Thrombolysis and clinical outcome in patients with stroke after implementation of the Tyrol Stroke Pathway: a retrospective observational study.

BACKGROUND: Intravenous thrombolysis for ischaemic stroke remains underused worldwide. We aimed to assess whether our statewide comprehensive stroke management programme would improve thrombolysis use and clinical outcome in patients. METHODS: In 2008-09, we designed the Tyrol Stroke Pathway, which provided information campaigns for the public and standardised the entire treatment pathway from stroke onset to outpatient rehabilitation. It was commenced in Tyrol, Austria, as a long-term routine-care programme and aimed to include all patients with stroke in the survey area. We focused on thrombolysis use and outcome in the first full 4 years of implementation (2010-13). FINDINGS: We enrolled 4947 (99%) of 4992 patients with ischaemic stroke who were admitted to hospitals in Tyrol; 675 (14%) of the enrollees were treated with alteplase. Thrombolysis administration in Tyrol increased after programme implementation, from 160 of 1238 patients (12·9%, 95% CI 11·1-14·9) in 2010 to 213 of 1266 patients (16·8%, 14·8-19·0) in 2013 (ptrend 2010-13<0·0001). Differences in use of thrombolysis in the nine counties of Tyrol in 2010 (range, 2·2-22·6%) were reduced by 2013 (12·1-22·5%). Median statewide door-to-needle time decreased from 49 min (IQR 35-60) in 2010 to 44 min (29-60) in 2013; symptomatic post-thrombolysis intracerebral haemorrhages occurred in 28 of 675 patients (4·1%, 95% CI 2·8-5·9) during 2010-13. In four Austrian states without similar stroke programmes, thrombolysis administration remained stable or declined between 2010 and 2013 (mean reduction 14·4%, 95% CI 10·9-17·9). Although the 3-month mortality was not affected by our programme (137 [13%] of 1060 patients in 2010 vs 143 [13%] of 1069 patients in 2013), 3-month functional outcome significantly improved (modified Rankin Scale score 0-1 in 375 [40%] of 944 patients in 2010 vs 493 [53%] of 939 in 2013; score 0-2 in 531 [56%] patients in 2010 and 615 [65%] in 2013; ptrend 2010-13<0·0001). INTERPRETATION: During the period of implementation of our comprehensive stroke management programme, thrombolysis administration increased and clinical outcome significantly improved, although mortality did not change. We hope that these results will guide health authorities and stroke physicians elsewhere when implementing similar programmes for patients with stroke. FUNDING: Reformpool of the Tyrolean Health Care Fund.

Efficacy of silver nanoparticles-impregnated external ventricular drain catheters in patients with acute occlusive hydrocephalus.

INTRODUCTION: Catheter-associated infection of cerebrospinal fluid (CSF) is a potentially life-threatening complication of external ventricular drainage (EVD). The purpose of this pilot study was to address the efficacy of silver-impregnated EVD catheters in neurological and neurosurgical patients requiring external CSF drainage due to acute occlusive hydrocephalus. METHODS: Nineteen consecutive patients were enrolled in the treatment arm of the study and data were prospectively recorded for these patients. The control group consisted of 20 patients for whom data were retrospectively assessed. CSF samples were drawn at least three times a week and routine bacterial cultures and CSF analyses were done according to standard protocols. The primary endpoint of the study was the occurrence of catheter-associated ventriculitis (CAV) proven by positive CSF culture. Secondary endpoints were bacterial colonization of the catheter tip and CSF pleocytosis. RESULTS: In 20 control patients, 5 CAVs were microbiologically diagnosed. In contrast, no positive CSF cultures were found in the treatment group. This difference was statistically significant (P < 0.05). All CAVs occurred later than day 10 after catheter placement. Colonization of the catheter tip was found in 6 patients in the control group and in 5 patients in the treatment group (not significant). CONCLUSIONS: This pilot study indicates that EVD catheters impregnated with silver nanoparticles might be a new option for preventing CAV in neurocritical care patients, and therefore evaluation in a large prospective randomized study is warranted.

Silver segregation and bacterial growth of intraventricular catheters impregnated with silver nanoparticles in cerebrospinal fluid drainages.

OBJECTIVES: Intraventricular catheters impregnated with silver nanoparticles are developed to reduce catheter-associated infections in cerebrospinal fluid (CSF) drainages. Silver released from these new catheters should have an anti-microbacterial effect. This study examines the silver ion release and a potential effect of bacterial growth in an in vitro experiment. METHODS: Seven original silver-coated ventricle catheters were rinsed thoroughly with an artificial CSF for 6 days. The collecting containers were replaced every 24 hours. In these samples, ion concentrations of silver were determined via trace analysis through atomic absorption spectroscopy. Furthermore, a bacterial growth was conducted on silver-impregnated and non-impregnated catheters. RESULTS: In none of the samples, a concentration of silver ions could be detected. For Staphylococcus aureus, a slightly decreased bacterial growth could be observed with silver-impregnated catheters. DISCUSSION: There is no risk of a toxic effect due to silver release into the CSF. However, the in vivo antibacterial effect has to be further investigated. We recommend clinical trials to prove the oligodynamic and anti-microbacterial effects of silver-impregnated ventricular catheters.

Survival and long-term functional outcome in 1,155 consecutive neurocritical care patients.

OBJECTIVE: To analyze survival, mortality, and long-term functional disability outcome and to determine predictors of unfavorable outcome in critically ill patients admitted to a neurologic intensive care unit (neuro-ICU). DESIGN: Retrospective cohort study with post-neuro-ICU health-related evaluation of functional long-term outcome. SETTING: Ten-bed neuro-ICU in a tertiary care university hospital. PATIENTS: A consecutive cohort of 1,155 patients admitted to a neuro-ICU during a 36-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,155 consecutive patients, of whom 41% were women, were enrolled in the study. The predominant reasons for neuro-ICU care were cerebrovascular diseases, such as intracerebral hemorrhage (20%), subarachnoid hemorrhage (16%), and complicated, malignant ischemic stroke (15%). A total of 213 patients (18%) died in the neuro-ICU. The Glasgow Outcome Scale and modified Rankin scale were dichotomized into two groups determining unfavorable vs. favorable outcome (Glasgow Outcome Scale scores 1-3 vs. 4-5 and modified Rankin scale scores 2-6 vs. 0-1). Factors associated with unfavorable outcome in the unselected cohort according to logistic regression analysis were admission diagnosis, age (p < .01), and a higher score in the simplified Therapeutic Intervention Scoring System (TISS-28) at time of admission (p < .01). Functional long-term outcome was evaluated by telephone interview for 662 patients after a median follow-up of approximately 2.5 yrs by evaluating modified Rankin scale and Glasgow Outcome Scale scores. Factors associated with unfavorable functional long-term outcome were admission diagnosis, sex, age of >70 yrs (odds ratio, 8.45; 95% confidence interval, 4.52-15.83; p < .01), TISS-28 of >40 points at admission (odds ratio, 4.05; 95% confidence interval, 2.54-6.44; p < .01), TISS-28 of >40 points at discharge from the neuro-ICU (odds ratio, 3.50; 95% confidence interval, 1.51-8.09; p < .01), and length of stay (odds ratio, 1.01; 95% confidence interval, 1.00-1.03; p = .02). CONCLUSION: We found admission diagnosis, age, length of stay, and TISS-28 scores at admission and discharge to be independent predictors of unfavorable long-term outcome in an unselected neurocritical care population.

Pharmacokinetics of intravenous linezolid in cerebrospinal fluid and plasma in neurointensive care patients with staphylococcal ventriculitis associated with external ventricular drains.

The pharmacokinetic profile of linezolid in cerebrospinal fluid (CSF) in five neurointensive care patients with staphylococcal ventriculitis was studied. The mean area under concentration-time curve (+/- standard deviation) was 63 +/- 18.9 mg x h/liter, with a CSF-to-plasma ratio of 0.8 +/- 0.3. Times above MIC in CSF were 99.8% and 57.2% for pathogens with MICs of 2 mg/liter and 4 mg/liter, respectively.

Scanning electron microscopy of the neuropathology of murine cerebral malaria.

BACKGROUND: The mechanisms leading to death and functional impairments due to cerebral malaria (CM) are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM) so far. The present study investigates the neuropathological features of murine CM by applying SEM. METHODS: C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. RESULTS: Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. CONCLUSION: The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

Case report: severe heat stroke with multiple organ dysfunction - a novel intravascular treatment approach.

INTRODUCTION: We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. METHODS: A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. RESULTS: Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard and CoolLine) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. CONCLUSION: In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy.

OBJECT: Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. METHODS: Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five(median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 +/- 0.4 micro/ml in Group 1 and 565.58 +/- 168.71 microg/ml 1 hour after vancomycin application in Group 2 (mean +/- standard deviation). Vancomycin levels above the recommended trough level of 5 microg/ml in CSF were never reached in Group 1, whereas in Group 2 they below the trough level (3.74 +/- 0.66 microg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. CONCLUSIONS: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Safety and efficacy of a novel intravascular cooling device to control body temperature in neurologic intensive care patients: a prospective pilot study.

OBJECTIVE: To determine the safety and efficacy of a novel intravascular cooling device (Cool Line catheter with Cool Gard system) to control body temperature (temperature goal <37 degrees C) in neurologic intensive care patients. DESIGN: A prospective, uncontrolled pilot study in 51 consecutive neurologic intensive care patients. SETTING: A neurologic intensive care unit at a tertiary care university hospital. PARTICIPANTS: Patients were 51 neurologic intensive care patients with an intracranial disease requiring a central venous catheter due to the primary (intracranial) disease. We excluded patients under the age of 19 yrs and those with active cardiac arrhythmia, full sepsis syndrome, bleeding diathesis and infection, or bleeding at the site of the intended catheter insertion. Male to female ratio was 31:20, and the median age was 55 yrs (range, 24-85 yrs). Forty-four of 51 patients (86.3%) had an initial Glasgow Coma Scale score of 3, three patients had a Glasgow Coma Scale score of 9, one patient presented with an initial Glasgow Coma Scale score of 11, two patients had an initial Glasgow Coma Scale score of 13, and one patient had an initial Glasgow Coma Scale score of 15. The mean initial tissue injury severity score was 45.1 and the median initial tissue injury severity score 45.0 (range, 19-70). INTERVENTIONS: Patients were enrolled prospectively in a consecutive way. Within 12 hrs after admission, the intravascular cooling device (Cool Line catheter) was placed, the temperature probe was located within the bladder (by Foley catheter), and the Cool Gard cooling device was initiated. This Cool Gard system circulates temperature-controlled sterile saline through two small balloons mounted on the distal end of the Cool Line catheter. The patient's blood is gently cooled as it is passed over the balloons. The Cool Gard system has been set with a target temperature of 36.5 degrees C. The primary purpose and end point of this study was to evaluate the cooling capacity of this intravascular cooling device. Efficacy is expressed by the calculation formula of fever burden, which is defined as the fever time product ( degrees C hours) under the fever curve. MEASUREMENTS AND MAIN RESULTS: The cooling device was in operation for a mean of 152.4 hrs. The ease of insertion was judged as easy in 42 of 51 patients; in a single patient, the catheter was malpositioned within the jugular vein, requiring early removal. The rate of infectious and noninfectious complications (nosocomial pneumonia, bacteremia, catheter-related ventriculitis, pulmonary embolism, etc.) was comparable to the rate usually observed in our neurologic intensive care patients with such severe intracranial diseases. The total fever burden within the entire study period of (on average) 152.4 hrs was 4.0 degrees C hrs/patient, being equivalent to 0.6 degrees C hrs/patient and day. Thirty of 51 patients showed an elevation of the body temperature (>37.9 degrees C) within 24 hrs after termination of the cooling study. One awake patient (subarachnoid hemorrhage, Glasgow Coma Scale score 15) experienced mild to moderate shivering throughout the entire period of 7 days. The mortality rate was 23.5%. CONCLUSION: This novel intravascular cooling device (Cool Line catheter and Cool Gard cooling device) was highly efficacious in prophylactically controlling the body temperature of neurologic intensive care patients with very severe intracranial disease (median Glasgow Coma Scale score, 3-15). Morbidity and mortality rates were consistent with the ranges reported in the literature for such neurologic intensive patients.

Temporal and spatial profile of Bid cleavage after experimental traumatic brain injury.

Apoptosis plays an essential role in the cascade of CNS cell degeneration after traumatic brain injury. However, the underlying mechanisms are poorly understood. The authors examined the temporal profile and cell subtype distribution of the proapoptotic protein Bid from 6 hours to 7 days after cortical impact injury in the rat. Increased protein levels of tBid were seen in the cortex ipsilateral to the injury site from 6 hours to 3 days after trauma. Immunohistologic examinations revealed expression of tBid in neurons, astrocytes, and oligodendrocytes from 6 hours to 3 days after impact injury, and concurrent assessment of DNA damage using TUNEL identified tBid-immunopositive cells with apoptoticlike morphology in the traumatized cortex. Moreover, Bid cleavage and activation of caspase-8 and caspase-9 occurred at similar time points and in similar brain regions (i.e., cortical layers 2 to 5) after impact injury. In contrast, there was no evidence of caspase-8 or caspase-9 processing or Bid cleavage in the ipsilateral hippocampus, contralateral cortex, and hippocampus up to 7 days after the injury. The results provide the first evidence of Bid cleavage in the traumatized cortex after experimental traumatic brain injury in vivo, and demonstrate that tBid is expressed in neurons and glial cells. Further, findings indicate that cleavage of Bid may be associated with the activation of the initiator caspase-8 and caspase-9. Finally, these data support the hypothesis that cleavage of Bid contributes to the apoptotic degeneration of different CNS cells in the injured cortex.