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.

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.

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.

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.

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°.

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.

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.

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 1^st 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.

BACKGROUND: Transient ischemic attack (TIA) is a common neurovascular disorder associated with a higher risk of stroke within the first 24 h after the first event. Acute cerebral and arterial neuroimaging combined with long-term electrocardiography (ECG) monitoring have been proven to be useful in determining etiology. Cardio-embolism constitutes 20%–26% etiology of TIAs most of them with atrial fibrillation (AF). Investigation of AF after TIA is very important because oral anticoagulants can reduce the risk of subsequent stroke by two thirds. MATERIALS AND METHODS: The present study included 45 patients suffering from TIA with undetermined source according to the Trial of Org 10172 in Acute Stroke Treatment criteria; the control group (n = 45) was selected from the patients admitted to cardiology outpatient clinic with nonspecific complaints without cerebrovascular and/or cardiovascular disease. All patients underwent echocardiography and 24 h Holter ECG monitoring (HM). RESULTS: There was no significant difference between the patient group and the control group in terms of age and gender. Cholesterol, low-density lipoprotein and urea levels, left atrium diameters and the incidence of hypertension, coronary artery diseases, and AF were significantly higher in TIA group (P < 0.05). In the results of HM, there were six patients with AF in the study group, and in the control group, there was no patients with AF (P = 0.03). DISCUSSION AND CONCLUSION: In acute phase of TIA, 24 h HM is important for determining the etiology and selecting an appropriate treatment that can protect patients from subsequent strokes.

BACKGROUND: Studies have shown that 4%–17% of acute ischemic strokes (AISs) occur in patients hospitalized for another reason; scanty data are available about the care delivery and outcome of this patient population. MATERIALS AND METHODS: All consecutive inhospital AISs over a 10-year period at our comprehensive stroke center were included in the study. We compared the meantime from last known neurologically intact to symptom detection and also eligibility for acute treatment of patients based on their physical location in the hospital with respect to the level of care when they were found to have the stroke symptoms. RESULTS: Fifty-three patients suffered inhospital AIS during this period (28 in intensive care units/emergency department [ICUs/ED] vs. 25 in regular floors). Only in four patients (7.5%), initial brain imaging was done within 25 min from symptom recognition (as recommended by the American Heart Association/American Society of Anesthesiologists guidelines). Forty-two (79%) underwent brain imaging within 6 h of symptom recognition; of them, 11 (26%) received intravenous thrombolysis (IVT) within the first 4.5 h of symptom onset and 7 (17%) underwent endovascular treatment (EVT). The mean (±standard deviation) time in minutes from last known neurologically intact to symptom detection for floor patients was significantly longer compared to the ICU/ED patients (194 [±149] vs. 74 [±45], P = 0.0003). Patients admitted to the ICU/ED had more chance of being recognized earlier and being eligible for IVT or/and EVT compared to the patients admitted to the regular floors (44% vs. 25%, P = 0.14); however, the difference did not reach statistical significance. CONCLUSIONS: ICU/ED patients had a significantly shorter time to stroke symptom detection from last known neurologically intact when compared to the regular floor patients. Furthermore, they had a trend toward a higher likelihood of being eligible for acute treatment compared to the regular floors, although the result did not reach statistical significance.

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.

Aneurysms that occur anywhere in intracranial except where primary aneurysms develop, are called “de novo aneurysms”. The risk factors and formation time of de novo aneurysms are not fully known. Congenital, environmental and hemodynamic factors can play a role in aneurysm development. The 43-year-old female patient was operated with the middle cerebral artery superior trunk aneurysm in our clinic. She came to us again after 17 months with a severe headache. In computed cranial tomography angiography, the middle cerebral artery superior trunk placement aneurysm was found to have a partial clip and “de novo aneurysm” was developed. She was re-operated for “de novo aneurysm”. In this study, the risk factors in development of “de novo aneurysms” were discussed in the light of literature through this patient.

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.

Stent infection is extremely rare, especially in stents placed in the internal carotid artery (ICA). Treatment in these cases remains controversial and no consensus has been reached, resulting in high mortality in all cases. We report the case of a 78-year-old man undergoing stent placement in the left ICA who, 20 days later, presented with infection at the stent site and a large pseudoaneurysm. The primary infectious focus was the teeth. The patient was treated with antibiotics and placement of a Casper stent, a dual layer braided metal stent with micro-mesh, intended to determine flow diversion and arterial wall reconstruction. Although the procedure was able to reduce the pseudoaneurysm, the patient eventually died of sepsis. We believe that the use of dual layer stents, with a flow-diverting effect, may be a treatment option in selected cases. However, further studies are needed to confirm this hypothesis.

Malignant cerebral infarction (MCI) is a large middle cerebral artery infarction. MCI frequently results in increased intracranial pressure (ICP) because of its extent of the infarction. MCI management focuses on lowering ICP, but monitoring ICP has not been a standard of care. Studies have found insignificant clinical value in monitoring ICP because of doubtful correlations between ICP values and clinical findings. However, this conclusion is largely based on unilateral ICP measurements. Bilateral ICP measurements and differentials accompanying clinical findings are needed to draw a concrete conclusion on the usage of ICP monitoring in MCI management.