Anterior Cerebral Artery Stroke: Role of Collateral Systems on Infarct Topography.

Background and Purpose: The circle of Willis (CoW) and leptomeningeal anastomoses play an important role in transforming infarct topography following middle cerebral artery occlusion. Their role in infarct topography following anterior cerebral artery occlusion is not well understood. The aim of this study was to evaluate the role of the CoW and leptomeningeal anastomoses in modifying regional variation in infarct topography following occlusion of the anterior cerebral artery and its branches. Methods: Perfusion and magnetic resonance imaging of patients with anterior cerebral artery stroke and evidence of vessel occlusion were segmented and manually registered to standard brain template for voxel-wise comparison. Next, a computer model of the cerebral arteries was formulated as network of nodes connected by cylindrical pipes. The experiments included occlusion of successive branches of the anterior cerebral artery while the configurations of the CoW were varied. Results: Forty-seven patients with a median age of 77.5 years (interquartile range, 68.0­84.5 years) were studied. The regions with the highest probabilities of infarction were the superior frontal gyrus (probability =0.26) and anterior cingulate gyrus (probability =0.24). The regions around the posterior cingulate gyrus (probability =0.08), paracentral lobule (probability =0.05), precuneus and superior parietal lobule (probability =0.03) had a low probability of infarction. Following occlusions distal to the anterior communicating artery, the computer model demonstrated an increase in flow (>30%) in neighboring cortical arteries with leptomeningeal anastomoses. Conclusions: Traditionally the CoW has been regarded as the primary collateral system. However, our computer model shows that the CoW is only helpful in redirecting flow following proximal vessel occlusions (pre-anterior communicating artery). More important are leptomeningeal anastomoses, which play an essential role in distal vessel occlusions, influencing motor outcome by modifying the posterolateral extent of infarct topography.

Clinical prognosis of isolated anterior cerebral artery territory infarction: a retrospective study.

BACKGROUND: Isolated anterior cerebral artery territory (ACA) infarction is a rare phenomenon, and is known to have distinctive clinical features. Little is known regarding the clinical prognosis of isolated ACA territory infarction with associated factors, and its impact on dwelling and job status. We investigated the short- and long-term outcomes of anterior cerebral artery (ACA) territory infarction, and the associated factors involved in the development of the distinctive symptoms. METHODS: This retrospective study in a prospective cohort of acute ischaemic stroke patients included consecutively enrolled patients with isolated ACA territory infarction. We investigated the functional status using the modified Rankin scale (mRS) score at discharge, three months' post-discharge, and one-year post-discharge. We also investigated the occlusion site of the ACA (proximal vs. distal); presence of distinctive symptoms of ACA territory infarction including behaviour changes, indifference, aphasia, and urinary incontinence; and the effect of these symptoms on dwelling and job status one year after discharge. RESULTS: Between April 2014 and March 2019, 47 patients with isolated ACA territory infarction were included. Twenty-nine patients (61.7 %) had good outcomes (mRS ≤ 2) at discharge; however, the mRS score increased at three months (40; 85.1 %, p < 0.001) and one year (41; 87.2 %) post-discharge. Occlusion of the ACA proximal segment was independently associated with the development of distinctive symptoms (adjusted odds ratio, 17.68; 95 % confidence interval: 2.55-122.56, p < 0.05). Twenty-one (48.8 %) patients with good outcomes at one year experienced a change in dwelling status and job loss; 20 (95.2 %) of them had distinctive ACA territory symptoms with proximal ACA occlusion. CONCLUSIONS: Short- and long-term outcomes of isolated ACA territory infarction were favourable. However, proximal segment occlusion was associated with the development of distinctive symptoms, possibly related to future dwelling and job status.

Supratentorial Cerebral Arterial Territories for Computed Tomograms: A Mapping Study in 1160 Large Artery Infarcts.

We recently generated a high-resolution supratentorial vascular topographic atlas using diffusion-weighed MRI in a population of large artery infarcts. These MRI-based topographic maps are not easily applicable to CT scans, because the standard-reference-lines for axial image orientation (i.e., anterior-posterior commissure line versus orbito-meatal line, respectively) are 'not parallel' to each other. Moreover, current, widely-used CT-based vascular topographic diagrams omit demarcation of the inter-territorial border-zones. Thus, we aimed to generate a CT-specific high-resolution atlas, showing the supratentorial cerebrovascular territories and the inter-territorial border-zones in a statistically rigorous way. The diffusion-weighted MRI lesion atlas is based on 1160 patients (67.0 ± 13.3 years old, 53.7% men) with acute (<1-week) cerebral infarction due to significant (>50%) stenosis or occlusion of a single large cerebral artery: anterior, middle, or posterior cerebral artery. We developed a software package enabling the transformation of our MR-based atlas into a re-oriented CT space corresponding to the axial slice orientations used in clinical practice. Infarct volumes are individually mapped to the three vascular territories on the CT template-set, generating brain maps showing the voxelwise frequency of infarct by the affected parent vessel. We then mapped the three vascular territories collectively, generating a dataset of Certainty-Index (CI) maps to reflect the likelihood of a voxel being a member of a specific vascular territory. Border-zones could be defined by using either relative infarct frequencies or CI differences. The topographic vascular territory atlas, revised for CT, will allow for easier and more accurate delineation of arterial territories and borders on CT images.

Rare presentation of AICA syndrome.

We report a rare presentation of an anterior inferior cerebellar artery (AICA) infarct in a 74-year-old woman with acute-onset nausea, vomiting, vertigo and gait instability long before the full onset of symptoms and a negative MRI on admission. Over the next several days the patient developed left facial weakness, numbness, hypoacusis, and limb and gait ataxia, and was found to have acute infarcts of the left pons and cerebellar peduncle consistent with an AICA syndrome. We discuss this rare stepwise presentation in AICA syndrome and possible underlying pathophysiology. Such patients at risk for cerebrovascular disease should undergo a careful history, exam and follow-up, even with negative MRI findings, as their symptoms may precede a serious vascular event.

Association of Computed Tomography Ischemic Lesion Location With Functional Outcome in Acute Large Vessel Occlusion Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic lesion volume (ILV) assessed by follow-up noncontrast computed tomography correlates only moderately with clinical end points, such as the modified Rankin Scale (mRS). We hypothesized that the association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened when taking the mRS relevance of the infarct location into account. METHODS: An anatomic atlas with 66 areas was registered to the follow-up noncontrast computed tomographic images of 254 patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). The anatomic brain areas were divided into brain areas of high, moderate, and low mRS relevance as reported in the literature. Based on this distinction, the ILV in brain areas of high, moderate, and low mRS relevance was assessed for each patient. Binary and ordinal logistic regression analyses with and without adjustment for known confounders were performed to assess the association between the ILVs of different mRS relevance and outcome. RESULTS: The odds for a worse outcome (higher mRS) were markedly higher given an increase of ILV in brain areas of high mRS relevance (odds ratio, 1.42; 95% confidence interval, 1.31-1.55 per 10 mL) compared with an increase in total ILV (odds ratios, 1.16; 95% confidence interval, 1.12-1.19 per 10 mL). Regression models using ILV in brain areas of high mRS relevance instead of total ILV showed a higher quality. CONCLUSIONS: The association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened by accounting for the mRS relevance of the affected brain areas. Future prediction models should account for the ILV in brain areas of high mRS relevance.

FLAIR vascular hyperintensities and 4D MR angiograms for the estimation of collateral blood flow in anterior cerebral artery ischemia.

PURPOSE: To assess FLAIR vascular hyperintensities (FVH) and dynamic (4D) angiograms derived from perfusion raw data as proposed magnetic resonance (MR) imaging markers of leptomeningeal collateral circulation in patients with ischemia in the territory of the anterior cerebral artery (ACA). METHODS: Forty patients from two tertiary care university hospitals were included. Infarct volumes and perfusion deficits were manually measured on DWI images and TTP maps, respectively. FVH and collateral flow on 4D MR angiograms were assessed and graded as previously specified. RESULTS: Forty-one hemispheres were affected. Mean DWI lesion volume was 8.2 (± 13.9; range 0-76.9) ml, mean TTP lesion volume was 24.5 (± 17.2, range 0-76.7) ml. FVH were observed in 26/41 (63.4%) hemispheres. Significant correlations were detected between FVH and TTP lesion volume (ρ = 0.4; P<0.01) absolute (ρ = 0.37; P<0.05) and relative mismatch volume (ρ = 0.35; P<0.05). The modified ASITN/SIR score correlated inversely with DWI lesion volume (ρ = -0.58; P<0.01) and positively with relative mismatch (ρ = 0.29; P< 0.05). ANOVA of the ASITN/SIR score revealed significant inter-group differences for DWI (P<0.001) and TTP lesion volumes (P<0.05). No correlation was observed between FVH scores and modified ASITH/SIR scores (ρ = -0.16; P = 0.32). CONCLUSIONS: FVH and flow patterns on 4D MR angiograms are markers of perfusion deficits and tissue at risk. As both methods did not show a correlation between each other, they seem to provide complimentary instead of redundant information. Previously shown evidence for the meaning of these specific MR signs in internal carotid and middle cerebral artery stroke seems to be transferrable to ischemic stroke in the ACA territory.

Frequency and outcome of total anterior circulation strokes without intracranial large-vessel occlusion.

BACKGROUND AND PURPOSE: The percentage of patients with clinical total anterior circulation infarct (TACI) syndrome treated with reperfusion therapies in the absence of intracranial large-vessel occlusion (ILVO) was determined and their characteristics and outcome are described. METHODS: Data from a population-based, prospective, externally audited registry of all stroke patients treated with intravenous thrombolysis (IVT) and endovascular therapies in Catalonia from January 2011 to December 2013 were used. Patients with a baseline TACI and initial stroke severity measured by the National Institute of Health Stroke Scale (NIHSS) ≥ 8, evaluated less than 4.5 h post-onset, for whom a vascular study prior to treatment was available (n = 1070) were selected. Clinical characteristics, outcome and radiological data for patients treated with IVT alone (n = 605) were compared between those with detected ILVO (n = 474) and non-ILVO patients (n = 131). RESULTS: A total of 1070 patients met study criteria; non-ILVO was found in 131 (12.2%). Analysing the 605 patients treated only with IVT, no significant differences were found between non-ILVO and ILVO patients in age, sex, risk factors, time-to-treatment and type of radiological studies performed. Although non-ILVO patients had lower initial stroke severity (P < 0.001) and a better prognosis (P = 0.001), 51.3% had a poor outcome and 16% were deceased at 90 days. In 66.4% of patients without ILVO, a recent anterior territorial infarct was detected. CONCLUSIONS: Intracranial artery patency was observed in 12.2% of TACI patients evaluated within 4.5 h. Although absence of ILVO was associated with slightly better prognosis, more than half had a poor outcome at 3 months.

Reappraisal of Microsurgical Revascularization for Anterior Circulation Ischemia in Patients with Progressive Stroke.

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator and endovascular treatment for acute ischemic stroke is becoming an established standard therapy. However, there is no consensus in the treatment of patients who are suffering from progressive neurologic symptoms in the later stages. The purpose of this study was to evaluate the safety and efficacy of microsurgical revascularization in such patients with progressive stroke. METHODS: We retrospectively reviewed the clinical and radiological records of 14 consecutive patients with progressive stroke who underwent emergency open surgery for anterior circulation occlusion within 7 days after onset. Surgical candidates were carefully selected on the basis of symptom severity, diffusion-weighted imaging, and perfusion study. Superficial temporal artery to middle cerebral artery bypass was applied for atherosclerotic occlusion, and microsurgical embolectomy was applied for embolic occlusion. RESULTS: Superficial temporal artery to middle cerebral artery bypass was performed in 12 patients, microsurgical embolectomy in 1, and the combination of these modalities in 1. As a result, complete revascularization was achieved in all patients. The National Institutes of Health Stroke Scale scores significantly improved after surgery (at third postoperative day, P < 0.05; at 14th postoperative day, P < 0.01). A favorable outcome (modified Rankin Scale 0-2) was achieved in 12 of the 14 (85.7%) patients. Minor intracerebral hemorrhage occurred in 1 patient and hyperperfusion syndrome occurred in 1 patients; however, the patients subsequently recovered without additional treatment. CONCLUSIONS: Microsurgical revascularization is a feasible treatment option for patients with progressive stroke due to anterior circulation major vessel occlusion.

Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model.

Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4-4.7 kg, n = 30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (n = 11), DDFPe + tPA (n = 7), and no therapy controls (n = 5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0-18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall, p = 0.0015, and vs. tPA alone, p = 0.0052. For %SV, DDFPe + tPA was improved overall, p = 0.0003 and vs. tPA alone, p = 0.0018. NAS controls and tPA alone were not different but %SV was, p = 0.0078. With delayed reperfusion, DDFPe + tPA was more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy.

[Analysis of the effect of N5, N10-methylenetetrahydrofolate reductase gene C(677)-->T polymorphism on the ischemic stroke development in persons with various risk factors].

The results ofMTHFR gene C(677)-->T (rs1801133) polymorphism determined in 170 patients with ischemic atherothrombotic stroke (IATS) and 124 healthy subjects (control group) are presented in the paper. It has been shown that in patients with IATS, the frequencies of main homozygotes (CC), heterozygotes (CT) and minor homozygotes (TT) are 52.4, 35.9, 11.8% (in control--46.0, 48.4, 5.6%, P = 0.044 by chi2-test). TT homozygotes have a greater chance of developing IATS than carriers of main C-allele (CT + CC) (OR = 2.3, CI = 0.911-5.449, P = 0.049). In the representatives of the Ukrainian population there is a relationship between the frequency of MTHFR gene C(677)-->T polymorphism genotypes and the risk of IATS. This connection is manifested in male patients, in persons with normal blood pressure, and in people who do not have the habit of smoking. The sex of the patients, body mass index, blood pressure and smoking affect the level of the studied polymorphism association with stroke.

Outcomes in severe middle cerebral artery ischemic stroke.

BACKGROUND: Severe middle cerebral artery stroke (MCA) is associated with a high rate of morbidity and mortality. We assessed the hypothesis that patient-specific variables may be associated with outcomes. We also sought to describe under-recognized patient-centered outcomes. METHODS: A consecutive, multi-institution, retrospective cohort of adult patients (≤70 years) was established from 2009 to 2011. We included patients with NIHSS score ≥15 and infarct volume ≥60 mL measured within 48 h of symptom onset. Malignant edema was defined as the development of midline brain shift of ≥5 mm in the first 5 days. Exclusion criterion was enrollment in any experimental trial. A univariate and multivariate logistic regression analysis was performed to model and predict the factors related to outcomes. RESULTS: 46 patients (29 female, 17 male; mean age 57.3 ± 1.5 years) met study criteria. The mortality rate was 28% (n = 13). In a multivariate analysis, only concurrent anterior cerebral artery (ACA) involvement was associated with mortality (OR 9.78, 95% CI 1.15, 82.8, p = 0.04). In the malignant edema subgroup (n = 23, 58%), 4 died (17%), 7 underwent decompressive craniectomy (30%), 7 underwent tracheostomy (30%), and 15 underwent gastrostomy (65%). CONCLUSIONS: Adverse outcomes after severe stroke are common. Concurrent ACA involvement predicts mortality in severe MCA stroke. It is useful to understand the incidence of life-sustaining procedures, such as tracheostomy and gastrostomy, as well as factors that contribute to their necessity.

Lesions to the prefrontal performance-monitoring network disrupt neural processing and adaptive behaviors after both errors and novelty.

Unexpected events can have internal causes (action errors) as well as external causes (perceptual novelty). Both events call for adaptations of ongoing behavior, resulting, amongst other things, in post-error and post-novelty slowing (PES/PNS) of reaction times (RT). Both types of events are processed in prefrontal brain areas, indexed by event-related potentials (ERPs): Errors are followed by a complex of ERPs comprised of the error-related negativity (ERN) and error positivity (Pe), whereas novels are followed by a N2/P3 complex. However, despite those overlapping properties, past neuroscientific studies of both types of events resulted in largely separate branches of research. Only recently have theoretical efforts proposed overlapping neuronal networks for the computation of 'unexpectedness' in general. Crucially, in a recent study, we have shown that both errors and novelty are indeed processed in the same neuronal network in the human brain: the prefrontal-cingulate performance-monitoring network (PCMN) underlying the ERN also explained significant parts of the N2/P3 complex. Here, we attempt to take this research further by investigating the causal role of the PCMN in both error and novelty processing. Eight patients with ischemic lesions to the PCMN and eight control participants performed a version of the flanker task in which they made errors, while also being presented with unexpected action effects on a subset of otherwise correct trials. In line with our predictions, lesions to the PCMN lead to significant reductions in ERP amplitude following both errors and perceptual novelty. Also, while the age-matched control participants showed the expected pattern of adaptive RT slowing to both errors and novelty, patients did not exhibit adaptive slowing behaviors following either event. These results support recent theoretical accounts according to which a general PCMN reacts to surprising events, regardless of valence and/or source of the unexpectedness.

Ischemic complications after pituitary surgery: a report of two cases.

BACKGROUND: Cerebral ischemic complications after pituitary surgery are not frequently reported. These vascular complications may be related to (1) direct trauma to the vessel wall, (2) compression of the internal carotid artery (ICA) due to pituitary apoplexy, (3) vasospasm secondary to subarachnoid hemorrhage or vasoactive tumor extract, or (4) hypothalamic injury. PATIENTS: We describe two cases where major vessel infarcts occurred after removal of pituitary tumor. One case has repeated episodes of thrombembolism probably due to a internal carotid artery (ICA) dissection triggered by minor intraoperative ICA injury during transsphenoidal excision. The other cases had a late-onset cerebral ischemia due vasospasm of middle cerebral artery after transcranial excision of a large pituitary tumor. RESULT: Both patients had a long hospital stay and were managed successfully with anticoagulant and antiplatelet drugs, aggressive supportive care in the intensive care unit, and rehabilitation. CONCLUSION: These cases highlight two different mechanisms of infarcts after pituitary surgery. The first case highlights the importance of ICA evaluation before surgery in elderly patients with risk factors, such as chronic smoking, hypertension, and atherosclerotic disease. Even minimal manipulation of the ICA can generate a cascade of thrombembolic events in such patients. The second case highlights the importance of observing the patient of a highly vascular giant pituitary adenoma in the hospital for a longer than usual time. Delayed vasospasm can occur like in aneurysmal subarachnoid hemorrhage and have a good outcome if detected early and managed judiciously.

The influence of anterior cerebral artery flow diversion measured by transcranial Doppler on acute infarct volume and clinical outcome in anterior circulation stroke.

INTRODUCTION: Anterior cerebral artery flow diversion, measured by transcranial Doppler ultrasound, is correlated with leptomeningeal collateral flow on digital subtraction angiography in the setting of middle cerebral artery occlusion. We aimed to assess the influence of flow diversion as a marker of leptomeningeal collateralization on infarct size and penumbral volume. METHODS: We assessed consecutive patients presenting within six-hours of ischaemic stroke. Anterior cerebral artery flow diversion, defined as ipsilateral mean velocity of at least 30% greater than the contralateral artery, was used as the Doppler index of leptomeningeal collateralization. Multivariable regression analysis was performed to assess the impact of anterior cerebral artery flow diversion, controlling for other important clinical variables. Leptomeningeal collateralization was also graded on computed tomography angiography. Infarct core and penumbral volumes were defined using computed tomography perfusion thresholds of cerebral blood volume and mean transit time. Infarct volume, reperfusion, and vessel status were measured at 24 h using magnetic resonance techniques. RESULTS: Fifty-three patients qualified for analysis. Anterior cerebral artery flow diversion was associated with good collateral flow on computed tomography angiography (P < 0·001) and was an independent predictor of admission infarct core volume (P < 0·001), and 24 h infarct volume (P < 0·001). The likelihood of a favourable outcome (modified Rankin Score 0-2) was higher (odds ratio = 27·5, P < 0·001) in those with flow diversion. CONCLUSIONS: Anterior cerebral artery flow diversion indicates effective leptomeningeal collateralization as measured by computed tomography angiography, and independently predicts acute infarct size and 90-day clinical outcome. Flow diversion appears to provide penumbral perfusion, offering some protection against infarct expansion. Acute bedside transcranial Doppler assessment of flow diversion aids prognostication and therapeutic decision making in anterior circulation stroke.

Anterior cerebral artery and Heubner's artery territory infarction.

Anterior cerebral artery (ACA) territory strokes account for 0.5-3% of all ischemic strokes. The etiological mechanisms of ACA territory strokes vary by race; ACA dissection is a frequent cause in Japan. The most prevalent symptom of such strokes is contralateral hemiparesis or monoparesis, usually affecting the leg predominantly. Predominant leg weakness is attributed to damage in the paracentral lobule, and weakness of the arm and face is associated with involvement of Heubner's artery and the medial striate arteries. Hypobulia, typically 'akinetic mutism', is also common. Several behavioral disorders, including the grasp reflex and the alien hand sign, can present as callosal disconnection signs. Transcortical aphasia and urinary incontinence are other frequent symptoms. A non-throbbing headache is common at stroke onset in patients with ACA dissection.

Delayed left anterior and middle cerebral artery hemorrhagic infarctions after attempted strangulation: a case report.

The 2 common carotid arteries bifurcate in the neck into the internal and external carotid arteries. The internal carotid artery enters the skull and further divides into the anterior and middle cerebral artery. During its short course in the neck, the carotid artery travels encased in the carotid sheath along with the vagus nerve and the internal jugular vein. During its course in the neck, the carotid artery is quite superficial, making it vulnerable to both penetrating and blunt traumatic injuries. We report here a case of a 40-year-old man who presented to the emergency department after sudden collapse and loss of consciousness a day after an attempted strangulation. Imaging revealed large hemorrhagic infarcts in the left anterior cerebral artery and middle cerebral artery territories as well as a smaller infarcts in the right anterior cerebral artery territory necessitating emergency decompressive hemicraniectomy. Our case report adds to the existing literature on nervous system injury due to strangulation. Physicians should be aware of the possibility of delayed presentation of neurological deficit after attempted strangulation.

Crossed aphasia following an infarction in the right corpus callosum.

A 68-year-old right-handed woman with no history of brain damage or familial left-handedness was admitted to our hospital due to the acute onset of speech difficulty; her speech was nonfluent. Literal and phonological paraphasias, agrammatism and paragrammatism were observed. Brain MRI revealed an acute infarction in the right anterior cerebral artery territory, involving the right corpus callosum. Moreover, cerebral blood flow was decreased not only in the area of the right corpus callosum but also in the left fronto-temporal lobe, suggesting crossed diaschisis. This is a rare case of crossed aphasia following an infarction in the right corpus callosum.