Langzeit-Prognose von Patienten mit juvenilem Insult

Zusammenfassung Bei 57 von 70 Patienten, die vor dem 40. Lebensjahr erstmals zerebrale Durchblutungsstörungen auf ischämischer Basis erlitten hatten, wurde der weitere Verlauf über durchschnittlich 84 Monate verfolgt. Innerhalb von 48 Monaten nach dem initialen Ereignis kam es bei 22 von 51 Patienten (43,1%) mit Spontanverlauf zu weiteren Manifestationen (Rezidivquote fur Patienten mit transitorischischämischen Attacken 78,6%, für Patienten mit prolongierten reversiblen Defekten 33,3%, für Patienten mit kompletten Schlaganfällen 28,6%), wobei 31,5% aller Patienten schon innerhalb des ersten Jahres neuerliche zerebrale Durchblutungsstörungen erlitten, die meisten sogar innerhalb der ersten wenigen Monate.Trotz der wesentlich höheren Rezidivrate waren Patienten mit initialen passageren zerebralen Durchblutungsstörungen am Ende des Beobachtungszeitraums (BZR) in sozialer Hinsicht weniger beeinträchtigt als Patienten mit kompletten Schlaganfällen als Erstmanifestation. 78,4% aller Patienten waren am Ende des BZR voll arbeitsfähig.Bei 72,2% der patienten mit neuerlichen zerebralen Durchblutungsstörungen war das Herdgeschehen einem anderen als dem urspriinglich betroffenen Gefäßgebiet zuzuordnen.Patienten mit arterieller Hypertonic im BZR halten eine etwas ungünstigere Langzeitprognose, während Nikotinkonsum wie auch relatives Körpergewicht auf den Schweregrad der sozialen Beeinträchtigung keinen Einfluß hatte.Trotz der eher günstigen Langzeitprognose weisen unsere Ergebnisse — besonders im Hinblick auf die hohe Rezidivquote innerhalb der ersten Monate nach der initialen Attacke — auf die Notwendigkeit einer unverzüglichen umfassenden diagnostischen Abklärung und Einleitung einer individuellen Therapie bei Patienten mit juvenilem Insult hin.     

Cerebral Ischemia and Neurogenesis: A Two-time Comparison

Background

This study compares the effect of mild and severe cerebral ischemia on neuronal damage and neurogenesis.

Methods

Sixteen Sprague–Dawley rats, anesthetized with 0.8 vol% halothane in O₂/air, were subjected to forebrain ischemia by bilateral common carotid artery occlusion plus hemorrhagic hypotension (mean arterial blood pressure = 40 mmHg) for 8 (mild) or 13 (severe) min. Four non-ischemic animals were investigated as naïve controls. Bromodeoxyuridine (50 mg/kg), a marker of new cells, was administrated for seven consecutive postischemic days. After 28 days, animals were perfused with 4% paraformaldehyde and the brains were sliced. Histopathological damage of the hippocampus and the volume of the dentate gyrus were assessed by HE-staining. With immunohistochemistry BrdU-positve cells were detected in the dentate gyrus. The amount of new generated neurons was identified by double-immunofluorescence-staining of BrdU and neuronal marker (NeuN).

Results

In the CA-1 region of the hippocampus, mild ischemia induced damage up to 10% (HE-index 0.8 ± 1.2) and severe ischemia up to 50% (HE-index 2.1 ± 1.4). There was no histopathological damage in naïve control animals. The amount of new neurons was increased by 250% after mild insult and by 160% after severe insult compared to the naïve control animals.

Conclusions

These data indicate that histopathological damage depends on the severity of the ischemic insult and that forebrain ischemia activates generation of new neurons. A mild ischemic challenge appears to be a more potent neurogenic stimulus than severe ischemia. The new neurons survive at least 28 days. This may relate to delayed histopathological and functional recovery after cerebral ischemia.     

Primär- und Sekundärbehandlung des ischämischen zerebralen Insultes

Zusammenfassung Dieser Artikel soll einen überblick über Pathophysiologie, klinisches Bild, Pathogenese, Risikofaktoren, diagnostisches Vorgehen sowie die pathogenetisch orientierte Therapie und Sekund?rprophylaxe zerebraler Isch?mien geben. Zerebrale isch?mische Insulte sind definiert als lokale zerebrale Hypoperfusion, vorwiegend aufgrund von Verschlüssen zerebraler Arterien durch arterio-arterielle oder kardiogene Embolien oder durch h?modynamisch oder mikroangiopathisch verursachte Perfusionsdefizite. Als klinisch relevante pathophysiologische Aspekte wird auf Sauerstoffbedarf, Glukosestoffwechsel, therapeutisches Zeitfenster, exzitatorische Neurotransmitter, Ca²⁺-Einstrom, freie Radikale und die Entwicklung des isch?mischen Hirn?dems eingegangen. Die frühen allgemeinen Ma?nahmen beinhalten ein Monitoring von Blutdruck, EKG, Sauerstoff- und Glukosekonzentration, Wasser- und Elektrolythaushalt. Da spezifische Therapieans?tze nur im Wissen der Pathogenese sinnvoll sind, ist die sofortige Durchführung einer Basisdiagnostik mit kurzer Anamnese, k?rperlicher Untersuchung, Laborwerten, vaskul?rem Ultraschall, cCT, EKG und Echokardiographie notwendig. Aus diesen Resultaten werden entsprechend den verschiedenen pathogenetischen Subgruppen zerebraler Isch?mien unterschiedliche therapeutische Konsequenzen gezogen. In den letzten Abschnitten wird versucht, einen kurzen gezielten überblick über die Wirksamkeit von ?demtherapie, neuroprotektiven Substanzen und Thrombolyse sowie Indikationen zur i. v.-Heparinisierung zur oralen Antikoagulation, Therapie mit Thrombozytenaggregationshemmern und zur chirurgischen Behandlung von Schlaganf?llen zu geben. Eingegangen: 15. April 1996 Akzeptiert: 9. Mai 1996     

Untersuchung zur Frage von persistierenden Veränderungen der Fibrinolyseparameter t-PA und PAI bei Patienten nach juvenilem ischämischen cerebralem Insult

Summary In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis.To investigate whether iuvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21–44 years) 3–24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22–46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors.Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.

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Abkürzungen t-PA tissue plasminogen activator - PAI plasminogen activator inhibitor - RIND reversibles ischämisches neurologisches Defizit - KS kompletter Schlaganfall - TIA transitorisch ischämische Attacke     

Erhöht Dusodril® den ATP-Gehalt im Gehirn?

Zusammenfassung In Untersuchungen zum Einfluß peroraler Dusodril®-Gabe auf den cerebralen Gehalt an energiereichen Substanzen bei der weißen Maus konnten wir zeigen, daß entgegen den Angaben von Meynaudet al. unter Dusodril® keine Erhöhung der ATP-Gewebsgehalte gegenüber Kontrolltieren auftritt. Auch der Gehalt an Phosphokreatin, der Summe der Adeninnukleotide oder das Energiepotential werden durch Dusodril®-Gabe nicht erhöht.Die von Meynaudet al. angegebenen Differenzen deuten jedoch auf mögliche Einflüsse des Dusodril® auf den Hirnstoffwechsel der Maus in Ischämie hin.     

Präklinisches Management des Patienten mit Schlaganfall

Stroke is the third leading cause of death and number one cause of disability in industrialised countries. Studies into the pathophysiology of acute ischaemic stroke have indicated that treatment options are likely to be optimized when early signs of stroke are recognized and treatment is initiated within 3 hours from symptom onset. Therefore, new conceptions heading towards early diagnosis, fast preclinical treatment, structured diagnostics, immediate initiation of acute therapy as well as early initiation of rehabilitation are required. It is well known that, for most patients, there is a long delay between the onset of symptoms and the start of therapy. Many factors are responsible for the time delay:signs and symptoms often go unrecognized and/or are minimized by patients, relatives and bystanders. Unlike trauma or myocardial infarction, stroke is not given a high priority by medical staff and/or emergency medical services (EMS). 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. At present the standard of care by the EMS personnel includes adequate cerebral oxygenation, treatment of cardiac arrhythmia, management of hypertension as well as therapy of hyperglycemia and hyperthermia. For the future, we hope that emergency medical services will be able to initiate therapies which must be administered within the first few hours of acute stroke after onset of symptoms. Early notification of hospitals would enable a particular stroke team to be present at the patient's admission.     

Allergènes de contact forts

Two important parameters control skin sensitization to a xenobiotic molecule: its sensitizing potential, an intrinsic property of each chemical, and exposure. It is often difficult to quantify a patient's exposure to a given allergen, which makes it difficult to define strong allergens. Indeed, the prevalence of an allergen, as determined by patch testing, reflects not its strength but a combination of sensitizing potential and exposure. The definition of strong sensitizers is therefore mainly derived from animal experiments where it is possible to assess a sensitization threshold or the dose per square centimeter that is able to induce significant sensitization. It has been shown in a limited number of case studies, that there is a good correlation between sensitization thresholds assessed in mice by the Local Lymph Node Assay (LLNA) and those obtained in humans with the Human Repeated Insult Patch Test (HRIPT). Based on this classification, one can recognize that strong sensitizers are quite common and that the general population is exposed regularly to them. Although the strong sensitizers include a broad diversity of chemicals, they have in common the ability to rapidly modify nucleophilic residues of proteins.     

Maternal-fetal blood incompatibility and neuromorphologic anomalies in schizophrenia: Preliminary findings

Prior research has shown that maternal-fetal Rhesus (Rh) and ABO blood incompatibility increase the risk for schizophrenia. In the present study, the relationship between blood incompatibility and volumes of brain structures previously implicated in schizophrenia was assessed in schizophrenia cases and controls from a large birth cohort. Rh/ABO incompatible cases had significantly reduced cortical gray matter volume compared to compatible cases, a finding which appears to be driven by significant volume reductions in the dorsolateral prefrontal cortex and inferior frontal cortex. Larger hippocampal and putamen volumes were also observed in exposed controls compared to unexposed controls. Although the sample size is small and replications are required, these data suggest that maternal-fetal blood incompatibility may increase the risk for altered brain morphology in both schizophrenia and in controls. The findings also suggest that the larger hippocampal volume in exposed controls may indicate a mechanism of adaptive resilience which diminishes the risk that controls will develop schizophrenia.