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Background Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT). Methods We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus. Results Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = −6.19, 95%CI = −11.69 to −1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62). Conclusion Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.

Dear Sirs,Bilateral symmetric thalamic infarcts are uncommon pre-sentations of ischemic stroke that mostly occur in the ter-ritories of the paramedian thalamic arteries [1]. Thesearteries arise either separately from the posterior cerebralarteries (PCAs) or exceptionally from a single commontrunk the artery of Percheron [2]. In this article, a case ofbithalamic paramedian and midbrain stroke presenting withdrowsiness, ophtalmoplegia, and life-threatening brady-cardia is presented. Despite it is known that different stroketopographic patterns can produce slowing of heart rate andasystolia, this is the first report of acute bradycardia inconcomitance to bilateral midbrain infarction [3–5].A 51-year-old man with a 3-year history of idiopathicarterial hypertension (on zofenopril) was admitted to ouremergency room after being found unresponsive in bed. Onadmission he showed fluctuating level of consciousness,dysarthria, anisocoria, and vertical gaze palsy (NIHSS 7,GCS 9). During examination, the patient suddenly devel-oped severe sinus bradycardia (pulse rate \30 beats perminute (bpm), for 3 minutes) that improved only afteratropine administration. Arterial blood pressure (BP),blood exams, toxicological screening, and brain CT scanwere all normal. Within 1 h, another self-limiting episodeof drowsiness and concomitant bradycardia ensued. Dif-fusion-weighted (DW) sequences on brain MRI demon-strated symmetric bilateral thalamic, hypothalamic, andmidbrain acute infarctions, thus, advocating the occlusionof a putative artery of Percheron (Fig. 1a). Top-of-the-basilar syndrome was ruled out documenting patency ofthe basilar artery and both PCAs by MRI angiography.Extensive cardiological workup showed no signs ofhypertensive cardiomyopathy both on ECG and echocar-diography, but revealed a patent foramen ovale (PFO) withsevere right-to-left atrial shunt. Anticoagulant therapy was,therefore, started and PFO closure suggested. In the fol-lowing days, episodes of bradycardia (nadir of 38 bpm,without major alterations of BP) tended to recur duringdrowsiness and night sleep. Particularly, diurnal fluctua-tions of vigilance paralleled recurrent sleep spindle patternson electroencephalography (Fig. 1b). Sinus bradycardiaoccurred less often and heart rate gradually increased in thefollowing weeks. At the 3-month follow-up, despite fullresolution of gaze palsy and arrhythmia, the patient stillpresented recurring episodes of hypersomnolence andimportant disability due to long-lasting apathy.Infarcts at the mesencephalic–diencephalic junctionresult in complex clinical syndromes contingent on thedeep brain structures involved. Supranuclear vertical gazepalsy and associated abnormal ocular reflexes are related tolesions of the rostral interstitial and Edinger–Westphalnuclei [6]. Fluctuating level of consciousness, coma, andhypersomnolence are attributed to the involvement ofintralaminar nuclei and reticular mesencephalic formation[7]. Notably, while presenting symptoms usually reverseover time, cognitive dysfunctions caused by limbic loopinterruption lead to long-term disability [8]. In our patient