Aged; Aged, 80 and over; Aging/physiology; Cerebral Small Vessel Diseases/diagnosis; Cerebral Small Vessel Diseases/epidemiology; Female; Humans; Hypertension/physiopathology; Male; Obesity/physiopathology; Retrospective Studies; Risk Factors; Multidisciplinary
Abstract :
[en] [en] OBJECTIVE: Although the clinical manifestation and risk factors of cerebral microangiopathy (CM) remain unclear, the number of diagnoses is increasing. Hence, patterns of association among lesion topography and severity, clinical symptoms and demographic and disease risk factors were investigated retrospectively in a cohort of CM patients.
METHODS: Patients treated at the Department of Neurology, University of Bonn for CM (n = 223; 98m, 125f; aged 77.32±9.09) from 2005 to 2010 were retrospectively enrolled. Clinical symptoms, blood chemistry, potential risk factors, demographic data and ratings of vascular pathology in the brain based on the Wahlund scale were analyzed using Pearson's chi square test and one-way ANOVA.
RESULTS: Progressive cognitive decline (38.1%), gait apraxia (27.8%), stroke-related symptoms and seizures (24.2%), TIA-symptoms (22%) and vertigo (17%) were frequent symptoms within the study population. Frontal lobe WMLs/lacunar infarcts led to more frequent presentation of progressive cognitive decline, seizures, gait apraxia, stroke-related symptoms, TIA, vertigo and incontinence. Parietooccipital WMLs/lacunar infarcts were related to higher frequencies of TIA, seizures and incontinence. Basal ganglia WMLs/lacunar infarcts were seen in patients with more complaints of gait apraxia, vertigo and incontinence. Age (p = .012), arterial hypertension (p<.000), obesity (p<.000) and cerebral macroangiopathy (p = .018) were positively related to cerebral lesion load. For increased glucose level, homocysteine, CRP and D-Dimers there was no association.
CONCLUSION: This underlines the association of CM with neurological symptoms upon admission in a topographical manner. Seizures and vertigo are symptoms of CM which may have been missed in previous studies. In addition to confirming known risk factors such as aging and arterial hypertension, obesity appears to increase the risk as well. Since the incidence of CM is increasing, future studies should focus on the importance of prevention of vascular risk factors on its pathogenesis.
Disciplines :
Neurology
Author, co-author :
Okroglic, Sandra; Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany
Widmann, Catherine N; Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany
Urbach, Horst; Department of Radiology, Neuroradiology Unit, University of Bonn, Bonn, Germany
Scheltens, Philip; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands
HENEKA, Michael ; Department of Neurology, Clinical Neuroscience Unit, University of Bonn, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Clinical symptoms and risk factors in cerebral microangiopathy patients.
This study had no sponsor. Funding for this study was provided by the Clinical Neuroscience Unit at the Department of Neurology, University of Bonn, Germany. S. Okroglic reports no disclosures. C.N. Widmann reports no disclosures. H. Urbach reports no disclosures. P. Scheltens serves/has served on the advisory boards of: Genentech, Novartis, Pfizer, Roche, Danone, Nutricia, Jansen AI, Baxter and Lundbeck. He has been a speaker at symposia organized by Lundbeck, Lilly, Merz, Pfizer, Jansen AI, Danone, Novartis, Roche and Genentech. He serves on the editorial board of Alzheimer's Research and Therapy and Alzheimer's Disease and Associated Disorders, is a member of the scientific advisory board of the EU Joint Programming Initiative and the French National Plan Alzheimer. The Alzheimer Center receives unrestricted funding from various sources through the VUmc Fonds. Dr. Scheltens receives no personal compensation for the activities mentioned above. M.T. Heneka serves on the editorial boards of the Journal of Chemical Neuroanatomy and the Journal of Neurochemistry. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Pantoni L, (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9: 689-701 doi:10.1016/S1474-4422(10)70104-6.
Pantoni L, Garcia JH, (1997) Cognitive impairment and cellular/vascular changes in the cerebral white matter. Ann N Y Acad Sci 826: 92-102.
Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, et al. (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatr 82: 126-135 doi:10.1136/jnnp.2009.204685.
Patel B, Markus HS, (2011) Magnetic resonance imaging in cerebral small vessel disease and its use as a surrogate disease marker. Int J Stroke 6: 47-59 doi:10.1111/j.1747-4949.2010.00552.x.
Baezner H, Blahak C, Poggesi A, Pantoni L, Inzitari D, et al. (2008) Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 70: 935-942 doi:10.1212/01.wnl.0000305959.46197.e6.
Poggesi A, Pracucci G, Chabriat H, Erkinjuntti T, Fazekas F, et al. (2008) Urinary complaints in nondisabled elderly people with age-related white matter changes: the Leukoaraiosis And DISability (LADIS) Study. J Am Geriatr Soc 56: 1638-1643 doi:10.1111/j.1532-5415.2008.01832.x.
Teodorczuk A, Firbank MJ, Pantoni L, Poggesi A, Erkinjuntti T, et al. (2010) Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study. Psychol Med 40: 603-610 doi:10.1017/S0033291709990857.
Inzitari M, Pozzi C, Rinaldi LA, Masotti G, Marchionni N, et al. (2007) Cognitive and functional impairment in hypertensive brain microangiopathy. J Neurol Sci 257: 166-173 doi:10.1016/j.jns.2007.01.026.
Kuo H-K, Lipsitz LA, (2004) Cerebral white matter changes and geriatric syndromes: is there a link? J Gerontol A Biol Sci Med Sci 59: 818-826.
Marchesi VT, (2011) Alzheimer's dementia begins as a disease of small blood vessels, damaged by oxidative-induced inflammation and dysregulated amyloid metabolism: implications for early detection and therapy. FASEB J 25: 5-13 doi:10.1096/fj.11-0102ufm.
Breteler MM, van Swieten JC, Bots ML, Grobbee DE, Claus JJ, et al. (1994) Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 44: 1246-1252.
Inzitari D, Diaz F, Fox A, Hachinski VC, Steingart A, et al. (1987) Vascular risk factors and leuko-araiosis. Arch Neurol 44: 42-47.
Dufouil C, Chalmers J, Coskun O, Besançon V, Bousser M-G, et al. (2005) Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation 112: 1644-1650 doi:10.1161/CIRCULATIONAHA.104.501163.
Mok VCT, Lam WWM, Fan YH, Wong A, Ng PW, et al. (2009) Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study. J Neurol 256: 750-757 doi:10.1007/s00415-009-5008-7.
Stewart R, Liolitsa D, (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16: 93-112.
Jagust W, Harvey D, Mungas D, Haan M, (2005) Central obesity and the aging brain. Arch Neurol 62: 1545-1548 doi:10.1001/archneur.62.10.1545.
Reitz C, Berger K, de Maat MPM, Stoll M, Friedrichs F, et al. (2007) CRP gene haplotypes, serum CRP, and cerebral small-vessel disease: the Rotterdam Scan Study and the MEMO Study. Stroke 38: 2356-2359 doi:10.1161/STROKEAHA.107.482661.
Isenegger J, Meier N, Lämmle B, Alberio L, Fischer U, et al. (2010) D-dimers predict stroke subtype when assessed early. Cerebrovasc Dis 29: 82-86 doi:10.1159/000256652.
de Lau LML, van Meurs JBJ, Uitterlinden AG, Smith AD, Refsum H, et al. (2010) Genetic variation in homocysteine metabolism, cognition, and white matter lesions. Neurobiol Aging 31: 2020-2022 doi:10.1016/j.neurobiolaging.2008.10.004.
Brouns R, Van Den Bossche J, De Surgeloose D, Sheorajpanday R, De Deyn PP, (2009) Clinical and biochemical diagnosis of small-vessel disease in acute ischemic stroke. J Neurol Sci 285: 185-190 doi:10.1016/j.jns.2009.06.032.
Vermeer SE, van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, et al. (2002) Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 51: 285-289.
van Dijk EJ, Prins ND, Vermeer SE, Vrooman HA, Hofman A, et al. (2005) C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 112: 900-905 doi:10.1161/CIRCULATIONAHA.104.506337.
Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, et al. (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32: 1318-1322.
SPSS Statistics (2008) Chicago, Illinois, USA: SPSS Inc. p. Available: http://www.spss.com/de/software/statistics/. Accessed 2011 Feb 18.
Oh S-H, Kim N-K, Kim S-H, Kim J-K, Kim H-S, et al. (2010) The prevalence and risk factor analysis of silent brain infarction in patients with first-ever ischemic stroke. J Neurol Sci 293: 97-101 doi:10.1016/j.jns.2010.02.025.
Lin H-J, Yeh P-S, Tsai T-C, Cheng T-J, Ke D, et al. (2007) Differential risks of subsequent vascular events for transient ischaemic attack and minor ischaemic stroke. J Clin Neurosci 14: 17-21 doi:10.1016/j.jocn.2005.07.026.
Schreiner A, Pohlmann-Eden B, Schwartz A, Hennerici M, (1995) Epileptic seizures in subcortical vascular encephalopathy. J Neurol Sci 130: 171-177.
De Reuck J, Nagy E, Van Maele G, (2007) Seizures and epilepsy in patients with lacunar strokes. J Neurol Sci 263: 75-78 doi:10.1016/j.jns.2007.06.004.
Miki Y, Grossman RI, Udupa JK, Wei L, Kolson DL, et al. (1998) Isolated U-fiber involvement in MS: preliminary observations. Neurology 50: 1301-1306.
Blahak C, Baezner H, Pantoni L, Poggesi A, Chabriat H, et al. (2009) Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study. J Neurol Neurosurg Psychiatr 80: 608-613 doi:10.1136/jnnp.2008.154633.
Viana-Baptista M, Bugalho P, Jordão C, Ferreira N, Ferreira A, et al. (2008) Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. J Neurol 255: 360-366 doi:10.1007/s00415-008-0661-9.
van Harten B, Oosterman JM, Potter van Loon B-J, Scheltens P, Weinstein HC, (2007) Brain lesions on MRI in elderly patients with type 2 diabetes mellitus. Eur Neurol 57: 70-74 doi:10.1159/000098054.
Jimenez-Conde J, Biffi A, Rahman R, Kanakis A, Butler C, et al. (2010) Hyperlipidemia and reduced white matter hyperintensity volume in patients with ischemic stroke. Stroke 41: 437-442 doi:10.1161/STROKEAHA.109.563502.
Karatas M, (2008) Central vertigo and dizziness: epidemiology, differential diagnosis, and common causes. Neurologist 14(6): 355-64 doi:10.1097/NRL.0b013e31817533a3.
