Abstract
Purpose
Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS.
Methods
In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms.
Results
WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion.
Conclusion
FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options.
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Abbreviations
- MS:
-
Multiple sclerosis
- FD:
-
Fabry disease
- CC:
-
Corpus callosum;
- WMLs:
-
White matter lesions
- eGFR:
-
Estimated glomerular filtration rate
- CKD-EPI:
-
Chronic Kidney Disease Epidemiology Collaboration
- GLA:
-
α-Galactosidase A
- ERT:
-
Enzyme replacement therapy
- DD:
-
Disease duration
- EDSS:
-
Expanded Disability Status Scale
- ARR:
-
Annualized Relapse Rate
- MSSS:
-
Multiple Sclerosis Severity Score
- CSF:
-
Cerebrospinal fluid
References
Zarate YA, Hopkin RJ (2008) Fabry’s disease. Lancet 372(9647):1427–1435. doi:10.1016/S0140-6736(08)61589-5
Ishii S, Chang HH, Kawasaki K, Yasuda K, Wu HL, Garman SC, Fan JQ (2007) Mutant alpha-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin. Biochem J 406(2):285–295. doi:10.1042/BJ20070479
Kolodny E, Fellgiebel A, Hilz MJ, Sims K, Caruso P, Phan TG, Politei J, Manara R, Burlina A (2015) Cerebrovascular involvement in Fabry disease: current status of knowledge. Stroke 46(1):302–313. doi:10.1161/STROKEAHA.114.006283
Sims K, Politei J, Banikazemi M, Lee P (2009) Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry. Stroke 40(3):788–794. doi:10.1161/STROKEAHA.108.526293
Fellgiebel A, Muller MJ, Ginsberg L (2006) CNS manifestations of Fabry’s disease. Lancet Neurol 5(9):791–795. doi:10.1016/S1474-4422(06)70548-8
Compston A, Coles A (2008) Multiple sclerosis. Lancet 372(9648):1502–1517. doi:10.1016/S0140-6736(08)61620-7
Filippi M, Rocca MA, Ciccarelli O, De Stefano N, Evangelou N, Kappos L, Rovira A, Sastre-Garriga J, Tintore M, Frederiksen JL, Gasperini C, Palace J, Reich DS, Banwell B, Montalban X, Barkhof F (2016) MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol 15(3):292–303. doi:10.1016/S1474-4422(15)00393-2
Gean-Marton AD, Vezina LG, Marton KI, Stimac GK, Peyster RG, Taveras JM, Davis KR (1991) Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis. Radiology 180(1):215–221. doi:10.1148/radiology.180.1.2052698
Palmer S, Bradley WG, Chen DY, Patel S (1999) Subcallosal striations: early findings of multiple sclerosis on sagittal, thin-section, fast FLAIR MR images. Radiology 210(1):149–153. doi:10.1148/radiology.210.1.r99ja38149
Simon JH, Holtas SL, Schiffer RB, Rudick RA, Herndon RM, Kido DK, Utz R (1986) Corpus callosum and subcallosal-periventricular lesions in multiple sclerosis: detection with MR. Radiology 160(2):363–367. doi:10.1148/radiology.160.2.3726114
Garg N, Reddel SW, Miller DH, Chataway J, Riminton DS, Barnett Y, Masters L, Barnett MH, Hardy TA (2015) The corpus callosum in the diagnosis of multiple sclerosis and other CNS demyelinating and inflammatory diseases. J Neurol Neurosurg Psychiatry 86(12):1374–1382. doi:10.1136/jnnp-2014-309649
Bottcher T, Rolfs A, Tanislav C, Bitsch A, Kohler W, Gaedeke J, Giese AK, Kolodny EH, Duning T (2013) Fabry disease—underestimated in the differential diagnosis of multiple sclerosis? PLoS One 8(8):e71894. doi:10.1371/journal.pone.0071894
Callegaro D, Kaimen-Maciel DR (2006) Fabry’s disease as a differential diagnosis of MS. Int MS J 13(1):27–30
Vucic Lovrencic M, Radisic Biljak V, Bozicevic S, Prasek M, Pavkovic P, Knotek M (2012) Estimating glomerular filtration rate (GFR) in diabetes: the performance of MDRD and CKD-EPI equations in patients with various degrees of albuminuria. Clin Biochem 45(18):1694–1696. doi:10.1016/j.clinbiochem.2012.07.115
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O’Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302. doi:10.1002/ana.22366
Fazekas F, Enzinger C, Schmidt R, Grittner U, Giese AK, Hennerici MG, Huber R, Jungehulsing GJ, Kaps M, Kessler C, Martus P, Putaala J, Ropele S, Tanislav C, Tatlisumak T, Thijs V, von Sarnowski B, Norrving B, Rolfs A (2015) Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event. Stroke 46(6):1548–1553. doi:10.1161/STROKEAHA.114.008548
deVeber GA, Schwarting GA, Kolodny EH, Kowall NW (1992) Fabry disease: immunocytochemical characterization of neuronal involvement. Ann Neurol 31(4):409–415. doi:10.1002/ana.410310410
Kaye EM, Kolodny EH, Logigian EL, Ullman MD (1988) Nervous system involvement in Fabry’s disease: clinicopathological and biochemical correlation. Ann Neurol 23(5):505–509. doi:10.1002/ana.410230513
Moore DF, Altarescu G, Barker WC, Patronas NJ, Herscovitch P, Schiffmann R (2003) White matter lesions in Fabry disease occur in ‘prior’ selectively hypometabolic and hyperperfused brain regions. Brain Res Bull 62(3):231–240
Rost NS, Cloonan L, Kanakis AS, Fitzpatrick KM, Azzariti DR, Clarke V, Lourenco CM, Germain DP, Politei JM, Homola GA, Sommer C, Uceyler N, Sims KB (2016) Determinants of white matter hyperintensity burden in patients with Fabry disease. Neurology 86(20):1880–1886. doi:10.1212/WNL.0000000000002673
Hashemi RH, Bradley WG Jr, Chen DY, Jordan JE, Queralt JA, Cheng AE, Henrie JN (1995) Suspected multiple sclerosis: MR imaging with a thin-section fast FLAIR pulse sequence. Radiology 196(2):505–510. doi:10.1148/radiology.196.2.7617868
Horowitz AL, Kaplan RD, Grewe G, White RT, Salberg LM (1989) The ovoid lesion: a new MR observation in patients with multiple sclerosis. AJNR Am J Neuroradiol 10(2):303–305
Becker J, Rolfs A, Karabul N, Berlit P, Kraemer M (2016) D313Y mutation in the differential diagnosis of white matter lesions: experiences from a multiple sclerosis outpatient clinic. Mult Scler. doi:10.1177/1352458516638747
Gregoire SM, Brown MM, Collas DM, Jacob P, Lachmann RH, Werring DJ (2009) Posterior circulation strokes without systemic involvement as the presenting feature of Fabry disease. J Neurol Neurosurg Psychiatry 80(12):1414–1416. doi:10.1136/jnnp.2008.158790
Lehmann HC, Hengge UR, Alswede L, Saleh A, von Geldern G, Hartung HP, Ruzicka T, Hemmer B (2006) A 32-year-old man with relapsing-progressive brainstem symptoms. Lancet Neurol 5(1):97–102. doi:10.1016/S1474-4422(05)70287-8
Saip S, Uluduz D, Erkol G (2007) Fabry disease mimicking multiple sclerosis. Clin Neurol Neurosurg 109(4):361–363. doi:10.1016/j.clineuro.2006.12.006
Invernizzi P, Bonometti MA, Turri E, Benedetti MD, Salviati A (2008) A case of Fabry disease with central nervous system (CNS) demyelinating lesions: a double trouble? Mult Scler 14(7):1003–1006. doi:10.1177/1352458508092355
Shribman SE, Shah AR, Werring DJ, Cockerell OC (2015) Fabry disease mimicking multiple sclerosis: lessons from two case reports. Mult Scler Relat Disord 4(2):170–175. doi:10.1016/j.msard.2015.01.001
Albrecht J, Dellani PR, Muller MJ, Schermuly I, Beck M, Stoeter P, Gerhard A, Fellgiebel A (2007) Voxel based analyses of diffusion tensor imaging in Fabry disease. J Neurol Neurosurg Psychiatry 78(9):964–969. doi:10.1136/jnnp.2006.112987
Fellgiebel A, Mazanek M, Whybra C, Beck M, Hartung R, Muller KM, Scheurich A, Dellani PR, Stoeter P, Muller MJ (2006) Pattern of microstructural brain tissue alterations in Fabry disease: a diffusion-tensor imaging study. J Neurol 253(6):780–787. doi:10.1007/s00415-006-0118-y
Paavilainen T, Lepomaki V, Saunavaara J, Borra R, Nuutila P, Kantola I, Parkkola R (2013) Diffusion tensor imaging and brain volumetry in Fabry disease patients. Neuroradiology 55(5):551–558. doi:10.1007/s00234-012-1131-8
Underhill HR, Golden-Grant K, Garrett LT, Uhrich S, Zielinski BA, Scott CR (2015) Detecting the effects of Fabry disease in the adult human brain with diffusion tensor imaging and fast bound-pool fraction imaging. J Magn Reson Imaging 42(6):1611–1622. doi:10.1002/jmri.24952
Simon JH, Li D, Traboulsee A, Coyle PK, Arnold DL, Barkhof F, Frank JA, Grossman R, Paty DW, Radue EW, Wolinsky JS (2006) Standardized MR imaging protocol for multiple sclerosis: consortium of MS centers consensus guidelines. AJNR Am J Neuroradiol 27(2):455–461
Traboulsee A, Li DK (2008) Conventional MR imaging. Neuroimaging Clin N Am 18(4):651–673 . doi:10.1016/j.nic.2008.07.001x
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50(1):121–127
Hernández V, Morris Z, Dickie DA, Royle NA, Munoz Maniega S, Aribisala BS, Bastin ME, Deary IJ, Wardlaw JM (2012) Close correlation between quantitative and qualitative assessments of white matter lesions. Neuroepidemiology 40(1):13–22
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AP has received reimbursement for attending symposiums, honorariums for speaking, funds for research and fees for consulting from Shire, Genzyme and Amicus companies.
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ET and AP share senior authorship.
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Cocozza, S., Olivo, G., Riccio, E. et al. Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis. Neuroradiology 59, 563–570 (2017). https://doi.org/10.1007/s00234-017-1829-8
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DOI: https://doi.org/10.1007/s00234-017-1829-8