Pathophysiology and Optimal Treatment of Intracranial Branch Atheromatous Disease.

Intracranial branch atheromatous disease (BAD) is a pathological condition characterized by the occlusion of a relatively large perforating branch (700-800 µm) near the orifice of a parent artery due to atherosclerotic plaque-based thrombus (microatheroma). BAD is refractory to treatment and follows a course of progressive exacerbation, especially motor paralysis. Uniform treatment for common atherothrombotic cerebral infarction or lacunar infarction does not prevent the progressive exacerbation of BAD, and consequently affects functional prognosis. To date, various combinations of treatments have been investigated and proposed to attenuate the worsening symptoms of BAD. However, no therapy with established efficacy is yet available for BAD. Since it is the most difficult condition to treat in the area of cerebral infarction, the establishment of optimal treatment methods for BAD is keenly awaited. This review presents an overview of the acute treatments available for BAD and discusses the prospects for optimal treatment.

Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.

Cerebral venous thrombosis: Diagnosis and management in the emergency department setting.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon neurologic emergency associated with significant morbidity and mortality that can be difficult to differentiate from other conditions. It is important for the emergency clinician to be familiar with this disease as it requires a high index of suspicion, and early diagnosis and management can lead to improved outcomes. OBJECTIVE: This narrative review provides an evidence-based update concerning the presentation, evaluation, and management of CVT for the emergency clinician. DISCUSSION: CVT is due to thrombosis of the cerebral veins resulting in obstruction of venous outflow and increased intracranial pressure. Early recognition is important but difficult as the clinical presentation can mimic more common disease patterns. The most common patient population affected includes women under the age of 50. Risk factors for CVT include pregnancy, medications (oral contraceptives), inherited thrombophilia, prior venous thromboembolic event, malignancy, recent infection, and neurosurgery. CVT can present in a variety of ways, but the most common symptom is headache, followed by focal neurologic deficit, seizure, and altered mental status. Imaging studies such as computed tomography (CT) venography or magnetic resonance (MR) venography should be obtained in patients with concern for CVT, as non-contrast CT will be normal or have non-specific findings in most patients. Treatment includes anticoagulation, treating seizures and elevated ICP aggressively, and neurosurgical or interventional radiology consultation in select cases. CONCLUSIONS: CVT can be a challenging diagnosis. Knowledge of the risk factors, patient presentation, evaluation, and management can assist emergency clinicians.

Ultra-Early Cerebral Thrombosis Formation After Experimental Subarachnoid Hemorrhage Detected on T2* Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: The mechanisms of brain damage during ultra-early subarachnoid hemorrhage (SAH) have not been well studied. The current study examined the SAH-induced hyperacute brain damage at 4 hours using magnetic resonance imaging and brain histology in a mouse model. METHODS: SAH was induced by endovascular perforation in adult mice. First, adult male wild-type mice underwent magnetic resonance imaging T2 and T2* 4 hours after an endovascular perforation or a sham operation and were euthanized to assess brain histology. Second, male and female adult lipocalin-2 knockout mice had SAH. All animals underwent magnetic resonance imaging at 4 hours, and the brains were harvested for brain histology. RESULTS: T2* hypointensity vessels were observed in the brain 4 hours after SAH in male wild-type mice. The numbers of T2*-positive vessels were significantly higher in SAH brains than in sham-operated mice. Brain histology showed thrombosis and erythrocyte plugs in the T2*-positive cerebral vessels which may be venules. The number of T2*-positive vessels correlated with SAH grade and the presence of T2 lesions. Brain thrombosis was also accompanied by albumin leakage and neuronal injury. LCN2 deficient male mice had lower numbers of T2*-positive vessels after SAH compared with wild-type male mice. CONCLUSIONS: SAH causes ultra-early brain vessel thrombosis that can be detected by T2* gradient-echo sequence at 4 hours after SAH. LCN2 deficiency decreased the number of T2*-positive vessels.

Mechanism of Stroke According to the Severity and Location of Atherosclerotic Middle Cerebral Artery Disease.

BACKGROUND AND PURPOSE: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease. METHODS: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated. RESULTS: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005). CONCLUSIONS: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion.

Clinical Implications of Preinterventional Thrombus Migration in Patients with Emergent Large Vessel Occlusion.

BACKGROUND: In patients treated with thrombectomy, thrombus migration (TM) to distal arterial segments is occasionally observed. We investigated the incidence of TM, factors associated with TM, and association between TM and clinical outcomes. METHODS: The study population consisted of 164 patients with anterior circulation stroke who underwent pretreatment brain computed tomography angiography and digital subtraction angiography before undergoing thrombectomy. TM was defined as a thrombus shift to a more distal arterial segment observed on digital subtraction angiography than that on computed tomography angiography. Successful and complete recanalization was defined as cerebral infarction perfusion scale scores of 2b-3 and 3, respectively. Good functional outcomes were defined as scores of ≤2 on the modified Rankin Scale at 3 months. The results are presented as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Thirty-two patients (19.5%) had TM. Intravenous thrombolysis (IVT) (OR, 5.238; 95% CI, 1.653-16.603) and female sex (OR, 2.874; 95% CI, 1.135-7.277) were associated with TM. IVT-related TM was not significantly associated with thrombus inaccessibility (P = 0.304). In addition, TM was not associated with successful (P = 0.960) or complete (P = 0.612) recanalization. However, TM (OR, 2.777; 95% CI, 1.019-7.569), together with IVT (OR, 2.982; 95% CI, 1.332-6.676), a low National Institutes of Health Stroke Scale score (OR, 0.906; 95% CI, 0.845-0.972), and successful recanalization (OR, 4.878; 95% CI, 1.940-12.266), were independently associated with good functional outcomes. CONCLUSIONS: TM is common, particularly after IVT. In addition, TM is associated with better functional outcomes, irrespective of the angiographic outcomes.

Determination of cerebral blood flow velocity and microembolic signals in essential thrombocytosis by transcranial doppler ultrasonography.

OBJECTIVES: The goal of treatment in essential thrombocytosis (ET) is to prevent vascular complications such as thrombosis and hemorrhage. This study aimed to evaluate the risk of cerebrovascular microembolism in ET patients due to detection of microembolic signals (MES) and measure cerebral blood flow velocity (CBFV) by Transcranial Doppler (TCD) ultrasonography. MATERIAL AND METHODS: In this prospective case-control study, forty patients with diagnosed ET and age and sex-matched forty healthy controls were examined by the TCD sonography. RESULTS: The ET group had a higher rate of MES (8/40) in the right MCA than that in the control group (none), as measured by TCD. Five patients had MES at the left MCA compared to that in no subjects in the control group. The comparison of the ET and control groups in terms of CBFV parameters showed significantly lower end-diastolic FV at the right MCA in the ET group compared to that in the control group (p < 0.05). On the other hand; both pulsatility and resistance indices in the right and left MCA and the ratios of systolic to diastolic blood flow rates in the right and left MCA were significantly higher in the ET group than that in the control group. DISCUSSION: This study revealed that MES seems to be more common in patients with ET despite treatment. We could suggest that ET patients should be monitored more closely to address the potential risk of developing a cerebrovascular disease, which can be estimated by detection MES and raised CBFV, combine antiplatelet therapies to standard treatments.

Small thrombus size, thrombus composition, and poor collaterals predict pre-interventional thrombus migration.

BACKGROUND: Different imaging characteristics such as clot burden score, collaterals, and pre-interventional thrombus migration are associated with functional outcome in patients with acute ischemic stroke. Moreover, histological thrombus composition is associated with pre-interventional thrombus migration. We hypothesized that smaller clots may more likely migrate and that collateral status in ischemic stroke patients may mediate this tendency of the clot to migrate. METHODS: In this prospective cohort of consecutive ischemic stroke patients, clot burden scores and collateral scores were rated and the retrieved thrombi were histologically analyzed. We then investigated the relationship between clot burden score, probability for thrombus migration, and collateral scores using mediation analysis. RESULTS: 163 patients are included of which 36 (22.1%) had a clot migration. Probability of thrombus migration was significantly associated with lower collateral scores (P<0.01), higher clot burden scores (P<0.01), shorter thrombi (P<0.01), and higher RBC count (P<0.01). In the mediator pathway, higher collateral scores were significantly associated with higher clot burden scores (P<0.01) and younger age (P=0.029). The total effect of an increase in clot burden score by one grade on thrombus migration is composed of the direct effect (+18%, P<0.01) and the collateral score-mediated indirect effect (-5%, P<0.01). CONCLUSIONS: Smaller, erythrocyte-rich thrombi tend to migrate more often. Good collaterals seem to have a considerable effect on limiting migration. This supports the hypothesis that larger clots have stronger adherence with the vessel wall and that good collaterals increase the counter pressure distal of the clot.

The clinical characteristic, diagnosis, treatment, and prognosis of cerebral cortical vein thrombosis: a systematic review of 325 cases.

Cerebral cortical vein thrombosis (CCVT) is a rare type of cerebral venous thrombosis, which is frequently combined with cerebral venous sinus thrombosis (CVST). We aimed to compare the difference of clinical features between the isolated and the combined subtypes of CCVT. A literature search was conducted utilizing the PubMed Central and EMBASE databases to identify studies up to Dec 2019. Clinical manifestations, presumable risk factors, imaging modalities, radiological findings, treatment, and prognosis in patients with CCVT were recorded. 335 publications were identified (n = 325, 141 males and 184 females, mean age 40.24 ± 16.26 years). Headaches (46.8%), motor/sensory disorders (43.3%), and seizures (42.5%) were commonly seen. Pregnancy/postpartum (n = 29), oral contraception use (n = 15), fertility drug use (n = 4) ranked the top three comorbidities of CCVT in female patients, while for general populations, thrombophilia, invasive interventions in the cerebrospinal system, as well as malignancy, would be the common risk factors. MRV and DSA were more likely to confirm diagnosis. More than 30% of CCVT presented brain lesions, including infarction (6.5%) and hemorrhage (24.0%). Isolated CCVT was prone to develop hemorrhagic infarction while combined CCVT was more likely to have ischemic lesions. More than 90% of the patients acquired good outcomes at discharge or short-term follow-up (within one year). There is a difference between Isolated CCVT and CCVT combined CVST on the sites and types of brain lesions. MRV and DSA may contribute to the final diagnosis. Most patients acquired complete or partial recovery of clinical symptoms or imaging presentations after long-term anticoagulation (3-6 months).

Management of Ischemic Stroke Following Left Ventricular Assist Device.

BACKGROUND: Acute ischemic stroke is a common complication and an important source of morbidity and mortality in patients with left ventricular assist devices. There are no standardized protocols to guide management of ischemic stroke among patients with left ventricular assist device. We evaluated our experience treating patients who had an acute ischemic stroke following left ventricular assist device placement. METHODS: We retrospectively reviewed all patients who underwent left ventricular assist device placement from 2010-2019 and identified patients who had acute ischemic stroke following left ventricular assist device placement. RESULTS: Of 216 patients having left ventricular assist device placement (mean±SD age 52.9±16.2 years, women 26.9%), 19 (8.8%) had acute ischemic stroke (mean±SD age 55.8±12.0 years, women 36.8%). Median (interquartile range) time to ischemic stroke following left ventricular assist device placement was 96 (29-461) days. At the time of the ischemic stroke, 16/19 (84.2%) patients were taking both antiplatelet and anticoagulation therapy, 1/19 (5.3%) patient was receiving only anticoagulants, 1/19 (5.3%) patient was taking aspirin and dipyridamole, and 1/19 (5.3%) patient was not taking antithrombic agents. INR was subtherapeutic (INR<2.0) in 7/17 (41.2%) patients. No patient was eligible to receive thrombolytic therapy, while 5/19 (26.3%) underwent mechanical thrombectomy. Anticoagulation was continued in the acute stroke phase in 11/19 (57.9%) patients and temporarily held in 8/19 (42.1%) patients. Hemorrhagic transformation of the ischemic stroke occurred in 6/19 (31.6%) patients. Anticoagulation therapy was continued following ischemic stroke in 4/6 (66.7%) patients with hemorrhagic transformation. CONCLUSIONS: While thrombolytic therapy is frequently contraindicated in the management of acute ischemic stroke following left ventricular assist device, mechanical thrombectomy remains a valid option in eligible patients. Anticoagulation is often continued through the acute phase of ischemic stroke secondary to concerns for LVAD thrombosis. The risks and benefits of continuing anticoagulation must be weighed carefully, especially in patients with large infarct volume, as hemorrhagic transformation remains a common complication.

Procesos cognitivos en trombosis de seno longitudinal superior: reporte de caso / Cognitive processes in superior longitudinal sinus thrombosis: case report

INTRODUCCIÓN: la trombosis de seno longitudinal superior es una enfermedad de difícil detección a causa de sus diferentes causas y debido al polimorfismo de sus manifestaciones neurológicas; además es común en el sexo femenino relacionado a los estímulos estrogénicos y otros factores hormonales, pero poco probable en menor de 40 años. PACIENTE: paciente menor de 40 años posterior a presentar dos episodios de accidentes cerebrovasculares isquémicos, se evalúa un año después de la lesión el estado cognitivo y funcional mediante la batería Neuropsi Atención y Memoria y el Inventario de Adaptabilidad Mayo-Portland; los procesos cognitivos afectados en un nivel de clasificación leve fueron la atención y concentración, el funcionamiento ejecutivo; en el estado funcional reportado por el cónyuge sugiere afectación de síntomas clínicos como irritabilidad, ira agresividad, dolores de cabeza, cansancio y reacciones a síntomas menores e interacción inadecuada, estos síntomas no fueron reportados por la paciente sugiriendo posible anosognosia en su proceso de adaptabilidad CONCLUSIÓN: Tras un proceso de lesión cerebral por afectación trombótica, las secuelas cognitivos y funcionales permanecen posterior a la recuperación espontanea, llevando a emplear procesos de rehabilitación.

INTRODUCTION: the superior longitudinal sinus thrombosis is a disease difficult to detect because of its different causes and because of the polymorphism of its neurological manifestations; It is also common in females related to estrogen stimuli and other hormonal factors, but unlikely in younger than 40 years. PATIENT: a patient younger than 40 years after having two episodes of ischemic strokes, cognitive and functional status is assessed one year after the injury using the neuropsi battery attention and memory and the mayo-portland adaptability inventory; Cognitive processes affected at a slight level of classification were attention and concentration, executive functioning; In the functional status reported by the spouse suggests involvement of clinical symptoms such as irritability, anger, aggression, headaches, fatigue and reactions to minor symptoms and inadequate interaction, these symptoms were not reported by the patient suggesting possible anosognosia in her process of adaptability CONCLUSIÓN: After a process of brain injury due to thrombotic involvement, the cognitive and functional sequelae remain after spontaneous recovery, suggesting the import of rehabilitation processes.

Headache in cerebrovascular diseases.

Headache is a common accompanying symptom of cerebrovascular diseases. The most common patterns of headache for different cerebrovascular disorders, aetiology and pathogenesis and diagnostic workup are reviewed with emphasis on distinguishing characteristics. It will be a clinical guide for physicians who treat patients with headache or cerebral vascular disease.

Adjustment of Stent Retriever Length to Clot Extent Affects First-Pass Reperfusion in Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND: Stent retriever technology has evolved, and significantly longer devices have become available for mechanical thrombectomy (MT) of large cerebral vessel occlusions in ischemic stroke. We hypothesized that increased stent retriever length may improve the rate of complete angiographic reperfusion and decrease the respective number of attempts, resulting in a better clinical outcome. METHODS: Retrospective analysis of patients with large vessel occlusion in the anterior and posterior circulation treated with stent retriever MT. The study group was dichotomized into short (20 mm) and long (>20 mm) retrievers using propensity matching. In the anterior circulation, the clot burden score was evaluated. Primary end points were first-pass modified thrombolysis in cerebral infarction (mTICI) 3 reperfusion and first-pass mTICI ≥ 2b reperfusion, and the secondary end point was functional independence (defined as modified Rankin Scale score 0-2) at discharge and 90 days. RESULTS: Overall, 394 patients were included in the analysis. In the anterior circulation, short stent retrievers had a significantly higher rate of first-pass reperfusion in cases with low clot burden (mTICI 3: 27% vs. 17%; p = 0.009; mTICI ≥ 2b: 42 vs. 30%; p = 0.005) and in middle cerebral artery occlusions (mTICI ≥ 2b: 51 vs. 41%; p = 0.024). Higher rates of favorable outcome at discharge and 90 days were observed for the short stent retriever group (p < 0.001). CONCLUSION: Stent retriever length should be adjusted to clot burden score and vessel occlusion site.

Relationship between Flow-mediated Endothelial Vasodilation and the Pulse Wave Velocity, and Cervical Carotid Artery Stenosis.

Carotid artery stenosis is elicited by atherosclerosis and is the main cause of cerebral thrombosis. Flow-mediated endothelial vasodilation (FMD) can be measured noninvasively to assess vascular endothelial function related to atherosclerosis. The pulse wave velocity (PWV) is used to evaluate the vascular media involved in atherosclerosis. We investigated the relationship between these measurements in 75 consecutive patients with atherosclerotic cerebral thrombosis. They were assigned to three equal groups based on the severity of carotid artery stenosis on ultrasonograms. Group 1 had no stenosis, group 2 manifested moderate stenosis (<60%), and group 3 presented with severe stenosis (≥60%). We compared the FMD and PWV among the three groups. The PWV was significantly lower in group 1 than the other two groups. The FMD was significantly lower in group 3; it was significantly lower in group 2 than group 1. There was an inverse correlation between the FMD and the severity of carotid artery stenosis. Our findings show that for assessing the severity of carotid artery stenosis, the FMD is more useful than the PWV.

Natural Y-shaped radial artery graft bypass for a complex middle cerebral artery aneurysm: A case report.

Giant thrombosed middle cerebral artery (MCA) aneurysms are difficult to treat and sometimes require complex revascularization using allografts. We describe a technical method using revascularization with a natural Y-shaped graft that provides a normal variation for a complex MCA aneurysm. A 65-year-old man with a giant thrombosed MCA aneurysm presented with right hemiparesis and aphasia. The patient had a history of clipping surgery for the ipsilateral side of the MCA aneurysm 25 years before, and a de novo aneurysm developed over the previous 18 years. For the giant thrombosed aneurysm, trapping and revascularization were performed. A natural radial artery Y-graft was used as the graft and anastomosed to both M2 trunks. The symptoms improved after surgery, and the patient was discharged 3 weeks later. This is the first report of a double-barrel bypass using a natural Y-graft. This method attained a normal variation, and the flow of the Y-graft was physiological. For the radical cure of giant thrombosed MCA aneurysms, multiple revascularizations might be required. With this natural Y-graft, complex transpositions could be avoided.

Acute ischaemic stroke interventions: large vessel occlusion and beyond.

Care for acute ischaemic stroke is one of the most rapidly evolving fields due to the robust outcomes achieved by mechanical thrombectomy. Large vessel occlusion (LVO) accounts for up to 38% of acute ischaemic stroke and comes with devastating outcomes for patients, families and society in the pre-intervention era. A paradigm shift and a breakthrough brought mechanical thrombectomy back into the spotlight for acute ischaemic stroke; this was because five randomised controlled trials from several countries concluded that mechanical thrombectomy for acute stroke offered overwhelming benefits. This review article will present a comprehensive overview of LVO management, techniques and devices used, and the future of stroke therapy. In addition, we review our institution experience of mechanical thrombectomy for posterior and distal circulation occlusion.

Risk Factors for Distal Clot Migration during Mechanical Thrombectomy of Anterior Circulation Large Vessel Occlusion.

INTRODUCTION: Distal clot migration (DCM) is a known complication of mechanical thrombectomy (MT), but neither risk factors for DCM nor ways of how it might affect clinical outcomes have been extensively studied to date. METHODS: To identify risk factors for and outcomes in the setting of DCM, the records of all patients with acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) treated with MT at a single center between May 2016 and June 2018 were retrospectively reviewed. Uni- and multivariable analyses were performed to evaluate predictors of DCM and good functional outcome (90-day modified Rankin Scale; mRS 0-2). RESULTS: A total of 65 patients were included, DCM was identified in 22 patients (33.8%). Patients with DCM had significantly higher pre-procedural intravenous tissue plasminogen activator (IV-tPA) administration (81.8 vs. 53.5%, p = 0.03), stentrievers thrombectomy (95.5 vs. 62.8%, p = 0.006), and longer median puncture to recanalization time (44 [34-97] vs. 30 [20-56] min, p = 0.028) as compared to group with non-DCM. Also, they had lower rates of Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization (p = 0.002), higher median National Institutes of Health Stroke Scale (NIHSS) scores at discharge (p = 0.01), and lower rates of 90-day mRS (0-2; 18.2 vs. 48.8%; p = 0.016). On subgroup analysis, patients with middle cerebral artery occlusions who underwent MT with stentrievers <40 mm in length had a higher risk of DCM (p = 0.026). On multivariable analysis, IV-tPA administration (OR; 5.019, 95% CI [1.319-19.102], p = 0.018) and stentrievers thrombectomy (OR; 10.031, 95% CI [1.090-92.344]; p = 0.04) remained significant predictors of DCM. Baseline NIHSS score (OR; 0.872, 95% CI [0.788-0.965], p = 0.008) and DCM (OR; 0.250, 95% CI [0.075-0.866], p = 0.03) were independent predictors of 90-day mRS 0-2. CONCLUSION: In patients undergoing MT for anterior circulation LVO, DCM is associated with lower rates of TICI 2b/3 recanalization and worse functional outcomes at 90 days. IV-tPA administration and MT with short stentrievers are independent predictors of DCM development.