Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2013

Open Access 01-12-2013 | Research

Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study

Authors: Sven Haller, Enikö Kövari, François R Herrmann, Victor Cuvinciuc, Ann-Marie Tomm, Gilbert B Zulian, Karl-Olof Lovblad, Panteleimon Giannakopoulos, Constantin Bouras

Published in: Acta Neuropathologica Communications | Issue 1/2013

Login to get access

Abstract

Background

White matter hyperintensities (WMH) lesions on T2/FLAIR brain MRI are frequently seen in healthy elderly people. Whether these radiological lesions correspond to irreversible histological changes is still a matter of debate. We report the radiologic-histopathologic concordance between T2/FLAIR WMHs and neuropathologically confirmed demyelination in the periventricular, perivascular and deep white matter (WM) areas.

Results

Inter-rater reliability was substantial-almost perfect between neuropathologists (kappa 0.71 - 0.79) and fair-moderate between radiologists (kappa 0.34 - 0.42). Discriminating low versus high lesion scores, radiologic compared to neuropathologic evaluation had sensitivity / specificity of 0.83 / 0.47 for periventricular and 0.44 / 0.88 for deep white matter lesions. T2/FLAIR WMHs overestimate neuropathologically confirmed demyelination in the periventricular (p < 0.001) areas but underestimates it in the deep WM (0 < 0.05). In a subset of 14 cases with prominent perivascular WMH, no corresponding demyelination was found in 12 cases.

Conclusions

MRI T2/FLAIR overestimates periventricular and perivascular lesions compared to histopathologically confirmed demyelination. The relatively high concentration of interstitial water in the periventricular / perivascular regions due to increasing blood–brain-barrier permeability and plasma leakage in brain aging may evoke T2/FLAIR WMH despite relatively mild demyelination.
Appendix
Available only for authorised users
Literature
1.
Garde E, Mortensen EL, Krabbe K, Rostrup E, Larsson HB: Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study. Lancet 2000, 356: 628–634. 10.1016/S0140-6736(00)02604-0CrossRefPubMed
2.
Ylikoski A, Erkinjuntti T, Raininko R, Sarna S, Sulkava R, Tilvis R: White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke 1995, 26: 1171–1177. 10.1161/01.STR.26.7.1171CrossRefPubMed
3.
Debette S, Markus HS: The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 2010, 341: c3666. 10.1136/bmj.c3666PubMedCentralCrossRefPubMed
4.
Launer LJ: Epidemiology of white matter lesions. Top Magn Reson Imaging 2004, 15: 365–367. 10.1097/01.rmr.0000168216.98338.8dCrossRefPubMed
5.
Xekardaki A, Santos M, Hof P, Kovari E, Bouras C, Giannakopoulos P: Neuropathological substrates and structural changes in late-life depression: the impact of vascular burden. Acta Neuropathol 2012,124(4):453. 10.1007/s00401-012-1021-5CrossRefPubMed
6.
Santos M, Kovari E, Hof PR, Gold G, Bouras C, Giannakopoulos P: The impact of vascular burden on late-life depression. Brain Res Rev 2009, 62: 19–32. 10.1016/j.brainresrev.2009.08.003PubMedCentralCrossRefPubMed
7.
Schmidt R, Berghold A, Jokinen H, Gouw AA, van der Flier WM, Barkhof F: White matter lesion progression in ladis: frequency, clinical effects, and sample size calculations. Stroke 2012,43(10):2643. 10.1161/STROKEAHA.112.662593CrossRefPubMed
8.
Kim JH, Hwang KJ, Kim JH, Lee YH, Rhee HY, Park KC: Regional white matter hyperintensities in normal aging, single domain amnestic mild cognitive impairment, and mild Alzheimer's disease. J Clin Neurosci 2011, 18: 1101–1106. 10.1016/j.jocn.2011.01.008CrossRefPubMed
9.
Smith EE, Salat DH, Jeng J, McCreary CR, Fischl B, Schmahmann JD: Correlations between MRI white matter lesion location and executive function and episodic memory. Neurology 2011, 76: 1492–1499. 10.1212/WNL.0b013e318217e7c8PubMedCentralCrossRefPubMed
10.
Yoshita M, Fletcher E, Harvey D, Ortega M, Martinez O, Mungas DM: Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology 2006, 67: 2192–2198. 10.1212/01.wnl.0000249119.95747.1fPubMedCentralCrossRefPubMed
11.
Krishnan MS, O'Brien JT, Firbank MJ, Pantoni L, Carlucci G, Erkinjuntti T: Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study. Int J Geriatr Psychiatry 2006, 21: 983–989. 10.1002/gps.1596CrossRefPubMed
12.
Herrmann LL, Le Masurier M, Ebmeier KP: White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 2008, 79: 619–624.CrossRefPubMed
13.
Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P: Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 2011, 82: 126–135. 10.1136/jnnp.2009.204685CrossRefPubMed
14.
Yamamoto Y, Ihara M, Tham C, Low RW, Slade JY, Moss T: Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL. Stroke 2009, 40: 2004–2011. 10.1161/STROKEAHA.108.528299PubMedCentralCrossRefPubMed
15.
Folstein MF, Folstein SE, McHugh PR: "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975, 12: 189–198. 10.1016/0022-3956(75)90026-6CrossRefPubMed
16.
Giannakopoulos P, Gold G, Kovari E, von Gunten A, Imhof A, Bouras C: Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol 2007, 113: 1–12.CrossRefPubMed
17.
Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991, 82: 239–259. 10.1007/BF00308809CrossRefPubMed
18.
McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996, 47: 1113–1124. 10.1212/WNL.47.5.1113CrossRefPubMed
19.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987, 149: 351–356. 10.2214/ajr.149.2.351CrossRefPubMed
20.
Kovari E, Gold G, Herrmann FR, Canuto A, Hof PR, Bouras C: Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia. Neurology 2007, 68: 927–931. 10.1212/01.wnl.0000257094.10655.9aCrossRefPubMed
21.
Scheltens P, Barkhof F, Leys D, Wolters EC, Ravid R, Kamphorst W: Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging. Neurology 1995, 45: 883–888. 10.1212/WNL.45.5.883CrossRefPubMed
22.
Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977, 33: 159–174. 10.2307/2529310CrossRefPubMed
23.
Pantoni L, Garcia JH: Pathogenesis of leukoaraiosis: a review. Stroke 1997, 28: 652–659. 10.1161/01.STR.28.3.652CrossRefPubMed
24.
O'Sullivan M, Lythgoe DJ, Pereira AC, Summers PE, Jarosz JM, Williams SC: Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis. Neurology 2002, 59: 321–326. 10.1212/WNL.59.3.321CrossRefPubMed
25.
Topakian R, Barrick TR, Howe FA, Markus HS: Blood–brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry 2010, 81: 192–197. 10.1136/jnnp.2009.172072CrossRefPubMed
26.
Fazekas F, Kleinert R, Offenbacher H, Schmidt R, Kleinert G, Payer F: Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology 1993, 43: 1683–1689. 10.1212/WNL.43.9.1683CrossRefPubMed
27.
Grafton ST, Sumi SM, Stimac GK, Alvord ECJ, Shaw CM, Nochlin D: Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter. Arch Neurol 1991, 48: 293–298. 10.1001/archneur.1991.00530150061019CrossRefPubMed
28.
van Swieten JC, van den Hout JH, van Ketel BA, Hijdra A, van Wokke JH, Gijn J: Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Brain 1991, 114: 761–774. 10.1093/brain/114.2.761CrossRefPubMed
29.
Young VG, Halliday GM, Kril JJ: Neuropathologic correlates of white matter hyperintensities. Neurology 2008, 71: 804–811. 10.1212/01.wnl.0000319691.50117.54CrossRefPubMed
30.
Platt J: Sequential minimal optimization: A fast algorithm for training support vector machines. Advances in Kernel Methods-Support Vector Learning 1999, 208: 1–21.
31.
Haller S, Lovblad KO, Giannakopoulos P: Principles of Classification Analyses in Mild Cognitive Impairment (MCI) and Alzheimer Disease. J Alzheimers Dis 2011,26(Suppl 3):389–394.PubMed
32.
Douek P, Turner R, Pekar J, Le Patronas N, Bihan D: MR color mapping of myelin fiber orientation. J Comput Assist Tomogr 1991, 15: 923–929. 10.1097/00004728-199111000-00003CrossRefPubMed
33.
Moseley ME, Cohen Y, Kucharczyk J, Mintorovitch J, Asgari HS, Wendland MF: Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 1990, 176: 439–445.CrossRefPubMed
34.
Wolff SD, Balaban RS: Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo. Magn Reson Med 1989, 10: 135–144. 10.1002/mrm.1910100113CrossRefPubMed
35.
Murray ME, Senjem ML, Petersen RC, Hollman JH, Preboske GM, Weigand SD: Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch Neurol 2010, 67: 1379–1385. 10.1001/archneurol.2010.280PubMedCentralCrossRefPubMed
36.
Vernooij MW, Ikram MA, Vrooman HA, Wielopolski PA, Krestin GP, Hofman A: White matter microstructural integrity and cognitive function in a general elderly population. Arch Gen Psychiatry 2009, 66: 545–553. 10.1001/archgenpsychiatry.2009.5CrossRefPubMed
37.
de Groot JC, de Leeuw FE, Oudkerk M, Hofman A, Jolles J, Breteler MM: Cerebral white matter lesions and depressive symptoms in elderly adults. Arch Gen Psychiatry 2000, 57: 1071–1076. 10.1001/archpsyc.57.11.1071CrossRefPubMed
38.
Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F: Progression of leukoaraiosis and cognition. Stroke 2007, 38: 2619–2625. 10.1161/STROKEAHA.107.489112CrossRefPubMed
Metadata
Title
Do brain T2/FLAIR white matter hyperintensities correspond to myelin loss in normal aging? A radiologic-neuropathologic correlation study
Authors
Sven Haller
Enikö Kövari
François R Herrmann
Victor Cuvinciuc
Ann-Marie Tomm
Gilbert B Zulian
Karl-Olof Lovblad
Panteleimon Giannakopoulos
Constantin Bouras
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/2051-5960-1-14

Other articles of this Issue 1/2013

Acta Neuropathologica Communications 1/2013 Go to the issue

Research

Nerve hyperplasia: a unique feature of ketamine cystitis

Research

Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination

Research

Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein

Review

The prion hypothesis in Parkinson's disease: Braak to the future

Research

NG2 cells, a new trail for Alzheimer’s disease mechanisms?

Research

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain