Acute Hypoperfusion Research Articles

Multifocal Cerebral Microinfarcts Modulate Early Alzheimer's Disease Pathology in a Sex-Dependent Manner.

Alzheimer’s disease (AD) constitutes a major cause of dementia, affecting more women than men. It is characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles (NFTs) formation, associated with a progressive cognitive decline. Evidence indicates that AD onset increases the prevalence of cerebral microinfarcts caused by vascular pathologies, which occur in approximately in half of AD patients. In this project, we postulated that multifocal cerebral microinfarcts decisively influence early AD-like pathology progression in a sex dependent manner in young APP/PS1 mice. For this purpose, we used a novel approach to model multifocal microinfarcts in APP/PS1 mice via the sporadic occlusions of the microvasculature. Our findings indicate that microinfarcts reduced Aβ deposits without affecting soluble Aβ levels in the brain of male and female APP/PS1 mice, while causing rapid and prolonged cognitive deficits in males, and a mild and transient cognitive decline in females. In male APP/PS1 mice, microinfarcts triggered an acute hypoperfusion followed by a chronic hyperperfusion. Whereas in female APP/PS1 mice, microinfarcts caused an acute hypoperfusion, which was recovered in the chronic phase. Microinfarcts triggered a robust microglial activation and recruitment of peripheral monocytes to the lesion sites and Aβ plaques more potently in female APP/PS1 mice, possibly accounting for the reduced Aβ deposition. Finally, expression of Dickkopf-1 (DKK1), which plays a key role in mediating synaptic and neuronal dysfunction in AD, was strongly induced at the lesion sites of male APP/PS1 mice, while its expression was reduced in females. Our findings suggest that multifocal microinfarcts accelerate AD pathology more potently in young males compared to young females independently upon Aβ pathology via modulation of neurovascular coupling, inflammatory response, and DKK1 expression. Our results suggest that the effects of microinfarcts should be taken into consideration in AD diagnosis, prognosis, and therapies.

CME/Answers: Metformin - Dos and Don'ts

CME/Answers: Metformin - Dos and Don'ts Abstract. CME/Answers: Metformin - Dos and Don'ts In the absence of contraindications metformin is still considered the initial medication in patients with diabetes mellitus type 2, although diabetes therapy is rapidly changing. Metformin is used both as monotherapy and in combination with any other diabetic medication. As a biguanide metformin improves glycemic control by inhibiting gluconeogenesis and increasing insulin-mediated glucose utilization in peripheral tissues. Metformin promotes modest weight reduction and provides several other advantages: no risk of hypoglycemia, excellent general tolerability, well-known long-term safety profile and low-cost. The most common gastrointestinal side effects are usually mild and transient, but vitamin B12 deficiency may develop. Metformin-associated lactic acidosis (MALA) is a rare, but relevant and life-threatening complication. The risk increases with renal impairment; therefore the metformin dose must be adjusted to the eGFR. The use of metformin is contraindicated with an eGFR <30 ml/min/1.73 m2. There are other contraindications: concurrent active or progressive severe liver disease, active alcohol abuse, unstable or acute heart failure, hypoperfusion and hemodynamic instability, as well as a past history of lactic acidosis. Since metformin remains a modern therapy, it is important to be aware of its indications and contraindications.

CME: Metformin - Dos and Don'ts

CME: Metformin - Dos and Don'ts Abstract. In the absence of contraindications metformin is still considered the initial medication in patients with diabetes mellitus type 2, although diabetes therapy is rapidly changing. Metformin is used both as monotherapy and in combination with any other diabetic medication. As a biguanide metformin improves glycemic control by inhibiting gluconeogenesis and increasing insulin-mediated glucose utilization in peripheral tissues. Metformin promotes modest weight reduction and provides several other advantages: no risk of hypoglycemia, excellent general tolerability, well-known long-term safety profile and low-cost. The most common gastrointestinal side effects are usually mild and transient, but vitamin B12 deficiency may develop. Metformin-associated lactic acidosis (MALA) is a rare, but relevant and life-threatening complication. The risk increases with renal impairment; therefore the metformin dose must be adjusted to the eGFR. The use of metformin is contraindicated with an eGFR <30 ml/min/1.73 m2. There are other contraindications: concurrent active or progressive severe liver disease, active alcohol abuse, unstable or acute heart failure, hypoperfusion and hemodynamic instability, as well as a past history of lactic acidosis. Since metformin remains a modern therapy, it is important to be aware of its indications and contraindications.

Modern approaches to the diagnosis and treatment of cardiogenic shock complicating acute myocardial infarction

Cardiogenic shock (CS) is the most severe complication of myocardial infarction, manifested by an acute tissue hypoperfusion as a result of impaired contractile function of the heart. CS occupies a leading place in the patterns of mortality in patients with myocardial infarction, despite all the advances in medicine. This review presents a modern classification of CS and a risk assessment score, considers the main aspects of epidemiology and pathophysiology of CS, discusses issues of its diagnosis and treatment.

Abstract WP156: Characterization of Tauopathy in a Rat Model of Post-Stroke Dementia Combining Acute Infarct and Chronic Cerebral Hypoperfusion

Post-stroke dementia (PSD) is a major neurodegenerative consequence of stroke. Tauopathy has been reported in diverse neurodegenerative diseases. We investigated cognitive impairments and pathomechanisms of tauopathy in a rat model of PSD by modeling acute ischemic stroke and underlying chronic cerebral hypoperfusion (CCH) in the same animal. We performed middle cerebral artery occlusion (MCAO) surgery in rats, to mimic acute ischemic stroke, followed by bilateral common carotid artery occlusion (BCCAo) surgery, to mimic CCH. We performed behavioral tests and focused on the characterization of tauopathy through histology. Parenchymal infiltration of cerebrospinal fluid (CSF) tracers after intracisternal injection was examined to evaluate glymphatic clearance. In an animal model of PSD, cognitive impairment was aggravated when BCCAo was superimposed on MCAO. Tauopathy, manifested by tau hyperphosphorylation, was prominent in the penumbra when CCH was combined with acute ischemic stroke. Synergistic accentuation of tauopathy was more evident in the white matter. Oligodendrocytes and some neurons were colocalized with tau hyperphosphorylation. Parenchymal infiltration of CSF tracers was attenuated in the PSD model. Our experimental results suggest that CCH may aggravate cognitive impairment and tau hyperphosphorylation in a rat model of PSD by interfering with tau clearance through glymphatic pathway. Therapeutic strategies to improve clearance of brain metabolic wastes, including tau, may be a promising approach to prevent PSD after stroke.

Acute arterial embolism of lower extremity after mitral valve replacement in a chronic lymphocytic leukaemia patient: a case report

Introduction Acute arterial embolism is a potential severe complication after cardiac surgery: it can be a clinical manifestation of early prosthetic valve (PV) thrombosis, whose incidence is higher in case of mechanical mitral valve or in presence of subtherapeutic anticoagulation, hemodynamic (atrial fibrillation) or haemostatic (obesity, anaemia, renal failure) predisposing factors (1). EACTA guidelines recommend to start anticoagulation during the first 24 hours after surgery, balancing the haemorragic risk(2). Although, in presence of specific comorbidities and risk factors, life-threatening thrombotic events can complicate postoperative period even following the international recommendations. Methods We report a 73-year-old man, suffering from chronic lymphocytic leukaemia (without treatment) and paroxysmal AF who received mitral mechanical valve replacement with a On-X 27/29 mm valve placed on anti-anatomic position because of a severe mitral insufficiency (with chordal systolic anterior movement) and single coronary artery by-pass graft. Unfractionated heparin (UFH) and acetylsalicylic acid were started 18 hours after surgery, in order to maintain an aPTT ratio of 1.5 to 2.5. On postoperative day (POD) 4 patient presented sudden pain and signs of acute hypoperfusion in left leg (distal femoral artery territory), requiring urgent surgery. Transthoracic echocardiography was performed but limited by artefacts and suboptimal acoustic windows. Considering the high risk surgery and the usefulness of early transoesophageal echocardiography (TOE), the patient received a general anaesthesia with tracheal intubation. Results Successful open embolectomy on the common femoral artery was performed; UFH perfusion was maintained during the whole duration of the procedure without haemorrhagic complication. Intraoperative TEO detected spontaneous echo contrast in left atrial appendage and reduced motion with impaired coaptation of the right leaflet (red arrows in figure); neither valvular-atrial-ventricular thrombus nor increased transvalvular gradient nor regurgitation were found. Postoperative TEO (POD 3) showed a PV with normal leaflets movement, without significative stenosis/regurgitation. Warfarin was started on POD 4 and heparin bridging was discontinued when INR target range was reached. Discussion In patient with multiple thrombotic risk factor (id malignancy, AF) adequate anticoagulation level can be difficult to reach: in these cases, serious thrombotic complications must be highly suspected even when guidelines have been followed. Prompt diagnosis and aggressive treatment are crucial to guarantee a good prognosis. Early TOE and a “tailored” anticoagulation therapy play a fundamental role in the management of such complications.

The importance of visuo-motor coordination in upper limb rehabilitation after ischemic stroke by robotic therapy

Abstract Stroke is an acute hypoperfusion of cerebral parenchyma that most often leads to outstanding motor deficits that can last for the rest of the patient’s life. The purpose of the neurorehabilitation process is to limit, as far is possible for the motor deficits and to bring the patient to an independent life. A modern method consists in robotic neurorehabilitation which is more and more used, associated with functional electrical stimulation (FES). At the lower limb, the use of robotic rehabilitation associated with FES is already considered a success due to relatively stereotypical movements of the lower limb. In opposition, the upper limb is more difficult to rehabilitate due to its more complex movements. Therefore, eye-hand coordination (EHC) constitutes an important factor that is conditioning the rehabilitation progress. The eye-hand coordination can be brutally disturbed by stroke with critical consequences on motor-executive component. The EHC development depends on the interaction between a feedback complex and the prediction of the upper limb motility in the space, and requires the association between visual system, oculomotor system and hand motor system. We analyzed the stroke impact on this sensorial-motor functional integration and looked for a possible solution for the interruption of coordination between eyes and the movements of the superior limb. We consider that our study can contribute to a better understanding and to a faster rehabilitation of the motor deficit in the upper limb after stroke. Key words: stroke, rehabilitation, eye-hand coordination, robotic neurorehabilitation,

The Acute Phase of Experimental Subarachnoid Hemorrhage: Intracranial Pressure Dynamics and Their Effect on Cerebral Blood Flow and Autoregulation.

Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome. We investigated the influence of ICP variability on acute changes after SAH by modulating injection velocity and composition in an experimental model of SAH. Five hundred microliters of arterial blood (AB) or normal saline (NS) were injected intracisternally over 1 (AB1, NS1), 10 (AB10, NS10), or 30min (AB30) with monitoring for 6h (n= 68). Rapid blood injection resulted in highest ICP peaks (AB1 median 142.7mmHg [1.Q 116.7-3.Q 230.6], AB30 33.42mmHg [18.8-38.3], p< 0.001) and most severe hypoperfusion (AB1 16.6% [11.3-30.6], AB30 44.2% [34.8-59.8]; p< 0.05). However, after 30min, all blood groups showed comparable ICP elevation and prolonged hypoperfusion. Cerebral autoregulation was disrupted initially due to the immediate ICP increase in all groups except NS10; only AB1, however, resulted in sustained impairment of autoregulation, as well as early neuronal cell loss. Rapidity and composition of hemorrhage resulted in characteristic hyperacute hemodynamic changes, with comparable hypoperfusion despite different ICP ranges. Only rapid ICP increase was associated with pronounced and early, but sustained disruption of cerebral autoregulation, possibly contributing to EBI.

The Dynamics of Impaired Blood-Brain Barrier Restoration in a Rat Model of Co-morbid Injury

Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aβ deposition as well as blood-brain barrier (BBB) disruption, and the etiological link between AD and ischemia are lacking. In this study, we employ in vivo sequential magnetic resonance imaging (MRI) and computed tomography (CT) imaging in a co-morbid rat model of β-amyloid toxicity (Aβ) and ischemia (ET1) with subsequent histopathology of striatal lesion core and penumbra at 1, 7, and 28days post injury. Within 24h, cerebral injury resulted in increased BBB permeability due to the dissolution of β-dystroglycan (β-DG) and basement membrane laminin by active matrix metalloproteinase9 (MMP9). As a result, net flow of circulating IgG down a hydrostatic gradient into the parenchyma led to vasogenic edema and impaired perfusion, thus increasing the apparent hyperintensity in true fast imaging with steady-state free precession (true FISP) imaging and acute hypoperfusion in CT. This was followed by a slow recruitment of reactive astroglia to the affected brain and depolarization of aquaporin4 (AQP4) expression resulting in cytotoxic edema-in an attempt to resolve vasogenic edema. On d28, functional BBB was restored in ET1 rats as observed by astrocytic MMP9 release, β-DG stabilization, and new vessel formation. This was confirmed by reduced hyperintensity on true FISP imaging and normalized cerebral blood flow in CT. While, Aβ toxicity alone was not detrimental enough, Aβ+ET1 rats showed delayed differential expression of MMP9, late recruitment of astroglial cells, protracted loss of AQP4 depolarization, and thus delayed BBB restoration and cerebral perfusion.

Increased variability of watershed areas in patients with high-grade carotid stenosis.

Watershed areas (WSAs) of the brain are most susceptible to acute hypoperfusion due to their peripheral location between vascular territories. Additionally, chronic WSA-related vascular processes underlie cognitive decline especially in patients with cerebral hemodynamic compromise. Despite of high relevance for both clinical diagnostics and research, individual in vivo WSA definition is fairly limited to date. Thus, this study proposes a standardized segmentation approach to delineate individual WSAs by use of time-to-peak (TTP) maps and investigates spatial variability of individual WSAs. We defined individual watershed masks based on relative TTP increases in 30 healthy elderly persons and 28 patients with unilateral, high-grade carotid stenosis, being at risk for watershed-related hemodynamic impairment. Determined WSA location was confirmed by an arterial transit time atlas and individual super-selective arterial spin labeling. We compared spatial variability of WSA probability maps between groups and assessed TTP differences between hemispheres in individual and group-average watershed locations. Patients showed significantly higher spatial variability of WSAs than healthy controls. Perfusion on the side of the stenosis was delayed within individual watershed masks as compared to a watershed template derived from controls, being independent from the grade of the stenosis and collateralization status of the circle of Willis. Results demonstrate feasibility of individual WSA delineation by TTP maps in healthy elderly and carotid stenosis patients. Data indicate necessity of individual segmentation approaches especially in patients with hemodynamic compromise to detect critical regions of impaired hemodynamics.

Acute cardiac support with intravenous milrinone promotes recovery from early brain injury in a murine model of severe subarachnoid haemorrhage.

Early brain injury/ischaemia (EBI) is a serious complication early after subarachnoid haemorrhage (SAH) that contributes to development of delayed cerebral ischaemia (DCI). This study aimed to determine the role of inotropic cardiac support using milrinone (MIL) on restoring acute cerebral hypoperfusion attributable to EBI and improving outcomes after experimental SAH. Forty-three male C57BL/6 mice were assigned to either sham surgery (SAH-sham), SAH induced by endovascular perforation plus postconditioning with 2% isoflurane (Control), or SAH plus isoflurane combined with MIL with and without hypoxia-inducible factor inhibitor (HIF-I) pretreatment. Cardiac output (CO) during intravenous MIL infusion (0.25-0.75μg/kg/min) between 1.5 and 2.5hours after SAH induction was monitored with Doppler echocardiography. Magnetic resonance imaging (MRI)-continuous arterial spin labelling was used for quantitative cerebral blood flow (CBF) measurements. Neurobehavioral function was assessed daily by neurological score and open field test. DCI was analyzed 3days later by determining infarction on MRI. Mild reduction of cardiac output (CO) and global cerebral blood flow (CBF) depression were notable early after SAH. MIL increased CO in a dose-dependent manner (P<.001), which was accompanied by improved hypoperfusion, incidence of DCI and functional recovery than Control (P<.05). The neuroprotective effects afforded by MIL or Control were attenuated by hypoxia-inducible factor (HIF) inhibition (P<.05). These results suggest that MIL improves acute hypoperfusion by its inotropic effect, leading to neurobehavioral improvement in mice after severe SAH, in which HIF may be acting as a critical mediator.

Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage

Background and purposeAcute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH. MethodsTwenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively. ResultsInitial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (P<0.05). MIL raised CBF in a dose-dependent manner (P<0.001), resulted in lower incidence of DCI (P=0.008) and better recovery from neurobehavioral decline than control (P<0.001). The CBF values on day 1 predicted DCI with a cut-off of 42.5ml/100g/min (82% specificity and 83% sensitivity), which was greater in mice treated with MIL than those of control (51.7 versus 37.6ml/100g/min; P<0.001). ConclusionMIL improves post-SAH acute hypoperfusion that can lead to the prevention of DCI and functional worsening, acting as a neurocardiac protective agent against EBI.

Dynamic cerebral autoregulation is unrelated to decrease in external carotid artery blood flow during acute hypotension in healthy young men.

What is the central question of this study? Dynamic cerebral autoregulation (CA) is impaired by sympathetic blockade, and the external carotid artery (ECA) vascular bed may prevent adequate internal carotid artery blood flow. We examined whether α1 -receptor blockade-induced attenuation of dynamic CA is related to reduced ECA vasoconstriction. What is the main finding and its importance? α1 -Receptor blockade attenuated dynamic CA, but in contrast to our hypothesis did not affect the ECA blood flow response to acute hypotension. These findings suggest that the recovery of cerebral blood flow during acute hypotension is unrelated to vasoconstriction within the ECA territory. External carotid artery (ECA) vasoconstriction may defend internal carotid artery (ICA) blood flow during acute hypotension. We hypothesized that the α1 -receptor blockade-induced delay in ICA recovery to the baseline level from acute hypoperfusion is related to attenuated ECA vasoconstriction. The ICA and ECA blood flow were determined by duplex ultrasound during thigh-cuff release-induced acute hypotension while the α1 -receptor blocker prazosin [1mg(20kg)(-1) ] was administered to nine seated young healthy men. Both ICA (mean±SD; by 17±8%, P=0.005) and ECA (by 37±15%, P<0.001) blood flow decreased immediately after occluded thigh-cuff release, with a more rapid ICA blood flow recovery to the baseline level (9±5s) than for the ECA blood flow (17±5s; P=0.019). The ICA blood flow recovery from hypoperfusion was delayed with prazosin (17±4s versus control 9±5s, P=0.006), whereas ECA recovery remained unchanged (P=0.313) despite a similar reduction in mean arterial pressure (-20±4mmHg versus control -23±7mmHg, P=0.148). These findings suggest that α1 -receptor blockade-induced attenuation of the ICA blood flow response to acute hypotension is unrelated to the reduction in ECA blood flow. The sympathetic nervous system via the ECA vascular bed does not contribute to dynamic CA during acute hypotension.

Overcoming Challenges in the Management of Critical Events During Cardiopulmonary Bypass

Critical events during cardiopulmonary bypass (CPB) can challenge the most experienced perfusionists, anesthesiologists, and surgeons and can potentially lead to devastating outcomes. Much of the challenge of troubleshooting these events requires a key understanding of these situations and a well-defined strategy for early recognition and treatment. Adverse situations may be anticipated prior to going on CPB. Atherosclerosis is pervasive, and a high plaque burden may have implications in surgical technique modification and planning of CPB. Hematologic abnormalities such as cold agglutinins, antithrombin III deficiency, and hemoglobin S have been discussed with emphasis on managing complications arising from their altered pathophysiology. Jehovah's witness patients require appropriate techniques for cell salvage to minimize blood loss. During initiation of CPB, devastating situations leading to acute hypoperfusion and multiorgan failure may be encountered in patients undergoing surgery for aortic dissection. Massive air emboli during CPB, though rare, necessitate an urgent diagnosis to detect the source and prompt management to contain catastrophic outcomes. Gaseous microemboli remain ubiquitous and continue to be a major concern for neurocognitive impairment despite our best efforts to improve techniques and refine the CPB circuit. During maintenance of CPB, adverse events reflect inability to provide optimal perfusion and can be ascribed to CPB machine malfunction or physiological aberrations. We also discuss critical events that can occur during perfusion and the need to monitor for organ perfusion in altered physiologic states emanating from hemodilution, hypothermia, and acid-base alterations.

Application of chemical exchange saturation transfer (CEST) MRI in acute stroke to visualize tissue acidosis and infarction risk

WCN 2013 No: 1574 Topic: 3 — Stroke Application of chemical exchange saturation transfer (CEST) MRI in acute stroke to visualize tissue acidosis and infarction risk J. Blicher, A. Tietze, I.K. Mikkelsen, L. Ostergaard, M. Strother, S. Smith, M. Donahue. CFIN, Neuroradiology, Aarhus University Hospital, Aarhus, Denmark; Neuroradiology, Aarhus University Hospital, Aarhus, Denmark; Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA Background: In stroke patients with uncertain symptom onset or patients beyond the current time window for ivTPA there is a need for better imaging modalities to guide clinical decision making. Currently, MRI (perfusion weighted imaging) can be used to assess acute cerebral hypoperfusion. However, the technique is invasive, limited to some patients, and distinguishing penumbra from benign oligemia remains difficult. Amide Proton Transfer (APT) MRI is a non-invasive technique sensitive to the exchange of protons between amide-groups and water. The exchange rate is base-catalyzed and thus pH-sensitive. Objective: To investigate the potential for APT imaging, which is sensitive to lactate formation and reduced pH in tissue at risk for infarction, in human acute stroke patients. Patients and methods: 10 patients with acute stroke were scanned on a Phillips 3 T system using our standard acute MRI protocol (including DWI and PWI) as well as a 3-minute APT-sequence. Patients were offered a follow-up scan and a clinical evaluation one month post-stroke. Results: We found a large variation in APT effect between patients. However, in patients with penumbra, based on DWI/PWI missmatch, we found a lower APT effect compared to the ischemic core pointing to early lowering of pH in the penumbra, and possibly changes in protein and water content in the ischemic core. Conclusions: These first results of APT in human acute stroke patients show that the technique could serve as a tool to show early tissue acidosis, and thus guide clinical decision making in stroke care. doi:10.1016/j.jns.2013.07.817 Abstract — WCN 2013 No: 1575 Topic: 3 — Stroke Clinical factors related to severity of post stroke dementia (A retrospective review from 50 geriatric hospitals in Korea) WCN 2013 No: 1575 Topic: 3 — Stroke Clinical factors related to severity of post stroke dementia (A retrospective review from 50 geriatric hospitals in Korea) J.H. Lee, J.H. Park, S.H. Hwang. Neurology, National Health Insurance Service Ilsan Hospital, Goyang-si, Republic of Korea; Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Republic of Korea; Neurology, Hallym University Sacred Heart Hospital, Seoul, Republic of Korea Background and purpose: The results of clinical studies about the severity of post-stroke dementia patients are limited in Korea. We investigate clinical factors related to severity of dementia and to inspect the clinical factors related to the progression of dementia severity. Methods: The patients who visited the hospital by first time between March 2010 and February 2012, among the patients with post-stroke dementia admitted to 50 geriatric hospitals spread all over Korea, formed the analysis cohorts. Retrospective review of medical records was performed. Results:A total of 2965 patients were included. The average duration of illness is 24.61 ± 28.18 months. By the severity of illness, mild cases were 1032 patients (34.81%), moderate 1278 (43.10%), severe 655 (22.09%), and mean score of MMSE was 14.82 ± 6.24. The severity of dementia is higher in patients with overweight by 3.10 times (p= 0.017) existence of inmate by 5.92 times (p= 0.0002), past history of aphasia symptom by 0.18 times (p= 0.0004). Among the clinical factors related to the progression of dementia severity, female patients showed longer duration of illness by 2.89 times comparedwith average, by the results of univariate analysis of 120 severe dementia patients. Conclusions: Among the clinical factors related to severity of poststroke dementia in inpatients of 50 geriatric hospitals in Korea, severity of dementia is higher in patients with overweight, existence of inmate, and past history of aphasia symptom. The progression speed of dementia is suggested to be slow in female, regarding longer duration of illness in severe dementia patients. doi:10.1016/j.jns.2013.07.818 Abstract — WCN 2013 No: 1557 Topic: 3 — Stroke Clinical and radiologic characteristics of RCVS (Reversible Cerebral Vasoconstriction Syndromes) in 23 patients WCN 2013 No: 1557 Topic: 3 — Stroke Clinical and radiologic characteristics of RCVS (Reversible Cerebral Vasoconstriction Syndromes) in 23 patients Y. Ito, H. Moriyoshi, A. Ogura, N. Nakai, S. Nishida, T. Yasuda. Stroke Center, Department of Neurology, TOYOTA Memorial Hospital,

Cortical Indocyanine Green Videography for Quantification of Acute Hypoperfusion After Subarachnoid Hemorrhage

Acute neurological deficits after subarachnoid hemorrhage (SAH) correlate with outcome, and a phase of acute hypoperfusion was characterized recently. Indocyanine green (ICG) videography is an established intraoperative imaging technique with important descriptive potential. To analyze whether ICG can be used to analyze and confirm perfusion changes early after SAH. We prospectively enrolled 11 patients with acute SAH within the past 24 hours and 14 patients undergoing surgery for unruptured aneurysms. Cortical ICG videography was performed, and offline analysis included the arterial, parenchymal, and venous cortical compartment. Transit times, signal gradient, maximum of fluorescence intensity, and the area under the curve were calculated as surrogate markers for perfusion characteristics. Arterial, parenchymal, and venous transit times were comparable in both groups. The velocity of signal change in SAH patients was significantly lower in all 3 compartments (P < .001, P < .01, P < .001, respectively), as was the peak fluorescence intensity (P < .001). In SAH patients, fluorescence intensity did not vary between areas with and without diffuse cortical blood. Area under the curve analysis showed significantly lower values in SAH patients compared with the control group (P < .001). Cortical ICG videography and analysis are feasible during surgery. Patients early after SAH have a significantly lower velocity of signal change, lower peak of fluorescence intensity, and lower overall area under the curve, but similar transit times. This technique can be used to quantify perfusion alteration, in this case, acute SAH, and may be used as an adapted measurement tool for intraoperative therapy.

MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS

Metabolic information is essential in the investigation of the pathophysiology of stroke-like episodes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Here, we used magnetic resonance imaging to evaluate the dynamic metabolic changes before and after a stroke-like episode in two patients with MELAS caused by the mitochondrial DNA mutation A3243G. We performed functional magnetic resonance imaging, including arterial spin labeling and oxygen extraction fraction imaging, and generated cerebral blood flow and oxygen extraction fraction maps. We recruited eight healthy volunteers to define the normal range of the oxygen extraction fraction. We detected a heterogeneous reduction in the oxygen extraction fraction in the brain in the interictal period as well as at the onset of a stroke-like attack. However, the oxygen extraction fraction in the stroke-like lesions normalized in the acute stage. The stroke-like lesions showed consistent hyperperfusion in the acute phase but hypoperfusion in the chronic phase. We have demonstrated the utility of using new magnetic resonance imaging techniques in the evaluation of the pathophysiology of stroke-like lesions. The increased utilization of oxygen in an acute lesion is a novel finding in our study, which might play a role in the oxidative stress.

Damage to White Matter Pathways in Chronic Visuospatial Neglect (S44.002)

Objective: To identify white matter correlates of chronic right visuospatial neglect signs. Background The exact anatomical location of the lesions in the right hemisphere that lead to signs of visuospatial neglect is currently the object of an intense debate. The effect of confounding factors such as acute diaschisis and hypoperfusion, visual field defects and lesion size may account for conflicting results obtained by previous studies. Design/Methods: Here we present a detailed and comprehensive anatomical study of the white matter lesions in 77 patients with chronic vascular strokes in the right hemisphere and varying signs of visuospatial neglect based on a recently published atlas of the human brain connections. We took into account both lesion size and the presence of visual field defects. Results: White matter analyses confirmed the crucial role of damage to the second branch of the superior longitudinal fasciculus (SLF) in the determinism of chronic signs of visuospatial neglect with a sensitivity of 0.8 and a specificity of 0.84 (p= 0.002). Fronto-parietal disconnection was confirmed with DTI-tractography in a case-control study of two perfectly matched patients. Our analyses also revealed a small subgroup of neglect patients with no SLF damage, but with a focal lesion in the latero-dorsal portion of the thalamus connecting the premotor cortex and the inferior parietal lobule. Conclusions: These results provide a solution to the debate concerning the lesional bases of visuospatial neglect, by precisely identifying in a large sample of patients a cortico-subcortical network subserving aspects of spatial attention, whose dysfunction is crucial to the occurrence of neglect signs. Disclosure: Dr. Thiebaut De Schotten has nothing to disclose. Dr. Tomaiuolo has nothing to disclose. Dr. Bartolomeo has nothing to disclose. Dr. Doricchi has nothing to disclose.

P.3.032 Acute mediofrontal and insular brain hypoperfusion after heroin administration in addicts: a within-subject arterial spin labeling study

P.3.032 Acute mediofrontal and insular brain hypoperfusion after heroin administration in addicts: a within-subject arterial spin labeling study

α-Adrenergic Blockade Unmasks a Greater Compensatory Vasodilation in Hypoperfused Contracting Muscle

We previously demonstrated that acute hypoperfusion in exercising human muscle causes an immediate increase in vascular resistance that is followed by a partial restoration (less than 100% recovery) of flow. In the current study we examined the contribution of α-adrenergic vasoconstriction in the initial changes in vascular resistance at the onset of hypoperfusion as well as in the recovery of flow over time. Nine healthy male subjects (29 ± 2) performed rhythmic forearm exercise (20% of maximum) during hypoperfusion evoked by intra-arterial balloon inflation. Each trial included; baseline, exercise prior to inflation, exercise with inflation, and exercise after deflation (3 min each). Forearm blood flow (FBF; ultrasound), local (brachial artery), and systemic arterial pressure (MAP; Finometer) were measured. The trial was repeated during phentolamine infusion (α-adrenergic receptor blockade). Forearm vascular conductance (FVC; ml min−1 100 mmHg−1) and resistance (mmHg ml min−1) was calculated from BF (ml min−1) and local MAP (mmHg). Recovery of FBF and FVC (steady state inflation plus exercise value − nadir)/[steady state exercise (control) value − nadir] with phentolamine was enhanced compared with the respective control (no drug) trial (FBF = 97 ± 5% vs. 81 ± 6%, P < 0.05; FVC = 126 ± 9% vs. 91 ± 5%, P < 0.01). However, the absolute (0.05 ± 0.01 vs. 0.06 ± 0.01 mmHg ml min−1; P = 0.17) and relative (35 ± 5% vs. 31 ± 2%; P = 0.41) increase in vascular resistance at the onset of balloon inflation was not different between the α-adrenergic receptor inhibition and control (no drug) trials. Therefore, our data indicate that α-adrenergic mediated vasoconstriction restricts compensatory vasodilation during forearm exercise with hypoperfusion, but is not responsible for the initial increase in vascular resistance at the onset of hypoperfusion.