M Mancuso1, M Arnold2, A Bersano3, A Burlina4, H Chabriat5, S Debette6, C Enzinger7, A Federico8, A Filla9, J Finsterer10, D Hunt11, S Lesnik Oberstein12, E Tournier-Lasserve13, H S Markus14. 1. Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy. 2. Department of Neurology, INSELSPITAL, University Hospital Bern, Bern, Switzerland. 3. Cerebrovascular Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. 4. Neurological Unit, St. Bassiano Hospital, Bassano del Grappa, Italy. 5. Department of Neurology and CERVCO, DHU Neurovasc, INSERM U1141, University of Paris, Paris, France. 6. Department of Neurology, INSERM Centre Bordeaux Population Health (U1219), Bordeaux University Hospital, University of Bordeaux, Bordeaux, France. 7. Department of Neurology and Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria. 8. Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. 9. Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Napoli, Italy. 10. Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria. 11. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. 12. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. 13. Department of Genetics, Lariboisière Hospital and INSERM U1141, Paris-Diderot University, Paris, France. 14. Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Abstract
BACKGROUND AND PURPOSE: Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and type IV collagen (COL4)A1/2. METHODS: We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management. RESULTS: We have proposed 'red-flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus. CONCLUSIONS: The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations.
BACKGROUND AND PURPOSE: Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and type IV collagen (COL4)A1/2. METHODS: We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management. RESULTS: We have proposed 'red-flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus. CONCLUSIONS: The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations.
Authors: Paul J Dunn; Rodney A Lea; Neven Maksemous; Robert A Smith; Heidi G Sutherland; Larisa M Haupt; Lyn R Griffiths Journal: Mol Neurobiol Date: 2022-09-29 Impact factor: 5.682