Rzadkie – monogenetyczne – przyczyny udaru mózgu związanego z małymi naczyniami

• Authors: Karol Jastrzębski , Magdalena Justyna Kacperska , Małgorzata Figlus

Title variants

EN

Uncommon – monogenetic – causes of small-vessel stroke

• Languages of publication: EN PL

Abstracts

EN

A brain stroke is the most common cause of disability and the third cause of mortality among adults. Every year 6.15 million people in the world die of stroke. According to a current and commonly used WHO definition, the stroke is a rapid occurrence of focal or global neurological deficit of strictly cerebrovascular cause that persists beyond 24 hours. It is estimated that even up to 85–90% of strokes is caused by an ischaemic aetiology, the remainder by haemorrhagic or subarachnoid bleeding. The aim of the paper is to acquaint clinicians with rare, nevertheless occurring in practice genetic causes of strokes connected with single gene mutation. The mentioned disorders are included in a wide spectrum of so called nonhypertensive, cerebral small-vessel diseases. Commonly they occur with concomitant syndromes such as progressive cognitive disturbances or spinal chronic pain syndromes. The multitude of disorders of theoretically unrelated organs also should be alarming although, according to the literature, there are known some oligosymptomatic cases. Additionally, in many cases, unclear radiological image seems to suggest the need for further investigations. After reading this article, clinicians should keep in mind that they especially inquisitively need to search for the reason of stroke in young patients without obvious hypertension in anamnesis, with recurrent vascular episodes, with abnormalities on physical examination that suggest the presence of certain complex of syndromes. Simultaneously, coexistence of typical risk factors such as using drugs affecting thrombosis, arterial hypertension or metabolic disorders should not excuse ignoring the rare diseases. An interdisciplinary team-work of specialists of cardiology, nephrology, dermatology or genetics seems to be invaluable for establishing the diagnosis in this cases.

PL

Udar mózgu to najczęstsza przyczyna niepełnosprawności i trzeci co do częstości powód zgonów wśród osób dorosłych. Wskutek udaru corocznie umiera na świecie około 6,15 mln ludzi. Według wciąż aktualnej i powszechnie stosowanej definicji WHO udar mózgu to nagłe wystąpienie ogniskowego lub uogólnionego zaburzenia czynności mózgu, które trwa dłużej niż 24 godz. i wynika wyłącznie z przyczyn naczyniowych. Szacuje się, że nawet około 85–90% udarów mózgu ma etiologię niedokrwienną, resztę stanowią udary krwotoczne i SAH (subarachnoid haemmorhage, krwotok podpajęczynówkowy). Celem pracy jest przybliżenie rzadkich – ale spotykanych w praktyce – genetycznych przyczyn udaru mózgu związanych z mutacjami w pojedynczych genach. Omówione jednostki chorobowe wpisują się w szerokie spektrum tzw. chorób małych naczyń mózgowych niezwiązanych z nadciśnieniem. Ich występowaniu często towarzyszą inne patologie ośrodkowego układu nerwowego, takie jak postępujące zaburzenia poznawcze czy przewlekłe zespoły bólowe kręgosłupa. Niepokoić powinna także mnogość zaburzeń ze strony innych, pozornie niepowiązanych funkcjonalnie narządów, chociaż według piśmiennictwa znane są przypadki skąpoobjawowe. Dodatkowo w wielu przypadkach niejednoznaczny obraz radiologiczny sugeruje potrzebę rozszerzenia diagnostyki. Warto, by klinicyści pamiętali, że należy szczególnie wnikliwie poszukiwać przyczyny udaru mózgu u osób młodych bez ewidentnego wywiadu w kierunku nadciśnienia tętniczego oraz z nawracającymi epizodami naczyniowymi i odchyleniami w badaniu fizykalnym – wskazującymi na obecność określonych zespołów. Jednocześnie współistnienie typowych czynników ryzyka, czyli stosowania leków wpływających na hemostazę, nadciśnienia tętniczego czy zaburzeń metabolicznych, nie zwalnia z obowiązku rozważania chorób rzadkich. W diagnostyce tych jednostek chorobowych nieoceniona wydaje się inter– dyscyplinarna współpraca specjalistów z dziedziny kardiologii, nefrologii, dermatologii i genetyki.

Keywords

EN

CADASIL; CARASIL; Fabry’s disease; amyloid angiopathy; angiopatia amyloidowa; brain stroke; chorobaFabry’ego; choroby małych naczyń; microangiopathy related with COL4A1 gene mutation; mikroangiopatia związana z mutacjami genu COL4A1; monogenetic disorders; przyczyny monogenetyczne; small vessel disease; udar mózgu

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Aktualności Neurologiczne
• Year: 2014
• Volume: 14
• Issue: 1
• Pages: 34-42

Contributors

author

Karol Jastrzębski

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym Uniwersyteckiego Szpitala Klinicznego im. WAM, Uniwersytet Medyczny w Łodzi

author

Magdalena Justyna Kacperska

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym, Uniwersytet Medyczny w Łodzi, USK im. WAM, ul. Żeromskiego 113, 90-546 Łódź

author

Małgorzata Figlus

• Klinika Neurologii i Epileptologii z Oddziałem Udarowym Uniwersyteckiego Szpitala Klinicznego im. WAM, Uniwersytet Medyczny w Łodzi

References

• 1. WHO: The Top Ten Causes of Death 2008. Fact sheet No 310, May 2011.
• 2. Mathers C.D., Loncar D.: Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006; 3: e442.
• 3. Sarti C., Restenyte D., Cepaitis Z., Tuomilehto J.: International trends in mortality from stroke, 1968 to 1994. Stroke 2000; 31: 1588-1601.
• 4. Wender M., Lenart-Jankowska D., Pruchnik D., Kowal P.: Epidemiology of stroke in the Poznań district of Poland. Stroke 1990; 21: 390-393.
• 5. Slowik A., Turaj W., Zwolińska G. i wsp.: Stroke attack rates and case fatality in the Krakow Stroke Registry. Neurol. Neurochir. Pol. 2007; 41: 291-295.
• 6. Czlonkowska A., Ryglewicz D., Weissbein T. i wsp.: A prospective community-based study of stroke in Warsaw, Poland. Stroke 1994; 25: 547-551.
• 7. Ryglewicz D., Barańska-Gieruszczak M., Lechowicz W., Hier D.B.: High case-fatality rates in the Warsaw stroke registry. J. Stroke Cerebrovasc. Dis. 1997; 6: 421-425.
• 8. Obraniak W.: Ludność Łodzi i innych wielkich miast w Polsce w latach 1984-2006. Urząd Statystyczny w Łodzi, Łódź 2007.
• 9. Whisnant J.P.: Special report from the National Institute of Neurological Disorders and Stroke. Classification of cerebrovascular diseases III. Stroke 1990; 21: 637-676.
• 10. Warlow C., Sudlow C., Dennis M. i wsp.: Stroke. Lancet 2003; 362: 1211-1224.
• 11. Adams H.P. Jr, Bendixen B.H., Kappelle L.J. i wsp.: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35-41.
• 12. Goldstein L.B., Jones M.R., Matchar D.B. i wsp.: Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Stroke 2001; 32: 1091-1098.
• 13. Ryglewicz D.: Epidemiologia udaru mózgu. W: Szczudlik A. (red.): Udar mózgu. Wydawnictwo Uniwersytetu Jagiellońskiego, Kraków 2007.
• 14. Polychronopoulos P., Gioldasis G., Ellul J. i wsp.: Family history of stroke in stroke types and subtypes. J. Neurol. Sci. 2002; 195: 117-122.
• 15. Brass L.M., Isaacsohn J.L., Merikangas K.R., Robinette C.D.: A study of twins and stroke. Stroke 1992; 23: 221-223.
• 16. Bak S., Gaist D., Sindrup S.H. i wsp.: Genetic liability in stroke: a long-term follow-up study of Danish twins. Stroke 2002; 33: 769-774.
• 17. Christensen K., Gaist D., Vaupel J.W., McGue M.: Genetic contribution to rate of change in functional abilities among Danish twins aged 75 years or more. Am. J. Epidemiol. 2002; 155: 132-139.
• 18. Touzé E., Rothwell P.M.: Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study. Lancet Neurol. 2007; 6: 125-133.
• 19. Halim A., Sacco R.L.: Genetyka udaru mózgu. W: Rowland L.P., Pedley T.A. (red.): Neurologia Merritta. Urban & Partner, Wroclaw 2000.
• 20. Kalaria R.N., Vitanen M., Kalimo H. i wsp.: The pathogenesis of CADASIL: an update. J. Neurol. Sci. 2004; 226: 35-39.
• 21. Joutel, A., Corpechot C., Ducros A.: Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383: 707-710.
• 22. Narayan S.K., Gorman G., Kalaria R.N. i wsp.: The minimum prevalence of CADASIL in northeast England. Neurology 2012; 78: 1025-1027.
• 23. Chabriat H., Joutel A., Dichgans M. i wsp.: CADASIL. Lancet Neurol. 2009; 8: 643-653.
• 24. Velizarova R., Mourand I., Serafini A. i wsp.: Focal epilepsy as first symptom in CADASIL. Seizure 2011; 20: 502-504.
• 25. Choi J.C., Kang S.Y., Kang J.H., Park J.K.: Intracerebral hemorrhages in CADASIL. Neurology 2006; 67: 2042-2044.
• 26. Ragno M., Berbellini A., Cacchio G. i wsp.: Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation. Stroke 2013; 44: 1147-1149.
• 27. Singhal S., Rich P., Markus H.S.: The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. AJNR Am. J. Neuroradiol. 2005; 26: 2481-2487.
• 28. Markus H.S., Martin R.J., Simpson M.A. i wsp.: Diagnostic strategies in CADASIL. Neurology 2002; 59: 1134-1138.
• 29. Viswanathan A., Gray F., Bousser M.G. i wsp.: Cortical neuronal apoptosis in CADASIL. Stroke 2006; 37: 2690-2695.
• 30. Gray F., Polivka M., Viswanathan A. i wsp.: Apoptosis in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J. Neuropathol. Exp. Neurol. 2007; 66: 597-607.
• 31. Kalimo H., Ruchoux M.M., Viitanen M., Kalaria R.N.: CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol. 2002; 12: 371-384.
• 32. Ruchoux M.M., Chabriat H., Bousser M.G. i wsp.: Presence of ultrastructural arterial lesions in muscle and skin vessels of patients with CADASIL. Stroke 1994; 25: 2291-2292.
• 33. Joutel A., Favrole P., Labauge P. i wsp.: Skin biopsy immuno-staining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet 2001; 358: 2049-2051.
• 34. Fukutake T.: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): from discovery to gene identification. J. Stroke Cerebrovasc. Dis. 2011; 20: 85-93.
• 35. Nishimoto Y., Shibata M., Ododera O., Suzuki N.: Neurological picture. Neuroaxonal integrity evaluated by MR spectroscopy in a case of CARASIL. J. Neurol. Neurosurg. Psychiatry 2011; 82: 860-861.
• 36. Mendioroz M., Fernández-Cadenas I., Del Rio-Espinola A. i wsp.: A missense HTRA1 mutation expands CARASIL syndrome to the Caucasian population. Neurology 2010; 75: 2033-2035.
• 37. Nishimoto Y., Shibata M., Nihonmatsu M. i wsp.: A novel mutation in the HTRA1 gene causes CARASIL without alopecia. Neurology 2011; 76: 1353-1355.
• 38. Zheng D.M., Xu F.F., Gao Y. i wsp.: A Chinese pedigree of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL): clinical and radiological features. J. Clin. Neurosci. 2009; 16: 847-849.
• 39. Hara K., Shiga A., Fukutake T. i wsp.: Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N. Engl. J. Med. 2009; 360: 1729-1739.
• 40. Peters F.P., Vermeulen A., Kho T.L.: Anderson-Fabry’s disease: a galactosidase deficiency. Lancet 2001; 357: 138-140.
• 41. Tylki-Szymańska A.: Choroby lizosomalne - wprowadzenie. W: Liberski P.P., Papierz W. (red.): Neuropatologia Mossakowskiego. Czelej, Lublin 2005.
• 42. Okeda R., Nisihara M.: An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementia. Neuropathology 2008; 28: 532-540.
• 43. Aerts J.M., Groener J.E., Kuiper S. i wsp.: Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc. Natl Acad. Sci. USA 2008; 105: 2812-2817.
• 44. Waldek S., Patel M.R., Banikazemi M. i wsp.: Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genet. Med. 2009; 11: 790-796.
• 45. Rolfs A., Böttcher T., Zschiesche M. i wsp.: Prevalence of Fabry disease in patients with cryptogenic stroke: a prospective study. Lancet 2005; 366: 1794-1796.
• 46. Rolfs A., Fazekas F., Grittner U. i wsp.: Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study. Stroke 2013; 44: 340-349.
• 47. Brennan P., Parkes O.: Case-finding in Fabry disease: experience from the North of England. J. Inherit. Metab. Dis. 2014; 37: 103-107.
• 48. Bekri S., Enica A., Ghafari T. i wsp.: Fabry disease in patients with end-stage renal failure: the potential benefits of screening. Nephron Clin. Pract. 2005; 101: c33-c38.
• 49. Beck M., Ricci R., Widmer U. i wsp.: Fabry disease: overall effects of agalsidase alfa treatment. Eur. J. Clin. Invest. 2004; 34: 838-844.
• 50. Laney D.A., Bennett R.L., Clarke V i wsp.: Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J. Genet. Couns. 2013; 22: 555-564.
• 51. Mehta A., Ricci R., Widmer U. i wsp.: Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur. J. Clin. Invest. 2004; 34: 236-242.
• 52. Mitsias P., Levine S.R.: Cerebrovascular complications of Fabry’s disease. Ann. Neurol. 1996; 40: 8-17.
• 53. Zenone T., Chan V: Young woman with recurrent ischemic strokes diagnosed as Fabry disease: lessons learned from a case report. Clin. Neurol. Neurosurg. 2011; 113: 586-588.
• 54. Lidove O., Klein I., Leliévre J.D. i wsp.: Imaging features of Fabry disease. AJR Am. J. Roentgenol. 2006; 186: 1184-1191.
• 55. Takanashi J., Barkovich A.J., Dillon WP. i wsp.: T1 hyperintensity in the pulvinar: key imaging feature for diagnosis of Fabry disease. AJNR Am. J. Neuroradiol. 2003; 24: 916-921.
• 56. Fellgiebel A., Keller I., Martus P. i wsp.: Basilar artery diameter is a potential screening tool for Fabry disease in young stroke patients. Cerebrovasc. Dis. 2011; 31: 294-299.
• 57. Gould D.B., Phalan F.C., Breedveld G.J. i wsp.: Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005; 308: 1167-1171.
• 58. Breedveld G., de Coo I.F., Leguin M.H. i wsp.: Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J. Med. Genet. 2006; 43: 490-495.
• 59. Plaisier E., Gribouval O., Alamowitch S. i wsp.: COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N. Engl. J. Med. 2007; 357: 2687-2695.
• 60. Sibon I., Coupry I., Menegon P. i wsp.: COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Ann. Neurol. 2007; 62: 177-184.
• 61. Shah S., Kumar Y., McLean B. i wsp.: A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. Eur. J. Paediatr. Neurol. 2010; 14: 182-187.
• 62. Lanfranconi S., Markus H.S.: COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke 2010; 41: e513-518.
• 63. Haniel A., Welge-Lüssen U., Kühn K., Pöschl E.: Identification and characterization of a novel transcriptional silencer in the human collagen type IV gene COL4A2. J. Biol. Chem. 1995; 270: 11209-11215.
• 64. Kłyszejko-Stefanowicz L.: Macierz zewnątrzkomórkowa. W: Kłyszejko-Stefanowicz L. (red.): Cytobiochemia. PWN, Warszawa 1998.
• 65. Jeanne M., Labelle-Dumais C., Jorgensen J. i wsp.: COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. Am. J. Hum. Genet. 2012; 90: 91-101.
• 66. Yoneda Y., Haginoya K., Arai H. i wsp.: De novo and inherited mutations in COL4A2, encoding the type IV collagen a2 chain cause porencephaly. Am. J. Hum. Genet. 2012; 90: 86-90.
• 67. Kuo D.S., Labelle-Dumais C., Gould D.B.: COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Hum. Mol. Genet. 2012; 21: R97-110.
• 68. Gould D.B., Phalan F.C., van Mil S.E.: Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N. Engl. J. Med. 2006; 354: 1489-1496.
• 69. Vahedi K., Alamowitch S.: Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease. Curr. Opin. Neurol. 2011; 24: 63-68.
• 70. Coupry I., Sibon I., Mortemousque B. i wsp.: Ophthalmological features associated with COL4A1 mutations. Arch. Ophthalmol. 2010; 128: 483-489.
• 71. Vahedi K., Kubis N., Boukobza A. i wsp.: COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage. Stroke 2007; 38: 1461-1464.
• 72. Weng Y.C., Sonni A., Labelle-Dumais C. i wsp.: COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann. Neurol. 2012; 71: 470-477.
• 73. de Vries L.S., Koopman C., Groenendaal F. i wsp.: COL4A1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage. Ann. Neurol. 2009; 65: 12-18.
• 74. Alamowitch S., Plaisier E., Favrole P. i wsp.: Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology 2009; 73: 1873-1882.
• 75. Shah S., Ellard S., Kneen R. i wsp.: Childhood presentation of COL4A1 mutations. Dev. Med. Child. Neurol. 2012; 54: 569-574.
• 76. Vahedi K., Massin P., Guichard J.P. i wsp.: Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy. Neurology 2003; 60: 57-63.
• 77. Greenberg S.M., Briggs M.E., Hyman B.T i wsp.: Apolipoprotein e4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy. Stroke 1996; 27: 1333-1337.
• 78. McCarron M.O., Nicoll J.A.: High frequency of apolipoprotein e4 allele is specific for patients with cerebral amyloid angiopathy-related haemorrhage. Neurosci. Lett. 1998; 247: 45-48.
• 79. Rost N.S., Greenberg S.M., Rosand J.: The genetic architecture of intracerebral hemorrhage. Stroke 2008; 39: 2166-2173.
• 80. Revesz T., Holton J.L., Lashley T i wsp.: Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol. 2009; 118: 115-130.
• 81. Brott T., Broderick J., Kothari R. i wsp.: Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997; 28: 1-5.
• 82. Vinters H.V.: Cerebral amyloid angiopathy. A critical review. Stroke 1987; 18: 311-324.
• 83. Bell R.D., Deane R., Chow N. i wsp.: SRF and myocardin regulate LPR-mediated amyloid-beta clearance in brain vascular cells. Nat. Cell Biol. 2009; 11: 143-153.
• 84. Knudsen K.A., Rosand J., Karluk D., Greenberg S.M.: Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56: 537-539.
• 85. Skeik N., Porten B.R., Delgado Almandoz J.E. i wsp.: A unique case report of cerebral amyloid angiopathy with literature review. Ann. Vasc. Surg. 2014; 28: 1316.e1-1316.e6.
• 86. Mendel T., Bertrand E., Szpak G.M. i wsp.: Cerebral amyloid angiopathy as a cause of an extensive brain hemorrhage in adult patient with Down’s syndrome - a case report. Folia Neuropathol. 2010; 48: 206-211.
• 87. Hornstrup L.S., Frikke-Schmidt R., Nordestgaard B.G., Tybjærg- Hansen A.: Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy. Arterioscler. Thromb. Vasc. Biol. 2013; 33: 1441–1447.
• 88. Auriel E., Greenberg S.M.: The pathophysiology and clinical presentation of cerebral amyloid angiopathy. Curr. Atheroscler. Rep. 2012; 14: 343-350.
• 89. Biffi A., Greenberg S.M.: Cerebral amyloid angiopathy: a systematic review. J. Clin. Neurol. 2011; 7: 1-9.
• 90. Peca S., McCreary C.R., Donaldson E. i wsp.: Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy. Neurology 2013; 81: 1659-1665.
• 91. Cheng A.L., Batool S., McCreary C.R. i wsp.: Susceptibility-weighted imaging is more reliable than T2*-weighted gradient-recalled echo MRI for detecting microbleeds. Stroke 2013; 44: 2782-2786.
• 92. Pontes-Neto O.M., Auriel E., Greenberg S.M.: Advances in our understanding of the pathophysiology, detection and management of cerebral amyloid angiopathy. Eur. Neurol. Rev. 2012; 7: 134-139.
• 93. Mendel T., Gromadzka G.: Polimorfizm genu apolipoprote-iny E (APOE) a ryzyko i rokowanie w krwotokach mózgowych spowodowanych przez mózgową angiopatię amyloidową. Neurol. Neurochir. Pol. 2010; 44: 591-597.
• 94. Ikeda S.I.: Cerebral amyloid angiopathy with familial transthyretin-derived oculoleptomeningeal amyloidosis. Brain Nerve 2013; 65: 831-842.
• 95. Carare R.O., Hawkes C.A., Jeffrey M. i wsp.: Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol. Appl. Neurobiol. 2013; 39: 593-611.
• 96. Gurol M.E., Viswanathan A., Gidicsin C. i wsp.: Cerebral amyloid angiopathy burden associated with leukoaraiosis: a positron emission tomography/magnetic resonance imaging study. Ann. Neurol. 2013; 73: 529-536.

• Document Type: article