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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
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.
  40,071 5,294 12
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
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.
  39,682 5,199 4
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
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.
  38,212 4,988 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
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.
  37,887 4,926 2
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
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.
  34,907 5,170 3
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
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.
  33,892 4,958 1
A link among schizophrenia, diabetes, and asthma: Role of Ca2+/cAMP signaling
Leandro Bueno Bergantin
July-September 2020, 6(3):145-151
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.
  31,527 5,683 -
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
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.
  31,412 5,354 14
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
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.
  32,968 3,174 5
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
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.
  27,857 2,760 14
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
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.
  25,731 2,739 2
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
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.
  25,262 2,628 2
Computed tomography angiographic anatomical features for successful transbrachial insertion of a balloon guide catheter for mechanical thrombectomy in acute ischemic stroke
Takahisa Mori, Shigen Kasakura, Kazuhiro Yoshioka
July-September 2020, 6(3):169-174
BACKGROUND AND PURPOSE: When the femoral approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS) is limited, trans-brachial or-radial access is an alternative. However, transbrachial insertion of a 9Fr (outer diameter [OD]) balloon guide catheter (BGC) into the carotid artery is not feasible. Computed tomographic (CT) angiography (CTA) may provide vascular anatomical information for successful insertion. We investigated CTA anatomical features for successful transbrachial insertion of a 9Fr BGC into the carotid artery. MATERIALS AND METHODS: We analyzed AIS patients who underwent CTA and transbrachial MT using a 9Fr BGC between 2014 and 2016. We evaluated the successful insertion rate and CT angiographic anatomical features. RESULTS: Twenty-four patients met our inclusion criteria. We achieved successful insertion in 18 (75%) of 24 cases: 7 (58.3%) of 12 for left carotid arteries and 11 (91.7%) of 12 for right carotid arteries. Successful insertion was achieved in 4 of 4 bovine aortic arch for left carotid occlusion and in 3 of 8 nonbovine aortic arches for left carotid occlusion. We achieved successful insertion in 3 nonbovine cases with takeoff angles ≥23° and failed insertion in 5 cases with takeoff angles <23°. We achieved successful insertion in 10 of the 10 cases with takeoff angles ≥25° in the right common carotid artery. The BGC was broken in 1 of 2 cases with takeoff angles <25°. CONCLUSIONS: The CTA provided a high likelihood of successful 9Fr OD BGC insertion without an introducer sheath. Successful transbrachial insertion was achieved in bovine left carotid cases, in nonbovine left carotid cases with takeoff angles ≥23°, and in right carotid cases with takeoff angles ≥25°.
  24,671 1,586 4
Teaching neurological disorders with ultrasound: A novel workshop for medical students
Varun S Shah, Maureen Cavalcanti, Seth Scheetz, David P Bahner, David L Dornbos III, Michael I Prats
January-March 2020, 6(1):38-46
INTRODUCTION: The goal of this study was to assess if a neurological disorder ultrasound workshop for the first-year medical students significantly enhanced the students' ability to retain and apply concepts related to neuroanatomy and neurophysiology. MATERIALS AND METHODS: We performed a prospective study to evaluate student performance before and after an optional ultrasound workshop. Data were collected through a within-population pretest–posttest design. Purposive sampling was used to recruit first-year medical students for this study. The six stations were transcranial doppler ultrasound, ocular ultrasound, ultrasound-guided external ventricular drain placement, high-intensity focused ultrasound for brain lesions, carotid artery scan with ultrasound, and ultrasound-guided central line placement. We used a pre–post workshop survey to identify opinions and perceptions about ultrasound and a pre–post workshop test to assess knowledge about neuroanatomy, neurophysiology, and related ultrasound topics. RESULTS: Twenty-two 22 first-year medical students consented to participate in this study. The Wilcoxon signed-rank test showed a statistically significant difference in pre- and posttest scores, suggesting that participants demonstrated higher levels of medical knowledge related to neurological physiology, anatomy, and ultrasound after participating in the workshop. The analysis of the pre–post survey showed participants attributed greater value to ultrasound as a useful tool for their future medical practice after participation in the event (Z = −2.45, P = 0.014). CONCLUSIONS: There is value in integrating experiences with ultrasound into the neurological disorder block of medical school. Future studies, with a larger sample size, are needed to further explore the efficacy of this workshop in enhancing knowledge retention.
  23,000 2,478 1
Transcranial Doppler and magnetic resonance angiography assessment of intracranial stenosis: An analysis of screening modalities
Ashkan Mowla, Banafsheh Shakibajahromi, Rasadul Kabir, Zsolt Garami, John J Volpi
July-September 2020, 6(3):181-184
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.
  22,217 2,385 1
Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review
Hayder M Al-Kuraishy, May H Abdulhadi, Nawar R Hussien, Marwa S Al-Niemi, Huda A Rasheed, Ali I Al-Gareeb
April-June 2020, 6(2):70-80
Orexin is a neuropeptide secreted from lateral hypothalamus and pre-frontal cortex concerned in the wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words during the search. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of monoaminergic system, which affect cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotropin and corticosteroid secretions via activation of central corticotropin-releasing hormone. Cerebrospinal fluid (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin serum levels are reduced Parkinson disease, Alzheimer dementia, Huntington's disease, amyotrphic lateral sclerosis, and multiple sclerosis. Orexin antagonist leads to significant reduction of sympathetic over-activity during withdrawal syndrome. As well, orexin antagonist improves sleep pattern. Orexinergic system is involved in the different psychiatric and neurological disorders; therefore, targeting of this system could be possible novel pathway in the management of these disorders. In addition, measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients.
  21,654 2,947 6
A preliminary exploration of acute intracranial pressure-cerebrospinal fluid production relationships in experimental hydrocephalus
Ahmad H Khasawneh, Petroj C Alexandra, Paul A Zajciw, Carolyn A Harris
July-September 2020, 6(3):200-207
CONTEXT: By occluding the fourth ventricle simultaneously obtaining telemetric data on intracranial pressure (ICP) and cerebrospinal fluid (CSF) production, the authors of this study investigate a variety of physiologic parameters in cases of experimental hydrocephalus. AIMS: The aim of this study is to provide a new context on the disrupted homeostasis in hydrocephalus and guide toward improved treatment based on multiple physiological parameters. MATERIALS AND METHODS: Hydrocephalus was induced in ten 21-day-old Sprague–Dawley rats by blocking the flow of CSF to the fourth ventricle with kaolin. Ten days post induction, when physical signs of ventriculomegaly reached Evan's ratio (ER) of ≥0.46, CSF flow and ICP were measured while manipulating body position (0°, 45°, 90°) and heart rate. RESULTS: In hydrocephalic animals (ER ≥0.46), we found a near-steady average acute ICP (13.638 ± 2.331) compared to age-matched controls (ER <0.30) (13.068 ± 8.781), whose ICP fluctuated with the position. Hydrocephalic and controls exhibited an insignificant degree of parabolic shifts in CSF production when body position was changed from prone to 90° and again when moved back to the prone position, a trend more noteworthy in controls (P = 0.1322 and 0.2772). A Pearson's Correlation found CSF production and ICP to be correlated at baseline 0° posture (P = 0.05) in the control group, but not the hydrocephalic group. Weight appeared to play a role when animals were held at 90°. No significant changes in ICP or CSF flow patterns were observed when the heart rate was increased within either group. CONCLUSIONS: These preliminary findings suggest that our standard assumptions of posture-dependent changes in ICP created using data from physiologic data may be inaccurate in the hydrocephalic patient, and thus describe a need to further explore these relationships.
  21,876 1,916 -
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.
  22,147 921 3
Pregabalin-associated movement disorders: A literature review
Jamir Pitton Rissardo, Ana Letícia Fornari Caprara
April-June 2020, 6(2):96-106
Central nervous system adverse effects are commonly reported with pregabalin (PGB). On the other hand, movement disorders (MDs) associated with this drug were rarely described. However, their occurrence could significantly affect the quality of life of PGB users. This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of PGB-associated MDs. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 46 reports containing 305 cases from 17 countries were assessed. The MDs encountered were as follows: 184 individuals with ataxia, 61 with tremors, 39 with myoclonus, 8 with parkinsonism, 1 with restless legs syndrome, 1 with dystonia, 1 with dyskinesia, and 1 with akathisia. The mean age was 62 years (range: 23–94). The male sex was slightly predominant with 54.34%. The mean PGB dose when the MD occurred was 238 mg, and neuropathic pain was the most common indication of PGB. The time from PGB start to MD was < 1 month at 75%. The time from PGB withdrawal to recovery was < 1 week at 77%. All the individuals where the follow-up was reported had a full recovery. The most common management was PGB withdrawal. In the literature, the majority of the cases did not report information about timeline events, neurological examination details, or electrodiagnostic studies. The best management for all MDs is probably PGB withdrawal. If the patient is on dialysis program, perhaps an increased number of sessions will decrease recovery time. Furthermore, the addition of a benzodiazepine could accelerate recovery.
  20,459 2,580 5
Neurocysticercosis and movement disorders: A literature review
Jamir Pitton Rissardo, Ana Letícia Fornari Caprara, Ícaro Durante
October-December 2020, 6(4):225-241
Neurocysticercosis (NCC) is a specific form of cysticercosis that affects the central nervous system. It is caused by the tapeworm Taenia solium, which is often found in pigs. NCC is considered one of the “great simulator/mimickers” of other diseases. In this context, movement disorders (MDs) can occur in a small percentage of individuals with NCC. This review aims to evaluate the clinicoepidemiological profile, pathological mechanisms, and historical features of NCC-associated MD. Relevant reports in six databases were identified and assessed by two reviewers without language restriction. A total of 71 reports containing 148 individuals who developed an MD related to NCC were identified. NCC-associated MD included parkinsonism (n = 47), ataxia (n = 32), chorea (n = 18), dystonia (n = 13), tremor (n = 8), myokymia (n = 6), myoclonus (n = 4), ballism (n = 1), tics (n = 1), and others (n = 18). The mean and median ages were 36.58 (standard deviation: 20.51) and 35 years (age range: 1–88 years), respectively. There was a slight predominance of female sex (52.17%). On follow-up, 58.90% of the individuals had a full recovery; two deaths were reported. We believe that the majority of cases reported were only diagnosed because patients had classical clinical manifestations generally investigated by neuroimaging, resulting in incidental findings suggestive of NCC, which were later supported by laboratory examinations. Therefore, the association between NCC and MD is probably underreported. Clinicians should be wary of this association, mainly in endemic areas for cysticercosis.
  20,038 2,521 1
Updates on the association of brain injury and Alzheimer's disease
Kara Klomparens, Yuchuan Ding
April-June 2020, 6(2):65-69
The purpose of this minireview is to outline the updates made on the association of Alzheimer's disease (AD) and brain injury. A review of the literature on this subject was conducted that included various aspects such as age of onset, severity of head trauma, and genetic influences. The results of this mini-review were that consistent associations of AD risk are seen when the severity of head trauma increases, the lag time decreases and when genetic links are present. Brain injury and AD have a complicated relationship that requires further studies to be fully understood.
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Brain-derived neurotrophic factor levels in acute stroke and its clinical implications
Poonam Chaturvedi, Ajai Kumar Singh, Vandana Tiwari, Anup Kumar Thacker
July-September 2020, 6(3):185-190
BACKGROUND: Brain-derived neurotrophic factor (BDNF) has a very important role in repairing intact and injured brain, also known as neuroplasticity. Risk factors may affect neuroplasticity. OBJECTIVES: In this study, our aim was to delineate the levels of BDNF in acute stroke with different etiology and impact of risk factors on its levels. METHODS: In this prospective study, 208 patients with first-ever stroke, between 18 and 75 years, were included. All individuals were assessed for severity and type of stroke, risk factors, levels of BDNF in the acute stroke, and its association with outcome of stroke. RESULTS: The mean age of the patients in our study was 55.29 ± 11.6 years. Compared to healthy controls, a significant decline in the levels of BDNF was observed after stroke (P < 0.01). Patients with National Institutes of Health Stroke Scale (NIHSS) <6 on the 1st day of stroke had significantly higher levels of BDNF than those with NIHSS >6 (9.8 ng/ml ± 3.8; P < 0.01). A significant difference in the levels of BDNF was observed on comparing the stroke patients and healthy individuals of age <55 and >55 years (<55 years: 10.4 ng/ml ± 3.2; >55 years: 9.8 ng/ml ± 4.5 and in healthy individuals <55 years: 22.97 ± 3.8, >55 years: 15.4 ± 4.9; P < 0.01). Risk factors have negative impact on levels of BDNF (diabetics, P = 0.001; alcoholics, P = 0.003; both diabetes mellitus + hypertension, P = 0.002; smokers, P = 0.001). The difference was not significant between hypertensives and nonhypertensives (P = 0.06). CONCLUSION: BDNF level is significantly reduced in acute stroke. The presence of risk factors further affects its level.
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Temporal limits of therapeutic hypothermia onset in clinical trials for acute ischemic stroke: How early is early enough?
Hangil Lee, Yuchuan Ding
July-September 2020, 6(3):139-144
Stroke is one of the leading causes of mortality and morbidity worldwide, and yet, current treatment is limited to thrombolysis through either t-PA or mechanical thrombectomy. While therapeutic hypothermia has been adopted in clinical contexts such as neuroprotection after cardiac resuscitation and neonatal hypoxic-ischemic encephalitis, it is yet to be used in the context of ischemic stroke. The lack of ameliorative effect in ischemic stroke patients may be tied to the delayed cooling induction onset. In the trials where the cooling was initiated with significant delay (mostly systemic cooling methods), minimal benefit was observed; on the other hand, when cooling was initiated very early (mostly selective cooling methods), there was significant efficacy. Another timing factor that may play a role in amelioration may be the onset of cooling relative to thrombolysis therapy. Current understanding of the pathophysiology of acute ischemic injury and ischemia-reperfusion injury suggests that hypothermia before thrombolysis may be the most beneficial compared to cooling initiation during or after reperfusion. As many of the systemic cooling methods tend to require longer induction periods and extensive, separate procedures from thrombolysis therapy, they are generally delayed to hours after recanalization. On the other hand, selective cooling was generally performed simultaneously to thrombolysis therapy. As we conduct and design therapeutic hypothermia trials for stroke patients, the key to their efficacy may lie in quick and early cooling induction, both respective to the symptom onset and thrombolysis therapy.
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Prevalence of atrial fibrillation in acute ischemic stroke patients:A hospital-based study from India
Deepak Goel, Rekha Gupta, Tulika Keshri, Sanyal Rana
January-March 2020, 6(1):19-25
BACKGROUND: Secondary stroke prevention is as important as the treatment of acute ischemic stroke in regards to halt neurological disability and to lower down mortality due to recurrent episodes. The effective secondary prevention depends on finding the specific risk factors leading to cerebro-vascular insult. AIMS AND OBJECTIVES: We aimed this study to find prevalence of persistent/Paroxysmal AF in stroke patients from single center hospital based study. METHODS: Hospital based study enrolled all prospective patients of acute ischemic stroke from January 2016 to December 2018. All patients were subjected to test for risk factors analysis after detail clinical history and examination of these patients. Following variables were recorded; age, gender, stroke territory, stroke severity by NIHSS (National Institute of Health Stroke Scale), LDL-C (Low Density Lipoprotein - cholesterol) of more than 100 mg/dl, HBA1C (Glycosylated Hemoglobin) of more than 6.5, Homocystine of more than 15 Mc Mol/L, 2D-Echocardiographic abnormalities, electrocardiography/24 hour Holter Monitoring, cerebral angiography of brain and neck findings and outcome of patients in 90 days follow-up based on Modified Rankin Scale. Results: Total 246 patients (69.5% men and 30.5% women) of Acute Ischemic stroke were recorded during study period. Mean age was 61.4 years, with 31 (12.4%) patients were below 45 years. Atrial fibrillation (AF) was detected either on conventional ECG or 24 hour Holter monitoring in 62 (25.2%) patients. CONCLUSION: Stroke with AF is found in 25% patients, more common in elderly, female large atrial size and associated with poor outcome.
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Frequency of thrombolytic targets in stroke patients presenting in an extended time window
Parisa Heidari, Sarah Blayney, Jarrhett Butler, Emi Hitomi, Marie Luby, Richard Leigh
July-September 2020, 6(3):163-168
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.
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