Markers of connective tissue dysplasia in cervical artery dissection and its predisposing factors

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Abstract

Introduction. Cervical artery dissection (CeAD) is the most frequent cause of ischemic stroke in young adults. Arterial wall dysplasia underlies its weakness and predisposes to dissection.

Objective. To assess clinical signs of connective tissue dysplasia (CTD) in patients with CeAD using special criteria of CTD, and to evaluate predisposing factors for the CeAD development.

Materials and methods. We examined 80 patients (mean age 38,5±13,5; 49 females) with CeAD, verified by MRI/MRA and20 healthy volunteers. We estimated 48 signs of CTD included in the Villefranche diagnostic criteria for the vascular type of Ehlers–Danlos syndrome, the Ghent criteria for Marfan syndrome, the Beighton criteria of joint hypermobility and some others, as well as history of headache. Each sign was counted as present or absent, yielding the individual and mean CTD group scores.

Results. Clinical CTD signs were more frequently detected in patients with CeAD than in controls (mean score 7.9 ± 3.6 vs. 4.6 ± 2.5; p < 0.0039). Significant signs (more than 8 points) were present in 53% of patients. Regression analysis was performed to determine diagnostic-prognostic value of CTD signs. The main diagnostic criteria included history of headache (p=0.022), arterial hypotension (р=0.012), extensive bruising (р=0.011), and widened atrophic scars (р=0.019). The additional diagnostic criteria included translucent skin (р=0.034), high palate (р=0.034), predisposition to constipation (р=0.050), nasal bleeding (р=0.043), and blue sclera (р=0.050). In the presence of the 4 main and 2 additional criteria, the predictive value of dissection according to regression model is 75–77% (ROC analysis: AUC 0.90, 95% CI, 0.84–0.96). Most patients 97% had various predisposing factors of CeAD development, either isolated 47% or combined 50%.

Conclusions. The presence of the 4 main and 2 additional diagnostic criteria of CTD has a high predictive value of CeAD and can be used as its diagnostic-prognostic criteria. Dissection of the arterial wall with signs of dysplasia is provoked by various additional factors.

About the authors

Maria V. Gubanova

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Lyudmila A. Kalashnikova

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Larisa A. Dobrynina

Research Center of Neurology

Author for correspondence.
Email: dobrla@mail.ru
ORCID iD: 0000-0001-9929-2725

D. Sci. (Med.), Head, 3rd Neurology department

Russian Federation, Moscow

Кamila V. Shamtieva

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Aleksandr B. Berdalin

M.V. Lomonosov Moscow State University

Email: dobrla@mail.ru
Russian Federation, Moscow

References

  1. Kalashnikova L.A., Dobrynina L.A. Dissektsiya arteriy golovnogo mozga: ishemicheskiy insul't i drugie klinicheskie proyavleniya [Cervical artery dissection: ischemic stroke and other clinical manifestations] Moscow: VAKO, 2013. 208 p. (In Russ.).
  2. Debette S., Simonetti B.G., Schilling S. et al. Familial occurrence and heritable connective tissue disorders in cervical artery dissection. Neurology 2014; 83: 2023–2031. doi: 10.1212/WNL.0000000000001027. PMID: 25355833.
  3. Robertson J.J., Koyfman A. Cervical artery dissection: a review. J Emerg Med 2016; 51(5): 508-518. doi: 10.1016/j.jemermed.2015.10.044. PMID: 27634674.
  4. Kissela B.M., Khoury J.C., Alwell K. et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology 2012; 79(17): 1781-1787. doi: 10.1212/WNL.0b013e318270401d. PMID: 23054237.
  5. Amarenco P., Bogousslavsky J., Caplan L.R. et al. The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping). Cerebrovasc Dis 2013; 36(1): 1-5. doi: 10.1159/000352050. PMID: 23899749.
  6. Debette S., Leys D. Cervical-artery dissections: predisposing factors, diagnosis, and outcome. Lancet Neurol 2009; 8:668–78. doi: 10.1016/S1474-4422(09)70084-5. PMID: 19539238.
  7. Dobrynina L.A., Kalashnikova L.A., Pavlova L.N. [Ischemic stroke in young age]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011; 111(3): 4-8. PMID: 21423109. (In Russ.).
  8. Kalashnikova L.A., Dobrynina L.A., Dreval' M.V. et al. [Neck pain and headache as the only manifestation of cervical artery dissection]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015; 115(3-1): 9-16. PMID: 21423109. doi: 10.17116/jnevro2015115319-16. (In Russ.).
  9. Kalashnikova L.A., Dobrynina L.A. [Clinical manifestations of internal carotid artery dissection]. Annals of Clinical and Experimental Neurology. 2014; 8(1): 56-60. (In Russ.).
  10. Lee V.H., Brown R.D., Mandrekar J.N., Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006; 67 (10):1809–1812. doi: 10.1212/01.wnl.0000244486.30455.71. PMID: 17130413.
  11. Southerland A.M, Meschia J.F., Worrall B.B. Shared associations of nonatherosclerotic, large vessel, cerebrovascular arteriopathies: considering intracranial aneurysms, cervical artery dissection, moya-moya disease and fibromuscular dysplasia. Curr Opin Neurol 2013, 26:13–28 doi: 10.1097/WCO.0b013e32835c607f. PMID: 23302803.
  12. Débette S. Pathophysiology and risk factors for cervical artery dissection: what have we learned from large hospital-based cohorts? Curr Opin Neurol 2014; 1: 20–28. doi: 10.1097/WCO.0000000000000056. PMID: 24300790.
  13. Hausser I., Muller U., Engelter S. et al. Different types of connective tissue alterations associated with cervical artery dissections. Acta Neuropathol 2004; 107(6): 509–514. doi: 10.1007/s00401-004-0839-x. PMID: 15067552.
  14. Martin J.J., Hausser I., Lyrer P. et al. Familial cervical artery dissections: clinical, morphologic, and genetic studies. Stroke 2006; 37(12): 2924-9. doi: 10.1161/01.STR.0000248916.52976.49. PMID: 17053184.
  15. Kalashnikova L.A., Gulevskaya T.S., Anufriev P.L. et al. [Ischemic stroke in young age due to dissection of intracranial carotid artery and its branches (clinical and morphological study)]. Annals of Clinical and Experimental Neurology. 2009; 3 (1): 18-24. (In Russ.).
  16. Kalashnikova L.A., Chaykovskaya R.P., Dobrynina L.A. et al. [Internal carotid artery dissection as a cause of severe ischemic stroke with lethal outcome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2015;115(12- 2):19-25. doi: 10.17116/jnevro201511512219-25. (In Russ.).
  17. Volker W., Besselmann M., Dittrich R., et al. Generalized arteriopathy in patients with cervical artery dissection. Neurology 2005; 64(9): 1508–1513. doi: 10.1212/01.WNL.0000159739.24607.98. PMID: 15883309.
  18. Schievink W.I., Wijdicks E.F., Michels V.V. et al. Heritable connective tissue disorders in cervical artery dissections: a prospective study. Neurology 1998; 50: 1166–1169. PMID: 9566419.doi: 10.1212/WNL.50.4.1166
  19. Grond-Ginsbach C., Debette S. The association of connective tissue disorders with cervical artery dissections. Curr Mol Med 2009; 9(2): 210–214. PMID: 19275629.doi: 10.2174/156652409787581547
  20. Kalashnikova L.A., Sakharova A.V., Dobrynina L.A. et al. [Ultrastructural changes of skin arteries in patients with spontaneous cerebal artery dissection]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011; 111:7: 54-60. PMID: 21947073. (In Russ.).
  21. Anderson R.M., Schechter MM. A case of spontaneous dissecting aneurysm of the internal carotid artery. J Neurol Neurosurg Psychiatry 1959; 22:195–201. PMID: 13793447.doi: 10.1136/jnnp.22.3.195
  22. Brandt T., Orberk E., Weber R. et al. Pathogenesis of cervical artery dissections: Association with connective tissue abnormalities. Neurology 2001; 57: 24–30. PMID: 11445623.doi: 10.1212/WNL.57.1.24
  23. Grond-Ginsbach C., Chen B., Krawczak M. et al. Genetic Imbalance in Patients with Cervical Artery Dissection. Curr Genomics 2017; 18(2): 206-213. doi: 10.2174/1389202917666160805152627. PMID: 28367076.
  24. Kalashnikova L.A., Sakharova A.V., Dobrynina L.A. et al. [Mitochondrial arteriopathy as a cause of spontaneous dissection of cerebral arteries]. Zh Nevrol Psikhiatr Im SS Korsakova. 2010; 110 (4-2): 3-11. PMID: 20738020. (In Russ.).
  25. Kalashnikova L.A., Dobrynina L.A., Sakharova A.V. et al. [The A3243G mitochondrial DNA mutation in cerebral artery dissections]. Zh Nevrol Psikhiatr Im SS Korsakova. 2012; 112(1): 84-89. PMID: 22678682. (In Russ.).
  26. Giossi A., Ritelli M., Costa P. et al. Connective tissue anomalies in patients with spontaneous cervical artery dissection. Neurology 2014; 83(22): 2032-7. doi: 10.1212/WNL.0000000000001030. PMID: 25355826.
  27. Dittrich R., Heidbreder A., Rohsbach D. et al. Connective tissue and vascular phenotype in patients with cervical artery dissection. Neurology 2007; 68(24):2120-2124. PMID: 17562832.doi: 10.1212/01.wnl.0000264892.92538.a9
  28. Beighton P., De Paepe A., Steinmann B. et al. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 1998; 77(1): 31-37. PMID: 9557891.
  29. Kadurina T.I. Nasledstvennye kollagenopatii [Hereditary collagenopathies]. Saint-Petersburg: Nevskiy Dialekt, 2000. 270 p. (in Russ.).
  30. Loeys B.L., Dietz H.C., Braverman A.C. et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010; 47(7): 476-85. doi: 10.1136/jmg.2009.072785. PMID: 20591885.
  31. Zemtsovskiy E.V. Soedinitel'notkannye displazii serdtsa [Connective tissue dysplasia of the heart]. Saint-Petersburg: TOO «Politekst-Nord-Vest», 2000. 115p. (in Russ.).
  32. Grahame R., Bird H.A., Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J Rheumatol 2000; 27: 1777–1779. PMID: 10914867
  33. Gubanova M.V., Dobrynina L.A., Kalashnikova L.A. [The vascular type of Ehlers–Danlos syndrome]. Annals of Clinical and Experimental Neurology. 2016; 10(4): 45-51.
  34. Guillon B, Berthet K, Benslamia L, et al. Infection and the risk of spontaneous cervical artery dissection: a case-control study. Stroke 2003; 34(7): 79–81. doi: 10.1161/01.STR.0000078309.56307.5C. PMID: 12805497.
  35. Engelter S.T., Grond-Ginsbach C., Metso T.M. et al. Cervical artery dissection: trauma and other potential mechanical trigger events. Neurology 2013; 80(21): 1950-7. doi: 10.1212/WNL.0b013e318293e2eb. PMID: 23635964.

Copyright (c) 2017 Gubanova M.V., Kalashnikova L.А., Dobrynina L.А., Shamtieva К.V., Berdalin А.B.

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