Ultra-Early Differential Diagnosis of Acute Cerebral Ischemia and Hemorrhagic Stroke by Measuring the Prehospital Release Rate of GFAP.

BACKGROUND: Plasma glial fibrillary acidic protein (GFAP) and tau are promising markers for differentiating acute cerebral ischemia (ACI) and hemorrhagic stroke (HS), but their prehospital dynamics and usefulness are unknown. METHODS: We performed ultra-sensitivite single-molecule array (Simoa®) measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms [National Institutes of Health Stroke Scale (NIHSS) ≥3]. Sequential sampling included 2 ultra-early samples, and a follow-up sample on the next morning. RESULTS: We included 272 cases (203 ACI, 60 HS, and 9 stroke mimics). Median (IQR) last-known-well to sampling time was 53 (35-90) minutes for initial prehospital samples, 90 (67-130) minutes for secondary acute samples, and 21 (16-24) hours for next morning samples. Plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the 2 very early samples was significantly higher in patients with HS than ACI [2.4 (0.6-14.1)] versus 0.3 (-0.3-0.9) pg/mL/minute, P < 0.001. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90-410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%). CONCLUSIONS: In comparison to single-point measurement, monitoring the prehospital GFAP release rate improves ultra-early differentiation of stroke subtypes. With serial measurement GFAP has potential to improve future prehospital stroke diagnostics.

Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Predictive Factors for Pre-operative Recurrence of Cerebrovascular Symptoms in Symptomatic Carotid Stenosis.

OBJECTIVE: Across stroke subtypes, carotid artery stroke carries the highest risk of recurrence. Despite initiation of best medical therapy (BMT), some patients suffer recurrent neurological events before undergoing carotid endarterectomy (CEA). The aim was to identify clinical predictors of early recurrent events in patients with symptomatic carotid stenosis (sCS) awaiting CEA on modern BMT. METHODS: The Helsinki Carotid Endarterectomy Study 2 (HeCES2) is a cross sectional, longitudinal, prospective, and consecutive cohort study, which enrolled 500 symptomatic or asymptomatic patients with carotid stenosis scheduled for CEA in a tertiary stroke centre. Symptomatic patients were included for this analysis (n = 324). RESULTS: Of all 324 patients with sCS, 39 (12%) had a recurrent cerebrovascular event at a median of six days after the index symptom: four had an ischaemic stroke (1.2%), 16 a hemispheric transient ischaemic attack (TIA; 4.9%), and 19 amaurosis fugax (AFX; 5.9%). The recurrence rate was 4.0 % (n = 13) within 48 h and 9.9% (n = 32) within two weeks. None of the patients (n = 108) presenting with ocular symptoms (AFX or retinal artery occlusion) suffered recurrent hemispheric TIA or stroke. In Cox regression analysis, comorbid hypertension (hazard ratio [HR] 6.58, 95% confidence interval [CI] 1.33-32.47), hemispheric TIA as the index symptom (HR 3.42, 95% CI 1.70-6.90), the number of prior attacks (HR 1.12, 95% CI 1.08-1.15), and high low density lipoprotein/high density lipoprotein ratio (HR 1.51, 95% CI 1.09-2.11) were independently associated with an increased risk of recurrent event, while a history of major cardiovascular event (HR 0.33, 95% CI 0.11-0.96) and high serum fibrinogen level (HR 0.59, 95% CI 0.41-0.86) were associated with a decreased risk. CONCLUSION: More than every tenth patient with sCS experienced an early recurrent cerebrovascular event prior to scheduled CEA, despite optimal medication. However, stroke recurrence was lower than in earlier observational studies, which could be explained by improved care pathways, more aggressive medication, and expedited CEA. All recurrent strokes occurred in patients initially presenting with minor stroke.

Extracellular Lipids Accumulate in Human Carotid Arteries as Distinct Three-Dimensional Structures and Have Proinflammatory Properties.

Lipid accumulation is a key characteristic of advancing atherosclerotic lesions. Herein, we analyzed the ultrastructure of the accumulated lipids in endarterectomized human carotid atherosclerotic plaques using three-dimensional (3D) electron microscopy, a method never used in this context before. 3D electron microscopy revealed intracellular lipid droplets and extracellular lipoprotein particles. Most of the particles were aggregated, and some connected to needle-shaped or sheet-like cholesterol crystals. Proteomic analysis of isolated extracellular lipoprotein particles revealed that apolipoprotein B is their main protein component, indicating their origin from low-density lipoprotein, intermediate-density lipoprotein, very-low-density lipoprotein, lipoprotein (a), or chylomicron remnants. The particles also contained small exchangeable apolipoproteins, complement components, and immunoglobulins. Lipidomic analysis revealed differences between plasma lipoproteins and the particles, thereby indicating involvement of lipolytic enzymes in their generation. Incubation of human monocyte-derived macrophages with the isolated extracellular lipoprotein particles or with plasma lipoproteins that had been lipolytically modified in vitro induced intracellular lipid accumulation and triggered inflammasome activation in them. Taken together, extracellular lipids accumulate in human carotid plaques as distinct 3D structures that include aggregated and fused lipoprotein particles and cholesterol crystals. The particles originate from plasma lipoproteins, show signs of lipolytic modifications, and associate with cholesterol crystals. By inducing intracellular cholesterol accumulation (ie, foam cell formation) and inflammasome activation, the extracellular lipoprotein particles may actively enhance atherogenesis.

Haptoglobin Hp2 Variant Promotes Premature Cardiovascular Death in Stroke Survivors.

BACKGROUND AND PURPOSE: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles (hp1/hp2) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke. METHODS: Hp was genotyped in SAM study (Helsinki Stroke Aging Memory, n=378). A total of 1426 individuals ascertained from a nationally representative cross-sectional health survey served as population controls. RESULTS: Hp genotype frequencies were 15.6% (hp1-1), 44.2% (hp1-2), and 40.2% (hp2-2) in patients with stroke. During a mean of 7.5-year follow-up after first-ever stroke, hp2 carriers had a substantially higher rate of cardiac deaths (24.5% versus 8.5%; P=0.006) and a trend toward more fatal strokes (23.5% versus 13.6%; P=0.122). The combined risk of ischemic cardiovascular deaths was 2.4-fold higher among hp2 carriers (95% confidence interval, 1.28-4.43) after adjustment for major cardiovascular risk factors. CONCLUSIONS: Hp2 allele is associated with premature ischemic cardiovascular deaths after first-ever ischemic stroke.

Recognizing subtle near-occlusion in carotid stenosis patients: a computed tomography angiographic study.

INTRODUCTION: Near-occlusion of the internal carotid artery (ICA) is a significant luminal diameter (LD) reduction beyond a tight atherosclerotic carotid stenosis (CS). Recognition of even subtle near-occlusions is essential to prevent underestimation of the stenosis degree. Our goal was to investigate the prevalence of near-occlusion among CS patients using a single standard criterion to facilitate its recognition, even when distal ICA LD reduction is not visually evident in computed tomography angiography (CTA). METHODS: We analysed carotid artery CTAs of 467 patients with moderate-to-severe CS scheduled for endarterectomy. We performed measurements of the bilateral distal ICA LDs from thin axial source images and utilized a 1.0 mm intra-individual side-to-side distal ICA LD difference to distinguish near-occlusions, based on a previous study, aware of the vagaries of measurement. For analysis stratification, we excluded cases with significant carotid pathology affecting LD measurements. RESULTS: We discovered 126 near-occlusions fulfilling our criterion of ipsilateral near-occlusion: the mean LD side-to-side difference (mm) with 95% confidence interval being 1.8 (1.6, 1.9) and a standard deviation of 0.8 mm. Among the 233 cases not meeting our near-occlusion criterion, we found 140 moderate (50-69%) and 93 severe (70-99%) ipsilateral stenoses. CONCLUSION: The utilization of 1.0 mm cut-off value for the intra-individual distal ICA LD side-to-side difference to distinguish atherosclerotic ICA near-occlusion leads to a relatively high incidence of near-occlusion. In CTA, recently suggested to be used for near-occlusion diagnosis, a discriminatory 1.0 mm cut-off value could function as a pragmatic tool to enhance the detection of even subtle near-occlusions.

Cutting the Prehospital On-Scene Time of Stroke Thrombolysis in Helsinki: A Prospective Interventional Study.

BACKGROUND AND PURPOSE: Significant portion of the prehospital delay consists of minutes spent on the scene with the patient. We implemented a training program for the emergency medical services personnel with the aim to optimize the on-scene time (OST) and to study the impact of different elements of prehospital practice to the OST duration. METHODS: In this prospective interventional study, key operational emergency medical service performance variables were analyzed from all thrombolysis candidates transported to the Helsinki University Hospital emergency department. The catchment period was 4 months before and 4 months after the implementation. RESULTS: One hundred and forty-one patients were managed as thrombolysis candidates before and 148 patients after the training program implementation. The OST duration for the groups was 25 (20.5-31) and 22.5 (18-28.5) minutes, respectively (P<0.001). Physician consultations via telephone were associated with a longer (odds ratio 0.546 [0.333-0.893]) and advanced life support training with a shorter OST (odds ration 1.760 [1.070-2.895]). CONCLUSIONS: Implementation of the emergency medical services training program successfully decreased the OST of thrombolysis candidates by 10%. Higher expertise level of the ambulance crew was associated with shorter OST, and decisions to consult a physician via telephone were reflected by longer OST.

Headache as symptom of intracranial hemorrhage.

The most important signs of danger of a headache patient include exceptionally intense or acute headache, transient loss or progressive impairment of consciousness, and neurological deficit symptoms. These patients are referred to an urgent assessment by a physician. Computed tomography scanning of the head is carried out in the case of suspected hemorrhage of a headache patient. Routine diagnosis employing cerebrospinal fluid analysis can be abandoned when excluding subarachnoid hemorrhage in a patient with headache symptoms, if blood is with certainty not observed in the CT scan of the head and no more than six hours have passed after the onset of the symptom. If subarachnoid hemorrhage is detected, cerebral CT angiography will be performed at the same time and a neurosurgeon consulted about the need of operative treatment.

Workflow for automated quantification of cerebromicrovascular gelatinase activity.

The gelatinase enzymes, matrix metalloproteinases -2 and -9, are central mediators of blood-brain barrier disruption, actively studied in experimental models of neurological disease. Staining with in situ zymography (ISZ) allows visualization of gelatinase activity directly in brain tissue sections. However, quantifying microvascular gelatinase activity from ISZ-images is challenging and time consuming, as surrounding cell types often show significant confounding activity. We describe validation and performance of a workflow for automated image analysis of cerebromicrovascular gelatinase activity, now released for open-access use. In comparison to manual analysis, the automated workflow showed superior accuracy, was faster to execute and allows for more detailed analysis of heterogeneity in the microvasculature. We further suggest recommendations for quantifying and reporting this type of activity in experimental studies, focusing on ischemic stroke.

Cerebral amyloid angiopathy related hemorrhage after stroke thrombolysis: case report and literature review.

Cerebral amyloid angiopathy (CAA) predisposes to symptomatic intracerebral hemorrhage (sICH) after combined thrombolytic and anticoagulant treatment of acute myocardial infarction. However, the role of CAA in stroke thrombolysis has not been established. Here, we describe a confirmed case of CAA-related hemorrhage in a patient receiving thrombolysis for acute ischemic stroke. On autopsy, immunohistochemistry revealed amyloid-ß positive staining in thickened cortical and meningeal arteries at sites of hemorrhage. Further research is urgently needed to determine the hemorrhage risk related to CAA in stroke thrombolysis and develop better diagnostic tools to identify CAA in the emergency room.

Intravenous thrombolysis of basilar artery occlusion: thrombus length versus recanalization success.

BACKGROUND AND PURPOSE: In middle cerebral artery occlusion, probability of recanalization after intravenous tissue-type plasminogen activator thrombolysis (IVT) was reported to drop <1% for thrombi exceeding 8 mm. We aimed to evaluate the effect of thrombus length and location on success of recanalization after IVT in basilar artery occlusion. METHODS: We evaluated 164 consecutive patients with angiography-proven basilar artery occlusion and available thrombus length. We excluded 24 patients who underwent endovascular treatment. All included patients (n=140) received IVT. Thrombolysis in myocardial infarction 2 to 3 was considered as successful recanalization. RESULTS: Of the 140 included patients, 37 (26.4%) lacked post-treatment angiography, mostly because of early death. Of the remaining 103 patients, those with recanalization had shorter thrombi (median, 5.5 mm and mean, 9.7 mm) when compared with those with nonrecanalized (median, 15.0 mm and mean, 16.6 mm; P<0.001). Thrombi shorter than 10 mm had 70% to 80% probability of recanalization, whereas 10 to 20 mm, 20 to 30 mm, and >30 mm long thrombi had probabilities of 50% to 70%, 30% to 50%, and 20% to 30%, respectively. Patients with thrombi <10 mm (n=52) and recanalization had more frequently top-of-the basilar (92.5%) and less frequently caudal or midbasilar (7.5%) clot location (P=0.01). In multivariable analysis, thrombus length was independently associated with recanalization (P=0.001). Their relationship remained linear across all lengths. CONCLUSIONS: Although recanalization of basilar artery occlusion with IVT depends on thrombus length, its probability even in patients with thrombi >30 mm (20%-30%) was substantially higher than minimal recanalization of middle cerebral artery thrombi exceeding 8 mm. There was no threshold length, beyond which basilar artery occlusion recanalization with IVT could ad hoc be deemed hopeless.

The atrial fibrillation epidemic is approaching the physician's door: will mobile technology improve detection?

The rising numbers of people with atrial fibrillation (AF) carry a heavy toll on our graying population. Epidemiological data suggest that AF exists in 1 in 10 individuals aged older than 80 years. The risk of embolic stroke increases along with well-known cardiovascular risk factors. Should there be systematic screening for the elderly? Although 1 in 10 is a huge hit rate in screening for any major illness, the initiative for such programs in AF remains in 'research and development'.At present, cardiologists can utilize implantable loop recorders in patients referred for specialist consultation. Novel technologies are also available, including cloud-based, algorithm-assisted, non-invasive monitoring patches, which allow extended observation periods. What about people in the community without a recognized need for cardiologic investigation? Mobile technology has made detection of pulse irregularity possible without medical attention. Smartphone apps enable opportunistic rhythm monitoring, but true arrhythmias need to be medically verified. AF may be the first common disorder to be effectively screened for by mobile technology. In the spirit of proactive campaigns such as 'Know Your Pulse', we should prepare for rapidly increasing reports of various pulse irregularities.

Thrombolysis of basilar artery occlusion: impact of baseline ischemia and time.

OBJECTIVE: To evaluate the impact of extensive baseline ischemic changes on functional outcome after thrombolysis of basilar artery occlusion (BAO), and to study the effect of time to treatment in the absence of such findings. METHODS: We prospectively evaluated 184 consecutive patients with angiography-proven BAO. The majority of patients received intravenous alteplase and concomitant full-dose heparin. Extensive baseline ischemia was defined as posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) < 8. Onset-to-treatment time (OTT) was evaluated both as a continuous and as a categorical variable (0-6 hours, 6-12 hours, 12-24 hours, and 24-48 hours). Successful recanalization means thrombolysis in myocardial infarction (TIMI) = 2 to 3. Symptomatic intracranial hemorrhage (sICH) was evaluated with National Institute of Neurological Disorders and Stroke, European Cooperative Acute Stroke Study II, and Safe Implementation of Thrombolysis in Stroke criteria. Poor 3-month outcome was defined as modified Rankin Scale score of 3 to 6. RESULTS: The majority (96%) of patients with baseline pc-ASPECTS < 8 had poor 3-month outcome, and a similar number (94%) was observed in those of them with confirmed recanalization (51.5%). In contrast, half of the patients with pc-ASPECTS ≥ 8 and successful recanalization (73.2%) achieved good outcome. In these patients, OTT was associated with poor outcome neither as a continuous nor as a categorical variable. Factors independently associated with poor outcome were greater age and baseline National Institutes of Health Stroke Scale, lack of recanalization, history of atrial fibrillation, and sICH. In the model including the whole cohort (patients with any pc-ASPECTS), pc-ASPECTS < 8 was independently associated with poor outcome (odds ratio = 5.83, 95% confidence interval = 1.09-31.07). INTERPRETATION: In the absence of extensive baseline ischemia, recanalization of BAO up to 48 hours was seldom futile and produced good outcomes in 50% of patients, which was independent of time to treatment.

[Can you recognize a candidate for thrombolytic treatment of ischemic stroke?]. / Tunnistatko aivoinfarktin liuotushoitokandidaatin?

Intravenous thrombolytic treatment of ischemic stroke is the central treatment option in patients presenting with acute stroke symptoms. The thrombolytic treatment chain is initiated in the emergency services call center immediately after stroke is suspected. Even one point on the FAST scale mandates urgent transport for assessment of thrombolytic treatment. The FAST test identifies eight out of ten strokes, and the stroke diagnosis is confirmed in the emergency department with immediate imaging. The most significant groups of differential diagnosis include epileptic seizures, migraine, incoherence associated with infection, syncope and psychiatric states. There is every reason to hasten the confirmation of diagnosis and implementation of treatment at all stages of the treatment chain.

[Investments of research and treatment of brain diseases will pay of time]. / Aivosairaudet ovat kalleimmat kansantautimme.

In 2010, a quarter of direct healthcare cost in Europe were spent on brain diseases. The importance of preventing and treating brain diseases and maintaining of functional capacity of the brain will increase in our society with ageing population and with increasing cognitive requirements of modern working life. Public funding of basic and clinical neuroscience has, however, frozen to levels achieved years ago, clinical research of brain diseases being at a particular risk. Research projects directed to prevention, treatment, and rehabilitation of brain diseases will pay off, also when assessed by economic measures.

IV Thrombolysis in Basilar Artery Occlusion: Outcomes and Comparison With Endovascular Thrombectomy.

BACKGROUND AND OBJECTIVES: Recanalization is considered a prerequisite for favorable outcome in basilar artery occlusion (BAO). Intravenous thrombolysis (IVT) has been successfully used for eligible patients with BAO well beyond the 4.5-hour time window but has been largely underrepresented in the best medical management arms in recent randomized controlled trials of recanalization therapy in BAO. We aimed to analyze the outcomes of patients with BAO treated with IVT only and to compare IVT with endovascular thrombectomy (EVT). METHODS: This observational single-center, retrospective cohort study included consecutive patients with BAO treated with IVT and/or EVT up to 48 hours of symptom onset during 1995-2022. The primary outcome was favorable functional outcome (modified Rankin Scale 0-3) at 3 months collected by a stroke physician by phone. In the first part, we described the outcomes and factors associated with functional outcome in the IVT-only cohort during 1995-2022. In the second part, we used doubly robust inverse probability-weighted regression adjustment models to compare functional outcome of patients treated with IVT vs EVT+/-IVT during 2010-2022. RESULTS: In the whole cohort of 376 patients with acute BAO treated with recanalization therapy, 245 (65.2%) received only IVT. In the IVT-only cohort, most patients had moderate-to-severe clinical presentation (median NIH Stroke Scale 18) but no extensive early ischemic changes in the posterior circulation on admission. Half of them had onset-to-treatment time over 6 hours. 46.5% of the IVT-treated patients achieved 3-month favorable functional outcome, whereas mortality was 35.9%. sICH occurred in 11.1%. In a multivariable analysis, younger age, milder symptom severity, and less baseline ischemic changes predicted favorable functional outcome. In the 2010-2022 cohort, when compared with patients treated with EVT+/-IVT (n = 121), the IVT-only cohort (n = 122) had higher odds for favorable functional outcome (IVT 58.2% vs EVT 43.0% (aOR 2.82 [95% CI 1.31-6.05]). DISCUSSION: IVT alone produced outcomes comparable with those in recent trials of endovascular BAO recanalization. Furthermore, in head-to-head comparison in our cohort, the IVT-only approach was more often associated with favorable outcome than EVT+/-IVT. Thus, it should not be overlooked as the first-line recanalization therapy in acute BAO, even in longer time windows. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that tPA is as effective as thrombectomy for basilar artery thrombosis.

MANF protein expression is upregulated in immune cells in the ischemic human brain and systemic recombinant MANF delivery in rat ischemic stroke model demonstrates anti-inflammatory effects.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) has cytoprotective effects on various injuries, including cerebral ischemia, and it can promote recovery even when delivered intracranially several days after ischemic stroke. In the uninjured rodent brain, MANF protein is expressed almost exclusively in neurons, but post-ischemic MANF expression has not been characterized. We aimed to investigate how endogenous cerebral MANF protein expression evolves in infarcted human brains and rodent ischemic stroke models. During infarct progression, the cerebral MANF expression pattern both in human and rat brains shifted drastically from neurons to expression in inflammatory cells. Intense MANF immunoreactivity took place in phagocytic microglia/macrophages in the ischemic territory, peaking at two weeks post-stroke in human and one-week post-stroke in rat ischemic cortex. Using double immunofluorescence and mice lacking MANF gene and protein from neuronal stem cells, neurons, astrocytes, and oligodendrocytes, we verified that MANF expression was induced in microglia/macrophage cells in the ischemic hemisphere. Embarking on the drastic expression transition towards inflammatory cells and the impact of blood-borne inflammation in stroke, we hypothesized that exogenously delivered MANF protein can modulate tissue recovery processes. In an attempt to enhance recovery, we designed a set of proof-of-concept studies using systemic delivery of recombinant MANF in a rat model of cortical ischemic stroke. Intranasal recombinant MANF treatment decreased infarct volume and reduced the severity of neurological deficits. Intravenous recombinant MANF treatment decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokine IL-10 in the infarcted cortex one-day post-stroke. In conclusion, MANF protein expression is induced in activated microglia/macrophage cells in infarcted human and rodent brains, and this could implicate MANF's involvement in the regulation of post-stroke inflammation in patients and experimental animals. Moreover, systemic delivery of recombinant MANF shows promising immunomodulatory effects and therapeutic potential in experimental ischemic stroke.

Long-term cognitive and neurovascular changes after carotid endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) has been associated with both cognitive decline and improvement, but the underlying neurovascular mechanisms are unclear. The aim of this study was to investigate the relationship between neurovascular indices and cognitive changes after CEA. METHODS: We studied 55 patients with severe (≥70%) symptomatic or asymptomatic carotid stenosis before and six months after CEA. A wide array of neuropsychological tests was arranged in eight cognitive domains and cognitive functions specific to hemisphere ipsilateral to operation. Differences in cognitive performance between patients and 38 matching healthy controls were studied with linear mixed models. Neurovascular functioning and microembolic signals were assessed with transcranial Doppler ultrasound of the middle cerebral artery. Associations between neurovascular indices and cognitive change were assessed with linear regression analyses. RESULTS: On group level, the CEA patients improved more than controls in working memory, whereas no cognitive deterioration was detected. Also on individual level, improvement was most frequently observed in working memory. Worse preoperative cerebrovascular reactivity was related with improvement in cognitive functions of the ipsilateral hemisphere. Low preoperative pulsatility index was associated with improvement in executive functioning and ipsilateral cognitive functions. Poorer preoperative blood flow velocity associated with improvement in complex attention. Microembolic signals were rare. CONCLUSION: The present findings suggest that CEA may have beneficial long-term effects on cognition. These effects may specifically involve patients with impaired preoperative circulatory adaptive mechanisms.

[Basilar artery occlusion--a diagnostic and therapeutic challenge]. / Basilaaritromboosin diagnostiikka ja hoito.

Acute basilar artery occlusion is a neurological emergency that almost invariably leads to death or severe disability if not recanalized. Therapeutic recanalization is attempted using thrombolytic therapy either intravenously alone or by bridging it to on-demand, endovascular procedures. Due to often demanding differential diagnosis, angiographic evidence of basilar artery occlusion is necessary before treatment decisions. The etiology is often cardioembolism or vertebrobasilar thromboembolism due to atherothrombotic disease, or vertebral artery dissection in less than one in ten cases. Different therapeutic approaches have not been compared in randomized controlled trials. The selection of recanalization therapies thus builds on empirical knowledge and availability of vascular interventional services in the local setting.