Showing papers by "Werner Hacke published in 1999"

A Standardized MRI Stroke Protocol: Comparison with CT in Hyperacute Intracerebral Hemorrhage

Abstract: Background and Purpose—Diagnostic imaging in hyperacute ischemic stroke has been revolutionized by the introduction of diffusion- and perfusion-weighted MRI (DWI and PWI). CT, however, is still needed to exclude intracerebral hemorrhage (ICH). The purpose of our study was to determine the diagnostic accuracy of a standardized, multimodal MRI (mMRI) stroke protocol in the qualitative and quantitative assessment of hyperacute ICH (<6 hours). Methods—We investigated 9 patients with hyperacute ICH with CT followed immediately by a standardized mMRI stroke protocol (DWI, PWI [T2*-WI], FLAIR, T2-WI, and MRA). The time interval between MRI and symptom onset ranged from 3 hours to 5 hours 45 minutes. We analyzed and compared the size of the hematoma on CT and all mMRI images by semiautomatic volumetry. Results—ICH was unambiguously identified on the basis of all mMRI sequences. With increasing susceptibility effect (T2*-WI), the ICH, appearing as an area of hyperintensity with central signal loss, became qualitat...

Thrombolysis in acute ischemic stroke: controlled trials and clinical experience.

Abstract: Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effective and, when administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.

Association of Cervical Artery Dissection With Recent Infection

Abstract: Background: Cervical artery dissection (CAD) is an important cause of ischemic stroke in younger patients. However, its cause is insufficiently understood. Objective: To test the hypothesis that CAD is frequently associated with recent infection. Subjects and Methods: We compared the prevalence of infection during the preceding week in 43 consecutive patients with acute CAD and 58 consecutive patients younger than 50 years with acute cerebral ischemia from other causes (control patients). In subgroups of patients, we correlated infectious status with electron microscopic studies of skin biopsy specimens and investigated pathways potentially linking infection and CAD. Results: Recent infection was more common in patients with CAD (25/43 [58.1%]) than in control patients (19/58 [32.8%]; P = .01). Respiratory tract infection was preponderant in both groups. Recent infection, but not the mechanical factors cough, sneezing, or vomiting, was independently associated with CAD in multivariate analysis. Investigation of serum antibodies against Chlamydia pneumoniae, smooth muscle cells, endothelial cells, collagen types I through IV, and heat shock protein 65 and assessment of serum a1-antitrypsin and HLA did not contribute to the understanding of the pathogenesis of CAD. More patients with pathologic findings in skin biopsy specimens tended to have had a recent infection (13/21 [62%]) than patients without pathologic findings (2/9 [22%]; P = .11). Conclusion: Our results suggest a significant association between recent infection and CAD that is not explained by mechanical factors occurring during infection. Arch Neurol. 1999;56:851-856

Controlled Safety Study of a Hemoglobin-Based Oxygen Carrier, DCLHb, in Acute Ischemic Stroke

Abstract: BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin.

Herpes simplex virus encephalitis: chronic progressive cerebral MRI changes despite good clinical recovery and low viral load - an experimental mouse study.

Abstract: Cranial magnetic resonance imaging (MRI) is a sensitive diagnostic tool for the in vivo detection of morphological abnormalities in herpes simplex virus encephalitis (HSVE). We performed a long-term MRI study in a mouse model of HSVE. Cranial MRI findings were compared with the viral load within brain tissue, the presence of HSV DNA in the cerebrospinal fluid (CSF), a daily clinical assessment and post-mortem neurohistopathological studies. A 1.5 T cranial MRI scanner with standard spin-echo sequences was used. Viral load within the brain and the presence of HSV DNA in cerebrospinal fluid were determined by a polymerase chain reaction assay. Clinically, animals were severely affected within the first 2 weeks and recovered thereafter. Focal histopathological and MRI abnormalities involved predominantly limbic structures, a pattern that mimics human disease. Severity and extent of abnormalities had increased at 6 months despite clinical improvement. HSV DNA was present in CSF during the acute disease only. Brain viral load peaked at day 10 and declined thereafter. MRI as an in vivo monitoring approach may reveal chronic progressive changes in HSVE, despite clinical recovery and low viral load in the brain. Secondary, not directly virus-mediated, mechanisms of tissue damage may contribute to tissue damage of HSVE.

Favorable recovery from bilateral loss of somatosensory evoked potentials

Abstract: Objectives: Bilateral loss of the cortical somatosensory evoked potentials (SEP) is usually regarded as a strong predictor for a very poor clinical outcome. We present four patients with a favorable recovery from bilaterally absent cortical SEP. Design: Case series. Setting: Neurocritical care unit at the University of Heidelberg. Patients: Four patients with viral encephalitis, carbamazepine intoxication, head trauma, and left-side, space-occupying hemispheric infarction, respectively. Interventions: Serial recording of somatosensory and auditory evoked potentials, therapy of increased intracranial pressure, including decompressive surgery, hypothermia, and barbiturate coma. Measurements and Main Results: Three patients had an excellent outcome (Glasgow Outcome Scale 4 and 5). In those three patients, the SEP became completely normal during the clinical course. In one patient who remained severely disabled, the SEP became detectable again over the contralateral hemisphere, but remained abnormal. Possible influencing factors were sedative and analgetic drugs in all patients, and hypothermia and barbiturate coma in one of the patients. Conclusions: The absence of cortical SEP does not invariably imply an unfavorable prognosis. Absent cortical SEP indicates a severe neuronal dysfunction, which may be completely reversible if the underlying disease does not lead to permanent structural damage.

Moderate Hypothermie zur Behandlung des malignen Mediainfarktes

Abstract: Es wurde die Wirksamkeit moderater Hypothermie nach ausgedehnter zerebraler Ischamie bei 30 Patienten untersucht. Uber eine 48 bis 72 h dauernde Hypothermie von 33°C Korperkerntemperatur gelang es, die Mortalitat von Patienten mit malignem Mediainfarkt, die bei einer historischen Kontrollgruppe ca. 80% betrug, auf 43% zu senken. Durch moderate Hypothermie konnte der intrakraniellen Druck signifikant gesenkt werden. Die Wiedererwarmung hypothermer Patienten ist eine besonders kritische Phase in der Hypothermiebehandlung. Todesursache der 13 Patienten, die trotz der Hypothermiebehandlung verstarben, war ein nicht beherrschbarer ICP-Anstieg nach Wiedererwarmung. Wichtigste Nebenwirkung der Behandlung war eine relativ hohe Anzahl von Pneumonien (40%). Daneben kam es regelhaft zu einem Anstieg verschiedener Infektionsparameter, wie CRP, Leukozytenzahl und Fibrinogen. Daruber hinaus wurden keine wesentlichen sonstigen systemischen Nebenwirkungen der Hypothermiebehandlung beobachtet. Durch moderate Hypothermie kann der Verlauf des malignen Mediainfarktes gunstig beeinflust werden.

Epstein-Barr virus meningoencephalitis with a lymphoma-like response in an immunocompetent host.

Abstract: We report the clinical and neuropathological findings in an immunocompetent 19-year-old patient with a fatal acute Epstein-Barr virus (EBV) meningoencephalitis and a lymphoma-like B-lymphocyte response. Our results suggest that an immunotoxic rather than direct viral neuronal invasion mediates brain damage in EBV encephalitis and rule out primary central nervous system lymphoma (PCNSL) in our patient. We discuss immunosuppression as a therapeutic option, because present strategies mainly consist of symptomatic therapy due to unclear pathogenesis and nonavailability of effective antiviral agents.

Acute central nervous system (CNS) toxicity of total body irradiation (TBI) measured using neuropsychological testing of attention functions.

Abstract: Purpose: The purpose of this study was to investigate acute normal tissue damage of low irradiation doses to the healthy, adult central nervous system (CNS) using neuropsychological testing of attention functions. Methods and Materials: Neuropsychological testing (IQ, attention [modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine]) was used to examine 40 patients (43 ± 10 years) before and immediately after the first fraction (1.2 Gy) of hyperfractionated total body irradiation (TBI) at the University of Heidelberg. The patients received antiemetic premedication. Test results are given as mean percentiles ± standard deviation, with 50 ± 34 being normal. Thirty-eight control patients (53 ± 15 years) were studied to quantify the influence of hospitalization, stress, and repeated testing. Results: The patients showed normal baseline test results (IQ = 101 ± 14, attention = 54 ± 28) and no decrease in test results after 1.2 Gy TBI. Attention functions improved (66 ± 25) corresponding to a practice effect of repeated testing that was seen in the control group, although alternate versions of the tests were used (IQ = 104 ± 10, attention before = 42 ± 29, attention after = 52 ± 31). Conclusion: Our data show no deterioration of neuropsychologic test results acutely after 1.2 Gy whole body exposure in adult patients without CNS disease receiving antiemetic medication.

Indomethacin for brain edema following stroke.

Abstract: Conventional therapies for raised intracranial pressure (ICP) frequently are not effective. We report a patient with raised ICP following a large hemispheric stroke. After conventional therapies had failed, indomethacin was repeatedly administered. After bolus infusion (50 mg), the ICP fell by a mean of 8.1 mm Hg, and the mean arterial blood pressure increased by a mean of 7.1 mm Hg, leading to a mean increase in the cerebral perfusion pressure by 15.3 mm Hg. After 1 h, the ICP had returned to baseline values after most infusions. Continuous infusion of indomethacin was not effective. We conclude that indomethacin may reduce elevated ICP over a short time in patients with ischemic brain edema even after conventional therapy has failed.

How did the results of ECASS II influence clinical practice of treatment of acute stroke

Abstract: INTRODUCTION AND DEVELOPMENT There appears to be a rationale for the use of thrombolysis in ischemic stroke. Streptokinase should no longer be used to treat acute ischemic stroke. However, thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) may have an important role in the management of acute stroke. The studies to-date highlight the importance of early intervention and careful patient selection. In the National Institute of Neurological Disorders and Stroke (NINDS) trial, treatment within three hours was associated with an improved functional outcome without an increase in mortality. In the European Cooperative Acute Stroke Study (ECASS), treatment of eligible patients resulted in improved neurologic and functional out come. In the Multicentre Acute Stroke Trial Europe (MAST-E) and Australian Streptokinase Trial (ASK) trials, later intervention was associated with an increased risk of cerebral hemorrhage and poor outcome. CONCLUSIONS Successful use of thrombolytic therapy with rt-PA, therefore, depends on rapid assessment to exclude patients with hemorrhagic stroke or those at risk of hemorrhagic complications. It has been shown to be beneficial in patients treated within three hours who conform to the strict inclusion and exclusion criteria of the NINDS trial. Moreover, after the results of ECASS II, and the recent metaanalyses of all three major rt-PA trials, it seems that with strict selection criteria, expert CT-reading, adherence to the protocols and a stroke unit type approach, the time window for thrombolysis may be as long as six hours in selected patients.

Thrombolysis in acute cerebrovascular disease: indications and limitations.

Abstract: Introduction: Large-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction (AMI). As most ischemic strokes are thromboembolic in origin,1 there appears to be a rationale for the use of thrombolytic agents in the management of ischemic stroke. Thrombolytic agents differ in their mechanisms of action, but in general, they act by promoting the conversion of plasminogen into plasmin, resulting in fibrin degradation and clot dissolution. Streptokinase and recombinant tissue plasminogen activator (rt-PA) are the agents that have been the most widely investigated in stroke studies. Ancrod, the active agent in the venom of the Malayan pit viper, is primarily considered an anticoagulant, although it does stimulate endogenous t-PA release from the vascular endothelium and may enhance local thrombolysis. Urokinase is used in local, intra-arterial thrombolysis but has not been subjected to large clinical trials since com-puted tomography (CT) diagnosis became widely available.

Fibrinolyse intraventrikulärer Hämatome mit rt-PA

Abstract: Die intraventrikulare Fibrinolyse ist eine experimentelle Therapie intraventrikularer Hamatome zur schnelleren Clearance intraventrikularen Blutes. Wesentliche Komplikationen wurden bisher nicht beobachtet. Wir berichten uber 9 Patienten (7 Manner, 2 Frauen, mittleres Alter 64 J.) mit intrazerebralen Hamatomen mit Ventrikeleinbruch, die wir mit intraventrikularer Infusion mit rt-PA (2–32 mg, mittlere Dosis 17 mg) behandelten. Bei 2 Patienten kam es zu einer mit der Fibrinolyse assoziierten klinisch signifikanten Zunahme des intraventrikularen Blutes; bei einer Patientin wurde die Fibrinolyse deswegen abgebrochen. Andere Komplikationen wurden nicht beobachtet. Bei 8 der 9 Patienten kam es wahrend der Fibrinolyse zu einer raschen und weitgehenden Reduktion des intraventrikularen Blutvolumens. Ein permanenter Shunt wurde bei 2 Patienten notwendig. Wir schliesen, das die intraventrikulare Lyse wahrscheinlich zu einer schnelleren Clearance des intraventrikularen Blutes fuhrt. Eine Shuntanlage wird nicht in jedem Fall verhindert. Die intraventrikulare Fibrinolyse ist eine potentiell gefahrliche Therapie mit dem Risiko von Infektionen und Blutungen.

Zeitbasiertes Management des akuten Schlaganfalls

Abstract: Progression in medical research and economic needs require new planning and organization of treatment strategies. This does also apply for stroke treatment: New pathophysiological knowledge, positive results of thrombolytic therapy and the demostrated importance of early treatment at Stroke Units justify that stroke must be regarded as an emergency. Timing is of utmost importance. Time-based management serves as a planning model for a new stroke treatment strategy. The treatment process is divided into three phases: alarming, pre-hospital and in-hospital phase. The effectiveness of each of these phases is influenced by several variables (personnel, technical equipment, course of the disease, etc.). Knowledge of each separate phase helps to discover weaknesses, which allows an aimed improvement, e.g. public education, training of paramedics and medical personnel. Modern communication systems allow new information transfer, which can help to avoid unnecessary transport of patients.

Anschlußheilbehandlung nach SchlaganfallEine Standortbestimmung

Abstract: Die Anschlusheilbehandlung (AHB) ist ein fester Bestandteil der postakuten Rehabilitation nach einem Schlaganfall. Zwar gibt es genaue Vorgaben zur AHB von Seiten der Kassen- und Rentenversicherungstrager, unklar ist jedoch, welche Patienten in eine AHB eingewiesen werden, welche Storungen sie noch aufweisen und welche Anforderungen sie an eine AHB stellen. Prospektiv wurden 200 Patienten untersucht, die nach einem Schlaganfall an einer AHB teilnahmen. Neben relevanten soziodemographischen und medizinischen Daten wurden verschiedene neurologische (Barthel, modifizierter Rankin Score, NIHSS u.a.) und neuropsychologische (Teile des HAWIE-R, BAT, Wilde u.a.) Mesinstrumente verwendet. Uber die Halfte der Patienten, die in eine AHB nach einem Schlaganfall eingewiesen wurden, stand noch im aktiven Erwerbsleben. Viele Patienten litten unter unzureichend behandelten Risikofaktoren und hatten bereits vaskulare Vorerkrankungen bevor sie den aktuellen Schlaganfall erlitten. Die neurologischen Storungen waren eher moderat, wohingegen durchschnittlich ganz erhebliche neuropsychologische Leistungseinbusen bestanden.

Status epilepticus Rationelle Diagnostik und aktuelle Therapiekonzepte

Abstract: Ein Status epilepticus (SE) liegt vor, wenn ein kontinuierlicher Anfall besteht oder mehrere Anfalle, zwischen denen der Patient das Bewustsein nicht wiedererlangt. Der SE ist eine haufige Erkrankung mit einer hohen Mortalitat. Es stehen heute eine Vielzahl effektiver medikamentoser Therapien zur Verfugung. Die aktuellen Behandlungsstrategien beruhen allerdings noch fast ausschlieslich auf theoretischen Uberlegungen und kleinen Fallserien. Zur optimalen Therapie ist ein standardisiertes Konzept notwendig. Die initiale Behandlung erfolgt mit Benzodiazepinen und ist bei den meisten Patienten erfolgreich, bei Erfolglosigkeit wird Phenytoin und Phenobarbital eingesetzt. Der therapierefraktare SE hat eine schlechte Prognose und mus auf einer spezialisierten Intensivstation mit der Moglichkeit eines EEG-Monitorings behandelt werden. In dieser Phase der Erkrankung ist das am besten geeignete Vorgehen noch nicht bekannt; Barbiturate, Midazolam und Propofol sind alternativ anwendbare wirksame Substanzen.

Systemische Thrombolysetherapie mit rt-PA beim akuten Mediaterritorialinfarkt Erfahrungen aus der klinischen Routine

Abstract: Seit dem Erscheinen der beiden grosen randomisierten Studien zur systemischen Lysetherapie des akuten Mediaterritorialinfarktes sind wenige Berichte mit Erfahrungen aus dem klinischem Alltag veroffentlich worden. Inwieweit extrakranielle Stenosen oder Verschlusse der A. carotis interna den Erfolg einer Lysetherapie beinflussen, ist aus diesen Studien nicht abzuleiten. In den Jahren 1995 bis Anfang 1998 wurden insgesamt 56 Patienten mit einer nicht langer als 6 h bestehender Ischamie im Versorgungsgebiet der A. cerebri media mit systemisch appliziertem rt-PA auserhalb prospektiver randomisierter Studien behandelt. Vor der Lysetherapie wurde in der Regel eine neurovaskulare Diagnostik mittels extra- und transkranieller Dopplersonografie oder CT-Angiografie durchgefuhrt. Verschlusse der intrakraniellen A. carotis interna (Karotis-T) wurden von der Lysetherapie ausgeschlossen. Die Rekanalisierungsrate sollte durch neurovaskulare Verlaufsuntersuchungen innerhalb von 24 h kontrolliert werden. Nach mindestens drei Monaten wurde das klinische Resultat mittels der Rankin-Skala beurteilt. Das mittlere Zeitintervall bis zur Lysetherapie lag bei 3,7 h. Es traten 4 parenchymatose Blutungen (7,1%) mit klinischer Verschlechterung auf. Acht Patienten (14,3%) waren bis zum Follow-up verstorben, 4 davon innerhalb der ersten 14 Tage. 39 Patienten hatten sich klinisch gebessert. Der klinische Zustand zum Zeitpunkt des Follow-up und die Rekanalisierungsrate der A. cerebri media zeigte keine Abhangigkeit von der Perfusion der extrakraniellen Abschnitte der ipsilateralen A. carotis interna. Auch auserhalb kontrollierter Studien kann unter Beachtung von Therapierichtlinien die systemische Lysetherapie des akuten Mediaterritorialinfarktes mit einem Zeitfenster von 6 h mit ausreichend niedriger Komplikationsrate durchgefuhrt werden. Das klinische Resultat der Patienten und die Rekanalisierungsrate der A. cerebri media wird nicht von der Perfusion der extrakraniellen A. carotis interna beeinflust.

Der Schlaganfall als medizinischer Notfall

Abstract: Studies into the pathophysiology of acute ischaemic stroke have indicated that treatment options are likely to be optimised when early signs of stroke are recognised and treatment is initiated within 3 hours from symptom onset. For most patients there is a long delay between the onset of symptoms and the start of therapy. Many factors are responsible for this time delay: signs and symptoms often go unrecognised by patients, relatives and bystanders and stroke is not given a high priority by medical staff. Although a small number of stroke patients is treated as emergency and attended to by the emergency medical services within this time window, this number could easily be increased by intensified public and emergency personnel education. For the future, we hope that emergency medical services (EMS) will be able to initiate therapies which must be administered within the first few hours of acute stroke. Standard of care by the EMS personnel includes maintenance of oxygenation, treatment of cardiac arrhythmia and hypertension as well as hyperglycemia and hyperthermia. Early notification by the emergency medical services about stroke patients would enable stroke teams to be present at admission, thus improving the likelihood of a better outcome for patients.

Rehabilitation treatment after stroke. An assessment of current status

Abstract: A standardized postacute inpatient rehabilitation program (Anschlussheilbehandlung) after stroke is well established in Germany. Yet the needs of patients being admitted to an Anschlussheilbehandlung (AHB) are not completely known. Therefore sociodemographic data, handicap, impairment and neuropsychologic deficits in 200 stroke patients were evaluated before admission to an AHB with different scores (Barthel, modified Rankin Score, NIHSS, HAWIE-R, Wilde, etc.). About half of the patients were still working prestroke. Most patients suffered from several vascular risk factors, which were insufficiently treated, and about a third of the patients had cerebrovascular disease prior to this stroke. At admission to the rehabilitation program the group of patients with severe neurological deficits was small. In average the disability was rather moderate (Rankin = 2.6). Mainly gait and finger dexterity were handicapped. Functional impairment was outweighed by neuropsychological deficits.

Emergency Treatment and Intensive Care in Ischemic Stroke

Abstract: Until recently, the acute care of stroke patients was characterized by therapeutic nihilism. Most patients were treated on normal wards in urban hospitals, and the principles of optimal general treatment strategies were rarely followed. In the last few years, the development of novel therapies for the treatment of acute stroke, based on increasing pathophysiologic knowledge, has led to a new-found optimism regarding the future of the stroke patient. Research has revealed that the treatment of stroke as a medical emergency improves long-term patient outcomes, as long as good clinical care and pharmacological therapy are initiated within hours of stroke onset. In this chapter, we present principles and guidelines for emergency management of acute ischemic stroke, discuss specific therapies and review intensive care of severe stroke focusing on malignant middle cerebral artery (MCA) infarction.