Multiple Ischemic Strokes Associated with Pulmonary Embolism Revealing Occult Pulmonary Adenocarcinoma: About Two (2) Cases and Review of the Literature
A rare clinical phenomenon has been reported. Patients with pulmonary adenocarcinoma consulted the neurology department due to multiple initial symptoms of cerebral ischaemia. Examination of each patient revealed pulmonary embolism, the underlying cause being a malignant lung tumour. Multiple ischaemic strokes (IS) associated with pulmonary embolism (PE) rarely indicate pulmonary adenocarcinoma. The concomitant presence of IS, PE and pulmonary adenocarcinoma increases the risk of complications and mortality. We report two (2) cases of diagnostic cascades marked by the discovery of multiple ischaemic strokes, followed by pulmonary embolisms and finally lung adenocarcinoma. Our patients, aged 58 and 55, were both smokers. Initially, the patients presented with focal neurological deficits symptomatic of multiple ischaemic strokes. The aetiological assessment revealed a state of hypercoagulability, which led to the discovery of pulmonary embolisms and lung adenocarcinoma. In terms of treatment, all of our patients received antiplatelet therapy and low molecular weight heparin. The outcome was marked by recurrent ischaemic strokes followed by the death of the patients from general complications.
References
[1]
Aloizou, A., Palaiodimou, L., Aloizou, D., Dardiotis, E., Gold, R., Tsivgoulis, G. et al. (2023). Acute Reperfusion Treatment and Secondary Prevention of Cancer-Related Stroke: Comprehensive Overview and Proposal of Clinical Algorithm. Therapeutic Advances in Neurological Disorders, 16, 1-11. https://doi.org/10.1177/17562864231180717
[2]
Baker, R., Bakali, Z., Crocker, J. S., Mowla, A., Smith, M., Grossman, A. et al. (2024). Tumor Embolic Stroke: The Importance of Pathological Assessment of Clots after Thrombectomy. Journal of Clinical Medicine, 13, Article 1834. https://doi.org/10.3390/jcm13071834
[3]
Bravo Anguiano, Y., Echavarría Iñiguez, A., Madrigal Lkhou, E., & Muñoz Martín, A. (2023). Ictus asociado a cáncer: estudio de prevalencia y factores predictores entre pacientes con ictus isquémico. Revista de Neurología, 76, 189-195. https://doi.org/10.33588/rn.7606.2022414
[4]
Brenner, B., Bikdeli, B., Tzoran, I., Madridano, O., López-Reyes, R., Suriñach, J. M. et al. (2018). Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism. The American Journal of Medicine, 131, 1095-1103. https://doi.org/10.1016/j.amjmed.2018.04.037
[5]
Cestari, D. M., Weine, D. M., Panageas, K. S., Segal, A. Z., & DeAngelis, L. M. (2004). Stroke in Patients with Cancer: Incidence and Etiology. Neurology, 62, 2025-2030. https://doi.org/10.1212/01.wnl.0000129912.56486.2b
[6]
Chi, X., Zhao, R., Pei, H., Xing, A., Hu, S., Chen, J. et al. (2020). Diffusion-Weighted Imaging‐documented Bilateral Small Embolic Stroke Involving Multiple Vascular Territories May Indicate Occult Cancer: A Retrospective Case Series and a Brief Review of the Literature. Aging Medicine, 3, 56-62. https://doi.org/10.1002/agm2.12105
[7]
Choueiri, T. K., Schutz, F. A. B., Je, Y., Rosenberg, J. E., & Bellmunt, J. (2010). Risk of Arterial Thromboembolic Events with Sunitinib and Sorafenib: A Systematic Review and Meta-Analysis of Clinical Trials. Journal of Clinical Oncology, 28, 2280-2285. https://doi.org/10.1200/jco.2009.27.2757
[8]
Cocho, D., Gendre, J., Boltes, A., Espinosa, J., Ricciardi, A. C., Pons, J. et al. (2015). Predictors of Occult Cancer in Acute Ischemic Stroke Patients. JournalofStrokeandCerebrovascularDiseases,24, 1324-1328. https://doi.org/10.1016/j.jstrokecerebrovasdis.2015.02.006
[9]
Dardiotis, E., Aloizou, A., Markoula, S., Siokas, V., Tsarouhas, K., Tzanakakis, G. et al. (2019). Cancer-Associated Stroke: Pathophysiology, Detection and Management (Review). InternationalJournalofOncology,54, 779-796. https://doi.org/10.3892/ijo.2019.4669
[10]
Geraldes, T., Pereira, L., Guarda, C., Grunho, M., Ribeiro, A. C., Coimbra, J. et al. (2017). Seguridad y efectividad del rtPA en el ictus isquémico agudo en pacientes con cáncer activo: Estudio de casos y controles. Revista de Neurología, 65, 13-18. https://doi.org/10.33588/rn.6501.2016510
[11]
Ghabaee, M., Zandieh, A., Mohebbi, S., Fakhri, M., Sadeghian, H., Divani, F. et al. (2014). Predictive Ability of C-Reactive Protein for Early Mortality after Ischemic Stroke: Comparison with NIHSS Score. Acta Neurologica Belgica, 114, 41-45. https://doi.org/10.1007/s13760-013-0238-y
[12]
Gomes, M., & Khorana, A. (2014). Risk Assessment for Thrombosis in Cancer. Seminars in Thrombosis and Hemostasis, 40, 319-324. https://doi.org/10.1055/s-0034-1370770
[13]
Gon, Y., Sakaguchi, M., Takasugi, J., Kawano, T., Kanki, H., Watanabe, A. et al. (2017). Plasma D-Dimer Levels and Ischaemic Lesions in Multiple Vascular Regions Can Predict Occult Cancer in Patients with Cryptogenic Stroke. European Journal of Neurology, 24, 503-508. https://doi.org/10.1111/ene.13234
[14]
Graber, J. J., Nayak, L., & DeAngelis, L. M. (2012). Use of Recombinant Tissue Plasminogen Activator in Cancer Patients with Acute Stroke. Journal of Neuro-Oncology, 107, 571-573. https://doi.org/10.1007/s11060-011-0780-5
[15]
Grilz, E., Königsbrügge, O., Posch, F., Schmidinger, M., Pirker, R., Lang, I. M. et al. (2018). Frequency, Risk Factors, and Impact on Mortality of Arterial Thromboembolism in Patients with Cancer. Haematologica, 103, 1549-1556. https://doi.org/10.3324/haematol.2018.192419
[16]
Guo, L., Wang, L., & Liu, W. (2020). Ability of the Number of Territories Involved on DWI-MRI to Predict Occult Systemic Malignancy in Cryptogenic Stroke Patients. Journal of Stroke and Cerebrovascular Diseases, 29, Article ID: 104823. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104823
[17]
Jin, Y., Ye, Y., Jin, Y., Zhu, X., Sha, M., Liu, R. et al. (2022). Risk Factors and Impact on Outcomes of Lung Cancer Patients Concurrent with Deep Vein Thrombosis. Cancer Control, 29, 1-8. https://doi.org/10.1177/10732748221145074
[18]
Kassubek, R., Bullinger, L., Kassubek, J., Dreyhaupt, J., Ludolph, A. C., Althaus, K. et al. (2017). Identifying Ischemic Stroke Associated with Cancer: A Multiple Model Derived from a Case-Control Analysis. Journal of Neurology, 264, 781-791. https://doi.org/10.1007/s00415-017-8432-0
[19]
Kim, S. J., Park, J. H., Lee, M., Park, Y. G., Ahn, M., & Bang, O. Y. (2012). Clues to Occult Cancer in Patients with Ischemic Stroke. PLOS ONE, 7, e44959. https://doi.org/10.1371/journal.pone.0044959
[20]
Lee, A. Y. Y., Levine, M. N., Baker, R. I., Bowden, C., Kakkar, A. K., Prins, M. et al. (2003). Low-Molecular-Weight Heparin versus a Coumarin for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer. New England Journal of Medicine, 349, 146-153. https://doi.org/10.1056/nejmoa025313
[21]
Leentjens, J., Chornenki, N. L. J., Spiegelenberg, J., Ly, V., Dowlatshahi, D., & Siegal, D. M. (2023). A Scoping Review Protocol on Diagnostic Strategies to Detect Occult Malignancies in Individuals with Ischemic Stroke. PLOS ONE, 18, e0289048. https://doi.org/10.1371/journal.pone.0289048
[22]
Lyman, G. H., Khorana, A. A., Kuderer, N. M., Lee, A. Y., Arcelus, J. I., Balaban, E. P. et al. (2013). Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology, 31, 2189-2204. https://doi.org/10.1200/jco.2013.49.1118
[23]
Mai, H., Xia, J., Wu, Y., Ke, J., Li, J., Pan, J. et al. (2015). Clinical Presentation and Imaging Characteristics of Occult Lung Cancer Associated Ischemic Stroke. Journal of Clinical Neuroscience, 22, 296-302. https://doi.org/10.1016/j.jocn.2014.05.039
[24]
Maia, R., Neves, I., Morais, A., & Queiroga, H. (2019). Venous and Lung Thromboembolism in the Context of Lung Cancer: Clinical Manifestations, Risk Factors and Prognosis. Acta Médica Portuguesa, 32, 647-653. https://doi.org/10.20344/amp.10260
[25]
Meschia, J. F., Bushnell, C., Boden-Albala, B., Braun, L. T., Bravata, D. M., Chaturvedi, S. et al. (2014). Guidelines for the Primary Prevention of Stroke. Stroke, 45, 3754-3832. https://doi.org/10.1161/str.0000000000000046
[26]
Navi, B. B., DeAngelis, L. M., & Segal, A. Z. (2007). Multifocal Strokes as the Presentation of Occult Lung Cancer. Journal of Neuro-Oncology, 85, 307-309. https://doi.org/10.1007/s11060-007-9419-y
[27]
Navi, B. B., Reiner, A. S., Kamel, H., Iadecola, C., Okin, P. M., Elkind, M. S. V. et al. (2017). Risk of Arterial Thromboembolism in Patients with Cancer. Journal of the American College of Cardiology, 70, 926-938. https://doi.org/10.1016/j.jacc.2017.06.047
[28]
Nezu, T., Kitano, T., Kubo, S., Uemura, J., Yamashita, S., Iwanaga, T. et al. (2018). Impact of D-Dimer Levels for Short-Term or Long-Term Outcomes in Cryptogenic Stroke Patients. Journal of Neurology, 265, 628-636. https://doi.org/10.1007/s00415-018-8742-x
[29]
Ohara, T., Farhoudi, M., Bang, O. Y., Koga, M., & Demchuk, A. M. (2020). The Emerging Value of Serum D-Dimer Measurement in the Work-Up and Management of Ischemic Stroke. International Journal of Stroke, 15, 122-131. https://doi.org/10.1177/1747493019876538
[30]
Selvik, H. A., Bjerkreim, A. T., Thomassen, L., Waje-Andreassen, U., Naess, H., & Kvistad, C. E. (2018). When to Screen Ischaemic Stroke Patients for Cancer. Cerebrovascular Diseases, 45, 42-47. https://doi.org/10.1159/000484668
[31]
Selvik, H. A., Thomassen, L., Bjerkreim, A. T., & Næss, H. (2015). Cancer-Associated Stroke: The Bergen NORSTROKE Study. Cerebrovascular Diseases Extra, 5, 107-113. https://doi.org/10.1159/000440730
[32]
Sener, U., & Keser, Z. (2022). Ischemic Stroke in Patients with Malignancy. Mayo Clinic Proceedings, 97, 2139-2144. https://doi.org/10.1016/j.mayocp.2022.09.003
[33]
Steuer, C. E., Behera, M., Kim, S., Patel, N., Chen, Z., Pillai, R. et al. (2015). Predictors and Outcomes of Venous Thromboembolism in Hospitalized Lung Cancer Patients: A Nationwide Inpatient Sample Database Analysis. Lung Cancer, 88, 80-84. https://doi.org/10.1016/j.lungcan.2015.01.022
[34]
Suzuki, T., Fujino, S., Inaba, S., Yamamura, R., Katoh, H., Noji, Y. et al. (2020). Venous Thromboembolism in Patents with Lung Cancer. Clinical and Applied Thrombosis/Hemostasis, 26, 1-5. https://doi.org/10.1177/1076029620977910
[35]
Thålin, C., Demers, M., Blomgren, B., Wong, S. L., von Arbin, M., von Heijne, A. et al. (2016). Netosis Promotes Cancer-Associated Arterial Microthrombosis Presenting as Ischemic Stroke with Troponin Elevation. Thrombosis Research, 139, 56-64. https://doi.org/10.1016/j.thromres.2016.01.009
[36]
Wang, J., Zhang, G., Zhuo, S., Wang, K., Hu, X., Zhang, H. et al. (2018). D-Dimer > 2.785 μg/ml and Multiple Infarcts ≥ 3 Vascular Territories Are Two Characteristics of Identifying Cancer-Associated Ischemic Stroke Patients. Neurological Research, 40, 948-954. https://doi.org/10.1080/01616412.2018.1504179
[37]
Włodarczyk, E., Wrona, P., Homa, T., Sobolewska, M., Wróbel, D., Rolkiewicz, D. et al. (2024). Long-Term Outcomes of Mechanical Thrombectomy in Acute Ischaemic Stroke Patients with Concomitant Malignancy. Advances in Interventional Cardiology, 20, 95-102. https://doi.org/10.5114/aic.2024.137433
[38]
Xie, W., Hsu, S., Lin, Y., Xie, L., Jin, X., Zhu, Z. et al. (2024). Malignancy-Associated Ischemic Stroke: Implications for Diagnostic and Therapeutic Workup. CNS Neuroscience & Therapeutics, 30, e14619. https://doi.org/10.1111/cns.14619
