Case and Commentary
Oct 2021
Peer-Reviewed

When Should Neuroendovascular Care for Patients With Acute Stroke Be Palliative?

Michael J. Young, MD, MPhil, Robert W. Regenhardt, MD, PhD, Leonard L. Sokol, MD, and Thabele M. Leslie-Mazwi, MD
AMA J Ethics. 2021;23(10):E783-793. doi: 10.1001/amajethics.2021.783.

Abstract

Noncurative surgeries intended to relieve suffering during serious illness or near end of life have been analyzed across palliative settings. Yet sparse guidance is available to inform clinical management decisions about whether, when, and which interventions should be offered when ischemic stroke and other neurological complications occur in patients whose survival is extended by other novel disease-modifying interventions. This case commentary examines key ethical and clinical considerations in palliative neuroendovascular care of patients with acute stroke.

Case

Mr J is a 64-year-old man with metastatic non-small cell lung cancer (NSCLC), who, while eating, abruptly developed right hemiplegia and aphasia. He had been diagnosed 10 months earlier with NSCLC; his estimated life expectancy was approximately 1 year. After a course of chemotherapy with pemetrexed and carboplatin, Mr J started pembrolizumab, an antiprogrammed death-1 immune checkpoint inhibitor offered possibly to extend his life but not as a cure for his cancer.1,2 Since diagnosis, Mr J has suffered multiple hematologic complications, including thrombosis and hemorrhage. When brought to an emergency department, he was confirmed as full code and intubated on arrival due to poor mental status and aspiration risk. Computed tomography (CT) imaging of his head and neck revealed normal brain parenchyma and occlusion of the proximal left middle cerebral artery (MCA), which supplies blood to most of the brain’s left hemisphere, including areas critical for language and right-side sensorimotor function.3 The mechanism of Mr J’s left MCA occlusion was presumed to be thromboembolism, to which he was predisposed by hypercoagulability of malignancy, pembrolizumab,4,5,6 and intracardiac hemostasis, given his known low left ventricular ejection fraction.

After discussion of acute stroke as a likely a complication of Mr J’s cancer, Mr J’s health care proxy, GG, consented to Mr J undergoing an emergent thrombectomy. This neuroendovascular procedure is a minimally invasive alternative to more invasive interventions and is the standard method for thrombectomy for acute ischemic stroke with large-vessel occlusion using an endovascular approach. Emergent thrombectomy utilizes femoral artery access to position an intracranial catheter system that permits intracerebral thrombus removal, with the goals of reestablishing blood flow to vascular territory downstream from an occlusion and enabling salvage of the ischemic penumbra to restore neurological function and prevent further impairment.7 If thrombectomy is not performed, a large proximal-vessel stroke typically occurs, potentially leading to extended brain tissue infarction, cerebral edema, and other symptoms of elevated intracranial pressure (eg, nausea, vomiting, headache, visual changes, and cranial neuropathies) that can exacerbate a patient’s impairment and suffering.8,9,10,11

Mr J’s thrombectomy was uncomplicated and resulted in rapid and successful left MCA territory reperfusion. A subsequent brain magnetic resonance (MR) image, however, revealed multifocal infarcts affecting the left and the right hemisphere of Mr J’s brain and bilateral cerebellar hemispheres, consistent with his presumed cardioembolic etiology. Mr J was unable to communicate or meaningfully interact. After neurological examination, Dr N informed GG of key findings, including bilateral infarcts expected to produce long-term bilateral weakness, disordered speech, and cognitive impairment. Dr N also explained to GG that Mr J would likely need life support, including tracheostomy, gastrostomy, and rehabilitation if he survived much longer. GG expressed understanding and asked the team to prioritize Mr J’s comfort.

Commentary

More than 1 in 10 patients who present with acute ischemic stroke are estimated to have comorbid cancer.12,13 As the median survival of patients with cancer improves with novel targeted therapies, the frequency of acute stroke and other neurologic complications in this expanding population is expected to rise.14,15,16,17,18 Malignancy can predispose patients to ischemic stroke through hypercoagulability, nonbacterial thrombotic endocarditis, systemic treatment effects, or, rarely, tumor embolism or angioinvasion.14,19 Since many patients seeking emergency evaluation of acute stroke symptoms might have comorbid cancer, clarifying ethical questions in these patients’ stroke care, especially for patients near the end of life, is key. Should clinicians try to preempt or reverse neurological dysfunction when the end of a patient’s life is near? When, to what extent, and according to whom should thrombectomy for patients with terminal illness be considered palliative? How should palliative or comfort care goals be set in order to guide appropriate neuroendovascular management decisions in the context of end-of-life care?

Palliative Thrombectomy Goals

Palliative care is defined by the World Health Organization (WHO) as “active total care of patients whose disease is not responsive to curative treatment” that aims to achieve “the best quality of life for patients and their families.”20 The Center to Advance Palliative Care (CAPC) conceives of the field as “specialized medical care for people with serious illnesses [that is] focused on providing patients with relief from the symptoms, pain, and stress of a serious illness.… The goal is to improve quality of life … and [palliative care] can be provided along with curative treatment.”21 Noncurative surgery intended to relieve symptoms in patients with serious illness or near the end of life has been analyzed in a range of contexts, particularly in surgical oncology.22,23,24,25,26,27,28,29,30,31 However, invasive neurological procedures intended to address indirect complications of terminal illnesses (eg, thrombosis due to hypercoagulability of malignancy) have received little clinical or ethical attention. Especially in clinical neuroscience, little evidence is available to guide neuroendovascular intervention decisions with patients who develop ischemic stroke or other neurological complications near the end of life.

Although in Mr J’s case, thrombectomy did not appreciably reduce disability near the end of his life, we argue that Dr N’s team’s decision to perform thrombectomy was ethically justifiable based on its concordance with Mr J’s goals that the team gleaned through conversations with GG. As highlighted by the WHO and CAPC definitions, appropriate palliative care consists not merely of pain control but of the active total care of a patient who strives for the best quality of life. To the extent that neurological symptoms, including sensorimotor dysfunction (eg, weakness and numbness), headache, delirium, aphasia, dysarthria, imbalance, gait disturbance, and cranial neuropathies can detract from quality of life, it is incumbent upon clinicians to diligently address symptoms throughout a patient’s illness.32,33,34,35 Among patients who experience acute ischemic stroke, more severe neurological impairment has been linked with significantly lower quality of life.35,36

Invasive neurological procedures intended to address indirect complications of terminal illnesses have received little clinical or ethical attention.

Neuroendovascular approaches, such as thrombectomy, are specifically intended to attenuate or prevent accumulated neurological disability37,38,39 and are supported by randomized clinical trials.40,41 The location and type of stroke and the extent of salvageable ischemic penumbra must be considered case by case in terms of whether foreseeable benefits of thrombectomy outweigh its risks. Eligibility criteria for late endovascular treatment trials for patient-subjects with acute ischemic stroke have included occlusion of proximal MCA or internal carotid artery on CT imaging or MR angiography, a score greater than 6 on the National Institutes of Health Stroke Scale up to 24 hours from the time the patient was last seen well, significant ischemic penumbra, and factors such as age, baseline modified Rankin Scale score, and life expectancy. Exclusion criteria have varied by trial and have been a source of practice variation across centers.42 Another source of complexity is that treatment decisions are typically made emergently.

Minimally invasive neuroendovascular interventions can aptly be considered palliative for a patient with limited life expectancy and should not be withheld based solely on a patient’s terminal comorbidity. Even if a patient is expected to live only a few weeks or months, any additional stroke-related neurological impairment could exacerbate their suffering near the end of life. Many patients who undergo thrombectomy experience reversal of neurologic impairment or return to functional independence due to their reduced risk of ischemic penumbra.40 Successful reperfusion of ischemic penumbra might forestall development of malignant cerebral edema, cerebral herniation, or other symptoms of increased intracranial pressure, as evidenced by lower rates of decompressive hemicraniectomy since the advent of mechanical thrombectomy.43,44,45,46 Following the ethical principles of doing good and avoiding harm47,48,49 likely requires clinicians to offer palliative thrombectomy, even when a patient has incurable comorbidity.

Decision Sharing

Patient-centered care requires assessing (1) a patient’s functional status at baseline; (2) their preferences, values, and goals, perhaps as expressed by surrogates; and (3) their prospects for recovery.50,51,52,53 Interpreting each stroke not as a discrete new disease but in the context of a patient’s broader health state, relevant comorbidities, and illness narrative can foster holistic, goal-concordant intervention and might help avoid unnecessary discontinuity or fragmentation in a patient’s care.54,55,56,57 Clinicians’ conversations with patients and surrogates should emphasize that estimates of an intervention’s effects are extrapolated from studies in which subjects were drawn not from the unique population of patients with terminal illnesses but from a general population with minimal preexisting disability. Decision sharing and informed consent require conveying uncertainty about how well the available evidence applies to a particular patient.

Equity and Evolving Therapies

Further research on the efficacy of palliative neuroendovascular care is essential, although the practical and ethical problems of conducting clinical research in patient-subjects with advanced illnesses deserve careful consideration.58,59,60,61 In one study of persons with metastatic NSCLC, newly diagnosed patients whose care plans integrated early palliative care experienced improved quality of life and mood,62 and the challenges of ensuring goal-concordant palliative care given the growth of novel interventions in the past decade are actively being studied.63,64 Equity as an organizational ethical value requires inclusion of all key stakeholders’ perspectives and goals—curative and palliative—when crafting policy and evaluating downstream implications of decisions to administer or withhold neuroendovascular interventions in individual cases.

In the case, Mr J had an acceptable health-related quality of life and—assuming his comparability to otherwise healthy patients with acute stroke—a higher chance of making a functional recovery with treatment than without it, at very low procedural risk.65 While caution must be exercised in generalizing from studies of acute stroke patients who did not have cancer, the data indicate that patients treated with thrombectomy for acute proximal MCA occlusion stroke lived the remainder of their lives with fewer neurologic impairments than if untreated and with reduced need for aggressive care and institutionalization following a sentinel cerebrovascular event.64,66,67,68

While not a factor in this Mr J’s case, do-not-intubate (DNI) orders are common and worthy of mention here. DNI orders should not independently influence stroke care decisions “unless otherwise explicitly indicated,” as emphasized by an American Heart Association/American Stroke Association statement (Class IIa recommendation).69 Generally, clinicians should express respect for patients’ right to decline interventions70 but should recognize that such interventions can have palliative roles by preventing debilitating neurological impairment and concomitant end-of-life suffering.71,72 Palliative radiotherapy, including stereotactic radiosurgery for patients with advanced cancer with brain metastases, has been pursued,73,74,75,76 as have deep brain stimulation for Parkinson disease management near the end of life77 and palliative decompressive spinal surgery for patients with metastatic spinal cord compression.78,79,80,81

Care Planning

Unlike decisions about specific palliative interventions, decisions about stroke care are typically made quickly, given the urgency of acute stroke, its impact on patients’ capacity to participate in decision making, and the exquisite time sensitivity of implementing acute stroke interventions. Although outcomes data for specific palliative neuroendovascular interventions are limited, advance care planning should include surrogate designation and discussion of minimally invasive intervention preferences, which could help safeguard value-concordant goal setting and decision sharing later.71,82

Ethically appropriate palliative neuroendovascular care for patients with acute stroke includes more than pain control and extends to management of distressing physical, spiritual, emotional, and psychosocial symptoms.83,84 Recognizing the relatively high frequency of neurological complications among patients with terminal illnesses,12,85,86,87,88,89 clinicians can implement patient-centered palliative neuroendovascular care with guidance from the ideas in the Table.

Table. Elements of Ethically Appropriate Palliative Neuroendovascular Care

 

Recognize palliative care as more than pain control; extend it to management of potentially disabling, distressing neurologic symptoms.83,84,90

Clarify the patient’s (or surrogate’s) values and goals of care.91

Avoid assumptions about a patient’s values, preferences, or goals.92

Discuss intended aims, prospective benefits, and possible risks of a neuroendovascular intervention with a patient or surrogate.

Explain the range of possible postprocedural outcomes to motivate transparency.

Discuss likely outcomes of no neuroendovascular intervention or alternative interventions.

Ensure that decision making is sensitive to patient preferences, values, and goals.

Clearly document and communicate decisions to colleagues and care team members.

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References

  1. Garon EB, Rizvi NA, Hui R, et al; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028.

    View Article PubMed Google Scholar

  2. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378(22):2078-2092.

    View Article PubMed Google Scholar

  3. Caplan LR. Caplan’s Stroke: A Clinical Approach. 5th ed. Cambridge University Press; 2016.

    Google Scholar
  4. Horio Y, Takamatsu K, Tamanoi D, et al. Trousseau’s syndrome triggered by an immune checkpoint blockade in a non-small cell lung cancer patient. Eur J Immunol. 2018;48(10):1764-1767.
    View Article PubMed Google Scholar
  5. Moik F, Chan WSE, Wiedemann S, et al. Incidence, risk factors and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood. 2021;137(12):1669-1678.
    View Article PubMed Google Scholar
  6. Ando Y, Hayashi T, Sugimoto R, et al. Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors. Invest New Drugs. 2020;38(4):1200-1206.
    View Article PubMed Google Scholar

  7. Regenhardt RW, Das AS, Stapleton CJ, et al. Blood pressure and penumbral sustenance in stroke from large vessel occlusion. Front Neurol. 2017;8:317.

    View Article PubMed Google Scholar

  8. Friedman DI. Headaches due to low and high intracranial pressure. Continuum (Minneap Minn). 2018;24(4, Headache):1066-1091.

    View Article PubMed Google Scholar
  9. Koenig MA. Cerebral edema and elevated intracranial pressure. Continuum (Minneap Minn). 2018;24(6):1588-1602.
    View Article PubMed Google Scholar

  10. Pandhi A, Krishnan R, Goyal N, Malkoff M. Increased intracranial pressure in critically ill cancer patients. In: Nates J, Price K, eds. Oncologic Critical Care. Springer; 2020:395-407.

    Google Scholar

  11. Arch AE, Sheth KN. Malignant cerebral edema after large anterior circulation infarction: a review. Curr Treat Options Cardiovasc Med. 2014;16(1):275.

    View Article PubMed Google Scholar

  12. Bang OY, Chung JW, Lee MJ, Seo WK, Kim GM, Ahn MJ; OASIS-Cancer Study Investigators. Cancer-related stroke: an emerging subtype of ischemic stroke with unique pathomechanisms. J Stroke. 2020;22(1):1-10.

    View Article PubMed Google Scholar

  13. Zaorsky NG, Zhang Y, Tchelebi LT, Mackley HB, Chinchilli VM, Zacharia BE. Stroke among cancer patients. Nat Commun. 2019;10(1):5172.

    View Article PubMed Google Scholar

  14. Dearborn JL, Urrutia VC, Zeiler SR. Stroke and cancer—a complicated relationship. J Neurol Transl Neurosci. 2014;2(1):1039.

    PubMed Google Scholar
  15. Kitano T, Sasaki T, Gon Y, et al. The effect of chemotherapy on stroke risk in cancer patients. Thromb Haemost. 2020;120(4):714-723.
    View Article PubMed Google Scholar

  16. Zhang J, Zhao J. Clinical characteristics and analysis of lung cancer-associated acute ischemic stroke. J Stroke Cerebrovasc Dis. 2020;29(10):105164.

    View Article PubMed Google Scholar
  17. Sands JM, Daly ME, Lee EQ. Neurologic complications of lung cancer. Cancer. 2020;126(20):4455-4465.
    View Article PubMed Google Scholar

  18. Abdelsalam M, Abu-Hegazy M, El-Hadaad HA, Wahba H, Egila H, Esmael A. Pathophysiology, mechanism, and outcome of ischemic stroke in cancer patients. J Stroke Cerebrovasc Dis. 2020;29(11):105299.

    View Article PubMed Google Scholar
  19. Bang OY, Seok JM, Kim SG, et al. Ischemic stroke and cancer: stroke severely impacts cancer patients, while cancer increases the number of strokes. J Clin Neurol. 2011;7(2):53-59.
    View Article PubMed Google Scholar

  20. World Health Organization. Cancer Pain Relief and Palliative Care: Report of a WHO Expert Committee. World Health Organization; 1990. Accessed August 6, 2021. http://apps.who.int/iris/bitstream/handle/10665/39524/WHO_TRS_804.pdf?sequence=1

  21. About palliative care. National Palliative Care Research Center. Accessed July 6, 2021. http://www.npcrc.org/content/15/About-Palliative-Care.aspx

  22. McCahill LE, Krouse RS, Chu DZ, et al. Decision making in palliative surgery. J Am Coll Surg. 2002;195(3):411-422.
    View Article PubMed Google Scholar
  23. Hallissey MT, Allum WH, Roginski C, Fielding JW. Palliative surgery for gastric cancer. Cancer. 1988;62(2):440-444.
    View Article PubMed Google Scholar
  24. Hirabayashi H, Ebara S, Kinoshita T, et al. Clinical outcome and survival after palliative surgery for spinal metastases: palliative surgery in spinal metastases. Cancer. 2003;97(2):476-484.
    View Article PubMed Google Scholar
  25. McCahill LE, Krouse R, Chu D, et al. Indications and use of palliative surgery—results of Society of Surgical Oncology survey. Ann Surg Oncol. 2002;9(1):104-112.
    View Article PubMed Google Scholar
  26. Hofmann B, Håheim LL, Søreide JA. Ethics of palliative surgery in patients with cancer. Br J Surg. 2005;92(7):802-809.
    View Article PubMed Google Scholar
  27. Ferguson HJM, Ferguson CI, Speakman J, Ismail T. Management of intestinal obstruction in advanced malignancy. Ann Med Surg (Lond). 2015;4(3):264-270.
    View Article PubMed Google Scholar

  28. Sigurdsson HK, Kørner H, Dahl O, Skarstein A, Søreide JA; Norwegian Rectal Cancer Group. Palliative surgery for rectal cancer in a national cohort. Colorectal Dis. 2008;10(4):336-343.

    View Article PubMed Google Scholar

  29. Perinel J, Adham M. Palliative therapy in pancreatic cancer—palliative surgery. Transl Gastroenterol Hepatol. 2019;4:28.

    View Article PubMed Google Scholar
  30. Lindvall C, Lilley EJ, Zupanc SN, et al. Natural language processing to assess end-of-life quality indicators in cancer patients receiving palliative surgery. J Palliat Med. 2019;22(2):183-187.
    View Article PubMed Google Scholar
  31. Kobayashi K, Ando K, Nakashima H, et al. Prognostic factors in the new Katagiri scoring system after palliative surgery for spinal metastasis. Spine (Phila Pa 1976). 2020;45(13):E813-E819.
    View Article PubMed Google Scholar
  32. Wong AWK, Lau SCL, Fong MWM, Cella D, Lai JS, Heinemann AW. Conceptual underpinnings of the Quality of Life in Neurological Disorders (Neuro-QoL): comparisons of core sets for stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. Arch Phys Med Rehabil. 2018;99(9):1763-1775.
    View Article PubMed Google Scholar
  33. Jonkman EJ, de Weerd AW, Vrijens NL. Quality of life after a first ischemic stroke. Long-term developments and correlations with changes in neurological deficit, mood and cognitive impairment. Acta Neurol Scand. 1998;98(3):169-175.
    View Article PubMed Google Scholar
  34. Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018;90(16):e1364-e1371.
    View Article PubMed Google Scholar
  35. Asaithambi G, Tipps ME. Quality of life among ischemic stroke patients eligible for endovascular treatment: analysis of the DEFUSE 3 trial. J Neurointerv Surg. 2021;13(8):703-706.
    View Article PubMed Google Scholar
  36. Askew RL, Capo-Lugo CE, Sangha R, Naidech A, Prabhakaran S. Trade-offs in quality-of-life assessment between the Modified Rankin Scale and Neuro-QoL measures. Value Health. 2020;23(10):1366-1372.
    View Article PubMed Google Scholar
  37. Regenhardt RW, Young MJ, Etherton MR, et al. Toward a more inclusive paradigm: thrombectomy for stroke patients with pre-existing disabilities. J Neurointerv Surg. 2021;13(10):865-868.
    View Article PubMed Google Scholar
  38. Young MJ, Regenhardt RW, Leslie-Mazwi TM, Stein MA. Disabling stroke in persons already with a disability: ethical dimensions and directives. Neurology. 2020;94(7):306-310.
    View Article PubMed Google Scholar
  39. Fargen KM, Leslie-Mazwi TM, Chen M, Hirsch JA. Physician, know thyself: implicit and explicit decision-making for mechanical thrombectomy in stroke. J Neurointerv Surg. 2020;12(10):952-956.
    View Article PubMed Google Scholar
  40. Martinez-Gutierrez JC, Leslie-Mazwi T, Chandra RV, et al. Number needed to treat: a primer for neurointerventionalists. Interv Neuroradiol. 2019;25(6):613-618.
    View Article PubMed Google Scholar
  41. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418.
    View Article PubMed Google Scholar
  42. Nannoni S, Strambo D, Sirimarco G, et al. Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center. J Neurointerv Surg. 2020;12(9):842-847.
    View Article PubMed Google Scholar
  43. Rumalla K, Ottenhausen M, Kan P, Burkhardt JK. Recent nationwide impact of mechanical thrombectomy on decompressive hemicraniectomy for acute ischemic stroke. Stroke. 2019;50(8):2133-2139.
    View Article PubMed Google Scholar
  44. Göttsche J, Flottmann F, Jank L, et al. Decompressive craniectomy in malignant MCA infarction in times of mechanical thrombectomy. Acta Neurochir (Wien). 2020;162(12):3147-3152.
    View Article PubMed Google Scholar

  45. Khattar NK, Ugiliweneza B, Fortuny EM, et al. Inverse national trends in decompressive craniectomy versus endovascular thrombectomy for stroke. World Neurosurg. 2020;138:e642-e651.

    View Article PubMed Google Scholar

  46. Mouchtouris N, Saiegh FA, Baldassari M, et al. Decompressive hemicraniectomy in the modern era of acute ischemic stroke: the impact of mechanical thrombectomy. Neurosurgery. 2020;67(suppl 1):nyaa447_292.

    Google Scholar
  47. Purves D. Harming as making worse off. Philos Stud. 2019;176(10):2629-2656.
    View Article Google Scholar
  48. Carlson E, Johansson J, Risberg O. Well-being counterfactualist accounts of harm and benefit. Australas J Philos. 2021;99(1):164-174.
    View Article Google Scholar
  49. Johansson J, Risberg O. Harming and failing to benefit: a reply to Purves. Philos Stud. 2020;177(6):1539-1548.
    View Article Google Scholar
  50. Regenhardt RW, Takase H, Lo EH, Lin DJ. Translating concepts of neural repair after stroke: structural and functional targets for recovery. Rest Neurol Neuroscience. 2020;38(1):67-92.
    View Article PubMed Google Scholar
  51. Steinhauser KE, Christakis NA, Clipp EC, McNeilly M, McIntyre L, Tulsky JA. Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA. 2000;284(19):2476-2482.
    View Article PubMed Google Scholar

  52. Nair KPS, Chandler B, Lee M, et al. Rehabilitation medicine in palliative care of chronic neurological conditions. BMJ Support Palliat Care. Published online August 24, 2020.

    View Article PubMed Google Scholar
  53. Creutzfeldt CJ, Holloway RG, Walker M. Symptomatic and palliative care for stroke survivors. J Gen Intern Med. 2012;27(7):853-860.
    View Article PubMed Google Scholar
  54. Creutzfeldt CJ, Holloway RG, Curtis JR. Palliative care: a core competency for stroke neurologists. Stroke. 2015;46(9):2714-2719.
    View Article PubMed Google Scholar
  55. Creutzfeldt CJ, Kluger B, Kelly AG, et al. Neuropalliative care: priorities to move the field forward. Neurology. 2018;91(5):217-226.
    View Article PubMed Google Scholar
  56. Connolly T, Coats H, DeSanto K, Jones J. The experience of uncertainty for patients, families and healthcare providers in post-stroke palliative and end-of-life care: a qualitative meta-synthesis. Age Ageing. 2021;50(2):534-545.
    View Article PubMed Google Scholar

  57. Visvanathan A, Mead GE, Dennis M, Whiteley WN, Doubal FN, Lawton J. The considerations, experiences and support needs of family members making treatment decisions for patients admitted with major stroke: a qualitative study. BMC Med Inform Decis Mak. 2020;20:98.

    View Article PubMed Google Scholar
  58. Abernethy AP, Capell WH, Aziz NM, et al. Ethical conduct of palliative care research: enhancing communication between investigators and institutional review boards. J Pain Symptom Manage. 2014;48(6):1211-1221.
    View Article PubMed Google Scholar
  59. Bloomer MJ, Hutchinson AM, Brooks L, Botti M. Dying persons’ perspectives on, or experiences of, participating in research: an integrative review. Palliat Med. 2018;32(4):851-860.
    View Article PubMed Google Scholar
  60. Oriani A, Fusi-Schmidhauser T, Guo P. Should end-of-life patients be enrolled as participants in clinical research? A best-fit framework synthesis. J Adv Nurs. 2021;77(4):1656-1666.
    View Article PubMed Google Scholar
  61. Vinches M, Neven A, Fenwarth L, et al. Clinical research in cancer palliative care: a metaresearch analysis. BMJ Support Palliat Care. 2020;10(2):249-258.
    View Article PubMed Google Scholar
  62. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-742.
    View Article PubMed Google Scholar
  63. Temel JS, Shaw AT, Greer JA. Challenge of prognostic uncertainty in the modern era of cancer therapeutics. J Clin Oncol. 2016;34(30):3605-3608.
    View Article PubMed Google Scholar
  64. Tokunboh I, Vales Montero M, Zopelaro Almeida MF, et al. Visual aids for patient, family, and physician decision making about endovascular thrombectomy for acute ischemic stroke. Stroke. 2018;49(1):90-97.
    View Article PubMed Google Scholar

  65. Goyal M, Menon BK, van Zwam WH, et al; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731.

    View Article PubMed Google Scholar
  66. Moshayedi P, Liebeskind DS, Jadhav A, et al. Decision-making visual aids for late, imaging-guided endovascular thrombectomy for acute ischemic stroke. J Stroke. 2020;22(3):377-386.
    View Article PubMed Google Scholar
  67. Kamal N, Rogers E, Stang J, et al. One-year healthcare utilization for patients that received endovascular treatment compared with control. Stroke. 2019;50(7):1883-1886.
    View Article PubMed Google Scholar

  68. Zerna C, Rogers E, Rabi DM, et al. Comparative effectiveness of endovascular treatment for acute ischemic stroke: a population-based analysis. J Am Heart Assoc. 2020;9(7):e014541.

    View Article PubMed Google Scholar

  69. Holloway RG, Arnold RM, Creutzfeldt CJ, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Palliative and end-of-life care in stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(6):1887-1916.

    View Article PubMed Google Scholar

  70. Rehmann-Sutter C. When a patient refuses life-sustaining treatments. In: Emmerich M, Malia P, Gordijn B, Pistoia F, eds. Contemporary European Perspectives on the Ethics of End of Life Care. Springer; 2020:297-314.

    View Article Google Scholar
  71. Sokol LL, Hauser JM, Lum HD, et al. Goal-concordant care in the era of advanced stroke therapies. J Palliat Med. 2021;24(2):297-301.
    View Article PubMed Google Scholar
  72. VanKerkhoff TD, Viglianti EM, Detsky ME, Kruser JM. Time-limited trials in the intensive care unit to promote goal-concordant patient care. Clin Pulm Med. 2019;26(5):141-145.
    View Article PubMed Google Scholar
  73. Caron JL, Souhami L, Podgorsak EB. Dynamic stereotactic radiosurgery in the palliative treatment of cerebral metastatic tumors. J Neurooncol. 1992;12(2):173-179.
    View Article PubMed Google Scholar

  74. Harrison RA, Bruera E. The palliative care of patients with brain metastases. In: Ahluwalia M, Metellus P, Soffietti R, eds. Central Nervous System Metastases. Springer; 2020:705-718.

    View Article Google Scholar

  75. Hong AM, Waldstein C, Shivalingam B, et al. Management of melanoma brain metastases: evidence-based clinical practice guidelines by Cancer Council Australia. Eur J Cancer. 2021;142:10-17.

    View Article PubMed Google Scholar
  76. Hatiboglu MA, Akdur K, Sawaya R. Neurosurgical management of patients with brain metastasis. Neurosurg Rev. 2020;43(2):483-495.
    View Article PubMed Google Scholar
  77. Sankary LR, Ford PJ, Machado AG, Hoeksema LJ, Samala RV, Harris DJ. Deep brain stimulation at end of life: clinical and ethical considerations. J Palliat Med. 2020;23(4):582-585.
    View Article PubMed Google Scholar
  78. Akram H, Allibone J. Spinal surgery for palliation in malignant spinal cord compression. Clin Oncol (R Coll Radiol). 2010;22(9):792-800.
    View Article PubMed Google Scholar
  79. Kakutani K, Sakai Y, Maeno K, et al. Prospective cohort study of performance status and activities of daily living after surgery for spinal metastasis. Clin Spine Surg. 2017;30(8):E1026-E1032.
    View Article PubMed Google Scholar
  80. Miyazaki S, Kakutani K, Sakai Y, et al. Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study. Int Orthop. 2017;41(6):1265-1271.
    View Article PubMed Google Scholar
  81. Tao F, Shi Z, Tao H, et al. Comparison of subtotal vertebral resection with reconstruction and percutaneous vertebroplasty for treatment of metastasis in the lumbar spine. Br J Neurosurg. 2020;34(3):308-312.
    View Article PubMed Google Scholar

  82. Sokol LL, Young MJ, Paparian J, et al. Advance care planning in Parkinson’s disease: ethical challenges and future directions. NPJ Parkinsons Dis. 2019;5:24.

    View Article PubMed Google Scholar

  83. Bindu B, Rath GP. Palliative care for neurologically injured patients: why and how? J Neuroanaesth Crit Care. 2019;6(1):5-12.

    View Article Google Scholar

  84. Creutzfeldt CJ, Kluger BM, Holloway RG. Neuropalliative care: an introduction. In: Creutzfeldt C, Kluger B, Holloway R, eds. Neuropalliative Care: A Guide to Improving the Lives of Patients and Families Affected by Neurologic Disease. Springer; 2019:1-8.

    View Article Google Scholar

  85. DeAngelis LM, Posner JB. Neurologic Complications of Cancer. 2nd ed. Oxford University Press; 2009. Contemporary Neurology; vol 73.

    Google Scholar
  86. Haugh AM, Probasco JC, Johnson DB. Neurologic complications of immune checkpoint inhibitors. Expert Opin Drug Saf. 2020;19(4):479-488.
    View Article PubMed Google Scholar
  87. Lee EQ. Neurologic complications in patients with cancer. Continuum (Minneap Minn). 2020;26(6):1629-1645.
    View Article PubMed Google Scholar
  88. Krishnan AV, Kiernan MC. Neurological complications of chronic kidney disease. Nat Rev Neurol. 2009;5(10):542-551.
    View Article PubMed Google Scholar
  89. Zhang F, Wang K, Du P, et al. Risk of stroke in cancer survivors: a meta-analys of population-based cohort studies. Neurology. 2021;96(4):e513-e526.
    View Article PubMed Google Scholar
  90. Sokol LL, Lum HD, Creutzfeldt CJ, et al. Meaning and dignity therapies for psychoneurology in neuropalliative care: a vision for the future. J Palliat Med. 2020;23(9):1155-1156.
    View Article PubMed Google Scholar
  91. Young MJ. Compassionate care for the unconscious and incapacitated. Am J Bioeth. 2020;20(2):55-57.
    View Article PubMed Google Scholar

  92. Chesney TR, Schwarze ML. Patient-centered surgical decision making. In: Rosenthal RA, Zenilman NE, Katlic MR, eds. Principles and Practice of Geriatric Surgery. 3rd ed. Springer; 2020:81-93.

    View Article Google Scholar

Editor's Note

Background image by Annie Broutman.

Citation

AMA J Ethics. 2021;23(10):E783-793.

DOI

10.1001/amajethics.2021.783.

Acknowledgements

This work was supported by Northwestern University Feinberg School of Medicine Department of Neurology’s Physician-Scientist Training Program, National Institutes of Health R25 CA190169 for Meaning-Centered Psychotherapy research and training at Memorial Sloan Kettering Cancer Center, National Institute of Neurological Disorders and Stroke of the National Institutes of Health Cooperative Agreement F32MH123001, the Tiny Blue Dot Foundation, and a Scientific Projects to Accelerate Research and Collaboration award from the Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital.

Conflict of Interest Disclosure

Dr Sokol serves as an ad hoc consultant for Tikvah for Parkinson and is an ad hoc reviewer for the Journal of Geriatric Psychiatry and Neurology, Pilot and Feasibility Studies, and Palliative Medicine Reports. The other authors had no conflicts of interest to disclose.

The people and events in this case are fictional. Resemblance to real events or to names of people, living or dead, is entirely coincidental. This article is the sole responsibility of the author(s) and does not necessarily represent the views of the National Institutes of Health, the Tiny Blue Dot Foundation, or the Henry and Allison McCance Center for Brain Health. The viewpoints expressed in this article are those of the author(s) and do not necessarily reflect the views and policies of the AMA.