Skip to main content
PMC home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;12(3):371–384. doi: 10.1111/j.1750-3639.2002.tb00451.x

CADASIL: a Common Form of Hereditary Arteriopathy Causing Brain Infarcts and Dementia

Hannu Kalimo 1,✉, Marie‐Magdaleine Ruchoux 2, Matti Viitanen 3, Raj N Kalaria 4
PMCID: PMC8096024  PMID: 12146805

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to cognitive decline and dementia. CADASIL usually begins with migraine in about one third of the patients. More severe manifestations, transient ischemic attacks or recurrent strokes, appear between 30 and 50 years of age. CADASIL, however, may be diagnosed well before the first stroke on the basis of characteristic white matter hyperintensities upon magnetic resonance imaging and presence of pathognomonic granular osmiophilic material in arterial walls, including dermal arteries, since the arteriopathy is generalized. Gradual destruction of vascular smooth muscle cells (VSMC) leads to progressive wall thickening and fibrosis and luminal narrowing in small and medium‐sized penetrating arteries. The reduced cerebral blood flow finally causes lacunar infarcts, mainly in the basal ganglia and fronto‐temporal white matter, which lead to cognitive deficits and dementia of the subcortical vascular type. CADASIL is caused by single missense mutations or small deletions in Notch3 gene encoding a transmembrane receptor Notch3, of which upon ligand binding a nuclear signaling protein is generated by regulated intramembrane proteolysis. Notch signaling is essential during development, regulating cellular differentiation. In adults Notch3 is expressed only in VSMCs and it may promote cell survival by inhibiting apoptosis, but its exact function is unknown. Mutations result in either a gain or loss of one (or rarely, 3) cysteine residue(s) in one of the 34 epidermal growth factor‐like repeats in the extracellular amino‐terminal region of Notch3. It is as yet unclear which disturbance in the Notch signaling pathway leads to the characteristic vascular pathology of CADASIL.

Full Text

The Full Text of this article is available as a PDF (685.9 KB).

References

  • 1. Allard JC, Tilak S, Carter AP (1988) CT and MR of MELAS syndrome. AJNR Am J Neuroradiol 9:1234–1238. [PMC free article] [PubMed] [Google Scholar]
  • 2. Artavanis‐Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776. [DOI] [PubMed] [Google Scholar]
  • 3. Beatus P, Lendahl U (1998) Notch and neurogenesis. J Neurosci Res 54:125–136. [DOI] [PubMed] [Google Scholar]
  • 4. Bischoff C, von Einsiedel HG (1997) Bedeutung der Leukoaraiosis. Nervenarzt 68:609–619. [DOI] [PubMed] [Google Scholar]
  • 5. Bruening R, Dichgans M, Berchtenbreiter C, Yousry T, Seelos KC, Wu RH, Mayer M, Brix G, Reiser M (2001) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance. Am J Neuroradiol 22:1268–1274. [PMC free article] [PubMed] [Google Scholar]
  • 6. Brulin P, Godfrain C, Leteurtre E, Ruchoux MM (2002) Morphometric analysis of ultrastrcutural vascular changes in CADASIL: analysis of 50 skin biopsy specimens and pathogenic implications. Acta Neuropathol (Berl), in press. [DOI] [PubMed] [Google Scholar]
  • 7. Ceroni M, Poloni TE, Tonietti S, Fabozzi D, Uggetti C, Frediani F, Simonetti F, Malaspina A, Alimonti D, Celano M, Ferrari M, Carrera P (2000) Migraine with aura and white matter abnormalities: Notch3 mutation. Neurology 54:1869–1871. [DOI] [PubMed] [Google Scholar]
  • 8. Chabriat H, Vahedi K, Iba‐Zizen M, Joutel A, Nibbio A, Nagy TG, Krebs MO, Julien J, Dubois B, Ducrocq X et al. (1995) Clinical spectrum of CADASIL: a study of 7 families. Lancet 346:934–939. [DOI] [PubMed] [Google Scholar]
  • 9. Chabriat H, Bousser M‐G, Pappata S (1995) Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A positron emission tomography study in two affected family members. Stroke 26:1729–1730. [PubMed] [Google Scholar]
  • 10. Chabriat H, Pappata S, Poupon C, Clark CA, Vahedi K, Poupon F, Mangin JF, Pachot‐Clouard M, Jobert A, Le Bihan D, Bousser MG (1999) Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI. Stroke 30:2637–2643. [DOI] [PubMed] [Google Scholar]
  • 11. Chabriat H, Levy C, Taillia H et al. (1998) Patterns of MRI lesions in CADASIL. Neurology 51:452–457. [DOI] [PubMed] [Google Scholar]
  • 12. Chabriat H, Pappata S, Ostergaard L, Clark CA, Pachot‐Clouard M, Vahedi K, Jobert A, Le Bihan D, Bousser MG (2000) Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking. Stroke 31:1904–1912. [DOI] [PubMed] [Google Scholar]
  • 13. De Lange RP, Bolt J, Reid E, da Silva R, Shaw DJ, Clair DM (2000) Screening British CADASIL families for mutations in the NOTCH3 gene. J Med Genet 37:224–225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. De Strooper B, Saftig P, Craessaerts K et al. (1998) Deficiency of presenilin‐1 inhibits the normal cleavage of amyloid precursor protein. Nature 391:387–390. [DOI] [PubMed] [Google Scholar]
  • 15. De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin‐1‐dependent gamma‐secretase‐like protease mediates release of Notch intracellular domain. Nature 398:518–522. [DOI] [PubMed] [Google Scholar]
  • 16. Dichgans M, Petersen D (1997) Angiographic complications in CADASIL. Lancet 349:776–777. [DOI] [PubMed] [Google Scholar]
  • 17. Dichgans M, Mayer M, Uttner DP et al. (1998) The phenotypic spectrum of CADASIL: Clinical findings in 102 cases. Ann Neurol 44:731–739. [DOI] [PubMed] [Google Scholar]
  • 18. Dichgans M, Ludwig H, Muller‐Hocker J, Messerschmidt A, Gasser T (2000) Small in‐frame deletions and missense mutations in CADASIL: 3D models predict mis‐folding of Notch 3 EGF‐like repeat domains. Eur J Hum Genet 4:280–285. [DOI] [PubMed] [Google Scholar]
  • 19. Dichgans M, Herzog J, Gasser T (2001) Notch3 mutation involving three cysteine residues in a family with typical CADASIL. Neurology 57:1714–1717. [DOI] [PubMed] [Google Scholar]
  • 20. Dichgans M, Holtmannspotter M, Herzog J, Peters N, Bergmann M, Yousry TA (2002) Cerebral microbleeds in CADASIL: a gradient‐echo magnetic resonance imaging and autopsy study. Stroke 33:67–71. [DOI] [PubMed] [Google Scholar]
  • 21. Dichgans M (2002) CADASIL: a monogenic condition causing stroke and subcortical vascular dementia. Cerebrovasc Dis 13 Suppl 5:37–41. [DOI] [PubMed] [Google Scholar]
  • 22. Ebinu JO, Yankner BA (2002) A RIP tide in neuronal signal transduction. Neuron 34:499–502. [DOI] [PubMed] [Google Scholar]
  • 23. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW (2000) Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl 59:23–30. [DOI] [PubMed] [Google Scholar]
  • 24. Escary JL, Cecillon M, Maciazek J, Lathrop M, Tournier‐Lasserve E, Joutel A (2000) Evaluation of DHPLC analysis in mutational scanning of Notch3, a gene with a high G‐C content. Hum Mutat 16:518–526. [DOI] [PubMed] [Google Scholar]
  • 25. Esler WP, Kimberly WT, Ostaszewski BL, Ye W, Diehl TS, Selkoe DJ, Wolfe MS (2002) Activity‐dependent isolation of the presenilin‐ g ‐secretase complex reveals nicastrin and a g substrate. Proc Natl Acad Sci U S A 99:2720–2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Feuerhake F, Volk B, Ostertag CB, Jungling FD, Kassubek J, Orszagh M, Dichgans M (2002) Reversible coma with raised intracranial pressure: an unusual clinical manifestation of CADASIL. Acta Neuropathol (Berl) 103:188–192. [DOI] [PubMed] [Google Scholar]
  • 27. Finnilä S, Tuisku S, Herva R, Majamaa K (2001) A novel mitochondrial DNA mutation and a mutation in the Notch3 gene in a patient with myopathy and CADASIL. J Mol Med 79:641–647. [DOI] [PubMed] [Google Scholar]
  • 28. Forteza AM, Brozman B, Rabinstein AA, Romano JG, Bradley WG (2001) Acetazolamide for the treatment of migraine with aura in CADASIL. Neurology 57:2144–2145. [DOI] [PubMed] [Google Scholar]
  • 29. Gutiérrez‐Molina M, Caminero‐Rodríquez A, Martínez García C et al. (1994) Small arterial granular degeneration in familial Binswanger's disease. Acta Neuropathol (Berl) 87:98–105. [DOI] [PubMed] [Google Scholar]
  • 30. Hardy J (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20:154–159. [DOI] [PubMed] [Google Scholar]
  • 31. Haritunians T, Boulter J, Hicks C, Buhrman J, DiSibio G, Shawber C, Weinmaster G, Nofziger D, Schanen C (2002) CADASIL Notch3 mutant proteins localize to the cell surface and bind ligand. Circ Res 90:506–508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Joutel A, Corpechot C, Ducros A et al. (1996) Notch3 mutations in CADASIL, a hereditary late‐onset condition causing stroke and dementia. Nature 383:707–710. [DOI] [PubMed] [Google Scholar]
  • 33. Joutel A, Vahedi K, Corpechot C et al. (1997) Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 350:1511–1515. [DOI] [PubMed] [Google Scholar]
  • 34. Joutel A, Andreux F, Gaulis S, Domenga V, Cecillon M, Battail N, Piga N, Chapon F, Godfrain C, Tournier‐Lasserve E (2000) The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients. J Clin Invest 105:597–605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Joutel A, Dodick DD, Parisi JE, Cecillon M, Tournier‐Lasserve E, Bousser MG (2000) De novo mutation in the Notch3 gene causing CADASIL. Ann Neurol 47:388–391. [PubMed] [Google Scholar]
  • 36. Joutel A, Favrole P, Labauge P, Chabriat H, Lescoat C, Andreux F, Domenga V, Cecillon M, Vahedi K, Ducros A, Cave‐Riant F, Bousser MG, Tournier‐Lasserve E. (2001) Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 358:2049–2051. [DOI] [PubMed] [Google Scholar]
  • 37. Kalaria RN (1996) Cerebral vessels in ageing and Alzheimer's disease. Pharm Therap 72:193–214. [DOI] [PubMed] [Google Scholar]
  • 38. Kalaria RN (2001) Advances in molecular genetics and pathology of cerebrovascular disorders. Trends Neurosci 24:392–400. [DOI] [PubMed] [Google Scholar]
  • 39. Kalaria RN, Cookson NJ, Mizuno T, Oakley A, Singleton AB, Morris CM, De Lange RPJ, Burn DJ, St Clair D (2000) Microvascular pathology in familial multiinfarct dementia or CADASIL: implications for cerebral blood flow In: Ischemic blood flow in the brain. Fukuuchi Y, Tomita M, Koto A (eds), Part 10, pp. 431–442, Springer‐Verlag, Hong‐Kong . [Google Scholar]
  • 40. Kalimo H, Kaste M, Haltia M (2002) Vascular diseases. In Greenfield's Neuropathology 7th edition, Graham DI, Lantos PL (eds.). pp. 281–355, Arnold: London . [Google Scholar]
  • 41. Kalimo H, Viitanen M, Amberla K, Juvonen V, Marttila R, Poyhonen M, Rinne JO, Savontaus M, Tuisku S, Winblad B (1999) CADASIL: hereditary disease of arteries causing brain infarcts and dementia. Neuropathol Appl Neurobiol 25:257–265. [DOI] [PubMed] [Google Scholar]
  • 42. Kalimo H, Viitanen M, Carlstrom C, Nordberg A, Bronge L (2002) CADASIL in monozygotic twins. Neuropathol Appl Neurobiol 28:151. [Google Scholar]
  • 43. Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ (2001) The intracellular domain of the beta‐amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch‐like manner. J Biol Chem 276:40288–40292. [DOI] [PubMed] [Google Scholar]
  • 44. Kotorii S, Takahashi K, Kamimura K, Nishio T, Arima K, Yamada H, Uyama E, Uchino M, Suenaga A, Matsumoto M, Kuchel G, Rouleau GA, Tabira T (2001) Mutations of the notch3 gene in non‐caucasian patients with suspected CADASIL syndrome. Dement Geriatr Cogn Disord 12:185–193. [DOI] [PubMed] [Google Scholar]
  • 45. Lagas PA, Juvonen V (2001) Schizophrenia in a patient with cerebral autosomally dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL disease). Nord J Psychiatry 55:41–42. [DOI] [PubMed] [Google Scholar]
  • 46. Lardelli M, Dahlstrand J, Lendahl U (1994) The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor‐repeats and is expressed in proliferating neuroepithelium. Mech Dev 46:123–136. [DOI] [PubMed] [Google Scholar]
  • 47. Lesnik Oberstein SA, Ferrari MD, Bakker E, Van Gestel J, Kneppers AL, Frants RR, Breuning MH, Haan J for the Dutch CADASIL Research Group (1999) Diagnostic Notch3 sequence analysis in CADASIL: three new mutations in Dutch patients. Neurology 52:1913–1915. [DOI] [PubMed] [Google Scholar]
  • 48. Lesnik Oberstein SA, van den Boom R, Van Buchem MA, Van Houwelingen HC, Bakker E, Vollebregt E, Ferrari MD, Breuning MH, Haan J; The Dutch CADASIL Research Group (2001) Cerebral microbleeds in CADASIL. Neurology 57:1066–1070. [DOI] [PubMed] [Google Scholar]
  • 49. Liebetrau M, Herzog J, Kloss CU, Hamann GF, Dichgans M (2002) Prolonged cerebral transit time in CADASIL: a transcranial ultrasound study. Stroke 33:509–512. [DOI] [PubMed] [Google Scholar]
  • 50. Levitan D, Greenwald I (1995) Facilitation of lin‐12‐mediated signalling by sel‐12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature 377:351–354. [DOI] [PubMed] [Google Scholar]
  • 51. Majamaa K, Turkka J, Kärppä M, Winqvist S, Hassinen IE (1997) The common MELAS mutation A3243G in mitochondrial DNA among young patients with an occipital brain infarct. Neurology 49:1331–1334. [DOI] [PubMed] [Google Scholar]
  • 52. Majamaa K, Finnilä S, Turkka J, Hassinen IE (1998) Mitochondrial DNA haplogroup U as a risk factor for occipital stroke in migraine. Lancet 352:455–456. [DOI] [PubMed] [Google Scholar]
  • 53. Mas JL, Dilouya A, De Recondo J (1992) A familial disorder with subcortical ischemic strokes, dementia, and leukoencephalopathy. Neurology 42:1015–1019. [DOI] [PubMed] [Google Scholar]
  • 54. Mayer M, Straube A, Bruening R, Uttner I, Pongratz D, Gasser T, Dichgans M, Muller‐Hocker J (1999) Muscle and skin biopsies are a sensitive diagnostic tool in the diagnosis of CADASIL. J Neurol 246:526–532. [DOI] [PubMed] [Google Scholar]
  • 55. Mellies JK, Bäumer T, Müller JA et al. (1998) SPECT study of a German CADASIL family. A phenotype with migraine and progressive dementia only. Neurology 50:1715–1721. [DOI] [PubMed] [Google Scholar]
  • 56. Oliveri RL, Muglia M, De Stefano N, Mazzei R, Labate A, Conforti FL, Patitucci A, Gabriele AL, Tagarelli G, Magariello A, Zappia M, Gambardella A, Federico A, Quattrone A (2001) A novel mutation in the Notch3 gene in an Italian family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: genetic and magnetic resonance spectroscopic findings. Arch Neurol 58:1418–1422. [DOI] [PubMed] [Google Scholar]
  • 57. Ophoff RA, Terwindt GM, Vergouwe MN et al. (1997) Wolff Award 1997. Involvement of a Ca2+ channel gene in familial hemiplegic migraine and migraine with and without aura. Headache 37:479–485. [DOI] [PubMed] [Google Scholar]
  • 58. Prakash N, Hansson E, Betsholtz C, Mitsiadis T, Lendahl U (2002) Mouse Notch 3 expression in the pre‐ and postnatal brain: relationship to the stroke and dementia syndrome CADASIL. Exp Cell Res, in press. [DOI] [PubMed] [Google Scholar]
  • 59. Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier‐Lasserve E (1994) Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 25:2291–2292. [DOI] [PubMed] [Google Scholar]
  • 60. Ruchoux MM, Chabriat H, Bousser MG, Baudrimont M, Tournier‐Lasserve E (1995) Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol (Berl) 89:500–512. [DOI] [PubMed] [Google Scholar]
  • 61. Ruchoux MM, Maurage CA (1997) CADASIL: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. J Neuropathol Exp Neurol 56:947–964. [PubMed] [Google Scholar]
  • 62. Schröder JM, Sellhaus B, Jorg J (1995) Identification of the characteristic vascular changes in a sural biopsy of a case with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Acta Neuropathol (Berl) 89:116–121. [DOI] [PubMed] [Google Scholar]
  • 63. Selkoe DJ (2001) Presenilin, Notch, and the genesis and treatment of Alzheimer's disease. Proc Natl Acad Sci U S A 98:11039–11041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64. Sonninen V, Savontaus ML (1987) Hereditary multiinfarct dementia. Eur Neurol 27:209–215. [DOI] [PubMed] [Google Scholar]
  • 65. Sourander P, Wålinder J (1977) Hereditary multi‐infarct dementia. Morphological and clinical studies of a new disease. Acta Neuropathol (Berl) 39:247–254. [DOI] [PubMed] [Google Scholar]
  • 66. Spinner NB (2000) CADASIL: Notch signaling defect or protein accumulation problem J Clin Invest 105:561–562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67. Stevens DL, Hewlett RH, Brownell B (1977) Chronic familial vascular encephalopathy. Lancet 1(8026):1364–1365. [DOI] [PubMed] [Google Scholar]
  • 68. Taillia H, Chabriat H, Kuetz A, Verin M, Levy C, Vahedi K, Tournier‐Lasserve E, Bousser MG (1998) Cognitive alterations in non‐demented CADASIL patients. Cerebrovasc Dis 8:97–101. [DOI] [PubMed] [Google Scholar]
  • 69. Tournier‐Lasserve E, Joutel A, Melki J at al. (1993) Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy maps to chromosome 19q12. Nature Genet 3:256–259. [DOI] [PubMed] [Google Scholar]
  • 70. Tuominen S, Juvonen V, Amberla K, Jolma T, Rinne JO, Tuisku S, Kurki T, Marttila R, Poyhonen M, Savontaus ML, Viitanen M, Kalimo H (2001) Phenotype of a homozygous CADASIL patient in comparison to 9 age‐matched heterozygous patients with the same R133C Notch3 mutation. Stroke 32:1767–1774. [DOI] [PubMed] [Google Scholar]
  • 71. Tzourio C, Tehindrazanarivelo A, Iglésias S, Alpérovitch A, Chedru F, D'Anglejan‐Chatillon J, Bousser MG (1995) Case‐control study of migraine and risk of ischaemic stroke in young women. Brit Med J 310:830–833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71a. Tzourio C, Kittner SJ, Bousser MG, Alperovitch A (2000) Migraine and stroke in young women. Cephalalgia 20:190–199. [DOI] [PubMed] [Google Scholar]
  • 72. Unlu M, De Lange RPJ, De Silva R, Kalaria RN, St Clair D (2000) Detection of complement Factor B in the cerebrospinal fluid of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease using two‐dimensional gel electrophoresis and mass spectroscopy. Neurosci Lett 282:149–152. [DOI] [PubMed] [Google Scholar]
  • 73. Van Bogaert L (1955) Encephalopathie sous‐corticale progressive (Binswanger) a evolution rapide chez deuz soeurs. Med Hellen 24:961–972. [Google Scholar]
  • 74. Verin M, Rolland Y, Landgraf F, Chabriat H, Bompais B, Michel A, Vahedi K, Martinet JP, Tournier‐Lasserve E, Lemaitre MH, Edan G (1995) New phenotype of the cerebral autosomal dominat arteriopathy mapped to chromosome 19: migraine as the prominent clinical feature. J Neurol Neurosurg Psychiatry 59:579–585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75. Wang T, Sharma SD, Fox N, Rossor M, Brown MJ, Sharma P (2000) Description of a simple test for CADASIL disease and determination of mutation frequencies in sporadic ischaemic stroke and dementia patients. J Neurol Neurosurg Psychiatry 69:652–654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76. Wang W, Prince C, Mou Y, Pollman MJ (2002) Notch3 signaling in vascular smooth muscle cells induces c‐FLIP expression via ERK/MAPK activation: Resistance to FasL‐induced apoptosis. J Biol Chem in press. [DOI] [PubMed] [Google Scholar]
  • 77. Wessman M, Kallela M, Kaunisto MA, Marttila P, Sobel E, Hartiala J, Oswell G, Leal SM, Papp JC, Hämäläinen E, Broas P, Joslyn G, Hovatta I, Hiekkalinna T, Kaprio J, Ott J, Cantor RM, Zwart JA, Ilmavirta M, Havanka H, Färkkilä M, Peltonen L, Palotie A (2002) A susceptibility locus for migraine with aura, on chromosome 4q24. Am J Hum Genet 70:652–662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78. Yanagawa S, Ito N, Arima K, Ikeda S (2002) Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy. Neurology 58:817–820. [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES