Intravascular Large B Cell Lymphoma as a Cause of Multifocal Cryptogenic Stroke

Anbil, Sriram; Fenerty, Kathleen; Feng, Zekun; Doughty, Reece; El-Farra, Neveen

doi:10.1016/j.amjmed.2021.03.045

Cited by 4 publications

(4 citation statements)

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“…These highly correlated tumors were not directly related to the brain, which may be due to the limited number of ischemic injury-associated genes we selected for analysis (top 50 highly expressed genes). However, there have also been some case reports showing the strong association between DLBC ( 52 ) and MESO ( 53 ) and stroke. Additionally, a recent study has demonstrated that RNA signatures in the blood can be used to identify cancer-associated acute ischemic stroke and to monitor patients with cryptogenic acute ischemic stroke for occult cancer ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke

et al. 2022

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BackgroundPrevious studies have shown that stroke is a potential first sign of neoplasia, but the relationship between stroke and cancer remains unclear. As a complex brain disease, ischemic stroke involves cell death and immunity. Thus, it is necessary to investigate the association of the tumor immune microenvironment and cell death with ischemic stroke.MethodsWe established a photothrombosis-induced ischemic injury model in mouse brain and skull. Subsequently, we sequenced the whole transcriptome of the injured mouse brain and skull and analyzed the expression profiles. To investigate the association of stroke with cell death and cancer, we systematically performed gene set enrichment analysis in pan-cell death (i.e., apoptosis, cuproptosis, ferroptosis, necroptosis, and pyroptosis) and the cancer hallmark pathways. The time-dependent immune cell abundance variations after ischemic injury were estimated. Furthermore, pan-cancer genomic and prognostic analyses of the ischemic injury-related gene sets were also performed.ResultsIn this study, we found that there exist temporal and spatial differences in the gene expression patterns of both the brain and skull with ischemic injury. The skull ischemic injury-induced changes in the brain transcriptome were particularly great, but could recover in a short period, while the skull transcriptome variation resulting from brain ischemic injury was long-lasting. In addition, the expression of the genes related to ischemic injury was also associated with pan-cell death and the cancer hallmark pathways. The changes in the abundance of immune cells indicate that brain ischemic injury may disrupt the immune microenvironment for a longer time, while the skull can balance the stability of the immune microenvironment better. Moreover, the brain ischemic injury-related gene sets were highly correlated with a variety of tumors, particularly glioblastoma multiforme (GBM), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and uveal melanoma (UVM), which carry a greater mortality risk after stroke.ConclusionThis systematic analysis not only helps in the understanding of the changes in the gene expression profiles of both the brain and skull with ischemic injury but also reveals the association of the tumor immune microenvironment and cell death with ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke

et al. 2022

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“…54,55 Malignant hematologic tumors, such as intravascular lymphoma, can directly obstruct blood vessels. 24,56,57 Additionally, accumulating evidence suggests that cancer is a risk factor for atrial fibrillation, likely due to shared risk factors and increased inflammation that may link cancer to left atrial cardiomyopathy. 58 Patients with cancer commonly develop immunosuppression from the tumor itself, cancer treatment including chemotherapies and steroids as well as cancer-associated malnutrition, and chemotherapy.…”

Section: Cancer-associated Mechanismsmentioning

confidence: 99%

“…54 55 Malignant hematologic tumors, such as intravascular lymphoma, can directly obstruct blood vessels. 24 56 57…”

Section: Stroke Mechanisms In Cancer Patientsmentioning

confidence: 99%

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment

Costamagna

Navi

Beyeler

et al. 2023

Semin Thromb Hemost

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Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile.

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“…Fifty-three cases of brain MRI showed either diffusion restriction (39.6%) or abnormal T2-lesions (56.6%), which were mostly located in the subcortical regions (58.5%). The dynamic pattern of MRI diffusion-weighted imaging (DWI)/T2 lesions was noted in multiple studies (n=23) where serial neuroimaging was performed [11,12,15,16,18,[20][21][22][23][24][26][27][28][29]31,32,[34][35][36][38][39][40]44,45]. Cerebral hemorrhages were noted in 11.3% of cases (n=53) [19,25,28,39,43,46].…”

Section: Figure 3: Frequency Of Non-lateralizing Symptoms Of All Casesmentioning

confidence: 99%

Intravascular Lymphoma-Associated Stroke: A Systematic Review of Case Studies

Bhagat,

Shahab,

Karki

et al. 2023

Cureus

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Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.

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Intravascular Large B Cell Lymphoma as a Cause of Multifocal Cryptogenic Stroke

Cited by 4 publications

References 4 publications

Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke

Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke

Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment

Intravascular Lymphoma-Associated Stroke: A Systematic Review of Case Studies

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