Spasticity often results from maladaptive neuroplastic changes in both the affected and nonaffected primary motor cortex (M1) that are accompanied by downstream effects on descending motor pathways. The aim of this study was to compare the effects of anodal transcranial direct current stimulation (a-tDCS) over the affected M1 and cathodal tDCS (c-tDCS) over the unaffected M1 in patients with stroke. Thirty-nine patients were divided into the following three groups with a block randomization method: (1) affected M1 a-tDCS, (2) unaffected M1 c-tDCS, and (3) sham tDCS. Additionally, all groups received routine physiotherapy (PT). Electromyographic activity of the lateral gastrocnemius (LG) and tibialis anterior (TA) muscles during passive and active dorsiflexion/plantarflexion (DF/PF), as well as the modified Ashworth scale (MAS) and the World Health Organization Quality of Life Questionnaire (WHOQOL), were assessed before, immediately, and 2 weeks after the interventions. The results indicated that TA activity during active DF increased immediately following the intervention in the affected M1 a-tDCS group compared to the other groups (p < 0.001). LG activity during both active and passive DF decreased, MAS and WHOQOL scores increased immediately and 2 weeks after the intervention in the a-tDCS group (p < 0.001). These findings highlight the immediate and short-term efficacies of affected M1 a-tDCS combined with PT in improving muscle spasticity and function, QOL in these patients. Trial Registration: IRCT20230104057044N1.

Ischemic stroke (IS) is a globally significant disease with complex pathological mechanisms. Traditional therapeutic strategies centered on central nervous system-targeted delivery face substantial limitations due to the presence of the blood-brain barrier (BBB) and the multifactorial nature of the disease. In recent years, the gut microbiota-gut-brain axis, which elucidates the multi-pathway dialogue between the gut and the brain, has provided a novel systemic intervention perspective for IS treatment. In this context, Plant-Derived Nanovesicles (PDNVs), a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Critically, IS itself rapidly induces gut dysbiosis and barrier disruption, creating a vicious cycle that amplifies neuroinflammation-a pathological feature shared with other inflammatory conditions such as colitis and Inflammatory bowel disease. In this context, PDNVs, a class of natural nanocarriers derived from plants, have emerged prominently due to their inherent multi-component synergistic properties, excellent biocompatibility, and cross-kingdom regulatory capabilities. Drawing on mechanistic insights from these related disease models, this article systematically discusses the multi-level integrated mechanism of PDNVs as novel "functional messengers", involving reshaping the gut microenvironment, mediating systemic metabolic-immune signals, and ultimately synergistically activating the central nervous repair network, thereby offering a new paradigm for IS therapy. This review not only summarizes the mechanisms of action of PDNVs but also systematically constructs a framework and strategy for their translation from experimental research to clinical application. Highlighting critical hurdles such as the need for standardized production and rigorous quality control to ensure batch-to-batch consistency.

Polycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm associated with thrombotic and vascular complications. Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that may involve the aorta and can present as aortitis or aneurysm formation. Coexistence of PV and GCA is uncommon and may complicate diagnosis and management. We report a 41-year-old man with low-risk PV (JAK2 V617F-positive) who presented 4 months later with an ischemic stroke and was incidentally found to have a 5.0 cm ascending aortic aneurysm. Despite cytoreduction and surveillance, the aneurysm enlarged to 5.6 cm and was repaired electively. Histopathology of the resected aortic wall showed granulomatous inflammation with multinucleated giant cells and elastic lamina fragmentation, consistent with GCA. The patient had no cranial or systemic features suggestive of active GCA at diagnosis; therefore, systemic corticosteroids were deferred and close rheumatology follow-up was arranged. This case underscores the need to consider inflammatory aortitis/large-vessel vasculitis when atypical vascular findings occur in PV and highlights the value of multidisciplinary evaluation.

Sjögren's syndrome is a long-standing autoimmune condition that predominantly affects the body's exocrine glands, most notably the eyes and mouth, leading to ocular and oral dryness. Neurological involvement, particularly affecting the central nervous system, is infrequently encountered, and the occurrence of stroke as an initial clinical manifestation remains exceptionally uncommon. We report a 42-year-old diabetic male who presented with an acute onset of right hemiplegia and aphasia, and was subsequently diagnosed with primary Sjögren's syndrome. Evaluation revealed multiple acute infarcts in the left middle cerebral artery territory with apical clot and ischemic heart disease. Positive antinuclear antibody by immunofluorescence, Ro-52 recombinant antibody positivity, and raised inflammatory markers suggested an autoimmune vasculitic process secondary to Sjögren's syndrome. The patient improved significantly after pulse methylprednisolone and hydroxychloroquine therapy. This case highlights the importance of considering autoimmune etiologies like Sjögren's syndrome in young stroke patients with systemic features.

Intracranial arterial stenosis is a major cause of ischemic stroke worldwide. It is particularly prevalent among Asian populations. Intracranial arterial stenosis was traditionally considered as a manifestation of atherosclerotic disease. Subsequent research has documented it as a heterogeneous group of vasculopathies with diverse underlying mechanisms. Advanced high-resolution vessel wall imaging and genetic studies have revealed that non-atherosclerotic intracranial arteriopathies occur more commonly than previously recognized. In addition, these arteriopathies often exhibit overlapping clinical and imaging features with atherosclerotic stenosis. In this narrative review, we summarize the representative non-atherosclerotic causes of intracranial arterial stenosis, focusing on their characteristic clinical contexts, imaging hallmarks, and key points for differential diagnosis. Particular attention is given to phenotypic overlap that complicates strict etiological classification in routine clinical practice. We further discuss emerging evidence supporting a genetic contribution to intracranial arterial vulnerability, with particular emphasis on the ring finger protein 213 (RNF213) gene. Originally identified as a major susceptibility gene for moyamoya disease, RNF213 has since been implicated in a broader spectrum of intracranial arterial stenosis, including lesions conventionally classified as atherosclerotic. In addition, accumulating evidence suggests that RNF213-associated vascular phenotypes are not confined to intracranial circulation but may also involve extracranial arterial beds, supporting the concept of RNF213-related vasculopathy. Clinical and imaging studies have indicated that RNF213 variant carriers exhibit distinctive features, such as negative vascular remodeling and accelerated disease progression. Overall, these observations support a conceptual framework in which intracranial arterial stenosis represents a continuum of overlapping phenotypes shaped by genetic susceptibility and acquired modifiers. A 2-hit hypothesis integrating RNF213-related vascular vulnerability with secondary factors such as inflammation, atherosclerosis, or metabolic disorders may provide a unifying model for understanding disease heterogeneity and guiding future research and therapeutic strategies.