Identifying ischemic stroke associated with cancer: a multiple model derived from a case–control analysis

Abstract

Ischemic stroke in patients with cancer is thought to be associated with a worse prognosis and might be the initial symptom of an unknown malignancy. However, diagnostic algorithms to reliably identify cancer-associated stroke have not been developed. In this retrospective single-centre analysis, 68 patients with ischemic stroke and an active solid malignancy were identified. Neurological assessment and outcome, cardiovascular risk factors, neuroimaging studies as well as laboratory findings were compared to 68 age- and sex-matched control subjects with ischemic stroke without diagnosis of cancer. Lung, pancreatic and renal cancer showed increased prevalences compared to those of the general population in Germany. Diagnosis of cancer was most often made within the 12 months preceding (32.4%) or during the diagnostic work-up for stroke (17.7%). Cancer-associated stroke was characterized by a more severe clinical deficit, frequent clinical deterioration (13.2 vs. 1.5%) or death (25 vs. 4.4%). Ischemic lesions often involved multiple territories (51.6 vs. 12.7%), more often with co-existing subacute and acute infarctions in imaging studies (54.8 vs. 11.1%). Patients with cancer had significantly higher levels of C-reactive protein, relative granulocytosis and serum lactate dehydrogenase activity. Using receiver operating characteristics-based multiple analysis, we developed a model using these parameters which detected cancer-associated stroke with a sensitivity of 75% and specificity of 95%. Our analysis suggests that a multiple algorithm combining the number of territories involved and laboratory signs of inflammation and cell turnover might identify patients with stroke suffering from previously unknown malignancy.

Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study

“…In this study, most NHLAIS patients had experienced ischemic stroke within 6 months after the diagnosis of NHL. Radiologically, they all had multiple vascular infarcts with a past history of ischemic stroke, which is consistent with the findings of previous studies [1,[18][19][20], highlighting the similar features that NHLAIS and CaIS patients would probably likely experience.…”

“…In addition, the multivariate analysis demonstrated that elevated levels of both FIB and D-dimer were independent risk factors for NHLAIS. However, elevated levels of FIB and D-dimer are reported to be biomarkers of the hypercoagulable state seen in patients with cancer [2,6], the pathogenesis of which has also been reported by several studies related to ischemic stroke [6,18,20,21]. Furthermore, Seok and colleagues [22] found an elevated D-dimer level linearly correlates to the frequency of microembolic signals in the internal carotid on transcranial Doppler ultrasound in cancer patients and patients with cryptogenic stroke.…”

Ischemic stroke in cancer patients: A review of an underappreciated pathology

“…24 Potential biomarkers for occult cancer in stroke patients include elevated D-dimer, fibrinogen, and C-reactive protein; infarction in multiple vascular territories; and poor nutritional status. [24][25][26][27][28][29] Most comorbid cancers in stroke patients are solid tumors of the lung, gastrointestinal tract, and breast. [30][31][32] In addition, most patients with cancer and stroke are elderly and male, although patients of any age, sex, or race/ethnicity can be affected.…”

“…This risk of incident, previously occult cancer appears highest in patients with cryptogenic stroke, in whom it is conceivable that the cancer caused or triggered the stroke through hypercoagulability . Potential biomarkers for occult cancer in stroke patients include elevated D‐dimer, fibrinogen, and C‐reactive protein; infarction in multiple vascular territories; and poor nutritional status . Most comorbid cancers in stroke patients are solid tumors of the lung, gastrointestinal tract, and breast .…”

Cancer-Related Stroke: An Emerging Subtype of Ischemic Stroke with Unique Pathomechanisms

“…13,53 The principal lesion patterns on DWI are multiple small cortical lesions extending to multiple vascular territories (in about 40% 13,54 ) and multi-staged acute and subacute ischemic lesions. 55,56 The level of D-dimer, a plasmin-derived degradation product of cross-linked fibrin, is a direct measure of activated coagulation. In cancer-related stroke, hypercoagulability as assessed by serial D-dimer levels was associated with early neurological deterioration, stroke recurrence and poor survival after stroke in patients with active cancer, suggesting that D-dimer level can be used in monitoring the effect of anticoagulation therapy.…”