Emergency transfer of acute stroke patients within the East Saxony telemedicine stroke network: a descriptive analysis.

BACKGROUND: Telemedicine may facilitate the selection of stroke patients who require emergency transfer to a comprehensive stroke center to receive additional therapies other than intravenous tissue plasminogen activator. AIMS AND/OR HYPOTHESIS: We sought to analyze frequency, patient characteristics, and specific therapies among emergently transferred patients within the telemedical Stroke East Saxony Network. METHODS: We reviewed consecutive patients who were transferred emergently from remote spoke sites to hub sites. Certified stroke neurologists performed teleconsultations 24/7, with access to high-speed videoconferencing and transfer of brain images. Emergent transfers were initiated when considered necessary by the stroke neurologist. RESULTS: In 2009 and 2010, we conducted 1413 teleconsultations and subsequently recommended transfer in 339 (24%) patients [mean age 64 ± 14 years, 54% males, median National Institutes of Health Stroke Scale score 5 (interquartile range, IQR 12). The mean teleconsultation-to-arrival time was 1·7 ± 0·8 h (median 1·6 h). Sixty-eight (20%) transferred patients had a nonstroke diagnosis. The remaining 271 (80%) patients had stroke diagnoses [ischemic stroke, 114 (34%); transient ischemic attack, 8 (2%); and intracranial haemorrhage, 149 (44%)]. Forty (35%) ischemic stroke patients received tissue plasminogen activator at spoke sites ('drip and ship'). Of the 240 stroke patients emergently transferred to the main hub site, 119 (49·6%) received at least one specific stroke therapy. CONCLUSIONS: A remarkable number of stroke patients can be transferred within a telemedical network to enable the delivery of specific stroke therapies that require advanced multispecialty expertise. Whether associated logistic efforts and costs have an impact on patients' clinical outcomes needs to be evaluated.

Genetic determinants of obesity and related vascular diseases.

Obesity is one of the major risk factors of vascular diseases, and its prevalence is increasing worldwide. In the past decade, progress has been made in the understanding of genetic determinants of obesity and obesity-associated diseases. Genome-wide association studies identified a number of genetic variants associated with obesity. In addition to common variants, FTO and MC4R, new loci, such as TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1 have been detected. In the past years, abdominal obesity has been shown to be a more important vascular risk factor than the body mass index. In the context of vascular risk assessment, identification of genetic polymorphisms associated with accumulation of visceral fat is of special importance. Some polymorphisms associated with abdominal obesity, such as variants of gene encoding microsomal triglyceride transfer protein, have been already discovered. In this chapter, we provide a review of genetic determinants of obesity and discuss their role in obesity-related vascular diseases.

Neuroborreliosis-associated cerebral vasculitis: long-term outcome and health-related quality of life.

Neuroborreliosis affects the nervous system after systemic infection with the spirochete Borrelia burgdorferi. Previously, cerebral vasculitis has been regarded as an extremely rare complication of neuroborreliosis. The data on the long-term outcome in patients with cerebral vasculitis due to neuroborreliosis are limited. The objective of this study was to perform a longitudinal analysis of cases of neuroborreliosis-associated cerebral vasculitis. We recruited all patients (n = 11) diagnosed with neuroborreliosis-associated in three neurological departments in an East German region. Inclusion criteria were sudden neurological deficits, magnetic resonance (MR) imaging findings that conform to cerebral ischemia or brain infarction, intrathecal synthesis of borrelia-specific antibodies, and non-atherosclerotic pathology of brain supplying arteries. Vasculitic changes were detected by digital subtraction angiography, MR angiography and/or transcranial Doppler ultrasound. Outcomes were measured by the modified Rankin scale (mRS) and EuroQoL Index. Cerebral vasculitis is a rare complication of Lyme disease (0.3% of all cases in the endemic area). Ten out of 11 patients diagnosed with neuroborreliosis-associated vasculitis cerebral vasculitis using clinical, radiological and immunological criteria developed ischemic stroke or transient ischemic attacks (TIA), 7 patients had recurrent stroke. Vasculitic alterations could be demonstrated in 8 patients that all except one developed ischemic lesions. The median mRS was 3 (range 0-4) at admission and 2 (range 0-6) at discharge. The posterior circulation was affected in 8 of 11 patients; thrombosis of the basilar artery was detected in 2 patients, one died in the acute stage. Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis. Lumbar puncture is needed for detection of this potentially life-threatening condition. Early recognition and adequate therapy would possibly improve outcome.

Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke.

BACKGROUND: Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach. METHODS: Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic. RESULTS: The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 µg/L (0.41-17.66) vs 0.08 µg/L (0.02-0.14), P<0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847-0.982), P<0.001]. A GFAP cutoff of 0.29 µg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic. CONCLUSIONS: Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.

Evaluation of the obesity genes FTO and MC4R and the type 2 diabetes mellitus gene TCF7L2 for contribution to stroke risk: The Mannheim-Heidelberg Stroke Study.

OBJECTIVE: Studies evaluating genetic markers for vascular risk and risk of stroke are limited, and none of them evaluated obesity genes. The objective was to investigate the genetic markers related to obesity genes FTO and MC4R and the gene of type 2 diabetes mellitus TCF7L2 for their contribution to risk of stroke and transient ischemic attacks (TIA). METHODS: We recruited 379 consecutive patients with stroke/TIA and 379 healthy population-based controls. The single-nucleotide polymorphisms (SNPs) rs9937053 (FTO), rs2229616 (MC4R V103I), rs17782313 (188kb downstream of MC4R), and rs7903146 (TCF7L2) were evaluated for association with stroke using logistic regression analyses. RESULTS: The odds ratios for stroke/TIA were 1.14 (95%CI 0.91-1.42) for rs9937053/FTO, 1.11 (95%CI 0.49-2.51) for rs2229616/MC4R, 1.05 (95%CI 0.82-1.3) for rs17782313/MC4R, and 0.99 (95%CI 0.78-1.25) for rs7903146/TCF7L2. Further exploration revealed that male patients with the T allele of rs7903146/TCF7L2 had a worse clinical outcome compared with male patients carrying the C allele. CONCLUSION: The observed trends of obesity risk alleles for risk of stroke/TIA as well as the possible sex-specific differences in clinical outcomes found for the TCF7L2 (rs7903146) require replication in future studies. Our study demonstrates that candidate gene studies for common stroke may benefit from focusing on polymorphisms that predispose to vascular risk.

Evaluation of costs and outcome in cardioembolic stroke or TIA.

The costs of acute stroke care, length of hospital stay (LOS), and outcome in patients with cardioembolic stroke or cardioembolic transient ischemic attacks (TIA) were investigated with the aim of estimating the clinical and health-economic impacts of cerebral cardioembolism. The study population consisted of 511 consecutive patients with the diagnosis of ischemic stroke (n = 379) or TIA (n = 132) treated at the Department of Neurology, Philipps University, Marburg. Cerebral cardioembolism was defined according to the criteria of the Cerebral Embolism Task Force. Clinical status was assessed by means of Barthel index (BI) and modified Rankin Scale. Costs were calculated using a bottom-up approach. All costs (in Euros) were inflated to the 2008 level. Compared to non-cardioembolic stroke (n = 278) patients, patients who had suffered cardioembolic stroke (n = 101) had more severe clinical deficits on admission (BI 46.3 +/- 27.0 vs. 59.3 +/- 34.1; P < 0.01), worse recovery (BI on discharge 59.2 +/- 28.9 vs. 73.1 +/- 33.4; P < 0.01), and increased LOS (12.6 +/- 5.7 vs. 10.0 +/- 7.8 days; P < 0.01). The latter also required a relatively higher daily resource utilization due to increased expenses for personnel and diagnostics. Mean costs of acute care for patients with cardioembolic stroke [euro 4890 per patient (95% confidence interval 4460-5200)] were significantly higher than those for patients with non-cardioembolic stroke [euro 3550 (95% confidence interval 3250-3850); P < 0.01]. The clinical and health-economic impact of cardiogenic cerebral embolism on stroke care is considerable. Patients with cardioembolic stroke/TIA are more severely impaired, and they require longer hospital treatment and increased resource utilization. Costs of acute care of cardioembolic stroke/TIA patients may exceed those of non-cardioembolic stroke/TIA by up to 40%.

Contribution of obesity and abdominal fat mass to risk of stroke and transient ischemic attacks.

BACKGROUND AND PURPOSE: Waist circumference has been shown to be a better predictor of cardiovascular risk than body mass index (BMI). Our case-control study aimed to evaluate the contribution of obesity and abdominal fat mass to the risk of stroke and transient ischemic attacks (TIA). METHODS: We recruited 1137 participants: 379 cases with stroke/TIA and 758 regional controls matched for age and sex. Associations between different markers of obesity (BMI, waist-to-hip ratio, waist circumference and waist-to-stature ratio) and risk of stroke/TIA were assessed by using conditional logistic regression adjusted for other risk factors. RESULTS: BMI showed a positive association with cerebrovascular risk which became nonsignificant after adjustment for physical inactivity, smoking, hypertension, and diabetes (odds ratio 1.18; 95% CI, 0.77 to 1.79, top tertile versus bottom tertile). Markers of abdominal adiposity were strongly associated with the risk of stroke/TIA. For the waist-to-hip ratio, adjusted odds ratios for every successive tertile were greater than that of the previous one (2nd tertile: 2.78, 1.57 to 4.91; 3rd tertile: 7.69, 4.53 to 13.03). Significant associations with the risk of stroke/TIA were also found for waist circumference and waist-to-stature ratio (odds ratio 4.25, 2.65 to 6.84 and odds ratio 4.67, 2.82 to 7.73, top versus bottom tertile after risk adjustment, respectively). CONCLUSIONS: Markers of abdominal adiposity showed a graded and significant association with risk of stroke/TIA, independent of other vascular risk factors. Waist circumference and related ratios can better predict cerebrovascular events than BMI.

Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice.

In recent years, several studies have unequivocally shown the occurrence of cortical spreading depressions (CSDs) after stroke and traumatic brain injury (TBI) in humans. The fundamental question, however, is whether CSDs cause or result from secondary brain damage. The aim of the current study was, therefore, to investigate the role of CSDs for secondary brain damage in an experimental model of TBI. C57/BL6 mice were traumatized by controlled cortical impact. Immediately after trauma, each animal showed one heterogeneous direct current (DC) potential shift accompanied by a profound depression of electroencephalogram (EEG) amplitude, and a temporary decrease of ipsi- and contralateral regional cerebral blood flow (rCBF) suggesting bilateral CSDs. Within the next 3 h after TBI, CSDs occurred at a low frequency (0.38 CSD/h per animal, n=7) and were accompanied by rCBF changes confined to the ipsilateral hemisphere. No significant relationship between the number of SDs and lesion size or intracranial pressure (ICP) could be detected. Even increasing the number of posttraumatic CSDs by application of KCl by more than six times did not increase ICP or contusion volume. We therefore conclude that CSDs may not contribute to posttraumatic secondary brain damage in the normally perfused and oxygenated brain.

Flow-dependent versus spreading-like impairment of brain tissue integrity during focal cerebral ischemia and its consequences for neuroprotective strategies.

Focal cerebral ischemic lesions demonstrate a gradual reduction of blood flow from the rim to the core. Flow reduction induces irreversible damage in the core region, whereas more peripheral tissue, i.e. penumbral tissue, is applicable to therapeutic interventions. Secondary mechanisms for lesion growth involve excitotoxicity, extracellular ion shifts, lactate generation, tissue acidosis, inflammation, spreading depolarization and many other processes. These toxic mediators accumulate in the ischemic core and endanger the still viable rim by diffusion or other spreading-like mechanisms, probably in part largely independent from blood flow. A substantial proportion of hemodynamic penumbral tissue could be demonstrated both in experimental settings and in clinical practice, whereas the precise spatial and temporary contribution of secondary mechanisms is much more difficult to investigate in our patients. Diffusion or spreading-mediated neurotoxicity will affect a small rim around the necrotic lesion. Due to the third power of volumetric analysis this would contribute to a large amount in small experimental lesions, but to a negligible amount of tissue in large clinical lesions and could therefore explain the difference in efficacy of neuroprotective strategies between experimental and clinical setups. Therefore, we discuss the likelihood of direct flow-dependent versus diffusion- or spreading-mediated impairment of endangered tissue in focal cerebral ischemia.

Failure to improve the effect of thrombolysis by memantine in a rat embolic stroke model.

OBJECTIVES: Partial and delayed recanalization is a regular finding after thrombolysis in stroke patients who may benefit from additional therapy with neuroprotectants. To translate this scenario into an experiment, memantine was combined with thrombolysis in an embolic stroke model and tissue outcome was assessed in terms of complete and incomplete damage. METHODS: Tissue plasminogen activator (tPA, 5 mg/kg, b.w.) was administered 1.5 or 3.5 hours after embolic middle cerebral artery (MCA) occlusion in rats. In both groups, rats were assigned to additional therapy with memantine (10 mg/kg, i.p.) or saline injection. Ischemia and eventual reperfusion were continuously monitored by laser-Doppler flowmetry. Reperfusion was defined as a lasting increase in post-thrombolytic cerebral blood flow to >60% of baseline (complete) or to a lesser degree (partial). Experiments were terminated 6 hours post-occlusion to obtain quantitative histopathology. RESULTS: tPA induced complete or partial recanalization in 54% of treated animals. Successful reperfusion reduced total ischemic lesion volume by 42% compared with non-reperfused animals (p<0.05), but increased significantly the percentage of scattered neuronal injury from 25.6 (non-reperfusion) to 36.3% (reperfusion, p<0.05). Memantine did not improve the effect of tPA-induced recanalization on infarct morphology whether applied at 1.5 or 3.5 hours post-occlusion. DISCUSSION: We conclude from our experiments that add-on therapy with memantine did not alter the effect of thrombolysis in an embolic stroke model. Recanalization appears to be a prerequisite to confer neuroprotective effects.

Costs of acute stroke care on regular neurological wards: a comparison with stroke unit setting.

OBJECTIVES: Stroke unit care has been shown to be beneficial but costly. In an own previous study, the resource utilization of stroke unit care has been evaluated. Since the resource utilization on regular neurological wards is widely unknown, we determined the costs for acute stroke care on regular neurological wards to compare both treatment settings. METHODS AND PATIENTS: We included 253 consecutive in-patients with the diagnosis of ischemic stroke (IS), intracerebral hemorrhage (ICH) or transient ischemic attack (TIA) treated on regular wards at a German University Department of Neurology, between 1 January and 30 June 1998. The modified Rankin scale (mRS) was used to assess outcome. Costs of stroke care were calculated from the perspective of the healthcare provider (hospital) by using a bottom-up approach. Resource utilization was compared to stroke unit care as determined in a previous study. Prices of 2002 were used (in Euros). RESULTS: IS was present in 78% (n=196), TIA in 13% (n=34), and ICH in 9% (n=23) of patients. Length of stay was 11.1+/-8.9 (mean+/-S.D., IS), 11.1+/-6.5 (TIA), and 16.9+/-15.5 (ICH) days (p>0.05). Mean costs of stroke care were euro 3060 (US$ 3180) for TIA, euro 3070 (US$ 3200) for IS and euro 5210 (US$ 5430) for ICH (p<0.05, ICH versus IS and TIA). The highest costs were due to non-medical care (46%) and personnel (25%). The mRS improved during hospitalization from 3.0+/-1.6 to 2.2+/-1.8 (p<0.01). Compared to care on regular neurological wards, mean costs per admission with treatment on stroke units increased by 7.0%, mean costs per day by 15.6%. CONCLUSION: The comparison - considering a potential bias of patient selection - shows that acute stroke unit care is approximately 16% more costly than treatment on regular neurological wards due to higher resource use of personnel and diagnostic procedures. Stroke unit treatment tends to decrease post-acute in-patient care costs.

Arterial hypotension triggers perifocal depolarizations and aggravates secondary damage in focal brain injury.

Perifocal depolarizations (PFD) have been observed after traumatic brain injury, are known to disturb cerebrovascular reactivity and thus may contribute to the morphological consequences of brain injury. In this investigation, the role of PFD was studied in focal brain lesions with/without induction of delayed hypotension. Cerebral freeze lesions were induced in anesthetized normotensive rats that underwent perfusion fixation of brains 5 min, 4 h or 24 h after lesioning, respectively, to obtain quantitative histopathology. In additional groups, a 45-min period of moderate hypobaric hypotension was applied 15 min post-trauma and brains were perfusion fixed after 4 h or 24 h. In a second series, the direct current (DC) potential and cortical laser-Doppler flow (LDF) were measured adjacent to lesions under normotensive or hypotensive conditions. Sham procedures were carried out in rats that underwent hypotension alone. Lesioning resulted in a significant LDF decrease to 50% of baseline, further decreased during hypotension to less than 40% of control (P < 0.05). Sham animals had LDF values between 60 and 70% of control when subjected to hypotension. Focal brain injury always induced a negative DC shift shortly after lesioning. In 6 of 8 rats that underwent cold lesion plus hypotension, a second PFD was observed approximately 2.5 min after onset of hypotension accompanied by a relative LDF increase by 25 +/- 12%. Lesion expansion was significantly worsened by hypotension (8.19 +/- 0.56 mm(3) at 24 h) compared with normotensive rats (7.01 +/- 0.3 mm(3) at 24 h, P < 0.01). We conclude that hypotension triggers depolarizations by an ischemic mechanism that contributes to final tissue damage.

Long-term outcome after stroke: evaluating health-related quality of life using utility measurements.

BACKGROUND AND PURPOSE: As stroke mortality rates decline, individuals are increasingly likely to live with their residual impairments and disabilities. Therefore, the quality of poststroke life is 1 of the pivotal topics that have to be considered beneath the functional outcome. However, data on health-related quality of life (HRQoL) have been infrequently used in stroke trials. The purpose of this study was to examine the long-term outcome (4 years after stroke) of HRQoL and to identify the determinants of HRQoL in stroke survivors. METHODS: Seventy-seven patients were included who were admitted to the Department of Neurology, Philipps-University Marburg, after experiencing an ischemic stroke, a transient ischemic attack, or a hemorrhagic stroke. All patients were examined by a physician, and assessment was performed using a standardized questionnaire. HRQoL was assessed using the German version of the EuroQoL Index (EQ-5D) and the Health Utility Index 2 and 3 (HUI2/3). RESULTS: Four years after stroke, besides physical functioning, neuropsychological sequelae such as depression and cognitive impairment contributed to a reduced HRQoL. In addition, the incidence of incontinence proved to be an important factor for HRQoL. Explained variances in regression analysis models were high (R2=0.802 for HUI and 0.633 for EQ-5D--visual analogue scale) and were based on a few important determinants, including physical state, depression, cognitive impairment, and incontinence. CONCLUSIONS: Our results underscore the importance of nonmotor symptoms on HRQoL in patients with stroke.

Status epilepticus after stroke is associated with increased long-term case fatality.

PURPOSE: The aim of this study was to determine the long-term case fatality of patients with a first episode of status epilepticus (SE group) of cerebrovascular etiology, as compared with that in acute stroke patients without SE (AS group). METHODS: Patients with SE who had been prospectively admitted to an epidemiologic study were retrospectively compared with a cohort of patients from the local stroke registry. The main outcome end point was overall survival. Survival curves were generated according to the Kaplan-Meier method and compared by using the log-rank test. An extended Cox model was used to examine the impact of patient group on the risk of death. Covariates considered potential confounders included age at diagnosis, sex, type of stroke, affected hemisphere, and localization of lesions. RESULTS: Of 166 patients who entered the study, 93 patients were in the SE group, and 73 patients were in the AS group; 53 SE patients and 35 AS patients died during the study. Patient group (SE vs. AS) showed no significant impact on survival (p=0.0832) in univariate analysis. In contrast, the results from a multivariable analysis suggest that after 6 months, patients with SE were at about twice the risk of death as were patients with AS [hazard ratio of 2.12 with 95% confidence interval, 1.04-4.32, p=0.0392]. CONCLUSIONS: The occurrence of SE in patients with cerebrovascular disease indicates a high risk of death within 3 years. In contrast, the case fatality risk attributable to recurrent status or seizures is lower.

Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus.

Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in acute stroke, but may provide information in the peri-ictal phase in epilepsy patients. Both transient reductions of brain water diffusion, namely a low apparent diffusion coefficient (ADC), and signs of hyperperfusion have been reported in experimental and human epilepsy case studies. We studied 10 patients with complex partial status epilepticus (CPSE) with serial MRI including DWI and PI. All patients showed regional hyperintensity on DWI, and a reduction of the ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10), (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal formation, the pulvinar and the cortex (one out of 10). In all patients a close spatial correlation of focal hyperperfusion with areas of ADC/DWI change was present. In two patients hyperperfusion was confirmed in additional SPECT (single photon emission computed tomography) studies. All patients received follow-up MRI examinations showing partial or complete resolution of diffusion and perfusion abnormalities depending on the length of the follow-up interval. The clinical course, EEG and SPECT results all indicate that MRI detected changes related to prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and tissue changes after CPSE in the hippocampus, thalamus and affected cortical regions.

Resource utilization and costs of stroke unit care in Germany.

OBJECTIVES: Stroke imposes a considerable economic burden on the individual and society. Recently, the concept of an integrated stroke unit has been established in several countries to improve the outcome of patients. This study evaluates the costs of acute care of the different cerebrovascular insults in a stroke unit. METHODS: The study population included 340 patients who were consecutively admitted to the Department of Neurology, Philipps University Marburg, with the diagnosis of stroke or transient ischemic attack (TIA) between January 1 and June 30, 2000. Clinical status and course were evaluated by using the Barthel index and the modified Rankin scale. Employing a "bottom-up" approach, we calculated the costs from the perspective of the hospital and the third-party payer using data from provider departments and other published sources. RESULTS: Inpatient costs were 3020 euros (3290 US dollars) for TIA, 3480 euros (3790 US dollars) for ischemic stroke (IS), and 5080 euros (5540 US dollars) for intracerebral hemorrhage (ICH) and differed significantly among these subgroups (P < .05). Patient subgroups ranked in the same order for average length of stay at 9.4 days for TIA, 10.2 days for IS, and 11.9 days for ICH (P > .05). Approximately 30% of the hospital costs are due to physician charges and care. Imaging amounted to 10% and lab investigations to 14% of total costs, independent of the diagnosis. Postacute treatment, including inpatient rehabilitation, cost 9880 euros per patient. Across all diagnostic groups, a mean clinical improvement was observed at time of discharge. CONCLUSIONS: Care of patients with cerebrovascular events in a stroke unit causes a high demand of resources and has a considerable impact on health-care expenditure. Therefore, investigations comparing the stroke unit concept with other strategies in stroke care are necessary to evaluate the stroke unit concept for a rational use of available resources in patients with cerebrovascular events.

Lesion evolution in cerebral ischemia.

There is sound evidence from histopathological and magnetic resonance imaging (MRI) studies that focal ischemic brain lesions tend to increase in size over time. Considerable lesion growth was observed in models of animal stroke as well as in patients presenting with hemispheric stroke. In focal cerebral ischemia, lesions predominantly enlarge early within 12 hours after onset. Ischemic injury is caused by complete necrosis in most of the affected tissue. By contrast, in global cerebral ischemia as seen after cardiac arrest, lesions appear late (>12 h) in selectively vulnerable brain regions such as the hippocampus, and neurons are damaged by apoptotic cell death. The high and regionally distinct vulnerability of the brain explains why prolonged periods of global ischemia result in widespread loss of energy metabolites combined with diffuse brain edema and global damage. Postulated mechanisms involved in lesion growth include among others excitotoxicity, periinfarct depolarizations, lactacidosis, microcirculatory disturbances, and flow-metabolism uncoupling. Research in the field faces two main challenges. First,maturation phenomena of injury may require special imaging techniques to detect early ischemic changes. Second, the dynamic nature of the changes underlines the need to conduct longitudinal studies with a variety of imaging techniques (e. g., metabolic imaging, diffusion/perfusion MRI, positron emission tomography) that require a differentiated interpretation of the alterations observed.

Combined MR measurements of magnetization transfer, tissue diffusion and proton spectroscopy. A feasibility study with neurological cases.

Magnetic resonance imaging (MRI) of diffusion and magnetization transfer was combined with 1H-spectroscopic imaging (CSI) to evaluate the clinical potential of in-vivo profiles of various brain pathologies. Ten patients (multiple sclerosis, cerebrovascular disease, leukodystrophy, Alzheimer dementia) and five healthy volunteers were investigated with diffusion-weighted MRI, magnetization transfer imaging, and CSI. Proton spectra were analyzed as ratios of NAA/Cr and Cho/Cr calculated from the peak areas of N-acetylaspartate (NAA), (phospho)-creatine (Cr) and choline (Cho). The apparent diffusion coefficient (ADC) and the magnetization transfer ratio (MTR) were determined in identical voxels to ensure identical partial volume effects compared to CSI. Compared to MTR and ADC assessments, the lower spatial resolution of CSI clearly indicates a hindrance at 1.5 T. In most demyelinating lesions, NAA/Cr reduction paralleled attenuated MTRs and elevated ADCs. By contrast, in acute stroke and some acute MS lesions the ADC was reduced, while MTR and NAA/Cr were also decreased. In Alzheimer's dementia, ADC was increased, MTR unchanged and Cho/Cr increased. In a case of leukodystrophy, ADC was pronouncedly increased, MTR and NAA/Cr both reduced, and Cho/Cr normal. Combined measurements of ADC, MTR and CSI are feasible and provide differential in-vivo information on various brain pathologies.