Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust

The gap

Consensus across the literature

Supporting evidence — 7 representative gaps

• The role of remote ischemic conditioning in ischemic stroke: neuroprotective mechanisms and future directions (2026) · doi

  Tianrui Yu 1,2†, Yanghang Chen 1,2,3†, Yutao Lu 1,2, Fan Yu 4, Yuanyuan Xiang 2, Xinyue Kou 1,2, Hui Yang 1,2, Diyang Lyu 5, Moxin Wu 2, Xiaoping Yin 1,2, Zhiying Chen 1,2,6 and Manqing Zhang 6* 1Department of Neurology, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China, 2Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, China, 3Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China, 4College of Life Sciences, Nanchang University, Nanchang, Jiangxi, China, 5Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China, 6Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, Jiangxi, China Despite advances in vessel recanalization, ischemic stroke remains a leading cause of mortality, highlighting the need for comprehensive neuroprotective strategies such as remote ischemic conditioning (RIC). This review evaluates the multitargeted mechanisms of RIC, its progress in clinical translation, and the key factors determining its efficacy. In preclinical models, RIC exerts neuroprotection by modulating neuroinflammation, preserving the blood-brain barrier, and pro- moting angiogenesis and remyelination. Notably, it suppresses multiple pro- grammed cell death pathways, including pyroptosis, apoptosis, ferroptosis, and disulfidptosis. However, analyses of recent high-quality clinical trials (e.g., SERIC- EVT, RESIST, and RICAMIS) reveal heterogeneous efficacy, indicating that clinical success is highly dependent on the specific execution protocol and successful cerebral reperfusion. Furthermore, critical patient-specific variables such as circadian rhythms, baseline systemic inflammation, and levels of both lipopro- tein(a) and mean corpuscular hemoglobin (MCH) significantly influence thera- peutic outcomes. Ultimately, while RIC is a highly translatable therapeutic strategy, its successful clinical application relies on the standardization of treat- ment protocols, the use of precision medicine to identify optimal responders, and its integration with existing therapies to maximize long-term stroke recovery. KEYWORDS remote ischemic conditioning, ischemic stroke, neuroinflammation, neuroprotection, combination therapy

  Keywords: jiujiang jiangxi china university clinical nanchang ischemic department neurology hospital precision medicine stroke ammation chen
• The utility of viscoelastic hemostatic assays in neurocritical illness (2026) · doi

  Critical evidence gaps remain. Future work should prioritize: 1. large, prospective neuro-specific cohorts using standardized viscoelastic thresholds. 2. randomized trials evaluating VHA-guided transfusion or reversal strategies in TBI and SAH. 3. harmonization of assay parameters and clinical definitions. 4. mechanistic studies linking VHA abnormalities with neurovascular pathophysiology. 5. and targeted evaluation of TEG-guided antiplatelet therapy in stroke populations.

  Keywords: guided critical evidence gaps remain future prioritize large prospective neuro specific cohorts using standardized viscoelastic
• The potential role of transcranial direct current stimulation in experimental ischemic stroke in adult male albino rats (2026) · doi

  Another limitation of the present study is the short observation period, as outcomes were assessed only at 24 h post-ischemia. Another limitation of this study is the relatively small sample size (n = 5 per group), which may reduce statistical power, particularly in the context of the inherent variability of experimental stroke models.

  Keywords: limitation present short observation period outcomes assessed post ischemia relatively small sample size group reduce
• Differential impact of cumulative cerebral small-vessel disease burden on ischemic versus hemorrhagic stroke recurrence in hemorrhage-prone patients (2026) · doi

  There are some methodological limitations to be consid- ered. First, this study is an exploratory post hoc analysis. While our results demonstrate strong associations between m-cSVD burden and recurrent stroke risk in hemorrhage- prone patients, they should be interpreted as suggesting potential relationships rather than establishing causality. Furthermore, as most prospective clinical trials including PICASSO largely excluded patients who are in poor medi- cal condition or in a functionally dependent state, our study population might not reflect a real-world setting. Second, significant baseline imbalances existed across m-cSVD groups; patients with higher scores were older and had greater clinical and vascular frailty. This disparity, poten- tially reflecting clinical caution regarding intensive therapy in patients with high hemorrhagic burden, is noteworthy given the established role of statins in secondary preven- tion. Although we performed multivariable adjustments to mitigate these imbalances, the possibility of residual con- founding remains, necessitating a cautious interpretation of the independent prognostic value attributed to the m-cSVD score. Third, the relatively low incidence of hemorrhagic stroke compared to ischemic events might have resulted in insufficient statistical power to provide precise estimates of the association with m-cSVD scores. Consequently, the find- ings regarding hemorrhagic risk should be interpreted with caution, and larger-scale studies are warranted to further validate these associations. Forth, given that the phenotypes of cSVD markers are heterogeneous and vary according to their numbers, simple scoring of total cSVD by adding a point may jeopardizes the precision of estimates for assess- ing recurrent stroke risk. A detailed cSVD scoring approach that quantitatively incorporated the severity of each pheno- type may be more informative. Fifth, our study did not dis- tinguish between the anatomical locations (deep vs. lobar) of ICH or CMBs, which could reflect different underlying etiologies such as hypertensive arteriopathy and CAA. However, since approximately nine out of ten participants had hypertension, our results may reflect the outcomes of a population with hypertensive arteriopathy. Lastly, the use of a m-cSVD score that excludes EPVS was necessitated by data availability within the PICASSO database, and this modified score has not undergone full external validation. However, WMH, CMBs/ICH, and lacune are considered the core imaging markers in predicting vascular outcomes, which may mitigate the potential impact of excluding EPVS on our primary findings regarding stroke recurrence risk. 1 3Neurological Sciences (2026) 47:511511 Page 8 of 9

  Keywords: csvd stroke risk patients clinical reflect regarding hemorrhagic score associations burden recurrent interpreted potential picasso
• Thrombotic molecular markers after intravenous thrombolysis are associated with early neurological deterioration in acute ischemic stroke (2026) · doi

  Early neurological deterioration (END) is a frequent and serious complication after intravenous thrombolysis in acute ischemic stroke (AIS), yet the clinical relevance of thrombotic molecular markers related to coagulation, fibrinolysis, and endothelial dysfunction remains incompletely understood.

  Keywords: early neurological deterioration frequent serious complication intravenous thrombolysis acute ischemic stroke clinical relevance thrombotic molecular
• Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke (2024) · doi

  Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.

  Keywords: stroke antiplatelet patients ischemic importance dual therapy superior single reducing recurrent among transient attack minor
• Acute ischemic stroke after scuba diving in a patient with patent foramen ovale: a case of paradoxical embolism (2026) · doi

  This case report is limited by its single-patient de- sign and therefore does not allow definitive causal inference. The presumed embolic mechanism re- mains indirect, as no thrombus or gas embolus was directly visualized. Although venous Doppler ultra- sonography was negative, occult thrombosis cannot be fully excluded. Reperfusion after intravenous thrombolysis was not angiographically confirmed and is inferred from rapid clinical recovery and dif- fusion-negative MRI findings. cONcLUsION Ischemic stroke is a medical emergency associat- ed with high disability and mortality rates. A multi- rEFErENcEs 1. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct;20(10):795-820. doi: 10.1016/S1474-4422(21)00252-0. 2. Dimitrova M. Diagnostic and therapeutical approaches in cryptogenic stroke. Sofia: J.A.M.G. BOOKS, 2021. p. 68. 3. Buttinelli C, Beccia M, Argentino C. Stroke in a scuba diver with patent foramen ovale. Eur J Neurol. 2002 Jan;9(1):89-91. doi: 10.1046/j.1468- 1331.2002.00347.x. 4. Ries S, Knauth M, Kern R, Klingmann C, Daffertshofer M, Sartor K, Hennerici M. Arterial gas embolism after decompression: correlation with right-to-left shunting. Neurology. 1999 Jan 15;52(2):401-4. doi: 10.1212/wnl.52.2.401. 5. Schwerzmann M, Seiler C, Lipp E, Guzman R, Lövblad KO, Kraus M, Kucher N. Relation between directly detected patent foramen ovale and ischemic brain lesions in sport divers. Ann Intern Med. 2001 Jan 2;134(1):21-4. doi: 10.7326/0003-4819-134-1-200101020-00009. 6. Gerriets T, Tetzlaff K, Liceni T, Schäfer C, Rosengarten B, Kopiske G, et al. Arteriovenous bubbles following cold water sport dives: relation to right-to- disciplinary approach is mandatory in order to iden- tify the etiological causes of its occurrence in young individuals. In patients with neurological symptoms after diving, paradoxical embolism through a PFO should be strongly considered. Assessing the individual risk profile is essential for implementing an optimal, personalized second- ary stroke prevention plan. Authors' contributions: Conceptualization, M.A., M.T.-M., and A.K.; clinical management of the patient, M.A., V.D.-K., M.T.-M., and A.K.; diagnostic evaluation and interpretation, M.A., V.D.-K., and A.K.; data collection and curation, M.A. and V.D.-K.; writing—original draft preparation, M.A. and M.T.-M.; writing—review and editing, M.A., V.D.-K., M.T.-M., and A.K.; supervision, M.T.-M. and A.K. All authors have read and agreed to the pub- lished version of the manuscript. Conflict of interest: The authors declare no conflict of interest. Financial support: This research received no specific grant from any funding agency in the public, comme

  Keywords: stroke authors patient directly negative clinical ischemic global burden risk neurol diagnostic patent foramen ovale