Impact of hospital admission during nonworking hours on patient outcomes after thrombolysis for stroke.

BACKGROUND AND PURPOSE: Whether the time of hospital admission is relevant for short-term outcome after stroke is under debate and may depend on care facilities. METHODS: We retrospectively analyzed medical records from patients who received thrombolytic therapy within 4.5 hours of stroke onset in a stroke unit of the Charité-University Hospital Berlin (Charité; n=291) or within the stroke telemedicine (TEMPiS) network, comprising 12 community hospitals with telestroke units in Bavaria (n=616). RESULTS: Thrombolytic therapy was administered during nonworking hours in 59.5% (Charité) and 55.0% (TEMPiS) of patients. A trend toward a lower rate of symptomatic intracranial hemorrhage (3.4% versus 9.2%; P=0.053), clinical worsening (11.9% versus 19.7%; P=0.079), and 7-day mortality (3.4% versus 8.7%; P=0.073) after admission during working hours was seen at Charité. However, multivariable analysis did not show a significant impact of the time of admission on clinical worsening, symptomatic intracranial hemorrhage, or 7-day mortality in both cohorts. Thrombolysis based on brain computed tomography instead of magnetic resonance imaging (odds ratio=4.98, 95% CI, 1.09 to 22.7) and more severe National Institutes of Health Stroke Scale score on admission (odds ratio=1.15 per point; 95% CI, 1.07 to 1.24) were associated with 7-day mortality at Charité. National Institutes of Health Stroke Scale score on admission (odds ratio=1.13 per point; 95% CI, 1.06 to 1.19) and older age (odds ratio=1.05 per year; 95% CI, 1.004 to 1.09) were correlated with 7-day mortality in TEMPiS. National Institutes of Health Stroke Scale on admission was the only independent predictor of symptomatic intracranial hemorrhage or clinical worsening in both cohorts. CONCLUSIONS: The majority of stroke patients received thrombolysis during nonworking hours. The time of hospital admission did not significantly influence the short-term outcome after thrombolysis.

Telemedically provided stroke expertise beyond normal working hours. The Telemedical Project for Integrative Stroke Care.

BACKGROUND: State-of-the-art stroke management requires neurological expertise for the recognition of complex cerebrovascular syndromes or stroke-mimicking symptoms and initiation of proven acute therapies. Many community hospitals struggle to fulfill these premises particularly at evening/nighttimes or weekends. Telemedicine can improve that situation by offering rapid access to neurological expertise, but it has not been shown to what extent it is used beyond working times. METHODS: The Telemedical Project for Integrated Stroke Care is a telemedical network of 2 stroke centers and 12 regional general hospitals with newly established stroke wards in Bavaria. This analysis comprises all teleconsultations from 1st February 2003 to 15th December 2006. The consultations were prospectively documented and categorized according to predefined indications and direct impact on clinical decisions. The teleconsultations were analyzed concerning whether they were requested during regular working time or during off-time (at evening/night times or weekends). RESULTS: A total of 10,239 teleconsultations were carried out in 8,326 patients. The 6,679 patients with cerebrovascular diagnosis comprised 51% of all admitted stroke cases between 2003 and 2006. During off-time 6,306 consultations (62%) were requested; 1,598 teleconsultations yielded nonstroke diagnoses, with 68% beyond working hours. Of all presented stroke patients 567 (8.5%) received systemic thrombolysis, with 58% off-time. Interhospital transports were initiated in 1,050 patients (10.5% of all), mainly for specific diagnostic workup or interventional treatments. Sixty percent of these transfers were launched off-time. CONCLUSIONS: The majority of teleconsultations were requested beyond normal working times and a significant proportion had an immediate impact on clinical decisions.

Admission facility is associated with outcome of basilar artery occlusion.

BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) is a stroke subtype with poor prognosis, but recanalizing therapies have been reported to be effective. We investigated whether initial admission to telemedically linked general hospitals with subsequent stroke-center transfer is related to poorer outcome than direct admission to stroke centers. METHODS: All BAO cases of 3 stroke centers in Munich and 1 center in Regensburg between March 1, 2003 and December 31, 2004 were included, either if patients were directly admitted to stroke centers (n=23) or had initial admission to general hospitals of the telemedical network for integrative stroke care (TEMPiS) and secondary transfer to stroke centers (n=16). BAO was defined as angiographically (CTA, MRI or conventional angiography) confirmed occlusion of the basilar artery. Baseline parameters and therapeutic procedures were recorded. One-year follow-up was conducted prospectively. RESULTS: Differences in baseline parameters were not statistically significant. Time from onset to first angiography was significantly longer in patients with secondary transfer (mean: 355+/-93 minutes versus 222+/-198 minutes; P<0.01), mainly attributable to transfer duration (mean:156+/-73 minutes). In-hospital mortality (22% versus 75%; P<0.01) and 1-year-mortality (30% versus 81%; P<0.01) were lower for patients with direct admission to stroke centers. Fifty-two percent of directly admitted patients versus 13% of patients with secondary transfer (P=0.02) were living at home after 1 year. CONCLUSIONS: BAO patients who were admitted primarily to community hospitals had a worse prognosis. Patients with typical symptoms should have direct access to stroke centers, or may need bridging therapies.

Comparison of tissue plasminogen activator administration management between Telestroke Network hospitals and academic stroke centers: the Telemedical Pilot Project for Integrative Stroke Care in Bavaria/Germany.

BACKGROUND AND PURPOSE: Systemic thrombolysis is the only therapy proven to be effective for ischemic stroke. Telemedicine may help to extend its use. However, concerns remain whether management and safety of tissue plasminogen activator (tPA) administration after telemedical consultation are equivalent in less experienced hospitals compared with tPA administration in academic stroke centers. METHODS: During the second year of the ongoing Telemedical Pilot Project for Integrative Stroke Care, all systemic thrombolyses in stroke patients of the 12 regional clinics and the 2 stroke centers were recorded prospectively. Patients' demographics, stroke severity (National Institutes of Health Stroke Scale), frequency of administration, time management, protocol violations, and safety were included in the analysis. RESULTS: In 2004, 115 of 4727 stroke or transient ischemic attack patients (2.4%) in the community hospitals and 110 of 1889 patients in the stroke centers (5.8%) received systemic thrombolysis. Prehospital latencies were shorter in the regional hospitals despite longer distances. Door to needle times were shorter in the stroke centers. Although blood pressure was controlled more strictly in community hospitals, symptomatic intracerebral hemorrhage rate (7.8%) was higher (P=0.14) than in stroke centers (2.7%) but still within the range of the National Institute of Neurological Disorders and Stroke trial. In-hospital mortality rate was low in community hospitals (3.5%) and in stroke centers (4.5%). CONCLUSIONS: Although with a lower rate of systemic thrombolysis, there was no evidence of lower treatment quality in the remote hospitals. With increasing numbers of tPA administration and growing training effects, the telestroke concept promises better coverage of systemic thrombolysis in nonurban areas.

Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy.

Middle cerebral artery occlusion (MCAO) in Fischer-344 rats results in a small variance of infarct size. However, complications are frequent especially in aged Fisher-344 rats undergoing endovascular suture occlusion of the middle cerebral artery. Analyzing our experiences with 165 Wistar, 13 Sprague-Dawley and 10 F-344 rats, we compared the incidence of impossible thread advancement and subarachnoid hemorrhage, respectively. Magnetic resonance angiography (MRA) was applied to study the course of the internal carotid artery (ICA) in Fischer and Wistar rats. Finally, we performed a structured review of the literature from 1991 to 2005 evaluating reports on Fischer rats subjected to intraluminal filament MCAO. Complications like fruitless filament advancement or subarachnoid hemorrhage were found to be significantly more frequent in Fischer rats than in other strains. MRA revealed significantly more pronounced kinking of the ICA in F-344 than in Wistar rats. In seven publications available on filament MCAO in F-344 rats, complication rates of 50-100% were reported, corroborating our data. Surgical difficulties accompanied by high complication rates due to their cerebrovascular anatomy make Fischer rats unsuitable for filament MCAO. If the use of Fischer rats for studies on focal cerebral ischemia is indicated, other ischemia models than intraluminal suture occlusion should be chosen.

Telemedicine for safe and extended use of thrombolysis in stroke: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria.

BACKGROUND AND PURPOSE: Systemic thrombolysis represents the only proven therapy for acute ischemic stroke, but safe treatment is reported only in established stroke units. One major goal of the ongoing Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria is to extend the use of tissue plasminogen activator (tPA) treatment in nonurban areas through telemedic support. METHODS: The stroke centers in Munich-Harlaching and in Regensburg established a telestroke network to provide consultations for 12 local hospitals in eastern Bavaria. The telemedic system consists of a digital network that includes a 2-way video conference system and CT/MRI image transfer with a high-speed data transmission up to 2 Mb/s. Each network hospital established specialized stroke wards in which qualified teams treat acute stroke patients. Physicians in these hospitals are able to contact the stroke centers 24 hours per day. RESULTS: A total of 106 systemic thrombolyses were indicated via teleconsultations between February 1, 2003, and April 7, 2004. During the first 12 months, the rate of thrombolyses was 2.1% of all stroke patients. Mean age was 68 years, and median National Institutes of Health Stroke Scale score was 13. Mean delay between onset and hospital admission was 65 minutes, and door-to-needle time was on average 76 minutes, which included 15 minutes for the teleconsultation. Symptomatic hemorrhage occurred in 8.5% of patients, and in-hospital mortality was 10.4%. CONCLUSIONS: The present data suggest that systemic thrombolysis indicated via stroke experts in the setting of teleconsultation exhibits similar complication rates to those reported in the National Institute of Neurological Disorders and Stroke trial. Therefore, tPA treatment is also safe in this context and can be extended to nonurban areas.

Application of clinical scanners in rats: experimental carotid imaging using magnetic resonance imaging, spiral computed tomography, and color duplex ultrasound.

BACKGROUND AND PURPOSE: Noninvasive small animal imaging allows for reduction of the required numbers of animals in research by providing the possibility of long-term follow-up at various time points. Additionally, correlation to the investigated respective human disease is possible as equivalent equipment is employed. The authors therefore evaluate feasibility and potential of color duplex sonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA) by the use of clinical scanners for carotid artery imaging in rats. METHODS: Male Wistar rats (n = 17) were subjected to color duplex sonography, CTA, and MRA of the common carotid artery (CCA) and the carotid bifurcation. Clinical scanners were used for the experiments and optimal parameter settings evaluated accounting for the different size of the animals. The applied imaging methods were analyzed in regard to image quality and practicability in laboratory settings. RESULTS: The CCA could be clearly displayed by all imaging modalities in all rats. Duplex sonography provided distinct images and reproducible basic functional information. CTA and MRA provided distinct images of the CCA and the carotid bifurcation in both axial and reconstructed 3-dimensional images. The authors further describe different indications for these imaging methods regarding spatial resolution, acquisition times, possible scanning range, and application of contrast agent. CONCLUSIONS: Color duplex sonography, CTA, and MRA are all feasible methods for imaging of the carotid arteries in rats. Images of sufficient clarity and resolution could be obtained by the use of clinical scanners, yielding information about vessel size, direction of blood flow, and adjacent structures. Further studies need to be performed that address investigations of pathological conditions such as flow disturbances or vessel stenosis.

Ketamine/xylazine anesthesia for radiologic imaging of neurologically impaired rats: dose response, respiratory depression, and management of complications.

In vivo imaging of rats represents an important tool for outcome evaluation in research on stroke, brain trauma, and other neurologic diseases. Since sedation of animals is necessary to avoid artifacts, a mixture of ketamine and xylazine is frequently used for anesthesia. We assessed the suitable dosage of narcotics and its correlation to severe respiratory adverse events in 269 cases of ketamine/xylazine anesthesia in male Wistar rats for performance of magnetic resonance imaging after middle cerebral artery occlusion (MCAO) or sham surgery. Anesthesia depth was not measured. Anesthesia was efficacious in avoiding movement artifacts during imaging. Necessary dosage was lower if rodents were subjected to MCAO instead of sham surgery, if body weight was below baseline, and if time since surgery was short. If anesthesia was induced during the first 2 days after surgery in animals with body weight loss, necessary dose rates were 27% below doses required for rats more than 10 days post-surgery with body weight above baseline (91.4/8.3 versus 125.1/11.3 mg of ketamine/xylazine/kg). A dose adaptation scale for the prediction of necessary dose rates was developed. Apnea developed in 3.3% of all animals. Use of ketamine/xylazine anesthesia for imaging procedures is feasible and safe, though it is associated with a small risk of respiratory arrest. In case of apnea, inspiration can be provoked by a puff of air into the rat's pelt. If unsuccessful, endotracheal intubation and mechanical ventilation are needed until spontaneous breathing is restored or xylazine effects are antagonized.

Depressive symptoms and quality of life after thrombolysis in stroke: the TEMPiS study.

Intravenous thrombolysis leads to a reduction of post-stroke disability. No data exist about whether depression and poor quality of life (QoL) remain relevant problems in patients with good functional outcome. We assessed mood and QoL at 3 and 6 months after stroke in consecutive patients who received intravenous thrombolysis in stroke centers and telemedicine hospitals within the TEMPiS network. The Beck Depression Inventory (BDI) was used with BDI ≥18 indicating clinically relevant depressive symptoms. Stroke specific quality of life (SSQOL) was used for QoL assessment with the definition of SSQOL total score <60% for poor QoL. Associations of BDI and SSQOL with baseline parameters and modified Rankin scale (mRS) in follow-up were analyzed. In patients with known mRS 0-4 at 3 months (N = 213), BDI was available in 74% and SSQOL in 77%. At 3 and 6 months, 23 and 18% of patients had clinically relevant depressive symptoms; 25 and 24% reported a poor QoL. The mRS at 3 months correlated with BDI (r = 0.43, p < 0.01) and SSQOL (r = -0.75, p < 0.01). BDI ≥18 was observed in 11% of patients with mRS 0-1 and 16% in mRS 0-2. Severe stroke (NIHSS ≥12) at admission (OR 1.23, 0.57-2.66; p = 0.57) was not predictive for depressive symptoms but for poor QoL (OR 2.77, 95%CI 1.34-5.74). Depressive symptoms and impaired QoL are observed in a substantial proportion of stroke patients at 3 months after intravenous thrombolysis. Health professionals should be aware that thrombolysed patients may have relevant mood disorders despite good functional outcome.

Closing microvascular lesions with fibrin sealant-attached muscle pads.

Fibrin sealants are used in a variety of surgical procedures, mainly for purposes of hemostasis and assisted wound healing. The combined use of fibrin sealant and autologous muscle pads for hemostasis was not reported previously. Arterial incisions in the common carotid artery in rats were closed by the combined application of fibrin sealant and an autologous muscle pad. Postsurgical vessel patency and degree of stenosis were evaluated by color duplex sonography, computed tomography angiography, and postmortem histology. The combined application of muscle pad and fibrin sealant and achievement of hemostasis was feasible in all animals. Seventy-eight percent of animals showed no or only slight postsurgical vessel stenosis. Our method is simple and quick to perform, showing a high potential for hemostasis in microvascular lesions. Therefore, it might be used in future experimental studies for conservation of vessel patency after arterial catheterization and in experimental or clinical vascular surgery.

Thrombolysis for stroke in the elderly.

INTRODUCTION: Systemic thrombolysis with intravenous recombinant tissue plasminogen activator (rt PA) for acute ischemic stroke had been licensed for patients up to 75 years in age in many European countries and was recently extended to 80 years. This age restriction results from the potential higher risk of cerebral bleeding in the elderly. The major rt PA trials included only 42 patients above 80 years showing a potential benefit from treatment. Further data is still rare. METHODS: Using our stroke database we identified all patients beyond 75 years with middle cerebral artery ischemia treated with intravenous rt PA in our stroke unit from 02/1999 until 07/2004. Clinical course and outcome until day 5 in addition to mortality after 3 and 6 months were analysed. RESULTS: Twenty-nine patients (80.8+/-4 years, 16 of them over 80 years old) met the inclusion criteria representing 21.2% of those receiving thrombolytic therapy. The median NIH-SS score on admission was 14 points. On day 5 after thrombolysis, 13/29 showed a good recovery (NIH-SS improvement >or=4 pts). The remaining exhibited only small or no benefit (n=11), deterioration (n=3) or died (n=2). A total of 3/29 patients developed non-symptomatic parenchymal hemorrhage or hemorrhagic transformation. One patient died due to space-occupying cerebral hemorrhage. Extracerebral bleeding was found in 3/29 requiring substitution in one. One other died for primary cardiac reasons. Median NIH-SS on day 5 was 10 points. Mortality after 3 and 6 months was 20.7%. We did not find factors predicting clinical outcome. Most importantly, there was no significant difference regarding outcome in patients 76--80 vs. 81--87 years old. DISCUSSION: Intravenous rt PA resulted in good neurological in-hospital outcome in almost 45% and six-months survival of almost 80% of the patients beyond 75 years. In 10.3% non-symptomatic and in 3.4% symptomatic cerebral bleeding was found. Thus, seniors beyond 75 and even beyond 80 years in good medical condition may benefit from systemic treatment with rt PA. Prospective studies are needed to clarify which part of the senior population might be most eligible for systemic thrombolysis.

The role of ECA transection in the development of masticatory lesions in the MCAO filament model.

In the intraluminal suture model of middle cerebral artery occlusion (MCAO) in the rat, lesions of the masticator muscles associated with impaired functional outcome occur. We evaluated the role of external carotid artery (ECA) transection. We assessed whether isolated interruption of an arterial or a venous connection to the ECA territory was sufficient to induce masticatory hypoperfusion and lesions. We also evaluated a direct access to the common carotid artery (CCA) with subsequent vascular closure with regard to its feasibility, frequency of masticatory lesions, complications, and cerebral ischemia. Cerebral and masticatory lesions and perfusion deficits were assessed by in vivo magnetic resonance imaging (MRI). Vessel patency was evaluated using computerized tomography angiography and histology. An interruption of arterial blood flow led to masticatory hypoperfusion. Masticatory lesions occurred in 6% of the rats. Access to and closure of the CCA were feasible in all animals, leading to moderate or severe vessel stenosis in 20%, and intraarterial thrombosis in 25% of the rats. Reproducible cerebral infarctions were obtained in all animals. In 24% of the rats, hyperintense MRI signal changes were observed in the ipsilateral temporal muscle. Thus, the induction of masticatory hypoperfusion and lesions by arterial transection supports the role of the ECA in this context. Direct access to the CCA with subsequent vessel closure led to stenosis in most animals. Preservation of ECA continuity was not suitable to fully prevent masticatory lesions.