Top

Published in:

01-11-2018 | Original Communication

Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease

Authors: Tim Godel, Anja Köhn, Nicole Muschol, Moritz Kronlage, Daniel Schwarz, Jennifer Kollmer, Sabine Heiland, Martin Bendszus, Victor-Felix Mautner, Philipp Bäumer

Published in: Journal of Neurology | Issue 11/2018

Abstract

Purpose

To examine dorsal root ganglia and the proximal nerve segments in female patients with Fabry disease by functional and morphometric magnetic resonance neurography.

Methods

In this prospective multicenter study the lumbosacral dorsal root ganglia and proximal sciatic nerve were examined in ten female patients with Fabry disease by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3–S2, permeability of dorsal root ganglia L5 and S1 and the spinal nerve L5 as well as the cross-sectional area of the proximal sciatic nerve were compared to 16 gender-matched healthy controls.

Results

Dorsal root ganglia were symmetrically enlarged by 54% (L3), 79% (L4), 60% (L5), 94% (S1), and 106% (S2) (p < 0.001). Additionally, permeability of the blood–tissue interface was decreased by 47% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglia, where the cell bodies of the primary sensory neurons are located (p < 0.001). While spinal nerve permeability showed no differences compared to healthy controls, proximal sciatic nerve cross-sectional area was mildly increased by 6% (p < 0.01).

Conclusion

Although heterozygous, Fabry females show severe enlarged dorsal root ganglia with a concomitant dysfunctional perfusion, even in patients with minor disease progression and in patients who are not considered for enzyme replacement therapy yet. Alterations in dorsal root ganglia volume and perfusion might serve as a very early in vivo marker for involvement of the peripheral nervous system in Fabry disease, even in patients with residual enzyme activity.

Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP, Fabry R (2008) Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 93(2):112–128. https://doi.org/10.1016/j.ymgme.2007.09.013 CrossRefPubMed

Schiffmann R, Warnock DG, Banikazemi M, Bultas J, Linthorst GE, Packman S, Sorensen SA, Wilcox WR, Desnick RJ (2009) Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy. Nephrol Dial Transplant 24(7):2102–2111. https://doi.org/10.1093/ndt/gfp031 CrossRefPubMedPubMedCentral

Eng CM, Fletcher J, Wilcox WR, Waldek S, Scott CR, Sillence DO, Breunig F, Charrow J, Germain DP, Nicholls K, Banikazemi M (2007) Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. J Inherit Metab Dis 30(2):184–192. https://doi.org/10.1007/s10545-007-0521-2 CrossRefPubMed

Germain DP, Charrow J, Desnick RJ, Guffon N, Kempf J, Lachmann RH, Lemay R, Linthorst GE, Packman S, Scott CR, Waldek S, Warnock DG, Weinreb NJ, Wilcox WR (2015) Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. J Med Genet 52(5):353–358. https://doi.org/10.1136/jmedgenet-2014-102797 CrossRefPubMedPubMedCentral

Hughes DA, Barba Romero MA, Hollak CE, Giugliani R, Deegan PB (2011) Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS–the Fabry outcome survey. Mol Genet Metab 103(3):207–214. https://doi.org/10.1016/j.ymgme.2011.03.022 CrossRefPubMed

Hopkin RJ, Bissler J, Banikazemi M, Clarke L, Eng CM, Germain DP, Lemay R, Tylki-Szymanska A, Wilcox WR (2008) Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry. Pediatr Res 64(5):550–555. https://doi.org/10.1203/PDR.0b013e318183f132 CrossRefPubMed

Politei JM, Bouhassira D, Germain DP, Goizet C, Guerrero-Sola A, Hilz MJ, Hutton EJ, Karaa A, Liguori R, Uceyler N, Zeltzer LK, Burlina A (2016) Pain in Fabry disease: practical recommendations for diagnosis and treatment. CNS Neurosci Ther 22(7):568–576. https://doi.org/10.1111/cns.12542 CrossRefPubMedPubMedCentral

Uceyler N, Ganendiran S, Kramer D, Sommer C (2014) Characterization of pain in fabry disease. Clin J Pain 30(10):915–920. https://doi.org/10.1097/AJP.0000000000000041 CrossRefPubMed

Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, Widmer U, Beck M, Investigators FOSE (2006) Clinical manifestations of fabry disease in children: data from the Fabry outcome survey. Acta Paediatr 95(1):86–92CrossRefPubMed

10.

Godel T, Baumer P, Pham M, Kohn A, Muschol N, Kronlage M, Kollmer J, Heiland S, Bendszus M, Mautner VF (2017) Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy. Neurology 89(12):1274–1282. https://doi.org/10.1212/WNL.0000000000004396 CrossRefPubMed

11.

Gadoth N, Sandbank U (1983) Involvement of dorsal root ganglia in Fabry’s disease. J Med Genet 20(4):309–312CrossRefPubMedPubMedCentral

12.

Godel T, Pham M, Heiland S, Bendszus M, Baumer P (2016) Human dorsal-root-ganglion perfusion measured in-vivo by MRI. Neuroimage 141:81–87. https://doi.org/10.1016/j.neuroimage.2016.07.030 CrossRefPubMed

13.

Cuenod CA, Balvay D (2013) Perfusion and vascular permeability: basic concepts and measurement in DCE-CT and DCE-MRI. Diagn Interv Imaging 94(12):1187–1204. https://doi.org/10.1016/j.diii.2013.10.010 CrossRefPubMed

14.

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. https://doi.org/10.1002/ana.410230513 CrossRefPubMed

15.

Whybra C, Kampmann C, Krummenauer F, Ries M, Mengel E, Miebach E, Baehner F, Kim K, Bajbouj M, Schwarting A, Gal A, Beck M (2004) The Mainz Severity Score Index: a new instrument for quantifying the Anderson-Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Clin Genet 65(4):299–307. https://doi.org/10.1111/j.1399-0004.2004.00219.x CrossRefPubMed

16.

Toth C, Brussee V, Cheng C, Zochodne DW (2004) Diabetes mellitus and the sensory neuron. J Neuropathol Exp Neurol 63(6):561–573CrossRefPubMed

17.

Rahman MH, Jha MK, Kim JH, Nam Y, Lee MG, Go Y, Harris RA, Park DH, Kook H, Lee IK, Suk K (2016) Pyruvate dehydrogenase kinase-mediated glycolytic metabolic shift in the dorsal root ganglion drives painful diabetic neuropathy. J Biol Chem 291(11):6011–6025. https://doi.org/10.1074/jbc.M115.699215 CrossRefPubMedPubMedCentral

18.

Choi L, Vernon J, Kopach O, Minett MS, Mills K, Clayton PT, Meert T, Wood JN (2015) The Fabry disease-associated lipid Lyso-Gb3 enhances voltage-gated calcium currents in sensory neurons and causes pain. Neurosci Lett 594:163–168. https://doi.org/10.1016/j.neulet.2015.01.084 CrossRefPubMedPubMedCentral

Title: Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease
Authors: Tim Godel
Anja Köhn
Nicole Muschol
Moritz Kronlage
Daniel Schwarz
Jennifer Kollmer
Sabine Heiland
Martin Bendszus
Victor-Felix Mautner
Philipp Bäumer
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 11/2018
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-018-9053-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2018

Effect of anti-seizure drugs on serum S100B in patients with focal seizure: a randomized controlled trial

Quality of life in a German cohort of Parkinson’s patients assessed with three different measures

The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): results from the German validation study

2017 revisions of McDonald criteria shorten the time to diagnosis of multiple sclerosis in clinically isolated syndromes

StartReact during gait initiation reveals differential control of muscle activation and inhibition in patients with corticospinal degeneration

Quantitative muscle MRI and ultrasound for facioscapulohumeral muscular dystrophy: complementary imaging biomarkers