Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by a cerebral non-atherosclerotic, non-amyloid angiopathy mainly affecting the small arteries penetrating the white matter. In the brain vessels of two patients with CADASIL, abnormal patches of granular osmiophilic material have recently been described. Here we report the observation of similar granular osmiophilic material within the vessel walls of muscle and skin biopsies from a 54-year-old woman belonging to a CADASIL family, who suffered from subcortical dementia with leukoencephalopathy demonstrated on neuroimaging. Postmortem examination disclosed changes of the vessel walls in all the organs chiefly leading to cerebral lesions. Ultrastructural study showed destruction of the vascular smooth muscle cells (VSMC) and the granular osmiophilic material already found in muscle and skin biopsies in this patient. Both changes were found all along the arterial tree. The findings of this study indicate that CADASIL is a systemic vascular disease involving arterial VSMC and that the lesions are different in each organ and vessel wall, depending on their fine structure. Moreover, it emphasizes that skin and muscle biopsies might be useful for diagnosis of and research into CADASIL.
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Babikian V, Ropper AH (1987) Binswanger's disease: a review. Stroke 18: 2–12
Baudrimont M, Dubas F, Joutel A, Tournier-Lasserve E, Bousser MG (1993) Autosomal dominant leukoencephalopathy and subcortical ischemic stroke. A clinicopathological study. Stroke 24: 122–125
Berthier E, Broussole E, Garcia-Marquier M, Tommasi M, Chazot G (1992) Leukoencéphalopathie artériopathique juvénile: étude anatomoclinique d'un cas. Rev Neurol (Paris) 148: 146–149
Binswanger O (1894) Die Abgrenzung der allgemeinen progressiven Paralyse. Berl Klin Wochenschr 31: 1103–1105, 1137–1139, 1180–1186
Bousser MG, Tournier-Lasserve E (1993) Summary of the proceedings of the first international workshop on CADASIL. Stroke 25: 704–707
Caplan LR, Schoene WC (1978) Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger's disease). Neurology 28: 1206–1215
Cervos-Navarro J, Rosas I (1978) The arteriole as a site of metabolic exchange. Adv Neurol 20: 17–24
Chabriat H, Tournier-Lasserve E, Vahedi K, Leys D, Joutel A, Nibbio A, Escaillas JP, Iba-Zizen MT, Bracard S, Tehindrazanarivelo A, Gastaut JL, Bousser MG (1995) Autosomal dominant migraine with MRI white-matter abnormalities mapping to the CADASIL locus. Neurology (in press)
Colmant HJ (1980) Familiäre zerebrale Gefäßerkrankung. Zentralbl Allg Pathol 124: 163
Corder EH, Saunders AM, Strittmatter WJ, Schemechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261: 921–923
Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Atherosclerosis 8: 1–21
Davous P, Fallet-Bianco C (1991) Démence sous-corticale familiale avec leukoencéphalopathie artériopathique. Observation clinico-pathologique. Rev Neurol (Paris) 147: 376–384
Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Scherrer V, Defossez A (1990) Pathological proteins tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease: demonstration with a panel of antibodies against tau proteins. Acta Neuropathol 80: 111–117
De Reuck J, Crevits L, De Coster W (1980) Pathogenesis of Binswanger chronic progressive subcortical encephalopathy. Neurology 30: 920–928
Doly M, Droy MT, Bonhomme B, Ruchoux MM, Braquet P (1988) Alteration of electrophysiological function of alloxan-induced diabetic rats ilsolated retina. Effect ofGinkgo biloba extract treatment. Neurochem Pathol 8: 15–25
Dubas F, Gray F, Roullet E, Escourolle R (1985) Leukoencéphalopathies artériopathiques. Rev Neurol (Paris) 141: 93–108
Duvernoy HM, Delon S, Vannson JL (1981) Cortical blood vessels of the human brain. Brain Res Bull 7: 519–579
Duvernoy HM, Delon S, Vannson JL (1983) The vascularization of the human cerebellar cortex. Brain Res Bull 11: 419–480
Gale AN, Brenton DP, Cusworth DC, Duchen LW, Stern GM (1982) Extra-pyramidal disturbance in homocystinuria. J Med Genet 19: 374
Garay RP (1987) Kinetic aspects of red blood cell sodium transport systems in essential hypertension. Hypertension 10 [Suppl 1]: 111–114
Gray F, Robert F, Labrecques R, Chretien F, Baudrimont M, Fallet-Bianco C, Mikol J, Vinters HV (1994) Autosomal dominant arteriopathic leukoencephalopathy and Alzheimer's disease. Neuropathol Appl Neurobiol 20: 22–30
Gutierrez-Molina M, Caminero-Rodriguez A, Martinez Garcia C, Arpa Gutierrez J, Morales Bastos C, Amer G (1994) Small arterial granular degeneration in familial Binswanger's syndrome. Acta Neuropathol 87: 98–105
Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325: 253–257
Jellinger K, Neumayer E (1964) Progressive subcorticale vasculäre encephalopathie Binswanger, eine klinische-neuropathologische Studie. Arch Psychiatr Nervenkr 205: 523–554
Jiang MH, Höög A, Ma K, Nie JX, Olsson Y, Zhang WW (1993) Endothelin-1-like immunoreactivity is expressed in reactive astrocytes of the human brain. Neuroreport 7: 935–937
Joutel A, Bousser MG, Biousse V, Labauge P, Chabriat H, Nibbio A, Maciazek J, Meyer B, Bach MA, Weissenbach J, Mark Lathrop G, Tournier Lasserve E (1993) A gene for familial hemiplegic migraine maps to chromosome 19. Nature Genet 5: 40–45
Maeda S, Nakayama H, Isaka K, Aihara Y, Nemoto S (1976) Familial unusual encephalopathy of Binswanger's type without hypertension. Folia Psychiatr Neurol Jpn 30: 165–177
Mas JL, Dilouya A, De Recondo J (1992) A familial disorder with subcortical ischemic strokes, dementia and leukoencephalopathy. Neurology 42: 1015–1019
Moskowitz MA (1993) Neurovascular mechanisms in the pathogenesis and treatment of migraine. Abstracts of the 7th World Congress on Pain. IASP Publications, Seattle, p 253
Owens GK, Schwartz M (1982) Alterations in vascular smooth muscle cell mass in the spontaneously hypertensive rat. Role in cellular hypertrophy, hyperploidy and hyperplasia. Circ Res 51: 280–289
Pavlakis SG, Philipps PC, Di Mauro S, De Vivo DC, Rowland LP (1984) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes: a distinctive clinical syndrome. Ann Neurol 16: 481–488
Pellisier JF, Poncet M (1989) Binswanger's encephalopathy. Handb Clin Neurol 10: 221–233
Pfeifer RA (1930) Grundlegende Untersuchungen für die Angioarchitektonik des menschlichen Gehirns. Springer, Berlin
Plant GT, Revesz T, Barnard RO, Harding AE, Gautier-Smith PC (1990) Familial cerebral amyiopathy with nonneuritic amyloid plaque formation. Brain 113: 721–747
Ruchoux MM (1992) Intêrets et limites des modèles animaux dans l'athérosclerose. Sci Vet Med Comp 94: 27–35
Ruchoux MM, Droy-Lefaix MT, Bakri F, Ruchoux P, Lhuintre Y (1990) Cicletanine and hypertensive retinopathy. Ophthalmic Res 22: 318–329
Ruchoux MM, Huguet F, Droy-Lefaix MT, Gelot A, Ruchoux P, Autret A (1989) The effect of cicletanine on cerebrovascular injury in stroke-prone spontaneously hypertensive rats, SHR-SP. Am J Hypertens 2: 683–689
Ruchoux MM, Droy-Lefaix MT, Bakri F, Berthet P, Bosquet D, Lhuintre Y (1989) Etude de la protection par le cicletanine des parois vasculaires du rat “stroke-prone” spontanément hypertendu. Arch Mal Coeur Vaiss 82: 1163–1168
Ruchoux MM, Huguet F, Droy MT, Guillemain J, Chauveau G, Lhuintre Y (1989) Effets du cicletanine sur les lésions liées à l'⇓ge. Arch Mal Coeur Vaiss 82:181–185
Ruchoux MM, Rosati C, Gelot A, Lhiuntre Y, Garay R (1992) Ultrastructural study of the choroid plexus of spontaneously hypertensive rats (SHR). Am J Hypertens 5: 851–856
Ruchoux MM, Chabriat H, Baudrimont M, Tournier-Lasserve E, Bousser MG (1994) Presence of CADASIL ultrastructural arterial lesions in muscle and skin vessels (letter). Stroke 25: 2291–2292
Salvi F, Michelucci R, Plasmati R, Parmeggini L, Zonari P, Mascalchi M, Tassinari CA (1992) Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan. Ital J Neurol Sci 13:1135–1140
Scheltens PH, Barkoff F, Valk J, Algra PR, Gerritsen Van Der Hoop R, Nauta J, Wolters ECH (1992) White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer's disease: evidence for heterogeneity. Brain 115: 735–748
Schröder JM, Szllhaus B, Jörg J (1995) Identification of the charactristic vascular changes in a sural nerve biopsy of a case with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Acta Neuropathol 89: 116–121
Sonninen V, Qavontaux ML (1987) Hereditary multi-infarct dementia. Eur Neurol 27: 209–215
Sourander P, Walinder J (1977) Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease. Acta Neuropathol (Berl) 39: 247–254
Spangler KM, Challa VR, Moody DM, Bell MA (1994) Arteriolar tortuosity of the white matter in aging and hypertension. A microradiographic study. J Neuropathol Exp Neurol 53: 22–26
Stevens DL, Hewlett RH, Brownell B (1977) Chronic familial vascular encephalopathy. Lancet I: 1364–1365
Tagami M, Nara Y, Kubota A, Fujino H, Yamori Y (1990) Ultrastructural changes in cerebral pericytes and astrocytes of stroke-prone spontaneously hypertensive rats. Stroke 21: 1064–1071
Tournier-Lasserve E, Iba-Zizen MT, Romero N, Bousser MG (1991) Autosomal dominant syndrome with stroke-like episodes and leukoencephalopathy. Stroke 22: 1297–1302
Tournier-Lasserve E, Joutel A, Melki J, Weissenbach J, Mark Lathrop G, Chabriat H, Mas L, Cabanis EA, Baudrimont M, Maciazek J, Bach MA, Bousser MG (1993) Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12. Nature Genet 3: 256–259
Vanhoute PM (1987) Endothelium-dependent contractions in arteries and veins. Blood Vessels 24: 141–142
Wisniewski HM, Wegiel J (1994) §-Amyloid formation by myocytes of leptomeningeal vessels Acta Neuropathol 87: 233–241
Yamori Y (1989) Predictive and preventive pathology of cardiovascular diseases. Acta Pathol Jpn 39: 683–705
Yamori Y, Igawa T, Kanbe T, Kihara M, Nara Y, Horie R (1981) Mechanism of structural vascular changes in genetic hypertension: analysis on cultured vascular smooth muscle cells from spontaneously hypertensive rats. Clin Sci 61 [Suppl 1]: 121s-123s
Yokoi S, Nakayama H (1985) Chronic progressive leukoencephalopathy with systemic arteriosclerosis in young adults. Clin Neuropathol 4: 165–170
Zhang WW, Ma KC, Andersen O, Sourander P, Tollesson PO, Olsson Y (1994) The microvascular changes in cases of hereditary multi-infarct disease of the brain. Acta Neuropathol 87: 317–324
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Ruchoux, M.M., Guerouaou, D., Vandenhaute, B. et al. Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Acta Neuropathol 89, 500–512 (1995). https://doi.org/10.1007/BF00571504
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DOI: https://doi.org/10.1007/BF00571504