Ischemic Stroke in Critically Ill Patients with Malignancy

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Suh 1, Joongbum Cho 1, Chi Ryang Chung 1, Chi-Min Park 1, Kyeongman Jeon 1

1 Ischemic Stroke in Critically Ill Patients with Malignancy Jeong-Am Ryu 1, Oh Young Bang 2, Daesang Lee 1, Jinkyeong Park 1, Jeong Hoon Yang 1, Gee Young Suh 1, Joongbum Cho 1, Chi Ryang Chung 1, Chi-Min Park 1, Kyeongman Jeon 1 Center for Intensive Care 1 ; Department of Neurology 2 Samsung Medical Center KOREA

3 Cancer Ischemic stroke (IS)

4 IS in cancer patients? IS in oncology ICU?

5 Background Ischemic stroke and cancer Cerebrovascular disease may occur commonly in cancer patients. From an autopsy study, 15% of cancer patients experienced thromboembolic events including ischemic stroke (IS) during their clinical course. Systemic cancer is related to ischemic stroke via various mechanisms.

6 Stroke mechanisms in cancer patients Cancer-unrelated mechanisms Conventional stroke mechanisms (CSM) Atherosclerosis, cardioembolic, lacunar, etc. Cancer-related mechanisms Coagulopathy Intravascular coagulation or nonbacterial thrombotic endocarditis Tumor occlusion Tumor embolism (lung or cardiac), intravascular lymphoma Direct tumor-related (metastasis or central nervous system tumor) Treatment-related mechanisms Chemotherapy causing coagulopathy Radiation or surgery causing vascular stenosis Medical comorbidities, such as fungal infection or infective endocarditis J Clin Neurol 2011;7:53-59

7 Single vs. Multiple CSM low D-dimer level Cancer-related stroke/cryptogenic high D-dimer level J Clin Neurol 2011;7:53-59

8 Objective We investigated the clinical characteristics and brain MRI findings of IS in cancer ICU.

9 Methods Retrospective cohort study Study period March 2010 to February 2014, who admitted in the oncology medical ICU of Samsung Medical Center in Korea. Inclusion Criteria A cohort of patients who underwent brain MRI for suspicion of IS during hospitalization in the oncology medical ICU Suspicion of IS (acute neurological abnormalities) Acute onset Altered mental status (decreased mentality or delirium) Focal or lateralizing neurological deficit (hemiparesis, aphasia, hemisensory disturbance, visual field disturbance) Seizure Exclusion Criteria Patients were excluded if they had a history of trauma, surgery, or chronic neurologic deficit on ICU admission.

10 Diagnosis of IS The diagnosis of IS IS was diagnosed by brain MRI scanning when ischemic regions had decreased ADC and high signal intensity on DWI. DWI patterns were classified as single lesion and multiple lesions. Multiple lesions were subdivided as a single arterial territory, small lesions involving multiple arterial territories, or small and large disseminated lesions. The subtype of IS classified by the Trial of Org in Acute Stroke Treatment (TOAST) system. Large-vessel atherosclerosis Cardioembolism Small-vessel occlusion Other Cryptogenic (undetermined) Conventional stroke mechanism

11 Statistical analyses The data are presented as the median and interquartile range (IQR) for continuous variables and as the number (percentage) for categorical variables. Data were compared using Mann-Whitney U tests for continuous variables and Chi-square or Fisher s exact test for categorical variables. Multiple logistic regression analysis was used to identify independent predictors of IS in critically ill cancer patients, as measured by the estimated odds ratio (OR) with 95% confidence intervals (CIs). Variables with a P value less than 0.2 on univariate analyses, as well as a priori variables that were clinically relevant were entered into the forward stepwise multiple logistic regression model. All tests were 2 sided, and P < 0.05 was considered statistically significant. Data were analysed using IBM SPSS statistics 20 (IBM, Armonk, NY).

12 Results

13 Oncology MICU ~ (n=2,258) Excluded Trauma Surgery Chronic neurologic deficit on ICU admission Included (n=88) Cancer patient Acute neurological abnormalities Underwent brain MRI for suspicion of IS Ischemic Stroke (n=43) Non-ischemic stroke (n=45)

14 Baseline characteristics on ICU admission Characteristics No. of patients (%) or median (IQR) Age, years 63 (53-69) Gender, male 51 (58) Type of malignancy Solid tumour Haematologic malignancy Status of malignancy on ICU admission First presentation Relapsed/refractory Extensive disease Major organ involvement Stem cell transplantation Duration of malignancy, months Major reasons for ICU admission Respiratory failure Severe sepsis or septic shock Cardiovascular Neurological Other Clinical status on ICU admission Recent chemotherapy prior to ICU admission within 4 weeks Need for mechanical ventilation Need for vasopressor support Need for renal replacement therapy D-dimer levels (μg/ml) Vascular risk factor Hypertension Diabetes mellitus Ex and current smoking Ischemic heart disease Hypercholesterolemia Atrial fibrillation Alcohol abuse 33 (38) 55 (63) 33 (38) 45 (51) 38 (43) 21 (24) 13 (15) 3.7 ( ) 37 (42) 34 (39) 5 (6) 6 (7) 6 (7) 44 (50) 58 (66) 33 (38) 7 (8) 4.51 ( ) 35 (40) 20 (23) 31 (35) 3 (3) 5 (6) 19 (22) 4 (5) Family history of stroke 7 (8)

15 Clinical characteristics of 88 critically ill cancer patients when to check brain MRI Characteristics No. of patients (%) Neurologic symptoms or signs Decreased mentality or delirium Hemiparesis Seizure Abnormal movement Anisocoric pupil or abnormal pupil reflex Abnormal respiratory pattern Other or median (IQR) 55 (63) 28 (32) 20 (23) 6 (7) 3 (3) 2 (2) 7 (8) Time interval from ICU admission to brain MRI, days 4.4 ( ) Recent chemotherapy 44 (50) Central line or PICC 71 (81) Fungal infection Infective endocarditis Anticoagulation use Antiplatelet use D-dimer levels (μg/ml) DIC 21 (24) 3 (3) 20 (23) 3 (3) 3.76 ( ) 36 (41)

16 Neurological symptoms or signs for clinical suspicion of ischemic stroke

17 Brain MRI finding (IS vs. non-is) Brain MRI findings No. of patients (%) Ischemic stroke patients Single lesion Multiple lesions A single arterial territory Small lesions involving multiple arterial territories Small and large disseminated lesions Non-ischemic stroke patients Pathologic brain MRI findings Brain metastasis Old stroke lesion Posterior reversible encephalopathy syndrome Intracranial haemorrhage (1 gyral SAH, 2 SDH) Seizure-related change Primary brain tumour Other Normal brain MRI findings 7 (8) 36 (41) 1 (1) 18 (20) 17 (19) 32 (36) 7 (8) 7 (8) 4 (5) 3 (3) 3 (3) 3 (3) 5 (6) 13 (15)

18 Stroke mechanism in 43 patients diagnosed with ischemic stroke Etiology No. of patients (%) Conventional stroke mechanism Large-vessel atherosclerosis Cardioembolism Small-vessel occlusion Other Cryptogenic 16 (37) 3 (7) 8 (19) 2 (5) 3 (7) 27 (63)

19 Cancer types in CSM vs. cryptogenic mechanism

20 IS vs. non-is IS (n = 43) Non-IS (n = 45) P value Age, years 64.5 (56-69) 62.5 (40-70) Gender, male 26 (61) 25 (56) Type of malignancy Solid Haematologic 16 (37) 27 (63) 17 (39) 28 (62) Resent chemotherapy 22 (51) 22 (49) Vascular risk factor Hypertension Ex and current smoking Ischemic heart disease Atrial fibrillation Diabetes mellitus Alcohol abuse 17 (40) 14 (33) 2 (5) 8 (19) 11 (26) 3 (7) 18 (40) 17 (38) 1 (2) 11 (24) 9 (20) 1 (2) Thrombotic event Previous thrombotic event Concomitant pulmonary thromboembolism Concomitant deep vein thrombosis Neurologic symptoms or signs Acute altered mentality Seizure Hemiparesis Anisocoric pupil or abnormal pupil reflex Abnormal movement Abnormal respiratory pattern Other Antiplatelet use Anticoagulant use Coagulopathy D-dimer levels (μg/ml) DIC Outcomes ICU mortality In-hospital mortality Length of stay in ICU, days 10 (23) 7 (16) 2 (5) 5 (12) 28 (65) 3 (7) 21 (49) 1 (2) 4 (9) 1 (2) 1 (2) 2 (5) 10 (23) 38 (88) 5.66 ( ) 19 (48) 19 (45) 34 (81) 15.2 ( ) 3 (7) 3(7) 0 (0) 1 (2) 27 (60) 17 (38) 7 (16) 2 (4) 2 (4) 1 (2) 5 (11) 1 (2) 10 (22) 33 (73) 3.53 ( ) 17 (46) 13 (29) 29 (64) 12.2 ( )

21 Summary Clinical characteristics and brain MRI findings of IS in cancer ICU Approximately half of the patients who showed acute neurological abnormalites diagnosed with IS Total thrombotic events were more common in IS group Acute change of mental status most common cause to check brain MRI Half of this symptom were revealed as IS Altered mentality may be related with multiple territorial lesion Newly diagnosed brain metastasis was relatively rare Cryptogenic and multiple territorial strokes Commonly observed in critically ill cancer patients May be associated with cancer-related stroke

22 Conclusion Although, it is generally difficult to differentiate between IS and non-is based on symptom or sign alone, caution and careful examination are required when acute neurological deficits are observed in critically ill cancer patients.

D-dimer levels and cerebral infarction in critically ill cancer patients

Ryu et al. BMC Cancer (2017) 17:591 DOI 10.1186/s12885-017-3588-7 RESEARCH ARTICLE Open Access D-dimer levels and cerebral infarction in critically ill cancer patients Jeong-Am Ryu 1, Oh Young Bang 2 and