chondroitin-sulfates and Brain-Ischemia

Topics: Acute Disease; Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Databases, Factual; Dermatan Sulfate; Drug Combinations; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Odds Ratio; Pulmonary Embolism; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Venous Thrombosis

Topics: Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Cost-Benefit Analysis; Dalteparin; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; MEDLINE; Thrombophlebitis

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

This report presents data from pilot studies of Org 10172 in the management of patients with acute ischemic stroke. The studies have established a potentially optimal dosage and treatment regimen and have provided information for the development of a large randomized trial. The trial of Org 10172 in acute stroke treatment is now underway in the United States.

Topics: Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Drug Evaluation; Factor Xa Inhibitors; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Incidence; Pilot Projects; Prothrombin; Thrombolytic Therapy; Treatment Outcome; United States

To delineate the frequency, course, risk factors, and neuroanatomy of hemispatial neglect in a large stroke cohort.. One thousand two hundred eighty-one patients with acute stroke were enrolled in a multicenter trial of an anticoagulant. Presence and severity of neglect were assessed with the NIH Stroke Scale (NIHSS) neglect item, assessing tactile extinction and visuospatial neglect at entry, daily for 1 week, and at 3 months. Head CT scans were obtained on day 7, and infarct location and size were characterized.. Neglect was common at presentation, occurring in 43% of right brain-lesioned (RBL) patients and 20% of left brain-lesioned (LBL) patients (p < 0.001). At 3 months, neglect was present in 17% of RBL patients and in 5% of LBL patients (p < 0.001). In RBL patients, neglect was most frequently associated with lesions involving the (in descending order) temporal, parietal, frontal, occipital lobes, basal ganglia, and thalamus. Neglect was more common and persistent with cortical than with subcortical lesions. Increasing age was associated with increased risk of neglect in RBL patients, whereas gender and handedness did not significantly affect neglect frequency.. This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Basal Ganglia; Brain Ischemia; Cerebral Cortex; Cerebral Infarction; Chondroitin Sulfates; Cohort Studies; Dermatan Sulfate; Dominance, Cerebral; Double-Blind Method; Drug Combinations; Female; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Perceptual Disorders; Risk Factors; Severity of Illness Index; Thalamus

The impact of early transcranial Doppler ultrasonography (TCD) upon stroke subtype diagnosis is unknown and may affect therapeutic strategies. In this study, the diagnostic usefulness of TCD in stroke subtype diagnosis according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) study was investigated in patients with acute cerebral ischemia.. TCD examination within 24 h of symptom onset was performed in 50 consecutive patients with acute cerebral ischemia. Of these 54% were female. Sixty percent of patients were black, 36% white, and 4% Asian. Initial TOAST stroke subtype diagnosis (ITSSD) was based upon clinical presentation and initial brain imaging studies. Modified TOAST stroke subtype diagnosis was determined subsequently after additional review of the TCD examination. Final TOAST stroke subtype diagnosis was determined at hospital discharge, incorporating all diagnostic studies. Using final TOAST stroke subtype diagnosis as the 'gold standard' ITSSD and modified TOAST stroke subtype diagnosis were compared in order to determine additional benefit from the information obtained by TCD. Data were collected retrospectively by a single investigator.. ITSSD classified 23 of 50 (46%) patients correctly. After TCD, 30 of 50 (60%) patients were classified correctly, for an absolute benefit of 14% and a relative benefit of 30% (p = 0.018). Most benefit from TCD was observed in the TOAST stroke subtype category large-artery atherosclerosis, in particular in patients with intracranial vascular disease. In this category, ITSSD had a sensitivity of 27% which increased to 64% after TCD (p = 0.002).. TCD within 24 h of symptom onset improves the accuracy of early stroke subtype diagnosis in patients with acute cerebral ischemia due to large-artery atherosclerosis. This may have clinical implications for early therapeutic interventions.

Topics: Acute Disease; Aged; Antifibrinolytic Agents; Brain Ischemia; Cerebrovascular Circulation; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparitin Sulfate; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial

To examine the responses to early IV administration of an anticoagulant or placebo started within 24 hours of stroke among persons with an ipsilateral occlusion or severe stenosis of the internal carotid artery (ICA) identified by carotid duplex imaging.. Patients with ischemic stroke of the cerebral hemisphere secondary to an ipsilateral occlusion or severe stenosis of the ICA generally have a poor prognosis. Early, accurate identification of these patients might permit improved treatment.. Exploratory analysis of outcomes at 7 days and 3 months was performed among patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) who had an ischemic stroke in the cerebral hemisphere ipsilateral to an occlusion or a stenosis >50% of the ICA identified by carotid duplex imaging.. Regardless of treatment, patients with duplex evidence of an occlusion of the ICA had more severe strokes and poorer outcomes at 7 days and 3 months than patients who had a stenosis. Favorable outcomes at 7 days were noted in 64 of 119 patients given danaparoid (53.8%) and 41 of 108 patients treated with placebo (38.0%; p = 0.023). By 3 months, favorable outcomes were noted in 82 patients given danaparoid (68.3%) and 58 patients administered placebo (53.2%; p = 0.021).. Early identification by duplex imaging of an occlusion or severe stenosis of the ICA ipsilateral to a hemispheric ischemic stroke might improve selection of patients who could be treated with emergent anticoagulation. Further testing of this approach is needed.

Topics: Anticoagulants; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Drug Combinations; Female; Fibrinolytic Agents; Functional Laterality; Glasgow Coma Scale; Heparitin Sulfate; Humans; Male; Placebos; Time Factors; Trauma Severity Indices; Treatment Outcome; Ultrasonography, Doppler, Duplex

While previous studies suggest that the peak time period for the occurrence of ischemic stroke is in the mid- to late-morning hours, detailed information pertaining to circadian variations among the various stroke subtypes has been limited. The purpose of our study was to define the circadian patterns of symptom onset in an acute stroke trial with an established system for stroke subtype classification.. An analysis was conducted on 1272 patients enrolled in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) study. All patients had a documented time of stroke symptom onset, and all stroke subtype determinations were made by a single rater.. The Greatest portion of atherothrombotic strokes (25.7%), cardioembolic strokes (30.5%), and strokes of other/unknown mechanism (27.1%) occurred between 6:01 AM and 12:00 noon. The greatest portion of lacunar strokes (31.6%) were present on awakening. More than one half of the infarcts in this series were either present on awakening or occurred in the mid- to late-morning hours. The correlation between stroke subtype and time of symptom onset did not reach statistical significance (P=0.07, Pearson's chi(2) method).. Although there is a trend for clustering of ischemic stroke in the morning hours, there is insufficient specificity to predict with any reasonable likelihood the stroke subtype according to the circadian pattern of symptom onset.

Topics: Anticoagulants; Brain Ischemia; Cerebrovascular Disorders; Chondroitin Sulfates; Circadian Rhythm; Dermatan Sulfate; Forecasting; Heparitin Sulfate; Humans

Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States.. This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible.. Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively.. Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.

Topics: Brain Ischemia; Certification; Chondroitin Sulfates; Dermatan Sulfate; Education, Medical, Continuing; Fibrinolytic Agents; Glycosaminoglycans; Heparitin Sulfate; Humans; Predictive Value of Tests; Reproducibility of Results; Treatment Outcome; United States

A multicentre, double-blind, randomized study was performed in 179 patients with acute ischaemic stroke resulting in limb paresis. The purpose was to compare the safety and efficacy of Org 10172 (1250 anti-Xa Units s.c. once daily) and heparin sodium (5000 IU s.c. twice daily) in preventing deep-vein thrombosis (DVT). Prophylaxis started within 72 hours of the onset of stroke and continued for at least 9 days. To detect DVT, patients underwent a daily 125I-fibrinogen leg scanning which, if found positive, was followed by venography. A first computed tomography scan of the brain was performed at screening to rule out cerebral haemorrhage and a second at cessation of treatment to detect any haemorrhagic transformations. At the 2-3-months' follow-up period the patients were examined for signs and symptoms of DVT or pulmonary embolism. On an intention-to-treat analysis, DVT occurred in 14.6% of patients receiving Org 10172 and in 19.8% of those receiving heparin during the treatment period (p = 0.392, NS). Pulmonary embolism was diagnosed in one patient in each group. Major conversion to a symptomatic haemorrhagic brain infarct was found in one patient in each group. Death occurred in 13.5% of patients treated with Org 10172 and in 6.7% of patients treated with heparin (p = 0.135, NS). Deaths were mainly related to pulmonary infection and cerebral oedema, thus considered to be due directly to the clinical status of the patients. 1250 anti-Xa Units of Org 10172 once daily is both safe and as effective as 5000 IU of heparin sodium twice daily given for DVT prophylaxis in patients with acute ischaemic stroke of recent onset.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Injections, Subcutaneous; Male; Thrombophlebitis; Treatment Outcome

The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).. A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician's certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests.. The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine.. The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.

Topics: Anticoagulants; Arteriosclerosis; Brain Ischemia; Cerebral Infarction; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Embolism; Glycosaminoglycans; Heparinoids; Heparitin Sulfate; Humans

Venous thrombo-embolism is a common complication in patients with acute ischaemic stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been evaluated for the prevention of deep vein thrombosis in patients with acute ischaemic stroke in two studies. In a double-blind study, 75 patients were randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The corresponding rates for proximal deep vein thrombosis were 0 and 16%, respectively (p = 0.01). There was one major haemorrhage in the treated group and one minor haemorrhage in the placebo group. In the second study, the safety and efficacy of Orgaran was compared with unfractionated heparin in the prevention of deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients with marked lower limb paralysis secondary to stroke were randomized to receive Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12-hourly or unfractionated heparin (42 patients) in a dose of 5,000 units subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p = 0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%, respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Glycosaminoglycans; Hemiplegia; Heparin; Heparinoids; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Pulmonary Embolism; Thrombophlebitis

This report presents data from pilot studies of Org 10172 in the management of patients with acute ischemic stroke. The studies have established a potentially optimal dosage and treatment regimen and have provided information for the development of a large randomized trial. The trial of Org 10172 in acute stroke treatment is now underway in the United States.

Topics: Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Drug Evaluation; Factor Xa Inhibitors; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Incidence; Pilot Projects; Prothrombin; Thrombolytic Therapy; Treatment Outcome; United States

To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke.. Double-blind randomized trial.. Seven Canadian university-affiliated hospitals.. Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis.. Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner.. Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically.. Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups.. Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Fibrinolytic Agents; Follow-Up Studies; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Thrombophlebitis

Topics: Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Heparitin Sulfate; History, 20th Century; Humans; Stroke

There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value.. We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit.. The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001).. The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units.

Topics: Acute Disease; Anticoagulants; Brain Damage, Chronic; Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Confounding Factors, Epidemiologic; Dermatan Sulfate; Female; Glasgow Outcome Scale; Heparitin Sulfate; Humans; Male; Middle Aged; Motor Activity; Movement Disorders; Multicenter Studies as Topic; Prognosis; Recovery of Function; Retrospective Studies; Severity of Illness Index; Stroke; Stroke Rehabilitation; Treatment Outcome

Outcome measures in acute stroke trials are being refined. Changes in neurological deficits might be useful outcome measures because they can measure the entire spectrum of deficits.. We analyzed data from the acute stroke treatment trial Trial of Org 10172 in Acute Stroke Treatment (TOAST). Using logistic regression analysis, we modeled the probability of the TOAST predefined very favorable outcome (VFO; both Glasgow Outcome Scale 1 and modified Barthel Index 19 to 20) at 3 months. Within-subject changes (baseline-3 months) on the National Institutes of Health Stroke Scale (NIHSS) was the main predictor of interest.. The baseline median NIHSS for the entire TOAST cohort was 7, and it improved by 4 points (interquartile range 3 to 6) among 603 patient with VFO and by 2 points (interquartile range -1 to 5) among 638 patients without a VFO (P<0.001). The odds for VFO increased by 2.29 (95% CI, 2.06 to 2.54; P<0.001) for each 1-point improvement on the NIHSS. In receiver operating characteristic analysis, final NIHSS < or =2 was a good predictor of VFO, but no single NIHSS change cut point was a good predictor of VFO.. NIHSS change appears to be a useful outcome measure for acute stroke trials and is not fully comparable to dichotomized functional outcomes.

Topics: Acute Disease; Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Cohort Studies; Data Interpretation, Statistical; Dermatan Sulfate; Heparitin Sulfate; Humans; National Institutes of Health (U.S.); Odds Ratio; Placebos; Regression Analysis; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Stroke; Treatment Outcome; United States

The aim of this study was to propose a classification system for childhood arterial ischaemic stroke (AIS). Subtypes from the Trial of Org 10172 in Acute Stroke Therapy (TOAST) classification, previously shown to be applicable to children, were retained in the proposed Paediatric Stroke Classification (PSC). Additional important paediatric AIS aetiologies were identified from a literature review. Preliminary validation was performed by three raters who categorized clinical vignettes from 135 patients (66 male; median age 6.3 y, range 0.1 to 16 y). Eight aetiological subtypes were identified and defined, as follows: (1) sickle cell disease; (2) cardioembolic; (3) moyamoya syndrome; (4) cervical arterial dissection; (5) steno-occlusive cerebral arteriopathy; (6) other determined aetiology; (7) multiple probable/possible aetiologies; and (8) undetermined aetiology. There was very good agreement between the raters about categorization of the vignettes. Causes of disagreement were identified and final categories and definitions were modified accordingly. We conclude that the PSC enables the categorization of children with AIS into aetiological subtypes relevant to this age group. This will be useful in multicentre studies of natural history and treatment but will require further independent validation.

Topics: Adolescent; Anemia, Sickle Cell; Brain Ischemia; Carotid Artery, Internal, Dissection; Cerebral Infarction; Child; Child, Preschool; Chondroitin Sulfates; Data Collection; Dermatan Sulfate; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Infant; Infant, Newborn; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Moyamoya Disease; Reproducibility of Results; Review Literature as Topic; Severity of Illness Index; Stroke

This study examines the alteration of oligodendrocyte progenitor cells which express membrane NG2 chondroitin sulfate proteoglycan after focal ischemia in the rat brain. Adult male Sprague-Dawley rats were subjected to 90 min occlusion of the middle cerebral artery, followed by reperfusion time of up to 2 weeks. The distribution and morphological changes in NG2-positive oligodendrocyte progenitor cells were immunohistochemically examined. Stellate-shaped NG2-positive cells with multiple branched processes were detected in both the gray and white matter of normal brain. After 2 weeks of reperfusion, NG2-positive cells in the area surrounding the infarction site (peri-infarct area) clearly showed enlarged cell bodies with hypertrophied processes. These stained strongly for NG2. Although the number of NG2-positive cells was increased significantly in the peri-infarct area, it decreased markedly in the infarct core compared to controls. Double immunostaining revealed that these NG2-positive cells were neither astrocytes nor microglia, but NG2-positive oligodendrocyte progenitor cells. These progenitor cells are known to differentiate into oligodendrocytes. As such, this upregulation of NG2 expression may be an adaptive mechanism attempting to remyelinate rat brain tissue after ischemic insult. Only further study will elucidate this hypothesis.

Topics: Animals; Antigens; Brain Ischemia; Chondroitin Sulfates; Male; Oligodendroglia; Proteoglycans; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Stem Cells

Topics: Anticoagulants; Brain Ischemia; Cerebral Hemorrhage; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparitin Sulfate; Humans; Time Factors; Treatment Outcome; United States

Topics: Acute Disease; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Heparitin Sulfate; Humans; Randomized Controlled Trials as Topic

We evaluated the safety and possible efficacy of large doses of the heparinoid ORG 10172 in 57 patients with acute or progressing ischemic stroke. Patients received a loading bolus of the drug followed by a maintenance intravenous infusion for 7 days. The plasma level of ORG 10172 was monitored by the degree of inhibition of coagulation factor Xa. In general, the drug was well tolerated and few hemorrhagic complications occurred. Two patients with large cardioembolic hemispheric strokes had intracranial hemorrhagic complications. Most patients improved during treatment. By 3 months after the stroke, 37 patients (65%) had a favorable outcome (minimal or no residual disability). This study suggests that high-dose intravenous infusions of ORG 10172 can be safely given to patients with acute ischemic stroke.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Ischemia; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparitin Sulfate; Humans; Injections, Intravenous; Middle Aged; Pilot Projects