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ORIGINAL ARTICLES
Exception from informed consent in the era of social media: The SEGA stroke trial experience
Mehmet Enes Inam, Aditya Sanzgiri, Elvira Lekka, Sunil A Sheth, Andrew D Barreto, Sean I Savitz, Carlos Artime, Claudia Pedroza, Allison Engstrom, Faheem G Sheriff, Alexander Ambrocik, Peng Roc Chen
October-December 2021, 7(4):253-258
DOI:10.4103/bc.bc_44_21  
INTRODUCTION: Patients with acute ischemic stroke (AIS) and neurologic deficits are often unable to provide consent and excluded from emergency research participation. Experiences with exception from informed consent (EFIC) to facilitate research on potentially life-saving emergency interventions are limited. Here, we describe our multifaceted approach to EFIC approval for an ongoing randomized clinical trial that compares sedation versus general anesthesia (SEGA) approaches for endovascular thrombectomy during AIS. METHODS: We published a university clinical trial website with EFIC information. We initiated a social media campaign on Facebook within a 50 mile radius of Texas Medical Center. Advertisements were linked to our website, and a press release was issued with information about the trial. In-person community consultations were performed, and voluntary survey information was collected. RESULTS: A total of 193 individuals (65% female, age 46.7 ± 16.6 years) participated in seven focus group community consultations. Of the 144 (75%) that completed surveys, 88.7% agreed that they would be willing to have themselves or family enrolled in this trial under EFIC. Facebook advertisements had 134,481 (52% females; 60% ≥45 years old) views followed by 1,630 clicks to learn more. The website had 1130 views (56% regional and 44% national) with an average of 3.85 min spent. Our Institutional Review Board received zero e-mails requesting additional information or to optout. CONCLUSION: Our social media campaign and community consultation methods provide a significant outreach to potential stroke patients. We hope that our experience will inform and help future efforts for trials seeking EFIC.
  42,704 5,433 -
REVIEW ARTICLES
Occludin regulation of blood–brain barrier and potential therapeutic target in ischemic stroke
Shuhua Yuan, Ke Jian Liu, Zhifeng Qi
July-September 2020, 6(3):152-162
DOI:10.4103/bc.bc_29_20  
Occludin is a key structural component of the blood–brain barrier (BBB) that has recently become an important focus of research in BBB damages. Many studies have demonstrated that occludin could regulate the integrity and permeability of the BBB. The function of BBB depends on the level of occludin protein expression in brain endothelial cells. Moreover, occludin may serve as a potential biomarker for hemorrhage transformation after acute ischemic stroke. In this review, we summarize the role of occludin in BBB integrity and the regulatory mechanisms of occludin in the permeability of BBB after ischemic stroke. Multiple factors have been found to regulate occludin protein functions in maintaining BBB permeability, such as Matrix metalloproteinas-mediated cleavage, phosphorylation, ubiquitination, and related inflammatory factors. In addition, various signaling pathways participate in regulating the occludin expression, including nuclear factor-kappa B, mitogen-activated protein kinase, protein kinase c, RhoK, and ERK1/2. Emerging therapeutic interventions for ischemic stroke targeting occludin are described, including normobaric hyperoxia, Chinese medicine, chemical drugs, genes, steroid hormones, small molecular peptides, and other therapies. Since occludin has been shown to play a critical role in regulating BBB integrity, further preclinical studies will help evaluate and validate occludin as a viable therapeutic target for ischemic stroke.
  41,109 5,384 21
Vascular tortuosity in endovascular mechanical thrombectomy
Jeffrey Farooq, Jea Young Lee
January-March 2021, 7(1):3-7
DOI:10.4103/bc.bc_5_21  
Endovascular mechanical thrombectomy effectively removes occlusive thrombi from the arterial lumen; however, there is little literature supporting the relevance of vascular geometry on surgical outcomes. Critical vessel characteristics including the degree of angulation and tortuosity influence the ability to advance stent retriever devices toward the site of occlusion. Therefore, it is crucial to evaluate the impact of carotid artery catheter pathway accessibility on the thrombectomy outcomes in acute ischemic stroke (AIS) patients. Traditional imaging modalities generate incomplete pictures of the vascular tortuosity and are prone to clinical judgment errors. Recent three-dimensional computed tomography angiography image analysis techniques circumvent these limitations to calculate accurate tortuosity and angulation measurements. These novel images facilitate classifying common anatomical variant patients into groups that may be treated with specially designed catheter devices. Importantly, this image analysis method reveals significant angulation in the common carotid artery and extracranial internal carotid artery that correlates with delays in reaching the occlusion site. Increased age, which is associated with increased risk of stroke, also increases the incidence of severe tortuosity. The semi-automated measurements technique also demonstrate that full 360° arterial loops are present in nearly 3% of catheter pathways and that the overall degree of angulation differs bilaterally. In this review, we examine the utility of this novel image analysis procedure and evaluate the recent literature relevant to neuroendovascular thrombectomy in AIS patients. Three literature databases – PubMed, Embase, and Web of Science were queried for original articles investigating both preclinical and clinical thrombectomy applications.
  39,188 6,167 1
ORIGINAL ARTICLES
Demographic age-related variation in Circle of Willis completeness assessed by digital subtraction angiography
Ryan G Eaton, Varun S Shah, David Dornbos III, Orel A Zaninovich, Nicole Wenger, Travis M Dumont, Ciarán J Powers
January-March 2020, 6(1):31-37
DOI:10.4103/bc.bc_43_19  
OBJECTIVE: Incomplete circle of Willis (CoW) configuration is an important risk factor for cerebrovascular pathology, namely aneurysm formation and ischemic stroke. This study was performed to characterize CoW variation using digital subtraction angiography and to identify demographic and physiologic features that may influence the risk of having an incomplete CoW configuration. MATERIALS AND METHODS: A retrospective review of 274 patients who underwent cerebral angiography by a single surgeon for any indication was conducted. Each CoW branch was graded as normal, hypoplastic, or aplastic. Univariate and multivariate regression analyses were conducted to assess the impact of age, gender, race, and certain comorbidities on CoW configuration. RESULTS: A complete CoW was identified in 37.23% of patients. In univariate analysis, patients <40 years old were more likely to have a complete CoW (odds ratio [OR]: 4.973, 95% confidence interval [CI]: 2.610–9.476, P < 0.001) as were patients <70 years old (OR: 2.849, 95% CI: 1.131–7.194, P < 0.05). Univariate analysis on demographic factors and comorbidities revealed CoW completeness to decrease with hypertension (OR: 0.575, 95% CI: 0.347–0.951, P = 0.031) and diabetes mellitus (OR: 0.368, 95% CI: 0.180–0.754, P = 0.006). Multivariable logistic regression analysis used to assess the impact of age on CoW completeness showed age to be an independent predictor of complete CoW, with an inverse correlation between increasing age and CoW completeness (OR: 0.955, 95% CI: 0.937–0.973, P < 0.001) after controlling for potential confounders including hypertension and diabetes mellitus. CONCLUSIONS: CoW configuration shows considerable variation with age; however, further investigation is required to elucidate the full impact of other demographic and vascular risk factors on CoW anatomy.
  40,050 5,236 5
REVIEW ARTICLES
Slit ventricle syndrome: Historical considerations, diagnosis, pathophysiology, and treatment review
Dimitrios Panagopoulos, Ploutarchos Karydakis, Marios Themistocleous
July-September 2021, 7(3):167-177
DOI:10.4103/bc.bc_29_21  
After the introduction of shunt treatment for the management of childhood hydrocephalus, a wide variety of complications related to this treatment modality have been recognized. The entity of slit ventricle syndrome (alternatively, symptomatic ventricular coaptation) is one of them, is frequently encountered in the pediatric population and its symptom complex resembles that of shunt failure. We conducted research on PubMed®, MEDLINE®, and Web of Science®, using the keywords: “slit ventricles,” “slit ventricle syndrome,” “SVS” and “ventricular coaptation.” The aim of our review was to trace the advances made through the past decades, concerning our knowledge about the clinical characteristics, pathophysiology, and treatment options of this entity. The discrepancy among researchers about the offending etiology and the optimum treatment algorithm of this entity, as well as the necessity of an updated concept regarding shunt over drainage is analyzed. The multiple treatment modalities proposed and pathophysiologic mechanisms implicated for the treatment of slit ventricle syndrome illustrate the complexity of this entity. Consequently, the issue requires more detailed evaluation. In this review, we comment on all the main facets related to shunt over drainage and the resultant slit ventricle syndrome.
  38,271 5,998 1
ORIGINAL ARTICLES
Regional leptomeningeal collateral score by computed tomographic angiography correlates with 3-month clinical outcome in acute ischemic stroke
D Chatterjee, K Nagarajan, Sunil K Narayan, R Lakshmi Narasimhan
April-June 2020, 6(2):107-115
DOI:10.4103/bc.bc_55_19  
PURPOSE: The aim of the study is to assess the correlation between regional leptomeningeal collateral (rLMC) Scores calculated on computed tomography (CT) angiography following acute anterior circulation ischemic stroke, with 3-month clinical outcome measured as modified Rankin Scale (mRS) and Barthel Index (BI). MATERIALS AND METHODS: A total of thirty patients were studied as per the exclusion and inclusion criteria and after informed consent. Multi-phase CT angiography was carried out within 24 h of stroke onset, and collateral scoring was done using rLMC score along with Alberta stroke programme early CT (ASPECT) scoring. At 3 months, patients were followed up to evaluate the clinical outcome using mRS and BI. Statistical analysis was performed to find out the correlation between rLMC score, ASPECT score, and clinical outcome and for association with demographic parameters and stroke risk factors. RESULTS: A strong correlation was noted between ASPECT and rLMC scores (P < 0.001) and between rLMC scores and clinical outcome at 3 months (mRS and BI). Correlation with mRS (P < 0.001) was nearly as strong as that of BI on follow-up (P < 0.001). The ASPECT score also was a predictor of clinical outcome and showed correlation with mRS (P < 0.001) and BI (P < 0.001). No significant association was found between various stroke risk factors and demographic parameters with rLMC scores. The rLMC scoring system showed substantial inter-rater reliability with Kappa = 0.7. CONCLUSIONS: rLMC score in CT angiography correlates with ASPECT Score and clinical outcome at 3 months. Hence, this scoring system can be used for collateral quantification as may be of use in predicting short-term clinical outcomes.
  38,572 5,016 1
Recanalization of cervicocephalic artery dissection
Smit D Patel, Rafique Haynes, Ilene Staff, Ajay Tunguturi, Sedeek Elmoursi, Amre Nouh
July-September 2020, 6(3):175-180
DOI:10.4103/bc.bc_19_20  
BACKGROUND AND PURPOSE: While there exists a substantial literature on the risk factors and clinical manifestations of cervical artery dissection (CeAD) including carotid and vertebral artery, little is known about postdissection recanalization. The goal of our study was to provide a descriptive analysis of CeAD and recanalization after dissection with neuroimaging follow up. METHODS: We retrospectively analyzed 51 consecutive patients with confirmed diagnoses of CeAD based on neuroimaging. Demographic data, risk factors, and dissection characteristics were recorded. Neuroimaging studies were performed at 0, 3, 6, and >6 months. RESULTS: Among 51 cases, the mean age of dissection (mean ± standard error) was 49.4 ± 1.92 years, and female comprised 58.8% of the patients. Extent of stenosis was 100% dissection in 37.3%, 51%–99% in 41.2%, and <51% in 21.5%. The most common presenting symptoms were headache (54.9%), neck pain (49.0%), and dizziness/gait imbalance (39.2%). The most common associated risk factors were recent history of trauma to the head and neck (41.2%) and hypertension (41.2%). In follow-up imaging, overall, 47.1% (24/51) had complete recanalization (CR), while 35.3% (18/51) did not; in the former group, 75% (18/24) recanalized completely during the first 6 months following symptom onset. A majority (84.3%) of the patients were discharged home, 15.7% were discharged to a facility, and no mortality was reported. Interestingly, location, type-/nature of dissection, and treatment did not statistically appear to influence the likelihood of recanalization. CONCLUSIONS: The recanalization of CeAD occurs mainly within the first 6 months after symptom onset, following which healing slows down. The study did not find an association between location, pattern, or nature of dissection on artery recanalization.
  38,260 4,955 3
Increased concentration of serum gamma-glutamyl transferase in ischemic stroke patients
Teja Ram Kalirawna, Jitendra Rohilla, Shyam Sunder Bairwa, Sunil Kumar Gothwal, Pinki Tak, Rajesh Jain
April-June 2021, 7(2):71-76
DOI:10.4103/bc.bc_47_20  
BACKGROUND: Stroke is responsible for the largest proportion of neurological disorders causing a significant morbidity. Gamma-glutamyl transferase (GGT) enzyme has an active involvement in atherosclerosis through its role in oxidative and inflammatory mechanisms. Recent evidence suggests that serum GGT is related to the risk and prognosis of cerebrovascular diseases. METHODS: A total of 200 patients (100 with acute ischemic stroke and 100 without stroke) were recruited from various medical wards and medical intensive care unit. Categorical variables were compared between two groups using Chi-squared test and odds ratio (OR). Independent sample t-test was used to see to compare mean GGT level of stroke patients with control. RESULTS: There was no statistical difference with respect to distribution of age groups (χ2 = 1.25, P = 0.741) and gender (χ2 = 2.678, P = 0.1018) between cases and controls. Mean age of stroke patients (mean [M] = 61.7, standard deviation [SD] = 13.8) did not differ from controls (M = 62.2, SD = 13.6), P = 0.80. The odds of suffering from diabetes were significantly higher in stroke patients than cases (OR = 2.25, P = 0.005). Independent sample t-test found a significant difference in serum GGT level between cases (M = 57.47, SD = 11.8) and control (M = 41.72, SD = 7.5), P ≤ 0.0001. CONCLUSIONS: Serum GGT was significantly higher in stroke patients than age-sex-matched nonstroke patients. Association remained significant in stroke patients irrespective of age, gender, and other risk factors. Stroke patients with diabetes, hypertension, dyslipidemia, obesity, and smoking had higher level serum GGT level than those without these risk factors. Prospective cohort studies can further explore the potential of GGT as a predictor of acute ischemic stroke.
  37,257 5,350 -
REVIEW ARTICLES
Mini-review (Part II): A clinical consideration on exercise and ischemic conditioning in stroke rehabilitation
Melissa Wills, Yuchuan Ding
October-December 2021, 7(4):225-229
DOI:10.4103/bc.bc_56_21  
Exercise therapy is commonly recommended and is often considered to be the gold standard of rehabilitation in patients with ischemic stroke. However, implementation and standardization of exercise therapy are challenging as patients vary in their abilities, disabilities, and willingness to participate in exercise rehabilitation after a cerebrovascular event. Remote ischemic conditioning (RIC) is a more passive and accessible therapy that, although remains in its infancy, has the potential to confer similar neuroprotective effects as exercise. In the previously published Part I of this Mini Review, we examined the biochemical evidence for exercise and RIC and noted that the in vitro results may be misleading outside of the context of clinical application. In the present review, we investigate the various clinical parameters by which exercise and RIC therapy may be most beneficial to ischemic stroke victims. We also extend our discussion to consider the therapeutic combination of RIC and exercise therapy to maximize functional outcomes after stroke.
  36,221 5,504 2
The unsolved mystery of hippocampal cholinergic neurostimulating peptide: A potent cholinergic regulator
Justin Y Cho, Noriyuki Matsukawa
January-March 2021, 7(1):29-32
DOI:10.4103/bc.bc_14_21  
This review discusses the potential of major histocompatibility complex (MHC) Class II constructs as stroke therapeutics. We focus on the delivery of MHC Class II construct, DRmQ, as a safe and effective treatment for ischemic stroke. DRmQ was observed to attenuate behavioral deficits and decrease microglia activation and proinflammatory cytokines, illustrating its ability to mitigate the secondary cell death following stroke. Similar anti-neuroinflammation treatments, such as transplantation of mesenchymal stem cells and mitochondrial transfers, are briefly discussed to provide further support that sequestration of inflammation stands as a robust therapeutic target for stroke.
  36,140 5,342 -
Mini review (Part I): An experimental concept on exercise and ischemic conditioning in stroke rehabilitation
Qingzhu Wang, Melissa Wills, Zhenzhen Han, Xiaokun Geng, Yuchuan Ding
October-December 2020, 6(4):242-247
DOI:10.4103/bc.bc_63_20  
Stroke remains a leading cause of adult death and disability. Poststroke rehabilitation is vital for reducing the long-term sequelae of brain ischemia. Recently, physical exercise training has been well established as an effective rehabilitation tool, but its efficacy depends on exercise parameters and the patient's capacities, which are often altered following a major cerebrovascular event. Thus, ischemic conditioning as a rehabilitation intervention was considered an “exercise equivalent,” but the investigation is still in its relative infancy. In this mini-review, we discuss the potential for physical exercise or ischemic conditioning and its relation to angiogenesis, neurogenesis, and plasticity in stroke rehabilitation. This allows the readers to understand the context of the research and the application of ischemic conditioning in poststroke rehabilitation.
  35,305 5,224 5
Multiphase adjuvant neuroprotection: A novel paradigm for improving acute ischemic stroke outcomes
Wenbo Zhao, Chuanjie Wu, David Dornbos III, Sijie Li, Haiqing Song, Yuping Wang, Yuchuan Ding, Xunming Ji
January-March 2020, 6(1):11-18
DOI:10.4103/bc.bc_58_19  
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.
  33,657 5,671 21
REVIEW ARTICLE
The 100 most cited articles in the endovascular treatment of brain arteriovenous malformations
Runlin Yang, Yifan Ren, Julian Maingard, Vincent Thijs, Dustin Viet Anh Le, Hong Kuan Kok, Michael J Lee, Joshua A Hirsch, Ronil V Chandra, Duncan Mark Brooks, Hamed Asadi
April-June 2021, 7(2):49-64
DOI:10.4103/bc.bc_46_20  
BACKGROUND: The literature base for endovascular treatment of brain arteriovenous malformations (BAVMs) has grown exponentially in recent decades. Bibliometric analysis has been used to identify impactful articles in other medical specialties. The aim of this citation analysis was to identify and characterize the top 100 most cited articles in the field of endovascular BAVM treatment. METHODS: The top-cited papers were identified by searching selected keywords (“endovascular treatment,” “interventional treatment,” “brain arteriovenous malformation,” “emboliz(s)ation”) on the Web of Science platform. The top 100 articles were ranked according to their number of citations. Each article was further evaluated to obtain predefined characteristics including citation(s) per year, year of publication, authorship, journal-title and impact factor, article topics, article type, and level of evidence. RESULTS: The top 100 most cited articles for endovascular BAVM treatment were published between 1960 and 2014. The total number of citations for these articles ranged from 56 to 471 (median 85.5). Most articles (76%) were published between 1990 and 2009 in three journals (56%), originated in the USA (52%) followed by France (16%). The most common topic related to embolization agents and the majority of articles constituted level IV or V evidence. CONCLUSIONS: This study provides a comprehensive overview of the most cited articles in the field of endovascular BAVM treatment. Our analysis recognizes key contributions from authors and institutions in the field and leads to a better understanding of the evidentiary framework for BAVM treatment.
  33,622 5,630 -
ORIGINAL ARTICLES
Ruptured Fisher grade 3 blister aneurysms have a higher incidence of delayed cerebral ischemia than ruptured Fisher grade 3 saccular aneurysms
Tejas Karnati, Tamar R Binyamin, Brian C Dahlin, Ben Waldau
April-June 2020, 6(2):116-122
DOI:10.4103/bc.bc_63_19  
BACKGROUND: Blister aneurysms are a rare subclass of aneurysms, which remain challenging to treat both with open cerebrovascular and endovascular techniques, and clinicians continue to see poor outcomes in some cases despite improvements in technology. Based on our clinical observations, we hypothesized that patients with a Fisher grade 3 subarachnoid hemorrhage (SAH) from a ruptured anterior circulation blister aneurysm are significantly more likely to develop poor outcome due to delayed cerebral ischemia than patients with a Fisher grade 3 SAH from a ruptured anterior circulation saccular aneurysm. METHODS: In this consecutive case series, we reviewed management, outcomes, and rates of delayed cerebral ischemia for all ruptured anterior circulation blister aneurysms from 2012 to 2018 at our institution and compared them to a concurrent cohort of ruptured saccular anterior circulation aneurysms. A blister aneurysm was defined as an aneurysm that arises from a nonbranching point and demonstrates hemispherical anatomy on diagnostic angiography. RESULTS: We identified 14 consecutive ruptured anterior circulation blister aneurysms. Thirteen aneurysms were treated operatively– 5 with clip remodeling and 8 with flow diversion embolization. While clip remodeling had a high intraoperative rupture rate (80%), there was only one (12.5%) intraoperative rupture with flow diversion embolization. Outcomes were worsened by delayed cerebral ischemia from vasospasm in patients with Fisher 3 hemorrhages from blister aneurysms (86%). The rate of delayed cerebral ischemia from vasospasm was significantly higher for ruptured blister aneurysms than for a concurrent cohort of ruptured saccular aneurysms (8.6%,P = 0.0001). CONCLUSION: Ruptured Fisher grade 3 anterior circulation blister aneurysms have a significantly higher incidence of delayed cerebral ischemia from vasospasm compared to saccular aneurysms, regardless of the treatment modality.
  34,224 4,983 1
Pipeline embolization of ruptured, previously coiled cerebral aneurysms: Case series and considerations for management
Jared B Cooper, Boyi Li, Gurmeen Kaur, Chirag D Gandhi, Justin G Santarelli
April-June 2021, 7(2):111-117
DOI:10.4103/bc.bc_59_20  
PURPOSE: Aneurysmal recurrence represents a significant drawback of endovascular coiling, particularly in aneurysms that have previously ruptured. Given the high recurrence rate of coiled aneurysms and particularly the risk of posttreatment rupture in previously ruptured aneurysms that have been treated by coiling, the question of how best to treat ruptured aneurysms that recur postcoiling remains. MATERIALS AND METHODS: We conducted a retrospective analysis of twenty patients who underwent pipeline embolization of previously ruptured, coiled cerebral aneurysms. RESULTS: Pipeline embolization device (PED) treatment resulted in complete aneurysmal occlusion in 10 patients (62.5%) at first angiographic follow-up, and 11 patients (68.75%) at last follow-up. No PED-related complications were encountered and there were no peri-procedural or postprocedural hemorrhages, or symptomatic ischemic events following flow diversion. CONCLUSIONS: PED as a second-line treatment is a safe and effective modality for achieving aneurysmal occlusion in recurrent, previously ruptured, primarily coiled aneurysms. Additionally, a staged coil-to-PED approach may be considered for the management of acutely ruptured aneurysms to achieve aneurysmal obliteration in an effort to mitigate recurrence, and reduce the amount of postprocedural studies.
  36,309 2,329 1
REVIEW ARTICLES
A link among schizophrenia, diabetes, and asthma: Role of Ca2+/cAMP signaling
Leandro Bueno Bergantin
July-September 2020, 6(3):145-151
DOI:10.4103/bc.bc_66_19  
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.
  32,009 5,722 1
ORIGINAL ARTICLES
The prevalence and risk factors of stroke among Sudanese individuals with diabetes: Cross-sectional survey
Ahmed Omer Almobarak, Safaa Badi, Wadie M Elmadhoun, Hanan Tahir, Mohamed H Ahmed
January-March 2020, 6(1):26-30
DOI:10.4103/bc.bc_15_19  
INTRODUCTION: Diabetes complications in Sudan were increasing at an alarming rate. The aim of this study was to assess the prevalence of stroke among Sudanese individuals with diabetes. METHODOLOGY: This cross-sectional study recruited 283 individuals with diabetes from three diabetes centers in Sudan. Data were collected using a standardized pretested questionnaire, and data were analyzed using Chi-square and logistic regression analysis. RESULTS: The average age of participants was 51 (±12 standard deviation) and 35% were aged between 51 and 60 years. Females were 66.8%, and most of the participants (73.9%) were from urban areas and 66.1% received formal education between primary school and university. Body mass index (BMI) classification showed that 34.3% were obese, 31.8% overweight, and 30.4% normal BMI. Diabetes for 1-5 years were observed in 71.7% and for more than 10 years (12%). The majority, i.e., 94.3% had type 2 diabetes mellitus while only 5.7% had type 1. Only one-third of the participants were able to achieve glycosylated hemoglobin (HbA1c) target for diabetes control. The prevalence of cerebrovascular accident (CVA) was 2.5%, hypertension (HTN) was 20%, ischemic heart disease 3.2%, and neuropathy was 45.6%. Chi-square test showed significant association between HbA1c, serum creatinine, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein level, and the presence of CVA. Logistic regression analysis showed HbA1c, and the duration of diabetes are significantly associated with the presence of CVA (P = 0.010, 0.014). CONCLUSION: The prevalence of stroke among Sudanese individuals with diabetes was around 2.5%. The main risk factors were HbA1c, HTN, and duration of diabetes.
  33,331 3,211 5
REVIEW ARTICLES
Role of vinpocetine in ischemic stroke and poststroke outcomes: A critical review
Hayder M Al-Kuraishy, Ali I Al-Gareeb, Marwa Thaier Naji, Farah Al-Mamorry
January-March 2020, 6(1):1-10
DOI:10.4103/bc.bc_46_19  
Vinpocetine (VPN) is a synthetic ethyl-ester derivative of the alkaloid apovincamine from Vinca minor leaves. VPN is a selective inhibitor of phosphodiesterase type 1 (PDE1) that has potential neurological effects through inhibition of voltage-gated sodium channel and reduction of neuronal calcium influx. VPN has noteworthy antioxidant, anti-inflammatory, and anti-apoptotic effects with inhibitory effect on glial and astrocyte cells during and following ischemic stroke (IS). VPN is effective as adjuvant therapy in the management of epilepsy; it reduces seizure frequency by 50% in a dose of 2 mg/kg/day. VPN improves psychomotor performances through modulation of brain monoamine pathway mainly on dopamine and serotonin, which play an integral role in attenuation of depressive symptoms. VPN recover cognitive functions and spatial memory through inhibition of hippocampal and cortical PDE1 with augmentation of cyclic adenosin monophosphate and cyclic guanosin monophosphate ratio, enhancement of cholinergic neurotransmission, and inhibition of neuronal inflammatory mediators. Therefore, VPN is an effective agent in the management of IS and plays an integral role in the prevention and attenuation of poststroke epilepsy, depression, and cognitive deficit through direct cAMP/cGMP-dependent pathway or indirectly through anti-inflammatory and antioxidant effects.
  30,857 3,141 17
COMMENTARIES
Neurological disorders of COVID-19 can be explained in terms of both “loss and gain of function” states of a solution for the nervous system
Kunjumon Ittira Vadakkan
July-September 2021, 7(3):217-222
DOI:10.4103/bc.bc_46_21  
  29,302 1,933 1
REVIEW ARTICLES
Clinical application of nitric oxide in ischemia and reperfusion injury: A literature review
Shangqian Jiang, Chaitu Dandu, Xiaokun Geng
October-December 2020, 6(4):248-253
DOI:10.4103/bc.bc_69_20  
Ischemia–reperfusion injury (IRI) is a series of multifactorial cellular events that lead to increased cellular dysfunction after the restoration of oxygen delivery to hypoxic tissue, which can result in acute heart failure and cerebral dysfunction. This injury is severe and would lead to significant morbidity and mortality and poses an important therapeutic challenge for physicians. Nitric oxide (NO) minimizes the deleterious effects of IRI on cells. NO donors, such as organic nitrates and sodium nitroprusside, are used systematically to treat heart failure, angina, and pulmonary hypertension. Inhaled NO gas was approved by the FDA in 1999 to treat hypoxic newborns, and its beneficial ameliorations reach outside the realm of lung disease. This review will summarize the clinical application of NO in IRI.
  26,145 2,793 3
ORIGINAL ARTICLES
Increase in cerebral blood flow indicated by increased cerebral arterial area and pixel intensity on brain magnetic resonance angiogram following correction of cervical lordosis
Evan A Katz, Seana B Katz, Curtis A Fedorchuk, Douglas F Lightstone, Chris J Banach, Jessica D Podoll
January-March 2019, 5(1):19-26
DOI:10.4103/bc.bc_25_18  PMID:31001596
CONTEXT: Loss of cervical lordosis is associated with decreased vertebral artery hemodynamics. AIM: The aim of this study is to evaluate cerebral blood flow changes on brain magnetic resonance angiogram (MRA) in patients with loss of cervical lordosis before and following correction of cervical lordosis. SETTINGS AND DESIGN: This study is a retrospective consecutive case series of patients in a private practice. MATERIALS AND METHODS: Cervical lordosis of seven patients (five females and two males, 28–58 years) was measured on lateral cervical radiographs ranging from −13.1° to 19.0° (ideal is −42.0°). Brain MRAs were analyzed for pixel intensities representing blood flow. Pixel intensity of the cerebral vasculature was quantified, and percentage change was determined. STATISTICAL ANALYSIS USED: A Student's t-test established significance of the percentage change in cerebral blood flow between pre- and postcervical lordosis adjustment images. Regression analysis was performed. An a priori analysis determined correlation between cervical lordosis and change in MRA pixel intensity. The statistician was blinded to the cervical lordosis. RESULTS: Pixel intensity increased 23.0%–225.9%, and a Student's t-test determined that the increase was significant (P < 0.001). Regression analysis of the change in pixel intensity versus the cervical lordosis showed that as the deviation from a normal cervical lordosis increases, percentage change in pixel intensity on MRA decreases. CONCLUSION: These results indicate that correction of cervical lordosis may be associated with an immediate increase in cerebral blood flow. Further studies are needed to confirm these findings and understand clinical implications.
  27,933 979 3
Colchicine for the prevention of ischemic stroke: An updated meta-analysis of randomized clinical trials
Ayman Al-Atta, Michal Kuzemczak, Mohammad Alkhalil
July-September 2021, 7(3):187-193
DOI:10.4103/bc.bc_24_21  
BACKGROUND: Inflammation is increasingly recognized as a target to reduce residual cardiovascular risk. Colchicine is an anti-inflammatory drug that was associated with improved cardiovascular outcomes. However, its effect on stroke reduction was not consistent across studies. Therefore, the aim of this study-level meta-analysis was to evaluate the influence of colchicine on stroke in patients with coronary artery disease (CAD). METHODS: Electronic databases were searched through October 2020, to identify randomized controlled trials using colchicine in patients with CAD. The incidence of clinical endpoints such as stroke, death, myocardial infarction (MI), study-defined major adverse cardiovascular events (MACE), and atrial fibrillation (AF) was compared between colchicine and placebo groups. RESULTS: A total number of 11,594 (5,806 in the colchicine arm) patients from 4 eligible studies were included in the final analysis. Stroke incidence was lower in the colchicine arm compared to placebo (rate ratio [RR] 0.48 [95% confidence interval [CI], 0.29–0.78], P = 0.003) whereby no significant difference was observed in the incidence of AF (odds ratio [OR] 0.86 [95% CI, 0.69–1.06], P = 0.16). Furthermore, a significant effect of colchicine on MACE [RR 0.65 (95% CI, 0.51–0.83), P = 0.0006] and MI (RR 0.65 (95% CI, 0.54–0.95], P = 0.02) was detected, with no influence on all-cause mortality (RR 1.04 [95% CI, 0.61–1.78], P = 0.88). CONCLUSIONS: This meta-analysis confirms a significant influence of colchicine on stroke in CAD patients. Despite its neutral effect on AF occurrence, other mechanisms related to plaque stabilization are plausible. The concept seems to be supported by contemporaneous MI reduction and posits that anti-inflammatory properties of colchicine may translate into a reduction of stroke risk.
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REVIEW ARTICLES
Mitochondrial activity of human umbilical cord mesenchymal stem cells
Blaise M Cozene, Eleonora Russo, Rita Anzalone, Giampiero La Rocca, Cesario V Borlongan
January-March 2021, 7(1):33-36
DOI:10.4103/bc.bc_15_21  
Human umbilical cord mesenchymal stem cells (hUC-MSCs) serve as a potential cell-based therapy for degenerative disease. They provide immunomodulatory and anti-inflammatory properties, multipotent differentiation potential and are harvested with no ethical concern. It is unknown whether MSCs collected from different areas of the human umbilical cord elicit more favorable effects than others. Three MSC populations were harvested from various regions of the human umbilical cord: cord lining (CL-MSCs), perivascular region (PV-MSCs), and Wharton's jelly (WJ-MSCs). Mesenchymal markers (CD90 and CD73) were expressed by all three cell populations. Stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and monocyte-macrophage marker (CD14) were expressed by WJ-MSCs, PV-MSCs, and CL-MSCs, respectively. Stroke presents with oxygen and glucose deprivation and leads to dysfunctional mitochondria and consequently cell death. Targeting the restoration of mitochondrial function in the stroke brain through mitochondrial transfer may be effective in treating stroke. In vitro exposure to ambient and OGD conditions resulted in CL-MSCs number decreasing the least post-OGD/R exposure, and PV-MSCs exhibiting the greatest mitochondrial activity. All three hUC-MSC populations presented similar metabolic activity and survival in normal and pathologic environments. These characteristics indicate hUC-MSCs potential as a potent therapeutic in regenerative medicine.
  25,856 2,617 4
How to remove those bloody collections: Nonsurgical treatment options for chronic subdural hematoma
Ho Jun Yun, Yuchuan Ding
October-December 2020, 6(4):254-259
DOI:10.4103/bc.bc_73_20  
Chronic subdural hematoma (CSDH) is one of the most prevalent neurosurgical disorders. Patients with CSDH commonly present with altered mental status, focal neurological deficit, and/or headache. The first-line treatment for CSDH is surgical evacuation. Although the surgical procedures for CSDH have been considered relatively “straightforward,” they are not without any risk. The elderly are especially prone to show poor surgical outcomes. To make matters worse, many elderly patients are on anticoagulants and antiplatelet agents, increasing the risk of re-bleeding before and after surgery. These complications have led clinicians to search for nonsurgical alternatives. Dexamethasone should be used with caution for selected patients given its side effects. Tranexamic acid may be utilized as an adjunct therapy to surgery, but more randomized clinical trials are needed to evaluate its definitive efficacy. Interesting results of middle meningeal artery embolization (MMAE) have been reported from case studies. However, the risks associated with MMAE, including intracerebral hemorrhage, stroke, and vasospasm, have not been properly studied yet. The clinical benefits of atorvastatin and angiotensin-converting enzyme inhibitors are uncertain for CSDH. In conclusion, surgical intervention continues to be the first-line treatment while nonsurgical treatment options may be considered an adjunct therapy especially for recurrent hematoma or to reduce the volume of a hematoma.
  25,646 2,687 3
Cell-based treatment for perinatal hypoxic-ischemic encephalopathy
You Jeong Park, Cesario V Borlongan, Mari Dezawa
January-March 2021, 7(1):13-17
DOI:10.4103/bc.bc_7_21  
Hypoxic-ischemic encephalopathy (HIE) is a major cause of acute neonatal brain injury and can lead to disabling long-term neurological complications. Treatment for HIE is limited to supportive care and hypothermia within 6 h injury which is reserved for full-term infants. Preclinical studies suggest the potential for cell-based therapies as effective treatments for HIE. Some clinical trials using umbilical cord blood cells, placenta-derived stem cells, mesenchymal stem cells (MSCs), and others have yielded promising results though more studies are needed to optimize protocols and multi-center trials are needed to prove safety and efficacy. To date, the therapeutic effects of most cell-based therapies are hypothesized to stem from the bystander effect of donor cells. Transplantation of stem cells attenuate the aberrant inflammation cascade following HIE and provide a more ideal environment for endogenous neurogenesis and repair. Recently, a subset of MSCs, the multilineage-differentiating stress-enduring (Muse) cells have shown to treat HIE and other models of neurologic diseases by replacing dead or ischemic cells and have reached clinical trials. In this review, we examine the different cell sources used in clinical trials and evaluate the underlying mechanism behind their therapeutic effects. Three databases–PubMed, Web of Science, and ClinicalTrials.gov–were used to review preclinical and clinical experimental treatments for HIE.
  25,031 2,968 3