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Published in: Current Treatment Options in Neurology 9/2017

01-09-2017 | Cerebrovascular Disorders (DG Jamieson, Section Editor)

CADASIL: Treatment and Management Options

Authors: Anna Bersano, MD, PhD, Gloria Bedini, PhD, Joshua Oskam, MD, Caterina Mariotti, MD, Franco Taroni, MD, Silvia Baratta, PhD, Eugenio Agostino Parati, MD

Published in: Current Treatment Options in Neurology | Issue 9/2017

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Opinion statement

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.
Literature
1.
go back to reference Ducros A, Nagy T, Alamowitch S, Nibbio A, Joutel A, Vahedi K, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval. Am J Hum Genet. 1996;58:171–81.PubMedPubMedCentral Ducros A, Nagy T, Alamowitch S, Nibbio A, Joutel A, Vahedi K, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval. Am J Hum Genet. 1996;58:171–81.PubMedPubMedCentral
2.
go back to reference Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8:643–53.CrossRefPubMed Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8:643–53.CrossRefPubMed
3.
go back to reference Sourander P, Wålinder J. Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease. Acta Neuropathol. 1977;39:247–54.CrossRefPubMed Sourander P, Wålinder J. Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease. Acta Neuropathol. 1977;39:247–54.CrossRefPubMed
4.
go back to reference Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia. Ann N Y Acad Sci. 1997;826:213–7.CrossRefPubMed Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia. Ann N Y Acad Sci. 1997;826:213–7.CrossRefPubMed
6.
go back to reference Dichgans M, Mayer M, Uttner I, Brüning R, Müller-Höcker J, Rungger G, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998;44:731.CrossRefPubMed Dichgans M, Mayer M, Uttner I, Brüning R, Müller-Höcker J, Rungger G, et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998;44:731.CrossRefPubMed
7.
go back to reference Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004;127:2533–9.CrossRefPubMed Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004;127:2533–9.CrossRefPubMed
8.
go back to reference del Río-Espínola A, Mendióroz M, Domingues-Montanari S, Pozo-Rosich P, Solé E, Fernández-Morales J, et al. CADASIL management or what to do when there is little one can do. Expert Rev Neurother. 2009;9:197–210.CrossRefPubMed del Río-Espínola A, Mendióroz M, Domingues-Montanari S, Pozo-Rosich P, Solé E, Fernández-Morales J, et al. CADASIL management or what to do when there is little one can do. Expert Rev Neurother. 2009;9:197–210.CrossRefPubMed
9.
go back to reference Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke. 1999;30:1230–3.CrossRefPubMed Desmond DW, Moroney JT, Lynch T, Chan S, Chin SS, Mohr JP. The natural history of CADASIL: a pooled analysis of previously published cases. Stroke. 1999;30:1230–3.CrossRefPubMed
10.
go back to reference Bousser M, Tournier-Lasserve E. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: from stroke to vessel wall physiology. J Neurol Neurosurg Psychiatry. 2001;70:285–7S.CrossRefPubMedPubMedCentral Bousser M, Tournier-Lasserve E. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: from stroke to vessel wall physiology. J Neurol Neurosurg Psychiatry. 2001;70:285–7S.CrossRefPubMedPubMedCentral
11.
go back to reference Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004;127:2031–8.CrossRefPubMed Singhal S, Bevan S, Barrick T, Rich P, Markus HS. The influence of genetic and cardiovascular risk factors on the CADASIL phenotype. Brain. 2004;127:2031–8.CrossRefPubMed
12.
go back to reference Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke. 2010;41:630–4.CrossRefPubMed Adib-Samii P, Brice G, Martin RJ, Markus HS. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: study in 200 consecutively recruited individuals. Stroke. 2010;41:630–4.CrossRefPubMed
14.
go back to reference Chabriat H, Vahedi K, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995;346:934–9.CrossRefPubMed Chabriat H, Vahedi K, Iba-Zizen MT, Joutel A, Nibbio A, Nagy TG, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995;346:934–9.CrossRefPubMed
15.
go back to reference Valenti R, Poggesi A, Pescini F, Inzitari D, Pantoni L. Psychiatric disturbances in CADASIL: a brief review. Acta Neurol Scand. 2008;118:291–5.CrossRefPubMed Valenti R, Poggesi A, Pescini F, Inzitari D, Pantoni L. Psychiatric disturbances in CADASIL: a brief review. Acta Neurol Scand. 2008;118:291–5.CrossRefPubMed
16.
go back to reference Choi JC, Kang SY, Kang JH, Park JK. Intracerebral hemorrhages in CADASIL. Neurology. 2006;67:2042–4.CrossRefPubMed Choi JC, Kang SY, Kang JH, Park JK. Intracerebral hemorrhages in CADASIL. Neurology. 2006;67:2042–4.CrossRefPubMed
17.
go back to reference Ragno M, Berbellini A, Cacchiò G, Manca A, Di Marzio F, Pianese L, et al. Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation. Stroke. 2013;44:1147–9.CrossRefPubMed Ragno M, Berbellini A, Cacchiò G, Manca A, Di Marzio F, Pianese L, et al. Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation. Stroke. 2013;44:1147–9.CrossRefPubMed
18.
go back to reference Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology. 2002;59:1134–8.CrossRefPubMed Markus HS, Martin RJ, Simpson MA, Dong YB, Ali N, Crosby AH, et al. Diagnostic strategies in CADASIL. Neurology. 2002;59:1134–8.CrossRefPubMed
19.
go back to reference • Zhu S, Nahas SJ. CADASIL: imaging characteristics and clinical correlation. Curr Pain Headache Rep. 2016;20:57. The study outlines the most important clinical and neuroimaging features of CADASIL confirming that subcortical ischemic changes, which occur early in CADASIL and typically progress to involve the anterior temporal poles, may differentiate CADASIL patients from other causes of small vessel ischemic diseaseCrossRefPubMed • Zhu S, Nahas SJ. CADASIL: imaging characteristics and clinical correlation. Curr Pain Headache Rep. 2016;20:57. The study outlines the most important clinical and neuroimaging features of CADASIL confirming that subcortical ischemic changes, which occur early in CADASIL and typically progress to involve the anterior temporal poles, may differentiate CADASIL patients from other causes of small vessel ischemic diseaseCrossRefPubMed
20.
go back to reference O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001;56:628–34.CrossRefPubMed O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001;56:628–34.CrossRefPubMed
21.
go back to reference Lesnik Oberstein SA, van den Boom R, van Buchem MA, van Houwelingen HC, Bakker E, Vollebregt E, et al. Dutch CADASIL research group. Cerebral microbleeds in CADASIL. Neurology. 2001;57:1066–70.CrossRefPubMed Lesnik Oberstein SA, van den Boom R, van Buchem MA, van Houwelingen HC, Bakker E, Vollebregt E, et al. Dutch CADASIL research group. Cerebral microbleeds in CADASIL. Neurology. 2001;57:1066–70.CrossRefPubMed
22.
go back to reference Joshi S, Yau W, Kermode A. CADASIL mimicking multiple sclerosis: the importance of clinical and MRI red flags. J Clin Neurosci. 2017;35:75–7.CrossRefPubMed Joshi S, Yau W, Kermode A. CADASIL mimicking multiple sclerosis: the importance of clinical and MRI red flags. J Clin Neurosci. 2017;35:75–7.CrossRefPubMed
23.
go back to reference • Pantoni L, Pescini F, Nannucci S, Sarti C, Bianchi S, Dotti MT, et al. Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients. Neurology. 2010;74:57–63. The authors did not find any clinical or neuroimaging findings that were pathognomonic for CADASIL, emphasizing that there are many patients with a CADASIL like phenotype, despite negative genetic testingCrossRefPubMed • Pantoni L, Pescini F, Nannucci S, Sarti C, Bianchi S, Dotti MT, et al. Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients. Neurology. 2010;74:57–63. The authors did not find any clinical or neuroimaging findings that were pathognomonic for CADASIL, emphasizing that there are many patients with a CADASIL like phenotype, despite negative genetic testingCrossRefPubMed
24.
go back to reference He D, Chen D, Li X, Hu Z, Yu Z, Wang W, et al. The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China. J Headache Pain. 2016;17:55.CrossRefPubMedPubMedCentral He D, Chen D, Li X, Hu Z, Yu Z, Wang W, et al. The comparisons of phenotype and genotype between CADASIL and CADASIL-like patients and population-specific evaluation of CADASIL scale in China. J Headache Pain. 2016;17:55.CrossRefPubMedPubMedCentral
25.
go back to reference Auer DP, Pütz B, Gössl C, Elbel G, Gasser T, Dichgans M. Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison. Radiology. 2001;218:443–51.CrossRefPubMed Auer DP, Pütz B, Gössl C, Elbel G, Gasser T, Dichgans M. Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison. Radiology. 2001;218:443–51.CrossRefPubMed
26.
go back to reference •• Bersano A, Markus HS, Quaglini S, Arbustini E, Lanfranconi S, Micieli G, et al., Lombardia GENS Group*. Clinical pregenetic screening for stroke monogenic diseases: results from Lombardia GENS Registry. Stroke. 2016;47:1702–9. The authors underline the need of clinical criteria for CADASIL suspicion. By applying standardized algorithm they identified 7% of patients with monogenic disease highlighting the role of familial history in the clinical suspicion of monogenic disease and specifically CADASILCrossRefPubMed •• Bersano A, Markus HS, Quaglini S, Arbustini E, Lanfranconi S, Micieli G, et al., Lombardia GENS Group*. Clinical pregenetic screening for stroke monogenic diseases: results from Lombardia GENS Registry. Stroke. 2016;47:1702–9. The authors underline the need of clinical criteria for CADASIL suspicion. By applying standardized algorithm they identified 7% of patients with monogenic disease highlighting the role of familial history in the clinical suspicion of monogenic disease and specifically CADASILCrossRefPubMed
27.
go back to reference Morroni M, Marzioni D, Ragno M, Di Bella P, Cartechini E, Pianese L, et al. Role of electron microscopy in the diagnosis of cadasil syndrome: a study of 32 patients. PLoS One. 2013;8:e65482.CrossRefPubMedPubMedCentral Morroni M, Marzioni D, Ragno M, Di Bella P, Cartechini E, Pianese L, et al. Role of electron microscopy in the diagnosis of cadasil syndrome: a study of 32 patients. PLoS One. 2013;8:e65482.CrossRefPubMedPubMedCentral
28.
29.
go back to reference Peters N, Opherk C, Bergmann T, Castro M, Herzog J, Dichgans M. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol. 2005;62:1091–4.CrossRefPubMed Peters N, Opherk C, Bergmann T, Castro M, Herzog J, Dichgans M. Spectrum of mutations in biopsy-proven CADASIL: implications for diagnostic strategies. Arch Neurol. 2005;62:1091–4.CrossRefPubMed
30.
go back to reference Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997;350:1511–5.CrossRefPubMed Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssière C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997;350:1511–5.CrossRefPubMed
31.
go back to reference Bersano A, Ranieri M, Ciammola A, Cinnante C, Lanfranconi S, Dotti MT, et al. Considerations on a mutation in the NOTCH3 gene sparing a cysteine residue: a rare polymorphism rather than a CADASIL variant. Funct Neurol. 2012;27:247–52.PubMed Bersano A, Ranieri M, Ciammola A, Cinnante C, Lanfranconi S, Dotti MT, et al. Considerations on a mutation in the NOTCH3 gene sparing a cysteine residue: a rare polymorphism rather than a CADASIL variant. Funct Neurol. 2012;27:247–52.PubMed
32.
go back to reference Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA. Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn. 2014;14:593–603.CrossRefPubMed Rutten JW, Haan J, Terwindt GM, van Duinen SG, Boon EM, Lesnik Oberstein SA. Interpretation of NOTCH3 mutations in the diagnosis of CADASIL. Expert Rev Mol Diagn. 2014;14:593–603.CrossRefPubMed
33.
go back to reference • Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770–6. In this review Notch signals is reported to control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. It is also explained how Notch activity affects differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesisCrossRefPubMed • Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770–6. In this review Notch signals is reported to control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. It is also explained how Notch activity affects differentiation, proliferation, and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesisCrossRefPubMed
34.
go back to reference • Joutel A, Corpechot C, Ducros A, Vahedi K, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 383:1996, 707–710. This research article first reported that specific mutations in the NOTCH3 gene cause serious disruption of the gene, indicating that Notch3 could be the defective protein in CADASIL patients • Joutel A, Corpechot C, Ducros A, Vahedi K, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 383:1996, 707–710. This research article first reported that specific mutations in the NOTCH3 gene cause serious disruption of the gene, indicating that Notch3 could be the defective protein in CADASIL patients
35.
go back to reference Joutel A. Pathogenesis of CADASIL: transgenic and knock-out mice to probe function and dysfunction of the mutated gene, Notch3, in the cerebrovasculature. BioEssays. 2011;33:73–80.CrossRefPubMed Joutel A. Pathogenesis of CADASIL: transgenic and knock-out mice to probe function and dysfunction of the mutated gene, Notch3, in the cerebrovasculature. BioEssays. 2011;33:73–80.CrossRefPubMed
36.
go back to reference Joutel A, Monet M, Domenga V, Riant F, Tournier-Lasserve E. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect Jagged1 binding and Notch3 activity via the RBP/JK signaling pathway. Am J Hum Genet. 2004;74:338–47.CrossRefPubMedPubMedCentral Joutel A, Monet M, Domenga V, Riant F, Tournier-Lasserve E. Pathogenic mutations associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy differently affect Jagged1 binding and Notch3 activity via the RBP/JK signaling pathway. Am J Hum Genet. 2004;74:338–47.CrossRefPubMedPubMedCentral
37.
go back to reference Dotti MT, Federico A, Mazzei R, Bianchi S, Scali O, Conforti FL, et al. The spectrum of Notch3 mutations in 28 Italian CADASIL families. J Neurol Neurosurg Psychiatry. 2005;76:736–8.CrossRefPubMedPubMedCentral Dotti MT, Federico A, Mazzei R, Bianchi S, Scali O, Conforti FL, et al. The spectrum of Notch3 mutations in 28 Italian CADASIL families. J Neurol Neurosurg Psychiatry. 2005;76:736–8.CrossRefPubMedPubMedCentral
38.
go back to reference •• Bianchi S, Zicari E, Carluccio A, Di Donato I, Pescini F, Nannucci S, et al. CADASIL in central Italy: a retrospective clinical and genetic study in 229 patients. J Neurol. 2015;262:134–41. This is the most extensive study on CADASIL in Italy. This study enlarges the number of pathogenic NOTCH3 gene mutations and highlights the heterogeneous mutational spectrum observed suggesting that full sequencing of exons 2–24 is mandatory for CADASIL screening in ItalyCrossRefPubMed •• Bianchi S, Zicari E, Carluccio A, Di Donato I, Pescini F, Nannucci S, et al. CADASIL in central Italy: a retrospective clinical and genetic study in 229 patients. J Neurol. 2015;262:134–41. This is the most extensive study on CADASIL in Italy. This study enlarges the number of pathogenic NOTCH3 gene mutations and highlights the heterogeneous mutational spectrum observed suggesting that full sequencing of exons 2–24 is mandatory for CADASIL screening in ItalyCrossRefPubMed
40.
go back to reference Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, et al. Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis. Hum Mol Genet. 2011 Aug 15;20(16):3256–65.CrossRefPubMed Duering M, Karpinska A, Rosner S, Hopfner F, Zechmeister M, Peters N, et al. Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis. Hum Mol Genet. 2011 Aug 15;20(16):3256–65.CrossRefPubMed
41.
go back to reference Smith RA, Curtain R, Ovcaric M, Tajouri L, Macmillan J, Griffiths L. Investigation of the NOTCH3 and TNFSF7 genes on C19p13 as candidates for migraine. Open Neurol J. 2008;2:1–7.CrossRefPubMedPubMedCentral Smith RA, Curtain R, Ovcaric M, Tajouri L, Macmillan J, Griffiths L. Investigation of the NOTCH3 and TNFSF7 genes on C19p13 as candidates for migraine. Open Neurol J. 2008;2:1–7.CrossRefPubMedPubMedCentral
42.
go back to reference • Wollenweber FA, Hanecker P, Bayer-Karpinska A, Malik R, Bäzner H, Moreton F, et al. Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in vitro. Stroke. 2015;46:786–92. This paper discusses and provides recommendations for the interpretation of NOTCH3 gene mutations in the diagnosis of CADASILCrossRefPubMed • Wollenweber FA, Hanecker P, Bayer-Karpinska A, Malik R, Bäzner H, Moreton F, et al. Cysteine-sparing CADASIL mutations in NOTCH3 show proaggregatory properties in vitro. Stroke. 2015;46:786–92. This paper discusses and provides recommendations for the interpretation of NOTCH3 gene mutations in the diagnosis of CADASILCrossRefPubMed
43.
go back to reference Joutel A, Monet-Leprêtre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest. 2010;120:433–45.CrossRefPubMedPubMedCentral Joutel A, Monet-Leprêtre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest. 2010;120:433–45.CrossRefPubMedPubMedCentral
44.
go back to reference Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Battail N, et al. The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients. J Clin Invest. 2000;105:597–605.CrossRefPubMedPubMedCentral Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Battail N, et al. The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients. J Clin Invest. 2000;105:597–605.CrossRefPubMedPubMedCentral
45.
go back to reference Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet. 2001;358:2049–51.CrossRefPubMed Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet. 2001;358:2049–51.CrossRefPubMed
46.
go back to reference Ishiko A, Shimizu A, Nagata E, Takahashi K, Tabira T, Suzuki N. Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL. Acta Neuropathol. 2006;112:333–9.CrossRefPubMed Ishiko A, Shimizu A, Nagata E, Takahashi K, Tabira T, Suzuki N. Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL. Acta Neuropathol. 2006;112:333–9.CrossRefPubMed
47.
go back to reference • Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N. Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol. 2015;78:887–900. In this research article pericytes are reported to be the first cells affected by Notch3 aggregation in CADASIL mice, causing opening of the blood brain barrier and microvascular dysfunction. Therefore, protecting pericytes may represent a novel therapeutic strategy for vascular dementiaCrossRefPubMed • Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N. Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol. 2015;78:887–900. In this research article pericytes are reported to be the first cells affected by Notch3 aggregation in CADASIL mice, causing opening of the blood brain barrier and microvascular dysfunction. Therefore, protecting pericytes may represent a novel therapeutic strategy for vascular dementiaCrossRefPubMed
48.
go back to reference Monet-Leprêtre M, Haddad I, Baron-Menguy C, Fouillot-Panchal M, Riani M, Domenga-Denier V, et al. Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL. Brain. 2013;136:1830–45.CrossRefPubMedPubMedCentral Monet-Leprêtre M, Haddad I, Baron-Menguy C, Fouillot-Panchal M, Riani M, Domenga-Denier V, et al. Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL. Brain. 2013;136:1830–45.CrossRefPubMedPubMedCentral
49.
go back to reference Morrow D, Guha S, Sweeney C, Birney Y, Walshe T, O’Brien C, et al. Notch and vascular smooth muscle cell phenotype. Circ Res. 2008;103:1370–82.CrossRefPubMed Morrow D, Guha S, Sweeney C, Birney Y, Walshe T, O’Brien C, et al. Notch and vascular smooth muscle cell phenotype. Circ Res. 2008;103:1370–82.CrossRefPubMed
50.
go back to reference Krebs LT, Xue Y, Norton CR, Sundberg JP, Beatus P, Lendahl U, et al. Characterization of Notch3-deficient mice: normal embryonic development and absence of genetic interactions with a Notch1 mutation. Genesis. 2003 Nov;37(3):139–43. Krebs LT, Xue Y, Norton CR, Sundberg JP, Beatus P, Lendahl U, et al. Characterization of Notch3-deficient mice: normal embryonic development and absence of genetic interactions with a Notch1 mutation. Genesis. 2003 Nov;37(3):139–43.
51.
go back to reference Domenga V, Fardoux P, Lacombe P, Monet M, Maciazek J, Krebs LT, et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev. 2004;18:2730–5.CrossRefPubMedPubMedCentral Domenga V, Fardoux P, Lacombe P, Monet M, Maciazek J, Krebs LT, et al. Notch3 is required for arterial identity and maturation of vascular smooth muscle cells. Genes Dev. 2004;18:2730–5.CrossRefPubMedPubMedCentral
52.
go back to reference Belin de Chantemèle EJ, Retailleau K, Pinaud F, Vessières E, Bocquet A, Guihot AL, et al. Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries. Arterioscler Thromb Vasc Biol. 2008;28:2216–24.CrossRefPubMed Belin de Chantemèle EJ, Retailleau K, Pinaud F, Vessières E, Bocquet A, Guihot AL, et al. Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries. Arterioscler Thromb Vasc Biol. 2008;28:2216–24.CrossRefPubMed
53.
go back to reference Rutten JW, Klever RR, Hegeman IM, Poole DS, Dauwerse HG, Broos LA, et al. The NOTCH3 score: a pre-clinical CADASIL biomarker in a novel human genomic NOTCH3 transgenic mouse model with early progressive vascular NOTCH3 accumulation. Acta Neuropathol Commun. 2015;3:89.CrossRefPubMedPubMedCentral Rutten JW, Klever RR, Hegeman IM, Poole DS, Dauwerse HG, Broos LA, et al. The NOTCH3 score: a pre-clinical CADASIL biomarker in a novel human genomic NOTCH3 transgenic mouse model with early progressive vascular NOTCH3 accumulation. Acta Neuropathol Commun. 2015;3:89.CrossRefPubMedPubMedCentral
54.
go back to reference •• Di Donato I, Bianchi S, De Stefano N, Dchgans M, Dotti MT, Duering M, et al. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. BMC Med. 15(1):41. The paper is an important updated review on clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on literature and on the personal experience of the authors, with a wide expertise in CADASIL research and care •• Di Donato I, Bianchi S, De Stefano N, Dchgans M, Dotti MT, Duering M, et al. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) as a model of small vessel disease: update on clinical, diagnostic, and management aspects. BMC Med. 15(1):41. The paper is an important updated review on clinical, neuroimaging, neuropathological, genetic, and therapeutic aspects based on literature and on the personal experience of the authors, with a wide expertise in CADASIL research and care
55.
go back to reference Khan MT, Murray A, Smith M. Successful use of intravenous tissue plasminogen activator as treatment for a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: acase report and review of literature. J Stroke Cerebrovasc Dis. 2016;25:e53–7. Khan MT, Murray A, Smith M. Successful use of intravenous tissue plasminogen activator as treatment for a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: acase report and review of literature. J Stroke Cerebrovasc Dis. 2016;25:e53–7.
56.
57.
go back to reference Holtmannspötter M, Peters N, Opherk C, Martin D, Herzog J, Brückmann H, et al. Diffusion magnetic resonance histograms as a surrogate marker and predictor of disease progression in CADASIL: a two-year follow-up study. Stroke. 2005;36:2559–65.CrossRefPubMed Holtmannspötter M, Peters N, Opherk C, Martin D, Herzog J, Brückmann H, et al. Diffusion magnetic resonance histograms as a surrogate marker and predictor of disease progression in CADASIL: a two-year follow-up study. Stroke. 2005;36:2559–65.CrossRefPubMed
58.
go back to reference Viswanathan A, Guichard JP, Gschwendtner A, Buffon F, Cumurcuic R, Boutron C, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain. 2006;129:2375–8.CrossRefPubMed Viswanathan A, Guichard JP, Gschwendtner A, Buffon F, Cumurcuic R, Boutron C, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study. Brain. 2006;129:2375–8.CrossRefPubMed
59.
go back to reference Peters N, Holtmannspötter M, Opherk C, Gschwendtner A, Herzog J, Sämann P, et al. Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology. 2006;66:1517–22.CrossRefPubMed Peters N, Holtmannspötter M, Opherk C, Gschwendtner A, Herzog J, Sämann P, et al. Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology. 2006;66:1517–22.CrossRefPubMed
60.
go back to reference Guo Z, Qiu C, Viitanen M, Fastbom J, Winblad B, Fratiglioni L. Blood pressure and dementia in persons 75+ years old: 3-year follow-up results from the Kungsholmen Project. J Alzheimers Dis. 2001;3:585–91.CrossRefPubMed Guo Z, Qiu C, Viitanen M, Fastbom J, Winblad B, Fratiglioni L. Blood pressure and dementia in persons 75+ years old: 3-year follow-up results from the Kungsholmen Project. J Alzheimers Dis. 2001;3:585–91.CrossRefPubMed
61.
go back to reference Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ. Low blood pressure and the risk of dementia in very old individuals. Neurology. 2003;61:1667–72.CrossRefPubMed Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ. Low blood pressure and the risk of dementia in very old individuals. Neurology. 2003;61:1667–72.CrossRefPubMed
62.
go back to reference Rufa A, Dotti MT, Franchi M, Stromillo ML, Cevenini G, Bianchi S, et al. Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2005;36:2554–8.CrossRefPubMed Rufa A, Dotti MT, Franchi M, Stromillo ML, Cevenini G, Bianchi S, et al. Systemic blood pressure profile in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2005;36:2554–8.CrossRefPubMed
63.
go back to reference Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD. Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet. 2005;365:224–32.CrossRefPubMed Casas JP, Bautista LE, Smeeth L, Sharma P, Hingorani AD. Homocysteine and stroke: evidence on a causal link from mendelian randomisation. Lancet. 2005;365:224–32.CrossRefPubMed
64.
go back to reference Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476–83.CrossRefPubMed Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476–83.CrossRefPubMed
65.
go back to reference Hassan A, Hunt BJ, O’Sullivan M, Bell R, D’Souza R, Jeffery S, et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain. 2004;127:212–9.CrossRefPubMed Hassan A, Hunt BJ, O’Sullivan M, Bell R, D’Souza R, Jeffery S, et al. Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain. 2004;127:212–9.CrossRefPubMed
66.
go back to reference Flemming KD, Nguyen TT, Abu-Lebdeh HS, Parisi JE, Wiebers DO, Sicks JD, et al. Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mayo Clin Proc. 2001 Dec;76:1213–8. Flemming KD, Nguyen TT, Abu-Lebdeh HS, Parisi JE, Wiebers DO, Sicks JD, et al. Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Mayo Clin Proc. 2001 Dec;76:1213–8.
67.
go back to reference Martí-Carvajal AJ, Solà I, Lathyris D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2015;1:CD006612.PubMed Martí-Carvajal AJ, Solà I, Lathyris D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2015;1:CD006612.PubMed
68.
go back to reference Park JH, Saposnik G, Ovbiagele B, Markovic D, Towfighi A. Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: a meta-analysis. Int J Stroke. 2016;11:206–11.CrossRefPubMed Park JH, Saposnik G, Ovbiagele B, Markovic D, Towfighi A. Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: a meta-analysis. Int J Stroke. 2016;11:206–11.CrossRefPubMed
70.
go back to reference Rinnoci V, Nannucci S, Valenti R, Donnini I, Bianchi S, Pescini F, et al. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330:45–51.CrossRefPubMed Rinnoci V, Nannucci S, Valenti R, Donnini I, Bianchi S, Pescini F, et al. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330:45–51.CrossRefPubMed
71.
go back to reference van den Boom R, Lesnik Oberstein SA, Spilt A, Behloul F, Ferrari MD, Haan J, et al. Cerebral hemodynamics and white matter hyperintensities in CADASIL. J Cereb Blood Flow Metab. 2003;23:599–604.CrossRefPubMed van den Boom R, Lesnik Oberstein SA, Spilt A, Behloul F, Ferrari MD, Haan J, et al. Cerebral hemodynamics and white matter hyperintensities in CADASIL. J Cereb Blood Flow Metab. 2003;23:599–604.CrossRefPubMed
72.
go back to reference Chabriat H, Pappata S, Ostergaard L, Clark CA, Pachot-Clouard M, Vahedi K, et al. Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Stroke. 2000;31:1904–12.CrossRefPubMed Chabriat H, Pappata S, Ostergaard L, Clark CA, Pachot-Clouard M, Vahedi K, et al. Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Stroke. 2000;31:1904–12.CrossRefPubMed
73.
go back to reference Tuominen S, Miao Q, Kurki T, Tuisku S, Pöyhönen M, Kalimo H, et al. Positron emission tomography examination of cerebral blood flow and glucose metabolism in young CADASIL patients. Stroke. 2004;35:1063–7.CrossRefPubMed Tuominen S, Miao Q, Kurki T, Tuisku S, Pöyhönen M, Kalimo H, et al. Positron emission tomography examination of cerebral blood flow and glucose metabolism in young CADASIL patients. Stroke. 2004;35:1063–7.CrossRefPubMed
74.
go back to reference Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M. Reduced cerebrovascular CO(2) reactivity in CADASIL: a transcranial Doppler sonography study. Stroke. 2001;32:17–21.CrossRefPubMed Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M. Reduced cerebrovascular CO(2) reactivity in CADASIL: a transcranial Doppler sonography study. Stroke. 2001;32:17–21.CrossRefPubMed
75.
go back to reference Campolo J, De Maria R, Frontali M, Taroni F, Inzitari D, Federico A, et al. Impaired vasoreactivity in mildly disabled CADASIL patients. J Neurol Neurosurg Psychiatry. 2012;8:268–74.CrossRef Campolo J, De Maria R, Frontali M, Taroni F, Inzitari D, Federico A, et al. Impaired vasoreactivity in mildly disabled CADASIL patients. J Neurol Neurosurg Psychiatry. 2012;8:268–74.CrossRef
76.
go back to reference Peters N, Freilinger T, Opherk C, Pfefferkorn T, Dichgans M. Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL. J Neurol Sci. 2007;260:100–5.CrossRefPubMed Peters N, Freilinger T, Opherk C, Pfefferkorn T, Dichgans M. Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL. J Neurol Sci. 2007;260:100–5.CrossRefPubMed
77.
go back to reference De Maria R, Campolo J, Frontali M, Taroni F, Federico A, Inzitari D, et al. Effects of sapropterin on endothelium-dependent vasodilation in patients with CADASIL: a randomized controlled trial. Stroke. 2014 Oct;45:2959–66. De Maria R, Campolo J, Frontali M, Taroni F, Federico A, Inzitari D, et al. Effects of sapropterin on endothelium-dependent vasodilation in patients with CADASIL: a randomized controlled trial. Stroke. 2014 Oct;45:2959–66.
78.
go back to reference Huang L, Yang Q, Zhang L, Chen X, Huang Q, Wang H. Acetazolamide improves cerebral hemodynamics in CADASIL. J Neurol Sci. 2010;292:77–80.CrossRefPubMed Huang L, Yang Q, Zhang L, Chen X, Huang Q, Wang H. Acetazolamide improves cerebral hemodynamics in CADASIL. J Neurol Sci. 2010;292:77–80.CrossRefPubMed
79.
go back to reference Mizuno T, Kondo M, Ishigami N, Tamura A, Itsukage M, Koizumi H, et al. Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine. Clin Neuropharmacol. 2009;32:113–6.CrossRefPubMed Mizuno T, Kondo M, Ishigami N, Tamura A, Itsukage M, Koizumi H, et al. Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine. Clin Neuropharmacol. 2009;32:113–6.CrossRefPubMed
80.
go back to reference Goldstein J, Hagen M, Gold M. Results of a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study comparing the fixed combination of acetaminophen, acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients with severe migraine. Cephalalgia. 2014;34:1070–8.CrossRefPubMed Goldstein J, Hagen M, Gold M. Results of a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study comparing the fixed combination of acetaminophen, acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients with severe migraine. Cephalalgia. 2014;34:1070–8.CrossRefPubMed
81.
go back to reference Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001 Nov 17;358(9294):1668–75. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001 Nov 17;358(9294):1668–75.
82.
go back to reference Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000;123:9–18.CrossRefPubMed Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000;123:9–18.CrossRefPubMed
83.
go back to reference Martikainen MH, Roine S. Rapid improvement of a complex migrainous episode with sodium valproate in a patient with CADASIL. J Headache Pain. 2012;13:95–7.CrossRefPubMed Martikainen MH, Roine S. Rapid improvement of a complex migrainous episode with sodium valproate in a patient with CADASIL. J Headache Pain. 2012;13:95–7.CrossRefPubMed
84.
go back to reference Finocchi C, Villani V, Casucci G. Therapeutic strategies in migraine patients with mood and anxiety disorders: clinical evidence. Neurol Sci. 2010;31(Suppl 1):S95–8.CrossRefPubMed Finocchi C, Villani V, Casucci G. Therapeutic strategies in migraine patients with mood and anxiety disorders: clinical evidence. Neurol Sci. 2010;31(Suppl 1):S95–8.CrossRefPubMed
85.
go back to reference Donnini I, Nannucci S, Valenti R, Pescini F, Bianchi S, Inzitari D, et al. Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary experience. J Headache Pain. 2012;13:299–302.CrossRefPubMedPubMedCentral Donnini I, Nannucci S, Valenti R, Pescini F, Bianchi S, Inzitari D, et al. Acetazolamide for the prophylaxis of migraine in CADASIL: a preliminary experience. J Headache Pain. 2012;13:299–302.CrossRefPubMedPubMedCentral
86.
go back to reference Lippi G, Mattiuzzi C, Meschi T, Cervellin G, Borghi L. Homocysteine and migraine. A narrative review. Clin Chim Acta. 2014;433:5–11.CrossRefPubMed Lippi G, Mattiuzzi C, Meschi T, Cervellin G, Borghi L. Homocysteine and migraine. A narrative review. Clin Chim Acta. 2014;433:5–11.CrossRefPubMed
87.
go back to reference Keverne JS, Low WC, Ziabreva I, Court JA, Oakley AE, Kalaria RN. Cholinergic neuronal deficits in CADASIL. Stroke. 2007;38:188–91.CrossRefPubMed Keverne JS, Low WC, Ziabreva I, Court JA, Oakley AE, Kalaria RN. Cholinergic neuronal deficits in CADASIL. Stroke. 2007;38:188–91.CrossRefPubMed
88.
go back to reference Manganelli F, Ragno M, Cacchiò G, Iodice V, Trojano L, Silvaggio F, et al. Motor cortex cholinergic dysfunction in CADASIL: a transcranial magnetic demonstration. Clin Neurophysiol. 2008;119:351–5.CrossRefPubMed Manganelli F, Ragno M, Cacchiò G, Iodice V, Trojano L, Silvaggio F, et al. Motor cortex cholinergic dysfunction in CADASIL: a transcranial magnetic demonstration. Clin Neurophysiol. 2008;119:351–5.CrossRefPubMed
89.
go back to reference Dichgans M, Markus HS, Salloway S, Verkkoniemi A, Moline M, Wang Q, et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol. 2008;7:310–8.CrossRefPubMed Dichgans M, Markus HS, Salloway S, Verkkoniemi A, Moline M, Wang Q, et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol. 2008;7:310–8.CrossRefPubMed
90.
go back to reference Schneider LS. Does donepezil improve executive function in patients with CADASIL? Lancet Neurol. 2008;7:287–9.CrossRefPubMed Schneider LS. Does donepezil improve executive function in patients with CADASIL? Lancet Neurol. 2008;7:287–9.CrossRefPubMed
91.
go back to reference Posada IJ, Ferrero M, Lopez-Valdes E, Goni-Imizcoz M. Galantamine therapy in dementia associated with CADASIL. Rev Neurol. 2008;47:299–300.PubMed Posada IJ, Ferrero M, Lopez-Valdes E, Goni-Imizcoz M. Galantamine therapy in dementia associated with CADASIL. Rev Neurol. 2008;47:299–300.PubMed
92.
go back to reference McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006:CD003154. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006:CD003154.
93.
go back to reference Ho RC, Cheung MW, Fu E, Win HH, Zaw MH, Ng A, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19:607–17.CrossRefPubMed Ho RC, Cheung MW, Fu E, Win HH, Zaw MH, Ng A, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19:607–17.CrossRefPubMed
94.
go back to reference Clarke R, Bennett D, Parish S, Lewington S, Skeaff M, Eussen SJ, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014;100:657–66.CrossRefPubMedPubMedCentral Clarke R, Bennett D, Parish S, Lewington S, Skeaff M, Eussen SJ, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014;100:657–66.CrossRefPubMedPubMedCentral
95.
go back to reference Andersson ER, Lendahl U. Therapeutic modulation of Notch signaling—are we there yet? Nat Rev Drug Discov. 2014;13:357–78.CrossRefPubMed Andersson ER, Lendahl U. Therapeutic modulation of Notch signaling—are we there yet? Nat Rev Drug Discov. 2014;13:357–78.CrossRefPubMed
96.
go back to reference Shin D, Oh YH, Eom CS, Park SM. Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis. J Neurol. 2014;261:686–95.CrossRefPubMed Shin D, Oh YH, Eom CS, Park SM. Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis. J Neurol. 2014;261:686–95.CrossRefPubMed
97.
go back to reference Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012 Nov 14;11:CD009286. Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012 Nov 14;11:CD009286.
99.
go back to reference Ho CS, Mondry A. CADASIL presenting as schizophreniform organic psychosis. Gen Hosp Psychiatry. 2015;37:273.e11–3.CrossRef Ho CS, Mondry A. CADASIL presenting as schizophreniform organic psychosis. Gen Hosp Psychiatry. 2015;37:273.e11–3.CrossRef
100.
go back to reference • Tikka S, Ng YP, Di Maio G, Mykkänen K, Siitonen M, Lepikhova T, et al. CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells. J Cereb Blood Flow Metab. 2012;32:2171–80. The results of the present study support the view that VSMCs in different vascular beds are dissimilar and consequently the pathogenic effects of mutated NOTCH3 gene are also dissimilar in different arteriesCrossRefPubMedPubMedCentral • Tikka S, Ng YP, Di Maio G, Mykkänen K, Siitonen M, Lepikhova T, et al. CADASIL mutations and shRNA silencing of NOTCH3 affect actin organization in cultured vascular smooth muscle cells. J Cereb Blood Flow Metab. 2012;32:2171–80. The results of the present study support the view that VSMCs in different vascular beds are dissimilar and consequently the pathogenic effects of mutated NOTCH3 gene are also dissimilar in different arteriesCrossRefPubMedPubMedCentral
101.
go back to reference • Rutten JW, Dauwerse HG, Peters DJ, Goldfarb A, Venselaar H, Haffner C, et al. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept. Brain. 2016;139:1123–35. This research article examined the technical feasibility of targeted NOTCH3 exon skipping, by designing antisense oligonucleotides targeting exons 2–3, 4–5 and 6, which together harbor the majority of distinct CADASIL-causing mutations. This novel application of exon skipping is a first step towards the development of a rational therapeutic approach applicable to up to 94% of CADASIL-causing mutationsCrossRefPubMed • Rutten JW, Dauwerse HG, Peters DJ, Goldfarb A, Venselaar H, Haffner C, et al. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept. Brain. 2016;139:1123–35. This research article examined the technical feasibility of targeted NOTCH3 exon skipping, by designing antisense oligonucleotides targeting exons 2–3, 4–5 and 6, which together harbor the majority of distinct CADASIL-causing mutations. This novel application of exon skipping is a first step towards the development of a rational therapeutic approach applicable to up to 94% of CADASIL-causing mutationsCrossRefPubMed
102.
go back to reference Gong L, Liu X-Y, Fang M. Recent progress on small vessel disease with cognitive impairment. Int J Clin Exp Med. 2015;8:7701–9.PubMedPubMedCentral Gong L, Liu X-Y, Fang M. Recent progress on small vessel disease with cognitive impairment. Int J Clin Exp Med. 2015;8:7701–9.PubMedPubMedCentral
103.
go back to reference MacLeod R, Tibben A, Frontali M, Evers-Kiebooms G, Jones A, Martinez-Descales A, et al. Editorial Committee and Working Group ‘Genetic Testing Counselling’ of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington’s disease. Clin Genet. 2013;83:221–31.CrossRefPubMed MacLeod R, Tibben A, Frontali M, Evers-Kiebooms G, Jones A, Martinez-Descales A, et al. Editorial Committee and Working Group ‘Genetic Testing Counselling’ of the European Huntington Disease Network. Recommendations for the predictive genetic test in Huntington’s disease. Clin Genet. 2013;83:221–31.CrossRefPubMed
104.
go back to reference Tikka S, Baumann M, Siitonen M, Pasanen P, Pöyhönen M, Myllykangas L, et al. CADASIL and CARASIL. Brain Pathol. 201(24):525–44. Tikka S, Baumann M, Siitonen M, Pasanen P, Pöyhönen M, Myllykangas L, et al. CADASIL and CARASIL. Brain Pathol. 201(24):525–44.
105.
go back to reference Peters N, Herzog J, Opherk C, Dichgans M. A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns and implications for clinical trials. Stroke. 2004;35:1603–8.CrossRefPubMed Peters N, Herzog J, Opherk C, Dichgans M. A two-year clinical follow-up study in 80 CADASIL subjects: progression patterns and implications for clinical trials. Stroke. 2004;35:1603–8.CrossRefPubMed
106.
go back to reference • Chabriat H, Hervé D, Duering M, Godin O, Jouvent E, Opherk C, et al. Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study. Stroke. 2016;47:4–11. This large prospective study on NOTCH3 gene mutation carriers reported that clinical status (particularly gait disturbance,) as well as the number of lacunes and brain volume, are a major independent predictor of clinical worseningCrossRefPubMed • Chabriat H, Hervé D, Duering M, Godin O, Jouvent E, Opherk C, et al. Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study. Stroke. 2016;47:4–11. This large prospective study on NOTCH3 gene mutation carriers reported that clinical status (particularly gait disturbance,) as well as the number of lacunes and brain volume, are a major independent predictor of clinical worseningCrossRefPubMed
Metadata
Title
CADASIL: Treatment and Management Options
Authors
Anna Bersano, MD, PhD
Gloria Bedini, PhD
Joshua Oskam, MD
Caterina Mariotti, MD
Franco Taroni, MD
Silvia Baratta, PhD
Eugenio Agostino Parati, MD
Publication date
01-09-2017
Publisher
Springer US
Published in
Current Treatment Options in Neurology / Issue 9/2017
Print ISSN: 1092-8480
Electronic ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-017-0468-z