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Biomedical subjects

M Hennerici

Publications and source records attributed to M Hennerici.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Heparin during acute ischemic stroke. Present data and clinical situation].

Therapy with low- or high-dose heparin in acute stroke is changing. Despite several clinical studies (>20), some with quite large numbers of patients, no statistically significant benefit was found for the clinical endpoints of death and functional outcome. This negative result remains even when considering the preventive effect of high-dose heparin on secondary acute embolic events (e.g., cardiac emboli-arrhythmia) and low-dose heparin on venous thrombosis. Based on study results, most reviews and therapy recommendations for the treatment of acute stroke generally decline the use of high-dose heparins and heparinoids with full anticoagulation for improving outcome or preventing secondary embolic events as well as low-dose applications for venous thrombosis prophylaxis. This paper reviews the literature and presents the data of a standardised survey on coagulation therapy in acute stroke patients from all university and major stroke units in Germany (n=33). Contrary to the restrictive recommendations, therapy with heparin is firmly established in most stroke units. Full anticoagulation with heparin ("full dose") is performed on selected patients in 32/33 stroke units (97%). The selection criteria and thus the frequency of high-dose heparin use varies widely among the different centers. Almost all German stroke units (97%) routinely use low-dose heparin to prevent venous thrombosis and pulmonary embolism.The heparin agents and dosage, however, vary. These data correspond to those from the USA and Canada,where daily routine also departs from evidence-based treatment recommendations. That may be due to individual pathophysiological and aetiological considerations and of course the low acceptance of treatment recommendations based on classic, randomised trials. This underlines the need for new concepts (e.g.observational trials, continuous registers, etc.) addressing the adaptation of study-related conditions to the much more complex situation of daily routine (with risk/benefit, safety, and economic variables).

Acute Disease↗
PubMed2003

[Current controversies in the diagnosis and management of cerebral venous and dural sinus thrombosis].

Over the last few years, the results from clinical studies and innovative radiological approaches have significantly altered the management of patients with cerebral venous thrombosis. In contrast to previously held beliefs, cerebral venous thrombosis is considered to be a relatively benign disease with an overall favourable prognosis. Mortality is <10%, and the vast majority of patients recover completely. Although the efficacy of heparin has not been unequivocally proven, it is employed in most centres as the standard therapy. There are not sufficient data supporting long-term anticoagulation. In patients with a proven hypercoagulability syndrome, anticoagulation therapy is generally recommended for a period of 6 months. Whether patients with idiopathic thrombosis should also be treated remains controversial. Non-invasive MR and CT angiography techniques have largely replaced conventional angiography for initial evaluation and follow-up examinations. Both methods have a high sensitivity for cerebral venous thrombosis. Local fibrinolytic therapy or other aggressive recanalizing methods can not be generally recommended.

Anticoagulants↗
PubMed2003

[Pathophysiology, etiology and diagnosis of stroke].

Vascular diseases including stroke increase with advancing age. Their occurrence reflects the lifestyle and eating habits of a society. In industrialized countries stroke causes a significant loss of DALYs. Each year, approximately 150 persons per 100,000 inhabitants suffer a stroke. Half a year after the stroke, two of three stroke victims are dead or dependent, and all stroke survivors are at risk to suffer recurrent strokes. Stroke is due to a focal ischemia. In the core of the ischemia blood flow is reduced substantially, mostly to a level below the infarction threshold. In the borderzone collaterals can still provide sufficient blood to preserve the neurons though the reduced blood flow does not suffice for neuronal functioning. This state below functional and above infarction threshold is called penumbra. When the stroke signs are recognized early and the occluded vessel is recanalized with thrombolytics or mechanically the brain tissue in the penumbra can be preserved and the fate of the stroke victim is improved compared to spontaneous course. Before administration of thrombolytics neurological examination and imaging of the brain using CT or MRI are necessary. After stroke, survivors will benefit significantly from secondary prevention. In order to perform an individually tailored prevention, additional investigations such as neurovascular and cardiac ultrasound, cardiac monitoring and blood examinations are necessary to define the cause of the stroke. In addition, recognition and modification of individual vascular risk factors are of paramount importance.

Atrial Fibrillation↗
PubMed2002

[Glioblastoma multiforme as a manifestation of Turcot syndrome].

Turcot's syndrome, clinically characterized by the coincident occurrence of primary tumors of the colon and the central nervous system, can genetically be divided into two syndromes: familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon carcinoma (HNPCC). In the present case, a 60-year-old patient with glioblastoma multiforme and a history of hereditary malignomas is described as an example of a HNPCC-associated Turcot's syndrome. New molecular biological methods and results give deeper insight into clinical syndromes, and the better understanding improves diagnostics, therapy, and outcome estimations, even in rare diseases. In the present case, a new germinal mutation could be identified.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Alterations of cortical electrical activity in patients with sacral neuromodulator.

OBJECTIVES: Sacral neuromodulation represents chronic stimulation of the sacral (S3) nerve. So far, the mode of action and neuro-anatomical basis is unclear. Sacral reflex mechanisms as well as pontine or cortical centers of modulation have been postulated. Our aim was to evaluate possible alterations in electroencephalogram (EEG) activity as an indicator of a supraspinally mediated mechanism of sacral neuromodulation. MATERIALS AND METHODS: We analyzed serial EEGs (apparatus: Kölner Vitaport System) using electrodes placed at Fz, Cz, Cz' and Pz in 10 patients. Subsequently, the sacral (S3) nerve was stimulated by means of an impulse generator (Medtronic, Interstim 3023) using an on-off paradigm with a 1.5s "on" interval followed by a 10s stimulation break. Raw data were analyzed using both Matlab 4.0 software and a specially developed averaging routine. RESULTS: All patients demonstrated a cortical potential complex following sacral root stimulation with an early electronegative component at 50 ms with a mean amplitude of 23 microV followed by a late potential component with a mean latency of 253 ms and a mean amplitude of 5 microV, both with a maximum at Cz, corresponding to the post-central gyrus. This finding occurred irrespective of patient's reports of actually feeling the neuromodulator being switched on and off. CONCLUSION: In neuromodulation responders, both short and long latency cortical potentials can be reproduced with a maximum at the sensory cortical area. Although these potentials are similar to cognitively mediated "event-related potentials", they are clearly distinct from any subjective sensory or even painful response since several patients of this series have not been able to feel any neuromodulator action. Therefore, this pilot study indicates a supraspinally mediated site of modulation, most probably in sensory cortex areas.

Adult↗
PubMed2002

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

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.

Acute Disease↗
PubMed2001

A diffusion-weighted MRI study of acute ischemic distal arm paresis.

OBJECTIVE: To study the site of the ischemic lesion, the underlying cause, and the prognosis of acute stroke with distal arm paresis. METHOD: The authors investigated 14 consecutive patients with acute distal arm paresis with a diagnostic stroke protocol and early MRI, including T2-weighted images, diffusion-weighted images (DWI), and perfusion-weighted images (PWI). Acute DWI lesions were shown on coregistered T2-weighted images for analysis of the exact anatomic lesion location. RESULTS: Patients showed a uniform (7/14), radial (3/14), or ulnar (4/14) distribution of hand paresis. In all cases, DWI identified small lesions located in the motor cortex. Topographic lesion analysis, which was correlated with the clinical deficit, showed lesions centered in the hand knob area (2/14), involving the lateral (6/14), medial (4/14), or both (2/14) borders of the hand knob. PWI (calculated time-to-peak maps) did not show a mismatch between the DWI lesion and the PWI lesion. In six patients, DWI and PWI lesions were identical in size and location; no definite perfusion deficit was seen in eight patients. In agreement with PWI, no patient showed clinical worsening, and six patients recovered completely within a week. Further investigations showed a potential source of embolus in 11 cases. CONCLUSIONS: Acute ischemic distal arm paresis is usually caused by a small cortical lesion in the motor hand cortex attributable to distal Rolandic artery obstruction without additional tissue at risk. These findings confirm the observed benign clinical course and its apparent main cause (artery-to-artery or cardiac embolism).

Acute Disease↗
PubMed2001

Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo.

Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated Abeta42 levels and the varepsilon4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of Abeta42 and Abeta40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral Abeta42 and Abeta40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing an important role in the development of Alzheimer's disease. Lowered levels of Abeta42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.

Alzheimer Disease↗
PubMed2001

Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic ultrasound.

Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.

Analysis of Variance↗
PubMed2001

Potential use of therapeutic ultrasound in ischemic stroke treatment.

Systemic treatment with rtPA approved for a 3-hour window is the only established causal therapy for acute stroke in the United States and Canada. Thrombolytic therapy with rtPA demonstrated a small, although significantly reduced morbidity, in a limited number of highly selected patients. As recently shown, intraarterial application is favorable and opens the window of treatment up to 6 hours. The combination of ultrasound with thrombolytic agents may further enhance the potential benefit by means of enzymatic-mediated thrombolysis, which has been demonstrated in different in vitro and in vivo experiments for an accelerated recanalization of occluded peripheral and coronary vessels. Whereas no or only small attenuation of ultrasound can be expected through skin and chest, intensity will be significantly attenuated if penetration of the skull is required. The transcranial penetration of ultrasound increases when the frequency is decreased to 20 kHz and may be transmitted through the skull transtemporally with tolerable attenuation up to 200 kHz. This results in efficacy in vitro with low intensities of 0.5-2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in the nonfocused ultrasound field. Application of ultrasound insonation increased rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it enhanced the recanalization rate from 30%-90% in a flow model. In vitro results suggest that 1 MHz ultrasound with 0.5 W/cm(2), established for diagnostic purposes, may already enhance rtPA- mediated thrombolysis. Before therapeutic ultrasound can be tested clinically in acute stroke, safety of transcranial exposure of the brain has to be confirmed. To date, animal experiments suggested no harm to the blood brain barrier or systemic heating with 2 W/cm(2). This combined treatment is one perspective in optimizing therapy in acute stroke within the acute phase and may be applied easily with few limitations.

Animals↗
PubMed2001

Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries.

Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH.

Adult↗
PubMed2001

Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.

BACKGROUND AND PURPOSE: To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). METHODS: We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. RESULTS: The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. CONCLUSIONS: Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

Adolescent↗
PubMed2001

Spermidine: A predictor for neurological outcome and infarct size in focal cerebral ischemia?

BACKGROUND AND PURPOSE: Polyamines are mainly restricted to the intracellular space. During focal cerebral ischemia, polyamines are released from the intracellular compartment. Experimental studies have implicated a marked elevation in brain tissue and blood. The aim of our study was to investigate whether the elevation of polyamines in the blood of patients with focal cerebral ischemia correlates with the clinical outcome and the infarct volume. METHODS: Polyamines were measured in 16 patients with focal cerebral ischemia and in 8 healthy control subjects. Blood samples for polyamine measurement were taken at admission and at fixed time points for the next 28 days. Polyamines were analyzed in red blood cells by a high-pressure liquid chromatography system. Clinical findings were recorded with the NIH Stroke Scale score. Volume of infarction was analyzed from cranial CT at admission and on days 4 to 6 after ischemia. RESULTS: A significant increase of the spermidine level in the peripheral blood could be observed in all patients with focal cerebral ischemia as compared with control subjects (P:<0.01), starting with the admission. Spermidine values correlated positively with the clinical outcome at several time points in the first 48 hours (r=0.90 to 0.40; P:<0.01) and with the infarct volume in cranial CT on days 4 to 6 (r=0.91; P:<0.01). CONCLUSIONS: As hypothesized from experimental data, polyamine levels in blood increase in patients after focal cerebral ischemia. The results indicate that the peripheral spermidine level is closely associated with the clinical outcome as well as with the infarction volume. Therefore, polyamines may be used as a novel predictor for the prognosis of patients with focal cerebral ischemia.

Aged↗
PubMed2001

Acute stroke patterns in patients with internal carotid artery disease: a diffusion-weighted magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MRI is a sensitive method that facilitates early stroke pattern identification. There are limited data about the influence of stenosis grade on the development of particular stroke patterns in internal carotid artery (ICA) disease. We therefore investigated the lesion patterns on DW MRI in acute stroke patients with ICA disease. METHODS: DW MRI was analyzed in 102 consecutive acute stroke patients with different degrees of ipsilateral ICA disease. Patients were assigned to 1 of 5 observed lesion patterns: (1) territorial ischemia, (2) subcortical ischemia without or (3) with embolus fragmentation, (4) disseminated lesions in distal cortical regions, and (5) multiple lesions in hemodynamic risk zones. In addition, perfusion-weighted (PW) MRI and MR angiography information was included in the assessment. RESULTS: All patterns were observed in the different stages of ICA disease. Half of the patients with high-grade or subtotal stenosis had lesions in hemodynamic risk zones. Territorial stroke occurred in 47.6% of patients with ICA occlusion. Statistical analysis showed a significant relationship between the degree of stenosis and the observed stroke pattern (P=0.001). In 77.8% of patients exhibiting high-grade ICA stenosis, subtotal stenosis, or occlusion, the perfusion lesion was larger than the diffusion lesion (PW/DW mismatch). CONCLUSIONS: Although in the individual patient any of the infarct patterns may occur, in statistical terms the incidence of a particular stroke pattern is clearly dependent on the degree of stenosis.

Aged↗