Acute Focal Lesions Research Articles

Antinociception role of 14,15-epoxyeicosatrienoic acid in a central post-stroke pain model in rats mediated by anti-inflammation and anti-apoptosis effect

Central post stroke pain (CPSP) is an intractable neuropathic pain syndrome that occurs after the acute focal lesion of the central nervous system (CNS) due to a cerebrovascular cause. Epoxyeicosatrienoic acids (EETs) exert many pharmacological effects in vivo and in vitro, such as anti-apoptosis, anti-inflammatory, and anti-oxidative stress. Neuroinflammation and apoptosis are the potential pathophysiological mechanisms of neuropathic pain. This study aimed to investigate whether 14,15-EET has an antinociception effect on CPSP rats through its anti-inflammation and anti-apoptosis mechanisms. Rats were treated with type IV collagenase (CPSP group) or saline (Sham group) via injection with a Hamilton syringe into the ventral posterior lateral nucleus (VPL) according to the stereotaxic coordinates. We first tested the mechanical withdrawal threshold, as well as neuroinflammation- and apoptosis-related protein expressions in the per-lesion site of CPSP and Sham rats. Sprague-Dawley rats were randomly divided into five groups, as follows: vehicle; EET at 0.025, 0.05, and 0.1 μg; and EET (0.1 μg) + EEZE (3.25 ng). EET or and vehicle were administered into VPL nuclei three consecutive days after hemorrhagic stroke. Immunostaining, ELISA, and Western blot were performed to evaluate neuroinflammation and apoptosis. Hemorrhagic stroke induced mechanical allodynia, glial activation, neuroinflammation, and apoptosis-related protein upregulation. However, early treatment with 14,15-EET inhibited glial cell activation, decreased proinflammatory cytokines and apoptosis-related protein, and alleviated the pain behavior of CPSP rats. Our results provided strong evidence that antinociception produced by 14,15-EET is partly mediated by the inhibition of neuroinflammation and apoptosis.

Effects of manual stretching and joint mobilization with neurodevelopmental treatment in improving functional mobility among stroke patients

Background: Stroke is classically characterized as a neurological deficit attributed to an acute focal lesion of the central nervous system (CNS) due to a vascular cause, which includes cerebral infarction, intracerebral hemorrhage (HIC) and subarachnoid hemorrhage (SAH) and is an important cause of disability and death worldwide. Objective: The main objective of the study was to determine the effects of manual stretching and joint mobilization with the treatment of neurological development to improve functional mobility among stroke patients. Methodology: Twenty-four subjects from the Shalamar hospital aged between 35 and 65 were considered after 2 weeks of stroke. Manual stretching and joint mobilization techniques have been applied with neurodevelopment techniques to analyze functional improvement among stroke patients. The pre-evaluation was carried out using the Berg equilibrium scale, Ashworth scale and Time up and Go (TUG). Each patient underwent 30 treatment sessions, 5 days a week. Patients were re-evaluated on the same scales after treatment. Data was analyzed using SPSS. Results: The paired sample t-test was used to see the effects of manual stretching and joint mobilization with neurodevelopment treatment to improve functional mobility among stroke patients. 24 patients received treatment with 30 sessions, 5 days a week. There was a significant improvement in their functional mobility. Their spasticity was also reduced. There was also a significant improvement in their cognitive abilities. Conclusion: The study concluded that techniques of manual stretching and joint mobilization with neurological development treatment show a significant improvement in functional mobility among stroke patients. Keywords: Stroke, Manual stretching, joint mobilization, neurodevelopmental techniques, functional mobility

Cognitive rehabilitation of patients with neurodegenerative diseases

Neurodegenerative diseases are the most common cause of cognitive disorders in the population, but their diagnosis and treatment face a number of difficulties, both purely clinical and organizational. Moreover, neurodegenerative diseases often serve as a background for the development of acute focal brain damage (for example, stroke), limiting the possibility of rehabilitation after them. In addition, degenerative changes in the brain associated with aging processes and early stages of neurodegenerative diseases make an important contribution to the formation of the «fragility of old age», which is the most important task of elderly medicine. Thus, acute focal lesions of the brain and neurodegenerative diseases require complex rehabilitation treatment aimed not only at motor, but also at cognitive functions. Drugs that mimic molecular signals initiating the processes of spontaneous recovery of neurons, glial cells and their connections in the brain can be used to expand the therapeutic window for rehabilitation. One of these drugs may be Cerebrolysin, which improves the results of restorative treatment of stroke and Alzheimer's disease.

Comparison of Clinical Characteristics between Transient Global Amnesia with and without Acute Focal Lesion in Hippocampus

Comparison of Clinical Characteristics between Transient Global Amnesia with and without Acute Focal Lesion in Hippocampus

Abstract WP230: No Difference of Cerebral Perfusion Between Transient Global Amnesia With and Without Acute Focal Lesion in Hippocampus

Introduction: In transient global amnesia (TGA), the etiology or pathogenesis is still in debate. It has been commonly suggested that TGA might be related to an ischemic event, migraine, or epileptic seizures. With the characteristic findings of diffusion-weighted images (DWI), cerebrovascular disease can be regarded as a cause of TGA. Hypothesis: Transient global amnesia may be associated with regional cerebral perfusion, especially in patients with DWI lesions. The aim of the present study is to reveal the clinical or radiological difference between TGA patients with and without acute lesions. Methods: We identified retrospectively TGA patients who fulfilled the standard criteria from January 2010 through March 2015. Within 72 hours from symptom onset, all patients were evaluated with brain MR images and an electroencephalography. According to the presence of acute lesion in the hippocampus, clinical features, vascular risk factors, and regional perfusion status with SPECT images were compared. Results: Of 61 TGA patients (mean age 60.6, female 18 patients), 20 patients had acute focal lesions in the hippocampus (size: 3.36 ± 0.64mm, 7 in the right, 9 in the left, and 2 in bilateral lesions). All lesions were located in the lateral border (CA1 region) of the hippocampus. In the comparison of clinical features, the duration of amnestic symptom was shorter in the lesion negative group than in the lesion positive group (5 hours, IQR 2.5-8.8 vs. 8 hours, IQR 5-13.5, p=0.07). However, there was no difference between TGA patients with and without DWI lesions in cerebrovascular risk factors or laboratory results. Of 23 patients underwent a cerebral SPECT, 6 patients who had DWI lesions had no abnormal findings. Of 17 patients without lesions, only 3 patients exhibited mild focal perfusion defect in both medial temporal, left frontal, and left fronto-temporal region, respectively. Conclusions: Except amnestic symptom duration, we failed to reveal any clinical difference including perfusion defect between TGA patients with and without DWI lesion. It might suggest the low probability of hypoperfusion in the hippocampus regardless of the presence of brain DWI lesions.

Structural correlates of motor adaptation deficits in patients with acute focal lesions of the cerebellum.

Studies of cerebellar patients employing modern lesion-symptom mapping techniques have provided valuable insights into the contribution of the cerebellum to motor adaptation. In patients with chronic focal lesions of the cerebellum, the process of adapting reaching movements to force field (FF) and visuomotor rotation (VM) perturbations relies on different anatomical structures located primarily within the territory of the superior hand area. By contrast, results within the territory of the inferior hand area are less consistent. Compensatory mechanisms may have masked the contribution of the inferior hand area. To test this hypothesis, reaching adaptation to FF and VM perturbations was investigated in 24 patients with acute and subacute lesions of the cerebellum. High-resolution magnetic resonance images were acquired to perform voxel-based lesion-symptom mapping (VLSM). VLSM confirmed that distinct and only partially overlapping areas located primarily within the territory of the superior hand area were crucial for adaptation to FF and VM. More specifically, current results add to previous findings that lobule V is of particular importance in FF adaptation, whereas lobule VI plays a more important role in VM adaptation. No clear evidence for a contribution of the inferior hand area to either task was found. Reach adaptation appears to depend primarily on the superior hand area within the cerebellum.

Visualization of acute focal lesions in rats with experimental autoimmune encephalomyelitis by magnetic nanoparticles, comparing different MRI sequences including phase imaging

To compare the sensitivity and specificity of phase imaging (PI) with other magnetic resonance imaging (MRI) methods in lesion detection in rats with experimental autoimmune encephalomyelitis (EAE), as an animal model for multiple sclerosis (MS). EAE was induced in rats (n = 14) by subcutaneous (s.c.) injection of myelin basic protein (MBP) and complete Freund's adjuvant (CFA). Control animals (n = 4) were given an s.c. injection of phosphate-buffered saline mixed with CFA. The development of local inflammatory processes, demyelinations, and blood-brain barrier (BBB) disruptions were monitored over 7 weeks in a 4.7T animal scanner by T1-, T2-, T2*-weighted images, magnetization transfer, and PI in the presence or absence of very small superparamagnetic iron oxide particles (VSOP) and confirmed by immunostaining using CD31, CD68, MBP, and albumin antibodies and Gallyas silver staining. EAE rats developed time-dependent local inflammations and BBB disruptions but no clear demyelinizations. In histological stainings these processes were trackable as accumulations of phagocytic monocytes and extravasal albumin. In MRI without application of VSOP inflammatory processes were not detectable. MRI in the presence of VSOP revealed inflammatory processes by the appearance of hypointense spots (hs). The specificity of PI to detect hs was similar to T1- and T2*-weighted images The calculated sensitivity was less than in corresponding T2*-weighted images. The diagnostic use of PI without VSOP as contrast agent to detect lesions is not recommended at field strength of 4.7T or lower.

Lesion-Symptom Mapping of the Human Cerebellum

High-resolution structural magnetic resonance imaging (MRI) has become a powerful tool in human cerebellar lesion studies. Structural MRI is helpful to analyse the localisation and extent of cerebellar lesions and to determine possible extracerebellar involvement. Functionally meaningful correlations between a cerebellar lesion site and behavioural data can be obtained both in subjects with degenerative as well as focal cerebellar disorders. In this review, examples are presented which demonstrate that MRI-based lesion-symptom mapping is helpful to study the function of cerebellar cortex and cerebellar nuclei. Behavioural measures were used which represent two main areas of cerebellar function, that is, motor coordination and motor learning. One example are correlations with clinical data which are in good accordance with the known functional compartmentalisation of the cerebellum in three sagittal zones: In patients with cerebellar cortical degeneration ataxia of stance and gait was correlated with atrophy of the medial (and intermediate) cerebellum, oculomotor disorders with the medial, dysarthria with the intermediate and limb ataxia with atrophy of the intermediate and lateral cerebellum. Similar findings were obtained in patients with focal lesions. In addition, in patients with acute focal lesions, a somatotopy in the superior cerebellar cortex was found which is in close relationship to animal data and functional MRI data in healthy control subjects. Finally, comparison of data in patients with acute and chronic focal lesions revealed that lesion site appears to be critical for motor recovery. Recovery after lesions to the nuclei of the cerebellum was less complete. Another example which extended knowledge about functional localisation within the cerebellum is classical conditioning of the eyeblink response, a simple form of motor learning. In healthy subjects, learning rate was related to the volume of the cortex of the posterior cerebellar lobe. In patients with focal cerebellar lesions, acquisition of eyeblink conditioning was significantly reduced in lesions including the cortex of the superior posterior lobe, but not the inferior posterior lobe. Disordered timing of conditioned eyeblink responses correlated with lesions of the anterior lobe. Findings are in good agreement with the animal literature. Different parts of the cerebellar cortex may be involved in acquisition and timing of conditioned eyeblink responses in humans. These examples demonstrate that MRI-based lesion-symptom mapping is helpful to study the contribution of functionally relevant cerebellar compartments in motor control and recovery in patients with cerebellar disease. In addition, information about the function of cerebellar cortex and nuclei can be gained.

Aphasia, neglect and extinction are no prominent clinical signs in children and adolescents with acute surgical cerebellar lesions

The aim of the present study was to examine if clinically significant signs of aphasia, neglect or extinction, which have a well-known cerebral lateralization, are present in children and adolescents with acute focal lesions following tumour surgery in the cerebellum. Eight children and adolescents with cerebellar tumours were tested within days after tumour surgery. None of the children had received radiation or chemotherapy at the time of testing. Eleven age- and education-matched control subjects with major orthopedic surgery participated. High-resolution magnetic resonance images showed lesions of the right cerebellar hemisphere in three and of the left hemisphere in five children. Standard aphasia tests revealed no statistically significant difference comparing children with right- and left-sided lesions and controls. Mild signs of language disturbance, however, were present in single subjects with right-sided cerebellar lesions. Neglect and extinction tasks revealed minor abnormalities, which lacked consistent lateralization and were best explained by more unspecific attentional deficits and motor disorders in acute post-surgical stage. Acute right-sided cerebellar lesions can be followed by mild signs of language disturbances in single subjects. Clinically significant signs of neglect and extinction, however, are not observed in children and adolescents with acute surgical cerebellar lesions.

Verb generation in children and adolescents with acute cerebellar lesions

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 of the children had received radiation or chemotherapy at or before the time of testing. Eleven age- and education-matched control subjects participated. Subjects had to generate verbs to blocked presentations of photographs of objects. As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Detailed analysis of individual 3D-MR images revealed that lesions affected cerebellar hemispheres in all children and adolescents. The right cerebellar hemisphere was affected in four and the left hemisphere in five subjects. In the present study, naming and verb generation accuracy were preserved in the majority of subjects with cerebellar lesions. No significant signs of learning deficits were observed, as reduction of reaction times over blocks was not different compared to controls. There was a trend of children and adolescents with right-hemispheric lesions to perform worse compared to controls. In this group, however, significant signs of dysarthria were present. In sum, no significant signs of disordered verb generation were observed in children and adolescents with acute cerebellar lesions. Findings suggest that the role of the cerebellum in verb generation may be less pronounced than previously suggested. Findings need to be confirmed in a larger group of subjects with acute focal lesions.

Fundus Lesions in Malignant Hypertension: VI. Hypertensive Choroidopathy

Experimental renovascular malignant arterial hypertension was produced, by modified Goldblatt's procedures, in 60 rhesus monkeys, and hypertensive fundus changes were studied in detail (by serial ophthalmoscopy and fluorescein fundus angiography in all monkeys on a long-term follow-up, and pathologically in 29 eyes). In hypertensive choroidopathy, retinal pigment epithelial (RPE) lesions and serous retinal detachment (RD) were the classic ophthalmoscopic lesions, whereas fluorescein fundus angiography and histopathologic studies revealed marked abnormalities in the choroidal vascular bed, in addition to the changes in the RPE. The RPE lesions could be subdivided into (1) initial acute focal lesions (due to focal RPE infarction), and (2) degenerative lesions, which developed later and were progressive in nature, maximally involving the macular and peripheral regions of the fundus. The RD developed most commonly in the posterior pole and infrequently involved the peripheral retina. The choroidal vascular bed showed impaired circulation and extensive occlusive and ischemic changes. These studies revealed that hypertensive choroidopathy is as important a fundus change as hypertensive retinopathy. The pathogenesis of hypertensive choroidopathy is discussed in detail; the evidence indicates that it is due to choroidal ischemia, and that hypertensive choroidopathy and retinopathy are two independent and unrelated manifestations of renovascular malignant hypertension.

Acute vascular lesions in developing coronary collaterals.

Three weeks after the onset of progressive obliteration of the left circumflex coronary artery a number of small arteriolar preexistent collaterals develop into small arteries. Acute focal lesions, localized in the central parts of the collateral, are described at the light microscopic and at the ultrastructural level.

Pneumonia and erythema multiforme exudativum: Report of four cases and three autopsies

Four cases of erythema multiforme exudativum are reported; three of them were fatal and the autopsy findings are presented. There was a diffuse miliary type of pneumonia in two of the fatal cases and in the one with recovery. The pneumonia in these patients resembled that of the severe and diffuse type of primary atypical pneumonia of unknown etiology in every respect —clinically, roentgenographically and pathologically; it resembled that of psittacosis in many respects. In one of the fatal instances there was a significant amount of secondary bacterial infection. Evidence suggesting a possible infection with a psittacosis-like virus was obtained in three cases. In Case I there was a significantly high titer of antibody for psittacosis virus demonstrated by complement fixation. In Case II there was a significant rise in titer of such antibodies during the course of the illness and a history of contact with a dead pigeon eight days before the first symptom. In Case IV there was only a history of contact with a sparrow during its fatal illness. The latter patient died on the fifth day of his disease and the lungs showed only a few acute focal lesions in the alveolar walls. No virus was isolated from any of the patients. Cold agglutinins were demonstrated in high titer in the serum of the patient in Case I and appeared during the course of the illness in the patients in Cases II and III.

The role of the circulation in the production of peptic ulcer

From histologic study of 161 cases of acute focal lesions of the gastric mucosa, we would conclude. 1. Regardless of etiology, focal gastric lesions are the result of chronic circulatory insufficiency to all the structures of the gastric wall. 2. Such circulatory deficiency is part of a generalized insufficiency intensified by intrinsic vascular peculiarities of the stomach, of an anatomical or vasomotor nature. 3. Generalized circulatory insufficiency may be established through quantitative, qualitative or vasomotor alterations in the circulatory system.