Stroke stands as one of the most common causes of death among adults worldwide. Currently, tissue plasminogen activator serves as the only approved drug by the Food and Drug Administration for the treatment of acute ischemic stroke. Stem cell therapy serves as a viable treatment option and has been deemed as a safe and effective treatment for stroke patients. Adult human bone marrow-derived NCS-01 cells serve as a potential treatment for stroke given their ability to reduce stroke-induced pathological deficits by increasing cell viability and mitochondrial activity. Recently, we demonstrated the use of adult bone marrow-derived NCS-01 cells both on both in vitro and in vivo models. Using NCS-01 cells in rat stroke models subjected to middle cerebral artery occlusion, an effective dosage of 7.5 × 106 cells/ml, administered through the intracarotid artery within 3 days poststroke, was shown to display significant improvements in motor and neurological behaviors, reductions in infarct area, and peri-infarct cell loss. NCS-01 cells, in comparison with other lines of stem cells (Li cells), are shown to produce greater therapeutic effects, most likely due to the observed filopodia formation that allows the stem cells to extend and target the ischemic cells. Given these findings, NCS-01 stem cells serve as a potential treatment for stroke through the demonstration of profound efficacy and further research that favors their filopodia-mediated mechanism of action.

OBJECTIVE:The objective of this study was to determine the proportion of stroke patients presenting in an extended time window who have a thrombolytic treatment target.BACKGROUND:Patients presenting up to 24 h after stroke onset have been found to have penumbral tissue on multimodal imaging. Stroke patients presenting in this extended time window without a large vessel occlusion (LVO) may benefit from reperfusion therapy using thrombolysis.METHODS:Patients seen at our institutions from 2011 through 2015 were reviewed to identify those who presented >4 h and <24 h from last seen normal (LSN) and did not receive acute treatment. Magnetic resonance imaging (MRI) scans were used to dichotomize patients using a diffusion–perfusion mismatch ratio of 1.2.RESULTS:During the study period, 3469 patients were evaluated by our stroke service, with 893 seen 4–24 h from LSN who were not treated. MRI was performed with diffusion and perfusion imaging in 439 patients, of whom 26 were excluded due to hemorrhage and 37 were excluded due to LVO. This left 376 patients who potentially could have been treated with thrombolysis in an extended time window and were included in the analysis. Of these, 156 (42%) demonstrated a mismatch ratio >1.2. Patients with a mismatch presented earlier (P = 0.012), were more likely to be female (P = 0.03), and had higher National Institutes of Health Stroke Scale (P < 0.001).CONCLUSIONS:Almost half of the patients presenting 4–24 h from LSN had a target for thrombolysis in our study. Multimodal imaging may be able to expand the population of treatable stroke patients given the results of recent clinical trials.

While several large pivotal clinical trials recently revealed a substantial benefit of endovascular thrombectomy for acute ischemic stroke (AIS) caused by large-vessel occlusion, many patients still experience mediocre prognosis. Enlargement of the ischemic core, failed revascularization, incomplete reperfusion, distal embolization, and secondary reperfusion injury substantially impact the salvaging of brain tissue and the functional outcomes of AIS. Here, we propose novel concept of “Multiphase Adjuvant Neuroprotection” as a new paradigm that may help guide our search for adjunctive treatments to be used together with thrombectomy. The premise of multiphase adjuvant neuroprotection is based on the diverse and potentially nonoverlapping pathophysiologic mechanisms that are triggered before, during, and after thrombectomy therapies. Before thrombectomy, strategies should focus on preventing the growth of the ischemic core; during thrombectomy, improving recanalization while reducing distal embolization and maximizing reperfusion are of significant importance; after reperfusion, strategies should focus on seeking targets to reduce secondary reperfusion injury. The concept of multiphase adjuvant neuroprotection, wherein different strategies are employed throughout the various phases of clinical care, might provide a paradigm to minimize the final infarct size and improve functional outcome in AIS patients treated with thrombectomy. With the success of thrombectomy in selected AIS patients, there is now an opportunity to revisit stroke neuroprotection. Notably, if the underlying mechanisms of these neuroprotective strategies are identified, their role in the distinct phases will provide further avenues to improve patient outcomes of AIS.

BACKGROUND:Time-of-flight (TOF) magnetic resonance angiography (MRA) of the head and transcranial Doppler (TCD) are used to diagnose intracranial stenosis, an important cause of ischemic stroke. We aimed to compare TCD findings with TOF-MRA results in a population of patients with symptoms of cerebrovascular disease in whom both tests were done within a short intervening period of each other.METHODS:This is a retrospective, single-center study. Among adult patients referred for symptoms of cerebrovascular disease in both outpatient and inpatient settings, those who received a TCD with adequate insonation of all intracranial arteries and underwent MRA within 3 months intervals of TCD were included in this study. We evaluated the agreement between the results of these two modalities, and also assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD through receiver-operating characteristic (ROC) curve analysis, while MRA considered as a comparator.RESULTS:Among eighty included patients, 720 arteries were examined. An overall significant agreement of 96.5% was observed between TCD and MRA (Kappa = 0.377, P < 0.001). Compared to MRA, TCD had sensitivity of 42.1%, specificity of 99.6%, PPV of 72.7%, and NPV of 98.4% (ROC area: 0.708 [0.594–0.822]). TCD is specifically accurate in evaluating middle cerebral artery (MCA) (ROC area = 0.83).CONCLUSIONS:The high NPV of TCD in our study indicates the utility of TCD as a diagnostic test to exclude the presence of intracranial stenosis. This study supports TCD as a convenient, safe, and reproducible imaging modality applicable in the screening of intracranial stenosis, especially to evaluate MCA.

Morning glory disc anomaly (MGDA) characterizes a congenital dysgenetic disorder of the optic disc, coexisting with arterial intracranial abnormalities, including Moyamoya vascular disease, a significantly rare disease in the European populations. We report a 2.5-year-old female child from Greece previously diagnosed with MGDA, who presented with right-hand paresis, accompanied by focal epileptic spasms, followed by an episode of brief absence seizure, as well as some arm clonic spasms. Magnetic resonance angiography scan revealed the presence of an anomalous origin of the anterior cerebral artery (ACA) from the internal carotid artery (ICA) along with vascular abnormalities, compatible with Moyamoya pattern. To the very best of our knowledge, this is the first reported case of anomalous origin of ACA from the supraclinoid ICA accompanied by severe occlusive intracranial disease (moyamoya-like pattern) in a patient with known MGDA, highlighting the embryonic character of the vascular manifestations in MGDA. It also verifies the association of Moyamoya pattern with MGDA, thus linking vascular dysgenesis as a possible cause of MGDA.

A nonagenarian patient developed a right middle cerebral artery syndrome during recovery after a right internal carotid artery (ICA) balloon angioplasty. Emergent head computed tomography (CT) revealed no acute ischemic changes; CT angiography (CTA) and CT perfusion (CTP) demonstrated a right ICA occlusion with a large right hemispheric predicted core infarct by cerebral blood flow thresholds and minimal mismatch volume. She underwent complete reperfusion in <45 min from symptom onset. Magnetic resonance imaging brain obtained within 48 h showed a decreased infarct volume as that estimated by CTP. This case emphasizes the limitations of estimating the ischemic core with CTP in the golden hour with ultra-early reperfusion and suggests that CTP thresholds should not be used to exclude patients from treatment in the very early time window.

Moyamoya disease (MMD), a rare cause of pediatric stroke, is a cerebrovascular occlusive disorder resulting from progressive stenosis of the distal intracranial carotid arteries and their proximal branches. In response to brain ischemia, there is the development of basal collateral vessels, which gives rise to the characteristic angiographic appearance of moyamoya (puff of smoke). If left untreated, the disease can result in overwhelming permanent neurological and cognitive deficits. Whereas MMD refers to the idiopathic form, moyamoya syndrome refers to the condition in which children with moyamoya also have a recognized clinical disorder. The classic pediatric presentation in moyamoya is recurrent transient ischemic attacks (TIAs) and/or completed/repeated ischemic strokes. Surgical revascularization, including direct and indirect techniques, remains the mainstay of treatment and has been shown to improve long-term outcome in children with MMD. Various risk factors identified for perioperative complications are as follows: history of TIAs, severity of disease, intraoperative hypotension, hypercapnia and hypovolemia, and substantial reduction in hematocrit intraoperatively. Thus, providing perianesthetic care to pediatric patients undergoing revascularization procedure for MMD is like walking a tightrope, and we present two such cases handled successfully.

Asthma has been associated with an increased risk for developing schizophrenia. In addition, schizophrenia has been associated with an increased risk for developing type 2 diabetes mellitus, resulting in an elevated cardiovascular risk and in a limited life expectancy. It is well discussed that dysregulations related to Ca2+ signaling could link these diseases, in addition to cAMP signaling pathways. Thus, revealing this interplay among schizophrenia, diabetes, and asthma may provide novel insights into the pathogenesis of these diseases. Publications involving Ca2+ and cAMP signaling pathways, schizophrenia, diabetes, and asthma (alone or combined) were collected by searching PubMed and EMBASE. Both Ca2+ and cAMP signaling pathways (Ca2+/cAMP signaling) control the release of neurotransmitters and hormones, in addition to airway smooth muscle contractility, then dysregulations of these cellular processes may be involved in these diseases. Taking into consideration, the experience of our group in this field, this narrative review debated the involvement of Ca2+/cAMP signaling in this link among schizophrenia, diabetes, and asthma, including its pharmacological implications.

Uric acid (UA) is a product of the catabolism of purine nucleotides, the principal constituents of DNA, RNA, and cellular energy stores, such as adenosine triphosphate. The main properties of UA include scavenging of hydroxyl radicals, superoxide anion, hydrogen peroxide, and peroxynitrite that make this compound to be the most potent antioxidant in the human plasma. As the result of two silencing mutations in the gene of the hepatic enzyme uricase which degrades UA to allantoin, humans have higher levels of UA than most mammals. However, these levels rapidly decrease following an acute ischemic stroke (AIS), and this decrement has been associated to worse stroke outcomes. This review highlights the safety and potential clinical value of UA therapy in AIS, particularly in patients more exposed to redox-mediated mechanism following the onset of ischemia, such as women, hyperglycemic patients, or patients treated with mechanical thrombectomy. The clinical findings are supported by preclinical data gathered in different laboratories, and in assorted animal species which include male and female individuals or animals harboring comorbidities frequently encountered in patients with AIS, such as hyperglycemia or hypertension. A remarkable finding in these studies is that UA targets its main effects in the brain vasculature since available evidence suggests that does not seem to cross the blood–brain barrier. Altogether, the available data with UA therapy extend the importance of vasculoprotection for effective neuroprotection at the bedside and reinforce the role of endothelial cells after brain ischemia for an increased survival of the whole neurovascular unit.