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W Hacke

Publications and source records attributed to W Hacke.

At least 145 records · Page 8Linked to original sources

[Antithrombotic therapy after cerebral ischemia].

Following cerebral ischaemia a recurrent stroke must be avoided in most patients by means of antithrombotic agents. Based on the results reviewed here of new therapy studies, we discuss the presently available antithrombotic treatment options for prophylaxis in ischaemic stroke. TASS (Ticlopidine Aspirin Stroke Study) and CATS (Canadian American Ticlopidine Study) are two multicentre studies investigating the effect of ticlopidine, a new antiplatelet agent of the thienopyridine family, compared to acetylsalicylic acid (ASA) respectively placebo, in the secondary prophylaxis of ischaemic stroke. A significant relative risk reduction of ticlopidine against ASA (21%) and against placebo (28.1%) was shown. CAPRIE (Clopidogrel vs. Aspirin in Patients with Risk of Ischemic Events) evaluated clopidogrel and ASA in the secondary prophylaxe of stroke, myocardial infarction and peripheral vascular occlusive disease. Clopidogrel has been shown to be as effective as ticlopidine compared to ASA in the secondary prevention of vascular disease but had the advantage of a far less severe side effect profile as ticlopidine. ESPS 2 (2nd European Stroke Prevention Study) compared dipyridamole and ASA alone and in combination against placebo in stroke prevention. The combination of agents showed a 24.4% relative risk reduction to suffer ischaemic stroke as opposed to placebo. The ranking of heparin and heparinoids in the secondary prevention of ischaemic stroke has not been completely established but seems to diminish according to recently published data from three major trials. The American TOAST study (Trial of Org 10172 in Acute Stroke Treatment) failed to prove any advantage of intravenous Orgaran compared to placebo. In IST (International Stroke Trial) and CAST (Chinese Acute Stroke Trial) the benefits of heparin are invalidated by a higher bleeding rate of patients on intravenous heparin therapy. Furthermore, the results of IST have to be judged critically because of significant methodical inadequacies. When applying antithrombotic agents, therapeutic effect and presumed better outcome should be weighed against the risk of associated bleedings. The indication for an antithrombotic treatment should be reevaluated in regular control examinations and the possibility of a less aggressive treatment should be considered.

Aspirin↗

Predominant involvement of motor fibres in patients with critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) is a recognized cause of muscle weakness and failure of weaning from a ventilator. In order to characterize the features of CIP, we have examined 28 consecutive surgical patients with severe sepsis using bedside electrophysiology. Of the 28 patients (median APACHE II score 31), 20 developed moderate to severe CIP, as shown by the presence of moderate to severe denervation activity on resting EMG. The median nerve compound muscle action potential (CMAP) amplitudes were reduced to 3.24 (SEM 0.48) mV, while sensory nerve action potential (SNAP) amplitudes obtained from the same nerve were normal (13.1 (1.9) microV). In approximately 50% of these patients, the reduction in CMAP exceeded 50% of the lower limit of normal. Similar results were obtained from stimulation of the ulnar nerve. We conclude that CIP is a major complication in patients with severe sepsis and prolonged artificial ventilation. It predominantly involves motor fibres and thus markedly interferes with weaning from the ventilator.

Adolescent↗

TPA in acute stroke.

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Cerebrovascular Disorders↗

Serum neuron-specific enolase as early predictor of outcome after cardiac arrest.

OBJECTIVE: To examine the prognostic value of serum neuron-specific enolase for early prediction of outcome in patients at risk for anoxic encephalopathy after cardiac arrest. DESIGN: Prospective study. SETTING: Coronary intensive care unit of the University of Heidelberg. PATIENTS: Forty-three patients (66.8 +/- 12.7 [SD] yrs, range 33 to 85) who had had either primary or secondary cardiac arrest, followed by cardiopulmonary resuscitation (CPR). INTERVENTIONS: Serial blood samples and clinical examinations. MEASUREMENTS AND MAIN RESULTS: Serum neuron-specific enolase concentrations were determined after CPR on 7 consecutive days. Twenty-five patients remained comatose and subsequently died; 18 patients survived the first 3 months and had no relevant functional deficit at 3-month follow-up. Neuron-specific enolase concentrations were correlated with neurologic outcome. Concentrations of >33 ng/mL predicted persistent coma with a high specificity (100%) and a positive predictive value of 100%. Overall sensitivity was 80%, with a negative predictive value of 78%. Serum concentrations of neuron-specific enolase exceeded this cutoff value no more than 3 days after cardiac arrest in 95% of patients in whom these concentrations had exceeded 33 ng/mL. CONCLUSIONS: In patients who have been resuscitated after cardiac arrest, serum neuron-specific enolase concentrations of >33 ng/mL predict persistent coma with a high specificity. Values below this cutoff level do not necessarily indicate complete recovery, because this method has a sensitivity of 80%.

Adult↗

Intraventricular brain-derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats.

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls (P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/- 56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/- 19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

Animals↗

Acute stroke: usefulness of early CT findings before thrombolytic therapy.

PURPOSE: To determine whether the extent of subtle parenchymal hypoattenuation detected on computed tomographic (CT) scans obtained within 6 hours of ischemic stroke is a factor in predicting patients' response to thrombolytic treatment. MATERIALS AND METHODS: The baseline CT scans of 620 patients, who received either recombinant tissue plasminogen activator (rt-PA) or a placebo, in a double-blind, randomized multicenter trial were prospectively evaluated and assigned to one of three categories according to the extent of parenchymal hypoattenuation: none, 33% or less (small), or more than 33% (large) of the middle cerebral artery territory. The association between the extent of hypoattenuation on the baseline CT scans and the clinical outcome in the placebo-treated and the rt-PA-treated groups after 3 months was analyzed. RESULTS: In 215 patients with a small hypoattenuating area, treatment increased the chance of good outcome. In 336 patients with a normal CT scan and in 52 patients with a large hypoattenuating area, rt-PA had no beneficial effect but increased the risk for fatal brain hemorrhage. CONCLUSION: The response to rt-PA in patients with ischemic stroke can be predicted on the basis of initial CT findings of the extent of parenchymal hypoattenuation in the territory of the middle cerebral artery.

Acute Disease↗

Acute and critical care in neurology.

The diagnostic and therapeutic management of selected neurological diseases requiring intensive treatment is summarized with special regard for current standards and new developments in therapy. Ischemic stroke is an emergency since the outcome can be improved by immediate and adequate general supporting as well as specific (thrombolytic) therapy in specialized stroke units. Surgical evacuation of supratentorial intracerebral hemorrhage is still controversial. We give an overview of conditions in which surgical therapy such as cerebellar hemorrhage and large, nondominant ganglionic hemorrhage might be advisable. Cerebral venous thrombosis is treated with full-dose intravenous heparin even if hemorrhage is present. In acute bacterial meningitis, early treatment of foci and empiric antibiotic therapy is crucial in order to prevent complications. The outcome of herpes simplex encephalitis can be favorably influenced by treatment with aciclovir and aggressive therapy of elevated ICP and seizures. Acute Guillain-Barré syndrome requires daily monitoring of vital functions in order to recognize the need for intensive care; intravenous immunoglobulins and plasmapheresis are equally recommended for clinical and financial reasons.

Acute Disease↗

Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury. Correlation with clinical course and infarct size.

BACKGROUND AND PURPOSE: Superoxide dismutase (SOD) is one of the major free radical scavenging systems that might play a role in both degenerative and acute diseases of the central nervous system. METHODS: We measured SOD activity in the serum of 41 patients with acute ischemic stroke with a chemiluminometric assay based on the generation of oxygen free radicals by xanthine and xanthine oxidase. RESULTS: SOD activity was significantly lower in patients with ischemic stroke than in age-matched control patients with nonvascular, neurological illnesses (n = 24; P < .034, Wilcoxon rank test). The activity was inversely correlated with the size of infarction on CT (P = .01, Spearman correlation) and the severity of neurological deficits (P < .001, Spearman correlation). The decreased SOD activity recovered within 5 days after stroke to values found in serum of control patients. CONCLUSIONS: Our data suggest that the SOD activity in serum is reduced in stroke patients, and replacement of antioxidative activity could be beneficial in the acute treatment of cerebral ischemia.

Acute Disease↗

Infection-associated cervical artery dissection. Three cases.

BACKGROUND: The pathogenesis of cervical artery dissection remains unknown. Infection-mediated damage of the arterial wall may be one contributing mechanism. We present three male patients with respiratory infection prior to cervical artery dissection. CASE DESCRIPTIONS: Case 1: During an upper respiratory tract infection, a 49-year-old patient developed bilateral carotid and vertebral artery dissection with complete vessel restitution. Case 2: Within 3 years, a 40-year-old patient experienced two episodes of bilateral internal carotid artery dissection, both preceded by febrile upper respiratory tract infection. Case 3: A 52-year-old patient developed right-sided and, 2 years later, left-sided internal carotid artery dissection, each following upper respiratory tract infection. CONCLUSIONS: Infection may be a trigger factor in the pathogenesis of cervical artery dissection.

Adult↗

Prognosis of stroke patients requiring mechanical ventilation in a neurological critical care unit.

BACKGROUND AND PURPOSE: Intubation and mechanical ventilation are sometimes necessary during treatment of acute stroke. Indications include neurological deterioration, pulmonary complications, and elective intubation for procedures and surgery. Prognosis in severe stroke patients requiring mechanical ventilation has often been reported to be poor. This study was performed to prospectively assess the prognosis of stroke patients who require ventilation in a neurological intensive care unit and to determine factors that may influence outcome. METHODS: Analysis was made of 124 consecutive stroke patients who required mechanical ventilation over a 2-year period. We determined the survival rate at 1 year after admission. Initial clinical data, history of previous diseases, and indication for intubation were analyzed for prognostic significance by univariate and multiple logistic regression analysis. RESULTS: The 1-year survival rate was 33.1% (n = 41). Sixty-five patients (52%) died in the neurological intensive care unit. Among 17 variables analyzed, seven were found to significantly influence 2-month fatality in the univariate analysis: age greater than 65 years, atrial fibrillation, bilateral absence of pupillary light reflex, bilateral absence of corneal reflex, bilateral Babinski's sign, infratentorial stroke, and Glasgow Coma Scale (GCS) score less than 10. Independent predictors of death at 2 months were age greater than 65 years (P = .03), GCS score less than 10 (P = .01), and intubation performed because of coma or acute respiratory failure (P = .04). CONCLUSIONS: Overall prognosis of ventilated patients with severe stroke is better than previously reported. Older patients comatose on admission who need to be intubated because of neurological or respiratory deterioration have the poorest prognosis. We conclude that intubation and mechanical ventilation of severe stroke patients should be performed in a timely manner, before irreversible damage occurs.

Activities of Daily Living↗

Association between acute cerebrovascular ischemia and chronic and recurrent infection.

BACKGROUND AND PURPOSE: We performed a case-control study to investigate whether chronic or recurrent respiratory, ear-nose-throat (ENT), and dental infections are risk factors for cerebrovascular ischemia. METHODS: Using a standardized questionnaire we investigated past infectious diseases in 166 consecutive patients with acute cerebrovascular ischemia and in 166 age- and sex-matched nonstroke neurological patient controls. In subgroups, we performed standardized ENT (69 patients, 66 control subjects) and dental examinations including orthopantomography (66 patients, 60 control subjects). Dental status was determined by a total dental index (TDI) that reflects caries, periapical lesions, periodontitis, and other dental lesions and by an orthopantomography index (OPGI) that was assessed blinded. RESULTS: Frequent (> or = 2 episodes in each of the 2 preceding years) or chronic bronchitis was associated with cerebrovascular ischemia in age-adjusted multiple logistic regression analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to 4.6). Groups were not different in ENT examination. Patients tended to have a worse dental status (TDI: P = .070; OPGI: P = .062) and had more severe periodontitis (P = .047) and periapical lesions (P = .027) than control subjects. In age-adjusted multiple logistic regression analysis with social status and established vascular risk factors, poor dental status (TDI) was independently associated with cerebrovascular ischemia (OR, 2.6; 95% CI, 1.18 to 5.7). CONCLUSION: Recurrent or chronic bronchial infection and poor dental status, mainly resulting from chronic dental infection, may be associated with an increased risk for cerebrovascular ischemia.

Acute Disease↗

Plasma insulin-like growth factor I and IGF binding protein 3 levels in patients with acute cerebral ischemic injury.

BACKGROUND AND PURPOSE: The insulin-like growth factors (IGF) are synthesized in the brain and are involved in fetal brain development. An increased expression of IGF-I and IGF-II occurs in cerebral regions with neuronal damage after experimental hypoxic injury. Furthermore, the expression of mRNAs coding for IGF-I and the binding proteins IGFBP-2 and IGFBP-3 is augmented in response to unilateral ischemia in animal models. The secretory dynamics of IGF-I in human cerebral ischemia have not yet been investigated. METHODS: Plasma IGF-I and IGFBP-3 were measured sequentially in 20 patients with acute ischemic stroke (within 24 hours and 3, 5, and 10 days thereafter). For analysis the patients were assigned to three groups according to the diameter of the infarct area as measured on CT scan: small (< 1.5 cm), moderate (> or = 1.5 cm and < or = 5 cm), and large (> 5 cm). Eight age-matched patients with nonvascular, neurological illnesses served as controls. RESULTS: Plasma IGF-I and IGFBP-3 plasma concentrations after acute cerebral ischemia were strikingly lower than those in control subjects and healthy individuals reported in the literature. Plasma IGF-I levels in patients with large infarcts were significantly statistically lower than those in control subjects (P < .05), and plasma IGFBP-3 levels were significantly lower than those in control subjects on days 5 and 10. CONCLUSIONS: IGF-I and IGFBP-3 plasma levels are decreased in patients after cerebral ischemia. After acute ischemic stroke, increased demand for growth factors, altered tissue distribution, and accelerated metabolic clearance rate or central inhibition of the somatotrophic axis may contribute to these low plasma concentrations. Growth factors such as IGF-I and IGFBP-3 may play an important role in the pathophysiology of acute cerebral ischemia, and growth factors may have a considerable effect on future therapeutic regimens.

Acute Disease↗

Craniectomy: an aggressive treatment approach in severe encephalitis.

BACKGROUND AND OBJECTIVE: Focal encephalitis may be associated with brain edema, which is often fatal. The control of intracranial pressure (ICP) is therefore crucial for further therapeutic strategies in space-occupying edema following encephalitis. However, aggressive treatment strategies such as hemicraniectomy have not been described in a larger series of patients. PATIENTS AND METHODS: We describe the clinical course and outcome in six patients who developed severe brain edema associated with acute encephalitis. All received maximum medical treatment for elevated ICP, but with signs of brainstem compression emerging, hemicraniectomy was performed to control ICP. RESULTS: All patients had a very severe encephalitic syndrome and were treated over the course of weeks in the neurocritical care unit (NCCU). However, all patients recovered almost completely and showed only mild or no neurologic deficit when reexamined after 4 months to 3 years. CONCLUSIONS: Hemicraniectomy should be considered in patients with severe brain edema following encephalitis as a potentially lifesaving therapeutic measure. Moreover, the initial neurologic deficit seems to have no impact on the long-term clinical outcome.

Adult↗

Brain temperature monitoring and modulation in patients with severe MCA infarction.

BACKGROUND: Brain temperature has been measured only occasionally in humans. After head trauma, a temperature gradient in brain temperature compared with body temperature of up to 3 degrees C degrees higher in the brain has been reported. Elevated temperature facilitates neuronal injury after ischemia. At present, no information concerning changes in brain temperature after acute stroke is available. METHODS: In 15 patients who had suffered severe ischemic stroke in the MCA territory, intracerebral temperature was recorded with use of two different thermocouples, with intraventricular, epidural, and parenchymatous measurements. Body-core temperature (Foley catheter temperature) and jugular bulb temperature (n = 5) were recorded simultaneously. Measures for reducing brain temperature were compared. RESULTS: In all patients, brain temperature exceeded body-core temperature by at least up to 1 degrees C (range, 1.0 to 2.1 degrees C). Temperature in the ventricles exceeded epidural temperature by up to 2.0 degrees C. Brain temperature modulation was independent of single pharmacologic (paracetamol, metamizol) treatments. Only systemic cooling was effective and sustained hypothermic (33 to 34 degrees C) brain temperatures. CONCLUSION: After MCA stroke, human intracerebral temperature is higher than central body-core temperature. There is also a temperature gradient within the brain, with the ventricles warmer than the surface. Mild hypothermia in the treatment of severe cerebral ischemia with use of cooling blankets is both easy to perform and effective in the therapy of severe hemispheric infarction.

Adult↗

Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid of patients with herpes simplex virus encephalitis.

We used a nested polymerase chain reaction assay to quantitate the number of viral copies in cells of CSF of eight patients with herpes simplex virus encephalitis (HSVE). The viral load was monitored in serial CSF samples during the course of disease and correlated to clinical symptoms, radiologic manifestations, efficacy of acyclovir treatment, and overall clinical outcome. Before treatment, HSV type 1 (HSV-1) copies were detected at a mean value of 1,786/10(5) (range, 5 to 8,333/10(5) cells; median, 81/10(5) cells). During therapy, HSV-1 DNA decreased gradually to a mean value of 6 copies/10(5) cells (range, 0 to 33 copies/10(5) cells; median, 0 copies/10(5) cells) within 6 to 21 days and disappeared or was barely detectable before treatment completion in most cases. The HSV-1 burden in the CSF did not clearly correlate with the severity of clinical signs or the degree of cranial imaging findings and overall outcome. Quantitation of HSV-1 copies allows rapid and reliable monitoring of antiviral therapy. The absence of a clear correlation between viral load in the CSF and morbidity may suggest a role for indirect mechanisms of brain injury in HSVE.

Acyclovir↗

Barbiturate coma in severe hemispheric stroke: useful or obsolete?

Barbiturates are administered in a variety of clinical conditions to control elevated intracranial pressure (ICP). However, their routine use to treat elevated ICP has been questioned because it may cause severe side effects. We therefore investigated the effect of high-dose barbiturate therapy on ICP and outcome in patients with severe brain edema after severe middle cerebral artery (MCA) or hemispheric infarction. Barbiturate coma was induced with thiopental infusion in 60 patients with critically increased ICP due to large hemispheric or MCA territory infarction, defined by CT. ICP was monitored in all patients during barbiturate therapy. Barbiturate coma was induced after a standardized treatment protocol for increased ICP after failure of osmotherapy and mild hyperventilation. During barbiturate administration, cerebral perfusion pressure (CPP) and mean arterial pressure were recorded. Clinical outcome of these patients and the individual effect on ICP were analyzed. Only five of 60 patients who were treated with barbiturate coma survived (8%). All other patients died after transtentorial herniation with subsequent brain death. Barbiturate infusion was followed by a drop in ICP in 50 patients and showed no effect on ICP values in 10 patients. CPP decreased with a mean of 9 mm Hg (range, 5 to 20 mm Hg). Although barbiturates were initially effective, only in some patients was ICP control sustained. Severe side effects of barbiturate therapy, besides arterial hypotension, were seen in 15 patients (25%). Barbiturate coma in the therapy of increased ICP after severe ischemic hemispheric stroke can lower critically elevated ICP levels. However, it seems to have no positive effect on neurologic outcome.

Adult↗