Pseudoexfoliation syndrome: Gray matter volume and microstructural changes revealed by histogram and brain surface analysis

Christos V Gkizas, Loukas G Astrakas, Anastasia K Zikou, Vasileios G Xydis, George Kitsos, Maria I Argyropoulou


Purpose: White matter (WM) abnormalities may occur in patients with pseudoexfoliation syndrome (PXS). The presence of gray matter (GM) abnormalities in patients with PXS without glaucoma was evaluated, applying histogram and brain surface analysis of MRI data.

Material and Methods: Brain MRI was conducted on 20 patients newly diagnosed with PXS without glaucoma, (mean age 68.7 ± 8.6 years) and 14 control subjects (mean age 63.3 ± 6.6 years). The histogram scalars of mean diffusivity (MD) and fractional anisotropy (FA) of GM and WM were evaluated. Brain surface analysis was performed on 3D T1-weighted images.

Results: The MD value of the WM showed higher mean, standard deviation, median and 75th percentile in the patients than in the control subjects. The FA values of GM showed higher mean, standard deviation, median and 75th percentile, and lower kurtosis and skewness in the patients than in the control subjects. Greater GM volume was observed in the patients in Brodmann areas 25 and 26.

Conclusions: Patients with PXS may present microstructural changes of the GM that could be associated with the deposition of extracellular fibrillar material and increased cortical volume in areas related to depression. 


Pseudoexfoliation syndrome; Diffusion tensor imaging; Histogram analysis; Cortical surface analysis; MR imaging; Brain

Full Text:



Ariga M, Nivean M, Utkarsha P. Pseudoexfoliation Syndrome. J Curr Glaucoma Pract 2013; 7(3): 118-120.

Sein J, Galor A, Sheth A, et al. Exfoliation syndrome: new genetic and pathophysiologic insights. Curr Opin Ophthalmol 2013; 24(2): 167-174.

Miglior S, Bertuzzi F. Exfoliative glaucoma: new evidence in the pathogenesis and treatment. Prog Brain Res 2015; 221: 233-241.

Akarsu C, Unal B. Cerebral haemodynamics in patients with pseudoexfoliation glaucoma. Eye (Lond) 2005; 19(12): 1297-1300.

Kaya E, Öztürk F. Evaluation of regional brain perfusion in patients with pseudoexfoliation syndrome. Neuro-Ophthalmology 2011; 35(5-6): 255-258.

Yuksel N, Anik Y, Kilic A, et al. Cerebrovascular blood flow velocities in pseudoexfoliation. Graefes Arch Clin Exp Ophthalmol 2006; 244(3): 316-321.

Zikou AK, Kitsos G, Astrakas LG, et al. Pseudoexfoliation syndrome without glaucoma: White matter abnormalities detected by conventional MRI and diffusion tensor imaging. Eur J Radiol 2018; 99: 82-87.

Nucifora PG, Verma R, Lee SK, et al. Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 2007; 245(2): 367-384.

Chiapponi C, Piras F, Piras F, et al. Cortical grey matter and subcortical white matter brain microstructural changes in schizophrenia are localised and age independent: a case-control diffusion tensor imaging study. PLoS One 2013; 8(10): e75115.

Jeon T, Mishra V, Uh J, et al. Regional changes of cortical mean diffusivities with aging after correction of partial volume effects. Neuroimage 2012; 62(3): 1705-1716.

Pfefferbaum A, Adalsteinsson E, Rohlfing T, et al. Diffusion tensor imaging of deep gray matter brain structures: effects of age and iron concentration. Neurobiol Aging 2010; 31(3): 482-493.

Weston PS, Simpson IJ, Ryan NS, et al. Diffusion imaging changes in grey matter in Alzheimer’s disease: a potential marker of early neurodegeneration. Alzheimers Res Ther 2015; 7(1): 47.

Cercignani M, Inglese M, Pagani E, et al. Mean diffusivity and fractional anisotropy histograms of patients with multiple sclerosis. AJNR Am J Neuroradiol 2001; 22(5): 952-958.

Della Nave R, Foresti S, Pratesi A, et al. Whole-brain histogram and voxel-based analyses of diffusion tensor imaging in patients with leukoaraiosis: correlation with motor and cognitive impairment. AJNR Am J Neuroradiol 2007; 28(7): 1313-1319.

Just N. Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 2014; 111(12): 2205-2213.

Pope WB, Qiao XJ, Kim HJ, et al. Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study. J Neurooncol 2012; 108(3): 491-498.

Tofts PS, Davies GR, Dehmeshki J. Histograms: Measuring subtle diffuse disease. In: Tofts PS (ed). Quantitative MRI of the brain: Measuring changes caused by disease. John Wiley & Sons, Ltd 2004, pp 581-610.

Welsh RC, Rahbar H, Foerster B, et al. Brain diffusivity in patients with neuropsychiatric systemic lupus erythematosus with new acute neurological symptoms. J Magn Reson Imaging 2007; 26(3): 541-551.

Pierpaoli C, Barnett A, Pajevic S, et al. Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture. Neuroimage 2001; 13(6 Pt 1): 1174-1185.

Figueroa-Vega N, Moreno-Frias C, Malacara JM. Alterations in adhesion molecules, pro-inflammatory cytokines and cell-derived microparticles contribute to intima-media thickness and symptoms in postmenopausal women. PLoS One 2015; 10(5): e0120990.

Lee DH, Park JW, Park SH, et al. Have you ever seen the impact of crossing fiber in DTI?: Demonstration of the corticospinal tract pathway. PLoS One 2015; 10(7): e0112045.

Roescher N, Tak PP, Illei GG. Cytokines in Sjogren’s syndrome: potential therapeutic targets. Ann Rheum Dis 2010; 69(6): 945-948.

Yang P, Gao Z, Zhang H, et al. Changes in proinflammatory cytokines and white matter in chronically stressed rats. Neuropsychiatr Dis Treat 2015; 11: 597-607.

Oouchi H, Yamada K, Sakai K, et al. Diffusion anisotropy measurement of brain white matter is affected by voxel size: underestimation occurs in areas with crossing fibers. AJNR Am J Neuroradiol 2007; 28(6): 1102-1106.

Schmahmann JD, Smith EE, Eichler FS, et al. Cerebral white matter: neuroanatomy, clinical neurology, and neurobehavioral correlates. Ann N Y Acad Sci 2008; 1142: 266-309.

Rollins N, Reyes T, Chia J. Diffusion tensor imaging in lissencephaly. AJNR Am J Neuroradiol 2005; 26(6): 1583-1586.

Kwee RM, Kwee TC. Virchow-Robin spaces at MR imaging. Radiographics 2007; 27(4): 1071-1086.

Pollock H, Hutchings M, Weller RO, et al. Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes. J Anat 1997; 191(Pt 3): 337-346.

Ryan NS, Keihaninejad S, Shakespeare TJ, et al. Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease. Brain 2013; 136(Pt 5): 1399-1414.

McLaren ME, Szymkowicz SM, O’Shea A, et al. Vertex-wise examination of depressive symptom dimensions and brain volumes in older adults. Psychiatry Res Neuroimaging 2017; 260: 70-75.

Cumurcu T, Cumurcu BE, Celikel FC, et al. Depression and anxiety in patients with pseudoexfoliative glaucoma. General Hosp Psychiatry 2006; 28(6): 509-515.

Hamani C, Mayberg H, Stone S, et al. The subcallosal cingulate gyrus in the context of major depression. Biol Psychiatry 2011; 69(4): 301-308.

Alexander L, Clarke HF, Roberts AC. A focus on the functions of Area 25. Brain Sci 2019; 9(6): 129



  • There are currently no refbacks.