {de Pagter}, {Anne P J} and Abraham Rutgers and {van Well}, {Gijs T J} and Coutinho, {Jonathan M} and Hak, {A Elisabeth} and {van Montfrans}, {Joris M} and Klouwer, {Femke C C}",

year = "2024",

month = jan,

doi = "10.1111/ene.16043",

language = "English",

volume = "31",

journal = "European Journal of Neurology",

issn = "1351-5101",

publisher = "Wiley",

number = "1",

}

Verschoof, MA, van Meenen, LCC, Andriessen, MVE, Brinkman, DMC, Kamphuis, S, Kuijpers, TW, Leavis, HL, Legger, GE, Mulders-Manders, CM, de Pagter, APJ, Rutgers, A, van Well, GTJ, Coutinho, JM, Hak, AE, van Montfrans, JM & Klouwer, FCC 2024, 'Neurological phenotype of ADA2 deficient patients: a cohort study', European Journal of Neurology, vol. 31, nr. 1, e16043. https://doi.org/10.1111/ene.16043

TY - JOUR

T1 - Neurological phenotype of ADA2 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-α 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-α inhibiting therapy and one while switching between TNF-α 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-α 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-α 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-α inhibiting therapy and one while switching between TNF-α 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-α 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.

U2 - 10.1111/ene.16043

DO - 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 -

Neurological phenotype of ADA2 deficient patients: a cohort study

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