Chronic Volumes Research Articles

Chronic Cough-Related Differences in Brain Morphometry in Adults: A Population-Based Study

Individuals with cough hypersensitivity have increased central neural responses to tussive stimuli, which may result in maladaptive morphometric changes in the central cough processing systems. Are the volumes of the brain regions implicated in cough hypersensitivity different in adults with chronic cough compared with adults without chronic cough? Between 2009 and 2014, participants in the Rotterdam Study, a population-based cohort, underwent brain MRI and were interviewed for chronic cough, which was defined as daily coughing for at least 3months. Regional brain volumes were quantified with the use of parcellation software. Based on literature review, we identified and studied seven brain regions that previously had been associated with altered functional brain activity in chronic cough. The relationship between chronic cough and regional brain volumes was investigated with the use of multivariable regression models. Chronic cough was prevalent in 9.6%(No.= 349) of the 3,620 study participants (mean age, 68.5 ± 9.0 years; 54.6%female). Participants with chronic cough had significantly smaller anterior cingulate cortex volume than participants without chronic cough (mean difference, -126.16mm3; 95%CI, -245.67 to -6.66; P= .039). Except for anterior cingulate cortex, there were no significant difference in the volume of other brain regions based on chronic cough status. The volume difference in the anterior cingulate cortex was more pronounced in the left hemisphere (mean difference, -88.11mm3; 95%CI, -165.16 to -11.06; P= .025) and in male participants (mean difference, -242.58mm3; 95%CI, -428.60 to -56.55; P= .011). Individuals with chronic cough have a smaller volume of the anterior cingulate cortex, which is a brain region involved in cough suppression. The Netherlands National Trial Registry (NTR; www.trialregister.nl) and the World Health Organization's International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under the joint catalogue number NTR6831.

Stroke Recurrence and Its Relationship With Language Abilities.

Purpose Many factors influence poststroke language recovery, yet little is known about the influence of previous stroke(s) on language after left hemisphere stroke. In this prospective longitudinal study, we investigated the role of prior stroke on language abilities following an acute left hemisphere ischemic stroke, while controlling for demographic and stroke-related factors, and examined if earlier stroke impacted language recovery at a chronic time point. Method Participants (n = 122) with acute left hemisphere ischemic stroke completed language evaluation and clinical neuroimaging. They were divided into two groups: single stroke (SS; n = 79) or recurrent stroke (RS; n = 43). A subset of participants (n = 31) completed chronic-stage re-evaluation. Factors studied included age, education, diabetes and hypertension diagnoses, lesion volume and broad location, group status, aphasia prevalence, and language scores. Results Groups did not differ in language performance across time points. The only significant group differences were that participants with RS were older, had smaller acute lesions, and were less educated. Stroke group membership (SS vs. RS) was not associated with language performance at either time point. In patients with prior stroke, large acute lesion volumes were associated with acute language performance, whereas both large acute and chronic volumes influenced recovery. Conclusions History of prior stroke in itself may not significantly influence language impairment after an additional acute left hemisphere stroke, unless it contributes substantially to the total volume of infarcted brain tissue. Chronic and acute lesion volumes should be accounted for in studies investigating poststroke language performance and recovery. Supplemental Material https://doi.org/10.23641/asha.14669715.

Determinants of hamstring fascicle length in professional rugby league athletes

ObjectivesInvestigate the determinants of hamstring fascicle length in professional rugby league players. DesignRetrospective cohort study MethodsThirty-three elite male athletes underwent testing in the pre-season and in-season periods. Fascicle length measurements of the biceps femoris long head, 3D kinematics and elapsed time-periods at thigh angular velocities between 20°/s to peak velocity during a single-leg Nordic hamstring strength test, GPS-derived running loads, age and previous injury history were all recorded. Fixed effect determinants for fascicle length were analyzed using multiple linear regression. ResultsSignificant determinants of hamstring fascicle length were observed. Multivariate regression analysis showed modifiable factors including chronic (56 days) running volumes >80% of measured peak velocity and maximum velocity itself collectively explained 43% of the variability in the fascicle length data, whilst peak eccentric strength and elapsed time under load from 20°/s to peak thigh angular velocity collectively contributed an additional 44%. Chronic running volumes >90% of individually measured peak velocity and the ‘break angle’ during a Nordic eccentric contraction were not significant contributors to the final model. Non-modifiable risk factors (age and previous injury) contributed the remaining 13%. ConclusionsManaging high velocity running exposure as well as eccentric strength allows for ˜90% of the controllable determinants in fascicle length within elite athlete populations. An important contributor to the explained variability within fascicle length (superseded only by chronic velocity exposure and peak eccentric strength) was an athletes ability to achieve a prolonged contraction at long lengths during eccentric strength training rather than the angle of failure during the contraction in itself.

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS).

Background and PurposeMigraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. MethodsIn a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. ResultsA cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). ConclusionsThese findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.

Abstract WMP116: Acute Infarct Volume in Childhood Stroke Can Be Accurately Estimated by Modelling Contraction of Chronic Infarction

Introduction: Arterial ischemic stroke (AIS) occurs in 1-2 children/100,000/year. Most children have neurologic deficits post-AIS, but the influence of infarct volume on neurologic outcome is understudied. While acute infarct volume {best measured as a percentage of total brain volume infarcted (%aTBVi) in the growing brain} likely predicts outcome, acute scans are not always available in children. Chronic infarct volumes are underestimated by direct measurement due to contraction. A method for estimating acute infarct volumes from chronic scans is needed. We developed and compared the reliability of three methods for estimating the %aTBVi from values measured on chronic images. Methods: A retrospective IRB-approved study studying children (age 1 month-17 years) with AIS enrolled 158 patients. Those with acute (&lt;3 days) and chronic (&gt;90 days) MRIs were manually segmented by a pediatric neuroradiologist. Method 1 (direct method, used as control) estimated %aTBVi by measuring chronic infarct volume (cVI) and dividing by total brain volume. Method 2 (OFC method) estimated %aTBVi by subtracting the total non-infarcted brain volume from an extrapolated total brain volume based on orbitofrontal circumference (OFC). Method 3 (contraction method, Figure 1) used a regression model to apply a correction factor to the direct measurement of cVI that was then divided by total brain volume to estimate %aTBVi. Intraclass correlation compared estimated %aTBVi of the three methods to the gold standard %aTBVi calculated from manual segmentation of acute scans. Results: Inclusion criteria were met by 86 patients. The control direct method had excellent reliability (ICC 0.79), although it was exceeded by the contraction method (Figure 1, ICC=0.86), while the OFC method reliability was poor (ICC=0.42). Conclusion: %aTBVi is reliably estimated in children with AIS with only chronic imaging via the contraction method.

Carbon dioxide narcosis due to inappropriate oxygen delivery: a case report

BackgroundOxygen delivery to patients with chronic obstructive pulmonary disease may be challenging because of their potential hypoxic ventilatory drive. However, some oxygen delivery systems such as non-rebreathing face masks with an oxygen reservoir bag require high oxygen flow for adequate oxygenation and to avoid carbon dioxide rebreathing.Case presentationA 72-year-old Caucasian man with severe chronic obstructive pulmonary disease was admitted to the emergency department because of worsening dyspnea and an oxygen saturation of 81% measured by pulse oximetry. Oxygen was administered using a non-rebreathing mask with an oxygen reservoir bag attached. For fear of removing the hypoxic stimulus to respiration the oxygen flow was inappropriately limited to 4L/minute. The patient developed carbon dioxide narcosis and had to be intubated and mechanically ventilated.ConclusionsNon-rebreathing masks with oxygen reservoir bags must be fed with an oxygen flow exceeding the patient’s minute ventilation (>6–10 L/minute.). If not, the amount of oxygen delivered will be too small to effectively increase the arterial oxygen saturation. Moreover, the risk of carbon dioxide rebreathing dramatically increases if the flow of oxygen to a non-rebreathing mask is lower than the minute ventilation, especially in patients with chronic obstructive pulmonary disease and low tidal volumes. Non-rebreathing masks (with oxygen reservoir bags) must be used cautiously by experienced medical staff and with an appropriately high oxygen flow of 10–15 L/minute. Nevertheless, arterial blood gases must be analyzed regularly for early detection of a rise in partial pressure of carbon dioxide in arterial blood in patients with chronic obstructive pulmonary disease and a hypoxic ventilatory drive. These patients are more safely managed using a nasal cannula with an oxygen flow of 1–2L/minute or a simple face mask with an oxygen flow of 5L/minute.

White matter hyperintensity volume predicts persistent cognitive impairment in transient ischemic attack and minor stroke.

Background Temporary and permanent cognitive changes following transient ischemic attack/minor stroke have been described previously. It is unknown if persisting cognitive deficits in these patients are correlated with acute infarction identified using magnetic resonance imaging. Aims We tested the hypothesis that persistent cognitive impairment after transient ischemic attack/minor stroke can be predicted by the volume of diffusion-weighted imaging lesions. Methods Acute transient ischemic attack/minor stroke (NIH stroke scale score ≤ 3) patients were prospectively recruited within 72 h of onset. Patients underwent Montreal cognitive assessment and magnetic resonance imaging, including diffusion-weighted imaging and Fluid-Attenuated Inverse Recovery sequences, at baseline, days 7 and 30. Cognitive testing was repeated at day 90. Diffusion-weighted imaging lesion and Fluid-Attenuated Inverse Recovery chronic white matter hyperintensity volumes were measured planimetrically. Cognitive impairment was defined a priori as Montreal cognitive assessment score < 26. Results One hundred fifteen patients were imaged at a median (inter-quartile range) of 24.0 (16.6) h after onset. Acute ischemic lesions were present in 91 (79%) patients. Cognitive impairment rates were similar in patients with (47/91, 52%) and without diffusion-weighted imaging lesions (13/24, 54%; p = 0.83). Although linear regression indicated no relationship between acute diffusion-weighted imaging lesion volume and day 30 Montreal cognitive assessment scores (β = -0.163, [-2.243, 0.334], p = 0.144), white matter hyperintensity volumes at baseline were predictive of persistent cognitive deficits after 30 days (β = 2.24, [1.956, 45.369], p = 0.005). Conclusions In most transient ischemic attack/minor stroke patients who suffer acute cognitive impairment post event, deficits are temporary. Deficits after 30 days of onset are correlated with chronic white matter hyperintensity, suggesting subclinical cognitive impairment and/or impaired ability to compensate for the effects of acute ischemic infarcts.

Tranexamic Acid for Treatment of Residual Subdural Hematoma After Bedside Twist-Drill Evacuation

Management of nonemergent, nonacute subdural hematomas (SDHs) ranges from observation to burr-hole evacuation or craniotomy, but recurrence rates are high. We evaluated the safety and efficacy of tranexamic acid (TXA) for the treatment of residual SDHs after bedside twist-drill evacuation. We performed a retrospective analysis of a prospectively maintained database from November 2013 to November 2014 for all patients who underwent placement of a bedside subdural evacuating port system (SEPS) followed by treatment with oral TXA (650 mg daily). All demographics, evidence of venous thromboembolism, and volumes of pertinent computed tomography were obtained. Twenty subdural hematomas in 14 patients met the inclusion criteria for this study. Most SDHs were mixed density. Mean SDH volume on presentation was 145.96 ± 40.22 cm(3) with a mean midline shift of 9.44 ± 4.84 mm. Mean volumes decreased to 80.00 ± 31.96 cm(3) and midline shift improved to 4.44 ± 3.29 mm after SEPS placement (P < 0.0001 and P= 0.0046). All patients were placed on TXA after their procedure. Mean follow-up with computed tomography was 92.1 ± 27.5 days, and mean SDH volume at last follow-up was 7.41 ± 15.54 cm(3) with a mean midline shift of 0.19 ± 0.69 mm (P < 0.0001 and P= 0.0002). Percent volume reduction was significantly higher after TXA than after SEPS (91.31% vs. 40.74%; P < 0.0001). No increase or delayed recurrence of the SDH was noted during TXA treatment. All but 1 clinical presenting symptom improved at follow-up. No venous thromboembolisms were noted among the patients. In our pilot study, chronic SDH volumes were reduced by 40.74% after SEPS drainage. The residual volume was reduced by an additional 91.31% during oral TXA treatment. No patients developed delayed recurrence or expansion of their SDHs. Further prospective studies are needed to evaluate the role of TXA for adjunctive treatment of chronic SDHs.

Abstract 15170: Persistent Microvascular Obstruction Leads to Localized Iron Deposition and Active Inflammation Within Chronic Myocardial Infarctions

Introduction: The mechanism by which persistent microvascular obstruction (PMO) post myocardial infarction (MI) exerts adverse long-term effects is not well understood. Hypothesis: We hypothesized that PMO, with or without reperfusion hemorrhage, can resolve into iron deposition within chronic MI (CMI) territories, and is associated with prolonged inflammation and adverse LV remodeling. Methods: Canines subjected to reperfused (n=17) and non-reperfused (n=16) MI underwent Cardiovascular Magnetic Resonance (CMR) at 7 (acute) and 56 days (chronic) post-MI. Cine, T2*-weighted and Late Gadolinium Enhancement images were used to characterize LV remodeling (End-Diastolic Sphericity Index (EDSI)), iron and PMO respectively. Histological analysis was used to examine chronic inflammation. Results: In the reperfused group, 9 canines had PMO and hemorrhage with subsequent chronic iron deposition (PMO+/T2*+), while 4 canines had no PMO, hemorrhage, or chronic iron deposition (PMO-/T2*-). The remaining 4 canines had PMO without hemorrhage (PMO+/T2*-), but all subsequently had chronic iron deposition. In the non-reperfused group, 15 canines had PMO, and acute and subsequent chronic iron deposition (NR-PMO+/T2*+); 1 canine had no PMO, acute or chronic iron deposition (NR-PMO-/T2*-). In both groups, PMO volume was significantly associated with both acute and chronic iron volumes (p&lt;0.001 all cases). In both groups, infarct and iron volumes measured in both acute and chronic phases were significant predictors of change in EDSI between acute and chronic phases (p&lt;0.01 all cases). Histological sections of the harvested hearts post day 56 CMR showed extensive newly recruited macrophage, IL-1β, TNF-α and MMP-9 activities highly localized with iron in CMI regions (p&lt;0.001 all cases). Conclusions: PMO, with or without reperfusion hemorrhage, can lead to iron deposition within CMIs, and is associated with active inflammation and adverse LV remodeling in canines.

Perindopril and residual chronic subdural hematoma volumes six weeks after burr hole surgery: A randomized trial

ObjectiveRecurrence rates of between 5% and 25% have been reported following surgery for chronic subdural hematoma (CSH). A previous study showed that the treatment with angiotensin converting enzyme (ACE) inhibitors decreases the risk of recurrence. To test the effects of ACE inhibitors on the recurrence CSH and CSH remnant six weeks after surgery, we conducted a prospective double-blinded randomized controlled clinical trial on patients with CSHs from July 2009 until October 2012. Patients and methodsPatients eligible for burr hole surgery for CSH were randomized into either an ACE inhibitor perindopril 5mg or placebo treatment daily for three months prior to surgery. Cerebral CT scans were performed after six weeks, and clinical follow-ups were performed three months after surgery. Additionally, a retrospective analysis of the data and CT scans from all nonrandomized patients from the same time period was performed. ResultsForty-seven patients were included in the randomized study. The patients’ preoperative Glasgow Coma Scale scores were 15. None of the patients in the randomized group developed a recurrence after surgery. Measurements of the sizes of the CSH before and six weeks after surgery revealed no difference between the placebo and perindopril-treated groups. In the retrospective group (245 patients), there was no correlation between the risk of recurrence and ACE inhibitor treatment. ConclusionOur data suggest that perindopril does not diminish the size of residual CSHs six weeks after burr hole surgery and that ACE inhibitors do not decrease the risk of CSH recurrence.

Predictive Value of Imaging Markers at Multiple Sclerosis Disease Onset Based on Gadolinium- and USPIO-Enhanced MRI and Machine Learning

ObjectivesA novel characterization of Clinically Isolated Syndrome (CIS) patients according to lesion patterns is proposed. More specifically, patients are classified according to the nature of inflammatory lesions patterns. It is expected that this characterization can infer new prospective figures from the earliest imaging signs of Multiple Sclerosis (MS), since it can provide a classification of different types of lesions across patients.MethodsThe method is based on a two-tiered classification. Initially, the spatio-temporal lesion patterns are classified. The discovered lesion patterns are then used to characterize groups of patients. The patient groups are validated using statistical measures and by correlations at 24-month follow-up with hypointense lesion loads.ResultsThe methodology identified 3 statistically significantly different clusters of lesion patterns showing p-values smaller than 0.01. Moreover, these patterns defined at baseline correlated with chronic hypointense lesion volumes by follow-up with an score of .ConclusionsThe proposed methodology is capable of identifying three major different lesion patterns that are heterogeneously present in patients, allowing a patient classification using only two MRI scans. This finding may lead to more accurate prognosis and thus to more suitable treatments at early stage of MS.

Automatic Detection, Localization, and Volume Estimation of Ischemic Infarcts in Noncontrast Computed Tomographic Scans

Sensitivity of noncontrast computed tomography (NCCT) in detecting hyperacute (< 8 hours) and acute (< 24 hours) cerebral infarction is low. We propose an automatic method to detect and localize ischemic infarct and to assess its volume from a single NCCT scan. The method automatically determines attenuation value ranges of cerebrospinal fluid and white and gray matter, separates the brain scan into the left and right hemispheres, and by analyzing hemisphere attenuation value distributions using percentile difference ratios, it detects, localizes, and quantifies the infarct without its segmentation. The method performance was evaluated on 576 patients with clinically confirmed stroke through NCCT scans acquired at 4 centers to measure how it matched with that of experts in detection, localization, and assessment of infarct volume. The time from the onset of symptoms ranged from 1.5 to 72 hours for 450 scans and more than 72 hours for 82 scans, most with pathologic findings in addition to cerebral infarction; the time was unavailable for 44 scans. In addition, the method was compared with the novice's (with 52 scans) and experienced readers' infarct detection (with 21 × 2 scans) in early ischemia detection (with the time from the onset of symptoms ranging from 1.5 to 7 hours). The method matches 100% the expert's infarct detection when chronic infarcts, leukoaraiosis cases, and infarct volumes less than 2 cm (determined by detection accuracy simulation) are excluded from the analysis. For all cases excluding infarct volumes less than 2 cm, the method detection accuracy is 95.7%. Overall, the method detection accuracy is 83.2%. The early method detection accuracy (≤ 3 hours) is 78.4%. The novice detection accuracy is 27.8% (≤ 3 hours), 37.5% (3 < to ≤ 8 hours), and 77.8% (> 8 hours), whereas the expert detection accuracy for these cases is 100%. Moreover, the method detected all 21 early infarcts, of which 15 were missed by the stroke experts and 14 of 15 were missed by a general radiologist. The method performs automatic analysis in approximately 7 seconds. The results demonstrate potential benefits of our method for enhancing expert's performance because it quickly localizes the infarct and detects cases missed by experts, and it is to be considered as an aid in the emergency department because it substantially outperforms novice readers (100% vs 27%) in infarct detection on NCCT.

Essential role of interleukin-6 in post-stroke angiogenesis

Ambivalent effects of interleukin-6 on the pathogenesis of ischaemic stroke have been reported. However, to date, the long-term actions of interleukin-6 after stroke have not been investigated. Here, we subjected interleukin-6 knockout (IL-6(-/-)) and wild-type control mice to mild brain ischaemia by 30-min filamentous middle cerebral artery occlusion/reperfusion. While ischaemic tissue damage was comparable at early time points, IL-6(-/-) mice showed significantly increased chronic lesion volumes as well as worse long-term functional outcome. In particular, IL-6(-/-) mice displayed an impaired angiogenic response to brain ischaemia with reduced numbers of newly generated endothelial cells and decreased density of perfused microvessels along with lower absolute regional cerebral blood flow and reduced vessel responsivity in ischaemic striatum at 4 weeks. Similarly, the early genomic activation of angiogenesis-related gene networks was strongly reduced and the ischaemia-induced signal transducer and activator of transcription 3 activation observed in wild-type mice was almost absent in IL-6(-/-) mice. In addition, systemic neoangiogenesis was impaired in IL-6(-/-) mice. Transplantation of interleukin-6 competent bone marrow into IL-6(-/-) mice (IL-6(chi)) did not rescue interleukin-6 messenger RNA expression or the early transcriptional activation of angiogenesis after stroke. Accordingly, chronic stroke outcome in IL-6(chi) mice recapitulated the major effects of interleukin-6 deficiency on post-stroke regeneration with significantly enhanced lesion volumes and reduced vessel densities. Additional in vitro experiments yielded complementary evidence, which showed that after stroke resident brain cells serve as the major source of interleukin-6 in a self-amplifying network. Treatment of primary cortical neurons, mixed glial cultures or immortalized brain endothelia with interleukin 6-induced robust interleukin-6 messenger RNA transcription in each case, whereas oxygen-glucose deprivation did not. However, oxygen-glucose deprivation of organotypic brain slices resulted in strong upregulation of interleukin-6 messenger RNA along with increased transcription of key angiogenesis-associated genes. In conclusion, interleukin-6 produced locally by resident brain cells promotes post-stroke angiogenesis and thereby affords long-term histological and functional protection.

Association between chronic kidney disease and small residual urine volumes in patients with benign prostatic hyperplasia

It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (<100 mL) are related to renal function. The present study was performed to examine the association between chronic kidney disease (CKD) and the post-void residual urine volume (PVR) in BPH patients. A cross-sectional study was performed in 160 consecutive BPH patients with PVR of less than 100 mL. We first determined the stage of CKD and compared the PVR in subjects with/without CKD. Next, we divided the subjects into three groups according to the extent of PVR (PVR < 12 mL, 12 mL ≤ PVR < 50 mL, 50 mL ≤ PVR < 100 mL) and compared the estimated glomerular filtration rate (eGFR) among these groups. Moreover, risk factors associated with CKD, including the presence of post-void residual urine, were explored by multiple logistic regression analysis. The PVR of the patients with CKD was significantly greater than that of the patients without CKD. The group with the normal PVR (group PVR < 12 mL) had a significantly higher eGFR compared with the other two groups. Multivariate analysis demonstrated that the presence of post-void residual urine (PVR ≥ 12 mL) was a significant and independent risk factor associated with the presence of CKD. In BPH patients, the PVR of the patients with CKD was significantly greater than that of the patients without CKD and the presence of post-void residual urine (PVR ≥ 12 mL) was independently associated with CKD, indicating a close association between CKD and small residual urine volumes.

Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid

BackgroundAlzheimer's disease (AD) and cerebrovascular disease (CVD) including chronic small vessel disease of the brain (SVD) are the most frequent causes of dementia. AD is associated with metabolism of amyloid precursor protein (APP) and low levels of amyloid-β peptide (Aβ) X-42 in the cerebrospinal fluid (CSF). CVD and SVD are established risk factors for AD, brain white matter lesions (WML) are established surrogate markers for SVD and are also associated with reduced CSF AβX-42.A cohort survey was performed to examine whether SVD or acute CVD affects APP metabolism and to explore a potential association between WML and APP metabolism in two groups; cognitively impaired patients, subjective and mild (SCI and MCI) and stroke patients. Through measurements of CSF APP metabolite levels in patients with a wide range of WML volumes, this study aimed to determine how SVD influences APP metabolism.MethodsSixty-three patients were included: 37 with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI) without stroke, and 26 after acute stroke. Chronic and acute WML volume and infarct volume were determined by magnetic resonance imaging (MRI) post-scan processing, and CSF levels of α- and β-cleaved soluble APP (sAPP-α and sAPP-β, AβX-38, AβX-40 and AβX-42) were determined. The Mann-Whitney test was used to compare the patient groups. Chronic and acute WML volumes, infarct volume, age, and sex were used as predictors for CSF biomarker levels in linear regression analysis.ResultsCSF levels of sAPP-α and sAPP-β were strongly correlated (r = 0.95, p < 0.001) and lower levels of these biomarkers were found in the stroke group than in the SCI/MCI group; median sAPP-α 499.5 vs. 698.0 ng/mL (p < 0.001), sAPP-β 258.0 vs. 329.0 ng/mL (p < 0.005). CSF levels of sAPP-α, sAPP-β, AβX-38, AβX-40 and AβX-42 were inversely correlated with chronic WML volume (p ≤ 0.005; p ≤ 0.01; p ≤ 0.01; p ≤ 0.05; p ≤ 0.05 respectively), but not with acute WML or infarct volumes.ConclusionsLower CSF levels of sAPP-α and sAPP-β in the stroke group than in the SCI/MCI group and an inverse correlation with chronic WML indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests that APP axonal transport or metabolism may be affected in SVD of the brain.

Vasoreactivity and peri-infarct hyperintensities in stroke

It is unknown if impaired cerebral vasoreactivity recovers after ischemic stroke, and whether it compromises perfusion in regions surrounding infarct and other vascular territories. We investigated the regional differences in CO2 vasoreactivity (CO2 VR) and their relationships to peri-infarct T2 hyperintensities (PIHs), chronic infarct volumes, and clinical outcomes. We studied 39 subjects with chronic large middle cerebral artery territory infarcts and 48 matched controls. Anatomic and three-dimensional continuous arterial spin labeling imaging at 3-Tesla MRI were used to measure regional cerebral blood flow (CBF) and CO2 VR during normocapnia, hypercapnia, and hypocapnia in main arteries distributions. Stroke patients showed a significantly lower augmentation of blood flow at increased CO2 but greater reduction of blood flow with decreased CO2 than the control group. This altered vasoregulatory response was observed both ipsilateral and contralateral to the stroke. Lower CO2 VR on the stroke side was associated with PIHs, greater infarct volume, and worse outcomes. The cases with PIHs (n = 27) had lower CBF during all conditions bilaterally (p < 0.0001) compared to cases with infarct only. Perfusion augmentation is inadequate in multiple vascular territories in patients with large artery ischemic infarcts, but vasoconstriction is preserved. Peri-infarct T2 hyperintensities are associated with lower blood flow. Strategies aimed to preserve vasoreactivity after an ischemic stroke should be tested for their effect on long-term outcomes.

Development of brain infarct volume as assessed by magnetic resonance imaging (MRI): follow-up of diffusion-weighted MRI lesions.

To investigate the development of ischemic brain lesions, as present in the acute stroke phase, by diffusion-weighted magnetic resonance imaging (DWI), and in the subacute and chronic phases until up to four months after stroke, in fluid-attenuated inversion recovery (FLAIR)- and T2-weighted (T2W) magnetic resonance (MR) images. Twelve consecutive patients with their first middle cerebral artery (MCA) infarction were included. Lesion volumes were assessed on T2W images recorded with a turbo spin echo (TSE) and on images recorded with the FLAIR sequence on average on day 8 and after about four months. They were compared with acute lesion volumes in perfusion and DWI images taken within 24 hours of stroke onset. On day 8, lesion volumes in images obtained with FLAIR exceeded the acute infarct volumes in DWI. The chronic lesion volumes were almost identical in T2W and FLAIR images but significantly reduced compared with the acute DWI lesions. The lesion volumes assessed on DWI images correlated highly with the lesions in the images obtained with TSE or FLAIR, as did the lesions in the images obtained with FLAIR and TSE. The secondary lesion shrinkage was accompanied by ventricular enlargement and perilesional sulcal widening, as most clearly visible in the images obtained with FLAIR. Our results show that the acute DWI lesions are highly predictive for the infarct lesion in the chronic stage after stroke despite a dynamic lesion evolution most evident in MR images obtained with FLAIR.

Lesion defined by Multiparametric MRI ISODATA correlates well with neurological deficit and PWI

P59 OBJECTIVE: To show that the lesion defined by ISODATA (Iterative Self Organizing Data Analysis Technique) has a greater correlation with the deficit on perfusion weighted image (PWI) and National Institute of Health Stroke Scale (NIHSS) compared to the lesion defined by diffusion weighted image (DWI) or T2 weighted image (T2WI). BACKGROUND: Early in the course of acute ischemic stroke, the PWI lesion area is usually larger than the DWI or T2WI lesion areas, and correlates best with clinical neurological deficit. The computer segmentation algorithm ISODATA integrates different MRI parameters (DWI, T2WI, T1WI) and provides complimentary information about status of the tissue. METHODS: We obtained MRI parameters of DWI, T2WI and T1WI from 11 patients at two time points after stroke, the acute (&lt;12 hrs) and chronic (3 months). The clinical neurological deficit was graded by the NIHSS at each time point. PWI was obtained at the acute time point. Relative mean transit time images (rMTT) were used to define the perfusion deficit. We compared PWI deficit area with DWI, ISODATA and T2WI lesion of the same location. The lesion areas were also correlated with NIHSS at acute time point. At chronic time point T2WI and ISODATA lesion volumes were compared with NIHSS. RESULTS: In acute phase PWI lesion area correlated best with NIHSS (r=0.72, p&lt;0.05), followed by ISODATA (r=0.62, p&lt;0.05), DWI (r =0.51, p&lt;0.05) &amp; T2WI (r=0.21, p&lt;0.05) lesion areas. ISODATA correlated best with PWI lesion (r=0.90, p&lt;0.05), and outperformed DWI (r=0.63, p&lt;0.05) and T2WI (r= 0.48, p&lt;0.05). We also noticed at chronic time point that there is a good correlation between ISODATA and T2WI(r= 0.97, p&lt;0.05), ISODATA and NIHSS (r= 0.70, p&lt;0.0.5), T2WI and NIHSS (r=0.68, p&lt;0.05). CONCLUSION: This preliminary study shows that the integrated ISODATA approach to tissue segmentation discriminates abnormal from normal tissue at each time point after stroke. The area of the ISODATA defined lesion correlates well with PWI at the acute and T2WI at the chronic time point and the clinical neurological status of the patient.

Abstracts of Literature

Abstracts of Literature

Ischemic lesion volumes in acute stroke by diffusion‐weighted magnetic resonance imaging correlate with clinical outcome

Diffusion-weighted magnetic resonance imaging detects ischemic injury within minutes after onset, and has been used to demonstrate drug efficacy in animal models of stroke. In 50 patients diagnosed with acute ischemic stroke (<24-hour duration) within the middle cerebral artery territory, lesion volume was measured by diffusion-weighted imaging. Thirty-four patients also had volumes measured by T2-weighted imaging chronically (median time, 7.5 weeks; mean, 15.9 weeks). Clinical severity was measured by the National Institutes of Health Stroke Scale Score and the Barthel index. Acute lesion volumes correlated with the acute stroke scale score (r = 0.56), the chronic stroke scale score (r = 0.63), and chronic lesion volumes (r = 0.84). Chronic volumes correlated with the chronic stroke scale score (r = 0.86) and the Barthel index (r = -0.60). When only cortically based lesions were considered, the correlations relating acute lesion volume measured by diffusion-weighted imaging (r = 0.61) and chronic lesion volume measured by T2-weighted imaging (r = 0.90) to the chronic stroke scale score were higher. These results provide evidence that lesion volumes determined by diffusion-weighted imaging acutely may be predictive of clinical severity and outcome, and may support a role for diffusion-weighted imaging in the assessment of acute stroke therapies in clinical trials.