Ruiting Zhang1,2, Elisa Ouin3, Lina Grosset1,4, Karine Ighilkrim5, Jessica Lebenberg1,4, Stéphanie Guey1,4, Véronique François5, Elisabeth Tournier-Lasserve1,6, Eric Jouvent1,4, Hugues Chabriat1,4. 1. Paris-Cité University, Inserm U1141 NeuroDiderot, Paris, France. 2. Department of Radiology, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China. 3. Department of Neurology, Amiens University Hospital, Laboratory of Functional Neurosciences1,6 (UR UPJV 4559), Jules Verne Picardy University, Amiens, France. 4. Lariboisière University Hospital, APHP, Translational Neurovascular Centre and Department of Neurology, Reference Center for Rare Vascular Diseases of the Central Nervous System and the Retina (CERVCO), FHU NeuroVasc, Paris, France. 5. Department of Geriatrics, Lariboisière University Hospital, APHP, Paris, France. 6. Department of Neurovascular Molecular Genetics, Saint-Louis Hospital, APHP, Paris, France.
Abstract
BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most devastating cerebral small vessel diseases. However, despite its progression with aging, some patients remain neurologically intact (Nint) even when they get older. Their main characteristics are poorly known. We aimed to delineate their clinical, imaging, and molecular features. METHODS: Individuals aged over 65 years were selected from a cohort of 472 CADASIL patients. Subjects who had no focal deficit, cognitive impairment, or disability were considered Nint. Their demographic, genetic, clinical, and imaging features were compared to those with permanent neurological symptoms (Nps). RESULTS: Among 129 patients, 23 (17.8%) individuals were considered Nint. The frequency of vascular risk factors and NOTCH3 cysteine mutations in epidermal growth factor-like repeat (EGFr) domains 7-34 did not differ between Nint and Nps patients but Nint patients had less stroke events and were more likely to have migraine with aura. The number of lacunes and microbleeds and degree of brain atrophy were lower in the Nint group, but the volume of white matter hyperintensities did not differ between the two groups. CONCLUSIONS: Nearly one in five CADASIL patients can remain Nint after the age of 65 years. Their clinical and imaging profile differed from that of other age-matched CADASIL patients. The location of NOTCH3 mutation inside or outside EGFr domains 1-6 cannot fully explain this discrepancy. The factors involved in their relative preservation of brain tissue from severe damage despite aging remain to be determined.
BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most devastating cerebral small vessel diseases. However, despite its progression with aging, some patients remain neurologically intact (Nint) even when they get older. Their main characteristics are poorly known. We aimed to delineate their clinical, imaging, and molecular features. METHODS: Individuals aged over 65 years were selected from a cohort of 472 CADASIL patients. Subjects who had no focal deficit, cognitive impairment, or disability were considered Nint. Their demographic, genetic, clinical, and imaging features were compared to those with permanent neurological symptoms (Nps). RESULTS: Among 129 patients, 23 (17.8%) individuals were considered Nint. The frequency of vascular risk factors and NOTCH3 cysteine mutations in epidermal growth factor-like repeat (EGFr) domains 7-34 did not differ between Nint and Nps patients but Nint patients had less stroke events and were more likely to have migraine with aura. The number of lacunes and microbleeds and degree of brain atrophy were lower in the Nint group, but the volume of white matter hyperintensities did not differ between the two groups. CONCLUSIONS: Nearly one in five CADASIL patients can remain Nint after the age of 65 years. Their clinical and imaging profile differed from that of other age-matched CADASIL patients. The location of NOTCH3 mutation inside or outside EGFr domains 1-6 cannot fully explain this discrepancy. The factors involved in their relative preservation of brain tissue from severe damage despite aging remain to be determined.
Entities:
Keywords:
Aging; CADASIL; Cerebral small vessel diseases; Magnetic resonance imaging; Mutation
Authors: Gido Gravesteijn; Johannes G Dauwerse; Maurice Overzier; Gwendolyn Brouwer; Ingrid Hegeman; Aat A Mulder; Frank Baas; Mark C Kruit; Gisela M Terwindt; Sjoerd G van Duinen; Carolina R Jost; Annemieke Aartsma-Rus; Saskia A J Lesnik Oberstein; Julie W Rutten Journal: Hum Mol Genet Date: 2020-07-21 Impact factor: 6.150