L Grangeon1, G Quesney2, X Ayrignac3, D Wallon2,4, M Verdalle-Cazes5, S Coulette3, D Renard6, A Wacongne6, T Allou7, N Olivier7, Y Boukriche8, G Blanchet-Fourcade9, P Labauge3, C Arquizan3, S Canaple10, O Godefroy10, O Martinaud11,12, P Verdure13, M Quillard-Muraine14, J Pariente15, E Magnin4, G Nicolas16, C Charbonnier16, D Maltête2, M Formaglio17, N Raposo15. 1. Department of Neurology, Rouen University Hospital, 76031, Rouen, France. lou.grangeon@chu-rouen.fr. 2. Department of Neurology, Rouen University Hospital, 76031, Rouen, France. 3. Department of Neurology, INM, Univ Montpellier, INSERM, Montpellier University Hospital, Montpellier, France. 4. Department of Neurology, Besancon Hospital, Besancon, France. 5. Department of Radiology, Rouen University Hospital, Rouen, France. 6. Department of Neurology, Nimes University Hospital, Nimes, France. 7. Department of Neurology, Perpignan Hospital, Perpignan, France. 8. Department of Neurology, Beziers Hospital, Beziers, France. 9. Department of Neurology, Narbonne Hospital, Narbonne, France. 10. Department of Neurology and Functional Neuroscience, Lab (UR UPJV 4559), Amiens University Hospital and University of Picardy Jules Verne, Amiens, France. 11. Department of Neurology, Caen University Hospital, Caen, France. 12. EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie Et Imagerie de La Mémoire Humaine, Normandie Univ, UNICAEN, PSL Research University, Caen, France. 13. Department of Neurology, Les Feugrais Hospital, Elbeuf, France. 14. Laboratoire de Biochimie, Rouen University Hospital and University of Rouen, Rouen, France. 15. Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier, Universitaire de Toulouse, Toulouse, France. 16. INSERM U1245, IRIB, Normandy University, CNR-MAJ, Rouen University Hospital, Rouen, France. 17. Department of Neurology, Lyon University Hospital, Lyon, France.
Abstract
OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.
OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression. Cerebral microbleeds (CMB), intracerebral hemorrhage, cortical superficial siderosis and hippocampal atrophy were analyzed as well as CSF biomarker profile and APOE genotype when available. Outcomes were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Data from 48 CAA-ri patients including 28 already reported and 20 new patients were analyzed. Over a mean of 3.1 years, 11 patients died (22.9%) and 18 (37.5%) relapsed. CAA-ri patients were more frequently institutionalized than non-inflammatory CAA patients (30% vs 8.3%, p < 0.001); mortality rates remained similar. MMSE and modified Rankin scale scores showed greater severity in CAA-ri at last follow-up. MRI showed a higher number of CMB at baseline and last follow-up in CAA-ri (p < 0.001 and p = 0.004, respectively). CSF showed lower baseline levels of Aß42 in CAA-ri than non-inflammatory CAA (373.3 pg/ml vs 490.8 pg/ml, p = 0.05). CAA-ri patients more likely carried at least one APOE ε4 allele (76% vs 37.5%, adjusted p = 0.05) particularly as homozygous status (56% vs 6.2%, p < 0.001). INTERPRETATION: CAA-ri appears to be more severe than non-inflammatory CAA with a significant loss of autonomy and global higher amyloid burden, shown by more CMB and a distinct CSF profile. This burden may be partially promoted by ε4 allele.
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