Guntram W. Ickenstein

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.

Predictors of survival after severe dysphagic stroke.

AbstractBackground and PurposeDysphagia is estimated to occur in up to 50% of the stroke neurorehabilitation population. Those patients with severe neurogenic oropharyngeal dysphagia (NOD) may receive feeding gastrostomy tubes (FGT) if noninvasive therapies prove ineffective in eliminating aspiration or sustaining adequate nutritional intake. Our aim was to quantify the recovery of swallowing function, and to identify variables predictive of survival after dysphagic stroke requiring FGT placement.MethodsWe identified consecutive stroke patients with severe dysphagic stroke requiring FGT placement admitted to a rehabilitation hospital between May 1998 and October 2001. The medical records were reviewed, and demographic, clinical, videofluoroscopic (VSS) and neuroimaging information were abstracted. A follow–up telephone interview was performed to determine whether the FGT was still in use, had been removed,or if the patient had died. State death certificate records were reviewed to ascertain date of death for subjects who had expired by the time of follow–up. Univariate and multivariate analyses were performed.Results11.6 % (77/664) of stroke patients admitted during the study period had severe dysphagic stroke with FGT insertion. Follow–up was available for 66 (85.7 %) of these individuals at a mean of two years after acute stroke. On follow–up 64% (42/66) of the patients were alive and 45 % had had the FGT removed and resumed oral diets. On univariate analysis patients who were alive at the time of follow–up had received FGT feeding for a shorter period of time (p < 0.0003), showed no signs of aspiration on the Clinical Assessment of Feeding & Swallowing (CAFS,p < 0.020) and on the Videofluoroscopic Swallowing Study (VSS, 0.001), had a better discharge FIM–Score (Functional Independence Measure) for eating (p < 0.0002) and cognitive function (p < 0.002) as well as better discharge FCM–Score (Functional Communication Measure) for swallowing (p < 0.0001). On multivariate analysis we developed a model consisting of FGT removal at discharge from the rehabilitation hospital (p < 0.011) and non–aspiration during VSS (p < 0.040) that was significantly associated with longer survival time during follow–up.ConclusionsSevere dysphagia requiring FGT is common in patients with stroke referred for neurorehabilitation. Patients who had a FGT in place at the time of discharge from the stroke rehabilitation unit or aspirated during VSS were substantially more likely to have died by the time of follow–up compared to those who had had the FGT removed and had no signs of aspiration on VSS. However functional outcome measurements (FIM, FCM) including the cognitive function (attention, concentration etc.) could play an important role for prediction of swallowing regeneration and survival in neurorehabilitation. These findings may have practical utility in guiding physicians and speech language pathologists when advising patients and families about prognosis in stroke survivors with severe dysphagia.

Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction.

The purpose of the current study was to evaluate myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) systems in a model of epinephrine‐induced cardiomyopathy in rabbits. Eight rabbits received four repetitive epinephrine infusions (300 mg/kg/60 min, i.v.) in 12‐day intervals and eight untreated rabbits served as controls (CTRL). Echocardiography demonstrated a significant deterioration of LV function as well as increased LV‐diameter and ‐mass index in catecholamine‐induced cardiomyopathy. Histological examination revealed that repetitive catecholamine infusion resulted in LV fibrous areas with collagenous content and an increase in myocyte width (16.9 ± 0.8 μm vs. CTRL 12.9 ± 0.9; P < 0.05). LV dysfunction was associated with a decreased total LV lactate dehydrogenase activity (LDH; 0.43 ± 0.03 IU/mg protein vs. CTRL 0.52 ± 0.04; P < 0.05) whereas total creatinine kinase activity was unchanged (CK; 7.30 ± 0.63 IU/mg protein vs. CTRL 9.20 ± 0.49, n.s.). Furthermore, myocardial LDH isoenzymes were shifted with a decrease in LDH1 and an increase in LDH2 and LDH3 (LDH1: 84.90 ± 2.60% vs. CTRL 94.50 ± 0.40; LDH2: 7.30 ± 1.20% vs. 1.50 ± 0.13; LDH3: 5.40 ± 0.90% vs. 3.20 ± 0.25; all P < 0.05). Foetal B‐CK isoenzymes were significantly increased (CK‐MB 5.30 ± 0.66 vs. 2.20 ± 0.35%; P < 0.05). The current study demonstrates changes in cardiac energy metabolism including an impaired LDH activity with a shift towards anaerobic isoenzymes as well as a more efficient CK system in a model of catecholamine‐induced LV dysfunction.

The use of telemedicine in combination with a new stroke-code-box significantly increases t-PA use in rural communities

AbstractBackground: The benefit of tissue plasminogen activator (t-PA) is strongly associated with the time to treatment. In Bavaria, Germany, only half of the population has the opportunity to be transferred to 1 of the 19 stroke units within the critical time window of less than 3 hours. The aim of this study was to investigate the benefit of a new stroke-code-box for t-PA thrombolysis combined with a telemedicine network system to increase the use of acute stroke thrombolysis. Methods: Two specialized stroke centers in Germany established a 24-hour telemedicine network (Telemedicine Pilot Project of an Integrated Stroke Care [TEMPiS]) to advise 12 community hospitals in eastern Bavaria. These clinics are linked via telemedicine in a 24-hour/7-day service network that allows patients to be examined by experts via a video-conference system Additionally, a special stroke-code-box for acute t-PA thrombolysis was designed to reduce time in the application and documentation process. Results: In the 12-month period before implementation of the TEMPiS network system, 10 patients had received systemic thrombolysis. In our 6-month study period (from July to December 2003) and after implementation of a stroke-code-box for t-PA thrombolysis within the telestroke network, 164 patients with acute stroke were presented with t-PA treatment indications. Of this patient population, 27.4% (45 of 164) received t-PA. Conclusions: Stroke care, including t-PA thrombolysis in non-urban areas, is feasible using a modern stroke unit concept within a telestroke network. With the expertise of specialized stroke centers accessed via telemedicine and the design of a stroke-code-box for t-PA thrombolysis, nearly one-third of patients presented with a possible indication for systemic thrombolysis can be treated with t-PA, thereby increasing the options for a successful stroke treatment.

Static posturography in aging and Parkinson's disease

Introduction: In clinical practice, evaluation of postural control is based on the neurological examination, including Rombergs test, examination of gait and performance of pull test as part of the Unified Parkinsons Disease Rating Scale (UPDRS). The goal of our study was to identify posturographic parameters since quantitative technical methods for the measurement of postural control are not established in clinical routine yet. Methods: In this cross-sectional study design we examined patients with Parkinsons disease (PD) (Hoehn and Yahr < 3; PD n = 12) on a static posturographic platform (eyes open and eyes closed), performing a standard Rombergs test during neurological examination and compared the results with an age-matched healthy adult control (HAC n = 10) and a healthy young control (HYC n = 21). Results: In the platform Rombergs test with open eyes, the patients with PD showed a significantly greater mean sway [PD: 14.98 vs. HAC: 8.77 (mm), p < 0.003 vs. HYC 7.80 (mm)], greater mean radius [PD: 28.31 vs. HAC: 16.36 (mm), p < 0.008 vs. HYC: 14.19 (mm)] and greater marked area [PD: 2.38 vs. HAC: 0.88 (cm2), p < 0.016 vs. HYC: 0.78 (cm2)] compared to the HAC. The Rombergs test with closed eyes revealed a significantly greater mean sway [PD: 13.83 vs. HAC: 10.12 (mm), p < 0.033 vs. HYC: 5.82 (mm)] and greater mean radius [PD: 25.03 vs. HAC: 18.15 (mm), p < 0.045 vs. HYC: 9.11 (mm)] compared to both groups. Conclusions: The platform Romberg-test with closed eyes detected significant differences in elderly people and patients with Parkinsons disease, which could be objectively quantified with static posturography testing. Age alone showed significant changes, only detectable with closed eyes. Therefore, balance testing with a new computerized approach could help to identify balance problems in a geriatric assessment in clinical routine, especially with the parameters marked area and mean sway.

Thrombolysis for Stroke in the Elderly

Introduction. Systemic thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) 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 rtPA 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 rtPA 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 ≥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 rtPA 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 rtPA. Prospective studies are needed to clarify which part of the senior population might be most eligible for systemic thrombolysis.

Relation between laterality and immune response after acute cerebral ischemia

Objective: During the last 2 decades, right/left hemisphere dominance was supposed to affect the immune system differently. Experimental and clinical observations indicate that the left hemisphere plays a crucial role in the development of the immune system. The true relationship between immune response and acute ischemic stroke laterality remains to be elucidated. Methods: We studied acute right-handed stroke patients admitted to a single acute neurology department with a specialized stroke unit. Being part of our clinical protocol, blood samples were taken within the first 24 h after the onset of stroke symptoms. The medical record of each patient was reviewed, and demographic, clinical laboratory (key criteria: C-reactive protein, CRP, and white blood cell count, WBC) and neuroimaging information was retrieved. All data were presented descriptively, and bivariate test statistics, ANOVA (log-transformed data) or linear correlations were calculated. Results: Fifty-six of the 187 patients admitted to our Stroke Unit between October 2003 and March 2004 with different stroke subtypes according to the TOAST criteria were retrospectively evaluated in order to characterize the impact of stroke laterality on immunoregulatory response measured by CRP levels and WBC. Correlation analysis revealed that left-sided ischemic stroke yielded a significantly higher correlation between CRP levels and WBC. Following left-sided stroke, a more marked variability in CRP and WBC was found compared to patients with right-sided ischemic stroke, although ANOVA did not show significant differences between immune response values as a function of stroke subtypes. Conclusions: We identified an association between stroke laterality and immunoregulatory response in patients with acute ischemic stroke. Left-sided stroke may be considered as a direct risk factor for infectious disease or immune deficits and should attract special attention. However, these preliminary results need be confirmed by controlled studies.

Hemodynamic changes and neurohumoral regulation during development of congestive heart failure in a model of epinephrine-induced cardiomyopathy in conscious rabbits

BACKGROUND The present study was designed to study the progression of heart failure in rabbits with catecholamine-induced cardiomyopathy. METHODS AND RESULTS We investigated the effects of three repetitive applications (at 16-day intervals) of high-dose epinephrine (first infusion, 5 micrograms/kg/min for 60 minutes; second and third infusions, 4 micrograms/kg/min for 60 minutes) on hemodynamics, echocardiographic parameters, and plasma hormone levels in eight conscious rabbits chronically instrumented with a Doppler flow probe around the proximal abdominal aorta and a catheter in the right atrium. Mean arterial pressure and blood flow velocity, as well as the acceleration of blood flow velocity (df/dt) in the proximal abdominal aorta were progressively reduced, and right atrial pressure was significantly elevated. On echocardiography, progressive left ventricular (LV) dilatation with depressed LV systolic function and an increase in LV mass were observed. Plasma atrial natriuretic peptide level was enhanced approximately fourfold after each epinephrine infusion, with a tendency to return to baseline values. Plasma renin activity (PRA) was increased after the first epinephrine application (3.0 +/- 0.5 to 6.4 +/- 0.9 ng angiotensin I (AI)/mL/h; P < .05), followed by a return to control levels. After the second epinephrine infusion, a significant decrease to 1.0 +/- 0.3 ng AI/mL/h (P < .05) was observed. After the third catecholamine treatment, PRA levels insignificantly increased. Plasma vasopressin level significantly increased from 0.5 +/- 0.2 to 1.1 +/- 0.5 pg/mL (P < .05) after the second epinephrine infusion. CONCLUSION Repetitive infusions of high doses of epinephrine induce a cardiomyopathy with progressive hemodynamic deterioration, LV dilatation and hypertrophy, depressed systolic function, and different stages of neurohumoral compensation. This model appears to be suitable to study the progression of chronic heart failure by serial measurements in a small animal preparation.

Using Routine Data for Quality Assessment in NeuroNet Telestroke Care

BACKGROUND Systematic clinical trials are often unavailable to evaluate and optimize operational telestroke networks. In a complementary approach, readily available routine clinical data were analyzed in this study to evaluate the effect of a telestroke network over a 4-year period. METHODS Routine clinical data from the HELIOS hospital information system were compared before and after implementation of the NeuroNet concept, including neurologic acute stroke teleconsultations, standard operating procedures, and peer review quality management in 3 hospital cohorts: 5 comprehensive stroke centers, 5 NeuroNet hospitals, and 5 matched control hospitals. RESULTS During the study period, the rate of thrombolytic therapy increased by 4.8% in NeuroNet hospitals, while ischemic stroke in-hospital mortality decreased (relative risk reduction ~29% in NeuroNet and control hospitals). The odds ratio for thrombolytic therapy in comprehensive stroke centers compared to NeuroNet hospitals was reduced from 3.7 to 1.3 between 2006 and 2009. Comprehensive stroke care coding according to German Diagnosis Related Groups definitions increased by 45% in NeuroNet (P < .0001) and by 18% in control hospitals. CONCLUSIONS Routine clinical data on in-hospital mortality, the rate of thrombolytic therapy, and comprehensive stroke care coding reflect different aspects of acute stroke care improvement related to the implementation of the telemedical NeuroNet concept and unified quality management (standard operating procedure teaching concept, peer review process). Similar evaluation processes could contribute to quality monitoring in other telestroke networks.

Modulation of renal blood flow by endogenous endothelin-1 in conscious rabbits with left ventricular dysfunction*

The current study addresses the functional status and role of the endothelin ET(A) receptor for renal vascular function in rabbits with and without heart failure (epinephrine-induced cardiomyopathy). Under baseline conditions, the ET(A) receptor antagonist BQ-123 did not change basal renal hemodynamics, but completely prevented endothelin-1 (ET-1)-induced renal vasoconstriction. In heart failure, in the presence of elevated plasma ET-1 concentrations (P < .05), renal vasoconstriction in response to exogenous ET-1 was intact. Unlike under baseline conditions, ET(A) receptor antagonism markedly increased renal blood flow (P <.05) and decreased renal vascular resistance (P < .05) in heart failure. The current study provides new insight into the pathophysiology of renal vasoconstriction associated with heart failure and the specific role of the renal ET(A) receptor in this pathophysiologic adaptation.