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Dolichoectasia: a brain arterial disease with an elusive treatment

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Abstract

Introduction

Dolichoectasia is a form of brain large artery disease associated with a high risk of mortality and morbidity. Progressive enlargement of arterial size is a predictor of mortality, but there are no specific treatments for arresting or slowing down dilatation. Additionally, dilated brain arteries can cause flow stagnation, which can trigger thrombosis and cause stroke. Pathology and genetic studies indicate a possible role for increased matrix metalloproteinase activation in arterial dilatation and thus in the pathophysiology of dolichoectasia. Therefore, therapeutic interventions aimed at slowing down arterial dilatation and preventing thrombosis could hypothetically play a role in treating patients with dolichoectasia.

Methods

We present four patients with dolichoectasia that exemplify therapeutic challenges worth discussing in the context of the current literature. Two patients were treated off-label with doxycycline (based on its antiMMP properties) and with apixaban, one patient was put on warfarin and later switched to aspirin, and the fourth patient underwent endovascular treatment.

Results

We report four cases, all men 50 years or older. Of the two patients treated with doxycycline, we noted a slowdown of the basilar artery (BA) growth, but the BA continued to grow in the other patient. Of the two patients who received apixaban, none had a subsequent stroke in 5 and 4 years of follow-up, respectively. One patient was admitted with a fatal BA thrombosis and rupture, and pathological examination of the brain arteries demonstrated advanced arterial wall degeneration but no atherosclerosis.

Discussion

These cases exemplify the challenges of treating people with dolichoectasia and highlight the need for better evidence regarding the best possible treatment for this population.

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References

  1. Lou M, Caplan LR (2010) Vertebrobasilar dilatative arteriopathy (dolichoectasia). Ann N Y Acad Sci 1184:121–133. https://doi.org/10.1111/j.1749-6632.2009.05114.x

    Article  PubMed  Google Scholar 

  2. Gutierrez J, Sacco RL, Wright CB (2011) Dolichoectasia-an evolving arterial disease. Nat Rev Neurol 7(1):41–50. https://doi.org/10.1038/nrneurol.2010.181

    Article  PubMed  Google Scholar 

  3. Gutierrez J, Bagci A, Gardener H, Rundek T, Ekind MS, Alperin N, Sacco RL, Wright CB (2014) Dolichoectasia diagnostic methods in a multi-ethnic, stroke-free cohort: results from the northern Manhattan study. J Neuroimaging 24(3):226–231. https://doi.org/10.1111/j.1552-6569.2012.00781.x

    Article  PubMed  Google Scholar 

  4. Del Brutto VJ, Gutierrez J, Goryawala MZ, Sacco RL, Rundek T, Romano JG (2021) Prevalence and clinical correlates of intracranial dolichoectasia in individuals with ischemic stroke. Stroke 52(7):2311–2318. https://doi.org/10.1161/STROKEAHA.120.032225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Caplan LR (2005) Dilatative arteriopathy (dolichoectasia): What is known and not known. Ann Neurol 57(4):469–471. https://doi.org/10.1002/ana.20447

    Article  PubMed  Google Scholar 

  6. Roth W, Morgello S, Goldman J, Mohr JP, Elkind MS, Marshall RS, Gutierrez J (2017) histopathological differences between the anterior and posterior brain arteries as a function of aging. Stroke. https://doi.org/10.1161/strokeaha.116.015630

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pico F, Jacob MP, Labreuche J, Soufir N, Touboul PJ, Benessiano J, Cambien F, Grandchamp B, Michel JB, Amarenco P (2010) Matrix metalloproteinase-3 and intracranial arterial dolichoectasia. Ann Neurol 67(4):508–515. https://doi.org/10.1002/ana.21922

    Article  CAS  PubMed  Google Scholar 

  8. Gutierrez J, Goldman J, Honig LS, Elkind MSV, Morgello S, Marshall RS (2014) Determinants of cerebrovascular remodeling: Do large brain arteries accommodate stenosis? Atherosclerosis 235(2):371–379. https://doi.org/10.1016/j.atherosclerosis.2014.05.925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gutierrez J, Honig L, Elkind MS, Mohr JP, Goldman J, Dwork AJ, Morgello S, Marshall RS (2016) Brain arterial aging and its relationship to Alzheimer dementia. Neurology 86(16):1507–1515. https://doi.org/10.1212/WNL.0000000000002590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Passero S, Filosomi G (1998) Posterior circulation infarcts in patients with vertebrobasilar dolichoectasia. Stroke 29(3):653–659. https://doi.org/10.1161/01.str.29.3.653

    Article  CAS  PubMed  Google Scholar 

  11. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D, Kamel H, Kernan WN, Kittner SJ, Leira EC, Lennon O, Meschia JF, Nguyen TN, Pollak PM, Santangeli P, Sharrief AZ, Smith SC Jr, Turan TN, Williams LS (2021) 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke 52(7):e364–e467. https://doi.org/10.1161/STR.0000000000000375

    Article  PubMed  Google Scholar 

  12. Shapiro SD, Goldman J, Morgello S, Honig L, Elkind MSV, Marshall RS, Mohr JP, Gutierrez J (2018) Pathological correlates of brain arterial calcifications. Cardiovasc Pathol 38:7–13. https://doi.org/10.1016/j.carpath.2018.09.003

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mizutani T, Miki Y, Kojima H, Suzuki H (1999) Proposed classification of nonatherosclerotic cerebral fusiform and dissecting aneurysms. Neurosurgery. 45(2):253–9 (discussion 9-60)

    Article  CAS  Google Scholar 

  14. Nakatomi H, Segawa H, Kurata A, Shiokawa Y, Nagata K, Kamiyama H, Ueki K, Kirino T (2000) Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms: insight on the mechanism of growth. Stroke 31(4):896–900

    Article  CAS  Google Scholar 

  15. Gutierrez J, Cheung K, Bagci A, Rundek T, Alperin N, Sacco RL, Wright CB, Elkind MS (2015) Brain arterial diameters as a risk factor for vascular events. J Am Heart Assoc 4(8):e002289. https://doi.org/10.1161/JAHA.115.002289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wolters FJ, Rinkel GJ, Vergouwen MD (2013) Clinical course and treatment of vertebrobasilar dolichoectasia: a systematic review of the literature. Neurol Res 35(2):131–137. https://doi.org/10.1179/1743132812Y.0000000149

    Article  PubMed  Google Scholar 

  17. Passero SG, Rossi S (2008) Natural history of vertebrobasilar dolichoectasia. Neurology 70(1):66–72. https://doi.org/10.1212/01.wnl.0000286947.89193.f3

    Article  PubMed  Google Scholar 

  18. Chen Z, Zhang S, Dai Z, Cheng X, Wu M, Dai Q, Liu X, Xu G (2019) Recurrent risk of ischemic stroke due to vertebrobasilar dolichoectasia. BMC Neurol 19(1).https://doi.org/10.1186/s12883-019-1400-9

  19. Wolfe T, Ubogu EE, Fernandes-Filho JA, Zaidat OO (2008) Predictors of clinical outcome and mortality in vertebrobasilar dolichoectasia diagnosed by magnetic resonance angiography. J Stroke Cerebrovasc Dis 17(6):388–393. https://doi.org/10.1016/j.jstrokecerebrovasdis.2008.06.006

    Article  PubMed  Google Scholar 

  20. Drake CG, Peerless SJ (1997) Giant fusiform intracranial aneurysms: review of 120 patients treated surgically from 1965 to 1992. J Neurosurg 87(2):141–162. https://doi.org/10.3171/jns.1997.87.2.0141

    Article  CAS  PubMed  Google Scholar 

  21. Telles JPM, Solla DJF, Yamaki VN, Rabelo NN, Da Silva SA, Caldas JGP, Teixeira MJ, Junior JR, Figueiredo EG (2021) Comparison of surgical and endovascular treatments for fusiform intracranial aneurysms: systematic review and individual patient data meta-analysis. Neurosurg Rev 44(5):2405–2414. https://doi.org/10.1007/s10143-020-01440-x

    Article  PubMed  Google Scholar 

  22. Anson JA, Lawton MT, Spetzler RF (1996) Characteristics and surgical treatment of dolichoectatic and fusiform aneurysms. J Neurosurg 84(2):185–193. https://doi.org/10.3171/jns.1996.84.2.0185

    Article  CAS  PubMed  Google Scholar 

  23. Bhogal P, Pérez MA, Ganslandt O, Bäzner H, Henkes H, Fischer S (2017) Treatment of posterior circulation non-saccular aneurysms with flow diverters: a single-center experience and review of 56 patients. J Neurointerv Surg 9(5):471–481. https://doi.org/10.1136/neurintsurg-2016-012781

    Article  CAS  PubMed  Google Scholar 

  24. Raphaeli G, Collignon L, Witte OD, Lubicz B (2011) Endovascular treatment of posterior circulation fusiform aneurysms: single-center experience in 31 patients. Neurosurgery 69(2):274–283. https://doi.org/10.1227/neu.0b013e31821723f2

    Article  PubMed  Google Scholar 

  25. Rosenberg GA (2009) Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 8(2):205–216. https://doi.org/10.1016/S1474-4422(09)70016-X

    Article  CAS  PubMed  Google Scholar 

  26. Ye S (2006) Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res 69(3):636–645. https://doi.org/10.1016/j.cardiores.2005.07.015

    Article  CAS  PubMed  Google Scholar 

  27. Gutierrez J, Menshawy K, Goldman J, Dwork AJ, Elkind MS, Marshall RS, Morgello S (2016) Metalloproteinases and brain arterial remodeling among individuals with and those without HIV infection. J Infect Dis 214(9):1329–1335. https://doi.org/10.1093/infdis/jiw385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Arslan Y, Arslan İB, Pekçevik Y, Şener U, Köse Ş, Zorlu Y (2016) Matrix metalloproteinase levels in cervical and intracranial carotid dolichoarteriopathies. J Stroke Cerebrovasc Dis 25(9):2153–2158. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.028

    Article  PubMed  Google Scholar 

  29. Griffin MO, Fricovsky E, Ceballos G, Villarreal F (2010) Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol 299(3):C539-48. https://doi.org/10.1152/ajpcell.00047.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Peterson JT (2004) Matrix metalloproteinase inhibitor development and the remodeling of drug discovery. Heart Fail Rev 9(1):63–79. https://doi.org/10.1023/B:HREV.0000011395.11179.af

    Article  CAS  PubMed  Google Scholar 

  31. Baxter BT, Pearce WH, Waltke EA, Littooy FN, Hallett JW Jr, Kent KC, Upchurch GR Jr, Chaikof EL, Mills JL, Fleckten B, Longo GM, Lee JK, Thompson RW (2002) Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study. J Vasc Surg 36(1):1–12. https://doi.org/10.1067/mva.2002.125018

    Article  PubMed  Google Scholar 

  32. Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA (1973) Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther 14(5):852–861. https://doi.org/10.1002/cpt1973145852

    Article  CAS  PubMed  Google Scholar 

  33. Baxter BT, Matsumura J, Curci JA, McBride R, Larson L, Blackwelder W, Lam D, Wijesinha M, Terrin M, Investigators NTC (2020) Effect of doxycycline on aneurysm growth among patients with small infrarenal abdominal aortic aneurysms: a randomized clinical trial. JAMA 323(20):2029–2038. https://doi.org/10.1001/jama.2020.5230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Naunheim MR, Walcott BP, Nahed BV, MacRae CA, Levinson JR, Ogilvy CS (2011) Arterial tortuosity syndrome with multiple intracranial aneurysms: a case report. Arch Neurol 68(3):369–71. https://doi.org/10.1001/archneurol.2011.29

    Article  PubMed  Google Scholar 

  35. Groenink M, den Hartog AW, Franken R, Radonic T, de Waard V, Timmermans J, Scholte AJ, van den Berg MP, Spijkerboer AM, Marquering HA, Zwinderman AH, Mulder BJ (2013) Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. Eur Heart J 34(45):3491–3500. https://doi.org/10.1093/eurheartj/eht334

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Johanna Etienne Krankenhaus, Neuss, Germany

    Edgar R. Lopez-Navarro

  2. Department of Neurology, Columbia University Irving Medical Center, 710 W 168th Street, 6th Floor, Suite 639, New York, NY, 10032, USA

    Soojin Park, Joshua Z. Willey & Jose Gutierrez

  3. Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA

    Soojin Park

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  1. Edgar R. Lopez-Navarro
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Correspondence to Jose Gutierrez.

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Conflict of interest

ERLN and JZW declare no competing interests.

SJ declares no conflict of interest related to this work. NIH grants (R21NS113055) unrelated to this work and is associate editor for Neurocritical Care for which she receives a stipend.

JG declares funding from NIH related to this work (R01AG057709 and 5TR01AG057709) and up-to-date royalties regarding intracranial atherosclerotic disease.

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Lopez-Navarro, E.R., Park, S., Willey, J.Z. et al. Dolichoectasia: a brain arterial disease with an elusive treatment. Neurol Sci 43, 4901–4908 (2022). https://doi.org/10.1007/s10072-022-06078-9

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