Background: Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodegenerative processes, identifying a new state of microglia: disease-associated microglia (DAM). The aim of this study is to investigate expression patterns of microglial-related genes in ALS spinal cord. Methods: We analyzed mRNA expression levels via RT-qPCR of several microglia-related genes in their homeostatic and DAM state in postmortem tissue (anterior horn of the spinal cord) from 20 subjects with ALS-TDP43 and 19 controls donors from the Navarrabiomed Biobank. Results: The expression levels of TREM2, MS4A, CD33, APOE and TYROBP were found to be elevated in the spinal cord from ALS subjects versus controls (p-value < 0.05). However, no statistically significant gene expression differences were observed for TMEM119, SPP1 and LPL. Conclusions: This study suggests that a DAM-mediated inflammatory response is present in ALS, and TREM2 plays a significant role in immune function of microglia. It also supports the role of C33 and MS4A in the physiopathology of ALS.

Background: Cancer-associated stroke (CAS) is a heterogeneous entity in which hypercoagulability represents the most common mechanism, whereas direct tumour embolism is rare and likely under-recognised. Case presentation: A 76-year-old white European man presented with acute left hemiplegia, hemianopsia and dysarthria (NIHSS 18). Non-contrast CT showed early ischaemic changes (ASPECTS 7), CT angiography demonstrated occlusion of the right middle cerebral artery, and CT perfusion revealed a favourable mismatch profile. Mechanical thrombectomy achieved partial recanalisation (TICI 2b). Histopathological examination of the retrieved thrombus revealed malignant epithelial cells. Immunohistochemical analysis was consistent with lung adenocarcinoma with high PD-L1 expression. Continuous cardiac monitoring and 72-h Holter-ECG showed no atrial fibrillation, and transthoracic echocardiography identified no major cardioembolic source. Laboratory testing showed only moderately elevated D-dimer levels. Subsequent chest CT identified a large necrotic mass in the left lung invading the pulmonary vein. Despite initiation of immunotherapy, the patient developed brain metastases and died 51 days after the index stroke. Conclusions: Tumour embolism is a rare but clinically relevant mechanism of ischaemic stroke. It should be considered in patients with embolic stroke of undetermined source, even in the absence of markedly elevated D-dimer levels. Histopathological analysis of thrombectomy specimens may provide clinically relevant diagnostic information and facilitate early detection of occult malignancy in selected patients.

Background: Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies. Methods: A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000–2025) was performed according to PRISMA 2020 guidelines. Search terms included “stroke”, “cancer”, “hypercoagulability”, “coagulopathy”, “disseminated intravascular coagulation”, and “non-bacterial or marantic thrombotic endocarditis”. Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively. Results: Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the ‘three territories sign’. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%. Conclusions: CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.