Biomedical subjects
Publications and source records attributed to M Siebler.
We report on a patient with a complicated course after surgical abdominal intervention and episodic life threatening respiratory failures successfully treated with carbamazepine after diagnosis of a ponto-medullary lesion in the MRI.
Depression is a frequent and important complication after stroke. The occurrence of a post-stroke-depression (PSD) has a significant impact on the functional and cognitive deficit, on mortality and on quality of life after stroke. In contrast to the clinical importance, PSD is often ignored in routine management of stroke patients and remains often untreated if diagnosed. The diagnostic uncertainty is aggravated by the lack of appropriate diagnostic criteria for PSD in the International Classification of Diseases (ICD-10) used in Germany. For the first time, we present an algorithm, which allows for a standardized examination of stroke patients on the presence of PSD. All stroke patients should be examined initially by a short and simple screening tool and are subjected to more extensive procedures only if PSD is assumed based on the screening result. Furthermore potentials and limitations to convert the diagnosis of PSD into a diagnostic related group (DRG) that is used to calculate the hospital's reimbursement are highlighted. Finally pharmacological treatment options for PSD are discussed.
The authors reviewed the histories of 33 patients (ages 44 to 50 years) treated with IV thrombolysis for acute stroke due to spontaneous cervical carotid artery dissection. Median NIH Stroke Scale (NIHSS) score on admission was 15. No new or worsened local signs, subarachnoid hemorrhage, pseudoaneurysm formation, or rupture of the cervical ICA were observed. At 3 months, median NIHSS was 7 and median modified Rankin Scale (mRS) 2.5; mRS < or = 2 was observed in 17 patients.
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To date, two new defects in the pentose phosphate pathway have been identified in patients with abnormalities in their polyol profiles. Some of them presented with neurological symptoms of so far unknown aetiology. The pathophysiological role of polyols, e.g. in the brain, is relatively unknown. We tested the neurotoxicity of polyols using a 'neurochip' model. After exposure of cortical rat neurons to D-arabitol and ribitol in increasing concentrations up to 10 mmol/L, the electrophysiological activity was measured. No acute effect on the spontaneous network activity of cortical neurons was observed. We speculate that polyols have only secondary effects on brain dysfunction.
BACKGROUND: Controversial data was published about the sodium channel-blocking effect of the endogenous pentapeptide QYNAD, which is elevated in patients with multiple sclerosis and Guillain-Barré-syndrome. In some experiments with single cells and nerve preparations QYNAD inhibited sodium currents to the same extent as the known sodium channel blocker lidocaine whereas in other laboratory testing QYNAD failed to show any effect at all. METHODS: Micro-electrode arrays with cultured neuronal networks are highly suitable to determine neuroactive activity of applied substances. The impact on electrophysiological parameter changes was compared between QYNAD and the established sodium channel blockers lidocaine and tetrodotoxin (TTX). RESULTS: QYNAD did not alter network activity whereas the sodium channel blockers lidocaine (IC50 14.9 micorM) and tetrodotoxin (IC50 1.1 nM) reversibly decreased network activity in similar concentrations as in patch-clamp experiments. This decrease of spontaneous electrophysiological activity was achieved by prolonging the interburst-interval. CONCLUSION: Although QYNAD might have mild effects on single-cell sodium currents, there is no significant effect on neuronal network function. These results raise concerns about QYNAD exhibiting a relevant impact on functional disability of the central nervous system in patients.
BACKGROUND: Current debates are focused on inflammatory processes in atherosclerotic lesions as a possible pathomechanism for destabilization and thrombembolism. In this prospective study the role of systemic and local infection in patients with high-grade internal carotid artery stenosis (ICA) was evaluated. PATIENTS AND METHODS: Serum antibody titers of 109 consecutive patients, who underwent surgery for ICA stenosis (asymptomatic n = 40, symptomatic n = 69) were prospectively measured for Chlamydia pneumoniae (Cpn) (IgA and IgG), Herpes simplex virus (HSV) (IgG, IgM) and Cytomegalovirus (CMV) (IgG, IgM) respectively. 53 carotis plaques of this group (asymptomatic n = 17, symptomatic n = 36) could be analyzed by polymerase chain reaction (PCR) for Cpn-, HSV- and CMV-DNA presence. RESULTS: Seropositivity was found in 61,5% for Cpn, 91,7% for HSV and 72,5% CMV respectively. No significant relation was found between symptomatic and asymptomatic patients as well as no difference was seen for presence of IgA antibodies against Cpn comparing both groups. Plaque-PCR revealed Cpn in 7 cases (13,2%), HSV in 2 cases (3,8%) and no CMV had been detected. Again, no significant relationship was found concerning symptomatic and asymptomatic patients. All 9 PCR-positive plaques displayed lesions of "complicated atherosclerosis" as central fibrous necrosis and calcification or plaque bleeding and surface thrombosis. CONCLUSIONS: Our results do not support the hypothesis that systemic Cpn, HSV or CMV- infection or evidence of Cpn-, HSV- or CMV-DNA in carotid plaques causes plaque destabilization and cerebral thromboembolism. Plaque infection could only be observed in cases with advanced atherosclerosis.
To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen activator (rtPA) and the body-weight adjusted platelet GPIIb/IIIa receptor antagonist tirofiban, the authors performed lesion volumetry on magnetic resonance perfusion and diffusion images recorded before thrombolysis and on T2-weighted magnetic resonance images on day 8. Treatment with rtPA and tirofiban (n = 13) resulted in a 50% lesion reduction (p < 0.03), while lesion reduction was less in rtPA treatment (n = 16) and absent in nontreated patients (n = 18).
BACKGROUND AND PURPOSE: Early reperfusion is one of the best predictors of good outcome after acute middle cerebral artery (MCA) occlusion. The purpose of this study was to analyze the frequency and relevance of incomplete recanalization for tissue and clinical outcome. METHODS: From a larger acute stroke database (Kompetenznetzwerk Schlaganfall B5), all patients (n=82) with MCA main stem occlusion (excluding carotid T-occlusions) were selected. These patients had received a multiparametric stroke MRI protocol including diffusion- and perfusion-weighted imaging (DWI, PWI) and MR angiography (MRA) within 6 hours after symptom onset, at day 1 and after 1 week. Recanalization status was determined with MRA on day 1 (according to Thrombolysis In Myocardial Infarction flow grades) and used to group patients into those with persistent occlusion (0) or minimal (1), partial (2), or complete (3) recanalization. RESULTS: Incomplete recanalization according to MRI criteria was found in 39 patients (grade 1: n=20; grade 2: n=19), complete recanalization in 10, and persistent occlusion in 33. There was no statistically significant difference in any of the clinical (National Institutes of Health Stroke Scale score) or MRI baseline parameters (DWI lesion, PWI deficit, mismatch volume, mismatch ratio). However, lesion growth was smaller in patients with recanalization (even in patients with only minimal recanalization) and outcome was related to the degree of recanalization (mean modified Rankin score at 90 days: 3.36, 2.70, 1.79, and 1.44 for the groups with no, minimal, partial, and complete recanalization, respectively). Both incomplete and complete recanalization was more frequent in patients receiving thrombolysis. CONCLUSIONS: Incomplete recanalization on day 1 is a frequent MR finding after MCA main stem occlusion, indicating a more favorable clinical course than persistent occlusion. MR indicators of early recanalization could be useful surrogates of efficacy in thrombolytic trials.
OBJECTIVES: evaluation of urgent carotid artery surgery with new diagnostic techniques and changing surgical considerations at a university hospital. DESIGN, MATERIAL AND METHODS: prospective monitoring and assessment of outcome in 67 patients who underwent urgent carotid surgery because of symptomatic extracranial carotid artery involvement. Patients were examined via the stroke unit: duplex sonography was mandatory for diagnosis of extracranial carotid artery disease, as was proof of an open middle cerebral artery (MCA). Assessment of intracerebral damage followed CT or MR imaging procedures. Perioperative and surgical management was standardized. Neurological impairment was assessed pre-, postoperatively and at follow-up using the Rankin scale. "Urgent" was defined as "immediate" after the final diagnostic step had been performed. RESULTS: within a period of 26 months 67 symptomatic patients (58% stroke, 42% TIA) underwent urgent carotid surgery. Median time from admission to surgery was 2 days. In all but five cases flow through the ICA could technically be restored (93%). Thirty-day mortality was 3% and disease-related morbidity 13%. The one and two year survival rates were 92 and 90%, respectively. No ipsilateral recurrent stroke occurred during follow-up. CONCLUSIONS: clinical decision-making based on stratified diagnostic workup by means of extra- and intracranial as well as intracerebral hemodynamics using new imaging techniques may select patients who will benefit more from urgent surgery than from conservative management.
UNLABELLED: Long-term results after carotid reconstruction in patients with completed stroke caused by cerebrovascular occlusive disease. BACKGROUND AND OBJECTIVE: In patients with completed stroke caused by cerebrovascular occlusive disease the reconstruction of high grade carotid artery stenosis is discussed as prophylaxis for prevention of recurrent stroke. The operative complications of all patients who underwent surgery for carotid occlusive disease in the Heinrich Heine University between 1990 and 1999 were evaluated in this study. PATIENTS AND METHODS: We present the results of 596 reconstructions in 537 patients (404 men, 133 women; mean age 64,5 plus minus 9,4 years). The operative technique of choice was thromboendarterectomy of the carotid bifurcation with vein-patch closure. RESULTS: A postoperative ipsilateral neurological deficit was observed in 41 patients (6,9 %): 4,7 % permanent, 2,2 % transitory. Thirtyeight percent of the permanent deficits appeared after reconstructions performed within six weeks after stroke and only 9 % after surgery between six and twelve weeks. The in-hospital mortality was 0,7 % for neurological and 1,0 % for cardiopulmonary complications. During long-term follow-up (mean follow-up time 50 plus minus 34 months) only 17 (3,7 %) of 462 patients, which could be evaluated, presented with a new neurological event for the reconstructed side. Fifty-eight percent had none or minimal neurological deficits. 115 Patients (24,0 %) died during follow-up. CONCLUSION: Even after completed stroke carotid reconstruction can be carried out successfully in selected patients with an acceptable complication rate in prophylaxis of recurrent stroke. In our retrospective study the optimal time for surgery seems to be between six and twelve weeks after stroke, but new imaging techniques may alter in the future the time window for operation in patients with an unstable neurological situation early after stroke. The reduction of social mobility and the high mortality in follow-up in correlation to patients without stroke are mostly related to accompanying severe cardiopulmonal risk factors.
In an open pilot study, the authors tested whether the nonpeptide glycoprotein (GP) IIb/IIIa antagonist tirofiban, a highly effective and selective blocker of platelet aggregation, prevents the transition of ischemic brain tissue into the infarct proper as defined by MRI (perfusion-weighted/T2-weighted) in patients with acute ischemic stroke. The infarct volume (T2 lesion after 1 week) was smaller in treated patients (n = 10) compared with matched control subjects (n = 10; p = 0.029) with similar initial perfusion deficit (TTP-maps). The authors conclude that GP IIb/IIIa antagonists have therapeutic potential in acute stroke therapy.
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BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.
In four patients with acute basilar artery thrombosis, complete arterial recanalization and good neurologic outcome were achieved with a treatment combining alteplase with tirofiban. In no cases were cerebral or extracerebral hemorrhagic complications observed. Combined fibrinolytic agents and glycoprotein IIb/IIIa inhibitors may have high potential in the treatment of acute cerebrovascular thrombosis.
BACKGROUND: Glycoprotein (gp) IIb/IIIa-receptor antagonists are highly effective antiplatelet agents with proven efficacy in the treatment of acute coronary and experimental cerebral ischemia. In this study we examined the rate of hemorrhagic transformation and major bleedings in patients with acute stroke treated with tirofiban, a nonpeptide gpIIb/IIIa antagonist. METHODS: Eighteen patients with progressively deteriorating acute ischemic stroke were treated with body-weight adjusted intravenous tirofiban for a mean period of 46 h and compared with a matched group of 17 acute ischemic clinically stable stroke patients. Cerebral hemorrhage was assessed by cranial imaging 6-10 days after symptom onset. RESULTS: No major intracranial hemorrhage was observed in either group. Clinically asymptomatic hemorrhagic infarctions type I/II/III were detected in 4/2/0 controls and in 4/1/1 patients of the tirofiban group, respectively (OR = 0.92; 95% CI 0.4-2.5). Clinical outcome scores were not different in both groups (p = 0.18). CONCLUSIONS: Tirofiban was not associated with a significantly increased cerebral bleeding rate in acute ischemic stroke. Randomized multicenter studies are needed to further evaluate the safety and efficacy of tirofiban in the treatment of acute stroke.
BACKGROUND AND PURPOSE: The procoagulant protein tissue factor (TF) has been implicated in thromboembolic complications associated with advanced atherosclerosis. In this study, we investigated whether TF expression in high-grade stenoses of the internal carotid artery (ICA) is associated with clinical features of plaque destabilization and addressed the relationship between TF expression and plaque inflammation. METHODS: In 36 consecutive patients undergoing surgery for high-grade ICA stenosis, clinical evidence of plaque instability was provided by the recent occurrence of ischemic symptoms attributable to the stenosis and the detection of cerebral microembolism by means of transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. Endarterectomy specimens were stained immunocytochemically for TF expression as well as macrophage (CD68) and T cell (CD3) infiltration. RESULTS: Morphologically, TF immunoreactivity was codistributed with plaque inflammation and predominantly localized to CD68+ macrophages. Accordingly, statistical analysis revealed a significant association of TF expression with plaque infiltration by macrophages (P<0.0001) and T cells (P=0.013). Plaques extensively stained for TF (median of TF+ total section area >40% in semiquantitative assessment) were more frequent in symptomatic (12/27) than in asymptomatic patients (1/9). Conversely, plaques exhibiting little TF expression (median of TF+ section area <20%) were more frequent in asymptomatic (3/9) than in symptomatic (1/27) patients (P=0.016). Likewise, we found a highly significant association of TF expression with the occurrence of cerebral microembolism (P=0.008). CONCLUSIONS: Induction of TF at sites of plaque inflammation may play an important role in the destabilization of high-grade ICA stenosis.
K(+) currents of activated glial cells surrounding ischemic infarcts are investigated using acutely dissociated cells from the periinfarct area after permanent middle cerebral artery occlusion in rats. Inwardly rectifying K(+) currents (K(IR)) were markedly reduced in cells neighboring infarcts with maximal alteration at day 3 after infarct followed by a partial recovery. This reduction of glial K(IR) currents may contribute to the functional disturbances in the periinfarct area.