Network localization of neurological symptoms from focal brain lesions.

PubMed

Boes, Aaron D; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S; Fox, Michael D

2015-10-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke.

PubMed

Barlow, Susan J

2016-06-01

Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n = 441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n = 42) or absence (n = 129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion-symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.

Association Between Traumatic Brain Injury-Related Brain Lesions and Long-term Caregiver Burden.

PubMed

Guevara, Andrea Brioschi; Demonet, Jean-Francois; Polejaeva, Elena; Knutson, Kristine M; Wassermann, Eric M; Grafman, Jordan; Krueger, Frank

2016-01-01

To investigate the association between traumatic brain injury (TBI)-related brain lesions and long-term caregiver burden in relation to dysexecutive syndrome. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. A total of 256 participants: 105 combat veterans with TBI, 23 healthy control combat veterans (HCv), and 128 caregivers. Caregiver burden assessed by the Zarit Burden Interview at 40 years postinjury. Participants with penetrating TBI were compared with HCv on perceived caregiver burden and neuropsychological assessment measures. Data of computed tomographic scans (overlay lesion maps of participants with a penetrating TBI whose caregivers have a significantly high burden) and behavioral statistical analyses were combined to identify brain lesions associated with caregiver burden. Burden was greater in caregivers of veterans with TBI than in caregivers of HCv. Caregivers of participants with lesions affecting cognitive and behavioral indicators of dysexecutive syndrome (ie, left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex) showed greater long-term burden than caregivers of participants with lesions elsewhere in the brain. The TBI-related brain lesions have a lasting effect on long-term caregiver burden due to cognitive and behavioral factors associated with dysexecutive syndrome.

Network localization of neurological symptoms from focal brain lesions

PubMed Central

Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D.

2015-01-01

A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10−5) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had

A Generative Probabilistic Model and Discriminative Extensions for Brain Lesion Segmentation--With Application to Tumor and Stroke.

PubMed

Menze, Bjoern H; Van Leemput, Koen; Lashkari, Danial; Riklin-Raviv, Tammy; Geremia, Ezequiel; Alberts, Esther; Gruber, Philipp; Wegener, Susanne; Weber, Marc-Andre; Szekely, Gabor; Ayache, Nicholas; Golland, Polina

2016-04-01

We introduce a generative probabilistic model for segmentation of brain lesions in multi-dimensional images that generalizes the EM segmenter, a common approach for modelling brain images using Gaussian mixtures and a probabilistic tissue atlas that employs expectation-maximization (EM), to estimate the label map for a new image. Our model augments the probabilistic atlas of the healthy tissues with a latent atlas of the lesion. We derive an estimation algorithm with closed-form EM update equations. The method extracts a latent atlas prior distribution and the lesion posterior distributions jointly from the image data. It delineates lesion areas individually in each channel, allowing for differences in lesion appearance across modalities, an important feature of many brain tumor imaging sequences. We also propose discriminative model extensions to map the output of the generative model to arbitrary labels with semantic and biological meaning, such as "tumor core" or "fluid-filled structure", but without a one-to-one correspondence to the hypo- or hyper-intense lesion areas identified by the generative model. We test the approach in two image sets: the publicly available BRATS set of glioma patient scans, and multimodal brain images of patients with acute and subacute ischemic stroke. We find the generative model that has been designed for tumor lesions to generalize well to stroke images, and the extended discriminative -discriminative model to be one of the top ranking methods in the BRATS evaluation.

A generative probabilistic model and discriminative extensions for brain lesion segmentation – with application to tumor and stroke

PubMed Central

Menze, Bjoern H.; Van Leemput, Koen; Lashkari, Danial; Riklin-Raviv, Tammy; Geremia, Ezequiel; Alberts, Esther; Gruber, Philipp; Wegener, Susanne; Weber, Marc-André; Székely, Gabor; Ayache, Nicholas; Golland, Polina

2016-01-01

We introduce a generative probabilistic model for segmentation of brain lesions in multi-dimensional images that generalizes the EM segmenter, a common approach for modelling brain images using Gaussian mixtures and a probabilistic tissue atlas that employs expectation-maximization (EM) to estimate the label map for a new image. Our model augments the probabilistic atlas of the healthy tissues with a latent atlas of the lesion. We derive an estimation algorithm with closed-form EM update equations. The method extracts a latent atlas prior distribution and the lesion posterior distributions jointly from the image data. It delineates lesion areas individually in each channel, allowing for differences in lesion appearance across modalities, an important feature of many brain tumor imaging sequences. We also propose discriminative model extensions to map the output of the generative model to arbitrary labels with semantic and biological meaning, such as “tumor core” or “fluid-filled structure”, but without a one-to-one correspondence to the hypo-or hyper-intense lesion areas identified by the generative model. We test the approach in two image sets: the publicly available BRATS set of glioma patient scans, and multimodal brain images of patients with acute and subacute ischemic stroke. We find the generative model that has been designed for tumor lesions to generalize well to stroke images, and the generative-discriminative model to be one of the top ranking methods in the BRATS evaluation. PMID:26599702

Brain lesions in septic shock: a magnetic resonance imaging study.

PubMed

Sharshar, Tarek; Carlier, Robert; Bernard, Francis; Guidoux, Céline; Brouland, Jean-Philippe; Nardi, Olivier; de la Grandmaison, Geoffroy Lorin; Aboab, Jérôme; Gray, Françoise; Menon, David; Annane, Djillali

2007-05-01

Understanding of sepsis-induced brain dysfunction remains poor, and relies mainly on data from animals or post-mortem studies in patients. The current study provided findings from magnetic resonance imaging of the brain in septic shock. Nine patients with septic shock and brain dysfunction [7 women, median age 63 years (interquartile range 61-79 years), SAPS II: 48 (44-56), SOFA: 8 (6-10)] underwent brain magnetic resonance imaging including gradient echo T1-weighted, fluid-attenuated inversion recovery (FLAIR), T2-weighted and diffusion isotropic images, and mapping of apparent diffusion coefficient. Brain imaging was normal in two patients, showed multiple ischaemic strokes in two patients, and in the remaining patients showed white matter lesions at the level of the centrum semiovale, predominating around Virchow-Robin spaces, ranging from small multiple areas to diffuse lesions, and characterised by hyperintensity on FLAIR images. The main lesions were also characterised by reduced signal on diffusion isotropic images and increased apparent diffusion coefficient. The lesions of the white matter worsened with increasing duration of shock and were correlated with Glasgow Outcome Score. This preliminary study showed that sepsis-induced brain lesions can be documented by magnetic resonance imaging. These lesions predominated in the white matter, suggesting increased blood-brain barrier permeability, and were associated with poor outcome.

Venous or arterial blood components trigger more brain swelling, tissue death after acute subdural hematoma compared to elderly atrophic brain with subdural effusion (SDE) model rats.

PubMed

Wajima, Daisuke; Sato, Fumiya; Kawamura, Kenya; Sugiura, Keisuke; Nakagawa, Ichiro; Motoyama, Yasushi; Park, Young-Soo; Nakase, Hiroyuki

2017-09-01

Acute subdural hematoma (ASDH) is a frequent complication of severe head injury, whose secondary ischemic lesions are often responsible for the severity of the disease. We focused on the differences of secondary ischemic lesions caused by the components, 0.4ml venous- or arterial-blood, or saline, infused in the subdural space, evaluating the differences in vivo model, using rats. The saline infused rats are made for elderly atrophic brain with subdural effusion (SDE) model. Our data showed that subdural blood, both venous- and arterial-blood, aggravate brain edema and lesion development more than SDE. This study is the first study, in which different fluids in rats' subdural space, ASDH or SDE are compared with the extension of early and delayed brain damage by measuring brain edema and histological lesion volume. Blood constituents started to affect the degree of ischemia underneath the subdural hemorrhage, leading to more pronounced breakdown of the blood-brain barrier and brain damage. This indicates that further strategies to treat blood-dependent effects more efficiently are in view for patients with ASDH. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Use of CT Perfusion For Diagnosis and Prediction of Lesion Growth in Acute Ischemic Stroke

PubMed Central

Huisa, Branko N; Neil, William P; Schrader, Ronald; Maya, Marcel; Pereira, Benedict; Bruce, Nhu T; Lyden, Patrick D

2012-01-01

Background and Purpose CT perfusion (CTP) mapping in research centers correlates well with diffusion weighted imaging (DWI) lesions and may accurately differentiate the infarct core from ischemic penumbra. The value of CTP in real-world clinical practice has not been fully established. We investigated the yield of CTP– derived cerebral blood volume (CBV) and mean transient time (MTT) for the detection of cerebral ischemia and ischemic penumbra in a sample of acute ischemic stroke (AIS) patients. Methods We studied 165 patients with initial clinical symptoms suggestive of AIS. All patients had an initial non-contrast head CT, CT Perfusion (CTP), CT angiogram (CTA) and follow up brain MRI. The obtained perfusion images were used for image processing. CBV, MTT and DWI lesion volumes were visually estimated and manually traced. Statistical analysis was done using R-2.14.and SAS 9.1. Results All normal DWI sequences had normal CBV and MTT studies (N=89). Seventy-three patients had acute DWI lesions. CBV was abnormal in 23.3% and MTT was abnormal in 42.5% of these patients. There was a high specificity (91.8%)but poor sensitivity (40.0%) for MTT maps predicting positive DWI. Spearman correlation was significant between MTT and DWI lesions (ρ=0.66, p>0.0001) only for abnormal MTT and DWI lesions>0cc. CBV lesions did not correlate with final DWI. Conclusions In real-world use, acute imaging with CTP did not predict stroke or DWI lesions with sufficient accuracy. Our findings argue against the use of CTP for screening AIS patients until real-world implementations match the accuracy reported from specialized research centers. PMID:23253533

Correlation of brain Magnetic Resonance Imaging of spontaneously lead poisoned bald eagles (Haliaeetus leucocephalus) with histological lesions: A pilot study.

PubMed

de Francisco, Olga Nicolas; Feeney, Daniel; Armién, Anibal G; Wuenschmann, Arno; Redig, Patrick T

2016-04-01

Six bald eagles with severe, acute lead poisoning based on blood lead values were analyzed by Magnetic Resonance Imaging (MRI) of the brain and histopathology. The aims of the study were to use MRI to locate brain lesions and correlate the changes in MRI signal with the histological character of the lesions at necropsy. All of the bald eagles presented with neurologic and non-neurologic signs suggestive of severe lead poisoning and had blood lead levels in excess of 1.0 ppm. Areas of change in image intensity in the brainstem, midbrain and cerebellum were detected in the MRI scans. Histopathology confirmed the presence of all suspected lesions. The character of the lesions suggested vascular damage as the primary insult. MRI was useful for detecting lesions and defining their three-dimensional distribution and extent. Future studies are needed to evaluate the utility of MRI for detection of lesions in less severely lead poisoned eagles and determining prognosis for treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Finding the imposter: brain connectivity of lesions causing delusional misidentifications.

PubMed

Darby, R Ryan; Laganiere, Simon; Pascual-Leone, Alvaro; Prasad, Sashank; Fox, Michael D

2017-02-01

SEE MCKAY AND FURL DOI101093/AWW323 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Focal brain injury can sometimes lead to bizarre symptoms, such as the delusion that a family member has been replaced by an imposter (Capgras syndrome). How a single brain lesion could cause such a complex disorder is unclear, leading many to speculate that concurrent delirium, psychiatric disease, dementia, or a second lesion is required. Here we instead propose that Capgras and other delusional misidentification syndromes arise from single lesions at unique locations within the human brain connectome. This hypothesis is motivated by evidence that symptoms emerge from sites functionally connected to a lesion location, not just the lesion location itself. First, 17 cases of lesion-induced delusional misidentifications were identified and lesion locations were mapped to a common brain atlas. Second, lesion network mapping was used to identify brain regions functionally connected to the lesion locations. Third, regions involved in familiarity perception and belief evaluation, two processes thought to be abnormal in delusional misidentifications, were identified using meta-analyses of previous functional magnetic resonance imaging studies. We found that all 17 lesion locations were functionally connected to the left retrosplenial cortex, the region most activated in functional magnetic resonance imaging studies of familiarity. Similarly, 16 of 17 lesion locations were functionally connected to the right frontal cortex, the region most activated in functional magnetic resonance imaging studies of expectation violation, a component of belief evaluation. This connectivity pattern was highly specific for delusional misidentifications compared to four other lesion-induced neurological syndromes (P < 0.0001). Finally, 15 lesions causing other types of delusions were connected to expectation violation (P < 0.0001) but not familiarity regions, demonstrating specificity for delusion content. Our

Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

ERIC Educational Resources Information Center

He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

2011-01-01

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

Brain lesion correlates of fatigue in individuals with traumatic brain injury.

PubMed

Schönberger, Michael; Reutens, David; Beare, Richard; O'Sullivan, Richard; Rajaratnam, Shantha M W; Ponsford, Jennie

2017-10-01

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

Transient widespread cortical and splenial lesions in acute encephalitis/encephalopathy associated with primary Epstein-Barr virus infection.

PubMed

Zhang, Shuo; Feng, Juan; Shi, Yifang

2016-01-01

Infection with Epstein-Barr virus (EBV) is very common and usually occurs in childhood or early adulthood. Encephalitis/encephalopathy is an uncommon but serious neurological complication of EBV. A case of EBV-associated encephalitis/encephalopathy with involvement of reversible widespread cortical and splenial lesions is presented herein. An 8-year-old Chinese girl who presented with fever and headache, followed by seizures and drowsiness, was admitted to the hospital. Magnetic resonance imaging revealed high signal intensities on diffusion-weighted imaging in widespread cortical and splenial lesions. The clinical and laboratory examination results together with the unusual radiology findings suggested acute encephalitis/encephalopathy due to primary EBV infection. After methylprednisolone pulse therapy together with ganciclovir, the patient made a full recovery without any brain lesions. The hallmark clinical-radiological features of this patient included severe encephalitis/encephalopathy at onset, the prompt and complete recovery, and rapidly reversible widespread involvement of the cortex and splenium. Patients with EBV encephalitis/encephalopathy who have multiple lesions, even with the widespread involvement of cortex and splenium of the corpus callosum, may have a favorable outcome with complete disappearance of all brain lesions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study.

PubMed

Haeusler, Karl Georg; Koch, Lydia; Herm, Juliane; Kopp, Ute A; Heuschmann, Peter U; Endres, Matthias; Schultheiss, Heinz-Peter; Schirdewan, Alexander; Fiebach, Jochen B

2013-01-01

Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF). Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function. Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure. There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation. According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure. © 2012 Wiley Periodicals, Inc.

Segmentation of brain structures in presence of a space-occupying lesion.

PubMed

Pollo, Claudio; Cuadra, Meritxell Bach; Cuisenaire, Olivier; Villemure, Jean-Guy; Thiran, Jean-Philippe

2005-02-15

Brain deformations induced by space-occupying lesions may result in unpredictable position and shape of functionally important brain structures. The aim of this study is to propose a method for segmentation of brain structures by deformation of a segmented brain atlas in presence of a space-occupying lesion. Our approach is based on an a priori model of lesion growth (MLG) that assumes radial expansion from a seeding point and involves three steps: first, an affine registration bringing the atlas and the patient into global correspondence; then, the seeding of a synthetic tumor into the brain atlas providing a template for the lesion; finally, the deformation of the seeded atlas, combining a method derived from optical flow principles and a model of lesion growth. The method was applied on two meningiomas inducing a pure displacement of the underlying brain structures, and segmentation accuracy of ventricles and basal ganglia was assessed. Results show that the segmented structures were consistent with the patient's anatomy and that the deformation accuracy of surrounding brain structures was highly dependent on the accurate placement of the tumor seeding point. Further improvements of the method will optimize the segmentation accuracy. Visualization of brain structures provides useful information for therapeutic consideration of space-occupying lesions, including surgical, radiosurgical, and radiotherapeutic planning, in order to increase treatment efficiency and prevent neurological damage.

Dorsal brain stem syndrome: MR imaging location of brain stem tegmental lesions in neonates with oral motor dysfunction.

PubMed

Quattrocchi, C C; Longo, D; Delfino, L N; Cilio, M R; Piersigilli, F; Capua, M D; Seganti, G; Danhaive, O; Fariello, G

2010-09-01

The anatomic extent of brain stem damage may provide information about clinical outcome and prognosis in children with hypoxic-ischemic encephalopathy and oral motor dysfunction. The aim of this study was to retrospectively characterize the location and extent of brain stem lesions in children with oral motor dysfunction. From January 2005 to August 2009, 43 infants hospitalized at our institution were included in the study because of a history of hypoxic-ischemic events. Of this group, 14 patients showed oral motor dysfunction and brain stem tegmental lesions detected at MR imaging. MR imaging showed hypoxic-ischemic lesions in supra- and infratentorial areas. Six of 14 patients revealed only infratentorial lesions. Focal symmetric lesions of the tegmental brain stem were always present. The lesions appeared hyperintense on T2-weighted images and hypointense on IR images. We found a strong association (P < .0001) between oral motor dysfunction and infratentorial lesions on MR imaging. Oral motor dysfunction was associated with brain stem tegmental lesions in posthypoxic-ischemic infants. The MR imaging examination should be directed to the brain stem, especially when a condition of prolonged gavage feeding is necessary in infants.

From the Cover: Magnetic Resonance Imaging Reveals Progressive Brain Injury in Rats Acutely Intoxicated With Diisopropylfluorophosphate

PubMed Central

Hobson, Brad A.; Sisó, Sílvia; Rowland, Douglas J.; Harvey, Danielle J.; Bruun, Donald A.; Garbow, Joel R.

2017-01-01

Abstract Acute intoxication with organophosphates (OPs) can trigger seizures that progress to status epilepticus, and survivors often exhibit chronic neuropathology, cognitive impairment, affective disorders, and/or electroencephalographic abnormalities. Understanding how acute injury transitions to persistent neurological sequelae is critical to developing medical countermeasures for mitigating damage following OP-induced seizures. Here, we used in vivo magnetic resonance imaging (MRI) to monitor the spatiotemporal patterns of neuropathology for 1 month after acute intoxication with diisopropylfluorophosphate (DFP). Adult male Sprague Dawley rats administered pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to successive administration of DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and 2-pralidoxime (25 mg/kg, im) exhibited moderate-to-severe seizure behavior. T2-weighted and diffusion-weighted MR imaging prior to DFP exposure and at 3, 7, 14, 21, or 28 days postexposure revealed prominent lesions, tissue atrophy, and ventricular enlargement in discrete brain regions. Lesions varied in intensity and/or extent over time, with the overall magnitude of injury strongly influenced by seizure severity. Importantly, lesions detected by MRI correlated spatially and temporally with histological evidence of brain pathology. Analysis of histogram parameters extracted from frequency distributions of regional apparent diffusion coefficient (ADC) values identified the standard deviation and 90th percentile of the ADC as robust metrics for quantifying persistent and progressive neuropathological changes. The interanimal and interregional variations observed in lesion severity and progression, coupled with potential reinjury following spontaneous recurrent seizures, underscore the advantages of using in vivo imaging to longitudinally monitor neuropathology and, ultimately, therapeutic response, following acute OP intoxication. PMID:28329842

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

PubMed

Navarrete, Marisol Galván; Hernández, Alma Dalia; Collado-Ortiz, Miguel Angel; Salinas-Lara, Citlaltepetl; Tena-Suck, Martha Lilia

2014-08-01

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

Central diabetes insipidus in children with acute brain insult.

PubMed

Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

2011-12-01

Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

Finding the imposter: brain connectivity of lesions causing delusional misidentifications

PubMed Central

Darby, R Ryan; Laganiere, Simon; Pascual-Leone, Alvaro; Prasad, Sashank; Fox, Michael D

2017-01-01

Abstract See McKay and Furl (doi:10.1093/aww323) for a scientific commentary on this article. Focal brain injury can sometimes lead to bizarre symptoms, such as the delusion that a family member has been replaced by an imposter (Capgras syndrome). How a single brain lesion could cause such a complex disorder is unclear, leading many to speculate that concurrent delirium, psychiatric disease, dementia, or a second lesion is required. Here we instead propose that Capgras and other delusional misidentification syndromes arise from single lesions at unique locations within the human brain connectome. This hypothesis is motivated by evidence that symptoms emerge from sites functionally connected to a lesion location, not just the lesion location itself. First, 17 cases of lesion-induced delusional misidentifications were identified and lesion locations were mapped to a common brain atlas. Second, lesion network mapping was used to identify brain regions functionally connected to the lesion locations. Third, regions involved in familiarity perception and belief evaluation, two processes thought to be abnormal in delusional misidentifications, were identified using meta-analyses of previous functional magnetic resonance imaging studies. We found that all 17 lesion locations were functionally connected to the left retrosplenial cortex, the region most activated in functional magnetic resonance imaging studies of familiarity. Similarly, 16 of 17 lesion locations were functionally connected to the right frontal cortex, the region most activated in functional magnetic resonance imaging studies of expectation violation, a component of belief evaluation. This connectivity pattern was highly specific for delusional misidentifications compared to four other lesion-induced neurological syndromes (P < 0.0001). Finally, 15 lesions causing other types of delusions were connected to expectation violation (P < 0.0001) but not familiarity regions, demonstrating specificity for delusion

Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

PubMed

Shahid, Hinna; Sebastian, Rajani; Schnur, Tatiana T; Hanayik, Taylor; Wright, Amy; Tippett, Donna C; Fridriksson, Julius; Rorden, Chris; Hillis, Argye E

2017-06-01

Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

PubMed

Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

1992-01-01

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

Relationship between brain lesion characteristics and communication in preschool children with cerebral palsy.

PubMed

Coleman, Andrea; Fiori, Simona; Weir, Kelly A; Ware, Robert S; Boyd, Roslyn N

2016-11-01

MRI shows promise as a prognostic tool for clinical findings such as gross motor function in children with cerebral palsy(CP), however the relationship with communication skills requires exploration. To examine the relationship between the type and severity of brain lesion on MRI and communication skills in children with CP. 131 children with CP (73 males(56%)), mean corrected age(SD) 28(5) months, Gross Motor Functional Classification System distribution: I=57(44%), II=14(11%), III=19(14%), IV=17(13%), V=24(18%). Children were assessed on the Communication and Symbolic Behavioral Scales Developmental Profile (CSBS-DP) Infant-Toddler Checklist. Structural MRI was analysed with reference to type and semi-quantitative assessment of the severity of brain lesion. Children were classified for motor type, distribution and GMFCS. The relationships between type/severity of brain lesion and communication ability were analysed using multivariable tobit regression. Children with periventricular white matter lesions had better speech than children with cortical/deep grey matter lesions (β=-2.6, 95%CI=-5.0, -0.2, p=0.04). Brain lesion severity on the semi-quantitative scale was related to overall communication skills (β=-0.9, 95%CI=-1.4, -0.5, p<0.001). Motor impairment better accounted for impairment in overall communication skills than brain lesion severity. Structural MRI has potential prognostic value for communication impairment in children with CP. WHAT THIS PAPER ADDS?: This is the first paper to explore important aspects of communication in relation to the type and severity of brain lesion on MRI in a representative cohort of preschool-aged children with CP. We found a relationship between the type of brain lesion and communication skills, children who had cortical and deep grey matter lesions had overall communication skills>1 SD below children with periventricular white matter lesions. Children with more severe brain lesions on MRI had poorer overall communication

Hypopituitarism after acute brain injury.

PubMed

Urban, Randall J

2006-07-01

Acute brain injury has many causes, but the most common is trauma. There are 1.5-2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding 10 billion dollars. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30-40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7-21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

PubMed

Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

2013-03-01

Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Bilateral spinal anterior horn lesions in acute motor axonal neuropathy.

PubMed

Sawada, Daisuke; Fujii, Katsunori; Misawa, Sonoko; Shiohama, Tadashi; Fukuhara, Tomoyuki; Fujita, Mayuko; Kuwabara, Satoshi; Shimojo, Naoki

2018-05-28

Guillain-Barré syndrome is an acute immune-mediated peripheral polyneuropathy. Neuroimaging findings from patients with this syndrome have revealed gadolinium enhancement in the cauda equina and in the anterior and posterior nerve roots, but intra-spinal lesions have never been described. Herein, we report, for the first time, bilateral spinal anterior horn lesions in a patient with an acute motor axonal neuropathy form of Guillain-Barré syndrome. The patient was a previously healthy 13-year-old Japanese girl, who exhibited acute-onset flaccid tetraplegia and loss of tendon reflexes. Nerve conduction studies revealed motor axonal damage, leading to the diagnosis of acute motor axonal neuropathy. Notably, spinal magnetic resonance imaging revealed bilateral anterior horn lesions on T2-weighted imaging at the Th11-12 levels, as well as gadolinium enhancement of the cauda equina and anterior and posterior nerve roots. The anterior horn lesions were most prominent on day 18, and their signal intensity declined thereafter. Although intravenous treatment with immunoglobulins was immediately administered, the motor function was not completely regained. We propose that anterior spinal lesions might be responsible for the prolonged neurological disability of patients with Guillain-Barré syndrome, possibly produced by retrograde progression from the affected anterior nerve roots to the intramedullary roots, and the anterior horn motor neurons. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Change in brain and lesion volumes after CEE therapies

PubMed Central

Espeland, Mark A.; Hogan, Patricia E.; Resnick, Susan M.; Bryan, R. Nick; Robinson, Jennifer G.; Goveas, Joseph S.; Davatzikos, Christos; Kuller, Lewis H.; Williamson, Jeff D.; Bushnell, Cheryl D.; Shumaker, Sally A.

2014-01-01

Objectives: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen–based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. Methods: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Results: Total brain volume decreased an average of 3.22 cm3/y in the active arm and 3.07 cm3/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm3/y (p = 0.88). Conclusions: Conjugated equine estrogen–based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings. PMID:24384646

Limitations on the Developing Preterm Brain: Impact of Periventricular White Matter Lesions on Brain Connectivity and Cognition

ERIC Educational Resources Information Center

Pavlova, Marina A.; Krageloh-Mann, Ingeborg

2013-01-01

Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and…

Impact of correction factors in human brain lesion-behavior inference.

PubMed

Sperber, Christoph; Karnath, Hans-Otto

2017-03-01

Statistical voxel-based lesion-behavior mapping (VLBM) in neurological patients with brain lesions is frequently used to examine the relationship between structure and function of the healthy human brain. Only recently, two simulation studies noted reduced anatomical validity of this method, observing the results of VLBM to be systematically misplaced by about 16 mm. However, both simulation studies differed from VLBM analyses of real data in that they lacked the proper use of two correction factors: lesion size and "sufficient lesion affection." In simulation experiments on a sample of 274 real stroke patients, we found that the use of these two correction factors reduced misplacement markedly compared to uncorrected VLBM. Apparently, the misplacement is due to physiological effects of brain lesion anatomy. Voxel-wise topographies of collateral damage in the real data were generated and used to compute a metric for the inter-voxel relation of brain damage. "Anatomical bias" vectors that were solely calculated from these inter-voxel relations in the patients' real anatomical data, successfully predicted the VLBM misplacement. The latter has the potential to help in the development of new VLBM methods that provide even higher anatomical validity than currently available by the proper use of correction factors. Hum Brain Mapp 38:1692-1701, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cortical venous disease severity in MELAS syndrome correlates with brain lesion development.

PubMed

Whitehead, M T; Wien, M; Lee, B; Bass, N; Gropman, A

2017-08-01

MELAS syndrome is a mitochondrial disorder typified by recurrent stroke-like episodes, seizures, and progressive brain injury. Abnormal mitochondria have been found in arterial walls implicating a vasculogenic etiology. We have observed abnormal cortical vein T2/FLAIR signal in MELAS patients, potentially representing wall thickening and sluggish flow. We sought to examine the relationship of hyperintense veins and brain lesions in MELAS. Imaging databases at two children's hospitals were searched for brain MRIs from MELAS patients. Artifact, sedated exams, and lack of 2D-T2/FLAIR sequences were exclusion criteria. Each exam was assigned a venous score based on number of T2/FLAIR hyperintense veins: 1 = <10, 2 = 10 to 20, 3 = >20. Cumulative brain lesions and venous score in MELAS and aged-matched normal exams were compared by Mann-Whitney test. A total of 106 exams from 14 unique MELAS patients (mean 16 ± 3 years) and 30 exams from normal aged-matched patients (mean 15 ± 3 years) were evaluated. Median venous score between MELAS and control patients significantly differed (3 versus 1; p < 0.001). In the MELAS group, venous score correlated with presence (median = 3) or absence (median = 1) of cumulative brain lesions. In all 8 MELAS patients who developed lesions, venous hyperintensity was present prior to, during, and after lesion onset. Venous score did not correlate with brain lesion acuity. Abnormal venous signal correlates with cumulative brain lesion severity in MELAS syndrome. Cortical venous stenosis, congestion, and venous ischemia may be mechanisms of brain injury. Identification of cortical venous pathology may aid in diagnosis and could be predictive of lesion development.

Deletion of aquaporin-4 is neuroprotective during the acute stage of micro traumatic brain injury in mice.

PubMed

Liang, Fengyin; Luo, Chuanming; Xu, Guangqing; Su, Fengjuan; He, Xiaofei; Long, Simei; Ren, Huixia; Liu, Yaning; Feng, Yanqing; Pei, Zhong

2015-06-26

Micro traumatic brain injury (TBI) is the most common type of brain injury, but the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet, which plays an important role in brain edema. However, little is known about the role of AQP4 in micro TBI. Here, we examined the role of AQP4 in the pathogenesis of micro TBI in a closed-skull brain injury model, using two-photon microscopy. Our results indicate that AQP4 deletion reduced cell death, water content, astrocyte swelling and lesion volume during the acute stage of micro TBI. Our data revealed that astrocyte swelling is a decisive pathophysiological factor in the acute phase of this form of micro brain injury. Thus, treatments that inhibit AQP4 could be used as a neuroprotective strategy for micro TBI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Application of diffusion tensor imaging in judging infarction time of acute ischemic cerebral infarction].

PubMed

Dai, Zhenyu; Chen, Fei; Yao, Lizheng; Dong, Congsong; Liu, Yang; Shi, Haicun; Zhang, Zhiping; Yang, Naizhong; Zhang, Mingsheng; Dai, Yinggui

2015-08-18

To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction. To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging. Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra. Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases. The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged. The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually

Limitations on the developing preterm brain: impact of periventricular white matter lesions on brain connectivity and cognition.

PubMed

Pavlova, Marina A; Krägeloh-Mann, Ingeborg

2013-04-01

Brain lesions to the white matter in peritrigonal regions, periventricular leukomalacia, in children who were born prematurely represent an important model for studying limitations on brain development. The lesional pattern is of early origin and bilateral, that constrains the compensatory potential of the brain. We suggest that (i) topography and severity of periventricular lesions may have a long-term predictive value for cognitive and social capabilities in preterm birth survivors; and (ii) periventricular lesions may impact cognitive and social functions by affecting brain connectivity, and thereby, the dissociable neural networks underpinning these functions. A further pathway to explore is the relationship between cerebral palsy and cognitive outcome. Restrictions caused by motor disability may affect active exploration of surrounding and social participation that may in turn differentially impinge on cognitive development and social cognition. As an outline for future research, we underscore sex differences, as the sex of a preterm newborn may shape the mechanisms by which the developing brain is affected.

Do brain lesions in stroke affect basic emotions and attachment?

PubMed

Farinelli, Marina; Panksepp, Jaak; Gestieri, Laura; Maffei, Monica; Agati, Raffaele; Cevolani, Daniela; Pedone, Vincenzo; Northoff, Georg

2015-01-01

The aim of the current study was to investigate basic emotions and attachment in a sample of 86 stroke patients. We included a control group of 115 orthopedic patients (matched for age and cognitive status) without brain lesions to control for unspecific general illness effects of a traumatic recent event on basic emotions and attachment. In order to measure basic emotions and attachment style we applied the Affective Neuroscience Personality Scale (ANPS) and the Attachment Style Questionnaire (ASQ). The stroke patients showed significantly different scores in the SEEKING, SADNESS, and ANGER subscales of the ANPS as well as in the Relationship as Secondary Attachment dimension of the ASQ when compared to the control group. These differences show a pattern influenced by lesion location mainly as concerns basic emotions. Anterior, medial, left, and subcortical patients provide scores significantly lower in ANPS-SEEKING than the control group; ANPS-SADNESS scores in anterior, right, medial, and subcortical patients were significantly higher than those of the control group. ANPS-ANGER scores in posterior, right, and lateral patients were significantly higher than those in the control group; finally, the ANPS-FEAR showed slightly lower scores in posterior patients than in the control group. Minor effects on brain lesions were also individuated in the attachment style. Anterior lesion patients showed a significantly higher average score in the ASQ-Need for Approval subscale than the control group. ASQ-Confidence subscale scores differed significantly in stroke patients with lesions in medial brain regions when compared to control subjects. Scores at ANPS and ASQ subscales appear significantly more correlated in stroke patients than in the control group. Such finding of abnormalities, especially concerning basic emotions in stroke brain-lesioned patients, indicates that the effect of brain lesions may enhance the interrelation between basic emotions and attachment with

Effects of brain lesions on moral agency: ethical dilemmas in investigating moral behavior.

PubMed

Christen, Markus; Müller, Sabine

2015-01-01

Understanding how the "brain produces behavior" is a guiding idea in neuroscience. It is thus of no surprise that establishing an interrelation between brain pathology and antisocial behavior has a long history in brain research. However, interrelating the brain with moral agency--the ability to act in reference to right and wrong--is tricky with respect to therapy and rehabilitation of patients affected by brain lesions. In this contribution, we outline the complexity of the relationship between the brain and moral behavior, and we discuss ethical issues of the neuroscience of ethics and of its clinical consequences. First, we introduce a theory of moral agency and apply it to the issue of behavioral changes caused by brain lesions. Second, we present a typology of brain lesions both with respect to their cause, their temporal development, and the potential for neural plasticity allowing for rehabilitation. We exemplify this scheme with case studies and outline major knowledge gaps that are relevant for clinical practice. Third, we analyze ethical pitfalls when trying to understand the brain-morality relation. In this way, our contribution addresses both researchers in neuroscience of ethics and clinicians who treat patients affected by brain lesions to better understand the complex ethical questions, which are raised by research and therapy of brain lesion patients.

Generative adversarial networks for brain lesion detection

NASA Astrophysics Data System (ADS)

Alex, Varghese; Safwan, K. P. Mohammed; Chennamsetty, Sai Saketh; Krishnamurthi, Ganapathy

2017-02-01

Manual segmentation of brain lesions from Magnetic Resonance Images (MRI) is cumbersome and introduces errors due to inter-rater variability. This paper introduces a semi-supervised technique for detection of brain lesion from MRI using Generative Adversarial Networks (GANs). GANs comprises of a Generator network and a Discriminator network which are trained simultaneously with the objective of one bettering the other. The networks were trained using non lesion patches (n=13,000) from 4 different MR sequences. The network was trained on BraTS dataset and patches were extracted from regions excluding tumor region. The Generator network generates data by modeling the underlying probability distribution of the training data, (PData). The Discriminator learns the posterior probability P (Label Data) by classifying training data and generated data as "Real" or "Fake" respectively. The Generator upon learning the joint distribution, produces images/patches such that the performance of the Discriminator on them are random, i.e. P (Label Data = GeneratedData) = 0.5. During testing, the Discriminator assigns posterior probability values close to 0.5 for patches from non lesion regions, while patches centered on lesion arise from a different distribution (PLesion) and hence are assigned lower posterior probability value by the Discriminator. On the test set (n=14), the proposed technique achieves whole tumor dice score of 0.69, sensitivity of 91% and specificity of 59%. Additionally the generator network was capable of generating non lesion patches from various MR sequences.

Clinical evaluation of acute phase nystagmus associated with cerebellar lesions.

PubMed

Ogawa, Y; Otsuka, K; Hagiwara, A; Inagaki, T; Shimizu, S; Nagai, N; Konomi, U; Itani, S; Kondo, T; Suzuki, M

2016-06-01

To determine the characteristics of acute phase nystagmus in patients with cerebellar lesions, and to identify a useful indicator for differentiating central lesions from peripheral lesions. Acute phase nystagmus and the appearance of neurological symptoms were retrospectively investigated in 11 patients with cerebellar stroke. At the initial visit, there were no patients with vertical nystagmus, direction-changing gaze evoked nystagmus or pure rotatory nystagmus. There were four cases with no nystagmus and seven cases with horizontal nystagmus at the initial visit. There were no neurological symptoms, except for vertigo and hearing loss, in any cases at the initial visit. The direction and type of nystagmus changed with time, and neurological symptoms other than vertigo appeared subsequently to admission. It is important to observe the changes in nystagmus and other neurological findings for the differential diagnosis of central lesions.

Do acute phase markers explain body temperature and brain temperature after ischemic stroke?

PubMed Central

Whiteley, William N.; Thomas, Ralph; Lowe, Gordon; Rumley, Ann; Karaszewski, Bartosz; Armitage, Paul; Marshall, Ian; Lymer, Katherine; Dennis, Martin

2012-01-01

Objective: Both brain and body temperature rise after stroke but the cause of each is uncertain. We investigated the relationship between circulating markers of inflammation with brain and body temperature after stroke. Methods: We recruited patients with acute ischemic stroke and measured brain temperature at hospital admission and 5 days after stroke with multivoxel magnetic resonance spectroscopic imaging in normal brain and the acute ischemic lesion (defined by diffusion-weighted imaging [DWI]). We measured body temperature with digital aural thermometers 4-hourly and drew blood daily to measure interleukin-6, C-reactive protein, and fibrinogen, for 5 days after stroke. Results: In 44 stroke patients, the mean temperature in DWI-ischemic brain soon after admission was 38.4°C (95% confidence interval [CI] 38.2–38.6), in DWI-normal brain was 37.7°C (95% CI 37.6–37.7), and mean body temperature was 36.6°C (95% CI 36.3–37.0). Higher mean levels of interleukin-6, C-reactive protein, and fibrinogen were associated with higher temperature in DWI-normal brain at admission and 5 days, and higher overall mean body temperature, but only with higher temperature in DWI-ischemic brain on admission. Conclusions: Systemic inflammation after stroke is associated with elevated temperature in normal brain and the body but not with later ischemic brain temperature. Elevated brain temperature is a potential mechanism for the poorer outcome observed in stroke patients with higher levels of circulating inflammatory markers. PMID:22744672

Cerebral venous thrombosis with nonhemorrhagic lesions: clinical correlates and prognosis.

PubMed

Ferro, José M; Canhão, Patrícia; Bousser, Marie-Germaine; Stam, Jan; Barinagarrementeria, Fernando; Stolz, Erwin

2010-01-01

Brain imaging of patients with acute cerebral venous thrombosis often shows parenchymal hemorrhagic and nonhemorrhagic lesions. The clinical relevance of nonhemorrhagic lesions is poorly known. In the International Study on Cerebral Vein and Dural Sinus Thrombosis cohort, demographic, clinical, risk factor, prognosis and imaging findings were compared between patients with parenchymal nonhemorrhagic lesions and no hemorrhagic lesions (NHL) and (1) patients with parenchymal hemorrhagic lesions (HL) and (2) patients without brain lesions. Predictors of prognosis at the end of follow-up in the NHL group were analyzed by bivariate and Cox regression methods. We identified 147 patients (23.6%) with NHL. When compared to patients without brain lesions (n = 309), those with NHL more often presented mental status disturbances, aphasia, decreased alertness, motor deficits, seizures, occlusions of the straight sinus, deep venous system and cortical veins. Patients with NHL had a better prognosis in the acute phase and at the end of follow-up than those with HL, but a worse one than patients without brain lesions, as more NHL patients were dead or dependent (modified Rankin Scale score = 3-6) at discharge (19.7 vs. 6.5%, p < 0.001) and final follow-up (14.3 vs. 7.4%, p = 0.03). In Cox regression analysis, coma (HR = 13.7; 95% CI = 4.3-43.7) and thrombosis of the deep venous system (HR = 3.5; 95% CI = 1.4-8.7) were associated with death or dependency at the end of follow-up. Cerebral venous thrombosis patients with NHL are intermediate between patients without brain lesions and those with HL, both in initial clinical picture and prognosis. Copyright 2010 S. Karger AG, Basel.

Plasma copeptin level predicts acute traumatic coagulopathy and progressive hemorrhagic injury after traumatic brain injury.

PubMed

Yang, Ding-Bo; Yu, Wen-Hua; Dong, Xiao-Qiao; Du, Quan; Shen, Yong-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie; Wang, Hao; Jiang, Li; Du, Yuan-Feng

2014-08-01

Higher plasma copeptin levels correlate with poor clinical outcomes after traumatic brain injury. Nevertheless, their links with acute traumatic coagulopathy and progressive hemorrhagic injury are unknown. Therefore, we aimed to investigate the relationship between plasma copeptin levels, acute traumatic coagulopathy and progressive hemorrhagic injury in patients with severe traumatic brain injury. We prospectively studied 100 consecutive patients presenting within 6h from head trauma. Progressive hemorrhagic injury was present when the follow-up computerized tomography scan reported any increase in size or number of the hemorrhagic lesion, including newly developed ones. Acute traumatic coagulopathy was defined as an activated partial thromboplastic time greater than 40s and/or international normalized ratio greater than 1.2 and/or a platelet count less than 120×10(9)/L. We measured plasma copeptin levels on admission using an enzyme-linked immunosorbent assay in a blinded fashion. In multivariate logistic regression analysis, plasma copeptin level emerged as an independent predictor of progressive hemorrhagic injury and acute traumatic coagulopathy. Using receiver operating characteristic curves, we calculated areas under the curve for progressive hemorrhagic injury and acute traumatic coagulopathy. The predictive performance of copeptin was similar to that of Glasgow Coma Scale score. However, copeptin did not obviously improve the predictive value of Glasgow Coma Scale score. Thus, copeptin may help in the prediction of progressive hemorrhagic injury and acute traumatic coagulopathy after traumatic brain injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain lesion-pattern analysis in patients with olfactory dysfunctions following head trauma

PubMed Central

Lötsch, Jörn; Ultsch, Alfred; Eckhardt, Maren; Huart, Caroline; Rombaux, Philippe; Hummel, Thomas

2016-01-01

The presence of cerebral lesions in patients with neurosensory alterations provides a unique window into brain function. Using a fuzzy logic based combination of morphological information about 27 olfactory-eloquent brain regions acquired with four different brain imaging techniques, patterns of brain damage were analyzed in 127 patients who displayed anosmia, i.e., complete loss of the sense of smell (n = 81), or other and mechanistically still incompletely understood olfactory dysfunctions including parosmia, i.e., distorted perceptions of olfactory stimuli (n = 50), or phantosmia, i.e., olfactory hallucinations (n = 22). A higher prevalence of parosmia, and as a tendency also phantosmia, was observed in subjects with medium overall brain damage. Further analysis showed a lower frequency of lesions in the right temporal lobe in patients with parosmia than in patients without parosmia. This negative direction of the differences was unique for parosmia. In anosmia, and also in phantosmia, lesions were more frequent in patients displaying the respective symptoms than in those without these dysfunctions. In anosmic patients, lesions in the right olfactory bulb region were much more frequent than in patients with preserved sense of smell, whereas a higher frequency of carriers of lesions in the left frontal lobe was observed for phantosmia. We conclude that anosmia, and phantosmia, are the result of lost function in relevant brain areas whereas parosmia is more complex, requiring damaged and intact brain regions at the same time. PMID:26937377

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI.

PubMed

Kim, Yong-Woo; Kim, Hak Jin; Choi, Seon Hee; Kim, Dong Chan

2014-10-01

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute

Brain lesions in mallard ducklings from parents fed methylmercury

USGS Publications Warehouse

Heinz, G.H.; Locke, L.N.

1976-01-01

Methylmercury dicyandiamide was fed to mallard ducks at 3 ppm mercury. Mercury accumulated in the eggs to an average of 7.18 and 5.46 ppm on a wet-weight basis in 2 successive years. Mercury in the eggs is believed to have caused brain lesions in the hatched ducklings. Lesions included demyelination, neuron shrink-age, necrosis, and hemorrhage in the meninges overlying the cerebellum. Brains of dead ducklings contained an average of 6.17 and 5.19 ppm mercury on a wet-weight basis in 2 successive years.

Effects of subfornical organ lesions on acutely induced thirst and salt appetite

NASA Technical Reports Server (NTRS)

Thunhorst, R. L.; Beltz, T. G.; Johnson, A. K.

1999-01-01

We examined the role of the subfornical organ (SFO) in stimulating thirst and salt appetite using two procedures that initiate water and sodium ingestion within 1-2 h of extracellular fluid depletion. The first procedure used injections of a diuretic (furosemide, 10 mg/kg sc) and a vasodilator (minoxidil, 1-3 mg/kg ia) to produce hypotension concurrently with hypovolemia. The resulting water and sodium intakes were inhibited by intravenous administration of ANG II receptor antagonist (sarthran, 8 micrograms . kg(-1). min(-1)) or angiotensin-converting enzyme inhibitor (captopril, 2.5 mg/h). The second procedure used injections of furosemide (10 mg/kg sc) and a low dose of captopril (5 mg/kg sc) to initiate water and sodium ingestion upon formation of ANG II in the brain. Electrolytic lesions of the SFO greatly reduced the water intakes, and nearly abolished the sodium intakes, produced by these relatively acute treatments. These results contrast with earlier findings showing little effect of SFO lesions on sodium ingestion after longer-term extracellular fluid depletion.

Disulfiram-induced acute organic brain syndrome.

PubMed

Kump, J G; Flaten, P A; Greenlaw, C W

1979-08-01

Reversible acute organic brain syndrome is described in a patient receiving disulfiram, 250 mg daily. Slowing of the electroencephalogram (3 to 4 cycles per second) in the occipital region resolved ten days after discontinuation of disulfiram. Acute organic brain syndrome induced by disulfiram is not rare but is often not correlated, and it should always be considered a possibility in patients receiving disulfiram therapy.

Analysis of brain and spinal cord lesions to occult brain damage in seropositive and seronegative neuromyelitis optica.

PubMed

Sun, Jie; Sun, Xianting; Zhang, Ningnannan; Wang, Qiuhui; Cai, Huanhuan; Qi, Yuan; Li, Ting; Qin, Wen; Yu, Chunshui

2017-09-01

According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (r s =-0.444, P=0.044) and with BLV in the seronegative group (r s =-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (r s =-0.682, P<0.001). Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute functional reorganisation of the human motor cortex during resection of central lesions: a study using intraoperative brain mapping

PubMed Central

Duffau, H

2001-01-01

OBJECTIVES—Brain plasticity is supposed to allow the compensation of motor function in cases of rolandic lesion. The aim was to analyse the mechanisms of functional reorganisation during surgery in the central area.
METHODS—A motor brain mapping was performed in three right handed patients without any neurological deficit, operated on for a slow growing lesion near the rolandic region (two precentral resected under general anaesthesia and one retrocentral removed under local anaesthesia to allow also sensory mapping) using intraoperative direct electrical stimulations (5 mm space tips bipolar stimulator probe, biphasic square wave pulse current: 1 ms/phase, 60 Hz, 4 to 18mA).
RESULTS—For each patient, the motor areas of the hand and forearm in the primary motor cortex (M1) were identified before and after lesion removal with the same stimulation parameters: the same eloquent sites were found, plus the appearance after resection of additional sites in M1 inducing the same movement during stimulations as the previous areas.
CONCLUSIONS—Multiple cortical representations for hand and forearm movements in M1 seem to exist. In addition, the results demonstrate the short term capacity of the brain to make changes in local motor maps, by sudden unmasking after tumour resection of a second redundant site participating in the same movement. Finally, it seems not necessary for the whole of the redundant sites to be functional to provide normal movement, a concept with potential implications for surgery within the central region.

 PMID:11254775

Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.

PubMed

Hillard, Virany H; Shih, Lynn L; Chin, Shing; Moorthy, Chitti R; Benzil, Deborah L

2003-07-01

Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents.

PubMed

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-02-01

To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema.

Does placental inflammation relate to brain lesions and volume in preterm infants?

PubMed

Reiman, Milla; Kujari, Harry; Maunu, Jonna; Parkkola, Riitta; Rikalainen, Hellevi; Lapinleimu, Helena; Lehtonen, Liisa; Haataja, Leena

2008-05-01

To evaluate the association between histologic inflammation of placenta and brain findings in ultrasound examinations and regional brain volumes in magnetic resonance imaging in very-low-birth-weight (VLBW) or in very preterm infants. VLBW or very preterm infants (n = 121) were categorized into 3 groups according to the most pathologic brain finding on ultrasound examinations until term. The brain magnetic resonance imaging performed at term was analyzed for regional brain volumes. The placentas were analyzed for histologic inflammatory findings. Histologic chorioamnionitis on the fetal side correlated to brain lesions in univariate but not in multivariate analyses. Low gestational age was the only significant risk factor for brain lesions in multivariate analysis (P < .0001). Histologic chorioamnionitis was not associated with brain volumes in multivariate analyses. Female sex, low gestational age, and low birth weight z score correlated to smaller volumes in total brain tissue (P = .001, P = .0002, P < .0001, respectively) and cerebellum (P = .047, P = .003, P = .001, respectively). In addition, low gestational age and low-birth-weight z score correlated to a smaller combined volume of basal ganglia and thalami (P = .0002). Placental inflammation does not appear to correlate to brain lesions or smaller regional brain volumes in VLBW or in very preterm infants at term age.

Cohort Study of Multiple Brain Lesions in Sport Divers: Role of a Patent Foramen Ovale

NASA Technical Reports Server (NTRS)

Knauth, Michael; Ries, Stefan; Pohimann, Stefan; Kerby, Tina; Forstring, Michael; Daffertshofer, Michael; Hennerici,Michael; Sartor, Klaus

1997-01-01

To investigate the role of a patent foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms. Design: Prospective double blind cohort study. . Setting Diving clubs around Heidelberg and departments of neuroradiology and neurology. Subjects: 87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus). Main outcome measures: Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonograhy. Results: 25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance. A total of 41 brain lesions were detected in 11 divers. There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P=0.004). Conclusions: Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale. This association suggests paradoxical gas embolism as the pathological mechanism. A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

PubMed

Jayasekeran, Vanoo; Singh, Salil; Tyrrell, Pippa; Michou, Emilia; Jefferson, Samantha; Mistry, Satish; Gamble, Ed; Rothwell, John; Thompson, David; Hamdy, Shaheen

2010-05-01

Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

White matter lesion extension to automatic brain tissue segmentation on MRI.

PubMed

de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

2009-05-01

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

Application of radiosurgical techniques to produce a primate model of brain lesions

PubMed Central

Kunimatsu, Jun; Miyamoto, Naoki; Ishikawa, Masayori; Shirato, Hiroki; Tanaka, Masaki

2015-01-01

Behavioral analysis of subjects with discrete brain lesions provides important information about the mechanisms of various brain functions. However, it is generally difficult to experimentally produce discrete lesions in deep brain structures. Here we show that a radiosurgical technique, which is used as an alternative treatment for brain tumors and vascular malformations, is applicable to create non-invasive lesions in experimental animals for the research in systems neuroscience. We delivered highly focused radiation (130–150 Gy at ISO center) to the frontal eye field (FEF) of macaque monkeys using a clinical linear accelerator (LINAC). The effects of irradiation were assessed by analyzing oculomotor performance along with magnetic resonance (MR) images before and up to 8 months following irradiation. In parallel with tissue edema indicated by MR images, deficits in saccadic and smooth pursuit eye movements were observed during several days following irradiation. Although initial signs of oculomotor deficits disappeared within a month, damage to the tissue and impaired eye movements gradually developed during the course of the subsequent 6 months. Postmortem histological examinations showed necrosis and hemorrhages within a large area of the white matter and, to a lesser extent, in the adjacent gray matter, which was centered at the irradiated target. These results indicated that the LINAC system was useful for making brain lesions in experimental animals, while the suitable radiation parameters to generate more focused lesions need to be further explored. We propose the use of a radiosurgical technique for establishing animal models of brain lesions, and discuss the possible uses of this technique for functional neurosurgical treatments in humans. PMID:25964746

Acute hydrocephalus caused by intraspinal neurocysticercosis: case report

PubMed Central

2014-01-01

Background Intraspinal neurocysticercosis is an uncommon manifestation that may present as an isolated lesion. Furthermore, acute hydrocephalus caused by isolated intraspinal neurocysticercosis without concomitant cerebral involvement is extremely rare. Case presentation A 64-year-old man presented with a history of severe headache, an unsteady gait, and occasional urinary incontinence. Magnetic resonance imaging of the thoraco-lumbar spine revealed multiple, cystic, contrast-enhancing intraspinal lesions. A computed tomographic scan of the brain showed marked ventricular dilatation but no intraparenchymal lesions or intraventricular cysticercal lesions. This case of acute hydrocephalus was found to be caused by isolated intraspinal neurocysticercosis and was treated by ventriculoperitoneal shunt placement and surgical removal of the intraspinal lesions (which were histologically confirmed as neurocysticercosis), followed by administration of dexamethasone and albendazole. Conclusion Isolated spinal neurocysticercosis should be considered in the differential diagnosis of acute hydrocephalus when no explanation is found in the brain, particularly in geographical regions endemic for cysticercosis. PMID:24383427

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents

PubMed Central

Dobrivojević, Marina; Bohaček, Ivan; Erjavec, Igor; Gorup, Dunja; Gajović, Srećko

2013-01-01

Aim To explore the possibility of brain imaging by microcomputed tomography (microCT) using x-ray contrasting methods to visualize mouse brain ischemic lesions after middle cerebral artery occlusion (MCAO). Methods Isolated brains were immersed in ionic or nonionic radio contrast agent (RCA) for 5 days and subsequently scanned using microCT scanner. To verify whether ex-vivo microCT brain images can be used to characterize ischemic lesions, they were compared to Nissl stained serial histological sections of the same brains. To verify if brains immersed in RCA may be used afterwards for other methods, subsequent immunofluorescent labeling with anti-NeuN was performed. Results Nonionic RCA showed better gray to white matter contrast in the brain, and therefore was selected for further studies. MicroCT measurement of ischemic lesion size and cerebral edema significantly correlated with the values determined by Nissl staining (ischemic lesion size: P=0.0005; cerebral edema: P=0.0002). Brain immersion in nonionic RCA did not affect subsequent immunofluorescent analysis and NeuN immunoreactivity. Conclusion MicroCT method was proven to be suitable for delineation of the ischemic lesion from the non-infarcted tissue, and quantification of lesion volume and cerebral edema. PMID:23444240

On imputing function to structure from the behavioural effects of brain lesions.

PubMed

Young, M P; Hilgetag, C C; Scannell, J W

2000-01-29

What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.

Lesions causing freezing of gait localize to a cerebellar functional network

PubMed Central

Fasano, Alfonso; Laganiere, Simon E.; Lam, Susy; Fox, Michael D.

2016-01-01

Objective Freezing of gait is a disabling symptom in Parkinson’s disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. Methods Fourteen cases of lesion-induced freezing of gait were identified from the literature and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. Results Lesion location was heterogeneous and no single region could be considered necessary for symptom generation. However, over 90% (13/14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). Interpretation Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson’s disease patients, advancing our understanding of the brain regions involved in freezing of gait. PMID:28009063

Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

PubMed

Nukui, Megumi; Kawawaki, Hisashi; Inoue, Takeshi; Kuki, Ichiro; Okazaki, Shin; Amo, Kiyoko; Togawa, Masao; Ishikawa, Junichi; Rinka, Hiroshi; Shiomi, Masashi

2018-06-07

Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

MR imaging of adult acute infectious encephalitis.

PubMed

Bertrand, A; Leclercq, D; Martinez-Almoyna, L; Girard, N; Stahl, J-P; De-Broucker, T

2017-05-01

Imaging is a key tool for the diagnosis of acute encephalitis. Brain CT scan must be urgently performed to rule out a brain lesion with mass effect that would contraindicate lumbar puncture. Brain MRI is less accessible than CT scan, but can provide crucial information with patients presenting with acute encephalitis. We performed a literature review on PubMed on April 1, 2015 with the search terms "MRI" and "encephalitis". We first described the various brain MRI abnormalities associated with each pathogen of acute encephalitis (HSV, VZV, other viral agents targeting immunocompromised patients or travelers; tuberculosis, listeriosis, other less frequent bacterial agents). Then, we identified specific patterns of brain MRI abnomalies that may suggest a particular pathogen. Limbic encephalitis is highly suggestive of HSV; it also occurs less frequently in encephalitis due to HHV6, syphillis, Whipple's disease and HIV primary infection. Rhombencephalitis is suggestive of tuberculosis and listeriosis. Acute ischemic lesions can occur in patients presenting with severe bacterial encephalitis, tuberculosis, VZV encephalitis, syphilis, and fungal infections. Brain MRI plays a crucial role in the diagnosis of acute encephalitis. It detects brain signal changes that reinforce the clinical suspicion of encephalitis, especially when the causative agent is not identified by lumbar puncture; it can suggest a particular pathogen based on the pattern of brain abnormalities and it rules out important differential diagnosis (vascular, tumoral or inflammatory causes). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cerebral Metastases of Lung Cancer Mimicking Multiple Ischaemic Lesions - A Case Report and Review of Literature.

PubMed

Zacharzewska-Gondek, Anna; Maksymowicz, Hanna; Szymczyk, Małgorzata; Sąsiadek, Marek; Bladowska, Joanna

2017-01-01

Restricted diffusion that is found on magnetic resonance diffusion-weighted imaging (DWI) typically indicates acute ischaemic stroke. However, restricted diffusion can also occur in other diseases, like metastatic brain tumours, which we describe in this case report. A 57-year-old male, with a diagnosis of small-cell cancer of the right lung (microcellular anaplastic carcinoma), was admitted with focal neurological symptoms. Initial brain MRI revealed multiple, disseminated lesions that were hyperintense on T2-weighted images and did not enhance after contrast administration; notably, some lesions manifested restricted diffusion on DWI images. Based on these findings, disseminated ischaemic lesions were diagnosed. On follow-up MRI that was performed after 2 weeks, we observed enlargement of the lesions; there were multiple, disseminated, sharply outlined, contrast-enhancing, oval foci with persistent restriction of diffusion. We diagnosed the lesions as disseminated brain metastases due to lung cancer. To our knowledge, this is the first description of a patient with brain metastases that were characterised by restricted diffusion and no contrast enhancement. Multiple, disseminated brain lesions, that are characterised by restricted diffusion on DWI, typically indicate acute or hyperacute ischemic infarcts; however, they can also be due to hypercellular metastases, even if no contrast enhancement is observed. This latter possibility should be considered particularly in patients with cancer.

[Stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain].

PubMed

Qin, F; Huang, Z C; Cai, M Q; Xu, X F; Lu, T T; Dong, Q; Wu, A M; Lu, Z Z; Zhao, C; Guo, Y

2018-06-12

Objective: To investigate the value of stereotactic biopsy in the accurate diagnosis of lesions in the brain stem and deep brain. Methods: A total of 29 consecutive patients who underwent stereotactic biopsy of brainstem and deep brain lesions between May 2012 and January 2018 were retrospectively reviewed. The Cosman-Roberts-Wells (CRW) stereotactic frame was installed under local anesthesia. Thin-layer CT and MRI scanning were performed. Target coordinates were calculated by inputting CT-MRI data into the radionics surgical planning system. The individualized puncture path was designed according to the location of the lesions and the characteristics of the image. Target distributions were as follows: 12 cases of midbrain or pons, 2 cases of internal capsule, 3 cases of thalamus, 12 cases of basal ganglia. The biopsy samples were used for further pathological and/or genetic diagnosis. Results: Twenty-eight of the 29 cases (96.6%) were diagnosed accurately by histopathology and genomic examination following stereotactic biopsy. Pathological results were as follows: 8 cases of lymphoma, 7 cases of glioma, 4 cases of demyelination, 2 cases of germ cell tumor, 2 cases of metastatic tumor, 1 cases of cerebral sparganosis, 1 case of tuberculous granuloma, 1 case of hereditary prion disease, 1 case of glial hyperplasia, 1 case of leukemia. The accurate diagnosis of one case required a combination of histopathology and genomic examination. Undefined diagnosis was still made in 1 cases (3.45%) after biopsy. After biopsy, there were 2 cases (6.9%) with symptomatic slight hemorrhage, 1 case (3.45%) with symptomatic severe hemorrhage, and 1 cass (3.45%) with permanent neurological dysfunction. No one died because of surgery or surgical complications. Conclusions: Stereotactic biopsy is fast, safe and minimally invasive. It is an ideal strategy for accurate diagnosis of lesions in brain stem and deep brain.

[Brain oedema and acute liver failure].

PubMed

Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Lesion characteristics driving right-hemispheric language reorganization in congenital left-hemispheric brain damage.

PubMed

Lidzba, Karen; de Haan, Bianca; Wilke, Marko; Krägeloh-Mann, Ingeborg; Staudt, Martin

2017-10-01

Pre- or perinatally acquired ("congenital") left-hemispheric brain lesions can be compensated for by reorganizing language into homotopic brain regions in the right hemisphere. Language comprehension may be hemispherically dissociated from language production. We investigated the lesion characteristics driving inter-hemispheric reorganization of language comprehension and language production in 19 patients (7-32years; eight females) with congenital left-hemispheric brain lesions (periventricular lesions [n=11] and middle cerebral artery infarctions [n=8]) by fMRI. 16/17 patients demonstrated reorganized language production, while 7/19 patients had reorganized language comprehension. Lesions to the insular cortex and the temporo-parietal junction (predominantly supramarginal gyrus) were significantly more common in patients in whom both, language production and comprehension were reorganized. These areas belong to the dorsal stream of the language network, participating in the auditory-motor integration of language. Our data suggest that the integrity of this stream might be crucial for a normal left-lateralized language development. Copyright © 2017. Published by Elsevier Inc.

Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury.

PubMed

Wright, Matthew J; McArthur, David L; Alger, Jeffry R; Van Horn, Jack; Irimia, Andrei; Filippou, Maria; Glenn, Thomas C; Hovda, David A; Vespa, Paul

2013-09-01

Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as 'frontal-temporal' in nature, suggesting a possible link between acute metabolic crisis-related brain atrophy and neurocognitive impairment in this population. While focal lesions and diffuse axonal injury have a well-established role in the neuropsychological deficits observed following traumatic brain injury, no studies to date have examined the possible contribution of acute metabolic crisis-related atrophy in the neuropsychological sequelae of traumatic brain injury. In the current study we employed positron emission tomography, magnetic resonance imaging, and neuropsychological assessments to ascertain the relationship between acute metabolic crisis-related brain atrophy and neurocognitive outcome in a sample of 14 right-handed traumatic brain injury survivors. We found that acute metabolic crisis-related atrophy in the frontal and temporal lobes was associated with poorer attention, executive functioning, and psychomotor abilities at 12 months post-injury. Furthermore, participants with gross frontal and/or temporal lobe atrophy exhibited numerous clinically significant neuropsychological deficits in contrast to participants with other patterns of brain atrophy. Our findings suggest that interventions that reduce acute metabolic crisis may lead to improved functional outcomes for traumatic brain injury survivors.

Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis.

PubMed

Dwyer, Michael G; Bergsland, Niels; Ramasamy, Deepa P; Jakimovski, Dejan; Weinstock-Guttman, Bianca; Zivadinov, Robert

2018-06-01

Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker. Therefore, we investigated the rate of brain lesion loss due to atrophy (atrophied lesion volume) in MS subtypes compared to baseline lesion volume and to new and enlarging lesion volumes, and evaluated the independent predictive value of this phenomenon for clinical disability. A total of 192 patients (18 clinically isolated syndrome, 126 relapsing-remitting MS, and 48 progressive) received 3T magnetic resonance imaging at baseline and 5 years. Lesions were quantified at baseline, and new/enlarging lesion volumes were calculated over the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived cerebrospinal fluid partial volume maps. Measures were compared between disease subgroups, and correlations with disability change (Expanded Disability Status Scale [EDSS]) were evaluated. Hierarchical regression was employed to determine the unique additive value of atrophied lesion volume. Atrophied lesion volume was different between MS subtypes (P = .02), and exceeded new lesion volume accumulation in progressive MS (298.1 vs. 75.5 mm 3 ). Atrophied lesion volume was the only significant correlate of EDSS change (r = .192 relapsing, r = .317 progressive, P < .05), and explained significant additional variance when controlling for brain atrophy and new/enlarging lesion volume (R 2 .092 vs. .045, P = .003). Atrophied lesion volume is a unique and clinically relevant imaging marker in MS, with particular promise in progressive MS. Copyright © 2018 by the American Society of Neuroimaging.

Lateralization of Egocentric and Allocentric Spatial Processing after Parietal Brain Lesions

ERIC Educational Resources Information Center

Iachini, Tina; Ruggiero, Gennaro; Conson, Massimiliano; Trojano, Luigi

2009-01-01

The purpose of this paper was to verify whether left and right parietal brain lesions may selectively impair egocentric and allocentric processing of spatial information in near/far spaces. Two Right-Brain-Damaged (RBD), 2 Left-Brain-Damaged (LBD) patients (not affected by neglect or language disturbances) and eight normal controls were submitted…

Voxel-based lesion-symptom mapping of stroke lesions underlying somatosensory deficits

PubMed Central

Meyer, Sarah; Kessner, Simon S.; Cheng, Bastian; Bönstrup, Marlene; Schulz, Robert; Hummel, Friedhelm C.; De Bruyn, Nele; Peeters, Andre; Van Pesch, Vincent; Duprez, Thierry; Sunaert, Stefan; Schrooten, Maarten; Feys, Hilde; Gerloff, Christian; Thomalla, Götz; Thijs, Vincent; Verheyden, Geert

2015-01-01

The aim of this study was to investigate the relationship between stroke lesion location and the resulting somatosensory deficit. We studied exteroceptive and proprioceptive somatosensory symptoms and stroke lesions in 38 patients with first-ever acute stroke. The Erasmus modified Nottingham Sensory Assessment was used to clinically evaluate somatosensory functioning in the arm and hand within the first week after stroke onset. Additionally, more objective measures such as the perceptual threshold of touch and somatosensory evoked potentials were recorded. Non-parametric voxel-based lesion-symptom mapping was performed to investigate lesion contribution to different somatosensory deficits in the upper limb. Additionally, structural connectivity of brain areas that demonstrated the strongest association with somatosensory symptoms was determined, using probabilistic fiber tracking based on diffusion tensor imaging data from a healthy age-matched sample. Voxels with a significant association to somatosensory deficits were clustered in two core brain regions: the central parietal white matter, also referred to as the sensory component of the superior thalamic radiation, and the parietal operculum close to the insular cortex, representing the secondary somatosensory cortex. Our objective recordings confirmed findings from clinical assessments. Probabilistic tracking connected the first region to thalamus, internal capsule, brain stem, postcentral gyrus, cerebellum, and frontal pathways, while the second region demonstrated structural connections to thalamus, insular and primary somatosensory cortex. This study reveals that stroke lesions in the sensory fibers of the superior thalamocortical radiation and the parietal operculum are significantly associated with multiple exteroceptive and proprioceptive deficits in the arm and hand. PMID:26900565

Identifying Lesions on Structural Brain Images-Validation of the Method and Application to Neuropsychological Patients

ERIC Educational Resources Information Center

Stamatakis, E.A.; Tyler, L.K.

2005-01-01

The study of neuropsychological disorders has been greatly facilitated by the localization of brain lesions on MRI scans. Current popular approaches for the assessment of MRI brain scans mostly depend on the successful segmentation of the brain into grey and white matter. These methods cannot be used effectively with large lesions because lesions…

Acute organic brain syndrome: a review of 100 cases.

PubMed

Purdie, F R; Honigman, B; Rosen, P

1981-09-01

A retrospective review of 100 admissions to Denver General Hospital with a diagnosis of acute organic brain syndrome was conducted. A total of 44% of the patients were found to have a chronic organic brain syndrome with a superimposed acute insult which caused decompensation. The other 56% of patients developed acute organic brain syndromes de novo for a variety of reasons. The most common etiologic factors producing decompensation of the chronic OBS were infections (in 23%) and environmental changes (in 17%). The most common etiologic factor causing AOBS de novo was drug-related. In most cases, a toxicologic screen, lumbar puncture, and CT scan of the brain should be a part of the investigation of any patient with AOBS.

Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.

PubMed

Hadzagic-Catibusic, Feriha; Avdagic, Edin; Zubcevic, Smail; Uzicanin, Sajra

2017-02-01

Unilateral spastic cerebral palsy (US CP) is the second most common subtype of cerebral palsy. The aim of the study was to analyze neuroimaging findings in children with unilateral spastic cerebral palsy. The study was hospital based, which has included 106 patients with US CP (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified into 5 groups: Brain maldevelopment, predominant white matter injury, predominant gray matter injury, non specific findings and normal neuroimaging findings. Predominant white matter lesions where the most frequent (48/106,45.28%; term 35/preterm 13), without statistically significant difference between term and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically significant difference between term and preterm born children (x2=0.902; p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were term born. Other finding had 2/106 children, 1.89%, both of them were term born. Normal neuroimaging findings were present in14/106 patients (13.21%). Neuroimaging may help to understand morphological background of motor impairment in children with US CP. Periventricular white matter lesions were the most frequent, then gray matter lesions.

Spectrum of MRI brain lesion patterns in neuromyelitis optica spectrum disorder: a pictorial review.

PubMed

Wang, Kevin Yuqi; Chetta, Justin; Bains, Pavit; Balzer, Anthony; Lincoln, John; Uribe, Tomas; Lincoln, Christie M

2018-06-01

Neuromyelitis optica is a neurotropic autoimmune inflammatory disease of the central nervous system traditionally thought to exclusively involve the optic nerves and spinal cord. With the discovery of the disease-specific aquaporin-4 antibody and the increasing recognition of clinical and characteristic imaging patterns of brain involvement in what is now termed neuromyelitis optica spectrum disorder (NMOSD), MRI now plays a greater role in diagnosis of NMOSD based on the 2015 consensus criteria and in distinguishing it from other inflammatory disorders, particularly multiple sclerosis (MS). Several brain lesion patterns are highly suggestive of NMOSD, whereas others may serve as red flags. Specifically, long corticospinal lesions, hemispheric cerebral white matter lesions and periependymal lesions in the diencephalon, dorsal brainstem and white matter adjacent to lateral ventricles are typical of NMOSD. In contrast, juxtacortical, cortical, or lesions perpendicularly oriented to the surface of the lateral ventricle suggests MS as the diagnosis. Ultimately, a strong recognition of the spectrum of MRI brain findings in NMOSD is essential for accurate diagnosis, and particularly in differentiating from MS. This pictorial review highlights the spectrum of characteristic brain lesion patterns that may be seen in NMOSD and further delineates findings that may help distinguish it from MS.

Involvement of neuronal IL-1β in acquired brain lesions in a rat model of neonatal encephalopathy.

PubMed

Savard, Alexandre; Lavoie, Karine; Brochu, Marie-Elsa; Grbic, Djordje; Lepage, Martin; Gris, Denis; Sebire, Guillaume

2013-09-05

Infection-inflammation combined with hypoxia-ischemia (HI) is the most prevalent pathological scenario involved in perinatal brain damage leading to life-long neurological disabilities. Following lipopolysaccharide (LPS) and/or HI aggression, different patterns of inflammatory responses have been uncovered according to the brain differentiation stage. In fact, LPS pre-exposure has been reported to aggravate HI brain lesions in post-natal day 1 (P1) and P7 rat models that are respectively equivalent - in terms of brain development - to early and late human preterm newborns. However, little is known about the innate immune response in LPS plus HI-induced lesions of the full-term newborn forebrain and the associated neuropathological and neurobehavioral outcomes. An original preclinical rat model has been previously documented for the innate neuroimmune response at different post-natal ages. It was used in the present study to investigate the neuroinflammatory mechanisms that underline neurological impairments after pathogen-induced inflammation and HI in term newborns. LPS and HI exerted a synergistic detrimental effect on rat brain. Their effect led to a peculiar pattern of parasagittal cortical-subcortical infarcts mimicking those in the human full-term newborn with subsequent severe neurodevelopmental impairments. An increased IL-1β response in neocortical and basal gray neurons was demonstrated at 4 h after LPS + HI-exposure and preceded other neuroinflammatory responses such as microglial and astroglial cell activation. Neurological deficits were observed during the acute phase of injury followed by a recovery, then by a delayed onset of profound motor behavior impairment, reminiscent of the delayed clinical onset of motor system impairments observed in humans. Interleukin-1 receptor antagonist (IL-1ra) reduced the extent of brain lesions confirming the involvement of IL-1β response in their pathophysiology. In rat pups at a neurodevelopmental age

A Fast Approach to Automatic Detection of Brain Lesions

PubMed Central

Koley, Subhranil; Chakraborty, Chandan; Mainero, Caterina; Fischl, Bruce; Aganj, Iman

2017-01-01

Template matching is a popular approach to computer-aided detection of brain lesions from magnetic resonance (MR) images. The outcomes are often sufficient for localizing lesions and assisting clinicians in diagnosis. However, processing large MR volumes with three-dimensional (3D) templates is demanding in terms of computational resources, hence the importance of the reduction of computational complexity of template matching, particularly in situations in which time is crucial (e.g. emergent stroke). In view of this, we make use of 3D Gaussian templates with varying radii and propose a new method to compute the normalized cross-correlation coefficient as a similarity metric between the MR volume and the template to detect brain lesions. Contrary to the conventional fast Fourier transform (FFT) based approach, whose runtime grows as O(N logN) with the number of voxels, the proposed method computes the cross-correlation in O(N). We show through our experiments that the proposed method outperforms the FFT approach in terms of computational time, and retains comparable accuracy. PMID:29082383

Change in brain and lesion volumes after CEE therapies: the WHIMS-MRI studies.

PubMed

Coker, Laura H; Espeland, Mark A; Hogan, Patricia E; Resnick, Susan M; Bryan, R Nick; Robinson, Jennifer G; Goveas, Joseph S; Davatzikos, Christos; Kuller, Lewis H; Williamson, Jeff D; Bushnell, Cheryl D; Shumaker, Sally A

2014-02-04

To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88). Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.

Fully automatic acute ischemic lesion segmentation in DWI using convolutional neural networks.

PubMed

Chen, Liang; Bentley, Paul; Rueckert, Daniel

2017-01-01

Stroke is an acute cerebral vascular disease, which is likely to cause long-term disabilities and death. Acute ischemic lesions occur in most stroke patients. These lesions are treatable under accurate diagnosis and treatments. Although diffusion-weighted MR imaging (DWI) is sensitive to these lesions, localizing and quantifying them manually is costly and challenging for clinicians. In this paper, we propose a novel framework to automatically segment stroke lesions in DWI. Our framework consists of two convolutional neural networks (CNNs): one is an ensemble of two DeconvNets (Noh et al., 2015), which is the EDD Net; the second CNN is the multi-scale convolutional label evaluation net (MUSCLE Net), which aims to evaluate the lesions detected by the EDD Net in order to remove potential false positives. To the best of our knowledge, it is the first attempt to solve this problem and using both CNNs achieves very good results. Furthermore, we study the network architectures and key configurations in detail to ensure the best performance. It is validated on a large dataset comprising clinical acquired DW images from 741 subjects. A mean accuracy of Dice coefficient obtained is 0.67 in total. The mean Dice scores based on subjects with only small and large lesions are 0.61 and 0.83, respectively. The lesion detection rate achieved is 0.94.

Cocaine Abuse, Traumatic Brain Injury, and Preexisting Brain Lesions as Risk Factors for Bupropion-Associated Psychosis.

PubMed

Barman, Rajdip; Kumar, Sanjeev; Pagadala, Bhuvaneshwar; Detweiler, Mark B

2017-08-01

Bupropion is generally considered safe and is widely used both as a monotherapy and as an augmentation agent for the treatment of major depression. Concerns have been raised about bupropion's propensity to precipitate new psychosis and worsen existing psychotic symptoms, although the mechanism is poorly understood. Three cases are reported in which bupropion use was associated with psychosis. The aim of the study was to explore the risk factors and possible mechanisms of psychosis in each case. Case 1 describes the interaction of cocaine abuse sensitization in a patient who developed psychosis with a lower dosage of bupropion. Cases 2 and 3 discuss the role of traumatic brain injury and structural brain lesions in increasing the risk of psychosis when using bupropion. Cocaine abuse, traumatic brain injury, and preexisting brain lesions appear to be risk factors for developing psychosis in persons taking bupropion. In such cases, clinicians should carefully assess the risks and benefits and closely monitor patients for symptoms of psychosis.

Acute brain trauma

PubMed Central

Martin, GT

2016-01-01

In the 20th century, the complications of head injuries were controlled but not eliminated. The wars of the 21st century turned attention to blast, the instant of impact and the primary injury of concussion. Computer calculations have established that in the first 5 milliseconds after the impact, four independent injuries on the brain are inflicted: 1) impact and its shockwave, 2) deceleration, 3) rotation and 4) skull deformity with vibration (or resonance). The recovery, pathology and symptoms after acute brain trauma have always been something of a puzzle. The variability of these four modes of injury, along with a variable reserve of neurones, explains some of this problem. PMID:26688392

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus.

PubMed

Roldan, Paola C; Jung, Rex E; Sibbitt, Wilmer L; Qualls, Clifford R; Flores, Ranee A; Roldan, Carlos A

2018-06-13

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm 3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p < 0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p = 0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function (r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are

Association between right-to-left shunts and brain lesions in sport divers.

PubMed

Gerriets, Tibo; Tetzlaff, Kay; Hutzelmann, Alfred; Liceni, Thomas; Kopiske, Gerrit; Struck, Niklas; Reuter, Michael; Kaps, Manfred

2003-10-01

Recent studies suggest that healthy sport divers may develop clinically silent brain damage, based on the association between a finding of multiple brain lesions on MRI and the presence of right-to-left shunt, a pathway for venous gas bubbles to enter the arterial system. We performed echocontrast transcranial Doppler sonography in 42 sport divers to determine the presence of a right-to-left shunt. Cranial MRI was carried out using a 1.5 T magnet. A lesion was counted if it was hyperintense on both T2-weighted and T2-weighted fluid attenuated inversion recovery sequences. To test the hypothesis that the occurrence of postdive arterial gas emboli is related to brain lesions on MRI, we measured postdive intravascular bubbles in a subset of 15 divers 30 min after open water scuba dives. Echocontrast transcranial Doppler sonography revealed a right-to-left shunt in 16 of the divers (38%). Only one hyperintensive lesion of the central white matter was found and that was in a diver with no evidence of a right-to-left shunt. Postdive arterial gas emboli were detected in 3 out of 15 divers; they had a right-to-left shunt, but no pathologic findings on cranial magnetic resonance imaging. Our data support the theory that right-to-left shunts can serve as a pathway for venous gas bubbles into the arterial circulation. However, we could not confirm an association between brain lesions and the presence of a right-to-left shunt in sport divers.

Acute alcohol intoxication, diffuse axonal injury and intraventricular bleeding in patients with isolated blunt traumatic brain injury.

PubMed

Matsukawa, Hidetoshi; Shinoda, Masaki; Fujii, Motoharu; Takahashi, Osamu; Murakata, Atsushi; Yamamoto, Daisuke

2013-01-01

The influence of blood alcohol level (BAL) on outcome remains unclear. This study investigated the relationships between BAL, type and number of diffuse axonal injury (DAI), intraventricular bleeding (IVB) and 6-month outcome. This study reviewed 419 patients with isolated blunt traumatic brain injury. First, it compared clinical and radiological characteristics between patients with good recovery and disability. Second, it compared BAL among DAI lesions. Third, it evaluated the correlation between the BAL and severity of IVB, number of DAI and corpus callosum injury lesions. Regardless of BAL, older age, male gender, severe Glasgow Coma Scale score (<9), abnormal pupil, IVB and lesion on genu of corpus callosum were significantly related to disability. There were no significant differences between the BAL and lesions of DAI. Simple regression analysis revealed that there were no significant correlation between BAL and severity of IVB, number of DAI and corpus callosum injury lesions. Acute alcohol intoxication was not associated with type and number of DAI lesion, IVB and disability. This study suggested that a specific type of traumatic lesion, specifically lesion on genu of corpus callosum and IVB, might be more vital for outcome.

Macrostructural and Microstructural Brain Lesions Relate to Gait Pathology in Children With Cerebral Palsy.

PubMed

Meyns, Pieter; Van Gestel, Leen; Leunissen, Inge; De Cock, Paul; Sunaert, Stefan; Feys, Hilde; Duysens, Jacques; Desloovere, Kaat; Ortibus, Els

2016-10-01

Background Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP. © The Author(s) 2016.

pH imaging reveals worsened tissue acidification in diffusion kurtosis lesion than the kurtosis/diffusion lesion mismatch in an animal model of acute stroke.

PubMed

Wang, Enfeng; Wu, Yin; Cheung, Jerry S; Zhou, Iris Yuwen; Igarashi, Takahiro; Zhang, XiaoAn; Sun, Phillip Zhe

2017-10-01

Diffusion weighted imaging (DWI) has been commonly used in acute stroke examination, yet a portion of DWI lesion may be salvageable. Recently, it has been shown that diffusion kurtosis imaging (DKI) defines the most severely damaged DWI lesion that does not renormalize following early reperfusion. We postulated that the diffusion and kurtosis lesion mismatch experience heterogeneous hemodynamic and/or metabolic injury. We investigated tissue perfusion, pH, diffusion, kurtosis and relaxation from regions of the contralateral normal area, diffusion lesion, kurtosis lesion and their mismatch in an animal model of acute stroke. Our study revealed significant kurtosis and diffusion lesion volume mismatch (19.7 ± 10.7%, P < 0.01). Although there was no significant difference in perfusion and diffusion between the kurtosis lesion and kurtosis/diffusion lesion mismatch, we showed lower pH in the kurtosis lesion (pH = 6.64 ± 0.12) from that of the kurtosis/diffusion lesion mismatch (6.84 ± 0.11, P < 0.05). Moreover, pH in the kurtosis lesion and kurtosis/diffusion mismatch agreed well with literature values for regions of ischemic core and penumbra, respectively. Our work documented initial evidence that DKI may reveal the heterogeneous metabolic derangement within the commonly used DWI lesion.

Isolated, relative aproverbia without focal lesion.

PubMed

Brown, Cora; Smith-Benjamin, Sarah; Patira, Riddhi; Altschuler, Eric L

2016-06-01

We have seen a patient with a profound, isolated, and quite selective deficit in proverb interpretation-aproverbia. The patient presented to us after an anoxic brain injury with aproverbia. Interestingly, the aproverbia appeared to be premorbid to the presenting event. Furthermore, the patient had no brain lesion that has been associated or even proposed as a cause of deficit in proverb or metaphor interpretation. The patient did have acute bilateral hippocampi lesions and associated severe anterograde amnesia, but he retained good retrograde memory with which he is able to give good, logical but concrete explanations for proverbs. This case highlights the need, importance, and interest in further neuropsychologic, imaging and functional studies of proverb and interpretation in patients and normal subjects populations.

Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

PubMed

Ito, Keiichi; Asano, Yoshitaka; Ikegame, Yuka; Shinoda, Jun

2016-01-01

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage.

Induction of acute brain injury in mice by irradiation with high-LET charged particles

NASA Astrophysics Data System (ADS)

Liu, Yang; Zhang, Hong

The present study was performed to evaluate the induction of acute brain injury in mice after 235 Mev/u carbon ion irradiation. In our study, young outbred Kunming mice were divided into four treatment groups according to the penetration depth of carbon ions. Animals were irradiated with a sublethal dose of carbon ion beams prior to the Bragg curve. An experiment was performed to evaluate the acute alterations in histology, DNA double-strand breaks (DNA DSBs) as well as p53and Bax expression in the brain 96 h post-irradiation. The results demonstrated that various histopathological changes, a significant number of DNA DSBs and elevated p53 and Bax protein expression were induced in the brain following exposure to carbon ions. This was particularly true for mice irradiated with ions having a 9.1 cm-pentration depth, indicating that carbon ions can led to deleterious lesions in the brain of young animals within 96 h. Moreover, there was a remarkable increase in DNA DSBs and in the severity of histopathological changes as the penetration depths of ions increased, which may be associated with the complex track structure of heavy ions. These data reveal that carbon ions can promote serious neuropathological degeneration in the cerebral cortex of young mice. Given that damaged neurons cannot regenerate, these findings warrant further investigation of the adverse effects of the space radiation and the passage of a therapeutic heavy ion beam in the plateau region of the Bragg curve through healthy brain tissue.

Simulation of spread and control of lesions in brain.

PubMed

Thamattoor Raman, Krishna Mohan

2012-01-01

A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios.

Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis.

PubMed

van Horssen, Jack; van der Pol, Susanne; Nijland, Philip; Amor, Sandra; Perron, Hervé

2016-07-01

Attempts to identify a causative agent of Multiple Sclerosis (MS) among environmental viruses have consistently failed suggesting that development of MS is a result from gene-environment interactions. A new pathogenic player within human genes, a human endogenous retrovirus (HERV) was identified from MS cells, named MS-associated retrovirus element (MSRV) and unveiled homologous multicopy HERVs (HERV-W). As independent studies revealed biological features of HERV-W on immune-mediated inflammation and on remyelinating cells, the present study characterized the presence of HERV-W envelope protein (MSRV-Env) at the cellular level, in different MS lesion stages to extend and validate previous studies. Immunohistological analysis of HERV-W envelope cellular expression in different lesion stages from a cohort of MS brains versus controls, using well-characterized and highly specific monoclonal antibodies. HERV-W envelope protein was detected in all MS brains and quite essentially in lesions. Immunohistochemistry showed dominant expression in macrophages and microglia, coinciding with areas of active demyelination, spread over the active lesions, or limited to the rim of active microglia in chronic active lesions or in few surviving astrocytes of inactive plaques. Weak expression was seen in MS normal appearing white matter. In active plaques, few lymphoid cells and astrocytes were also stained. This HERV-W expression was not observed in control brains. HERV-W was expressed in demyelinated lesions from MS brains, which were all positive for this endogenous pathogenic protein. Pronounced HERV-W immunoreactivity in active MS lesions was intimately associated with areas of active demyelination throughout the successive stages of lesion evolution in MS brains. Based on its pathogenic potential, this HERV-W (MSRV) endogenous toxin thus appears to be a novel therapeutic target in MS. It also has a unique positioning as an early and lifelong expressed pathogenic agonist, acting

Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury.

PubMed

Isokuortti, Harri; Iverson, Grant L; Silverberg, Noah D; Kataja, Anneli; Brander, Antti; Öhman, Juha; Luoto, Teemu M

2018-01-12

OBJECTIVE The incidence of intracranial abnormalities after mild traumatic brain injury (TBI) varies widely across studies. This study describes the characteristics of intracranial abnormalities (acute/preexisting) in a large representative sample of head-injured patients who underwent CT imaging in an emergency department. METHODS CT scans were systematically analyzed/coded in the TBI Common Data Elements framework. Logistic regression modeling was used to quantify risk factors for traumatic intracranial abnormalities in patients with mild TBIs. This cohort included all patients who were treated at the emergency department of the Tampere University Hospital (between 2010 and 2012) and who had undergone head CT imaging after suffering a suspected TBI (n = 3023), including 2766 with mild TBI and a reference group with moderate to severe TBI. RESULTS The most common traumatic lesions seen on CT scans obtained in patients with mild TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an intracranial lesion compared with 5 of 6 patients (85.6%) in the group with moderate to severe TBI. The distribution of different types of acute traumatic lesions was similar among mild and moderate/severe TBI groups. Preexisting brain lesions were a more common CT finding among patients with mild TBIs than those with moderate to severe TBIs. Having a past traumatic lesion was associated with increased risk for an acute traumatic lesion but neurodegenerative and ischemic lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls, and chronic alcohol abuse were associated with higher risk of acute intracranial lesion in patients with mild TBI. CONCLUSIONS These findings underscore the heterogeneity of neuropathology associated with the mild TBI classification. Preexisting brain lesions are common in patients with mild TBI, and the incidence of preexisting lesions

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Predicting Outcome after Pediatric Traumatic Brain Injury by Early Magnetic Resonance Imaging Lesion Location and Volume

PubMed Central

Smitherman, Emily; Hernandez, Ana; Stavinoha, Peter L.; Huang, Rong; Kernie, Steven G.; Diaz-Arrastia, Ramon

2016-01-01

Abstract Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13–17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19–16.0) for developing an unfavorable outcome. PMID:25808802

Anomalous frequency-dependent ionic conductivity of lesion-laden human-brain tissue

NASA Astrophysics Data System (ADS)

Emin, David; Akhtari, Massoud; Fallah, Aria; Vinters, Harry V.; Mathern, Gary W.

2017-10-01

We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (˜1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (˜94%) samples, the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (˜0.4 mm) diffusion of solvated sodium cations before encountering intrinsic impenetrable blockages such as cell membranes, blood vessels, and cell walls. By contrast, the low-frequency ionic conductivity of some (˜6%) brain-tissue samples falls with increasing applied frequency. We attribute this unusual frequency-dependence to the electric-field induced liberation of sodium cations from traps introduced by the unusually severe pathology observed in samples from these patients. Thus, the anomalous frequency-dependence of the ionic conductivity indicates trap-producing brain lesions.

Extensive brain masses and cavitary lung lesions associated with toxoplasmosis and acquired immunodeficiency syndrome.

PubMed

Ayoade, Folusakin; Todd, John; Al-Delfi, Firas; King, John

2017-10-01

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another Metastatic Lesion in Malignant Melanoma Patients.

PubMed

Imafuku, Keisuke; Yoshino, Koji; Yamaguchi, Kei; Tsuboi, Satoshi; Ohara, Kuniaki; Hata, Hiroo

2017-01-01

Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the Food and Drug Administration as a treatment option for patients with unresectable melanoma without brain metastasis. In the literature, vemurafenib has been reported to be also effective against brain metastasis. We encountered 3 cases with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was clinically effective against metastatic lesions other than those in the brain. The brain lesions developed after the metastatic lesion had occurred. Therefore, we assume that the melanomas of the patients acquired resistance against vemurafenib. The brain metastases were treated with the cyberknife. Patients 1 and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH elevation died despite the treatment. We need to carefully follow patients on vemurafenib therapy because brain metastasis can suddenly occur even if the metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib against brain metastasis is poor in cases with LDH elevation.

MRI in acute disseminated encephalomyelitis following Semple antirabies vaccine.

PubMed

Murthy, J M

1998-07-01

I reviewed MRI findings in five patients with acute disseminated encephalomyelitis following vaccination with Semple antirabies vaccine. MRI in two patients with encephalitis features showed multiple white matter lesions in the cerebrum, cerebellar peduncles and brain stem. Two patients who had features of cord involvement showed signal alterations in the cord extending over a few segments. Asymptomatic lesions in the cerebrum were seen in two patients. In a patient with encephalomyelitis MRI 50 days later showed resolution of the lesions. The white matter lesions described were indistinguishable from those seen in acute disseminated encephalomyelitis following other infections.

Acute brain herniation from lead toxicity.

PubMed

Berkowitz, Sheldon; Tarrago, Rod

2006-12-01

A 4-year-old black boy was admitted to the hospital with vomiting, low-grade fever, and dehydration that were thought to be caused by viral gastroenteritis. He proceeded over the next 12 hours to rapidly deteriorate with brain herniation leading to brain death. The ultimate cause of death was found to be acute lead intoxication from a swallowed foreign body.

A human brain network derived from coma-causing brainstem lesions.

PubMed

Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C

2016-12-06

To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

A human brain network derived from coma-causing brainstem lesions

PubMed Central

Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.

2016-01-01

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400

Accuracy for detection of simulated lesions: comparison of fluid-attenuated inversion-recovery, proton density--weighted, and T2-weighted synthetic brain MR imaging

NASA Technical Reports Server (NTRS)

Herskovits, E. H.; Itoh, R.; Melhem, E. R.

2001-01-01

OBJECTIVE: The objective of our study was to determine the effects of MR sequence (fluid-attenuated inversion-recovery [FLAIR], proton density--weighted, and T2-weighted) and of lesion location on sensitivity and specificity of lesion detection. MATERIALS AND METHODS: We generated FLAIR, proton density-weighted, and T2-weighted brain images with 3-mm lesions using published parameters for acute multiple sclerosis plaques. Each image contained from zero to five lesions that were distributed among cortical-subcortical, periventricular, and deep white matter regions; on either side; and anterior or posterior in position. We presented images of 540 lesions, distributed among 2592 image regions, to six neuroradiologists. We constructed a contingency table for image regions with lesions and another for image regions without lesions (normal). Each table included the following: the reviewer's number (1--6); the MR sequence; the side, position, and region of the lesion; and the reviewer's response (lesion present or absent [normal]). We performed chi-square and log-linear analyses. RESULTS: The FLAIR sequence yielded the highest true-positive rates (p < 0.001) and the highest true-negative rates (p < 0.001). Regions also differed in reviewers' true-positive rates (p < 0.001) and true-negative rates (p = 0.002). The true-positive rate model generated by log-linear analysis contained an additional sequence-location interaction. The true-negative rate model generated by log-linear analysis confirmed these associations, but no higher order interactions were added. CONCLUSION: We developed software with which we can generate brain images of a wide range of pulse sequences and that allows us to specify the location, size, shape, and intrinsic characteristics of simulated lesions. We found that the use of FLAIR sequences increases detection accuracy for cortical-subcortical and periventricular lesions over that associated with proton density- and T2-weighted sequences.

Frontal assessment battery (FAB) performance following traumatic brain injury hospitalized in an acute care setting.

PubMed

Rojas, Natalia; Laguë-Beauvais, Maude; Belisle, Arielle; Lamoureux, Julie; AlSideiri, Ghusn; Marcoux, Judith; Maleki, Mohammed; Alturki, Abdulrahman Y; Anchouche, Sonia; Alquraini, Hanan; Feyz, Mitra; Guise, Elaine de

2018-01-19

The Frontal Assessment Battery (FAB) has been shown to be useful in several clinical settings. The aim of the present study was to examine the performance of patients with traumatic brain injury (TBI) on the FAB and to predict their acute outcome. The FAB was administered to 89 patients with mild (27 = uncomplicated and 39 = complicated) and moderate (n = 23) TBI during hospitalization in an acute care setting. The length of stay in days (LOS), Glasgow Outcome Scale-Revised score (GOSE) and Disability Rating Scale (DRS) score were collected. Results showed no significant differences between the three groups on the FAB score, but age and education were significantly associated with the FAB score. Parietal lesions were associated with lower total FAB score, and with the Similarities, Motor series and Conflicting instructions subscales, while frontal lesions were associated with lower performance on the Motor series and Conflicting instructions subscales. Total FAB score was significantly correlated with all outcome measures, and together the FAB total score and the Glasgow Coma Scale (GCS) score explained 30.8% of the variance in the DRS score. The FAB may be useful clinically to acutely assess frontal and parietal lobe functions at bedside in patients with TBI and, in combination with the GCS score to measure TBI severity, can enable clinicians to predict early outcome.

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed

Ng, S C; Lee, M K; Teh, A

1989-11-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome.

Identification of disappearing brain lesions with intraoperative magnetic resonance imaging prevents surgery.

PubMed

Sutherland, Christina S; Kelly, John Jp; Morrish, William; Sutherland, Garnette R

2010-10-01

Typically, neurosurgery is performed several weeks after diagnostic imaging. In the majority of cases, histopathology confirms the diagnosis of neoplasia. In a small number of cases, a different diagnosis is established or histopathology is nondiagnostic. The frequency with which these outcomes occur has not been established. To determine the frequency and outcome of disappearing brain lesions within a group of patients undergoing surgery for suspected brain tumor. Over the past decade, 982 patients were managed in the intraoperative magnetic resonance imaging unit at the University of Calgary, Calgary, Alberta, Canada. These patients have been prospectively evaluated. In 652 patients, a brain tumor was suspected. In 6 of the 652 patients, histopathology indicated a nontumor diagnosis. In 5 patients, intraoperative images, acquired after induction of anesthesia, showed complete or nearly complete resolution of the suspected tumor identified on diagnostic magnetic resonance imaging acquired 6 ± 4 (mean ± SD) weeks previously. Anesthesia was reversed, and the surgical procedure aborted. The lesions have not progressed with 6 ± 2 years of follow-up. Intraoperative magnetic resonance imaging prevented surgery on 5 patients with disappearing lesions.

Temporally consistent probabilistic detection of new multiple sclerosis lesions in brain MRI.

PubMed

Elliott, Colm; Arnold, Douglas L; Collins, D Louis; Arbel, Tal

2013-08-01

Detection of new Multiple Sclerosis (MS) lesions on magnetic resonance imaging (MRI) is important as a marker of disease activity and as a potential surrogate for relapses. We propose an approach where sequential scans are jointly segmented, to provide a temporally consistent tissue segmentation while remaining sensitive to newly appearing lesions. The method uses a two-stage classification process: 1) a Bayesian classifier provides a probabilistic brain tissue classification at each voxel of reference and follow-up scans, and 2) a random-forest based lesion-level classification provides a final identification of new lesions. Generative models are learned based on 364 scans from 95 subjects from a multi-center clinical trial. The method is evaluated on sequential brain MRI of 160 subjects from a separate multi-center clinical trial, and is compared to 1) semi-automatically generated ground truth segmentations and 2) fully manual identification of new lesions generated independently by nine expert raters on a subset of 60 subjects. For new lesions greater than 0.15 cc in size, the classifier has near perfect performance (99% sensitivity, 2% false detection rate), as compared to ground truth. The proposed method was also shown to exceed the performance of any one of the nine expert manual identifications.

[Effect of Huperzine A on neural lesion of acute organophosphate poisoning in mice].

PubMed

Liu, Li; Wang, Jian; Xie, Guangyun; Sun, Jinxiu

2013-05-01

Effects of neurophathologic changes and expression of Glu and 60 nNOS were observed in acute isocarbophos and phoxim poisoning in mice. KM male mice were randomly divided into three groups, which were control, non-treated and Huperzine A (HupA)-treated groups. The control group was given tween-80. Nontreated group was given isocarbophos (14.7 mg/kg) or phoxim (1702 mg/kg). HupA-treated group was given HupA 2h before phoxim or isocarbophos. Twenty-four hours after exposure, the whole brain was removed and adjacent coronal sections was obtained. One part of sections were stained with toluidine blue. The part of sections were used to assessed the expression of Glu and nNOS in the cortex and hippocampal of brain by immunohistochemistry. Compared to control group, non-treated group was observed nissal body nembers reduced and dyeing light. The animals of HupA protective group were observed nissal body nembers reduced, but the lesional degree was lighter obviously than non-treated group. The statistically reduced of the expression of Glu (P<0.01), the elevation of nNOS (P<0.01), after Isocarbophos intoxication were observed. Compared to non-treated group, the significant elevation of Glu (P<0.01) and reduced of nNOS (P<0.01) was observed on HupA-treated groups. Whereas for phoxim treatment, no changes were observed. HupA have protective effect against glutamatergic systems disorder caused by Isocarbophos poisoning. Administration of HupA have no effects of the neurotransmitter changes induces by acute poisoning of phoxim. It is different for the toxic effect mechanism of the two organophosphate.

Acute organic brain syndrome due to drug-induced eosinophilia.

PubMed Central

Ng, S. C.; Lee, M. K.; Teh, A.

1989-01-01

A 72 year old man developed acute organic brain syndrome associated with marked eosinophilia following self medication with a variety of drugs. Investigations revealed no other known causes of eosinophilia. Withdrawal of drugs resulted in dramatic drop in eosinophil count paralleled by clinical resolution of neurological problems. To our knowledge drug-induced eosinophilia has not previously been associated with acute organic brain syndrome. PMID:2616421

Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

PubMed

Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

2010-11-01

The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

Semisupervised learning using denoising autoencoders for brain lesion detection and segmentation.

PubMed

Alex, Varghese; Vaidhya, Kiran; Thirunavukkarasu, Subramaniam; Kesavadas, Chandrasekharan; Krishnamurthi, Ganapathy

2017-10-01

The work explores the use of denoising autoencoders (DAEs) for brain lesion detection, segmentation, and false-positive reduction. Stacked denoising autoencoders (SDAEs) were pretrained using a large number of unlabeled patient volumes and fine-tuned with patches drawn from a limited number of patients ([Formula: see text], 40, 65). The results show negligible loss in performance even when SDAE was fine-tuned using 20 labeled patients. Low grade glioma (LGG) segmentation was achieved using a transfer learning approach in which a network pretrained with high grade glioma data was fine-tuned using LGG image patches. The networks were also shown to generalize well and provide good segmentation on unseen BraTS 2013 and BraTS 2015 test data. The manuscript also includes the use of a single layer DAE, referred to as novelty detector (ND). ND was trained to accurately reconstruct nonlesion patches. The reconstruction error maps of test data were used to localize lesions. The error maps were shown to assign unique error distributions to various constituents of the glioma, enabling localization. The ND learns the nonlesion brain accurately as it was also shown to provide good segmentation performance on ischemic brain lesions in images from a different database.

Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

PubMed

Broocks, Gabriel; Flottmann, Fabian; Ernst, Marielle; Faizy, Tobias Djamsched; Minnerup, Jens; Siemonsen, Susanne; Fiehler, Jens; Kemmling, Andre

2018-04-01

Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P < 0.0001; mean ± SD difference, -0.29% ± 0.39%, not different from 0, P < 0.0001). In the study cohort, the mean ± SD uptake of water within infarct measured by volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly

Functional MRI Preprocessing in Lesioned Brains: Manual Versus Automated Region of Interest Analysis

PubMed Central

Garrison, Kathleen A.; Rogalsky, Corianne; Sheng, Tong; Liu, Brent; Damasio, Hanna; Winstein, Carolee J.; Aziz-Zadeh, Lisa S.

2015-01-01

Functional magnetic resonance imaging (fMRI) has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI) analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant’s structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions, such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant’s non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error) that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise, but may provide a more accurate estimate of brain response. In this study, commonly used automated and manual approaches to ROI analysis were directly compared by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study, involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. Significant differences were identified in task-related effect size and percent-activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design. PMID:26441816

Neuroprotective effect of ethanol in acute carbon monoxide intoxication: A retrospective study.

PubMed

Kim, Hyuk-Hoon; Choi, Sang Chun; Chae, Minjung Kathy; Min, Young-Gi

2018-01-01

In acute carbon monoxide (CO) intoxication, treatment of neurologic injury and prevention of neurological sequelae are primary concerns. Ethanol is the one of the frequent substances which is co-ingested in intentional CO poisoning. Neuroprotective effect of ethanol was highlighted and demonstrated in isolated brain injury recently. We assessed the neuroprotective effect of ethanol in acute CO intoxication using magnetic resonance imaging (MRI).We retrospectively reviewed medical records for patients who visited an emergency medical center of a university-affiliated hospital during a period of 73 months, from March 2009 to April 2015. Enrolled patients were divided into 2 groups, patients with or without abnormal brain lesion in brain MRI. Multivariate logistic regression analysis was performed to assess the factors associated with brain injury in MRI.A total of 109 patients with acute CO intoxication were evaluated of which 66 (60.55%) tested positive in brain MRI. MRI lesion-positive patients were more likely to have electrocardiogram change, elevation of serum troponin I and s100 protein level and lower serum ethanol level. Serum ethanol positivity was an independent factor for prevalence of brain injury in MRI in acute CO poisoning.This study revealed that ethanol which is co-ingested in acute CO intoxication may work the neuroprotective effect and could consequence more favorable neurological outcome in acute CO intoxication. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Brain Regions Influencing Implicit Violent Attitudes: A Lesion-Mapping Study.

PubMed

Cristofori, Irene; Zhong, Wanting; Mandoske, Valerie; Chau, Aileen; Krueger, Frank; Strenziok, Maren; Grafman, Jordan

2016-03-02

Increased aggression is common after traumatic brain injuries and may persist after cognitive recovery. Maladaptive aggression and violence are associated with dysfunction in the prefrontal and temporal cortex, but such dysfunctional behaviors are typically measured by explicit scales and history. However, it is well known that answers on explicit scales on sensitive topics--such as aggressive thoughts and behaviors--may not reveal true tendencies. Here, we investigated the neural basis of implicit attitudes toward aggression in humans using a modified version of the Implicit Association Task (IAT) with a unique sample of 112 Vietnam War veterans who suffered penetrating brain injury and 33 healthy controls who also served in combat in Vietnam but had no history of brain injury. We hypothesized that dorsolateral prefrontal cortex (dlPFC) lesions, due to the crucial role of the dlPFC in response inhibition, could influence performance on the IAT. In addition, we investigated the causal contribution of specific brain areas to implicit attitudes toward violence. We found a more positive implicit attitude toward aggression among individuals with lesions to the dlPFC and inferior posterior temporal cortex (ipTC). Furthermore, executive functions were critically involved in regulating implicit attitudes toward violence and aggression. Our findings complement existing evidence on the neural basis of explicit aggression centered on the ventromedial prefrontal cortex. These findings highlight that dlPFC and ipTC play a causal role in modulating implicit attitudes about violence and are crucially involved in the pathogenesis of aggressive behavior. Maladaptive aggression and violence can lead to interpersonal conflict and criminal behavior. Surprisingly little is known about implicit attitudes toward violence and aggression. Here, we used a range of techniques, including voxel-based lesion-symptom mapping, to examine the causal role of brain structures underpinning implicit

Aspirin resistance in the acute stages of acute ischemic stroke is associated with the development of new ischemic lesions.

PubMed

Kim, Joon-Tae; Heo, Suk-Hee; Lee, Ji Sung; Choi, Min-Ji; Choi, Kang-Ho; Nam, Tai-Seung; Lee, Seung-Han; Park, Man-Seok; Kim, Byeong C; Kim, Myeong-Kyu; Cho, Ki-Hyun

2015-01-01

Aspirin is a primary antiplatelet agent for the secondary prevention of ischemic stroke. However, if aspirin fails to inhibit platelet function, as is expected in acute ischemic stroke (AIS), it may increase the rate of early clinical events. Therefore, we sought to determine whether aspirin resistance in the acute stage was associated with early radiological events, including new ischemic lesions (NILs). This study was a single-center, prospective, observational study conducted between April 2012 and May 2013. Aspirin 300 mg was initially administered followed by maintenance doses of 100 mg daily. The acute aspirin reaction unit (aARU) was consistently measured after 3 hours of aspirin loading. An aARU value ≥550 IU was defined as biological aspirin resistance (BAR). NILs on follow-up diffusion-weighted imaging (DWI) were defined as lesions separate from index lesions, which were not detected on the initial DWI. A total of 367 patients were analyzed in this study. BAR in aARU was detected in 60 patients (16.3%). On follow-up DWI, 81 patients (22.1%) had NILs, which were frequently in the same territory as the index lesions (79%), pial infarcts (61.7%), and located within the cortex (59.3%). BAR was independently associated with NILs on follow-up DWI (adjusted OR 2.00, 95% CIs 1.01-3.96; p = 0.047). In conclusion, BAR in aARU could be associated with NILs on follow-up DWI in AIS. Therefore, a further prospective study with a longer follow-up period is necessary to evaluate the clinical implications of aARU in AIS.

Automatic segmentation and volumetry of multiple sclerosis brain lesions from MR images

PubMed Central

Jain, Saurabh; Sima, Diana M.; Ribbens, Annemie; Cambron, Melissa; Maertens, Anke; Van Hecke, Wim; De Mey, Johan; Barkhof, Frederik; Steenwijk, Martijn D.; Daams, Marita; Maes, Frederik; Van Huffel, Sabine; Vrenken, Hugo; Smeets, Dirk

2015-01-01

The location and extent of white matter lesions on magnetic resonance imaging (MRI) are important criteria for diagnosis, follow-up and prognosis of multiple sclerosis (MS). Clinical trials have shown that quantitative values, such as lesion volumes, are meaningful in MS prognosis. Manual lesion delineation for the segmentation of lesions is, however, time-consuming and suffers from observer variability. In this paper, we propose MSmetrix, an accurate and reliable automatic method for lesion segmentation based on MRI, independent of scanner or acquisition protocol and without requiring any training data. In MSmetrix, 3D T1-weighted and FLAIR MR images are used in a probabilistic model to detect white matter (WM) lesions as an outlier to normal brain while segmenting the brain tissue into grey matter, WM and cerebrospinal fluid. The actual lesion segmentation is performed based on prior knowledge about the location (within WM) and the appearance (hyperintense on FLAIR) of lesions. The accuracy of MSmetrix is evaluated by comparing its output with expert reference segmentations of 20 MRI datasets of MS patients. Spatial overlap (Dice) between the MSmetrix and the expert lesion segmentation is 0.67 ± 0.11. The intraclass correlation coefficient (ICC) equals 0.8 indicating a good volumetric agreement between the MSmetrix and expert labelling. The reproducibility of MSmetrix' lesion volumes is evaluated based on 10 MS patients, scanned twice with a short interval on three different scanners. The agreement between the first and the second scan on each scanner is evaluated through the spatial overlap and absolute lesion volume difference between them. The spatial overlap was 0.69 ± 0.14 and absolute total lesion volume difference between the two scans was 0.54 ± 0.58 ml. Finally, the accuracy and reproducibility of MSmetrix compare favourably with other publicly available MS lesion segmentation algorithms, applied on the same data using default parameter

Verb Generation in Children and Adolescents with Acute Cerebellar Lesions

ERIC Educational Resources Information Center

Frank, B.; Schoch, B.; Hein-Kropp, C.; Dimitrova, A.; Hovel, M.; Ziegler, W.; Gizewski, E. R.; Timmann, D.

2007-01-01

The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None…

Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

PubMed

Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

2017-04-01

Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Diffusion-weighted imaging score of the brain stem: A predictor of outcome in acute basilar artery occlusion treated with the Solitaire FR device.

PubMed

Mourand, I; Machi, P; Nogué, E; Arquizan, C; Costalat, V; Picot, M-C; Bonafé, A; Milhaud, D

2014-06-01

The prognosis for ischemic stroke due to acute basilar artery occlusion is very poor: Early recanalization remains the main factor that can improve outcomes. The baseline extent of brain stem ischemic damage can also influence outcomes. We evaluated the validity of an easy-to-use DWI score to predict clinical outcome in patients with acute basilar artery occlusion treated by mechanical thrombectomy. We analyzed the baseline clinical and DWI parameters of 31 patients with acute basilar artery occlusion, treated within 24 hours of symptom onset by using a Solitaire FR device. The DWI score of the brain stem was assessed with a 12-point semiquantitative score that separately considered each side of the medulla, pons, and midbrain. Clinical outcome was assessed at 180 days by using the mRS. According to receiver operating characteristic analyses, the cutoff score determined the optimal positive predictive value for outcome. The Spearman rank correlation coefficient assessed the correlation between the DWI brain stem score and baseline characteristics. Successful recanalization (Thrombolysis in Cerebral Infarction 3-2b) was achieved in 23 patients (74%). A favorable outcome (mRS ≤ 2) was observed in 11 patients (35%). An optimal DWI brain stem score of <3 predicted a favorable outcome. The probability of a very poor outcome (mRS ≥ 5) if the DWI brain stem score was ≥5 reached 80% (positive predictive value) and 100% if this score was ≥6. Interobserver reliability of the DWI brain stem score was excellent, with an intraclass correlation coefficient of 0.97 (95% CI, 0.96-0.99). The DWI brain stem score was significantly associated with baseline tetraplegia (P = .001) and coma (P = .005). In patients with acute basilar artery occlusion treated by mechanical thrombectomy, the baseline DWI brain lesion score seems to predict clinical outcome. © 2014 by American Journal of Neuroradiology.

Bilateral pallidal hemorrhage in toxoplasmosis update of acute symmetric lesions of deep nuclei.

PubMed

Finelli, Pasquale F; Wrubel, Gregory L

2015-08-01

As acute symmetric lesions of deep gray nuclei are often associated with an impaired level of consciousness and neuroimaging by itself cannot distinguish between etiologies, diagnosis may be problematic. Appreciation of the cause of the various neuroimaging patterns in conjunction with the history, examination and laboratory investigations allows for accurate diagnosis in the vast majority of cases. Given the metabolic vulnerability of deep gray nuclei, other than bi-thalamic infarction, it follows that toxic-metabolic and hypoxic-ischemic events account for the majority of cases. Nevertheless, the differential diagnosis is broad and diverse. We here describe two cases of bilateral pallidal hemorrhage in AIDS-associated toxoplasmosis, and review conditions recently described with acute symmetric deep gray nuclei lesions on neuroimaging. © The Author(s) 2015.

Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury

PubMed Central

Pardini, M.; Krueger, F.; Hodgkinson, C.; Raymont, V.; Ferrier, C.; Goldman, D.; Strenziok, M.; Guida, S.

2011-01-01

Objective: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI). Methods: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a). Results: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group. Conclusions: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI. PMID:21422455

Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment.

PubMed

Ishibashi, Masato; Kimura, Noriyuki; Aso, Yasuhiro; Matsubara, Etsuro

2018-05-01

To evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment. Seventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and 99m Tc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8. Of all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions. In subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Role of Interleukin-10 in Acute Brain Injuries

PubMed Central

Garcia, Joshua M.; Stillings, Stephanie A.; Leclerc, Jenna L.; Phillips, Harrison; Edwards, Nancy J.; Robicsek, Steven A.; Hoh, Brian L.; Blackburn, Spiros; Doré, Sylvain

2017-01-01

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation. PMID:28659854

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

PubMed

Swirsky-Sacchetti, T; Mitchell, D R; Seward, J; Gonzales, C; Lublin, F; Knobler, R; Field, H L

1992-07-01

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

[Experimental study of acute brain swelling under acute intracranial hypertension (author's transl)].

PubMed

Shigemori, M; Watanabe, M; Kuramoto, S

1976-12-01

There are many problems about the cause, pathophysiology and treatment of acute brain swelling under intracranial hypertension frequently encountered in the neurosurgical clinics. Generally, rapid increase of the cerebral vasoparesis caused by unknown etiology is thought to be the main cause of acute brain swelling under intracranial hypertension. Moreover, disturbance of the cerebral venous circulatory system is discussed recently by many authors. But, research from the point of systemic respiration and hemodynamics is necessary for resolving these problems. This experiment was designed to study the effects of respiration and hemodynamics on the cerebral vasoparesis. Using 22 adult dogs, acute intracranial hypertension was produced by epidural balloon inflation sustained at the level of 300 - 400 mmH2O. Simultaneously with measurement of intracranial pressure at the epidural space, superior sagittal sinus pressure, respirogram, systemic blood pressure (femoral artery), central venous pressure, common carotid blood flow, EKG and bipolar lead EEG were monitored continuously. The experimental group was divided by the respiratory loading into 5 groups as follows: control (6 cases), 10% CO2 hypercapnia (4 cases), 10% O2 hypoxia (4 cases), stenosis of airway (5 cases), 100% O2-controled respiration (3 cases). 1) Cerebral vasoparesis under acute intracranial hypertension took place earlier and showed more rapid progression in groups of stenosis of airway, hypercapnia and hypoxia than control group of spontaneous respiration in room air. No occurrence of cerebral vasoparesis was found out in a group of 100% O2 controlled respiration. It is proved that increased airway resistance or asphyxia, hypercapnia and hypoxia have strictly reference to the occurrence and progression of cerebral vasoparesis and for the prevention of cerebral vasoparesis, correct 100% O2 cont rolled respiration is effective. 2) From the hemodynamic change, the progression of rapid increase of cerebral

Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients.

PubMed

Pereira, Celestino Esteves; Lynch, Jose Carlos

2017-01-01

The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D'Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients' records, surgical descriptions, imaging studies, and histopathological material were reviewed. Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients.

Intractable epilepsy and structural lesions of the brain: mapping, resection strategies, and seizure outcome.

PubMed

Awad, I A; Rosenfeld, J; Ahl, J; Hahn, J F; Lüders, H

1991-01-01

Forty-seven patients with structural brain lesions on neuroimaging studies and partial epilepsy intractable to medical therapy were studied. Prolonged noninvasive interictal and ictal EEG recording was performed, followed by more focused mapping using chronically implanted subdural electrode plates. Surgical procedures included lesion biopsy, maximal lesion excision, and/or resection of zones of epileptogenesis depending on accessibility and involvement of speech or other functional areas. The epileptogenic zone involved exclusively the region adjacent to the structural lesion in 11 patients. It extended beyond the lesion in 18 patients. Eighteen other patients had remote noncontiguous zones of epileptogenesis. Postoperative control of epilepsy was accomplished in 17 of 18 patients (94%) with complete lesion excision regardless of extent of seizure focus excision. Postoperative control of epilepsy was accomplished in 5 of 6 patients (83%) with incomplete lesion excision but complete seizure focus excision and in 12 of 23 patients (52%) with incomplete lesion excision and incomplete focus excision. The extent of lesion resection was strongly associated with surgical outcome either in itself (p less than 0.003), or in combination with focus excision. Focus resection was marginally associated with surgical outcome as a dichotomous variable (p = 0.048) and showed a trend toward significance (p = 0.07) only as a three-level outcome variable. We conclude that structural lesions are associated with zones of epileptogenesis in neighboring and remote areas of the brain. Maximum resection of the lesion offers the best chance at controlling intractable epilepsy; however, seizure control is achieved in many patients by carefully planned subtotal resection of lesions or foci.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancing Brain Lesions during Acute Optic Neuritis and/or Longitudinally Extensive Transverse Myelitis May Portend a Higher Relapse Rate in Neuromyelitis Optica Spectrum Disorders.

PubMed

Orman, G; Wang, K Y; Pekcevik, Y; Thompson, C B; Mealy, M; Levy, M; Izbudak, I

2017-05-01

Neuromyelitis optica spectrum disorders are inflammatory demyelinating disorders with optic neuritis and/or longitudinally extensive transverse myelitis episodes. We now know that neuromyelitis optica spectrum disorders are associated with antibodies to aquaporin-4, which are highly concentrated on astrocytic end-feet at the blood-brain barrier. Immune-mediated disruption of the blood-brain barrier may manifest as contrast enhancement on brain MR imaging. We aimed to delineate the extent and frequency of contrast enhancement on brain MR imaging within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and to correlate contrast enhancement with outcome measures. Brain MRIs of patients with neuromyelitis optica spectrum disorders were evaluated for patterns of contrast enhancement (periependymal, cloudlike, leptomeningeal, and so forth). The Fisher exact test was used to evaluate differences between the proportion of contrast enhancement in patients who were seropositive and seronegative for aquaporin-4 antibodies. The Mann-Whitney test was used to compare the annualized relapse rate and disease duration between patients with and without contrast enhancement and with and without seropositivity. Brain MRIs of 77 patients were evaluated; 59 patients (10 males, 49 females) were scanned within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and were included in the analysis. Forty-eight patients were seropositive, 9 were seronegative, and 2 were not tested for aquaporin-4 antibodies. Having brain contrast enhancement of any type during an acute attack was significantly associated with higher annualized relapse rates ( P = .03) and marginally associated with shorter disease duration ( P = .05). Having periependymal contrast enhancement was significantly associated with higher annualized relapse rates ( P = .03). Brain MRIs of patients with neuromyelitis optica spectrum disorders with contrast

SU-G-BRC-14: Multi-Lesion, Multi-Rx, Brain Radiosurgery with Novel Single Isocenter Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Honig, N; Alani, S; Schlocker, A

Purpose: There is a strong trend to treat multiple brain metastases with radiosurgery rather than whole brain irradiation. This feasibility study investigates a novel planning technique for radio-surgical treatment of multiple brain lesions with differing dose prescriptions, a single isocenter, and dynamic conformal arcs. The novel technique will be compared to the well-established single-isocenter volumetric modulated arc therapy (VMAT) technique commonly used for treating brain lesions. Methods: Six patients with metastatic brain lesions were selected for a prospective treatment planning study to evaluate Interdigitating MLC Dynamic Conformal Arc (IMDCA) technique. Arcs were planned for simultaneous irradiation to maximize beam deliverymore » efficiency. To accommodate varying PTV dose prescriptions, selected arcs were re-irradiated in reverse. Beam weights were adjusted until all prescription constraints were met. The number of lesions ranged between 2 to 4 (mode = 3). For comparison, SRS VMAT plans were generated utilizing an established single-isocenter, 3 arc planning template. All plans were compared by means of Paddick conformity index (PCI), RTOG Conformity Index (RCI), gradient index (GI), and the normal brain volume receiving 10% (V10) of the highest prescription dose. The monitor units and delivery time were tabulated for each plan. Results: IMDCA achieved conformal plans (PCI = 0.72±0.03, RCI = 1.33±0.03) with steep dose fall-off (GI = 3.79±0.03) on average for all of the plans evaluated. The VMAT plans had slightly better conformity (PCI = 0.85 ± 0.03, RCI = 1.13 ± 0.03) than IMDCA, but overall worse GI (4.29 ± 0.06). IMDCA plans had lower V10% values, required 50% fewer MUs, and had 34% shorter beam delivery time on average compared to VMAT plans. Conclusion: IMDCA plans with varying dose prescriptions for multiple lesions, had comparable dosimetric coverage as VMAT plans, but were obtained with significantly lower integral dose, fewer

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Psychological problems, self-esteem and body dissatisfaction in a sample of adolescents with brain lesions: A comparison with a control group.

PubMed

Pastore, Valentina; Colombo, Katia; Maestroni, Deborah; Galbiati, Susanna; Villa, Federica; Recla, Monica; Locatelli, Federica; Strazzer, Sandra

2015-01-01

This study aims to describe psychological problems, self-esteem difficulties and body dissatisfaction in a sample of adolescents with acquired brain lesions and to compare them with an age- and gender-matched control group. In an experimental design, the psychological profile of 26 adolescents with brain lesions of traumatic or vascular aetiology, aged 12-18 years, was compared with that of 18 typically-developing subjects. Moreover, within the clinical group, patients with TBI were compared with patients with vascular lesions. The psychological and adaptive profile of the adolescents was assessed by a specific protocol, including CBCL, VABS, RSES, EDI-2 and BES. Adolescents with brain lesions showed more marked psychological problems than their healthy peers; they also presented with a greater impairment of adaptive skills and a lower self-esteem. No significant differences were found between patients with traumatic lesions and patients with vascular lesions. Adolescents with acquired brain lesions were at higher risk to develop psychological and behavioural difficulties. Furthermore, in the clinical sample, some variables such as the long hospitalization and isolation from family and peers were associated to a greater psychological burden than the aetiology of the brain damage.

Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction.

PubMed

Dharmasaroja, Pornpatr A

2016-02-01

Evidence of the appropriate amount of fluid intake during the first few days after acute stroke was scarce. Concerns were raised in patients with acute malignant middle cerebral infarction, who tended to have malignant brain edema later. The purpose of the study was to evaluate the effect of fluid intake on the occurrence of malignant brain edema in patients with acute middle cerebral artery infarction. Patients with acute middle cerebral artery infarction who had National Institute of Health Stroke Scale (NIHSS) score of at least 15 were included. Baseline characteristics and amount of fluid intake during the first few days were compared in patients with and without malignant brain edema. One hundred ninety-three patients were studied. Mean NIHSS score was 20. Malignant brain edema occurred in 69 patients (36%). Higher amount of fluid intake (>1650 ml or >28 ml/kg/day or >93% of daily maintenance fluid) showed a significant association with malignant brain edema (OR = 13.86, 95% CI 5.11-37.60, p value <0.001). Decompressive surgery was performed in 35 patients (18%). With mean follow-up of 12 months, 49 patients (49/184, 27%) had favorable outcomes (modified Rankin scale (mRS) 0-2) at final follow-up. Seventy-nine patients (79/184, 43%) died. In the subgroup of patients with malignant brain edema, 39 patients (39/65, 60%) died and only 11% (7/65 patients) had favorable outcome. High amount of fluid intake in the first few days of acute middle cerebral infarction was related to the occurrence of malignant brain edema.

Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

PubMed

Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

2016-05-01

Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

A Novel Imaging Technique (X-Map) to Identify Acute Ischemic Lesions Using Noncontrast Dual-Energy Computed Tomography.

PubMed

Noguchi, Kyo; Itoh, Toshihide; Naruto, Norihito; Takashima, Shutaro; Tanaka, Kortaro; Kuroda, Satoshi

2017-01-01

We evaluated whether X-map, a novel imaging technique, can visualize ischemic lesions within 20 hours after the onset in patients with acute ischemic stroke, using noncontrast dual-energy computed tomography (DECT). Six patients with acute ischemic stroke were included in this study. Noncontrast head DECT scans were acquired with 2 X-ray tubes operated at 80 kV and Sn150 kV between 32 minutes and 20 hours after the onset. Using these DECT scans, the X-map was reconstructed based on 3-material decomposition and compared with a simulated standard (120 kV) computed tomography (CT) and diffusion-weighted imaging (DWI). The X-map showed more sensitivity to identify the lesions as an area of lower attenuation value than a simulated standard CT in all 6 patients. The lesions on the X-map correlated well with those on DWI. In 3 of 6 patients, the X-map detected a transient decrease in the attenuation value in the peri-infarct area within 1 day after the onset. The X-map is a powerful tool to supplement a simulated standard CT and characterize acute ischemic lesions. However, the X-map cannot replace a simulated standard CT to diagnose acute cerebral infarction. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.

PubMed

Redjal, Navid; Agarwalla, Pankaj K; Dietrich, Jorg; Dinevski, Nikolaj; Stemmer-Rachamimov, Anat; Nahed, Brian V; Loeffler, Jay S

2015-08-01

We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients

PubMed Central

Pereira, Celestino Esteves; Lynch, Jose Carlos

2017-01-01

Background: The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Methods: Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D’Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients’ records, surgical descriptions, imaging studies, and histopathological material were reviewed. Results: Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. Conclusions: We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients. PMID:28303207

Microglial activation in white matter lesions and nonlesional white matter of ageing brains.

PubMed

Simpson, J E; Ince, P G; Higham, C E; Gelsthorpe, C H; Fernando, M S; Matthews, F; Forster, G; O'Brien, J T; Barber, R; Kalaria, R N; Brayne, C; Shaw, P J; Stoeber, K; Williams, G H; Lewis, C E; Wharton, S B

2007-12-01

White matter lesions (WML), a common feature in brain ageing, are classified as periventricular (PVL) or deep subcortical (DSCL), depending on their anatomical location. Microglial activation is implicated in a number of neurodegenerative diseases, but the microglial response in WML is poorly characterized and its role in pathogenesis unknown. We have characterized the microglial response in WML and control white matter using immunohistochemistry to markers of microglial activation and of proliferation. WML of brains from an unbiased population-based autopsy cohort (Medical Research Council's Cognitive Function and Ageing Study) were identified by post mortem magnetic resonance imaging and sampled for histology. PVL contain significantly more activated microglia, expressing major histocompatibility complex (MHC) class II and the costimulatory molecules B7-2 and CD40, than either control white matter (WM) or DSCL. Furthermore, we show that significantly more microglia express the replication licensing protein minichromosome maintenance protein 2 within PVL, suggesting this is a more proliferation-permissive environment than DSCL. Although microglial activation occurs in both PVL and DSCL, our findings suggest a difference in pathogenesis between these lesion-types: the ramified, activated microglia associated with PVL may reflect immune activation resulting from disruption of the blood brain barrier, while the microglia within DSCL may reflect an innate, amoeboid phagocytic phenotype. We also show that microglia in control WM from lesional cases express significantly more MHC II than control WM from nonlesional ageing brain, suggesting that WML occur in a 'field-effect' of abnormal WM.

Use of prism adaptation in children with unilateral brain lesion: Is it feasible?

PubMed

Riquelme, Inmaculada; Henne, Camille; Flament, Benoit; Legrain, Valéry; Bleyenheuft, Yannick; Hatem, Samar M

2015-01-01

Unilateral visuospatial deficits have been observed in children with brain damage. While the effectiveness of prism adaptation for treating unilateral neglect in adult stroke patients has been demonstrated previously, the usefulness of prism adaptation in a pediatric population is still unknown. The present study aims at evaluating the feasibility of prism adaptation in children with unilateral brain lesion and comparing the validity of a game procedure designed for child-friendly paediatric intervention, with the ecological task used for prism adaptation in adult patients. Twenty-one children with unilateral brain lesion randomly were assigned to a prism group wearing prismatic glasses, or a control group wearing neutral glasses during a bimanual task intervention. All children performed two different bimanual tasks on randomly assigned consecutive days: ecological tasks or game tasks. The efficacy of prism adaptation was measured by assessing its after-effects with visual open loop pointing (visuoproprioceptive test) and subjective straight-ahead pointing (proprioceptive test). Game tasks and ecological tasks produced similar after-effects. Prismatic glasses elicited a significant shift of visuospatial coordinates which was not observed in the control group. Prism adaptation performed with game tasks seems an effective procedure to obtain after-effects in children with unilateral brain lesion. The usefulness of repetitive prism adaptation sessions as a therapeutic intervention in children with visuospatial deficits and/or neglect, should be investigated in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

PubMed

Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

2016-09-01

In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

Investigation of human multiple sclerosis lesions using high resolution spectrally unmixed CARS microscopy

NASA Astrophysics Data System (ADS)

Poon, Kelvin W.; Brideau, Craig; Teo, Wulin; Schenk, Geert J.; Klaver, Roel; Klauser, Antoine M.; Kawasoe, Jean H.; Geurts, Jeroen J. G.; Stys, Peter K.

2013-03-01

The pathology of multiple sclerosis (MS) involves both the gray and white matter regions of the brain and spinal cord. It is characterized by various combinations of demyelination, inflammatory infiltration, axonal degeneration, and later gliosis in chronic lesions. While acute and chronic white matter plaques are well characterized and easily identified, evidence indicates that the CNS of MS patients may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM) and in diffusely abnormal white matter (DAWM) where histochemical stains and advanced magnetic resonance imaging indicate altered tissue composition. Thus, the prototypical acute inflammatory lesion may merely represent the most obvious manifestation of a chronic widespread involvement of the CNS, which is difficult to examine reliably. The current study deals with the microstructure and biochemistry of demyelination, remyelination and axonal loss in various regions of post-mortem human MS brain, including NAWM, areas of remyelination and more typical acute and chronic lesions. The myelin sheath, neuroglia and perivascular spaces were investigated using a novel Coherent Anti-Stokes Raman Scattering (CARS) microscope with simultaneous Two-Photon Excited Fluorescence (TPEF) imaging. The active CH stretching region between 2800 and 3000 cm-1 was probed to provide chemically specific, high resolution, label-free imaging pertaining to the progression of the disease. CARS data were correlated with TPEF and conventional histochemical and immunohistochemical stains. Our novel CARS microscopy system provides detailed morphological and biochemical information regarding CNS pathology in MS and that may be applicable to a broad range of other human brain and spinal cord disorders.

Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

PubMed

Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

2018-02-15

Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

PubMed

Di Filippo, M; Anderson, V M; Altmann, D R; Swanton, J K; Plant, G T; Thompson, A J; Miller, D H

2010-02-01

Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

The role of autophagy in acute brain injury: A state of flux?

PubMed

Wolf, Michael S; Bayır, Hülya; Kochanek, Patrick M; Clark, Robert S B

2018-04-26

It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

PubMed

Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

2017-03-15

Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination. Copyright © 2016 Elsevier B.V. All rights reserved.

Demyelinating and ischemic brain diseases: detection algorithm through regular magnetic resonance images

NASA Astrophysics Data System (ADS)

Castillo, D.; Samaniego, René; Jiménez, Y.; Cuenca, L.; Vivanco, O.; Rodríguez-Álvarez, M. J.

2017-09-01

This work presents the advance to development of an algorithm for automatic detection of demyelinating lesions and cerebral ischemia through magnetic resonance images, which have contributed in paramount importance in the diagnosis of brain diseases. The sequences of images to be used are T1, T2, and FLAIR. Brain demyelination lesions occur due to damage of the myelin layer of nerve fibers; and therefore this deterioration is the cause of serious pathologies such as multiple sclerosis (MS), leukodystrophy, disseminated acute encephalomyelitis. Cerebral or cerebrovascular ischemia is the interruption of the blood supply to the brain, thus interrupting; the flow of oxygen and nutrients needed to maintain the functioning of brain cells. The algorithm allows the differentiation between these lesions.

Solitary tuberculous brain lesions: 24 new cases and a review of the literature.

PubMed

Psimaras, D; Bonnet, C; Heinzmann, A; Cárdenas, G; Hernández José Luis, S; Tungaria, A; Behari, S; Lacrois, D; Mokhtari, K; Karantoni, E; Sokrab Tag, E; Idris Mohamed, N; Sönmez, G; Caumes, E; Roze, E

2014-01-01

A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a glioma, metastasis or other infectious disease, especially from a pyogenic brain abscess. We analyzed the clinical characteristics, diagnostic procedures and outcomes of 24 patients with STBL diagnosed in three centers from France, India and Mexico. We also reviewed 92 STBL cases previously reported in the literature. General symptoms were found in 54% of our patients, including enlarged lymph nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were hypointense on T1-weighted sequences, while T2-weighted sequences showed both a peripheral hypersignal and a central hyposignal. The diagnosis was documented microbiologically or supported histologically in 71% of cases. Clinical outcome was good in 83% of cases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy MRI Measurements in Alzheimer’s Disease

PubMed Central

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S. Ali; Toledo, Jon B.; Erus, Guray; Xie, Sharon X.; Trojanowski, John Q.; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer’s disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly. PMID:26402108

Syringe Port: A Convenient, Safe, and Cost-Effective Tubular Retractor for Transportal Removal of Deep-Seated Lesions of the Brain.

PubMed

Singh, Harnarayan; Patir, Rana; Vaishya, Sandeep; Miglani, Rahul; Kaur, Amandeep

2018-06-01

Minimally invasive transportal resection of deep intracranial lesions has become a widely accepted surgical technique. Many disposable, mountable port systems are available in the market for this purpose, like the ViewSite Brain Access System. The objective of this study was to find a cost-effective substitute for these systems. Deep-seated brain lesions were treated with a port system made from disposable syringes. The syringe port could be inserted through minicraniotomies placed and planned with navigation. All deep-seated lesions like ventricular tumours, colloid cysts, deep-seated gliomas, and basal ganglia hemorrhages were treated with this syringe port system and evaluated for safety, operative site hematomas, and blood loss. 62 patients were operated on during the study period from January 2015 to July 2017, using this innovative syringe port system for deep-seated lesions of the brain. No operative site hematoma or contusions were seen along the port entry site and tract. Syringe port is a cost-effective and safe alternative to the costly disposable brain port systems, especially for neurosurgical setups in developing countries for minimally invasive transportal resection of deep brain lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

Processing verbal morphology in patients with congenital left-hemispheric brain lesions.

PubMed

Knecht, Marion; Lidzba, Karen

2016-01-01

The goal of this study was to test whether children, teenagers and adults with congenital left-hemispheric brain lesions master the regularities of German verbal inflectional morphology. Thirteen patients and 35 controls without brain damage participated in three experiments. A grammaticality judgment task, a participle inflection task and a nonce-verb inflection task revealed significant differences between patients and controls. In addition, a main effect of verb type could be observed as patients and controls made more mistakes with irregular than with regular verbs. The findings indicate that the congenitally damaged brain not only has difficulties with complex syntactic structures during language development, as reported by earlier studies, but also has persistent deficits on the morphological level. These observations suggest that the plasticity of the developing brain cannot fully compensate for congenital brain damage which affects regions associated with language functions. Copyright © 2016 Elsevier Inc. All rights reserved.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study.

PubMed

Windham, B Gwen; Deere, Bradley; Griswold, Michael E; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

2015-07-07

Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. National Heart, Lung, and Blood Institute.

Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate.

PubMed

González-Cortés, Carolina; Salinas-Lara, Citlaltepetl; Gómez-López, Marcos Artemio; Tena-Suck, Martha Lilia; Pérez-De La Cruz, Verónica; Rembao-Bojórquez, Daniel; Pedraza-Chaverrí, José; Gómez-Ruiz, Celedonio; Galván-Arzate, Sonia; Ali, Syed F; Santamaría, Abel

2008-01-01

It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO(-)) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain [V. Pérez-De La Cruz, C. González-Cortés, S. Galván-Arzate, O.N. Medina-Campos, F. Pérez-Severiano, S.F. Ali, J. Pedraza-Chaverrí, A. Santamaría, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.]. The aim of this work was to investigate whether ONOO(-) can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO(-) decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/microl) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP, IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO(-) is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage.

A new look on brain mechanisms of acute illness anorexia.

PubMed

Asarian, Lori; Langhans, Wolfgang

2010-07-14

Bacterial lipopolysaccharide (LPS) and other microbial substances trigger the organism's acute phase response and cause acute illness anorexia. Pro-inflammatory cytokines are major endogenous mediators of acute illness anorexia, but how LPS or cytokines stimulate the brain to inhibit eating is not fully resolved. One emerging mechanism involves the activation of the enzyme cyclooxygenase-2 (COX-2) in blood-brain barrier endothelial cells and the subsequent release of prostaglandin E2 (PGE2). Serotonin neurons in the midbrain raphe are targets of PGE2, and serotonergic projections from the midbrain raphe to the hypothalamus appear to be crucial for LPS anorexia. That is, raphe projections activate (1) the corticotrophin-releasing hormone neurons in the paraventricular nucleus which then elicit the stress response and (2) the pro-opiomelanocortin neurons in the arcuate nucleus which then release alphaMSH and elicit anorexia. Here we review available data to support a role for this brain mechanism in acute illness anorexia by center staging PGE2 signaling pathways that converge on central neural circuits that control normal eating. In addition, we review interactions between gonadal hormones and immune function that lead to sex differences in acute illness anorexia. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009. 2010 Elsevier Inc. All rights reserved.

Risk factor analysis of new brain lesions associated with carotid endarterectmy.

PubMed

Lee, Jae Hoon; Suh, Bo Yang

2014-01-01

Carotid endarterectomy (CEA) is the standard treatment for carotid artery stenosis. New brain ischemia is a major concern associated with CEA and diffusion weighted imaging (DWI) is a good imaging modality for detecting early ischemic brain lesions. We aimed to investigate the surgical complications and identify the potential risk factors for the incidence of new brain lesions (NBL) on DWI after CEA. From January 2006 to November 2011, 94 patients who had been studied by magnetic resonance imaging including DWI within 1 week after CEA were included in this study. Data were retrospectively investigated by review of vascular registry protocol. Seven clinical variables and three procedural variables were analyzed as risk factors for NBL after CEA. The incidence of periprocedural NBL on DWI was 27.7%. There were no fatal complications, such as ipsilateral disabling stroke, myocardial infarction or mortality. A significantly higher incidence of NBL was found in ulcer positive patients as opposed to ulcer negative patients (P = 0.029). The incidence of NBL after operation was significantly higher in patients treated with conventional technique than with eversion technique (P = 0.042). Our data shows CEA has acceptable periprocedural complication rates and the existence of ulcerative plaque and conventional technique of endarterectomy are high risk factors for NBL development after CEA.

Cerebellar Growth Impairment Characterizes School-Aged Children Born Preterm without Perinatal Brain Lesions.

PubMed

Pieterman, K; White, T J; van den Bosch, G E; Niessen, W J; Reiss, I K M; Tibboel, D; Hoebeek, F E; Dudink, J

2018-05-01

Infants born preterm are commonly diagnosed with structural brain lesions known to affect long-term neurodevelopment negatively. Yet, the effects of preterm birth on brain development in the absence of intracranial lesions remain to be studied in detail. In this study, we aim to quantify long term consequences of preterm birth on brain development in this specific group. Neonatal cranial sonography and follow-up T1-weighted MR imaging and DTI were performed to evaluate whether the anatomic characteristics of the cerebrum and cerebellum in a cohort of school-aged children (6-12 years of age) were related to gestational age at birth in children free of brain lesions in the perinatal period. In the cohort consisting of 36 preterm (28-37 weeks' gestational age) and 66 term-born infants, T1-weighted MR imaging and DTI at 6-12 years revealed a reduction of cerebellar white matter volume (β = 0.387, P < .001), altered fractional anisotropy of cerebellar white matter (β = -0.236, P = .02), and a reduction of cerebellar gray and white matter surface area (β = 0.337, P < .001; β = 0.375, P < .001, respectively) in relation to birth age. Such relations were not observed for the cerebral cortex or white matter volume, surface area, or diffusion quantities. The results of our study show that perinatal influences that are not primarily neurologic are still able to disturb long-term neurodevelopment, particularly of the developing cerebellum. Including the cerebellum in future neuroprotective strategies seems therefore essential. © 2018 by American Journal of Neuroradiology.

Single-digit arithmetic processing—anatomical evidence from statistical voxel-based lesion analysis

PubMed Central

Mihulowicz, Urszula; Willmes, Klaus; Karnath, Hans-Otto; Klein, Elise

2014-01-01

Different specific mechanisms have been suggested for solving single-digit arithmetic operations. However, the neural correlates underlying basic arithmetic (multiplication, addition, subtraction) are still under debate. In the present study, we systematically assessed single-digit arithmetic in a group of acute stroke patients (n = 45) with circumscribed left- or right-hemispheric brain lesions. Lesion sites significantly related to impaired performance were found only in the left-hemisphere damaged (LHD) group. Deficits in multiplication and addition were related to subcortical/white matter brain regions differing from those for subtraction tasks, corroborating the notion of distinct processing pathways for different arithmetic tasks. Additionally, our results further point to the importance of investigating fiber pathways in numerical cognition. PMID:24847238

Frameless Stereotactic Insertion of Viewsite Brain Access System with Microscope-Mounted Tracking Device for Resection of Deep Brain Lesions: Technical Report

PubMed Central

Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J

2017-01-01

The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions. PMID:28331774

Frameless Stereotactic Insertion of Viewsite Brain Access System with Microscope-Mounted Tracking Device for Resection of Deep Brain Lesions: Technical Report.

PubMed

White, Tim; Chakraborty, Shamik; Lall, Rohan; Fanous, Andrew A; Boockvar, John; Langer, David J

2017-02-04

The surgical management of deep brain tumors is often challenging due to the limitations of stereotactic needle biopsies and the morbidity associated with transcortical approaches. We present a novel microscopic navigational technique utilizing the Viewsite Brain Access System (VBAS) (Vycor Medical, Boca Raton, FL, USA) for resection of a deep parietal periventricular high-grade glioma as well as another glioma and a cavernoma with no related morbidity. The approach utilized a navigational tracker mounted on a microscope, which was set to the desired trajectory and depth. It allowed gentle continuous insertion of the VBAS directly to a deep lesion under continuous microscopic visualization, increasing safety by obviating the need to look up from the microscope and thus avoiding loss of trajectory. This technique has broad value for the resection of a variety of deep brain lesions.

Dermal fibroblasts from acute inflamed atopic dermatitis lesions display increased eotaxin/CCL11 responsiveness to interleukin-4 stimulation.

PubMed

Gahr, N; Fölster-Holst, R; Weichenthal, M; Christophers, E; Schröder, J-M; Bartels, J

2011-03-01

The presence of eosinophils and/or eosinophil-derived products in the dermis is characteristic for involved skin of patients with atopic dermatitis and contributes to the observed tissue injury. CCL11 is a potent chemoattractant and activator of human eosinophils and interleukin (IL)-4 is a potent inducer of CCL11 expression in dermal fibroblasts. As increased fibroblast CCL11 expression may explain eosinophilic infiltration of involved skin areas in atopic dermatitis, we asked whether dermal fibroblasts from atopic patients differ from fibroblasts of healthy individuals in their ability to express CCL11. We compared IL-4-induced CCL11 mRNA expression using reverse transcription-polymerase chain reaction from cultured dermal fibroblasts derived from biopsies of chronic lesional and acute lesional atopic skin as well as from skin biopsies derived from normal skin of healthy donors. Considerable variability in IL-4-induced relative CCL11 mRNA expression was detected in fibroblasts derived from biopsies of different individuals. The lowest median IL-4 concentration inducing half maximal CCL11 mRNA expression (EC(50)) was found in fibroblasts derived from acute inflamed atopic lesions. Inducibility of CCL11 in dermal fibroblasts upon stimulation with Th2 cytokines explains the tissue eosinophilia observed in the presence of Th2 cytokines and the localization of eosinophils to the dermis. Decreased EC(50) values of IL-4-induced CCL11 expression in fibroblasts from acute inflamed atopic skin lesions indicates increased IL-4 responsiveness in these lesions and further substantiates the special role for IL-4-induced dermal fibroblast CCL11 expression in acute lesions. Variable CCL11 expression in fibroblasts from different patients with atopic dermatitis indicates heterogeneity of factors determining atopic phenotype in atopic dermatitis. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Interictal Electroencephalography (EEG) Findings in Children with Epilepsy and Bilateral Brain Lesions on Magnetic Resonance Imaging (MRI).

PubMed

Zubcevic, Smail; Milos, Maja; Catibusic, Feriha; Uzicanin, Sajra; Krdzalic, Belma

2015-12-01

Neuroimaging procedures and electroencephalography (EEG) are basic parts of investigation of patients with epilepsies. The aim is to try to assess relationship between bilaterally localized brain lesions found in routine management of children with newly diagnosed epilepsy and their interictal EEG findings. Total amount of 68 patients filled criteria for inclusion in the study that was performed at Neuropediatrics Department, Pediatric Hospital, University Clinical Center Sarajevo, or its outpatient clinic. There were 33 girls (48,5%) and 35 boys (51,5%). Average age at diagnosis of epilepsy was 3,5 years. Both neurological and neuropsychological examination in the moment of making diagnosis of epilepsy was normal in 27 (39,7%) patients, and showed some kind of delay or other neurological finding in 41 (60,3%). Brain MRI showed lesions that can be related to antenatal or perinatal events in most of the patients (ventricular dilation in 30,9%, delayed myelination and post-hypoxic changes in 27,9%). More than half of patients (55,9%) showed bilateral interictal epileptiform discharges on their EEGs, and further 14,7% had other kinds of bilateral abnormalities. Frequency of bilateral epileptic discharges showed statistically significant predominance on level of p<0,05. Cross tabulation between specific types of bilateral brain MRI lesions and EEG finding did not reveal significant type of EEG for assessed brain lesions. We conclude that there exists relationship between bilaterally localized brain MRI lesions and interictal bilateral epileptiform or nonspecific EEG findings in children with newly diagnosed epilepsies. These data are suggesting that in cases when they do not correlate there is a need for further investigation of seizure etiology.

Reproducibility of Ultrasound-Guided High Intensity Focused Ultrasound (HIFU) Thermal Lesions in Minimally-Invasive Brain Surgery

NASA Astrophysics Data System (ADS)

Zahedi, Sulmaz

This study aims to prove the feasibility of using Ultrasound-Guided High Intensity Focused Ultrasound (USg-HIFU) to create thermal lesions in neurosurgical applications, allowing for precise ablation of brain tissue, while simultaneously providing real time imaging. To test the feasibility of the system, an optically transparent HIFU compatible tissue-mimicking phantom model was produced. USg-HIFU was then used for ablation of the phantom, with and without targets. Finally, ex vivo lamb brain tissue was imaged and ablated using the USg-HIFU system. Real-time ultrasound images and videos obtained throughout the ablation process showing clear lesion formation at the focal point of the HIFU transducer. Post-ablation gross and histopathology examinations were conducted to verify thermal and mechanical damage in the ex vivo lamb brain tissue. Finally, thermocouple readings were obtained, and HIFU field computer simulations were conducted to verify findings. Results of the study concluded reproducibility of USg-HIFU thermal lesions for neurosurgical applications.

Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis.

PubMed

Tauhid, Shahamat; Chu, Renxin; Sasane, Rahul; Glanz, Bonnie I; Neema, Mohit; Miller, Jennifer R; Kim, Gloria; Signorovitch, James E; Healy, Brian C; Chitnis, Tanuja; Weiner, Howard L; Bakshi, Rohit

2015-11-01

Multiple sclerosis (MS) commonly affects occupational function. We investigated the link between brain MRI and employment status. Patients with MS (n = 100) completed a Work Productivity and Activity Impairment (WPAI) (general health version) survey measuring employment status, absenteeism, presenteeism, and overall work and daily activity impairment. Patients "working for pay" were considered employed; "temporarily not working but looking for work," "not working or looking for work due to age," and "not working or looking for work due to disability" were considered not employed. Brain MRI T1 hypointense (T1LV) and T2 hyperintense (T2LV) lesion volumes were quantified. To assess lesional destructive capability, we calculated each subject's ratio of T1LV to T2LV (T1/T2). Normalized brain parenchymal volume (BPV) assessed brain atrophy. The mean (SD) age was 45.5 (9.7) years; disease duration was 12.1 (8.1) years; 75 % were women, 76 % were relapsing-remitting, and 76 % were employed. T1LV, T1/T2, Expanded Disability Status Scale (EDSS) scores, and activity impairment were lower and BPV was higher in the employed vs. not employed group (Wilcoxon tests, p < 0.05). Age, disease duration, MS clinical subtype, and T2LV did not differ between groups (p > 0.05). In multivariable logistic regression modeling, adjusting for age, sex, and disease duration, higher T1LV predicted a lower chance of employment (p < 0.05). Pearson correlations showed that EDSS was associated with activity impairment (p < 0.05). Disease duration, age, and MRI measures were not correlated with activity impairment or other WPAI outcomes (p > 0.05). We report a link between brain atrophy and lesions, particularly lesions with destructive potential, to MS employment status.

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

PubMed Central

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-01-01

AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement. PMID:28839430

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.

PubMed

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-08-07

To counteract/reveal celecoxib-induced toxicity and NO system involvement. Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

Lesion localization of global aphasia without hemiparesis by overlapping of the brain magnetic resonance images

PubMed Central

Kim, Woo Jin; Paik, Nam-Jong

2014-01-01

Global aphasia without hemiparesis is a striking stroke syndrome involving language impairment without the typically manifested contralateral hemiparesis, which is usually seen in patients with global aphasia following large left perisylvian lesions. The objective of this study is to elucidate the specific areas for lesion localization of global aphasia without hemiparesis by retrospectively studying the brain magnetic resonance images of six patients with global aphasia without hemiparesis to define global aphasia without hemiparesis-related stroke lesions before overlapping the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Lesions where the images of more than three patients overlapped were considered significant. The overlapped global aphasia without hemiparesis related stroke lesions of six patients revealed that the significantly involved anatomical lesions were as follows: frontal lobe, sub-gyral, sub-lobar, extra-nuclear, corpus callosum, and inferior frontal gyrus, while caudate, claustrum, middle frontal gyrus, limbic lobe, temporal lobe, superior temporal gyrus, uncus, anterior cingulate, parahippocampal, amygdala, and subcallosal gyrus were seen less significantly involved. This study is the first to demonstrate the heterogeneous anatomical involvement in global aphasia without hemiparesis by overlapping of the brain magnetic resonance images. PMID:25657725

In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

PubMed Central

Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

2017-01-01

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction.

PubMed

Saito, Tsukasa; Hayashi, Keisuke; Nakazawa, Hajime; Ota, Tetsuo

2016-08-01

Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition.

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury.

PubMed

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O; Fair, Joseph E; Brock Frost, R; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D; Gardner, Scott; Stevens, Mark; Larson, Michael J

2017-01-01

Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a level one trauma center. Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor Functional Independence Measure (FIM) scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. The DOI quantitative injury lesion volumes and degree of midline shift were obtained from DOI brain computed tomography scans. A multiple stepwise regression model including 13 independent variables was created. This model was used to predict postrehabilitation outcomes, including FIM scores and ability to return to home. A p value less than 0.05 was considered significant. Ninety-six patients were enrolled in the study. Mean age was 43 ± 21 years, admission Glasgow Coma Score was 8.4 ± 4.8, Injury Severity Score was 24.7 ± 9.9, and head Abbreviated Injury Scale score was 3.73 ± 0.97. Acute hospital LOS was 12.3 ± 8.9 days, and rehabilitation LOS was 15.9 ± 9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p = 0.004) and discharge (p = 0.004) and inversely associated with ability to be discharged to home after rehabilitation (p = 0.006). In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller-injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury

PubMed Central

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O.; Fair, Joseph E.; Frost, R. Brock; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D.; Gardner, Scott; Stevens, Mark; Larson, Michael J.

2016-01-01

Introduction Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a Level One Trauma Center. Methods Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor FIM scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. DOI quantitative injury lesion volumes and degree of midline shift were obtained from day-of-injury (DOI) brain computed tomography (CT) scans. A multiple step-wise regression model including 13 independent variables was created. This model was used to predict post-rehabilitation outcomes, including FIM scores and ability to return to home. P<0.05 was considered significant. Results 96 patients were enrolled in the study. Mean age was 43±21 years, admission Glasgow Coma Score 8.4±4.8, Injury Severity Score 24.7±9.9, and head Abbreviated Injury Scale score 3.73±0.97. Acute hospital length of stay (LOS) was 12.3±8.9 days and rehabilitation LOS was 15.9±9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p=0.004) and discharge (p=0.004) and inversely associated with ability to be discharged to home after rehabilitation (p=0.006). Conclusion In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may

Globus pallidus lesions associated with high mountain climbing.

PubMed Central

Jeong, Jee Hyang; Kwon, Jay C.; Chin, Juhee; Yoon, Soo Jin; Na, Duk L.

2002-01-01

Acute mountain sickness (AMS) occurs commonly in hikers who are rapidly exposed to high altitude environments. Despite the numerous reports of AMS, few studies have reported pallidal lesions associated with altitude sickness. A previously healthy 49-yr-old Korean patient, after ascent to 4,700 m, suffered symptoms consistent with AMS. After returning home, the patient showed changes in personality characterized by abulia, indifference, and indecisiveness. T2 weighted brain magnetic resonance imaging showed high signal lesions involving bilateral globus pallidus. Our case suggests that globus pallidus injury should be included in the differential diagnosis of patients with personality or cognitive change after recovery from AMS. PMID:12483018

[Clinical features of focal brain lesions in the left-handed and ambidextrous].

PubMed

Chebysheva, L N; Bragina, N N; Dobrokhotova, T A

1977-01-01

On the basis of a study of 31 patients who demonstrated deviations from dextrality (Simistrals and ambidextrals) the authors describe some traits of the nervous and mental changes in focal brain lesions. There are insignificant correlations between the character of nervous and mental changes and the side of a brain lesion. The study demonstrated a wide variability of the clinical symptomatology, a peculiarity of each neurological and psychopathological phenomenon, distinguishing them from similar changes in dextrals. The studied contingent revealed prevalence of a disturbed sensory cognition in the clinical picture; the presence of special phenomena which most likely are not seen in dextrals and which are also related to a pathology of sensory cognition. It is being assumed that these clinical traits may testify to an insufficiency of speech lateralization in sinistrals and that an insufficient speech lateralization is accompanied by other than in dextrals organization of sensory processes.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Acute stress promotes post-injury brain regeneration in fish.

PubMed

Sinyakov, Michael S; Haimovich, Amihai; Avtalion, Ramy R

2017-12-01

The central nervous system and the immune system, the two major players in homeostasis, operate in the ongoing bidirectional interaction. Stress is the third player that exerts strong effect on these two 'supersystems'; yet, its impact is studied much less. In this work employing carp model, we studied the influence of preliminary stress on neural and immune networks involved in post-injury brain regeneration. The relevant in vivo models of air-exposure stress and precisely directed cerebellum injury have been developed. Neuronal regeneration was evaluated by using specific tracers of cell proliferation and differentiation. Involvement of immune networks was accessed by monitoring the expression of selected T cells markers. Contrast difference between acute and chronic stress manifested in the fact that chronically stressed fish did not survive the brain injury. Neuronal regeneration appeared as a biphasic process whereas involvement of immune system proceeded as a monophasic route. In stressed fish, immune response was fast and accompanied or even preceded neuronal regeneration. In unstressed subjects, immune response took place on the second phase of neuronal regeneration. These findings imply an intrinsic regulatory impact of acute stress on neuronal and immune factors involved in post-injury brain regeneration. Stress activates both neuronal and immune defense mechanisms and thus contributes to faster regeneration. In this context, paradoxically, acute preliminary stress might be considered a distinct asset in speeding up the following post-injury brain regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk of no-reflow in culprit lesion versus culprit vessel PCI in acute STEMI.

PubMed

Arslan, Uğur; Yaman, Mehmet; Kocaoğlu, İbrahim; Turan, Oğuzhan Ekrem; Yücel, Huriye; Aksakal, Aytekin; Günaydin, İlksen Atasoy; Hakan Ateş, Ahmet

2015-09-01

The present report describes patients with acute ST-elevation myocardial infarction who had at least two lesions in the culprit vessel (CV) during primary percutaneous coronary intervention (PCI). Here, we aimed to examine two different strategies, namely, PCI of only culprit lesion (CL) versus PCI of all lesions in the CV in the setting of acute ST-elevation myocardial infarction. Patients who underwent primary PCI were examined for the presence of an additional lesion in the infarct-related artery and divided into two groups according to the PCI strategy: CV versus CL groups. Coronary angiograms were examined for coronary thrombolysis in myocardial infarction (TIMI) flow and major clinical outcomes were determined. Of 637 patients, 472 (74.1%) underwent primary PCI for the CV (CV group) and 165 (25.9%) underwent primary PCI only for CL (CL group). TIMI flow before primary PCI and after stenting of the CL was similar; however, TIMI flow after completion of the procedure was significantly better in the CL group (P=0.022). The composite of death, nonfatal myocardial infarction and repeat revascularization was significantly better in the CL group (P=0.041) and early stent thrombosis was observed more commonly in the CV group [14 (3.0%) patients vs. 1 (0.6%) patient, P=0.09]. In the presence of an additional lesion in the CV during primary PCI, deferring stenting for the non-CL in the culprit artery after stenting the CL may be considered to prevent the development of no-reflow or slow-reflow, and thus major clinical adverse events may be reduced.

[Study of 3D-pcASL in differentiation of acute cerebral infarction and acute encephalitis].

PubMed

Mao, Chuanwan; Fu, Yuchuan; Ye, Xinjian; Wu, Aiqin; Yan, Zhihan

2015-06-16

To investigate the value of three-dimentional pseudo-continuous arterial spin labeling (ASL) perfusion imaging in differentiating acute cerebral infarction from acute encephalitis. From September 2013 to September 2014, 42 patients with actue stroke onset and 20 healthy volunteers underwent conventional brain MRI DWI and 3D-ASL Perfusion Imaging in our hospital. Only 20 patients whose lesions located in the middle cerebral artery (MCA) territory were enrolled in this study. Of these cases, 12 cases were diagnosed with acute cerebral infarction, 8 were diagnosed with encephalitis. First, we analyzed the imaging features of the 20 patients and 20 volunteers. Then, CBF values of the lesions in the 20 patients and the gray matter of MCA territory in the 20 volunteers were measured on 3D-pcASL images. Third, the difference of mean CBF values between patients and volunteers were analyzed. Out of 20 study group, 19 patients whose lesions presented high signal intensity on DWI images, 12 cases were acute cerebral infarction and 8 were encephalitis. All the lesions of 20 cases showed abnormal perfusion on 3D-pcASL images. 3D-pcASL has good consistency with DWI in diagnostic capabilities (χ² = 0.565, P = 0.01). On 3D-pcASL, 11 acute cerebral infarction patients presented perfusion defects or low perfusion, 1 acute cerebral infarction patients showed high perfusion, 8 encephalitis patients showed inhomogeneous perfusion. The mean value of CBF was (17 ± 6) ml · min⁻¹ · 100 g⁻¹ in 12 acute cerebral infarction patients, (136 ± 69) ml · min⁻¹ · 100 g⁻¹ in 8 encephalitis patients and (68 ± 12) ml · min⁻¹ · 100 g⁻¹ three in 20 healthy volunteers. The difference in mean value of CBF among the three groups was statistically significant (P < 0.01). Acute cerebral infarction often shows low perfusion and acute encephalitis shows high perfusion on 3D-pcASL images, which has a higher application value in diagnosis and differentiation of acute cerebral

CT characteristics of Morel-Lavallée lesions: an under-recognized but significant finding in acute trauma imaging.

PubMed

McKenzie, Gavin A; Niederhauser, Blake D; Collins, Mark S; Howe, Benjamin M

2016-08-01

To highlight the significance and imaging characteristics of Morel-Lavallée (ML) lesions, which have been well characterized on MRI, but are potentially under-recognized on CT. Twenty-eight Morel-Lavallée lesions were identified in 18 patients and were all clinically or surgically confirmed. Lesions were grouped into acute (<3 days), subacute (3-30 days), and chronic (>30 days) at the time of CT imaging. Charts were reviewed to gather patient characteristics, injury patterns, radiologist interpretation, treatment, and outcomes. Sixteen male and 2 female patients with a mean age of 50 years (range 19-80) at the date of their initial evaluation were identified. All patients had significant trauma that accounted for 28 ML lesions, all of which were in a characteristic subcutaneous location overlying the muscular fascial plane. Lesions on CT went through an evolution from hyperdense, poorly or moderately marginated without a pseudocapsule to being hypodense, with internal fat globules or septations and well marginated with a complete enhancing pseudocapsule. Only 1 (4 %) of the ML lesions was suggested and 7 (25 %) lesions were not commented on at all by the interpreting radiologist. Morel-Lavallée lesions are post-traumatic closed, internal, soft-tissue, degloving lesions that are potentially underrecognized on CT. Most acute ML lesions are nonspecific, resembling simple hematomas or contusions. ML lesions evolve as they age with subacute and chronic lesions demonstrating the known features described on MR imaging that should allow for an accurate imaging diagnosis.

Magnetic resonance and computed tomographic imaging in the evaluation of acute neuropsychiatric disease in systemic lupus erythematosus.

PubMed Central

Sibbitt, W L; Sibbitt, R R; Griffey, R H; Eckel, C; Bankhurst, A D

1989-01-01

Magnetic resonance (MR) imaging and computed tomography (CT) are useful for the evaluation of central nervous system (CNS) lupus. This report describes the use of cranial MR and CT in 21 patients with systemic lupus erythematosus (SLE) with acute neuropsychiatric symptoms manifested by headache, seizures, focal neurological deficits, psychosis, or organic brain syndrome. Computed tomography was found to be insensitive and detected only diffuse atrophy (two cases), cerebral infarct (one case), and intracerebral haemorrhage (one case) in the 21 patients. Cranial MR images obtained with a General Electric 1.5 tesla Signa unit detected labile and fixed areas of increased proton intensity interpreted as focal oedema (eight cases), infarct (10 cases), haemorrhage (one), atrophy (seven), and acute sinusitis (two). Focal oedema was characterised by labile, high intensity lesions in the gray or white matter of the cerebellum, cerebrum, or brain stem, which completely resolved after aggressive corticosteroid treatment. Most high intensity reversible or fixed lesions evident on MR were not apparent on cranial CT images. In several patients sequential MR images were valuable in monitoring the efforts of treatment. Although histological confirmation of the high intensity brain lesions apparent on MR is desirable, prior necropsy studies suggest that pathological confirmation may be difficult owing to the paucity of recognisable brain lesions in patients with CNS lupus. It is concluded that for the evaluation of acute neuropsychiatric SLE MR is useful and provides more information than cranial CT. Images PMID:2619353

Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.

PubMed

Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos

2015-01-01

Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.

Prickly Pear Cactus (Opuntia ficus indica var. saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats

PubMed Central

Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha

2012-01-01

Abstract The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague–Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800–1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production. PMID:23062184

Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

PubMed

Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

2012-11-01

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

A case of a brain stem abscess with a favorable outcome

PubMed Central

Bulthuis, Vincent J.; Gubler, Felix S.; Teernstra, Onno P. M.; Temel, Yasin

2015-01-01

Background: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. Case Description: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed tomography showed a space-occupying lesion in the brain stem. She became shortly after comatose, and we decided to perform an acute stereotactic aspiration of the abscess. Soon after surgery, her neurological condition improved dramatically. Conclusion: A brainstem abscess is a life-threatening condition with a potentially good outcome if treated adequately. PMID:26543670

Nitric oxide as an initiator of brain lesions during the development of Alzheimer disease.

PubMed

Aliev, Gjumrakch; Palacios, Hector H; Lipsitt, Amanda E; Fischbach, Kathryn; Lamb, Bruce T; Obrenovich, Mark E; Morales, Ludis; Gasimov, Eldar; Bragin, Valentin

2009-10-01

Nitric oxide (NO) is an important regulatory molecule for the host defense that plays a fundamental role in the cardiovascular, immune, and nervous systems. NO is synthesized through the conversion of L-arginine to L-citrulline by the enzyme NO synthase (NOS), which is found in three isoforms classified as neuronal (nNOS), inducible (iNOS), and endothelial (eNOS). Recent evidence supports the theory that this bioactive molecule has an influential role in the disruption of normal brain and vascular homeostasis, a condition known to elucidate chronic hypoperfusion which ultimately causes the development of brain lesions and the pathology that typify Alzheimer disease (AD). In addition, vascular NO activity appears to be a major contributor to this pathology before any overexpression of NOS isoforms is observed in the neuron, glia, and microglia of the brain tree, where the overexpression the NOS isoforms causes the formation of a large amount of NO. We hypothesize that since an imbalance between the NOS isoforms and endothelin-1 (ET-1), a human gene that encodes for blood vessel constriction, can cause antioxidant system insufficiency; by using pharmacological intervention with NO donors and/or NO suppressors, the brain lesions and the downstream progression of brain pathology and dementia in AD should be delayed or minimized.

Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

PubMed

Lane, E L; Cheetham, S; Jenner, P

2008-01-01

The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

Small brain lesions and incident stroke and mortality: A cohort study

PubMed Central

Windham, B Gwen; Deere, Bradley; Griswold, Michael E.; Wang, Wanmei; Bezerra, Daniel C; Shibata, Dean; Butler, Kenneth; Knopman, David; Gottesman, Rebecca F; Heiss, Gerardo; Mosley, Thomas H

2015-01-01

Background Although cerebral lesions ≥3mm on imaging are associated with incident stroke, lesions < 3mm are typically ignored. Objective To examine stroke risks associated with subclinical brain lesions by size (< 3 mm only, lesions ≥3 mm only, both < 3 mm and ≥3 mm) and white matter hyperintensities (WMH). Design Community cohort, Atherosclerosis Risk in Communities (ARIC) Study Setting Two ARIC sites with magnetic resonance imaging (MRI) data (1993–95) Participants 1,884 (99%) adults (50–73 years, 40% men; 50% black) with MRI and no prior stroke; average 14.5 years follow-up. Measurements MRI lesions: none (n=1611), < 3 mm only (n=50), ≥3 mm only (n=185), or both < 3 and ≥3 mm lesions (n=35); WMH score (0–9 scale). Outcomes: incident stroke (n=157), overall mortality (n=576), stroke mortality (n=50). Hazard Ratios (HR) estimated with proportional hazards models. Results Compared to no lesions, stroke risk was tripled with lesions < 3mm only (HR=3.47, 95% CI:1.86-6.49), doubled with lesions ≥3 mm only (HR=1.94, 95% CI:1.22-3.07), and was 8-fold higher with both < 3 mm and ≥3 mm-sized lesions (HR=8.59, 95% CI:4.69-15.73). Stroke risk doubled with WMH ≥3 (HR=2.14, 95% CI:1.45-3.16). Stroke mortality risk tripled with lesions < 3 mm only (HR=3.05, 95% CI:1.04-8.94), doubled with lesions ≥3 mm (HR=1.9, 95% CI:1.48-2.44) and was seven-times higher with both lesion sizes (HR=6.97, 95% CI:2.03-23.93). Limitations Few stroke events (n=147), especially hemorrhagic (n=15); limited numbers of participants with only lesions ≤3mm (n=50) or with both lesions ≤3mm and 3–20mm (n=35). Conclusions Very small cerebrovascular lesions may be associated with increased risks of stroke and mortality; having both < 3 mm and ≥3 mm lesions may represent a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PMID:26148278

Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

PubMed

Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E

2013-01-01

Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.

Lesion network localization of criminal behavior

PubMed Central

Darby, R. Ryan; Horn, Andreas; Fox, Michael D.

2018-01-01

Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior. PMID:29255017

Creating Brain Lesions by Low Intensity Focused Ultrasound with Microbubbles: A Rat Study at Half MHz

PubMed Central

Huang, Yuexi; Vykhodtseva, Natalia I.; Hynynen, Kullervo

2014-01-01

Low intensity focused ultrasound was applied with microbubbles (Definity, 0.02 mL/kg) to produce brain lesions in 50 rats at 558 kHz. Burst sonications (burst length: 10 ms; pulse repetition frequency: 1 Hz; total exposure: 5 min; acoustic powers: 0.47-1.3W) generated ischemic or hemorrhagic lesions at the focal volume revealed by both MR imaging and histology. Shorter burst (2 ms) or shorter sonication time (1 min) reduced the probability of lesion production. Longer pulses (200ms, 500ms and continuous wave) caused significant near-field damages. Using microbubbles with focused ultrasound significantly reduced the acoustic power levels, therefore avoided skull heating issues and potentially can extend the treatable volume of transcranial focused ultrasound to the brain tissues close to the skull. PMID:23743099

Neglect severity after left and right brain damage.

PubMed

Suchan, Julia; Rorden, Chris; Karnath, Hans-Otto

2012-05-01

While unilateral spatial neglect after left brain damage is undoubtedly less common than spatial neglect after a right hemisphere lesion, it is also assumed to be less severe. Here we directly test this latter hypothesis using a continuous measure of neglect severity: the so-called Center of Cancellation (CoC). Rorden and Karnath (2010) recently validated this index for right brain damaged neglect patients. A first aim of the present study was to evaluate this new measure for spatial neglect after left brain damage. In a group of 48 left-sided stroke patients with and without neglect, a score greater than -0.086 on the Bells Test and greater than -0.024 on the Letter Cancellation Task turned out to indicate neglect behavior for acute left brain damaged patients. A second aim was to directly compare the severity of spatial neglect after left versus right brain injury by using the new CoC measure. While neglect is less frequent following left than right hemisphere injury, we found that when this symptom occurs it is of similar severity in acute left brain injury as in patients after acute right brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

PubMed Central

2011-01-01

Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

Distribution and severity of hypoxic-ischaemic lesions on brain MRI following therapeutic cooling: selective head versus whole body cooling.

PubMed

Sarkar, Subrata; Donn, Steven M; Bapuraj, Jayapalli R; Bhagat, Indira; Barks, John D

2012-09-01

Whole body cooling (WBC) cools different parts of the brain uniformly, and selective head cooling (SHC) cools the superficial brain more than the deeper brain structures. In this study, the authors hypothesised that the hypoxic-ischaemic lesions on brain MRI following cooling would differ between modalities of cooling. To compare the frequency, distribution and severity of hypoxic-ischaemic lesions on brain MRI between SHC or WBC. In a single centre retrospective study, 83 infants consecutively cooled using either SHC (n=34) or WBC (n=49) underwent brain MRI. MRI images were evaluated by a neuroradiologist, who was masked to clinical parameters and outcomes, using a basal ganglia/watershed (BG/W) scoring system. Higher scores (on a scale of 0 to 4) were given for more extensive injury. The score has been reported to be predictive of neuromotor and cognitive outcome at 12 months. The two groups were similar for severity of depression as assessed by a history of an intrapartum sentinel event, Apgar scores, initial blood pH and base deficit and early neurological examination. However, abnormal MRI was more frequent in the SHC group (SHC 25 of 34, 74% vs WBC 22 of 49, 45%; p=0.0132, OR 3.4, 95% CI 1.3 to 8.8). Infants from the SHC group also had more severe hypoxic-ischaemic lesions (median BG/W score: SHC 2 vs WBC 0, p=0.0014). Hypoxic-ischaemic lesions on brain MRI following therapeutic cooling were more frequent and more severe with SHC compared with WBC.

Headache Following Occipital Brain Lesion: A Case of Migraine Triggered by Occipital Spikes?

PubMed

Vollono, Catello; Mariotti, Paolo; Losurdo, Anna; Giannantoni, Nadia Mariagrazia; Mazzucchi, Edoardo; Valentini, Piero; De Rose, Paola; Della Marca, Giacomo

2015-10-01

This study describes the case of an 8-year-old boy who developed a genuine migraine after the surgical excision, from the right occipital lobe, of brain abscesses due to selective infestation of the cerebrum by Entamoeba histolytica. After the surgical treatment, the boy presented daily headaches with typical migraine features, including right-side parieto-temporal pain, nausea, vomiting, and photophobia. Electroencephalography (EEG) showed epileptiform discharges in the right occipital lobe, although he never presented seizures. Clinical and neurophysiological observations were performed, including video-EEG and polygraphic recordings. EEG showed "interictal" epileptiform discharges in the right occipital lobe. A prolonged video-EEG recording performed before, during, and after an acute attack ruled out ictal or postictal migraine. In this boy, an occipital lesion caused occipital epileptiform EEG discharges without seizures, probably prevented by the treatment. We speculate that occipital spikes, in turn, could have caused a chronic headache with features of migraine without aura. Occipital epileptiform discharges, even in absence of seizures, may trigger a genuine migraine, probably by means of either the trigeminovascular or brainstem system. © EEG and Clinical Neuroscience Society (ECNS) 2014.

On brain lesions, the milkman and Sigmunda.

PubMed

Izquierdo, I; Medina, J H

1998-10-01

Lesion studies have been of historical importance in establishing the brain systems involved in memory processes. Many of those studies, however, have been overinterpreted in terms of the actual role of each system and of connections between systems. The more recent molecular pharmacological approach has produced major advances in these two areas. The main biochemical steps of memory formation in the CAI region of the hippocampus have been established by localized microinfusions of drugs acting on specific enzymes of receptors, by subcellular measurements of the activity or function of those enzymes and receptors at definite times, and by transgenic deletions or changes of those proteins. The biochemical steps of long-term memory formation in CAI have been found to be quite similar to those of long-term potentiation in the same region, and of other forms of plasticity. Connections between the hippocampus and the entorhinal and parietal cortices in the formation and modulation of short- and long-term memory have also been elucidated using these techniques. Lesion studies, coupled with imaging studies, still have a role to play; with regard to human memory, this role is in many ways unique. But these methods by themselves are not informative as to the mechanisms of memory processing, storage or modulation.

[Asymmetry of brain lesions and immunobiologic reactivity].

PubMed

Semenov, S F; Chuprikov, A P

1975-01-01

The authors compare some clinico-psychopathological traits in the development and frequency of detected antibrain antibodies and allergical states in epilepsy with a different lateralization in the hemispheres. In a sinistral localization of the lesion there is a significant increase of an unfavourable development of the disease and a more frequent detection of antibodies to the homologous brain. In a dextral localization there is a relatively favourable development of the basic disorder. The authors discuss the influence of the sex factor on the immunobiological indices and the lateralization of the hemisphere. A theory is suggested that the left and right hemispheres are involved in different ways in the different links of immunity, and their pathology may provoke different changes in the body reactivity.

Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

PubMed

Hainsworth, Atticus H; Minett, Thais; Andoh, Joycelyn; Forster, Gillian; Bhide, Ishaan; Barrick, Thomas R; Elderfield, Kay; Jeevahan, Jamuna; Markus, Hugh S; Bridges, Leslie R

2017-10-01

We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T 2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P =0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P =0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P =0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P =0.007). Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers. © 2017 American Heart Association, Inc.

MRI-Based Neuroanatomical Predictors of Dysphagia, Dysarthria, and Aphasia in Patients with First Acute Ischemic Stroke
.

PubMed

Flowers, Heather L; AlHarbi, Mohammed A; Mikulis, David; Silver, Frank L; Rochon, Elizabeth; Streiner, David; Martino, Rosemary

2017-01-01

Due to the high post-stroke frequency of dysphagia, dysarthria, and aphasia, we developed comprehensive neuroanatomical, clinical, and demographic models to predict their presence after acute ischemic stroke. The sample included 160 randomly selected first-ever stroke patients with confirmed infarction on magnetic resonance imaging from 1 tertiary stroke center. We documented acute lesions within 12 neuroanatomical regions and their associated volumes. Further, we identified concomitant chronic brain disease, including atrophy, white matter hyperintensities, and covert strokes. We developed predictive models using logistic regression with odds ratios (OR) and their 95% confidence intervals (95% CI) including demographic, clinical, and acute and chronic neuroanatomical factors. Predictors of dysphagia included medullary (OR 6.2, 95% CI 1.5-25.8), insular (OR 4.8, 95% CI 2.0-11.8), and pontine (OR 3.6, 95% CI 1.2-10.1) lesions, followed by brain atrophy (OR 3.0, 95% CI 1.04-8.6), internal capsular lesions (OR 2.9, 95% CI 1.2-6.6), and increasing age (OR 1.4, 95% CI 1.1-1.8). Predictors of dysarthria included pontine (OR 7.8, 95% CI 2.7-22.9), insular (OR 4.5, 95% CI 1.8-11.4), and internal capsular (OR 3.6, 95% CI 1.6-7.9) lesions. Predictors of aphasia included left hemisphere insular (OR 34.4, 95% CI 4.2-283.4), thalamic (OR 6.2, 95% CI 1.6-24.4), and cortical middle cerebral artery (OR 4.7, 95% CI 1.5-14.2) lesions. Predicting outcomes following acute stroke is important for treatment decisions. Determining the risk of major post-stroke impairments requires consideration of factors beyond lesion localization. Accordingly, we demonstrated interactions between localized and global brain function for dysphagia and elucidated common lesion locations across 3 debilitating impairments.
. © 2017 The Author(s)
. Published by S. Karger AG, Basel.

Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009--associated encephalopathy in children.

PubMed

Ishida, Yu; Kawashima, Hisashi; Morichi, Shinichiro; Yamanaka, Gaku; Okumura, Akihisa; Nakagawa, Satoshi; Morishima, Tsuneo

2015-02-01

Pandemic influenza A (H1N1) 2009 has been shown to be associated more with neurological complications than the seasonal influenza virus. In this study, we focused on the clinical usefulness of magnetic resonance imaging (MRI) in the acute phase of influenza A (H1N1) 2009-associated encephalopathy. A questionnaire was distributed to pediatric and general hospitals in Japan that treat children with encephalopathy. We conducted a questionnaire-based study involving the collection of information regarding 207 patients with encephalopathy. Brain MRI was performed in 97 of these 207 patients in the age group of 9 months to 15 years (mean, 7.5 years) within 48 hours after the development of encephalopathy symptoms. Sixty-six patients (68%) showed normal imaging. Diffuse brain edema was visible in five patients and an abnormal signal in the deep gray matter in two patients which is consistent with acute necrotizing encephalopathy. Abnormal signals of the splenial lesion, subcortical white matter (bright tree appearance), and cortical area were observed in 15, 1, and 8 patients, respectively. From our findings based on the questionnaire results, we suggest that MRI is useful for determining fatal cases of pandemic influenza A (H1N1) 2009 infection when performed in the acute phase. However, MRI is not useful in predicting the development of sequelae. Georg Thieme Verlag KG Stuttgart · New York.

Corticosterone and dehydroepiandrosterone in songbird plasma and brain: effects of season and acute stress

PubMed Central

Newman, Amy E. M.; Soma, Kiran K.

2010-01-01

Prolonged increases in plasma glucocorticoids can exacerbate neurodegeneration. In rats, these neurodegenerative effects can be reduced by dehydroepiandrosterone (DHEA), an androgen precursor with anti-glucocorticoid actions. In song sparrows, season and acute restraint stress affect circulating levels of corticosterone and DHEA, and the effects of stress differ in plasma collected from the brachial and jugular veins. Jugular plasma is an indirect index of the neural steroidal milieu. Here, we directly measured corticosterone and DHEA in several brain regions and jugular plasma, and examined the effects of season and acute restraint stress (30 min) (n = 571 samples). Corticosterone levels were up to 10× lower in brain than in jugular plasma. In contrast, DHEA levels were up to 5× higher in brain than in jugular plasma and were highest in the hippocampus. Corticosterone and DHEA concentrations were strongly seasonally regulated in plasma but, surprisingly, not seasonally regulated in brain. Acute stress increased corticosterone levels in plasma and brain, except during the molt, when stress unexpectedly decreased corticosterone levels in the hippocampus. Acute stress increased DHEA levels in plasma during the molt but had no effects on DHEA levels in brain. This is the first study to measure (i) corticosterone or DHEA levels in the brain of adult songbirds and (ii) seasonal changes in corticosterone or DHEA levels in the brain of any species. These results highlight several critical differences between systemic and local steroid concentrations and the difficulty of using circulating steroid levels to infer local steroid levels within the brain. PMID:19473242

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury.

PubMed

Saber, Maha; Kokiko-Cochran, Olga; Puntambekar, Shweta S; Lathia, Justin D; Lamb, Bruce T

2017-01-15

Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2 -/- ) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 days post-injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Further, Trem2 -/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2 -/- mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.

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

PubMed

Ernst, Marielle; Boers, Anna M M; Aigner, Annette; Berkhemer, Olvert A; Yoo, Albert J; Roos, Yvo B; Dippel, Diederik W J; van der Lugt, Aad; van Oostenbrugge, Robert J; van Zwam, Wim H; Fiehler, Jens; Marquering, Henk A; Majoie, Charles B L M

2017-09-01

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. 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. 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. 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. © 2017 American Heart Association, Inc.

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

NASA Astrophysics Data System (ADS)

Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

2016-06-01

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Automated metastatic brain lesion detection: a computer aided diagnostic and clinical research tool

NASA Astrophysics Data System (ADS)

Devine, Jeremy; Sahgal, Arjun; Karam, Irene; Martel, Anne L.

2016-03-01

The accurate localization of brain metastases in magnetic resonance (MR) images is crucial for patients undergoing stereotactic radiosurgery (SRS) to ensure that all neoplastic foci are targeted. Computer automated tumor localization and analysis can improve both of these tasks by eliminating inter and intra-observer variations during the MR image reading process. Lesion localization is accomplished using adaptive thresholding to extract enhancing objects. Each enhancing object is represented as a vector of features which includes information on object size, symmetry, position, shape, and context. These vectors are then used to train a random forest classifier. We trained and tested the image analysis pipeline on 3D axial contrast-enhanced MR images with the intention of localizing the brain metastases. In our cross validation study and at the most effective algorithm operating point, we were able to identify 90% of the lesions at a precision rate of 60%.

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

PubMed Central

Thom, Vivien; Arumugam, Thiruma V.; Magnus, Tim; Gelderblom, Mathias

2017-01-01

Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg. PMID:28824617

Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

PubMed

Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

2018-02-01

Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

PubMed

Datta, Gourab; Colasanti, Alessandro; Rabiner, Eugenii A; Gunn, Roger N; Malik, Omar; Ciccarelli, Olga; Nicholas, Richard; Van Vlierberghe, Eline; Van Hecke, Wim; Searle, Graham; Santos-Ribeiro, Andre; Matthews, Paul M

2017-11-01

Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnetization

[Hyperbaric oxygen therapy and inert gases in cerebral ischemia and traumatic brain injury].

PubMed

Chhor, V; Canini, F; De Rudnicki, S; Dahmani, S; Gressens, P; Constantin, P

2013-12-01

Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

PubMed Central

Santoro, Giovanni C; Carrion, Joseph; Dewey, Stephen L

2017-01-01

The rate of opioid overdose continues to rise, necessitating improved treatment options. Current therapeutic approaches rely on administration of either a blocking agent, such as naloxone, or chronic treatment with replacement drugs, including methadone and/or buprenorphine. Recent findings suggest that males and females respond to these treatments uniquely. In an effort to better understand this sex-specific variation in treatment efficacy, we investigated the effects of acute opioid withdrawal in male and female rats using 18FDG and microPET. These data demonstrate that acute opioid withdrawal produces metabolic alterations in brain regions associated with reward and drug dependence, namely corpus striatum, thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are unique to males. Specifically, males demonstrated increased metabolism in the anterior cingulate cortex and the ventral hippocampus (CA3) following acute opioid withdrawal. If males and females exhibit sex-specific changes in regional brain metabolism following acute opioid withdrawal, then perhaps it is not surprising that they respond to treatment differently. PMID:29046888

Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients.

PubMed

Guo, Ruo-Mi; Li, Qing-Ling; Zhong, Li-Ru; Guo, Yu; Jiao, Ju; Chen, Shao-Qiong; Wang, Jin; Zhang, Yong

2018-06-01

Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 μmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.

In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

PubMed

Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

1997-09-19

The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

Motor skill learning and offline-changes in TGA patients with acute hippocampal CA1 lesions.

PubMed

Döhring, Juliane; Stoldt, Anne; Witt, Karsten; Schönfeld, Robby; Deuschl, Günther; Born, Jan; Bartsch, Thorsten

2017-04-01

Learning and the formation of memory are reflected in various memory systems in the human brain such as the hippocampus based declarative memory system and the striatum-cortex based system involved in motor sequence learning. It is a matter of debate how both memory systems interact in humans during learning and consolidation and how this interaction is influenced by sleep. We studied the effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on-line condition) and off-line changes of a motor skill in patients with a transient global amnesia (TGA). Sixteen patients (68 ± 4.4 yrs) were studied in the acute phase and during follow-up using a declarative and procedural test, and were compared to controls. Acute TGA patients displayed profound deficits in all declarative memory functions. During the acute amnestic phase, patients were able to acquire the motor skill task reflected by increasing finger tapping speed across the on-line condition, albeit to a lesser degree than during follow-up or compared to controls. Retrieval two days later indicated a greater off-line gain in motor speed in patients than controls. Moreover, this gain in motor skill performance was negatively correlated to the declarative learning deficit. Our results suggest a differential interaction between procedural and declarative memory systems during acquisition and consolidation of motor sequences in older humans. During acquisition, hippocampal dysfunction attenuates fast learning and thus unmasks the slow and rigid learning curve of striatum-based procedural learning. The stronger gains in the post-consolidation condition in motor skill in CA1 lesioned patients indicate a facilitated consolidation process probably occurring during sleep, and suggest a competitive interaction between the memory systems. These findings might be a reflection of network reorganization and plasticity in older humans and in the presence of CA1 hippocampal pathology. Copyright © 2016

The value of whole lesion ADC histogram profiling to differentiate between morphologically indistinguishable ring enhancing lesions-comparison of glioblastomas and brain abscesses.

PubMed

Horvath-Rizea, Diana; Surov, Alexey; Hoffmann, Karl-Titus; Garnov, Nikita; Vörkel, Cathrin; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Bäzner, Hansjörg; Gihr, Georg Alexander; Kalman, Marcell; Henkes, Elina; Henkes, Hans; Schob, Stefan

2018-04-06

Morphologically similar appearing ring enhancing lesions in the brain parenchyma can be caused by a number of distinct pathologies, however, they consistently represent life-threatening conditions. The two most frequently encountered diseases manifesting as such are glioblastoma multiforme (GBM) and brain abscess (BA), each requiring disparate therapeutical approaches. As a result of their morphological resemblance, essential treatment might be significantly delayed or even ommited, in case results of conventional imaging remain inconclusive. Therefore, our study aimed to investigate, whether ADC histogram profiling reliably can distinguish between both entities, thus enhancing the differential diagnostic process and preventing treatment failure in this highly critical context. 103 patients (51 BA, 52 GBM) with histopathologically confirmed diagnosis were enrolled. Pretreatment diffusion weighted imaging (DWI) was obtained in a 1.5T system using b values of 0, 500, and 1000 s/mm 2 . Whole lesion ADC volumes were analyzed using a histogram-based approach. Statistical analysis was performed using SPSS version 23. All investigated parameters were statistically different in comparison of both groups. Most importantly, ADCp10 was able to differentiate reliably between BA and GBM with excellent accuracy (0.948) using a cutpoint value of 70 × 10 -5 mm 2 × s -1 . ADC whole lesion histogram profiling provides a valuable tool to differentiate between morphologically indistinguishable mass lesions. Among the investigated parameters, the 10th percentile of the ADC volume distinguished best between GBM and BA.

Inability to empathize: brain lesions that disrupt sharing and understanding another’s emotions

PubMed Central

2014-01-01

Emotional empathy—the ability to recognize, share in, and make inferences about another person’s emotional state—is critical for all social interactions. The neural mechanisms underlying emotional empathy have been widely studied with functional imaging of healthy participants. However, functional imaging studies reveal correlations between areas of activation and performance of a task, so that they can only reveal areas engaged in a task, rather than areas of the brain that are critical for the task. Lesion studies complement functional imaging, to identify areas necessary for a task. Impairments in emotional empathy have been mostly studied in neurological diseases with fairly diffuse injury, such as traumatic brain injury, autism and dementia. The classic ‘focal lesion’ is stroke. There have been scattered studies of patients with impaired empathy after stroke and other focal injury, but these studies have included small numbers of patients. This review will bring together data from these studies, to complement evidence from functional imaging. Here I review how focal lesions affect emotional empathy. I will show how lesion studies contribute to the understanding of the cognitive and neural mechanisms underlying emotional empathy, and how they contribute to the management of patients with impaired emotional empathy. PMID:24293265

Topography of acute stroke in a sample of 439 right brain damaged patients.

PubMed

Sperber, Christoph; Karnath, Hans-Otto

2016-01-01

Knowledge of the typical lesion topography and volumetry is important for clinical stroke diagnosis as well as for anatomo-behavioral lesion mapping analyses. Here we used modern lesion analysis techniques to examine the naturally occurring lesion patterns caused by ischemic and by hemorrhagic infarcts in a large, representative acute stroke patient sample. Acute MR and CT imaging of 439 consecutively admitted right-hemispheric stroke patients from a well-defined catchment area suffering from ischemia (n = 367) or hemorrhage (n = 72) were normalized and mapped in reference to stereotaxic anatomical atlases. For ischemic infarcts, highest frequencies of stroke were observed in the insula, putamen, operculum and superior temporal cortex, as well as the inferior and superior occipito-frontal fascicles, superior longitudinal fascicle, uncinate fascicle, and the acoustic radiation. The maximum overlay of hemorrhages was located more posteriorly and more medially, involving posterior areas of the insula, Heschl's gyrus, and putamen. Lesion size was largest in frontal and anterior areas and lowest in subcortical and posterior areas. The large and unbiased sample of stroke patients used in the present study accumulated the different sub-patterns to identify the global topographic and volumetric pattern of right hemisphere stroke in humans.

Treadmill sideways gait training with visual blocking for patients with brain lesions.

PubMed

Kim, Tea-Woo; Kim, Yong-Wook

2014-09-01

[Purpose] The aim of this study was to verify the effect of sideways treadmill training with and without visual blocking on the balance and gait function of patients with brain lesions. [Subjects] Twenty-four stroke and traumatic brain injury subjects participated in this study. They were divided into two groups: an experimental group (12 subjects) and a control group (12 subjects). [Methods] Each group executed a treadmill training session for 20 minutes, three times a week, for 6 weeks. The sideways gait training on the treadmill was performed with visual blocking by the experimental group and with normal vision by the control group. A Biodex Gait Trainer 2 was used to assess the gait function. It was used to measure walking speed, walking distance, step length, and stance time on each foot. The Five-Times-Sit-To-Stand test (FTSST) and Timed Up and Go test (TUG) were used as balance measures. [Results] The sideways gait training with visual blocking group showed significantly improved walking speed, walking distance, step length, and stance time on each foot after training; FTSST and TUG times also significantly improved after training in the experimental group. Compared to the control group, the experimental group showed significant increases in stance time on each foot. [Conclusion] Sideways gait training on a treadmill with visual blocking performed by patients with brain lesions significantly improved their balance and gait function.

Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

PubMed

Kent, Marc; Creevy, Kate E; Delahunta, Alexander

2010-01-01

Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

Cognitive Deficits and Related Brain Lesions in Patients With Chronic Heart Failure.

PubMed

Frey, Anna; Sell, Roxane; Homola, György A; Malsch, Carolin; Kraft, Peter; Gunreben, Ignaz; Morbach, Caroline; Alkonyi, Bálint; Schmid, Eric; Colonna, Isabella; Hofer, Edith; Müllges, Wolfgang; Ertl, Georg; Heuschmann, Peter; Solymosi, László; Schmidt, Reinhold; Störk, Stefan; Stoll, Guido

2018-05-31

This study sought to determine the spectrum of brain lesions seen in heart failure (HF) patients and the extent to which lesion type contributes to cognitive impairment. Cognitive deficits have been reported in patients with HF. A total of 148 systolic and diastolic HF patients (mean age 64 ± 11 years; 16% female; mean left ventricular ejection fraction 43 ± 8%) were extensively evaluated within 2 days by cardiological, neurological, and neuropsychological testing and brain magnetic resonance imaging (MRI). A total of 288 healthy, sex- and age-matched subjects sampled from the Austrian Stroke Prevention Study served as MRI controls. Deficits in reaction times were apparent in 41% of patients and deficits in verbal memory in 46%. On brain MRI, patients showed more advanced medial temporal lobe atrophy (MTA) (Scheltens score) compared to controls (2.1 ± 0.9 vs. 1.0 ± 0.6; p < 0.001). The degree of MTA was strongly associated with the severity of cognitive impairment, whereas the extent of white matter hyperintensities was similar in patients and controls. Moreover, patients had a 2.7-fold increased risk for presence of clinically silent lacunes. HF patients exhibit cognitive deficits in the domains of attention and memory. MTA but not white matter lesion load seems to be related to cognitive impairment. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Neuronal network-based mathematical modeling of perceived verticality in acute unilateral vestibular lesions: from nerve to thalamus and cortex.

PubMed

Glasauer, S; Dieterich, M; Brandt, T

2018-05-29

Acute unilateral lesions of vestibular graviceptive pathways from the otolith organs and semicircular canals via vestibular nuclei and the thalamus to the parieto-insular vestibular cortex regularly cause deviations of perceived verticality in the frontal roll plane. These tilts are ipsilateral in peripheral and in ponto-medullary lesions and contralateral in ponto-mesencephalic lesions. Unilateral lesions of the vestibular thalamus or cortex cause smaller tilts of the perceived vertical, which may be either ipsilateral or contralateral. Using a neural network model, we previously explained why unilateral vestibular midbrain lesions rarely manifest with rotational vertigo. We here extend this approach, focussing on the direction-specific deviations of perceived verticality in the roll plane caused by acute unilateral vestibular lesions from the labyrinth to the cortex. Traditionally, the effect of unilateral peripheral lesions on perceived verticality has been attributed to a lesion-based bias of the otolith system. We here suggest, on the basis of a comparison of model simulations with patient data, that perceived visual tilt after peripheral lesions is caused by the effect of a torsional semicircular canal bias on the central gravity estimator. We further argue that the change of gravity coding from a peripheral/brainstem vectorial representation in otolith coordinates to a distributed population coding at thalamic and cortical levels can explain why unilateral thalamic and cortical lesions have a variable effect on perceived verticality. Finally, we propose how the population-coding network for gravity direction might implement the elements required for the well-known perceptual underestimation of the subjective visual vertical in tilted body positions.

Right medial thalamic lesion causes isolated retrograde amnesia.

PubMed

Miller, L A; Caine, D; Harding, A; Thompson, E J; Large, M; Watson, J D

2001-01-01

Pervasive retrograde amnesia without anterograde memory impairment has rarely been described as a consequence of circumscribed brain damage. We report this phenomenon in a 33 yr-old, right-handed man (JG) in association with the extension in the right thalamus of a previously small, bilateral thalamic lesion. JG presented with a dense amnesia for autobiographical material more than a few years old, with some sparing of recent memories. Furthermore, he was completely unable to recognise famous people or world events. Many other aspects of semantic knowledge were intact and there was no evidence of general intellectual impairment, executive dysfunction or loss of visual imagery. Magnetic resonance imaging revealed an acute lesion in the right thalamus and two small, symmetrical, bilateral non-acute thalamic lesions. Follow-up neuropsychological assessment indicated a stable pattern of impaired retrograde and spared anterograde memory over 18 months and psychiatric assessments yielded no evidence of confabulation, malingering or other symptoms to suggest psychogenic amnesia. JG's profile indicates that the division of declarative memory into just two categories - episodic and semantic - is inadequate. Rather, his case adds to the growing body evidence to suggest that world knowledge pertaining to people and events is stored or accessed similarly to autobiographical information and differently from other types of more general factual knowledge. We hypothesize that the right mediodorsal thalamic nucleus and immediately surrounding regions comprise the central processing mechanism referred to by McClelland (Revue Neurologique, 150 (1994) 570) and Markowitsch (Brain Research Review, 21 (1995) 117) as responsible for inducing and co-ordinating the recall of these sorts of cortically stored memory engrams.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke.

PubMed

Carpenter, Randall S; Iwuchukwu, Ifeanyi; Hinkson, Cyrus L; Reitz, Sydney; Lee, Wonhee; Kukino, Ayaka; Zhang, An; Pike, Martin M; Ardelt, Agnieszka A

2016-05-15

Estrogens have previously been shown to protect the brain against acute ischemic insults, by potentially augmenting cerebrovascular function after ischemic stroke. The current study hypothesized that treatment with sustained release of high-dose 17β-estradiol (E2) at the time of reperfusion from middle cerebral artery occlusion (MCAO) in rats would attenuate reperfusion injury, augment post-stroke angiogenesis and cerebral blood flow, and attenuate lesion volume. Female Wistar rats underwent ovariectomy, followed two weeks later by transient, two-hour right MCAO (tMCAO) and treatment with E2 (n=13) or placebo (P; n=12) pellets starting at reperfusion. E2 treatment resulted in significantly smaller total lesion volume, smaller lesions within striatal and cortical brain regions, and less atrophy of the ipsilateral hemisphere after six weeks of recovery. E2-treated animals exhibited accelerated recovery of contralateral forelimb sensorimotor function in the cylinder test. Magnetic resonance imaging (MRI) showed that E2 treatment reduced the formation of lesion cysts, decreased lesion volume, and increased lesional cerebral blood flow (CBF). K(trans), a measure of vascular permeability, was increased in the lesions. This finding, which represents lesion neovascularization, was not altered by E2 treatment. Ischemic stroke-related angiogenesis and vessel formation was confirmed with immunolabeling of brain tissue and was not altered with E2 treatment. In summary, E2 treatment administered immediately following reperfusion significantly reduced lesion size, cyst formation, and brain atrophy while improving lesional CBF and accelerating recovery of functional deficits in a rat model of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

PubMed

Soman, S; Liu, Z; Kim, G; Nemec, U; Holdsworth, S J; Main, K; Lee, B; Kolakowsky-Hayner, S; Selim, M; Furst, A J; Massaband, P; Yesavage, J; Adamson, M M; Spincemallie, P; Moseley, M; Wang, Y

2018-04-01

Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology. Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident. Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Ichimiya, Yuko; Kaku, Noriyuki; Sakai, Yasunari; Yamashita, Fumiya; Matsuoka, Wakato; Muraoka, Mamoru; Akamine, Satoshi; Mizuguchi, Soichi; Torio, Michiko; Motomura, Yoshitomo; Hirata, Yuichiro; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Takada, Hidetoshi; Maehara, Yoshihiko; Ohga, Shouichi

2017-08-01

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury.

PubMed

Li, Lian; Chopp, Michael; Ding, Guang Liang; Qu, Chang Sheng; Li, Qing Jiang; Lu, Mei; Wang, Shiyang; Nejad-Davarani, Siamak P; Mahmood, Asim; Jiang, Quan

2012-11-01

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

ERIC Educational Resources Information Center

Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

2008-01-01

Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

Damage to ventral and dorsal language pathways in acute aphasia

PubMed Central

Hartwigsen, Gesa; Kellmeyer, Philipp; Glauche, Volkmar; Mader, Irina; Klöppel, Stefan; Suchan, Julia; Karnath, Hans-Otto; Weiller, Cornelius; Saur, Dorothee

2013-01-01

Converging evidence from neuroimaging studies and computational modelling suggests an organization of language in a dual dorsal–ventral brain network: a dorsal stream connects temporoparietal with frontal premotor regions through the superior longitudinal and arcuate fasciculus and integrates sensorimotor processing, e.g. in repetition of speech. A ventral stream connects temporal and prefrontal regions via the extreme capsule and mediates meaning, e.g. in auditory comprehension. The aim of our study was to test, in a large sample of 100 aphasic stroke patients, how well acute impairments of repetition and comprehension correlate with lesions of either the dorsal or ventral stream. We combined voxelwise lesion-behaviour mapping with the dorsal and ventral white matter fibre tracts determined by probabilistic fibre tracking in our previous study in healthy subjects. We found that repetition impairments were mainly associated with lesions located in the posterior temporoparietal region with a statistical lesion maximum in the periventricular white matter in projection of the dorsal superior longitudinal and arcuate fasciculus. In contrast, lesions associated with comprehension deficits were found more ventral-anterior in the temporoprefrontal region with a statistical lesion maximum between the insular cortex and the putamen in projection of the ventral extreme capsule. Individual lesion overlap with the dorsal fibre tract showed a significant negative correlation with repetition performance, whereas lesion overlap with the ventral fibre tract revealed a significant negative correlation with comprehension performance. To summarize, our results from patients with acute stroke lesions support the claim that language is organized along two segregated dorsal–ventral streams. Particularly, this is the first lesion study demonstrating that task performance on auditory comprehension measures requires an interaction between temporal and prefrontal brain regions via the

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging: earlier administration of chelating therapy can reduce the damage to the brain.

PubMed

Kozić, Duško B; Petrović, Igor; Svetel, Marina; Pekmezović, Tatjana; Ragaji, Aleksandar; Kostić, Vladimir S

2014-11-01

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson's disease during the long-term chelating therapy using magnetic resonance imaging and a possible significance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson's disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into: group A, where chelating therapy was initiated < 24 months from the first symptoms and group B, where the therapy started ≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a significant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions (P = 0.005 and P = 0.024, respectively). If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be expected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Structure changes of human brain gray matter neurons and astrocytes in acute local ischemic injury.

PubMed

Sergeeva, S P; Shishkina, L V; Litvitskiy, P F; Breslavich, I D; Vinogradov, E V

2016-01-01

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex. Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained. The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury. The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

Random motor generation in a finger tapping task: influence of spatial contingency and of cortical and subcortical hemispheric brain lesions

PubMed Central

Annoni, J.; Pegna, A.

1997-01-01

OBJECTIVE—To test the hypothesis that, during random motor generation, the spatial contingencies inherent to the task would induce additional preferences in normal subjects, shifting their performances farther from randomness. By contrast, perceptual or executive dysfunction could alter these task related biases in patients with brain damage.
METHODS—Two groups of patients, with right and left focal brain lesions, as well as 25 right handed subjects matched for age and handedness were asked to execute a random choice motor task—namely, to generate a random series of 180 button presses from a set of 10 keys placed vertically in front of them.
RESULTS—In the control group, as in the left brain lesion group, motor generation was subject to deviations from theoretical expected randomness, similar to those when numbers are generated mentally, as immediate repetitions (successive presses on the same key) are avoided. However, the distribution of button presses was also contingent on the topographic disposition of the keys: the central keys were chosen more often than those placed at extreme positions. Small distances were favoured, particularly with the left hand. These patterns were influenced by implicit strategies and task related contingencies.
 By contrast, right brain lesion patients with frontal involvement tended to show a more square distribution of key presses—that is, the number of key presses tended to be more equally distributed. The strategies were also altered by brain lesions: the number of immediate repetitions was more frequent when the lesion involved the right frontal areas yielding a random generation nearer to expected theoretical randomness. The frequency of adjacent key presses was increased by right anterior and left posterior cortical as well as by right subcortical lesions, but decreased by left subcortical lesions.
CONCLUSIONS—Depending on the side of the lesion and the degree of cortical-subcortical involvement, the

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

PubMed

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.

PubMed

de Guise, E; LeBlanc, J; Feyz, M; Lamoureux, J; Greffou, S

2017-01-01

The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting. Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma. Length of post-traumatic amnesia (PTA) was the best predictor of behavioural, memory and executive function variables within a month post TBI. The odds of being agitated, labile, irritable and disinhibited at one month post trauma were almost six times higher for those with PTA that lasted more than 7 days compared to those with a PTA of less than 24 hours. Also, the odds of having a higher mental manipulation score (less significant executive function impairment) were almost two times lower for those with frontal lesions, and three to six times lower for those with PTA of more than 24 hours. In addition, TBI severity, education and age were considered good predictors of some aspects of neuropsychological outcome. This model may help clinicians and administrators recognize the probable post-traumatic deficits as quickly as possible and to plan interventions as well as post-acute discharge orientation accordingly and early on.

Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

PubMed

Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

2014-04-01

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteolytic bone lesions, severe hypercalcemia without circulating blasts: unusual presentation of childhood acute lymphoblastic leukemia

PubMed Central

Bechir, Achour; Haifa, Regaieg; Atef, Ben Abdelkader; Emna, Bouslema; Asma, Achour; Nesrine, Ben Sayed; Yosra, Ben Youssef; Abdrrahim, Khelif

2017-01-01

Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood. We report a case of a 3 years old boy who presented with prolonged fever, nausea, vomiting and increasing lower limbs pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities. Her physical examination showed multiple cervical lymph nodes. In laboratory tests, he had severe hypercalcemia. Parathyroid hormone (PTH) was not elevated. Despite the absence of circulating blasts, bone marrow biopsy revealed B-precursor (ALL). Hypercalcemia was initially treated with intravenous isotonic sodium chloride solution and diuretics but the serum calcium level normalized only after the beginning of corticosteroids and chemotherapy. The child responded initially to chemotherapy and eventually relapsed and died of septic shock. Acute leukemia must be considered in differential diagnosis in patients with hypercalcemia. A detailed examination even when there no circulating blasts in their peripheral blood smear, and if in doubt bone marrow aspiration should must be taken into consideration. PMID:28690758

Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

PubMed

Folkerth, Rebecca D; Habbe, Donald M; Boyd, Theonia K; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J

2013-01-01

The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions

PubMed Central

Furusho, M; Roulois, A; Franklin, RJM; Bansal, R

2015-01-01

Remyelination is a potent regenerative process in demyelinating diseases, such as multiple sclerosis, the effective therapeutic promotion of which will fill an unmet clinical need. The development of pro-regenerative therapies requires the identification of key regulatory targets that are likely to be involved in the integration of multiple signaling mechanisms. Fibroblast growth factor (FGF) signaling system, which comprises multiple ligands and receptors, potentially provides one such target. Since the FGF/FGF receptor (FGFR) interactions are complex and regulate multiple diverse functions of oligodendrocyte lineage cells, it is difficult to predict their overall therapeutic potential in the regeneration of oligodendrocytes and myelin. Therefore, to assess the integrated effects of FGFR signaling on this process, we simultaneously inactivated both FGFR1 and FGFR2 in oligodendrocytes and their precursors using two Cre-driver mouse lines. Acute and chronic cuprizone-induced or lysolecithin-induced demyelination was established in Fgfr1/Fgfr2 double knockout mice (dKO). We found that in the acute cuprizone model, there was normal differentiation of oligodendrocytes and recovery of myelin in the corpus callosum of both control and dKO mice. Similarly, in the spinal cord, lysolecithin-induced demyelinated lesions regenerated similarly in the dKO and control mice. In contrast, in the chronic cuprizone model, fewer differentiated oligodendrocytes and less efficient myelin recovery were observed in the dKO compared to control mice. These data suggest that while cell-autonomous FGF signaling is redundant during recovery of acute demyelinated lesions, it facilitates regenerative processes in chronic demyelination. Thus, FGF-based therapies have potential value in stimulating oligodendrocyte and myelin regeneration in late-stage disease. PMID:25913734

Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro-Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice.

PubMed

Sebastiani, Anne; Granold, Matthias; Ditter, Anja; Sebastiani, Philipp; Gölz, Christina; Pöttker, Bruno; Luh, Clara; Schaible, Eva-Verena; Radyushkin, Konstantin; Timaru-Kast, Ralph; Werner, Christian; Schäfer, Michael K; Engelhard, Kristin; Moosmann, Bernd; Thal, Serge C

2016-02-01

The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. However, acute brain lesions, such as traumatic brain injury, reactivate developmental-like programs and increase p75 neurotrophin receptor expression, probably to foster reparative processes, which in turn could render the brain sensitive to propofol-mediated neurotoxicity. This study investigates the influence of delayed single-bolus propofol applications at the peak of p75 neurotrophin receptor expression after experimental traumatic brain injury in adult mice. Randomized laboratory animal study. University research laboratory. Adult C57BL/6N and nerve growth factor receptor-deficient mice. Sedation by IV propofol bolus application delayed after controlled cortical impact injury. Propofol sedation at 24 hours after traumatic brain injury increased lesion volume, enhanced calpain-induced αII-spectrin cleavage, and increased cell death in perilesional tissue. Thirty-day postinjury motor function determined by CatWalk (Noldus Information Technology, Wageningen, The Netherlands) gait analysis was significantly impaired in propofol-sedated animals. Propofol enhanced pro-brain-derived neurotrophic factor/brain-derived neurotrophic factor ratio, which aggravates p75 neurotrophin receptor-mediated cell death. Propofol toxicity was abolished both by pharmacologic inhibition of the cell death domain of the p75 neurotrophin receptor (TAT-Pep5) and in mice lacking the extracellular neurotrophin binding site of p75 neurotrophin receptor. This study provides first evidence that propofol sedation after acute brain lesions can have a deleterious impact and implicates a role for the pro-brain-derived neurotrophic factor-p75 neurotrophin receptor pathway. This observation is important as sedation

Evaluation of Disease Lesions in the Developing Canine MPS IIIA Brain.

PubMed

Winner, Leanne K; Marshall, Neil R; Jolly, Robert D; Trim, Paul J; Duplock, Stephen K; Snel, Marten F; Hemsley, Kim M

2018-06-20

Mucopolysaccharidosis IIIA (MPS IIIA) is an inherited neurodegenerative disease of childhood that results in early death. Post-mortem studies have been carried out on human MPS IIIA brain, but little is known about early disease development. Here, we utilised the Huntaway dog model of MPS IIIA to evaluate disease lesion development from 2 to 24 weeks of age. A significant elevation in primarily stored heparan sulphate was observed in all brain regions assessed in MPS IIIA pups ≤9.5 weeks of age. There was a significant elevation in secondarily stored ganglioside (GM3 36:1) in ≤9.5-week-old MPS IIIA pup cerebellum, and other brain regions also exhibited accumulation of this lipid with time. The number of neural stem cells and neuronal precursor cells was essentially unchanged in MPS IIIA dog brain (c.f. unaffected) over the time course assessed, a finding corroborated by neuron cell counts. We observed early neuroinflammatory changes in young MPS IIIA pup brain, with significantly increased numbers of activated microglia recorded in all but one brain region in MPS IIIA pups ≤9.5 weeks of age (c.f. age-matched unaffected pups). In conclusion, infant-paediatric-stage MPS IIIA canine brain exhibits substantial and progressive primary and secondary substrate accumulation, coupled with early and robust microgliosis. Whilst early initiation of treatment is likely to be required to maintain optimal neurological function, the brain's neurodevelopmental potential appears largely unaffected by the disease process; further investigations confirming this are warranted.

Cognitive correlates of white matter lesion load and brain atrophy

PubMed Central

Dong, Chuanhui; Nabizadeh, Nooshin; Caunca, Michelle; Cheung, Ying Kuen; Rundek, Tatjana; Elkind, Mitchell S.V.; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov

2015-01-01

Objective: We investigated white matter lesion load and global and regional brain volumes in relation to domain-specific cognitive performance in the stroke-free Northern Manhattan Study (NOMAS) population. Methods: We quantified white matter hyperintensity volume (WMHV), total cerebral volume (TCV), and total lateral ventricular (TLV) volume, as well as hippocampal and cortical gray matter (GM) lobar volumes in a subgroup. We used general linear models to examine MRI markers in relation to domain-specific cognitive performance, adjusting for key covariates. Results: MRI and cognitive data were available for 1,163 participants (mean age 70 ± 9 years; 60% women; 66% Hispanic, 17% black, 15% white). Across the entire sample, those with greater WMHV had worse processing speed. Those with larger TLV volume did worse on episodic memory, processing speed, and semantic memory tasks, and TCV did not explain domain-specific variability in cognitive performance independent of other measures. Age was an effect modifier, and stratified analysis showed that TCV and WMHV explained variability in some domains above age 70. Smaller hippocampal volume was associated with worse performance across domains, even after adjusting for APOE ε4 and vascular risk factors, whereas smaller frontal lobe volumes were only associated with worse executive function. Conclusions: In this racially/ethnically diverse, community-based sample, white matter lesion load was inversely associated with cognitive performance, independent of brain atrophy. Lateral ventricular, hippocampal, and lobar GM volumes explained domain-specific variability in cognitive performance. PMID:26156514

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

PubMed

Jiang, Xiao-Han; Wang, Si-Bo; Tian, Qian; Zhong, Chi; Zhang, Guan-Ling; Li, Ya-Jie; Lin, Pan; You, Yong; Guo, Rong; Cui, Ying-Hua; Xing, Ying-Qi

2018-02-14

Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. No. NCT02425696 ; registered on April 21, 2015.

Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus

PubMed Central

Sekiguchi, Kenji; Yasui, Naoko; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

2016-01-01

We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination. PMID:27803416

Imaging of Traumatic Brain Injury.

PubMed

Bodanapally, Uttam K; Sours, Chandler; Zhuo, Jiachen; Shanmuganathan, Kathirkamanathan

2015-07-01

Imaging plays an important role in the management of patients with traumatic brain injury (TBI). Computed tomography (CT) is the first-line imaging technique allowing rapid detection of primary structural brain lesions that require surgical intervention. CT also detects various deleterious secondary insults allowing early medical and surgical management. Serial imaging is critical to identifying secondary injuries. MR imaging is indicated in patients with acute TBI when CT fails to explain neurologic findings. However, MR imaging is superior in patients with subacute and chronic TBI and also predicts neurocognitive outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute amaurotic epilepsy caused by lead poisoning in non-human primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zook, B.C.; Sauer, R.M.; Garner, F.M.

1972-09-15

Lead poisoning was diagnosed in all of 14 simian primates that died of acute amaurotic epilepsy at the National Zoological Park. Two primates from the Antwerp Zoo included in the original description of acute amaurotic epilepsy were also retrospectively found to have lead poisoning. Diagnosis was based on history, clinical signs, histologic brain lesions, available source of lead, acid-fast intranuclear inclusion bodies in renal and hepatic cells, and excess lead in liver specimens. It was concluded that acute amaurotic epilepsy should be considered a clinical syndrome of lead intoxication.

Neuroanatomical substrates of action perception and understanding: an anatomic likelihood estimation meta-analysis of lesion-symptom mapping studies in brain injured patients

PubMed Central

Urgesi, Cosimo; Candidi, Matteo; Avenanti, Alessio

2014-01-01

Several neurophysiologic and neuroimaging studies suggested that motor and perceptual systems are tightly linked along a continuum rather than providing segregated mechanisms supporting different functions. Using correlational approaches, these studies demonstrated that action observation activates not only visual but also motor brain regions. On the other hand, brain stimulation and brain lesion evidence allows tackling the critical question of whether our action representations are necessary to perceive and understand others’ actions. In particular, recent neuropsychological studies have shown that patients with temporal, parietal, and frontal lesions exhibit a number of possible deficits in the visual perception and the understanding of others’ actions. The specific anatomical substrates of such neuropsychological deficits however, are still a matter of debate. Here we review the existing literature on this issue and perform an anatomic likelihood estimation meta-analysis of studies using lesion-symptom mapping methods on the causal relation between brain lesions and non-linguistic action perception and understanding deficits. The meta-analysis encompassed data from 361 patients tested in 11 studies and identified regions in the inferior frontal cortex, the inferior parietal cortex and the middle/superior temporal cortex, whose damage is consistently associated with poor performance in action perception and understanding tasks across studies. Interestingly, these areas correspond to the three nodes of the action observation network that are strongly activated in response to visual action perception in neuroimaging research and that have been targeted in previous brain stimulation studies. Thus, brain lesion mapping research provides converging causal evidence that premotor, parietal and temporal regions play a crucial role in action recognition and understanding. PMID:24910603

The need for improved brain lesion segmentation techniques for children with cerebral palsy: A review.

PubMed

Pagnozzi, Alex M; Gal, Yaniv; Boyd, Roslyn N; Fiori, Simona; Fripp, Jurgen; Rose, Stephen; Dowson, Nicholas

2015-12-01

Cerebral palsy (CP) describes a group of permanent disorders of posture and movement caused by disturbances in the developing brain. Accurate diagnosis and prognosis, in terms of motor type and severity, is difficult to obtain due to the heterogeneous appearance of brain injury and large anatomical distortions commonly observed in children with CP. There is a need to optimise treatment strategies for individual patients in order to lead to lifelong improvements in function and capabilities. Magnetic resonance imaging (MRI) is critical to non-invasively visualizing brain lesions, and is currently used to assist the diagnosis and qualitative classification in CP patients. Although such qualitative approaches under-utilise available data, the quantification of MRIs is not automated and therefore not widely performed in clinical assessment. Automated brain lesion segmentation techniques are necessary to provide valid and reproducible quantifications of injury. Such techniques have been used to study other neurological disorders, however the technical challenges unique to CP mean that existing algorithms require modification to be sufficiently reliable, and therefore have not been widely applied to MRIs of children with CP. In this paper, we present a review of a subset of available brain injury segmentation approaches that could be applied to CP, including the detection of cortical malformations, white and grey matter lesions and ventricular enlargement. Following a discussion of strengths and weaknesses, we suggest areas of future research in applying segmentation techniques to the MRI of children with CP. Specifically, we identify atlas-based priors to be ineffective in regions of substantial malformations, instead propose relying on adaptive, spatially consistent algorithms, with fast initialisation mechanisms to provide additional robustness to injury. We also identify several cortical shape parameters that could be used to identify cortical injury, and shape

Brain Lesions

MedlinePlus

... seen on a brain-imaging test, such as magnetic resonance imaging (MRI) or computerized tomography (CT). On ... A cohort study. PLOS One. 2013;8:e71467. Magnetic resonance imaging (MRI). National Multiple Sclerosis Society. http:// ...

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

PubMed

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H; Valcour, Victor

2012-01-01

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

Is the spatial distribution of brain lesions associated with closed-head injury predictive of subsequent development of attention-deficit/hyperactivity disorder? Analysis with brain-image database

NASA Technical Reports Server (NTRS)

Herskovits, E. H.; Megalooikonomou, V.; Davatzikos, C.; Chen, A.; Bryan, R. N.; Gerring, J. P.

1999-01-01

PURPOSE: To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. RESULTS: Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. CONCLUSION: Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data.

Severe Traumatic Brain Injury, Frontal Lesions, and Social Aspects of Language Use: A Study of French-Speaking Adults

ERIC Educational Resources Information Center

Dardier, Virginie; Bernicot, Josie; Delanoe, Anaig; Vanberten, Melanie; Fayada, Catherine; Chevignard, Mathilde; Delaye, Corinne; Laurent-Vannier, Anne; Dubois, Bruno

2011-01-01

The purpose of this study was to gain insight into the social (pragmatic) aspects of language use by French-speaking individuals with frontal lesions following a severe traumatic brain injury. Eleven participants with traumatic brain injury performed tasks in three areas of communication: production (interview situation), comprehension (direct…

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

PubMed

Rosenthal, M J; Smith, D; Yaguez, L; Giampietro, V; Kerr, D; Bullmore, E; Brammer, M; Williams, S C R; Amiel, S A

2007-07-01

Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.

Anatomo-clinical overlapping maps (AnaCOM): a new method to create anatomo-functional maps from neuropsychological tests and structural MRI scan of subjects with brain lesions

NASA Astrophysics Data System (ADS)

Kinkingnehun, Serge R. J.; du Boisgueheneuc, Foucaud; Golmard, Jean-Louis; Zhang, Sandy X.; Levy, Richard; Dubois, Bruno

2004-04-01

We have developed a new technique to analyze correlations between brain anatomy and its neurological functions. The technique is based on the anatomic MRI of patients with brain lesions who are administered neuropsychological tests. Brain lesions of the MRI scans are first manually segmented. The MRI volumes are then normalized to a reference map, using the segmented area as a mask. After normalization, the brain lesions of the MRI are segmented again in order to redefine the border of the lesions in the context of the normalized brain. Once the MRI is segmented, the patient's score on the neuropsychological test is assigned to each voxel in the lesioned area, while the rest of the voxels of the image are set to 0. Subsequently, the individual patient's MRI images are superimposed, and each voxel is reassigned the average score of the patients who have a lesion at that voxel. A threshold is applied to remove regions having less than three overlaps. This process leads to an anatomo-functional map that links brain areas to functional loss. Other maps can be created to aid in analyzing the functional maps, such as one that indicates the 95% confidence interval of the averaged scores for each area. This anatomo-clinical overlapping map (AnaCOM) method was used to obtain functional maps from patients with lesions in the superior frontal gyrus. By finding particular subregions more responsible for a particular deficit, this method can generate new hypotheses to be tested by conventional group methods.

SU-G-IeP1-07: Inaccuracy of Lesion Blood Flow Quantification Related to the Proton Density Reference Image in Arterial Spin Labeling MRI of Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jen, M; Johnson, J; Hou, P

Purpose: Cerebral blood flow quantification in arterial spin labeling (ASL) MRI requires an estimate of the equilibrium magnetization of blood, which is often obtained by a set of proton density (PD) reference image. Normally, a constant blood-brain partition coefficient is assumed across the brain. However, this assumption may not be valid for brain lesions. This study aimed to evaluate the impact of lesion-related PD variations on ASL quantification in patients with brain tumors. Methods: MR images for posttreatment evaluation of 42 patients with brain tumors were retrospectively analyzed. These images were acquired on a 3T MRI scanner, including T2-weighted FLAIR,more » 3D pseudo-continuous ASL and post-contrast T1-weighted images. Anatomical images were coregistered with ASL images using the SPM software. Regions of interest (ROIs) of the enhancing and FLAIR lesions were manually drawn on the coregistered images. ROIs of the contralateral normal appearing tissues were also determined, with the consideration of approximating coil sensitivity patterns in lesion ROIs. Relative lesion blood flow (lesion/contralateral tissue) was calculated from both the CBF map (dependent on the PD) and the ΔM map for comparison. Results: The signal intensities in both enhancing and FLAIR lesions were significantly different than contralateral tissues on the PD reference image (p<0.001). The percent signal difference ranged from −15.9 to 19.2%, with a mean of 5.4% for the enhancing lesion, and from −2.8 to 22.9% with a mean of 10.1% for the FLAIR lesion. The high/low lesion-related PD signal resulted in inversely proportional under-/over-estimation of blood flow in both enhancing and FLAIR lesions. Conclusion: Significant signal differences were found between lesions and contralateral tissues in the PD reference image, which introduced errors in blood flow quantification in ASL. The error can be up to 20% in individual patients with an average of 5- 10% for the group of

Monophasic demyelination reduces brain growth in children

PubMed Central

Weier, Katrin; Longoni, Giulia; Fonov, Vladimir S.; Bar-Or, Amit; Marrie, Ruth Ann; Yeh, E. Ann; Narayanan, Sridar; Arnold, Douglas L.; Verhey, Leonard H.; Banwell, Brenda; Collins, D. Louis

2017-01-01

Objective: To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time. Methods: We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specific z scores, and used mixed-effect models to investigate their relationship with time from demyelinating illness. Results: Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories. Conclusions: Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process. PMID:28381515

Monophasic demyelination reduces brain growth in children.

PubMed

Aubert-Broche, Bérengère; Weier, Katrin; Longoni, Giulia; Fonov, Vladimir S; Bar-Or, Amit; Marrie, Ruth Ann; Yeh, E Ann; Narayanan, Sridar; Arnold, Douglas L; Verhey, Leonard H; Banwell, Brenda; Collins, D Louis

2017-05-02

To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time. We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specific z scores, and used mixed-effect models to investigate their relationship with time from demyelinating illness. Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories. Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process. © 2017 American Academy of Neurology.

Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

NASA Astrophysics Data System (ADS)

Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

2015-03-01

Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

[Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats].

PubMed

Li, F; Zhang, Y; Ma, S L

2016-12-01

To observe the changes of expression of α-synuclein （α-syn） and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t -test were also performed. The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism. Copyright© by the Editorial Department of Journal of Forensic Medicine

Astrocytic TYMP and VEGFA drive blood–brain barrier opening in inflammatory central nervous system lesions

PubMed Central

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M.; Mariani, John N.; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S.

2015-01-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood–brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood–brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood–brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood–brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood–brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood–brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP

Delayed Methylene Blue Improves Lesion Volume, Multi-Parametric Quantitative Magnetic Resonance Imaging Measurements, and Behavioral Outcome after Traumatic Brain Injury

PubMed Central

Long, Justin Alexander; Boggs, Robert Cole; Manga, Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q.

2016-01-01

Abstract Traumatic brain injury (TBI) remains a primary cause of death and disability in both civilian and military populations worldwide. There is a critical need for the development of neuroprotective agents that can circumvent damage and provide functional recovery. We previously showed that methylene blue (MB), a U.S. Food and Drug Administration–grandfathered drug with energy-enhancing and antioxidant properties, given 1 and 3 h post-TBI, had neuroprotective effects in rats. This study aimed to further investigate the neuroprotection of delayed MB treatment (24 h postinjury) post-TBI as measured by lesion volume and functional outcomes. Comparisons were made with vehicle and acute MB treatment. Multi-modal magnetic resonance imaging and behavioral studies were performed at 1 and 3 h and 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. We found that delaying MB treatment 24 h postinjury still minimized lesion volume and functional deficits, compared to vehicle-treated animals. The data further support the potential for MB as a neuroprotective treatment, especially when medical teatment is not readily available. MB has an excellent safety profile and is clinically approved for other indications. MB clinical trials on TBI can thus be readily explored. PMID:25961471

Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, David J.; Li Yong; Chao, Moses V.

2010-05-15

Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but maymore » incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.« less

detecting multiple sclerosis lesions with a fully bioinspired visual attention model

NASA Astrophysics Data System (ADS)

Villalon-Reina, Julio; Gutierrez-Carvajal, Ricardo; Thompson, Paul M.; Romero-Castro, Eduardo

2013-11-01

The detection, segmentation and quantification of multiple sclerosis (MS) lesions on magnetic resonance images (MRI) has been a very active field for the last two decades because of the urge to correlate these measures with the effectiveness of pharmacological treatment. A myriad of methods has been developed and most of these are non specific for the type of lesions and segment the lesions in their acute and chronic phases together. On the other hand, radiologists are able to distinguish between several stages of the disease on different types of MRI images. The main motivation of the work presented here is to computationally emulate the visual perception of the radiologist by using modeling principles of the neuronal centers along the visual system. By using this approach we are able to detect the lesions in the majority of the images in our population sample. This type of approach also allows us to study and improve the analysis of brain networks by introducing a priori information.

Real-Time Ultrasound-Guided Catheter Navigation for Approaching Deep-Seated Brain Lesions: Role of Intraoperative Neurosonography with and without Fusion with Magnetic Resonance Imaging.

PubMed

Manjila, Sunil; Karhade, Aditya; Phi, Ji Hoon; Scott, R Michael; Smith, Edward R

2017-01-01

Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion. With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique. Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm). Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions. © 2017 S. Karger AG, Basel.

T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

PubMed Central

Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

2014-01-01

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection

PubMed Central

IKEGAMI, HISASHI; TAKEDA, MAKIO; DOI, KUNIO

1997-01-01

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 × 104 plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system. PMID:9203984

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

PubMed Central

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

2012-01-01

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

Pediatric Awake Craniotomy for Brain Lesions.

PubMed

Akay, Ali; Rükşen, Mete; Çetin, H Yurday; Seval, H Özer; İşlekel, Sertaç

2016-01-01

Awake craniotomy is a special method to prevent motor deficits during the resection of lesions that are located in, or close to, functional areas. Although it is more commonly performed in adult patients, reports of pediatric cases undergoing awake craniotomy are limited in the literature. In our clinic, where we frequently use awake craniotomy in adult patients, we performed this method in 2 selected pediatric cases for lesion surgery. At an early age, these 2 cases diagnosed with epilepsy presented cerebral lesions, but since the lesions enclosed functional areas, surgical resection was not regarded as a treatment option at this time. In these 2 pediatric cases, we successfully completed lesion surgery with awake craniotomy. The method and the techniques employed during surgery are presented concomitant with other reports in the literature. © 2016 S. Karger AG, Basel.

Marking multi-channel silicon-substrate electrode recording sites using radiofrequency lesions.

PubMed

Brozoski, Thomas J; Caspary, Donald M; Bauer, Carol A

2006-01-30

Silicon-substrate multi-channel electrodes (multiprobes) have proven useful in a variety of electrophysiological tasks. When using multiprobes it is often useful to identify the site of each channel, e.g., when recording single-unit activity from a heterogeneous structure. Lesion marking of electrode sites has been used for many years. Electrolytic, or direct current (DC) lesions, have been used successfully to mark multiprobe sites in rat hippocampus [Townsend G, Peloquin P, Kloosterman F, Hetke JF, Leung LS. Recording and marking with silicon multichannel electrodes. Brain Res Brain Res Protoc 2002;9:122-9]. The present method used radio-frequency (rf) lesions to distinctly mark each of the 16 recording sites of 16-channel linear array multiprobes, in chinchilla inferior colliculus. A commercial radio-frequency lesioner was used as the current source, in conjunction with custom connectors adapted to the multiprobe configuration. In vitro bench testing was used to establish current-voltage-time parameters, as well as to check multiprobe integrity and radio-frequency performance. In in vivo application, visualization of individual-channel multiprobe recording sites was clear in 21 out of 33 sets of collicular serial-sections (i.e., probe tracks) obtained from acute experimental subjects, i.e., maximum post-lesion survival time of 2h. Advantages of the rf method include well-documented methods of in vitro calibration as well as low impact on probe integrity. The rf method of marking individual-channel sites should be useful in a variety of applications.

Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis.

PubMed

Singh, Shailender; Dallenga, Tobias; Winkler, Anne; Roemer, Shanu; Maruschak, Brigitte; Siebert, Heike; Brück, Wolfgang; Stadelmann, Christine

2017-03-17

Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions. Furthermore, we studied the effects of Wallerian degeneration blockage on clinical severity, inflammatory pathology, acute axonal damage, and long-term axonal loss in experimental autoimmune encephalomyelitis using Wallerian degeneration slow (Wld S ) mutant mice. The highest numbers of axons undergoing Wallerian degeneration were found in the perilesional white matter of multiple sclerosis patients early in the disease course and with actively demyelinating lesions. Furthermore, Wallerian degeneration was more abundant in patients harboring chronic active as compared to chronic inactive lesions. No co-localization of neuropeptide Y-Y1 receptor, a bona fide immunohistochemical marker of Wallerian degeneration, with amyloid precursor protein, frequently used as an indicator of acute axonal transport disturbance, was observed in human and mouse tissue, indicating distinct axon-degenerative processes. Experimentally, a delay of Wallerian degeneration, as observed in Wld S mice, did not result in a reduction of clinical disability or acute axonal damage in experimental autoimmune encephalomyelitis, further supporting that acute axonal damage as reflected by axonal transport disturbances does not share common molecular mechanisms with Wallerian degeneration. Furthermore, delaying Wallerian degeneration

Total target volume is a better predictor of whole brain dose from gamma stereotactic radiosurgery than the number, shape, or location of the lesions

PubMed Central

Narayanasamy, Ganesh; Smith, Adam; Van Meter, Emily; McGarry, Ronald; Molloy, Janelle A.

2013-01-01

Purpose: To assess the hypothesis that the volume of whole brain that receives a certain dose level is primarily dependent on the treated volume rather than on the number, shape, or location of the lesions. This would help a physician validate the suitability of GammaKnife® based stereotactic radiosurgery (GKSR) prior to treatment. Methods: Simulation studies were performed to establish the hypothesis for both oblong and spherical shaped lesions of various numbers and sizes. Forty patients who underwent GKSR [mean age of 54 years (range 7–80), mean number of lesions of 2.5 (range 1–6), and mean lesion volume of 4.4 cm3 (range 0.02–22.2 cm3)] were also studied retrospectively. Following recommendations of QUANTEC, the volume of brain irradiated by the 12 Gy (VB12) isodose line was measured and a power-law based relation is proposed here for estimating VB12 from the known tumor volume and the prescription dose. Results: In the simulation study on oblong, spherical, and multiple lesions, the volume of brain irradiated by 50%, 10%, and 1% of maximum dose was found to have linear, linear, and exponentially increasing dependence on the volume of the treated region, respectively. In the retrospective study on 40 GKSR patients, a similar relationship was found to predict the brain dose with a Spearman correlation coefficient >0.9. In both the studies, the volume of brain irradiated by a certain dose level does not have a statistically significant relationship (p ≥ 0.05) with the number, shape, or position of the lesions. The measured VB12 agrees with calculation to within 1.7%. Conclusions: The results from the simulation and the retrospective clinical studies indicate that the volume of whole brain that receives a certain percentage of the maximum dose is primarily dependent on the treated volume and less on the number, shape, and location of the lesions. PMID:24007147

Intraoperative Squash and Touch Preparation Cytology of Brain Lesions Stained with H+E and Diff-Quik™: A 20-Year Retrospective Analysis and Comparative Literature Review.

PubMed

Hamasaki, Makoto; Chang, Karen H F; Nabeshima, Kazuki; Tauchi-Nishi, Pamela S

2018-01-01

Squash preparation (SP) is a rapid technique for the intraoperative assessment of brain lesions. Only a few studies have employed touch preparation (TP) cytology and Diff-QuikTM (DQ) staining in conjunction with SP. Our study aimed to assess the diagnostic efficacy of SP of brain lesions at our institution, ascertain the additional effect of TP and DQ staining, examine factors affecting the sensitivity and specificity of our methods, and compare our findings with those of previous investigations. Our database was searched for all SP/TP of brain lesions examined from January 1996 to December 2016. During this 20-year study period, our search revealed 400 brain lesions diagnosed by SP/TP cytology. There were 338 (84.5%) neoplasms and 62 (15.5%) nonneoplastic lesions. The most common neoplasms were glioblastoma multiforme (24.6%), metastatic cancer (18.3%), meningioma (16.9%), astrocytoma (11.5%), lymphoma (8.3%), oligoastrocytoma (3.3%), and pituitary adenoma (3.3%). There was discordance between the SP/TP and histological diagnoses in 19/338 (5.6%) cases, i.e., 12 misclassifications of tumor subtype and 7 sampling errors. No false-positive cases were detected. Brain SP/TP stained with H+E/DQ demonstrated high sensitivity (97.9%), specificity (100%), and overall diagnostic accuracy (95.3%). The combined methods, in particular, aided in the diagnosis of brain tumors prone to smearing artifacts and certain metastatic malignancies. © 2017 S. Karger AG, Basel.

Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

PubMed

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

2015-06-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

PubMed Central

Shear, Deborah A.; Deng-Bryant, Ying; Leung, Lai Yee; Wei, Guo; Chen, Zhiyong; Tortella, Frank C.

2016-01-01

Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (≤24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7–21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13–17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple

Intestinal lesions in dogs with acute hemorrhagic diarrhea syndrome associated with netF-positive Clostridium perfringens type A.

PubMed

Leipig-Rudolph, Miriam; Busch, Kathrin; Prescott, John F; Mehdizadeh Gohari, Iman; Leutenegger, Christian M; Hermanns, Walter; Wolf, Georg; Hartmann, Katrin; Verspohl, Jutta; Unterer, Stefan

2018-04-01

Acute hemorrhagic diarrhea syndrome (AHDS), formerly named canine hemorrhagic gastroenteritis, is one of the most common causes of acute hemorrhagic diarrhea in dogs, and is characterized by acute onset of diarrhea, vomiting, and hemoconcentration. To date, histologic examinations have been limited to postmortem specimens of only a few dogs with AHDS. Thus, the aim of our study was to describe in detail the distribution, character, and grade of microscopic lesions, and to investigate the etiology of AHDS. Our study comprised 10 dogs with AHDS and 9 control dogs of various breeds, age, and sex. Endoscopic biopsies of the gastrointestinal tract were taken and examined histologically (H&E, Giemsa), immunohistochemically ( Clostridium spp., parvovirus), and bacteriologically. The main findings were acute necrotizing and neutrophilic enterocolitis (9 of 10) with histologic detection of clostridia-like, gram-positive bacteria on the necrotic mucosal surface (9 of 10). Clostridium perfringens isolated from the duodenum was identified as type A (5 of 5) by multiplex PCR (5 of 5). In addition, each of the 5 genotyped isolates encoded the pore-forming toxin netF. Clostridium spp. (not C. perfringens) were cultured from duodenal biopsies in 2 of 9 control dogs. These findings suggest that the pore-forming netF toxin is responsible for the necrotizing lesions in the intestines of a significant proportion of dogs with AHDS. Given that the stomach was not involved in the process, the term "acute hemorrhagic diarrhea syndrome" seems more appropriate than the frequently used term "hemorrhagic gastroenteritis."

Machine learning algorithm for automatic detection of CT-identifiable hyperdense lesions associated with traumatic brain injury

NASA Astrophysics Data System (ADS)

Keshavamurthy, Krishna N.; Leary, Owen P.; Merck, Lisa H.; Kimia, Benjamin; Collins, Scott; Wright, David W.; Allen, Jason W.; Brock, Jeffrey F.; Merck, Derek

2017-03-01

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. Time to treatment is often related to patient outcome. Access to cerebral imaging data in a timely manner is a vital component of patient care. Current methods of detecting and quantifying intracranial pathology can be time-consuming and require careful review of 2D/3D patient images by a radiologist. Additional time is needed for image protocoling, acquisition, and processing. These steps often occur in series, adding more time to the process and potentially delaying time-dependent management decisions for patients with traumatic brain injury. Our team adapted machine learning and computer vision methods to develop a technique that rapidly and automatically detects CT-identifiable lesions. Specifically, we use scale invariant feature transform (SIFT)1 and deep convolutional neural networks (CNN)2 to identify important image features that can distinguish TBI lesions from background data. Our learning algorithm is a linear support vector machine (SVM)3. Further, we also employ tools from topological data analysis (TDA) for gleaning insights into the correlation patterns between healthy and pathological data. The technique was validated using 409 CT scans of the brain, acquired via the Progesterone for the Treatment of Traumatic Brain Injury phase III clinical trial (ProTECT_III) which studied patients with moderate to severe TBI4. CT data were annotated by a central radiologist and included patients with positive and negative scans. Additionally, the largest lesion on each positive scan was manually segmented. We reserved 80% of the data for training the SVM and used the remaining 20% for testing. Preliminary results are promising with 92.55% prediction accuracy (sensitivity = 91.15%, specificity = 93.45%), indicating the potential usefulness of this technique in clinical scenarios.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

PubMed

Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

PubMed Central

Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

CT Perfusion in Acute Stroke: "Black Holes" on Time-to-Peak Image Maps Indicate Unsalvageable Brain.

PubMed

Meagher, Ruairi; Shankar, Jai Jai Shiva

2016-11-01

CT perfusion is becoming important in acute stroke imaging to determine optimal patient-management strategies. The purpose of this study was to examine the predictive value of time-to-peak image maps and, specifically, a phenomenon coined a "black hole" for assessing infarcted brain tissue at the time of scan. Acute stroke patients were screened for the presence of black holes and their follow-up imaging (noncontrast CT or MR) was reviewed to assess for infarcted brain tissue. Of the 23 patients with signs of acute ischemia on CT perfusion, all had black holes. The black holes corresponded with areas of infarcted brain on follow-up imaging (specificity 100%). Black holes demonstrated significantly lower cerebral blood volumes (P < .001) and cerebral blood flow (P < .001) compared to immediately adjacent tissue. Black holes on time-to-peak image maps represent areas of unsalvageable brain. Copyright © 2016 by the American Society of Neuroimaging.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights

Surgical management of brain-stem cavernous malformations: report of 137 cases.

PubMed

Wang, Chung-cheng; Liu, Ali; Zhang, Jun-ting; Sun, Bo; Zhao, Yuan-li

2003-06-01

With the improvement in neuroimaging and microsurgical techniques, brain stem cavernous malformations are no longer considered inoperable. Surgical indications for brainstem cavernoma are evolving, with better understanding of its natural history and decreasing surgical complications. During 1986 through 1998, a series of 137 patients (4 patients each with two brain stem lesions, total number of lesions, 141) with brain stem cavernous malformations were treated microsurgically at Beijing Neurosurgery Institute. The age distribution, lesion location, and clinical presentations were analyzed. The bleeding rate, surgical indications and microsurgical techniques were also discussed. In our series, 92 of 137 cases (67.2%) suffered more than one hemorrhage. Female patients had a higher risk of recurrent hemorrhage than that of male patients. Unlike cavernomas malformations from other locations, repeated hemorrhages from brain stem malformations are much more common and usually lead to new neurologic deficits. Among all 137 surgically treated patients, there was no operative mortality. Ninety-nine patients (72.3%) either improved or remained clinically stable postoperatively. The size of the cavernoma/hematoma does not necessarily correlate with the surgical result. While the acute hematoma can facilitate the surgical dissection, longer clinical history with multiple hemorrhages often makes total surgical resection difficult, partially because of the firmer capsule that may not shrink or collapse after hematoma is released. Pathologically those capsules were associated with more hyaline degeneration, fibrous proliferation and even calcifications. During the follow-up period between 0.5 to 11 years in 129 cases, 115 patients (89.2%) have been working, studying, or doing house work. Three patients (2.3%) suffered recurrent hemorrhages. Surgical indications of brain stem cavernoma include (1) progressive neurologic deficits; (2) overt acute or subacute hemorrhage on MRI

Brief report: Preliminary study on evaluation of spasticity in patients with brain lesions using mechanomyography.

PubMed

Jun, Sang Woo; Yong, Suk Joong; Jo, Min; Kim, Young Ho; Kim, Sung Hoon

2018-05-01

Electromyography and the modified Ashworth scale (MAS) are among the most effective methods for evaluating spasticity; however, these are often inappropriate for clinical use, owing to the complicated procedure and subjective evaluation outcomes. A passive stretch reflex test was performed on 10 subjects with brain lesions. Furthermore, mechanomyography and electromyography were conducted on the vastus lateralis muscle (agonist) and semitendinosus muscle (antagonist) of the subjects with brain lesions. A new equation to define the normalized hull area; that is, the mechanomyography (MMG) ratio, was applied to quantify the triaxial motion of the agonist muscle versus antagonist muscles, reflecting the electromyographic firing point of the spastic muscle. The MMG ratio was proposed, which statistically distinguishes the spastic and normal muscles (p = 0.01) and exhibits a concordance with the conventional mean MAS (r = 0.69, p = 0.01). Patients suspected to have spasticity of 0 to 1+ grade can be quantitatively evaluated using the normalized hull area ratio, which can be used as an additional clinical indicator for spasticity evaluation. The study was conducted in conformity with the Helsinki declaration principles and performed in the Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); 2010; KCT0002385; A new approach of spasticity measurement using mechanomyography in patients with brain lesions: A randomized pilot study for a parallel randomized controlled trial; October 8, 2015 [Cited on July 21, 2017]; [1 screen]. Available from: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7805<ype=&rtype=. Copyright © 2018. Published by Elsevier Ltd.

Relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Will, B.E.; Rosenzweig, M.R.; Bennett, E.L.

1977-01-01

Enriched postlesion experience aided in overcoming effects of simultaneous bilateral cerebral lesions made at 30 days of age in one experiment with inbred Fischer rats and in a second experiment with the Berkeley S/sub 1/ strain. The lesions were directed to the occipital cortex, but in most cases there was also some impairment of the hippocampus. For 60 days after operations, half of the rats lived in small individual cages and half lived in groups in large enriched-environment cages. They were then pretrained and tested on the standard 12 Hebb-Williams problems. Daily injections of methamphetamine (vs. saline) during the periodmore » of differential experience in the first experiment produced no effect on the behavioral scores. The second experiment included groups that received only 2 hr/day of enriched experience, and they benefited as much as groups that remained in the enriched environment 24 hr/day. The results of both experiments demonstrated significant beneficial effects of environment when bilateral lesions were made at a later age and when the periods of enriched experience were shorter than had previously been tested. Two additional experiments revealed significant effects of both lesions and environment on weight and RNA/DNA of brain regions.« less

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

PubMed

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

PubMed

Rosen, Allyson C; Soman, Salil; Bhat, Jyoti; Laird, Angela R; Stephens, Jeffrey; Eickhoff, Simon B; Fox, P Mickle; Long, Becky; Dinishak, David; Ortega, Mario; Lane, Barton; Wintermark, Max; Hitchner, Elizabeth; Zhou, Wei

2018-01-01

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences.

PubMed

Moen, Kent G; Brezova, Veronika; Skandsen, Toril; Håberg, Asta K; Folvik, Mari; Vik, Anne

2014-09-01

The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical

Blood Aggravates Histological and Functional Damage after Acute Subdural Hematoma in Rats.

PubMed

Jussen, Daniel; Krenzlin, Harald; Papaioannou, Chrysostomos; Ens, Swetlana; Kempski, Oliver; Alessandri, Beat

2017-02-15

Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. In a histological study, we investigated the effects on acute ICP, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), tissue oxygen changes, and brain damage at 2, 24, and 96 h post-infusion. Inflammatory reaction was analyzed by immuno-staining for microglia (ionized calcium binding adaptor molecule 1 [Iba1]) and activated astrocytes (glial fibrillary acidic protein [GFAP]). Besides acute ICP and CBF changes, we investigated the development of behavior (neuroscore and beamwalk test) for up to 4 days after injury in a behavioral study. Despite comparably increased ICP, there was a more pronounced lesion growth in the blood infusion group during the first 96 h. Further, there was an increased peri-lesional immunoreactive area of Iba1 and GFAP 96 h post-infusion, primarily in the blood infusion group, whereas hippocampal damage was comparable in both infusion groups. In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.

Using the Physical Examination to Diagnose Patients with Acute Dizziness and Vertigo.

PubMed

Edlow, Jonathan A; Newman-Toker, David

2016-04-01

Emergency department (ED) patients who present with acute dizziness or vertigo can be challenging to diagnose. Roughly half have general medical disorders that are usually apparent from the context, associated symptoms, or initial laboratory tests. The rest include a mix of common inner ear disorders and uncommon neurologic ones, particularly vertebrobasilar strokes or posterior fossa mass lesions. In these latter cases, misdiagnosis can lead to serious adverse consequences for patients. Our aim was to assist emergency physicians to use the physical examination effectively to make a specific diagnosis in patients with acute dizziness or vertigo. Recent evidence indicates that the physical examination can help physicians accurately discriminate between benign inner ear conditions and dangerous central ones, enabling correct management of peripheral vestibular disease and avoiding dangerous misdiagnoses of central ones. Patients with the acute vestibular syndrome mostly have vestibular neuritis, but some have stroke. Data suggest that focused eye movement examinations, at least when performed by specialists, are more sensitive for detecting early stroke than brain imaging, including diffusion-weighted magnetic resonance imaging. Patients with the triggered episodic vestibular syndrome mostly have benign paroxysmal positional vertigo (BPPV), but some have posterior fossa mass lesions. Specific positional tests to provoke nystagmus can confirm a BPPV diagnosis at the bedside, enabling immediate curative therapy, or indicate the need for imaging. Emergency physicians can effectively use the physical examination to make a specific diagnosis in patients with acute dizziness or vertigo. They must understand the limitations of brain imaging. This may reduce misdiagnosis of serious central causes of dizziness, including posterior circulation stroke and posterior fossa mass lesions, and improve resource utilization. Copyright © 2016 Elsevier Inc. All rights reserved.

Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Ljubanović, D; Separović, J; Gjurasin, M; Bratulić, M; Artuković, B; Jelovac, N; Buljat, G

1996-07-01

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 microg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutory effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.

Relationship between somatosensory deficit and brain somatosensory system after early brain lesion: A morphometric study.

PubMed

Perivier, Maximilien; Delion, Matthieu; Chinier, Eva; Loustau, Sebastien; Nguyen, Sylvie; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickael

2016-05-01

Cerebral Palsy (CP) is a group of permanent motor disorders due to non-progressive damage to the developing brain. Poor tactile discrimination is common in children with unilateral CP. Previous findings suggest the crucial role of structural integrity of the primary (S1) and secondary (S2) somatosensory areas located in the ipsilesional hemisphere for somatosensory function processing. However, no focus on the relationship between structural characteristics of ipsilesional S1 and S2 and tactile discrimination function in paretic hands has been proposed. Using structural MRI and a two-point discrimination assessment (2 PD), we explore this potential link in a group of 21 children (mean age 13 years and 7 months) with unilateral CP secondary to a periventricular white matter injury (PWMI) or middle cerebral artery infarct (MCA). For our whole sample there was a significant negative correlation between the 2 PD and the gray matter volume in the ipsilesional S2 (rho = -0.50 95% confidence interval [-0.76, -0.08], one-tailed p-value = 0.0109) and in the ipsilesional S1 (rho = -0.57, 95% confidence interval [-0.81, -0.19], one-tailed p-value = 0.0032). When studying these relationships with regard to the lesion types, we found these correlations were non-significant in the patients with PWMI but stronger in patients with MCA. According to our results, the degree of sensory impairment is related to the spared gray matter volume in ipsilesional S1 and S2 and is marked after an MCA stroke. Our work contributes to a better understanding of why some patients with CP have variable somatosensory deficit following an early brain lesion. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Characterizing Signals Within Lesions and Mapping Brain Network Connectivity After Traumatic Axonal Injury: A 7 Tesla Resting-State FMRI Study.

PubMed

Lee, Seul; Polimeni, Jonathan R; Price, Collin M; Edlow, Brian L; McNab, Jennifer A

2018-06-01

Resting-state functional magnetic resonance imaging (RS-FMRI) has been widely used to map brain functional connectivity, but it is unclear how to probe connectivity within and around lesions. In this study, we characterize RS-FMRI signal time course properties and evaluate different seed placements within and around hemorrhagic traumatic axonal injury (hTAI) lesions. RS-FMRI was performed on a 7 Tesla scanner in a patient who recovered consciousness after traumatic coma and in three healthy controls. Eleven lesions in the patient were characterized in terms of (1) temporal signal-to-noise ratio (tSNR); (2) physiological noise, through comparison of noise regressors derived from the white matter (WM), cerebrospinal fluid (CSF), and gray matter (GM); and (3) seed-based functional connectivity. Temporal SNR at the center of the lesions was 38.3% and 74.1% lower compared with the same region in the contralesional hemisphere of the patient and in the ipsilesional hemispheres of the controls, respectively. Within the lesions, WM noise was more prominent than CSF and GM noise. Lesional seeds did not produce discernable networks, but seeds in the contralesional hemisphere revealed networks whose nodes appeared to be shifted or obscured due to overlapping or nearby lesions. Single-voxel seed analysis demonstrated that placing a seed within a lesion's periphery was necessary to identify networks associated with the lesion region. These findings provide evidence of resting-state network changes in the human brain after recovery from traumatic coma. Furthermore, we show that seed placement within a lesion's periphery or in the contralesional hemisphere may be necessary for network identification in patients with hTAI.

Acute dimethyl sulfoxide therapy in brain edema. Part 3: effect of a 3-hour infusion.

PubMed

Del Bigio, M; James, H E; Camp, P E; Werner, R; Marshall, L F; Tung, H

1982-01-01

Albino rabbits with experimental brain edema produced by a combined cryogenic left hemisphere lesion and metabolic 6-aminonicotinamide lesion were administered a 3-hour intravenous infusion of dimethyl sulfoxide (DMSO). Simultaneous recording of intracranial pressure (ICP), systolic arterial pressure (SAP), and central venous pressure (CVP) and electroencephalography were performed while the animals were being ventilated mechanically to produce a constant Pa CO2 value (38-42 torr). At the end of the infusion, the brain water and electrolyte contents were measured. There was a persistent and progressive reduction of ICP during the infusion, the nadir occurring at 3 hours (p less than 0.005 from zero time), with no change in SAP or CVP. There was a reduction of brain water in both hemispheres when compared to untreated controls, but this was significant for the right hemisphere only (p less than 0.005). There was a significant reduction of the brain sodium content for both hemispheres, but no significant change occurred in brain potassium content. The DMSO infusion was effective not only in reducing ICP, but also in sustaining this reduction for 3 hours.

Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

PubMed

Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

2017-10-01

Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Quantitative phase and texture angularity analysis of brain white matter lesions in multiple sclerosis

NASA Astrophysics Data System (ADS)

Baxandall, Shalese; Sharma, Shrushrita; Zhai, Peng; Pridham, Glen; Zhang, Yunyan

2018-03-01

Structural changes to nerve fiber tracts are extremely common in neurological diseases such as multiple sclerosis (MS). Accurate quantification is vital. However, while nerve fiber damage is often seen as multi-focal lesions in magnetic resonance imaging (MRI), measurement through visual perception is limited. Our goal was to characterize the texture pattern of the lesions in MRI and determine how texture orientation metrics relate to lesion structure using two new methods: phase congruency and multi-resolution spatial-frequency analysis. The former aims to optimize the detection of the `edges and corners' of a structure, and the latter evaluates both the radial and angular distributions of image texture associated with the various forming scales of a structure. The radial texture spectra were previously confirmed to measure the severity of nerve fiber damage, and were thus included for validation. All measures were also done in the control brain white matter for comparison. Using clinical images of MS patients, we found that both phase congruency and weighted mean phase detected invisible lesion patterns and were significantly greater in lesions, suggesting higher structure complexity, than the control tissue. Similarly, multi-angular spatial-frequency analysis detected much higher texture across the whole frequency spectrum in lesions than the control areas. Such angular complexity was consistent with findings from radial texture. Analysis of the phase and texture alignment may prove to be a useful new approach for assessing invisible changes in lesions using clinical MRI and thereby lead to improved management of patients with MS and similar disorders.

The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

PubMed

Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas

2014-07-01

The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

There is less MRI brain lesions and no characteristic MRI Brain findings in IIDDs patients with positive AQP4 serology among Malaysians.

PubMed

Abdullah, Suhailah; Fadzli, Farhana; Ramli, Norlisah; Tan, Chong Tin

2017-02-01

The recently introduced International Consensus diagnostic criteria for diagnosis of neuromyelitis spectrum disorder include patients who are seronegative for AQP4 antibody. The criteria are dependent on typical MRI changes in the spinal cord, optic nerve and brain. This study aims to determine whether there are significant differences in the MRI brain images between AQP4 positive and negative patients with IIDDs. MRI brain of patients with a diagnosis of IIDDs presented to the Hospital from 2010 to 2015 was analysed. The MRI was assessed by 2 radiologists blinded to the AQP4 status, on features said to be typical of NMOSD and MS. Thirty nine patients fulfilled the criteria and were included in the study. They consisted of 19 AQP4 seropositive and 20 AQP4 seronegative patients. The mean age was older (37.0 vs. 28.8 years) among the AQP4 positive group. The majority of the patients were ethnic Chinese (72%), followed by the Malays and Indians. Those with AQP4 seropositive status generally has less brain lesions, and significantly less fulfilling the McDonald DIS criteria as compared to those with AQP4 seronegative status (15.8% vs. 60.0%, p=0.005). None of the seven cerebral MRI features highlighted in NMOSD 2015 diagnostic criteria, said to be characteristic of NMOSD was more common among the AQP4 positive patients. These features were in fact seen less frequently among the AQP4 seropositive patients. An example was the extensive hemispheric lesion seen in 10.5% of AQP4 seropositive patients vs. 45% of that AQP4 seronegative group. There was no characteristic MRI brain features in the Malaysian AQP4 seropositive IIDD patients versus those who are seronegative. This could be a reflection of ethnical difference. Copyright © 2017 Elsevier B.V. All rights reserved.

Injury-Related Production of Cysteinyl Leukotrienes Contributes to Brain Damage following Experimental Traumatic Brain Injury

PubMed Central

Farias, Santiago; Frey, Lauren C.; Murphy, Robert C.

2009-01-01

Abstract The leukotrienes belong to a family of biologically active lipids derived from arachidonate that are often involved in inflammatory responses. In the central nervous system, a group of leukotrienes, known as the cysteinyl leukotrienes, is generated in brain tissue in response to a variety of acute brain injuries. Although the exact clinical significance of this excess production remains unclear, the cysteinyl leukotrienes may contribute to injury-related disruption of the brain-blood barrier and exacerbate secondary injury processes. In the present study, the formation and role of cysteinyl leukotrienes was explored in the fluid percussion injury model of traumatic brain injury in rats. The results showed that levels of the cysteinyl leukotrienes were elevated after fluid percussion injury with a maximal formation 1 hour after the injury. Neutrophils contributed to cysteinyl leukotriene formation in the injured brain hemisphere, potentially through a transcellular biosynthetic mechanism. Furthermore, pharmacological reduction of cysteinyl leukotriene formation after the injury, using MK-886, resulted in reduction of brain lesion volumes, suggesting that the cysteinyl leukotrienes play an important role in traumatic brain injury. PMID:19886806

Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

PubMed

Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

2018-05-01

The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

PubMed Central

Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens

2013-01-01

Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS. PMID:24109235

Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

ERIC Educational Resources Information Center

Martinez, Sarah; Davalos, Deana

2016-01-01

Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

Expression of the plasminogen activator system and the inhibitors PAI-1 and PAI-2 in posttraumatic lesions of the CNS and brain injuries following dramatic circulatory arrests: an immunohistochemical study.

PubMed

Dietzmann, K; von Bossanyi, P; Krause, D; Wittig, H; Mawrin, C; Kirches, E

2000-01-01

Plasminogen activators as inducible extracellular serine proteases are involved in a variety of processes, such as the degradation of brain structures. In regions of brain degradation, an increase in the expression of genes encoding cytokines and proteinases has recently been demonstrated. We tested the hypothesis, whether the plasminogen activator system as well as the plasminogen activator inhibitors are expressed and possibly involved in a proteolytic cascade that breaks down the extracellular matrix as a result of ischemic or posttraumatic brain destructions. To study this supposition, we investigated immunohistochemically the expression of tPA, uPA and its receptor, the plasminogen activator inhibitors PAI-1 and PAI-2, tetranectin as well as the laminin breakdown as an event of secondary brain injury. Brain tissue from 21 autopsy cases with severe brain injuries, material from 14 ischemic infarcts and 11 controls with acute hypoxia were used. All components of the plasminogen activator system studied were over-expressed immunohistochemically in reactive astrocytes, microglia and endothelial cells around the lesion zone. Tetranectin showed an analogous distribution to the plasminogen activator system. A reduced immunoreactivity of laminin within the identical region of destruction was detected concomitant with laminin remnants in perivascular macrophages, so that a remarkable role of the plasmin cascade in the degradation of extracellular matrix proteins in the brain is taken into consideration.

SNP-array lesions in core binding factor acute myeloid leukemia

PubMed Central

Duployez, Nicolas; Boudry-Labis, Elise; Roumier, Christophe; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Helevaut, Nathalie; Celli-Lebras, Karine; Terré, Christine; Fenneteau, Odile; Cuccuini, Wendy; Luquet, Isabelle; Lapillonne, Hélène; Lacombe, Catherine; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2018-01-01

Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia. PMID:29464086

SNP-array lesions in core binding factor acute myeloid leukemia.

PubMed

Duployez, Nicolas; Boudry-Labis, Elise; Roumier, Christophe; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Helevaut, Nathalie; Celli-Lebras, Karine; Terré, Christine; Fenneteau, Odile; Cuccuini, Wendy; Luquet, Isabelle; Lapillonne, Hélène; Lacombe, Catherine; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2018-01-19

Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.

Numeracy Skills in Patients With Degenerative Disorders and Focal Brain Lesions

PubMed Central

Cappelletti, Marinella; Butterworth, Brian; Kopelman, Michael

2012-01-01

Objective: To characterize the numerical profile of patients with acquired brain disorders. Method: We investigated numeracy skills in 76 participants—40 healthy controls and 36 patients with neurodegenerative disorders (Alzheimer dementia, frontotemporal dementia, semantic dementia, progressive aphasia) and with focal brain lesions affecting parietal, frontal, and temporal areas as in herpes simplex encephalitis (HSE). All patients were tested with the same comprehensive battery of paper-and-pencil and computerized tasks assessing numerical abilities and calculation. Degenerative and HSE patients also performed nonnumerical semantic tasks. Results: Our results, based on nonparametric group statistics as well as on the analysis of individual patients, and all highly significant, show that: (a) all patients, including those with parietal lesions—a key brain area for numeracy processing—had intact processing of number quantity; (b) patients with impaired semantic knowledge had much better preserved numerical knowledge; and (c) most patients showed impaired calculation skills, with the exception of most semantic dementia and HSE patients. Conclusion: Our results allow us, for the first time, to characterize the numeracy skills in patients with a variety of neurological conditions and to suggest that the pattern of numerical performance can vary considerably across different neurological populations. Moreover, the selective sparing of calculation skills in most semantic dementia and HSE suggest that numerical abilities are an independent component of the semantic system. Finally, our data suggest that, besides the parietal areas, other brain regions might be critical to the understanding and processing of numerical concepts. PMID:22122516

Contribution of fetal brain MRI in management of severe fetal anemia.

PubMed

Ghesquière, L; Houfflin-Debarge, V; Verpillat, P; Fourquet, T; Joriot, S; Coulon, C; Vaast, P; Garabedian, C

2018-06-06

Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Gastroprotection studies of Schiff base zinc (II) derivative complex against acute superficial hemorrhagic mucosal lesions in rats.

PubMed

Golbabapour, Shahram; Gwaram, Nura Suleiman; Hassandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Hadi, A Hamid A; Majid, Nazia Abdul

2013-01-01

The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats. The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10(-5) M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10(-5) and 4.362×10(-5) M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10(-5) M/kg). The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

Gastroprotection Studies of Schiff Base Zinc (II) Derivative Complex against Acute Superficial Hemorrhagic Mucosal Lesions in Rats

PubMed Central

Golbabapour, Shahram; Gwaram, Nura Suleiman; Hassandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Abdulla, Mahmood Ameen; Ali, Hapipah Mohd; Hadi, A. Hamid A; Majid, Nazia Abdul

2013-01-01

Background The study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats. Methodology/Principal Finding The animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10−5 M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10−5 and 4.362×10−5 M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (<87.241×10−5 M/kg). Conclusion/Significance The gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism. PMID:24058648

Size-weight illusion and anticipatory grip force scaling following unilateral cortical brain lesion.

PubMed

Li, Yong; Randerath, Jennifer; Goldenberg, Georg; Hermsdörfer, Joachim

2011-04-01

The prediction of object weight from its size is an important prerequisite of skillful object manipulation. Grip and load forces anticipate object size during early phases of lifting an object. A mismatch between predicted and actual weight when two different sized objects have the same weight results in the size-weight illusion (SWI), the small object feeling heavier. This study explores whether lateralized brain lesions in patients with or without apraxia alter the size-weight illusion and impair anticipatory finger force scaling. Twenty patients with left brain damage (LBD, 10 with apraxia, 10 without apraxia), ten patients with right brain damage (RBD), and matched control subjects lifted two different-sized boxes in alternation. All subjects experienced a similar size-weight illusion. The anticipatory force scaling of all groups was in correspondence with the size cue: higher forces and force rates were applied to the big box and lower forces and force rates to the small box during the first lifts. Within few lifts, forces were scaled to actual object weight. Despite the lack of significant differences at group level, 5 out of 20 LBD patients showed abnormal predictive scaling of grip forces. They differed from the LBD patients with normal predictive scaling by a greater incidence of posterior occipito-parietal lesions but not by a greater incidence of apraxia. The findings do not support a more general role for the motor-dominant left hemisphere, or an influence of apraxia per se, in the scaling of finger force according to object properties. However, damage in the vicinity of the parietal-occipital junction may be critical for deriving predictions of weight from size. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acute and non-acute effects of cannabis on brain functioning and neuropsychological performance.

PubMed

Gonzalez, Raul

2007-09-01

Cannabis has an ancient history of human use and is currently one of the most commonly used drugs worldwide. Understanding its impact on neurobehavioral functioning is of significant public health concern. In recent decades, substantial progress has been made in understanding the impact of cannabis use on neurobehavioral functioning. This has been fueled, in part, by characterization of an endocannabinoid signaling system in the brain through which cannabis exerts its psychoactive effects. Acute intoxication with cannabis causes marked changes in subjective mental status, brain functioning, and neuropsychological performance. Some of these changes are consistently detected and well characterized, yet others are not. Changes in brain functioning and neuropsychological performance are also reported after abstinence, but appear to be mild, circumscribed, and transient. On the other hand, functional neuroimaging often reveals subtle differences in the brain functioning of abstinent cannabis users compared with controls. The persistence and clinical significance of these differences, however, remains to be determined. Neuropsychological deficits and differences in brain functioning are most consistently observed only among frequent, heavy users, who are those most likely addicted to cannabis. The dire impact of drug addiction on a person's life and everyday functioning suggests that the large number of individuals addicted to cannabis experience substantial negative effects from its use. This manuscript reviews the scientific literature on the aforementioned topics in detail, providing evidence for converging findings, and highlighting areas in need of further investigation.

Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging.

PubMed

Kirov, Ivan I; Liu, Shu; Tal, Assaf; Wu, William E; Davitz, Matthew S; Babb, James S; Rusinek, Henry; Herbert, Joseph; Gonen, Oded

2017-08-01

Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume. Within 10 patients with relapsing-remitting course, there were 180 regions-of-interest consisting of up to seven semi-annual follow-ups of normal-appearing white matter (NAWM, n = 10), pre-lesional tissue giving rise to acute lesions which resolved (n = 3) or persisted (n = 3), and of moderately (n = 9) and severely hypointense (n = 6) chronic lesions. Compared with NAWM, pre-lesional tissue had higher Cr and Cho, while compared with lesions, pre-lesional tissue had higher NAA. Resolving acute lesions showed similar NAA levels pre- and post-formation, suggesting no long-term axonal damage. In chronic lesions, there was an increase in mI, suggesting accumulating astrogliosis. Lesion volume was a better predictor of axonal health than T1-hypointensity, with lesions larger than 1.5 cm 3 uniformly exhibiting very low (<4.5 millimolar) NAA concentrations. A positive correlation between longitudinal changes in Cho and in lesion volume in moderately hypointense lesions implied that lesion size is mediated by chronic inflammation. These and other results are integrated in a discussion on the steady-state metabolism of lesion evolution in multiple sclerosis, viewed in the context of conventional MRI measures. Hum Brain Mapp 38:4047-4063, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Histopathologic lesions in conventional pigs experimentally infected with Haemophilus parasuis serovar 5.

PubMed

Palzer, A; Austin-Busse, R-L; Ladinig, A; Balka, G; Zoels, S; Ritzmann, M

2015-01-01

In the present study various tissues of pigs were investigated for the presence of histopathologic lesions after an experimental infection with Haemophilus (H.) parasuis serovar 5. Conventional pigs (n = 36) were divided into a control group B (n = 9) and a challenge group A (n = 27), which was infected intratracheally. Pigs that did not die prior to study termination were euthanized on day 14 post inoculation. Postmortem samples of the lung, heart, liver, kidney, spleen, left tarsal joint capsule and brain were collected. All but one pig with detectable histopathologic lesions (n = 11) showed typical macroscopic changes. Histopathologic examination of all tissue samples identified pyelitis (n = 10), synovitis (n = 7) and meningitis (n = 7) and all those animals were euthanized prior to study termination. No histopathologic lesions were found in pigs of the control group. The correlations between pyelitis and meningitis, pyelitis and synovitis and synovitis and meningitis were significant (p < 0.001). No significant correlation could be observed between the histopathologic and the clinical examination of the joints. The investigation of samples from the joints by PCR was not significantly correlated with the observed synovitis. The clinical observation of neurologic signs was significantly correlated with meningitis (p = 0.03). A significant correlation (p < 0.001) could be detected between meningitis and the detection of H. parasuis by PCR in brain samples. H. parasuis constantly causes clinical signs and pathologic lesions as soon as it infects the brain while it can infect the joints without causing histopathologic lesions. Pigs with histopathologic lesions do not always show typical clinical signs. Only few studies described the finding of kidney lesions in pigs with Glässer's disease and this is the first study to describe a pyelitis in pigs experimentally infected with H. parasuis. The observed pyelitis mainly occurred in acute cases.

A novel application of the fluorescent dye bis-ANS for labeling neurons in acute brain slices.

PubMed

Mozes, Emese; Hunya, Akos; Toth, Aniko; Ayaydin, Ferhan; Penke, Botond; Datki, Zsolt L

2011-10-10

The cell-impermeant oligomer-(e.g. beta-amyloid-, or tubulin-) specific fluorescent dye, bis-ANS (4,4'-bis-1-anilinonaphtalene-8-sulfonate), was successfully used for labeling mechanically damaged but still viable neuron bodies, neurites and neurite cross sections in acute brain slices. Acute hippocampal brain slices of rats were co-stained with bis-ANS and the cell-impermeant, DNA-specific dye propidium iodide (PI) and were then analyzed using fluorescence and confocal microscopes. Both the neuron bodies and the neurites were found to exhibit increased fluorescence intensities, suggesting that using this method they can be detected more easily. In addition, bis-ANS showed good region - but not cell specific co-localization with the neuron-specific fluorescent dye Dil (1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). These two dyes label different neuronal structures: Dil binds specifically to intact cell membranes while bis-ANS can enter cells with compromised cell membranes and then stain the microtubules in the cytoplasm. For a quick (10min) staining of acute brain slices with bis-ANS both HEPES and NaHCO(3) were needed in order to achieve high signal intensity. Labeling with bis-ANS fluorescent dye is an easy method for imaging the neuronal structures on the surface of acute brain slices. Copyright © 2011 Elsevier Inc. All rights reserved.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Global aphasia without hemiparesis: language profiles and lesion distribution

PubMed Central

Hanlon, R.; Lux, W.; Dromerick, A.

1999-01-01

OBJECTIVES—Global aphasia without hemiparesis (GAWH) is an uncommon stroke syndrome involving receptive and expressive language impairment, without the hemiparesis typically manifested by patients with global aphasia after large left perisylvian lesions. A few cases of GAWH have been reported with conflicting conclusions regarding pathogenesis, lesion localisation, and recovery. The current study was conducted to attempt to clarify these issues.
METHODS—Ten cases of GAWH were prospectively studied with language profiles and lesion analysis; five patients had multiple lesions, four patients had a single lesion, and one had a subarachnoid haemorrhage. Eight patients met criteria for cardioembolic ischaemic stroke.
RESULTS—Cluster analysis based on acute language profiles disclosed three subtypes of patients with GAWH; these clusters persisted on follow up language assessment. Each cluster evolved into a different aphasia subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia (TCM). Composite lesion analysis showed that persistent GAWH was related to lesioning of the left superior temporal gyrus. Patients with acute GAWH who evolved into TCM type aphasia had common lesioning of the left inferior frontal gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved into Wernicke's type aphasia were characterised by lesioning of the left precentral and postcentral gyri. Recovery of language was poor in all but one patient.
CONCLUSIONS—Although patients with acute GAWH are similar on neurological examination, they are heterogeneous with respect to early aphasia profile, language recovery, and lesion profile.

 PMID:10084536

Advanced imaging in acute stroke management-Part I: Computed tomographic.

PubMed

Saini, Monica; Butcher, Ken

2009-01-01

Neuroimaging is fundamental to stroke diagnosis and management. Non-contrast computed tomography (NCCT) has been the primary imaging modality utilized for this purpose for almost four decades. Although NCCT does permit identification of intracranial hemorrhage and parenchymal ischemic changes, insights into blood vessel patency and cerebral perfusion are limited. Advances in reperfusion strategies have made identification of potentially salvageable brain tissue a more practical concern. Advances in CT technology now permit identification of acute and chronic arterial lesions, as well as cerebral blood flow deficits. This review outlines principles of advanced CT image acquisition and its utility in acute stroke management.

[Possibilities of magnetic-laser therapy in comprehensive treatment of patients with brain concussion in acute period].

PubMed

Zubkova, O V; Samosiuk, I Z; Polishchuk, O V; Shul'ga, N M; Samosiuk, N I

2012-01-01

The efficacy of magnetic-laser therapy used according to the method developed by us was studied in patients having the brain concussion (BC) in an acute period. The study was based on the dynamics of values of the evoked vestibular potentials and the disease clinical course. It was shown that following the magnetic-laser therapy in combination with traditional pharmacotherapy in BC acute period, the statistically significant positive changes were registered in the quantitative characteristics of the evoked vestibular brain potentials that correlated with the dynamics of the disease clinical course. The data obtained substantiate the possibility of using the magnetic-laser therapy in patients with a mild craniocereblal injury in an acute period.

Relationships among neuroscore, magnetic resonance imaging features, and intracranial pressure in sheep affected by slow-growing brain lesions.

PubMed

Evangelisti, Maria A; Deiana, Roberta; Melosu, Valentino; Burrai, Giovanni P; Ballocco, Isabella; Varcasia, Antonio; Scala, Antonio; Manunta, Maria L

2018-05-01

Diagnosing high intracranial pressure by clinical and diagnostic imaging is particularly challenging for chronic or slow-growing lesions. The aim of this prospective case-control study is to determine whether the neuroscore and brain magnetic resonance imaging (MRI) are related to the direct measurement of intracranial pressure in sheep affected by intracranial slow-growing lesions due to chronic cerebral coenurosis (Coenurus cerebralis). Seventeen affected and 10 control sheep were included. All animals underwent a neurological examination, MRI of the brain, and direct measurement of intracranial pressure. The severity of clinical signs and MRI findings were scored. Data were statistically analyzed. The invasive intracranial pressure value was higher in affected animals. A severely altered neuroscore is related to an increased intracranial pressure beyond the normal threshold (P < 0.05). The volume of the calvarium was larger in affected animals than in control animals (P = 0.0001) and was positively influenced by the presence and volume of the parasitic cyst (r = 0.7881, P < 0.01). Several degrees of deviation and deformation of both the ventricular system and brain parenchyma were detected by MRI. Subjective MRI findings were not associated with intracranial hypertension. In conclusion, this study shows that in sheep affected by slow-growing lesions, severe alterations in the neuroscore and the results of objective MRI are related to an increased intracranial pressure beyond the normal threshold. © 2017 American College of Veterinary Radiology.

IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure.

PubMed

Bémeur, Chantal; Qu, Hong; Desjardins, Paul; Butterworth, Roger F

2010-01-01

Previous reports suggested that brain-derived proinflammatory cytokines are involved in the pathogenesis of hepatic encephalopathy (HE) and brain edema in acute liver failure (ALF). To further address this issue, expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were measured in the brains of mice with acute liver failure resulting from exposure to azoxymethane. In addition, time to severe encephalopathy (coma) was assessed in mice lacking genes coding for interferon-gamma, the tumor necrosis factor receptor-1 or the interleukin-1 type 1 receptor. Interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma expression were quantified using RT-PCR. Significant increases in interleukin-1beta and tumor necrosis factor-alpha mRNA were observed in the frontal cortex of azoxymethane-treated wild-type mice at coma stages of encephalopathy. Interferon-gamma, however, could not be detected in the brains of these animals. Onset of severe encephalopathy (coma) and brain edema in ALF mice were significantly delayed in interleukin-1 type 1 receptor or tumor necrosis factor receptor-1 knockout mice. Deletion of the interferon-gamma gene, on the other hand, had no significative effect on the neurological status or brain water content of acute liver failure mice. These results demonstrate that toxic liver injury resulting from exposure to azoxymethane is associated with selective induction of proinflammatory cytokines in the brain and that deletion of tumor necrosis factor receptor-1 or interlukin-1 type 1 receptor delays the onset of coma and brain edema in this model of acute liver failure. These findings further support a role for selective brain-derived cytokines in the pathogenesis of the cerebral complications in acute liver failure and suggest that anti-inflammatory strategies could be beneficial in their prevention. Copyright 2009 Elsevier Ltd. All rights reserved.

Predicting the Risk of Developing New Cerebral Lesions After Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastases from Renal Cell Carcinoma.

PubMed

Rades, Dirk; Dziggel, Liesa; Blanck, Oliver; Gebauer, Niklas; Bartscht, Tobias; Schild, Steven E

2018-05-01

To create an instrument for estimating the risk of new brain metastases after stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) alone in patients with renal cell carcinoma (RCC). In 45 patients with 1-3 brain metastases, seven characteristics were analyzed for association with freedom from new brain metastases (age, gender, performance score, number and sites of brain metastases, extra-cerebral metastasis, interval from RCC diagnosis to SRS/FSRT). Lower risk of subsequent brain lesions after RT was associated with single metastasis (p=0.043) and supratentorial involvement only (p=0.018). Scoring points were: One metastasis=1, 2-3 metastases=0, supratentorial alone=1, infratentorial with/without supratentorial=0. Scores of 0, 1 and 2 points were associated with 6-month rates of freedom from subsequent brain lesions of 25%, 74% and 92% (p=0.008). After combining groups with 1 and 2 points, 6-month rates were 25% for those with 0 points and 83% for those with 1-2 points (p=0.002). Two groups were identified with different risks of new brain metastases after SRS or FSRT alone. High-risk patients may benefit from additional whole-brain irradiation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The brain is a target organ after acute exposure to depleted uranium.

PubMed

Lestaevel, P; Houpert, P; Bussy, C; Dhieux, B; Gourmelon, P; Paquet, F

2005-09-01

The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144+/-10 microg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 microg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70+/-8 microg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed.

Traumatic brain injury shows better functional recovery than brain tumor: a rehabilitative perspective.

PubMed

Bilgin, S; Kose, N; Karakaya, J; Mut, M

2014-02-01

The similar symptoms seen in the brain tumor (BT) and traumatic brain injury (TBI) population. However, functional comparisons between these two diagnostic groups have been limited. To compare functional outcomes in patients with supratentorial BT and TBI after early rehabilitation. This was a retrospective database analysis. Setting. Patients admitted to an Acute Care Unit as inpatient (Hacettepe Hospital, Ankara-Turkey). Population. The population included patients with BT and TBI. Thirty-four patients with BT and TBI were matched one-to-one by lesion side and sex. The Barthel Index was used to assess functional status at the pre- and postrehabilitation. The change rate and efficiency in BI were also calculated. The time between injury onset and admission to rehabilitation (the onset to admission interval, OAI) and length of stay in rehabilitation (LOS rehab) were recorded. In addition, the influence of lesion side (left and right) and age on functional outcome were analyzed. The functional level was significantly lower in TBI patients than in patients BT before rehabilitation (P<0.05). The post-rehabilitation BI score was similar in patients with BT and TBI (P>0.05). Patients with TBI had greater the change rate and efficiency in BI (P<0.05). The OAI and LOS rehab was longer in patients with TBI (P<0.05). In terms of lesion side comparisons, no differences were found (P>0.05). The age had no effect on functional outcome in patients with TBI and BT (P>0.05), expect the age group 45-59 (P<0.05). The early rehabilitation program improved functional ability of patients with brain tumors, as well as patients with traumatic brain injury. Despite the lower functional status, patients with TBI displayed better functional recovery than patients with BT. Lesion side had no effect on functional outcome in patients with TBI and BT. Differences in functional status begin to appear even in patients with TBI between 45 and 59 years. Further investigations with more detailed

The validity of the Brain Injury Cognitive Screen (BICS) as a neuropsychological screening assessment for traumatic and non-traumatic brain injury.

PubMed

Vaughan, Frances L; Neal, Jo Anne; Mulla, Farzana Nizam; Edwards, Barbara; Coetzer, Rudi

2017-04-01

The Brain Injury Cognitive Screen (BICS) was developed as an in-service cognitive assessment battery for acquired brain injury patients entering community rehabilitation. The BICS focuses on domains that are particularly compromised following TBI, and provides a broader and more detailed assessment of executive function, attention and information processing than comparable screening assessments. The BICS also includes brief assessments of perception, naming, and construction, which were predicted to be more sensitive to impairments following non-traumatic brain injury. The studies reported here examine preliminary evidence for its validity in post-acute rehabilitation. In Study 1, TBI patients completed the BICS and were compared with matched controls. Patients with focal lesions and matched controls were compared in Study 2. Study 3 examined demographic effects in a sample of normative data. TBI and focal lesion patients obtained significantly lower composite memory, executive function and attention and information processing BICS scores than healthy controls. Injury severity effects were also obtained. Logistic regression analyses indicated that each group of BICS memory, executive function and attention measures reliably differentiated TBI and focal lesion participants from controls. Design Recall, Prospective Memory, Verbal Fluency, and Visual Search test scores showed significant independent regression effects. Other subtest measures showed evidence of sensitivity to brain injury. The study provides preliminary evidence of the BICS' sensitivity to cognitive impairment caused by acquired brain injury, and its potential clinical utility as a cognitive screen. Further validation based on a revised version of the BICS and more normative data are required.

Efficient multi-scale 3D CNN with fully connected CRF for accurate brain lesion segmentation.

PubMed

Kamnitsas, Konstantinos; Ledig, Christian; Newcombe, Virginia F J; Simpson, Joanna P; Kane, Andrew D; Menon, David K; Rueckert, Daniel; Glocker, Ben

2017-02-01

We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network's soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

PubMed

Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

2015-06-15

Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

[Mental disorders due to brain lesions in the DSM-5 in the light of the previous versions].

PubMed

Derouesné, Christian

2013-12-01

The DSM-5 introduces major modifications in the category of mental disorders due to brain lesions compared to the previous DSM versions, which are reviewed in this paper. The description of the category Major neurocognitive disorder, as a substitute for dementia, seems to fit better for patients and families, and more adapted to many neurodegenerative cognitive disorders for which memory impairment is not predominant. Similarly, the introduction of the category of Mild neurocognitive disorder appears to be an improvement although some difficulty still remains for distinguishing mild cognitive disorder from normal aging. The addition of new etiological categories such as fronto-temporal NCD or NCD with Lewy bodies should also to be considered as a significant improvement. Despite these advances, to circumscribe the mental disorders due to brain lesions to cognitive deficits and biological mechanisms remains highly questionable, and does not provide an adequate care for the patients and families if not complemented by a psychological and environmental approach.

Automated tissue segmentation of MR brain images in the presence of white matter lesions.

PubMed

Valverde, Sergi; Oliver, Arnau; Roura, Eloy; González-Villà, Sandra; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Rovira, Àlex; Lladó, Xavier

2017-01-01

Over the last few years, the increasing interest in brain tissue volume measurements on clinical settings has led to the development of a wide number of automated tissue segmentation methods. However, white matter lesions are known to reduce the performance of automated tissue segmentation methods, which requires manual annotation of the lesions and refilling them before segmentation, which is tedious and time-consuming. Here, we propose a new, fully automated T1-w/FLAIR tissue segmentation approach designed to deal with images in the presence of WM lesions. This approach integrates a robust partial volume tissue segmentation with WM outlier rejection and filling, combining intensity and probabilistic and morphological prior maps. We evaluate the performance of this method on the MRBrainS13 tissue segmentation challenge database, which contains images with vascular WM lesions, and also on a set of Multiple Sclerosis (MS) patient images. On both databases, we validate the performance of our method with other state-of-the-art techniques. On the MRBrainS13 data, the presented approach was at the time of submission the best ranked unsupervised intensity model method of the challenge (7th position) and clearly outperformed the other unsupervised pipelines such as FAST and SPM12. On MS data, the differences in tissue segmentation between the images segmented with our method and the same images where manual expert annotations were used to refill lesions on T1-w images before segmentation were lower or similar to the best state-of-the-art pipeline incorporating automated lesion segmentation and filling. Our results show that the proposed pipeline achieved very competitive results on both vascular and MS lesions. A public version of this approach is available to download for the neuro-imaging community. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies.

PubMed

Zimmermann, Kathrin; Eschen, Anne

2017-04-01

Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.

An object-based approach for detecting small brain lesions: application to Virchow-Robin spaces.

PubMed

Descombes, Xavier; Kruggel, Frithjof; Wollny, Gert; Gertz, Hermann Josef

2004-02-01

This paper is concerned with the detection of multiple small brain lesions from magnetic resonance imaging (MRI) data. A model based on the marked point process framework is designed to detect Virchow-Robin spaces (VRSs). These tubular shaped spaces are due to retraction of the brain parenchyma from its supplying arteries. VRS are described by simple geometrical objects that are introduced as small tubular structures. Their radiometric properties are embedded in a data term. A prior model includes interactions describing the clustering property of VRS. A Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC) optimizes the proposed model, obtained by multiplying the prior and the data model. Example results are shown on T1-weighted MRI datasets of elderly subjects.

Cognitive activity limitations one year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury.

PubMed

Sommer, Jens Bak; Norup, Anne; Poulsen, Ingrid; Morgensen, Jesper

2013-09-01

To examine cognitive activity limitations and predictors of outcome 1 year post-trauma in patients admitted to sub-acute rehabilitation after severe traumatic brain injury. The study included 119 patients with severe traumatic brain injury admitted to centralized sub-acute rehabilitation in the Eastern part of Denmark during a 5-year period from 2005 to 2009. Level of consciousness was assessed consecutively during rehabilitation and at 1 year post-trauma. Severity of traumatic brain injury was classified according to duration of post-traumatic amnesia. The cognitive subscale of Functional Independence MeasureTM (Cog-FIM) was used to assess cognitive activity limitations. Multivariate logistic regression analyses were performed to identify predictors of an independent level of functioning. The majority of patients progressed to a post-confusional level of consciousness during the first year post-trauma. At follow-up 33-58% of patients had achieved functional independence within the cognitive domains on the Cog-FIM. Socio-economic status, duration of acute care and post-traumatic amnesia were significant predictors of outcome. Substantial recovery was documented among patients with severe traumatic brain injury during the first year post-trauma. The results of the current study suggest that absence of consciousness at discharge from acute care should not preclude patients from being referred to specialized sub-acute rehabilitation.

Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

PubMed

Gass, Carlton S; Rogers, David; Kinne, Erica

2017-01-01

The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

Cognitive benefit and cost of acute stress is differentially modulated by individual brain state.

PubMed

Kohn, Nils; Hermans, Erno J; Fernández, Guillén

2017-07-01

Acute stress is associated with beneficial as well as detrimental effects on cognition in different individuals. However, it is not yet known how stress can have such opposing effects. Stroop-like tasks typically show this dissociation: stress diminishes speed, but improves accuracy. We investigated accuracy and speed during a stroop-like task of 120 healthy male subjects after an experimental stress induction or control condition in a randomized, counter-balanced cross-over design; we assessed brain-behavior associations and determined the influence of individual brain connectivity patterns on these associations, which may moderate the effect and help identify stress resilience factors. In the mean, stress was associated to increase in accuracy, but decrease in speed. Accuracy was associated to brain activation in a distributed set of brain regions overlapping with the executive control network (ECN) and speed to temporo-parietal activation. In line with a stress-related large-scale network reconfiguration, individuals showing an upregulation of the salience and down-regulation of the executive-control network under stress displayed increased speed, but decreased performance. In contrast, individuals who upregulate their ECN under stress show improved performance. Our results indicate that the individual large-scale brain network balance under acute stress moderates cognitive consequences of threat. © The Author (2017). Published by Oxford University Press.

Human herpesvirus 6 encephalitis followed by acute disseminated encephalomyelitis in an immunocompetent adult.

PubMed

Horie, Junichi; Suzuki, Keisuke; Nakamura, Toshiki; Okamura, Madoka; Iwasaki, Akio; Hirata, Koichi

2017-04-28

A 26-year-old, otherwise healthy man presented with visual abnormality followed by loss of consciousness and convulsion. The patient then developed headache and fever 14 days later. Brain MRI showed hyperintensities in the left cingulate cortex. The cerrebrospinal fluid examinations showed mononuclear pleocytosis and positive PCR results for human herpesvirus 6 (HHV-6). A diagnosis of HHV-6 encephalitis and symptomatic epilepsy was made. The patient's clinical symptoms improved promptly following acyclovir treatment. However, 3 months later the patient noticed dysesthesia in the trunk, the left upper limb and the right lower limb. Brain and spine MRI showed multiple brain white matter lesions, the middle cerebellar peduncle and cervical spinal lesions. The symptoms resolved following methylprednisolone pulse therapy only. We report an adult patient with HHV-6 encephalitis followed by acute disseminated encephalomyelitis whose initial presentation was epilepsy. HHV-6 encephalitis should be included in the differential diagnosis of encephalitis of unknown etiology in an immunocompetent adult.

Differential Associations of Socioeconomic Status With Global Brain Volumes and White Matter Lesions in African American and White Adults: the HANDLS SCAN Study.

PubMed

Waldstein, Shari R; Dore, Gregory A; Davatzikos, Christos; Katzel, Leslie I; Gullapalli, Rao; Seliger, Stephen L; Kouo, Theresa; Rosenberger, William F; Erus, Guray; Evans, Michele K; Zonderman, Alan B

2017-04-01

The aim of the study was to examine interactive relations of race and socioeconomic status (SES) to magnetic resonance imaging (MRI)-assessed global brain outcomes with previously demonstrated prognostic significance for stroke, dementia, and mortality. Participants were 147 African Americans (AAs) and whites (ages 33-71 years; 43% AA; 56% female; 26% below poverty) in the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN substudy. Cranial MRI was conducted using a 3.0 T unit. White matter (WM) lesion volumes and total brain, gray matter, and WM volumes were computed. An SES composite was derived from education and poverty status. Significant interactions of race and SES were observed for WM lesion volume (b = 1.38; η = 0.036; p = .028), total brain (b = 86.72; η = 0.042; p < .001), gray matter (b = 40.16; η = 0.032; p = .003), and WM (b = 46.56; η = 0.050; p < .001). AA participants with low SES exhibited significantly greater WM lesion volumes than white participants with low SES. White participants with higher SES had greater brain volumes than all other groups (albeit within normal range). Low SES was associated with greater WM pathology-a marker for increased stroke risk-in AAs. Higher SES was associated with greater total brain volume-a putative global indicator of brain health and predictor of mortality-in whites. Findings may reflect environmental and interpersonal stressors encountered by AAs and those of lower SES and could relate to disproportionate rates of stroke, dementia, and mortality.

Normobaric oxygen worsens outcome after a moderate traumatic brain injury

PubMed Central

Talley Watts, Lora; Long, Justin Alexander; Manga, Venkata Hemanth; Huang, Shiliang; Shen, Qiang; Duong, Timothy Q

2015-01-01

Traumatic brain injury (TBI) is a multifaceted injury and a leading cause of death in children, young adults, and increasingly in Veterans. However, there are no neuroprotective agents clinically available to counteract damage or promote repair after brain trauma. This study investigated the neuroprotective effects of normobaric oxygen (NBO) after a controlled cortical impact in rats. The central hypothesis was that NBO treatment would reduce lesion volume and functional deficits compared with air-treated animals after TBI by increasing brain oxygenation thereby minimizing ischemic injury. In a randomized double-blinded design, animals received either NBO (n=8) or normal air (n=8) after TBI. Magnetic resonance imaging (MRI) was performed 0 to 3 hours, and 1, 2, 7, and 14 days after an impact to the primary forelimb somatosensory cortex. Behavioral assessments were performed before injury induction and before MRI scans on days 2, 7, and 14. Nissl staining was performed on day 14 to corroborate the lesion volume detected from MRI. Contrary to our hypothesis, we found that NBO treatment increased lesion volume in a rat model of moderate TBI and had no positive effect on behavioral measures. Our results do not promote the acute use of NBO in patients with moderate TBI. PMID:25690469

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total

Using transcranial magnetic stimulation of the undamaged brain to identify lesion sites that predict language outcome after stroke.

PubMed

Lorca-Puls, Diego L; Gajardo-Vidal, Andrea; Seghier, Mohamed L; Leff, Alexander P; Sethi, Varun; Prejawa, Susan; Hope, Thomas M H; Devlin, Joseph T; Price, Cathy J

2017-06-01

unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

PubMed

Baek, Hyun Seok; Lee, Se-Jin

2015-01-01

Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

Glucose and oxygen metabolism after penetrating ballistic-like brain injury.

PubMed

Gajavelli, Shyam; Kentaro, Shimoda; Diaz, Julio; Yokobori, Shoji; Spurlock, Markus; Diaz, Daniel; Jackson, Clayton; Wick, Alexandra; Zhao, Weizhao; Leung, Lai Y; Shear, Deborah; Tortella, Frank; Bullock, M Ross

2015-05-01

Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies.

Segmentation of Brain Lesions in MRI and CT Scan Images: A Hybrid Approach Using k-Means Clustering and Image Morphology

NASA Astrophysics Data System (ADS)

Agrawal, Ritu; Sharma, Manisha; Singh, Bikesh Kumar

2018-04-01

Manual segmentation and analysis of lesions in medical images is time consuming and subjected to human errors. Automated segmentation has thus gained significant attention in recent years. This article presents a hybrid approach for brain lesion segmentation in different imaging modalities by combining median filter, k means clustering, Sobel edge detection and morphological operations. Median filter is an essential pre-processing step and is used to remove impulsive noise from the acquired brain images followed by k-means segmentation, Sobel edge detection and morphological processing. The performance of proposed automated system is tested on standard datasets using performance measures such as segmentation accuracy and execution time. The proposed method achieves a high accuracy of 94% when compared with manual delineation performed by an expert radiologist. Furthermore, the statistical significance test between lesion segmented using automated approach and that by expert delineation using ANOVA and correlation coefficient achieved high significance values of 0.986 and 1 respectively. The experimental results obtained are discussed in lieu of some recently reported studies.

Lesion studies of human emotion and feeling.

PubMed

Feinstein, Justin S

2013-06-01

The lesion method provides unique insight into how the human brain generates emotion and feeling. Recent work has explored a number of interesting topics including the dissociation of emotional experience from memory in patients with amnesia, the reliability of specific emotional deficits following focal brain damage (including fear and the amygdala), and the investigation of compensatory neural mechanisms in lesion patients. Several detailed case studies have challenged the necessary role of the insular cortex in both awareness and feeling by showing that even in rare instances of complete bilateral insula destruction, the patient remains fully sentient and capable of expressing and feeling emotion. These findings highlight the distributed nature of emotion processing in the human brain and emphasize the importance of utilizing the lesion method for elucidating brain-behavior relationships. Copyright © 2012 Elsevier Ltd. All rights reserved.

The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae.

PubMed

Tsai, Chung-Fen; Yip, Ping-Keung; Chen, Shao-Yuan; Lin, Jen-Cheng; Yeh, Zai-Ting; Kung, Lan-Yu; Wang, Cheng-Yi; Fan, Yu-Ming

2014-04-01

Acute carbon monoxide (CO) poisoning poses a significant threat to the central nervous system. It can cause brain injury and diverse neurological deficits including persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). The study aimed to investigate the long-term impacts of acute CO poisoning on brain perfusion and neurological function, and to explore potential differences between PNS and DNS patients. We evaluated brain perfusion using (99m)Tc ethyl cysteinate (ECD) brain single photon emission computed tomography (SPECT) and assessed clinical neurological symptoms and signs one month following acute poisoning. For DNS patients, ECD SPECT and clinical evaluation were performed when their delayed symptoms appeared. All patients had follow-up SPECT imaging, along with clinical assessments six months following poisoning. 12 PNS and 12 DNS patients were recruited between 2007 and 2010. Clinically, the main characteristic presentations were cognitive decline, emotional instability, and gait disturbance. SPECT imaging demonstrated consistent frontal hypoperfusion of varying severities in all patients, which decreased in severity at follow-up imaging. DNS patients usually had more severe symptoms and perfusion defects, along with worse clinical outcomes than the PNS group. These results suggest that acute CO poisoning might lead to long term brain injuries and neurological sequelae, particularly in DNS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Clinical Correlates and Prognostic Significance of Lateralized Periodic Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control Study.

PubMed

Sainju, Rup K; Manganas, Louis N; Gilmore, Emily J; Petroff, Ognen A; Rampal, Nishi; Hirsch, Lawrence J; Gaspard, Nicolas

2015-12-01

Lateralized periodic discharges (LPDs, also known as periodic lateralized epileptiform discharges) in conjunction with acute brain injuries are known to be associated with worse prognosis but little is known about their importance in absence of such acute injuries. We studied the clinical correlates and outcome of patients with LPDs in the absence of acute or progressive brain injury. This is a case-control study of 74 patients with no acute brain injury undergoing continuous EEG monitoring, half with LPDs and half without, matched for age and etiology of remote brain injury, if any, or history of epilepsy. Lateralized periodic discharges were found in 145/1785 (8.1%) of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive brain injury. Those with LPDs were more likely to have abnormal consciousness (86% vs. 57%; P = 0.005), seizures (70% vs. 24%; P = 0.0002), and functional decline (62% vs. 27%; P = 0.005), and were less likely to be discharged home (24% vs. 62%; P = 0.002). On multivariate analysis, LPDs and status epilepticus were associated with abnormal consciousness (P = 0.009; odds ratio = 5.2, 95% CI = 1.60-20.00 and P = 0.017; odds ratio = 5.0, 95% CI = 1.4-21.4); and LPDs were independently associated with functional decline (P = 0.001; odds ratio = 4.8, 95% CI = 1.6-15.4) and lower likelihood of being discharged home (P = 0.009; odds ratio = 0.2, 95% CI = 0.04-0.6). Despite absence of acute or progressive brain injury, LPDs were independently associated with abnormal consciousness and worse outcome at hospital discharge.

Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

PubMed

Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

2017-12-01

Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.