Biomedical subjects

J Berrouschot

Publications and source records attributed to J Berrouschot.

At least 19 recordsLinked to original sources

PubMed2006

Aspirin resistance in secondary stroke prevention.

BACKGROUND: We investigated the platelet function in stroke patients treated with aspirin [acetylsalicylic acid (ASA)] for secondary stroke prevention during a follow-up period of 1 year. METHODS: In this prospective study 291 patients with first initiated aspirin therapy (300 mg/day) for secondary stroke prevention were included. Platelet aggregation measurements were performed 24 h, 3, 6, and 12 months after starting medication. RESULTS: Twenty-one of 291 patients (7.2%) were identified as primary ASA-non-responders (initial insufficient platelet inhibition) and 4.1% as secondary ASA-non-responders (insufficient platelet inhibition during follow-up). There were no significant differences between ASA-responders and ASA-non-responders concerning age, gender, risk factors, and stroke characteristics. CONCLUSION: Aspirin resistance in stroke patients is not uncommon. The clinical usefulness of routine platelet function tests needs to be proved by further trials.

Aged↗

PubMed2004

Hyperbaric and normobaric reoxygenation of hypoxic rat brain slices--impact on purine nucleotides and cell viability.

Hyperbaric oxygen treatment has been suggested as able to reduce hypoxia induced neuronal damage. The aim of the study was to compare the impact of different reoxygenation strategies on early metabolical (purine nucleotide content determined by HPLC) and morphological changes (index of cell injury after celestine blue/acid fuchsin staining) of hypoxically damaged rat neocortical brain slices. For this purpose slices (300 microm and 900 microm) were subjected to either 5 or 30 min of hypoxia by gassing the incubation medium with nitrogen. During the following reoxygenation period treatment groups were administered either 100% oxygen (O) or room air (A) at normobaric (1 atm absolute, NB-O; NB-A) or hyperbaric (2.5 atm absolute, HB-O; HB-A) conditions. After 5 min of hypoxia, both HB-O and NB-O led to a complete nucleotide status restoration (ATP/ADP; GTP/GDP) in 300 microm slices. However, reoxygenation after 30 min of hypoxia was less effective, irrespective of the oxygen pressure. Furthermore, administering hyperbaric room air resulted in no significant posthypoxic nucleotide recovery. In 900 microm slices, both control incubation as well as 30 min of hypoxia resulted in significantly lower trinucleotide and higher dinucleotide levels compared to 300 microm slices. While there was no significant difference between HB-O and NB-O on the nucleotide status, morphological evaluation revealed a better recovery of the index of cell injury (profoundly injured/intact cell-ratio) in the HB-O group. Conclusively, the posthypoxic recovery of metabolical characteristics was dependent on the duration of hypoxia and slice thickness, but not on the reoxygenation pressure. A clear restorative effect on purine nucleotides was found only in early-administered HB-O as well as NB-O in contrast to room air treated slices. However, these pressure independent metabolic changes were morphologically accompanied by a significantly improved index of cell injury, indicating a possible neuroprotective role of HB-O in early posthypoxic reoxygenation.

Adenosine Diphosphate↗

PubMed2002

Early biochemical and histological changes during hyperbaric or normobaric reoxygenation after in vitro ischaemia in primary corticoencephalic cell cultures of rats.

In a first series of experiments, the morphological changes of corticoencephalic cells by ischaemia were determined by staining with celestine blue-acid fuchsin in order to classify cells as intact, dark basophilic (supposedly reversibly injured) and preacidophilic or acidophilic (profoundly injured). Hypoxia and glucose-deprivation (in vitro ischaemia) markedly decreased the number of intact cells and correspondingly increased the number of both reversibly and profoundly damaged cells. The morphological characteristics indicated a partial recovery during reoxygenation either in the absence or presence of glucose and irrespective of whether normobaric or hyperbaric oxygen was used. In a second series of experiments, nucleoside triphosphate and diphosphate levels were determined in corticoencephalic cultures by high-performance liquid chromatography. Hypoxia in combination with glucose-deficiency markedly decreased the ATP:ADP, GTP:GDP and UTP:UDP ratios. A still larger fall of these ratios was observed both after normobaric and hyperbaric reoxygenation. In contrast, both normobaric and hyperbaric reoxygenation in the presence of glucose led to an almost complete recovery near the control normoxic values. In conclusion, the histological changes were not adequately reflected by changes in the nucleoside triphosphate:diphosphate ratios and, in addition, hyperbaric oxygen had neither favourable nor unfavourable effects on the early morphological and functional restitution of ischaemically damaged cells under the conditions of the present study.

Adenine Nucleotides↗

PubMed2002

[Diagnosis of aphasia on the stroke unit].

The first weeks of aphasia are called the acute stage. The rapid change and possible fluctuation of language deficits at that stage as well as concurrent phenomena such as drive disturbances, apraxia, or perseveration pose particular requirements for aphasia diagnosis. Professional language diagnosis in a stroke unit is necessary for detailed description of the language deficits, differential diagnosis of concomitant cognitive or functional disturbances, and a description of the dynamics of the deficits to start with specific therapeutical interventions as soon as the patient's health status allows. There are three published German aphasia test batteries especially constructed for diagnosis of acute aphasia language deficits. They differ with respect to content and pragmatic aspects and offer a range of applications, including the diagnosis of aphasia, recommendations for therapy, and the use in scientific studies.

Aphasia↗

PubMed2001

Prospective value of perfusion and X-ray attenuation imaging with single-photon emission and transmission computed tomography in acute cerebral ischemia.

BACKGROUND AND PURPOSE: The aim of the present study was to test the hypothesis that perfusion single-photon emission computed tomography (SPECT), carried out in addition to transmission computed tomography (TCT), improves the predictive value of brain imaging within the therapeutically relevant time window after acute cerebral ischemia. METHODS: Using TCT and [(99m)Tc]ethyl cysteinate dimer (ECD)-SPECT within 6 hours after symptom onset, we examined 108 patients (44 women, 64 men; mean age 65+/-13 years) with acute ischemic stroke attributed to the territory of the middle cerebral artery (MCA). In each case, 3 experts prospectively evaluated the early SPECT and TCT images. We correlated these ratings with follow-up TCT findings for the final infarction as well as with clinical outcome (Scandinavian Stroke Scale, Barthel Index, Modified Rankin Scale) after 30 and 90 days. RESULTS: Severe activity deficits on SPECT, not caused by local atrophy on TCT, were the best predictors (positive predictive value [PPV ]94%, 95% CI 89% to 99%; negative predictive value [NPV] 90%, 95% CI 78% to 100%; P<0.001) for evolving cerebral infarction. Complete MCA infarctions were predicted with significantly higher accuracy with early SPECT (area under receiver operating characteristic curve [AUC] index 0.91) compared with early TCT (AUC index 0.77) and clinical parameters (AUC index 0.73, P<0.05). Logistic regression analysis revealed 1 independent predictor for completed MCA territory infarction: SPECT activity deficits in the corresponding areas (PPV 88%, 95% CI 65% to 100%; NPV 96%, 95% CI 92% to 100%; P<0.001). Furthermore, death after stroke was optimally predicted by [(99m)Tc]ECD-SPECT. Clinical outcome up to 90 days after the stroke event best correlated with the degree of activity deficits in early SPECT (r=0.53, P<0.001). CONCLUSIONS: [(99m)Tc]ECD brain perfusion SPECT that completes TCT definitely improves the predictive value of brain imaging after acute cerebral ischemia. Thus, the combined imaging of brain edema and of cerebral perfusion early after stroke is recommended for clinical use.

Acute Disease↗

PubMed2001

Feasibility and safety of moderate hypothermia after massive hemispheric infarction.

BACKGROUND AND PURPOSE: Moderate hypothermia decreases ischemic damage in experimental stroke models. This multicenter study was performed to evaluate (1) the safety and feasibility of moderate hypothermia and (2) its potential to reduce intracranial hypertension in acute stroke patients. METHODS: Fifty prospective patients with cerebral infarction involving at least the complete middle cerebral artery territory treated with moderate hypothermia were evaluated. Hypothermia was induced with the use of cooling blankets as well as alcohol and ice bags within 22+/-9 hours after stroke onset and maintained for 24 to 72 hours; subsequently, patients passively rewarmed over a mean duration of 17 hours. Outcome was assessed at 4 weeks and at 3 months. RESULTS: Time required for cooling to <33 degrees C varied from 3.5 to 11 hours. The most frequent complications of hypothermic therapy were thrombocytopenia (70%), bradycardia (62%), and pneumonia (48%). Four patients (8%) died during hypothermia as a result of severe coagulopathy, cardiac failure, or uncontrollable intracranial hypertension. An additional 15 patients (30%) died during or after rewarming because of rebound increase in intracranial pressure (ICP) and fatal herniation. A shorter (<16 hours) rewarming period was associated with a more pronounced rise of ICP. Elevated ICP values were significantly reduced under hypothermia. Neurological outcome according to the National Institutes of Health Stroke Scale score 4 weeks after stroke was 29, and Rankin Scale score 3 months after stroke was 2.9. CONCLUSIONS: Moderate hypothermia is feasible in patients with acute stroke, although it is associated with several side effects. Most deaths occur during rewarming as a result of excessive ICP rise. Our preliminary observation that a longer duration of the rewarming period limits the ICP increase remains to be confirmed in future studies.

Acute Disease↗

PubMed2001

Predictors of fatal brain edema in massive hemispheric ischemic stroke.

BACKGROUND AND PURPOSE: Early identification of stroke patients at risk for fatal brain edema may be useful in selecting patients for aggressive interventions. Prior studies suggested that early nausea/vomiting and major hypodensity on baseline computed tomography (CT) were predictive of herniation. METHODS: This study was a retrospective multicenter case-control study of patients with large middle cerebral artery (MCA) strokes admitted within 48 hours of symptom onset. Medical records, laboratory data, and CT scans were analyzed. Cases, defined as patients who died of massive brain swelling, were compared with all remaining patients as controls. RESULTS: Two hundred one patients with large MCA strokes were identified: 94 (47%) died of brain swelling, 12 (6%) died of non-neurological causes, and 95 (47%) survived at day 30. Multivariable analysis, adjusted for age and clustered by center, identified the following predictors of fatal brain edema: history of hypertension (OR 3.0, 95% CI 1.2 to 7.6, P=0.02), history of heart failure (OR 2.1, 95% CI 1.5 to 3.0, P<0.001), elevated white blood cell count (OR 1.08 per 1000 white blood cells/microL, 95% CI 1.01 to 1.14, P=0.02), >50% MCA hypodensity (OR 6.3, 95% CI 3.5 to 11.6, P<0.001), and involvement of additional vascular territories (anterior cerebral artery, posterior cerebral artery, or anterior choroidal artery; OR 3.3, 95% CI 1.2 to 9.4, P=0.02). Initial level of consciousness, National Institutes of Health Stroke Scale score, early nausea/vomiting, and serum glucose were associated with neurological death in bivariable but not multivariable analyses. CONCLUSIONS: Among patients with large MCA infarctions, an increased risk of fatal brain edema is associated with history of hypertension or heart failure, increased baseline white blood cell count, major early CT hypodensity involving >50% of the MCA territory, and involvement of additional vascular territories. These data confirm and expand on prior research with a broad-based patient population. The presence of these risk factors identifies those stroke patients who may require aggressive therapeutic approaches.

Acute Disease↗

PubMed2000

Rheopheresis: rheologic, functional, and structural aspects.

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis for extracorporeal hemorheotherapy, eliminating an exactly defined spectrum of high molecular weight proteins from human plasma (e.g.: fibrinogen, alpha-2-macroglobulin, low-density lipoprotein cholesterol, IgM). This results in the improvement of blood flow and microcirculation initiated by lowering blood and plasma viscosity, and erythrocyte aggregation. In this context, microcirculation stands not only for the patency of small blood vessels, but for the complete interactive network between plasma, blood cells, the vessel wall, and cellular and extracellular compartments of the surrounding tissue. Insufficient tissue oxygenation leads to tissue damage, e.g., a microcirculatory disorder develops, creating acute as well as chronic symptoms. Therefore, impaired microcirculation has a rheologic, functional, and structural dimension with respect to involved organs or tissues. Rheopheresis represents a specific therapeutic approach with an acute rheologic as well as chronic functional and structural effects, which was confirmed in pilot and controlled clinical studies for several organ systems. Data from 2 controlled clinical trials are available for the safe and effective treatment in patients with age-related macular degeneration.

Adolescent↗

PubMed2000

Potential of rheopheresis for the treatment of acute ischemic stroke when initiated between 6 and 12 hours.

Improvement of hemorheology is one of the most important approaches in the treatment of acute ischemic stroke. We investigated the influence of extracorporal rheopheresis (ER) on cerebral blood flow in patients with acute ischemic stroke and evaluated its therapeutic effect. Thirty-three patients (rheopheresis group, 17; control group, 16; mean age 64 +/- 10 years) with acute ischemic stroke were included in our prospective randomized trial. The first treatment was started within 12 h after onset of symptoms, and treatment was repeated 3 times at an interval of 24 h. Hemorheological parameters were measured before and after each session. The cerebral blood flow was analyzed using 99mTc-ECD-SPECT. The functional and neurological outcomes were determined by follow-up investigations after 3 months. The hemorheological parameters were significantly different between the rheopheresis group (18% decrease of plasma viscosity, 55% decrease of red blood cell aggregation) and the control group (no decrease of both parameters). The single photon emission computed tomography (SPECT) analysis showed early reperfusion in 35% of the patients treated with rheopheresis and in 37% of the control group (NS). There were no differences in the neurological outcomes between the 2 groups. Extracorporal rheopheresis is practicable and safe. It rapidly and consistently improved the hemorheological parameters. Although this did not impact on cerebral perfusion or clinical outcome in patients with acute ischemic stroke in this report, we propose that ER deserves to be further evaluated by initiating the first treatment within 6 h post-insult.

Adolescent↗

PubMed2000

Mechanical ventilation in patients with hemispheric ischemic stroke.

OBJECTIVE: Whether stroke patients should be ventilated mechanically is still a contentious issue, because their outcome is very poor. We wanted to investigate how often mechanical ventilation is indicated in patients with hemispheric ischemic stroke as well as the outcome of these patients and the factors by which outcome is influenced. DESIGN: Prospective case series. SETTING: University hospital, neurocritical care unit. SUBJECTS: Subjects were 218 patients who met the following inclusion criteria: age 18-85 yrs, acute hemispheric ischemic infarction, clinical examination, and computed tomography within 6 hrs after the onset of symptoms. INTERVENTIONS: Mechanical ventilation was instituted with one or more of the following conditions: deterioration of consciousness with the inability to protect the airway; PaO2 of <60; P(CO2) of >60 mm Hg; breath rate of >40 breaths/min; and left heart insufficiency with definitive or impending pulmonary edema. MEASUREMENTS AND MAIN RESULTS: Mechanical ventilation was indicated for 52 (24%) of the 218 patients: in 47 (90%) patients because of deterioration of consciousness, and in five (10%) patients because of heart insufficiency and/or pneumonia. In a logistic regression model, the history of hypertension and a size of infarction exceeding two thirds of the middle cerebral artery territory were independent variables for the application of mechanical ventilation. After 3 months, 42 (81%) of these 52 patients had died. The most common cause of death was fatal midbrain herniation caused by complete middle cerebral artery infarction. Patients who survived had a good-to-fair outcome. CONCLUSIONS: New therapeutic strategies (e.g., hemicraniectomy) must be developed to reduce mortality and improve the outcome for this subgroup of ischemic stroke patients. Mechanical ventilation is and will remain a crucial element within such new concepts.

Adolescent↗

PubMed2000

Reperfusion and metabolic recovery of brain tissue and clinical outcome after ischemic stroke and thrombolytic therapy.

BACKGROUND AND PURPOSE: It is unclear from recent clinical trials whether thrombolytic agents are capable of facilitating reperfusion and metabolic recovery over time or whether a beneficial effect is counteracted by an increase in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment on metabolic recovery after reperfusion and clinical outcome. METHODS: Patients were prospectively studied with (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD-SPECT) before treatment with recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo (n=26) 6 to 8 hours after treatment and at 7+/-1 days. Activity deficits were graded, compared between the treatment groups, and correlated with clinical outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic brain tissue was defined as a 25% decrease on the SPECT graded scale. RESULTS: Patients with metabolic recovery (n=28) had a better chance of being functionally unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5, 95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36+/-38 versus 167+/-162 mL), regardless of whether metabolic recovery was observed within 6 to 8 hours of treatment or at 7 days. None of the 28 patients with metabolic recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without recovery (P=0.016). Treatment did not affect the incidence of brain tissue metabolic recovery. CONCLUSIONS: Brain tissue metabolic recovery after ischemic stroke was associated with a beneficial effect on clinical outcome and was not facilitated by treatment with 0.9 mg of intravenous rTPA.

Aged↗

PubMed1999

Extracorporeal rheopheresis in the treatment of acute ischemic stroke: A randomized pilot study.

BACKGROUND AND PURPOSE: Extracorporeal rheopheresis is a safe method to optimize hemorheology. Our aim was to determine whether treatment with extracorporeal rheopheresis in patients with acute ischemic hemispheric stroke improves cerebral perfusion as assessed with serial 99mTc-ethyl-cysteinate-dimer single-photon emission CT (99mTc-ECD SPECT). We also investigated how clinical outcome is associated with treatment and imaging results. METHODS: Thirty-three patients (mean age, 64+/-10 years) with acute ischemic hemispheric stroke were included in a prospective, randomized, parallel group pilot study. First treatment with or without extracorporeal rheopheresis took place within 12 hours after the onset of symptoms and was repeated 3 times at intervals of 24 hours. Hemorheological parameters were measured before and after each session. Each patient underwent 99mTc-ECD SPECT immediately before treatment, 6 to 8 hours after treatment, and after 5 days. A semiquantitative SPECT graded scale was used to measure depth and extent of activity deficits and thus to quantify the perfusion deficit. RESULTS: Seventeen patients were actively treated with extracorporeal rheopheresis, and 16 patients did not receive extracorporeal rheopheresis. After 3 months, no differences were found in the functional or neurological outcome. Despite a rapid, sustained decrease of plasma viscosity and erythrocyte aggregation in the rheopheresis group, there was no significant difference in the SPECT graded scale after therapy between the 2 groups. Patients with early reperfusion (decrease in the SPECT graded scale >25% 6 to 8 hours after therapy compared with the baseline examination) experienced a better functional outcome (Modified Rankin Scale) after 3 months compared with patients without reperfusion (P=0.04). CONCLUSIONS: Since quantitative flow mapping and clinical follow-up did not reveal any differences between patients who were treated with extracorporeal rheopheresis and controls, it appears very unlikely that extracorporeal rheopheresis enhances reperfusion after acute cerebral ischemia.

Acute Disease↗

PubMed1998

[Hyperbaric oxygen therapy (HBO) after acute focal cerebral ischemia].

For a large number of patients with stroke no therapeutic option can be offered, even after approval of thrombolytic therapy for treatment of acute ischemic stroke in the US. In cerebral ischemia local anoxia and energy failure lead to further cellular damage and finally to complete stroke. All therapeutic concepts try to salvage structurally intact tissue which is at risk for irreversible damage (so-called penumbra). Hyperbaric oxygen (HBO) treatment has been reported in animal models of cerebral ischemia, and in a few clinical reports. In general, the results of these studies have been promising. This review focuses on the clinical perspective of HBO therapy and summarizes both the clinical and experimental data available on HBO therapy following ischemic stroke.

Acute Disease↗

PubMed1998

Mortality of space-occupying ('malignant') middle cerebral artery infarction under conservative intensive care.

OBJECTIVE: To find what the mortality rate of space-occupying ('malignant') middle cerebral artery (MCA) infarction is under maximum conservative intensive care. To establish whether any early indicators of survival exist. DESIGN: Prospective descriptive study. SETTING: Neuro-critical care unit of a university hospital. PATIENTS: Fifty-three patients (mean age 64 +/- 10 years) with 'malignant' MCA infarction. INTERVENTIONS: Maximum conservative intensive care using a standardized protocol (heparin, osmotherapy, tromethamol, mild hyperventilation). The start of therapy was within 12 h after the onset of symptoms. MEASUREMENTS AND RESULTS: The Glasgow Coma Scale (GCS) and Scandinavian Stroke Scale (SSS) were recorded daily. A computed tomography (CT) scan was performed on admission, on day 3 and on day 7. SSS, Barthel Index and Rankin Scale of the surviving patients were recorded after 3 months. On admission, the mean GCS was 13 +/- 3 points and mean SSS 18 +/- 7 points. All patients had to undergo mechanical ventilation (23 +/- 26 h after the onset of symptoms) and were comatose after 28 +/- 30 h. Of 53 patients, 37 (70%) suffered brain death in the intensive care unit (ICU) after an average of 90 +/- 59 h. After 3 months 42/53 (79 %) patients had died. The Barthel Index of the surviving patients was 54 +/- 12 points, the SSS 25 +/- 9 points and the Rankin Scale 3 +/- 1 points. The deceased patients had a significantly higher body temperature on admission than the surviving patients (36.8 degrees C vs 36.3 degrees C). CONCLUSIONS: The mortality of patients with 'malignant' MCA infarction is very high despite maximum conservative intensive care.

Adult↗

PubMed1998

Differentiation between transient ischemic attack and ischemic stroke within the first six hours after onset of symptoms by using 99mTc-ECD-SPECT.

The aim of this study was to define the accuracy of 99mTc-ethyl cysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT) in distinguishing transient ischemic attack from completed ischemic stroke at early stages after the onset of symptoms. In a prospective study we examined 82 patients within 6 hours after the onset of symptoms (neurologic deficit caused by middle cerebral artery ischemia) using both 99mTc-ECD-SPECT and computed tomography (CT). The follow-up was based on Scandinavian Stroke Scale (SSS) 24 hours and 5-7 days, as well as on CT 7 days, after the event. SPECT evaluation was performed both visually and using semiquantitative region-of-interest (ROI) analysis. According to visual SPECT analysis, on admission 59 of 82 patients had activity deficits in the symptomatic hemisphere. After 7 days, all these patients had neurologic symptoms (SSS 28 +/- 12 points), caused by a cerebral infarction as evidenced with CT. Twenty-three of 82 patients displayed no early activity deficit despite clinical symptoms. None of these patients had neurologic symptoms after 7 days (indicating transient ischemic attack or prolonged reversible ischemic neurologic deficit). In the semiquantitative SPECT analysis, all patients had abnormal count densities in the respective ROI (activity < 90% compared with the contralateral side). All patients with transient ischemia (n = 23) had count rate densities more than 70% of the respective contralateral ROI, whereas all patients with subsequent infarction (n = 59) had values < 70%. Use of 99mTc-ECD-SPECT allows transient ischemia to be distinguished from ischemic infarction using relative regional activity thresholds within the first 6 hours after onset of symptoms.

Adult↗

PubMed1998

Extracorporeal membrane differential filtration--a new and safe method to optimize hemorheology in acute ischemic stroke.

OBJECTIVE: Can extracorporeal membrane differential filtration be used on patients with acute stroke to optimize their hemorheology without reducing the number of oxygen carriers (erythrocytes) - and is this form of treatment safe? SUBJECTS AND METHODS: In a prospective pilot study, 10 patients (67+/-4 years) suffering severe middle cerebral artery (MCA) stroke were treated with membrane differential filtration, which was first performed within 12 h following the onset of symptoms and repeated three times at intervals of 24 h. Hemorheological parameters were measured before and after each treatment session. RESULTS: Extracorporeal membrane differential filtration treatment immediately led to a significant and sustained drop in all hemorheological parameters (fibrinogen by 54%, alpha2-macroglobulin by 76%, total cholesterol by 65%, LDL by 82%, and HDL by 38%). Plasma viscosity dropped from 1.3 to 1.1 mPa s, erythrocyte aggregation by 57%. By contrast, hematocrit and the erythrocyte count remained constant. Treatment had no side-effects. CONCLUSIONS: Extracorporeal membrane differential filtration is a safe method to optimize hemorheology in patients with acute ischemic stroke.

Aged↗

PubMed1998

Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke.

BACKGROUND AND PURPOSE: To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. METHODS: An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. RESULTS: The pharmacokinetic target levels (enlimomab serum levels of >/=10 microg/ml) were consistently achieved in all patients receiving dose regimens III and IV. Non-serious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. CONCLUSIONS: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.

Acute Disease↗

PubMed1998

99m technetium-ethyl-cysteinate-dimer single-photon emission CT can predict fatal ischemic brain edema.

BACKGROUND AND PURPOSE: We sought to study the prognostic value of early 99mtechnetium-ethyl-cysteinate-dimer single-photon emission CT (99mTc-ECD SPECT) for fatal ischemic brain edema in patients with middle cerebral artery (MCA) stroke compared with the prognostic value of CT and of clinical findings. METHODS: We prospectively studied 108 patients clinically, with 99mTc-ECD SPECT, and with CT within 6 hours of symptom onset (Scandinavian Stroke Scale <40 points) appropriate to MCA ischemia. The follow-up consisted of Scandinavian Stroke Scale and CT on days 1 and 7, Barthel Index, and Modified Rankin Scale after 3 months. An activity deficit of the complete MCA territory on the SPECT scans and a parenchymal hypoattenuation of the complete MCA territory on CT scans were considered as predictors for a fatal MCA infarction due to mass effect and midbrain herniation. RESULTS: In 11 of 108 patients (10%), the MCA infarction was the cause of death. The sensitivity of SPECT for fatal outcome was 82% in both visual and semiquantitative analyses, while specificity was 98% and 99%, respectively. The sensitivity and specificity of baseline CT were 36% and 100%, respectively; the sensitivity and specificity of clinical findings (Scandinavian Stroke Scale, depressed level of consciousness, gaze deviation) varied from 36% to 73% and from 45% to 88%, respectively. In a multivariate logistic regression model, only SPECT findings were found to be independent predictors of malignant MCA infarction/death. CONCLUSIONS: We were able to identify patients with fatal MCA infarction with high accuracy by using 99mTc-ECD SPECT within 6 hours of stroke onset. This technique offers great potential to select stroke patients for specific therapies, eg, decompressive hemicraniectomy, soon after onset of symptoms.

Adolescent↗