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Biomedical subjects

Peter D Schellinger

Publications and source records attributed to Peter D Schellinger.

At least 37 records · Page 2Linked to original sources
PubMed2005

The evolving role of advanced MR imaging as a management tool for adult ischemic stroke: a Western-European perspective.

New and more advanced diagnostic imaging techniques for acute stroke triage have the potential to not only improve the quality of care but also reduce health care costs. Although sufficiently large and methodologically sound studies with regard to cost effectiveness of MR imaging are lacking, the overall impression is that MR imaging has revolutionized not only the diagnosis but also the open and investigational management of neurologically ill patients.

Adult↗
PubMed2005

Efficacy and costs of secondary prevention with antiplatelets after ischaemic stroke.

Ischaemic stroke and other atherothrombotic events substantially increase the medico-economic burden because of their high treatment costs and long-lasting disabilities with need for chronic care. Studies have shown that the cost of stroke represents approximately 3 - 5% of the annual health budget. Antiplatelet agents play a major role in secondary stroke prevention. Acetylsalicylic acid (ASA), ASA combined with extended-release dipyridamole (ER-Dip), and clopidogrel are all acceptable choices for first-line treatment in the secondary prevention of stroke. The newer antiplatelets, however, are more expensive than ASA, and their cost-effectiveness is not easily estimated. ASA has to be given to 33 stroke patients to prevent one future stroke, myocardial infarction (MI) or vascular death compared with placebo. Adding ER-Dip to ASA increases the benefit for the patients. A total of 33 stroke patients had to be treated with this combination, instead of ASA, to prevent one stroke. However, the combination of ASA plus ER-Dip does not prevent MI, vascular death or the combined end point of either stroke or death. Clopidogrel is more effective than ASA in preventing a combined end point of ischaemic stroke, MI, or vascular death, but it has not been shown to be superior to ASA in preventing recurrent stroke in transient ischaemic attack or stroke patients. Several subgroups, such as stroke patients with additional peripheral artery disease, patients with prior coronary artery bypass, patients with insulin-dependent diabetes, and patients with recurrent vascular events, were identified, in whom the benefit of clopidogrel is amplified. Taking economical aspects into account, the fixed combination of ASA and ER-Dip can be recommended for secondary stroke prevention as a first-line alternative to ASA in patients without major comorbidity. In patients with higher comorbidity, clopidogrel may be more effective for the individual patient compared with ASA, and might also be cost-effective. Furthermore, in patients with ASA intolerance clopidogrel is a useful, but expensive, alternative.

Aspirin↗
PubMed2005

Diagnostic and prognostic value of early MR Imaging vessel signs in hyperacute stroke patients imaged <3 hours and treated with recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Analogous to the CT hyperattenuated vessel sign (HMCAS), MR imaging may show hypo- or hyperintense vessels in acute ischemic stroke (AIS) patients. We assessed the diagnostic and prognostic strength of early MR imaging vessel signs in AIS patients treated with intravenous thrombolysis (IVT) within 3 hours of the onset of symptoms. METHODS: We studied AIS patients both treated with IVT and stroke MR imaged within 3 hours of the onset of symptoms and at 2 hours and 24 hours after treatment. We assessed the presence or absence of early vessel signs (hyperintense fluid-attenuated inversion recovery sign [FLAIR HVS]; gradient-echo susceptibility vessel sign [GRE SVS]) compared with a combined MR angiography/perfusion-weighted imaging reference and their strength for predicting clinical outcome (favorable vs. poor, independent vs. dependent, or dead, death), recanalization (by clot composition and flow), and hemorrhage in uni- and multivariate analysis. RESULTS: Fifty-six patients (age range, 76 years +/- 13 years; median National Institutes of Health stroke scale score [NIHSSS], 11) met the inclusion criteria. Forty-four patients (78.6%) had a vessel occlusion at baseline; 22 of them (50%) recanalized. Nineteen patients (33.9%) suffered some form of intracranial hemorrhage (ICH), 24 patients (42.9%) had an independent outcome, 18 patients (32.1%) a favorable outcome, and 14 patients died. Compared with our combined reference for vessel status PWI/MRA, the sensitivities of CT HMCAS, FLAIR HVS, and GRE SVS were 40%, 66%, and 34%, respectively, and improved during the hours that followed. Localization was accurately reflected by FLAIR HVS but not by GRE SVS. Only NIHSSS and age were independent predictors for recanalization and all clinical outcomes in multiple logistic regression analysis. CONCLUSION: Although early vessel signs can be helpful in the diagnosis of intravascular disease, they do not independently predict recanalization, ICH, or any of the three clinical outcomes in a multivariate logistic regression model. Thrombus composition as reflected by signal intensity characteristics on GRE and FLAIR does not predict the therapeutic effect of IVT.

Aged↗
PubMed2004

Experimental herpes simplex virus encephalitis: a long-term study of interleukin-6 expression in mouse brain tissue.

This study aimed to investigate the expression of interleukin-6 (IL-6) in acute and chronic herpes simplex virus encephalitis. In the brain of 15 SJL mice infected with herpes simplex virus type 1, strain F, and 14 control animals we performed a sequential quantitative analysis of expression of IL-6 mRNA with reverse transcription real-time polymerase chain reaction. The viral burden peaked in the acute disease, and then returned to a low baseline value. At day 7 following infection, IL-6 expression was significantly (2.05-fold) increased as compared with the baseline expression in uninfected animals. Twenty-one days after infection the mRNA expression still was significantly (1.78-fold) upregulated. No significant differences of IL-6 mRNA expression between infected and control mice were found after 2 and 6 months. We observed a 2.5-fold increase of IL-6 mRNA expression in control mice with increasing age of animals. We have additionally studied the clinical evolution of HSVE in IL-6 deficient mice. In experimental herpes simplex virus encephalitis IL-6, as a potent mediator of neuronal injury, is upregulated in the acute but not in the chronic disease. IL-6 deficient mice presented early and severe clinical signs of HSVE as compared to the wild-type C57/bl6 mice.

Animals↗
PubMed2004

Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration.

BACKGROUND AND PURPOSE: We aimed to determine the diagnostic value of perfusion computed tomography (PCT) and CT angiography (CTA) including CTA source images (CTA-SI) in comparison with perfusion-weighted magnetic resonance imaging (MRI) (PWI) and diffusion-weighted MRI (DWI) in acute stroke <6 hours. METHODS: Noncontrast-enhanced CT, PCT, CTA, stroke MRI, including PWI and DWI, and MR angiography (MRA), were performed in patients with symptoms of acute stroke lasting <6 hours. We analyzed ischemic lesion volumes on patients' arrival as shown on NECT, PCT, CTA-SI, DWI, and PWI (Wilcoxon, Spearman, Bland-Altman) and compared them to the infarct extent as shown on day 5 NECT. RESULTS: Twenty-two stroke patients underwent CT and MRI scanning within 6 hours. PCT time to peak (PCT-TTP) volumes did not differ from PWI-TTP (P=0.686 for patients who did not undergo thrombolysis/P=0.328 for patients who underwent thrombolysis), nor did PCT cerebral blood volume (PCT-CBV) differ from PWI-CBV (P=0.893/P=0.169). CTA-SI volumes did not differ from DWI volumes (P=0.465/P=0.086). Lesion volumes measured in PCT maps significantly correlated with lesion volumes on PWI (P=0.0047, r=1.0/P=0.0019, r=0.897 for TTP; P=0.0054, r=0.983/P=0.0026, r=0.871 for CBV). Also, PCT-CBV lesion volumes significantly correlated with follow-up CT lesion volumes (P=0.0047, r=1.0/P=0.0046, r=0.819). CONCLUSIONS: In hyperacute stroke, the combination of PCT and CTA can render important diagnostic information regarding the infarct extent and the perfusion deficit. Lesions on PCT-TTP and PCT-CBV do not differ from lesions on PWI-TTP and PWI-CBV; lesions on CTA source images do not differ from lesions on DWI. The combination of noncontrast-enhanced CT (NECT), perfusion CT (PCT), and CT angiography (CTA) can render additional information within <15 minutes and may help in therapeutic decision-making if PWI and DWI are not available or cannot be performed on specific patients.

Adult↗
PubMed2004

Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study.

BACKGROUND AND PURPOSE: We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain. METHODS: Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA. RESULTS: Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits. CONCLUSIONS: The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

Blood Flow Velocity↗
PubMed2004

Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging.

BACKGROUND AND PURPOSE: Although modern multisequence stroke MRI protocols are an emerging imaging routine for the diagnostic assessment of acute ischemic stroke, their sensitivity for intracerebral hemorrhage (ICH), the most important differential diagnosis, is still a matter of debate. We hypothesized that stroke MRI is accurate in the detection of ICH. To evaluate our hypotheses, we conducted a prospective multicenter trial. METHODS: Stroke MRI protocols of 6 university hospitals were standardized. Images from 62 ICH patients and 62 nonhemorrhagic stroke patients, all imaged within the first 6 hours after symptom onset (mean, 3 hours 18 minutes), were analyzed. For diagnosis of hemorrhage, CT served as the "gold standard." Three readers experienced in stroke imaging and 3 final-year medical students, unaware of clinical details, separately evaluated sets of diffusion-, T2-, and T2*-weighted images. The extent and phenomenology of the hemorrhage on MRI were assessed separately. RESULTS: Mean patient age was 65.5 years; median National Institutes of Health Stroke Scale score was 10. The experienced readers identified ICH with 100% sensitivity (confidence interval, 97.1 to 100) and 100% overall accuracy. Mean ICH size was 17.3 mL (range, 1 to 101.5 mL). The students reached a mean sensitivity of 95.16% (confidence interval, 90.32 to 98.39). CONCLUSIONS: Hyperacute ICH causes a characteristic imaging pattern on stroke MRI and is detectable with excellent accuracy. Even raters with limited film-reading experience reached good accuracy. Stroke MRI alone can rule out ICH and demonstrate the underlying pathology in hyperacute stroke.

Acute Disease↗
PubMed2004

Therapeutic time window of thrombolytic therapy following stroke.

Stroke is the third leading cause of death after myocardial infarction and cancer and the leading cause of permanent disability and of disability-adjusted loss of independent life-years in Western countries. Thrombolysis is the treatment of choice for acute stroke within 3 hours after symptom onset. Treatment beyond the 3-hour time window has not been shown to be effective in any single trial; however, meta-analyses suggest a somewhat less but still significant effect within 3 to 6 hours after stroke. It seems reasonable to apply improved selection criteria that would allow one to differentiate patients with a relevant indication for thrombolytic therapy from those who do not have one. We present an overview of a diagnostic approach to acute stroke management that allows the clinician to individualize patient management based on pathophysiologic reasoning and not rigid time windows established by randomized controlled trials. Therefore, this review concentrates on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke and then develops a treatment algorithm based on pathophysiologic information rendered by a multiparametric stroke magnetic resonance imaging protocol.

Brain Ischemia↗
PubMed2004

Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke--an MRI study.

Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33 degrees C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8% +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset.

Animals↗
PubMed2004

An update on thrombolytic therapy for acute stroke.

PURPOSE OF REVIEW: Stroke is the third leading cause of death after myocardial infarction and cancer, and is the leading cause of permanent disability and disability-adjusted loss of independent life-years in western countries. Thrombolysis is the treatment of choice for acute stroke within 3 h after the onset of symptoms. We present an overview of a diagnostic approach to acute stroke management that allows the individualization of patient management based on pathophysiological reasoning and not rigid time windows established by randomized controlled trials. RECENT FINDINGS: This review concentrates in the first part on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke, and in the second part develops a treatment algorithm based on pathophysiological information rendered by a multiparametric stroke magnetic resonance imaging protocol. SUMMARY: Thrombolysis is an effective therapy for ischemic stroke, whether performed intravenously within 3 h or intra-arterially within 3-6 h. Meta-analyses have provided evidence of an effect of intravenous thrombolysis beyond the 3 h time window, especially when improved selection criteria such as modern magnetic resonance imaging protocols are applied. Sadly, thrombolysis is still underused. Positive results from studies currently underway may encourage more centers to offer this therapy to an increasing number of stroke patients, and thereby reduce the considerable socioeconomic burden of stroke.

Cerebral Infarction↗
PubMed2004

Intracranial hemorrhage: the role of magnetic resonance imaging.

The initial and exclusive use of MRI in patients with a stroke syndrome is feasible, probably cost-effective, and even time saving when considering its potential wealth of information. MRI may be the diagnostic tool of choice in patients with all stages of stroke, especially in the hyperacute assessment of ICH, and could be equivalent to CT and CTA in SAH diagnosis. The authors' aim is to provide a comprehensive review about the potential role of MRI in evaluating ICH and SAH. Emerging applications, such as the assessment of microbleeds as a risk factor for secondary hemorrhage after thrombolysis and perihemorrhagic ischemic changes as a potential marker for patients likely to benefit from hematoma evacuation, are reviewed.

Cerebral Hemorrhage↗
PubMed2004

Acute stroke patients are being underfed: a nitrogen balance study.

INTRODUCTION: Patients with acute neurological illness may be hypercatabolic. The Harris-Benedict Equation (HBE) is used to estimate energy needs in acute stroke. A "stress factor" for stroke does not exist, and it is not known if the HBE accurately estimates the energy expenditure needs in acute ischemic or hemorrhagic stroke. We sought to assess nitrogen balance in patients with acute stroke and to determine the variables associated with negative nitrogen balance. MATERIALS AND METHODS: This was a case series, single-center study. Eligibility criteria included acute stroke requiring enteral nutrition, tolerating tube feedings at goal, normal urine output, and no underlying catabolic illness. Enteral feeding was adjusted to meet HBE requirements. After 24 hours of goal feeding, a 12-hour urine collection for nitrogen excretion was done. We determined if any of the following variables were associated with negative nitrogen balance: gender, glucose 6.6 mmol/L or more, age 80 years or older, National Institutes of Health Stroke Scale (NIHSS) 20 or higher, mechanical ventilation, and diabetes mellitus. RESULTS: We studied 27 patients (10 with intracranial hemorrhages and 17 with ischemic strokes) during an 18-month period. The median age was 80 (range: 48-90), and the median NIHSS was 19 (range: 4-38). The median time to feeding was 2 days (range: 1-8), the median time from onset to nitrogen balance was 5 days (range: 2-11), and the median interval between initiation of feeding and nitrogen collection was 2 days (range: 1-5)Negative nitrogen balance was seen in 12 of 27 (44%) patients. There was no relation between age, NIHSS, stroke type, admission glucose, history of diabetes, and mechanical ventilation use and nitrogen balance. Only 11 of 27 patients were anabolic. CONCLUSION: Critically ill stroke patients are being underfed using the current methods to estimate caloric needs. Hypercatabolism is common in acute stroke; clinical variables do not seem to allow prediction of this catabolic state.

Aged↗
PubMed2003

Stroke MRI in intracerebral hemorrhage: is there a perihemorrhagic penumbra?

BACKGROUND AND PURPOSE: Cerebral ischemia has been proposed as a contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). The search for surrogate parameters that allow treatment stratification for spontaneous ICH continues. We sought to assess the presence and prognostic effect of perihemorrhagic ischemic changes and hypoperfusion in a prospective stroke MRI study. METHODS: We performed stroke MRI in 32 patients with hyperacute ICH (mean, 16.9+/-17.2 mL) within 6 hours after symptom onset (mean, 3.1+/-1.3 hours). Clinical data at baseline (National Institutes of Health Stroke Scale) and on day 90 (Barthel Index, modified Rankin Scale) were assessed. Perihemorrhagic perfusion- and diffusion-weighted imaging changes were assessed in a 1-cm-wide area around the clot. RESULTS: Despite a mild perihemorrhagic mean transit time prolongation of 0.7+/-1.1 second, there were no significant perihemorrhagic apparent diffusion coefficient or mean transit time changes indicating irreversible ischemia or hypoperfusion. ICH size, time to imaging, or clinical severity at baseline or outcome were not reflected by changes of relative apparent diffusion coefficient or perfusion-weighted imaging. ICH size correlated with baseline clinical severity (r=0.51, P=0.005). There was a significant association (P=0.0494) and a significant negative correlation (r=-0.468, P=0.0103) of perihemorrhagic perfusion change with time from symptom onset not associated with ICH size. CONCLUSIONS: Perihemorrhagic hypoperfusion probably is a consequence of reduced metabolic demand (diaschisis) rather than a sign of ischemia. We found no evidence for a perihemorrhagic and potentially salvageable ischemic penumbra in hyperacute ICH. Further studies should address metabolic, toxic, apoptotic, and microvascular aspects.

Acute Disease↗
PubMed2003

Local intra-arterial fibrinolysis of thromboemboli occurring during neuroendovascular procedures with recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: There is a lack of systematic data regarding local intra-arterial fibrinolysis (LIF) of thromboemboli occurring during neuroendovascular procedures with the use of recombinant tissue plasminogen activator (rtPA). We report our technique for treating LIF of intracerebral thromboemboli occurring during neuroendovascular procedures. METHODS: Nine of 723 patients (1.2%) who underwent neuroendovascular procedures during the period from January 1997 to September 2002 suffered thromboembolic complications. These patients were treated by LIF with a maximum dose of 0.9 mg rtPA per kilogram body weight. Recanalization was categorized as successful (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) versus unsuccessful (TIMI grade 0 or 1), and clinical outcome was categorized as independent (Rankin Scale score 0 to 2) versus dependent or dead (Rankin Scale score 3 to 6). RESULTS: The minimum time between thrombus detection and beginning of LIF was 10 minutes, and the maximum time was 90 minutes. Successful recanalization was achieved in 4 of 9 patients (44%). All 9 patients suffered cerebral ischemic infarctions, and none of the patients sustained intracerebral hemorrhage. Two patients (22%) died from malignant brain infarctions. Four patients (44%) remained moderately disabled, and 3 patients (33%) were severely disabled 3 months after LIF. CONCLUSIONS: Although we used relatively high doses of rtPA, the recanalization rates and clinical outcome of LIF in our patients were not satisfactory. Strategies for the prevention of thromboemboli during neuroendovascular procedures must be improved, and novel fibrinolytic or thrombolytic techniques should be developed.

Adult↗
PubMed2003

MRI-guided therapy in acute stroke.

Stroke is the third leading cause of death after myocardial infarction and cancer and the leading cause of permanent disability and of disability-adjusted loss of independent life-years in Western countries. Thrombolysis is the treatment of choice for acute stroke within 3 h after onset of symptoms. Treatment beyond the 3-h time window has not been shown to be effective in any single trial, however, meta-analyses suggest a somewhat less but still significant effect within 3 to 6 h after stroke. It seems reasonable to apply improved selection criteria that allow the differentiation of patients with a relevant indication for thrombolytic therapy from those who have not. An overview of a diagnostic approach to acute stroke management that allows patient management individualization based on pathophysiological reasoning and not rigid time windows, established by randomized controlled trials is presented. Therefore, this review concentrates in the first part on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke, and in the second part, develops a treatment algorithm based on pathophysiological information rendered by a multiparametric stroke magnetic resonance imaging protocol.

Algorithms↗
PubMed2003

Imaging-based decision making in thrombolytic therapy for ischemic stroke: present status.

BACKGROUND: Thrombolysis is the treatment of choice for acute stroke within 3 hours after symptom onset. Treatment beyond the 3-hour time window has not been shown to be effective in any single trial; however, meta-analyses suggest a somewhat lesser but still significant effect within 3 to 6 hours after stroke. It seems reasonable to apply improved selection criteria that allow differentiation between patients with and without a relevant indication for thrombolytic therapy. SUMMARY OF REVIEW: The present literature on imaging in stroke has been thoroughly reviewed, covering Doppler ultrasound (DU), arteriography, CT, and MRI and including modern techniques such as perfusion CT, diffusion- and perfusion-weighted MRI (DWI, PWI), CT angiography and MR angiography (CTA, MRA), and CTA source image analysis (CTA-SI). The authors present their view of a comprehensive diagnostic approach to acute stroke, which challenges the concept of a rigid therapeutic time window. CONCLUSIONS: Information about the presence or absence of a vessel occlusion, whether by means of DU, CTA, or MRA, is essential before recombinant tissue plasminogen activator is given in the 3- to 6-hour time window. Clear demarcation of the irreversibly damaged infarct core and the ischemic but still viable and thus salvageable tissue at risk of infarction as seen on DWI/PWI/MRA or alternatively CT/CTA/CTA-SI should be obtained before thrombolysis is initiated within 3 to 6 hours. Once these advanced techniques are used, the therapeutic time window can be extended with acceptable safety. However, comprehensive informed consent is mandatory, especially when thrombolytic therapy is considered beyond established time windows.

Angiography, Digital Subtraction↗