Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology

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

Affiliations

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.

PMID: 32196841
DOI: 10.1111/ene.14183

Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology

M Mancuso et al. Eur J Neurol. 2020 Jun.

. 2020 Jun;27(6):909-927.

doi: 10.1111/ene.14183. Epub 2020 Mar 20.

Authors

Affiliations

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.

PMID: 32196841
DOI: 10.1111/ene.14183

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.

Keywords: Fabry; cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL); cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL); cerebral small-vessel disease; lactic acidosis and stroke-like episodes (MELAS); mitochondrial encephalopathy; monogenic cerebral small-vessel disease; pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL); retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S); type IV collagen (COL4)A1/2.

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Comment in

Diagnosis and management of monogenic cerebral small vessel diseases.
Saito R, Lioutas VA. Saito R, et al. Eur J Neurol. 2020 Jul;27(7):1097-1098. doi: 10.1111/ene.14222. Epub 2020 May 12. Eur J Neurol. 2020. PMID: 32189410 No abstract available.
Monogenic small vessel diseases - rare but still important.
Werring DJ, Lynch DS. Werring DJ, et al. Nat Rev Neurol. 2020 Aug;16(8):407-408. doi: 10.1038/s41582-020-0363-1. Nat Rev Neurol. 2020. PMID: 32355255 No abstract available.
Response to Carvalho et al.: Diagnosis of monogenic small-vessel disease - "real- world" application of the consensus recommendation of the European Academy of Neurology.
Mancuso M, Markus HS. Mancuso M, et al. Eur J Neurol. 2021 Jun;28(6):e37. doi: 10.1111/ene.14817. Epub 2021 Mar 22. Eur J Neurol. 2021. PMID: 33690956 No abstract available.
Diagnosis of monogenic small vessel disease-"real-world" application of the consensus recommendation of the European Academy of Neurology.
Carvalho V, Ferreira P, Lima MJ, Calejo M, Tedim Cruz V. Carvalho V, et al. Eur J Neurol. 2021 Jun;28(6):e38-e39. doi: 10.1111/ene.14818. Epub 2021 Mar 24. Eur J Neurol. 2021. PMID: 33710705 No abstract available.

References

1. de Winter JCF, Dodou D. Five-point Likert items: t test versus Mann-Whitney-Wilcoxon. Pract Assessment Res Eval 2010; 15: 1-10.
1. Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383: 707-710.
1. Narayan SK, Gorman G, Kalaria RN, Ford GA, Chinnery PF. The minimum prevalence of CADASIL in northeast England. Neurology 2012; 78: 1025-1027.
1. Rutten JW, Van Eijsden BJ, Duering M, et al. The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1-6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7-34 pathogenic variant. Genet Med 2019; 21: 676-682.
1. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser M-G. Cadasil. Lancet Neurol 2009; 8: 643-653.

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Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology

Affiliations

Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology

Authors

Affiliations

Abstract

Comment in

References

Publication types

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LinkOut - more resources

Full Text Sources

Medical