A Systematic Review of Neurovascular Complications in Patients with Pseudoxanthoma Elasticum

Main Article Content

Colin Domzalski
Nancy Wei
Mark Lebwohl

Keywords

pseudoxanthoma elasticum, pxe, neurovascular, tia, cva, stroke

Abstract

Background: Pseudoxanthoma elasticum (PXE) is a rare, hereditary connective tissue disorder characterized by ectopic calcification of multiple organ systems. Cardiovascular complications secondary to accelerated atherosclerosis are well-documented in published literature; however, there is a paucity of studies that reviews serious neurovascular complications including CVA(cerebral vascular accident), TIA(Transient ischemic attack), and intracranial aneurysm development in PXE patients.  


Objective: We aim to review current literature reporting cases of serious ischemic and hemorrhagic neurovascular complications in PXE patients as of September 2020 and reexamine current guidelines on anticoagulation and antiplatelet therapy in PXE patients


Methods: A search of the PubMed database limited to English language case reports using the key words “pseudoxanthoma elasticum”, “neuro*”, “cerebr*”, “CVA”, “TIA”, and “aneurysm” was performed.


Results: A total of 67 cases of cerebral disease were reported; ranging from ages 2-71 years from 12 countries. The most common neurovascular complication seen was ischemic strokes (68.7%) followed by TIAs (20.8%), intracranial aneurysms (6.0%) and lastly hemorrhagic strokes (4.5%).


Conclusions: PXE patients have a greater incidence of ischemic strokes compared to the general population. Clinicians should thus carefully weigh the benefits of anticoagulation therapy in patients with known cardiovascular disease against the risk of bleeding.

References

1. Bergen, Arthur A. B., et al. “ABCC6 And Pseudoxanthoma Elasticum.” Pflügers Archiv - European Journal of Physiology, vol. 453, no. 5, 2006, pp. 685–691., doi:10.1007/s00424-005-0039-0.

2. D'Marco L, Lima-Martínez M, Karohl C, Chacín M, Bermúdez V. Pseudoxanthoma Elasticum: An Interesting Model to Evaluate Chronic Kidney Disease-Like Vascular Damage without Renal Disease. Kidney Dis (Basel). 2020;6(2):92-97. doi:10.1159/000505026

3. Ringpfeil F, McGuigan K, Fuchsel L, et al. Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity. J Invest Dermatol.2006;126(4):782-786. doi:10.1038/sj.jid.5700115

4. Risseeuw S, Ossewaarde-van Norel J, van Buchem C, Spiering W, Imhof SM, van Leeuwen R. The extent of angioid streaks correlates with macular degeneration in pseudoxanthoma elasticum [published online ahead of print, 2020 Jul 20]. Am J Ophthalmol. 2020;S0002-9394(20)30379-2. doi:10.1016/j.ajo.2020.07.022

5. Liaqat M, Heymann WR. Anticoagulation in Patients with Pseudoxanthoma Elasticum. Skinmed. 2017;15(4):319-320. Published 2017 Aug 1.

6. Veken, Bieke Van Der, et al. “Development of Atherosclerotic Plaques in a Mouse Model of Pseudoxanthoma Elasticum.” Acta Cardiologica, vol. 69, no. 6, 2014, pp. 687–692., doi:10.1080/ac.69.6.1000012.

7. Roach, E. Steve, and Monica P. Islam. “Pseudoxanthoma Elasticum.” Neurocutaneous Syndromes Handbook of Clinical Neurology, 2015, pp. 215–221., doi:10.1016/b978-0-444-62702-5.00015-9.

8. De Vilder EYG, Cardoen S, Hosen MJ, et al. Pathogenic variants in the ABCC6 gene are associated with an increased risk for ischemic stroke. Brain Pathol. 2018;28(6):822-831. doi:10.1111/bpa.12620

9. Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association [published correction appears in Circulation. 2018 Mar 20;137(12):e493]. Circulation. 2018;137(12):e67-e492. 11

10. Lanfranconi S, Ghione I, Valcamonica G, Corti SP, Bonato S, Bresolin N. Safety and efficacy of rt-PA treatment for acute stroke in pseudoxanthoma elasticum: the first report [published online ahead of print, 2020 May 26]. J Thromb Thrombolysis. 2020;10.1007/s11239-020-02150-3. doi:10.1007/s11239-020-02150-3

11. Li Q, Guo H, Chou DW, et al. Warfarin accelerates ectopic mineralization in Abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum. Am J Pathol. 2013;182(4):1139-1150. doi:10.1016/j.ajpath.2012.12.037

12. Aralikatti AK, Lee MW, Lipton ME, Kamath GG. Visual loss due to cerebral infarcts in pseudoxanthoma elasticum. Eye (Lond). 2002;16(6):785-786. doi:10.1038/sj.eye.6700173

13. Araki Y, Yokoyama T, Sagawa N, et al. Pseudoxanthoma elasticum diagnosed 25 years after the onset of cardiovascular disease. Intern Med. 2001;40(11):1117-1120. doi:10.2169/internalmedicine.40.1117

14. Bertamino M, Severino M, Grossi A, et al. ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum. Eur J Paediatr Neurol. 2018;22(4):725-728. doi:10.1016/j.ejpn.2018.04.002

15. Bock, Andreas, and Guido Schwegler. "Intracerebral haemorrhage as first manifestation of Pseudoxanthoma elasticum." Clinical neurology and neurosurgery 110.3 (2008): 262-264.

16. Defillo A, Nussbaum ES. Intracranial aneurysm formation in siblings with pseudoxanthoma elasticum: case report. J Neurosurg Sci. 2010;54(3):105-107.

17. Del Zotto E, Ritelli M, Pezzini A, et al. Clinical, neuroradiological and molecular features of a patient affected by pseudoxhantoma elasticum associated to carotid rete mirabile: case report. Clin Neurol Neurosurg. 2012;114(6):758-761. doi:10.1016/j.clineuro.2011.12.031

18. Hirano T, Hashimoto Y, Kimura K, Uchino M. Rinsho Shinkeigaku. 1996;36(5):633-639.

19. Kumar GN, Ragi KV, Nair PS. Pseudoxanthoma elasticum with cerebrovascular accident. Indian J Dermatol Venereol Leprol. 2007;73(3):191-193. doi:10.4103/0378-6323.32746

20. Pavlovic AM, Zidverc-Trajkovic J, Milovic MM, et al. Cerebral small vessel disease in pseudoxanthoma elasticum: three cases. Can J Neurol Sci. 2005;32(1):115-118. doi:10.1017/s0317167100016991

21. Kauw F, Kranenburg G, Kappelle LJ, et al. Cerebral disease in a nationwide Dutch pseudoxanthoma elasticum cohort with a systematic review of the literature. J Neurol Sci. 2017;373:167-172. doi:10.1016/j.jns.2016.12.053

22. K.H. Neldner, Pseudoxanthoma elasticum, Clin. Dermatol. 6 (1) (1988) 1–159.

23. van den Berg JS, Hennekam RC, Cruysberg JR, et al. Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum. Cerebrovasc Dis. 2000;10(4):315-319. doi:10.1159/000016076

24. Vanakker, Olivier M., et al. “Novel Clinico‐Molecular Insights in Pseudoxanthoma Elasticum Provide an Efficient Molecular Screening Method and a Comprehensive Diagnostic Flowchart.” Wiley Online Library, John Wiley & Sons, Ltd, 21 Dec. 2007, onlinelibrary.wiley.com/doi/10.1002/humu.9514/abstract.

25. Omarjee L, Fortrat JO, Larralde A, et al. Internal Carotid Artery Hypoplasia: A New Clinical Feature in Pseudoxanthoma Elasticum. J Stroke. 2019;21(1):108-111. doi:10.5853/jos.2018.02705