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Biomedical subjects

Wilhelm Küker

Publications and source records attributed to Wilhelm Küker.

At least 19 recordsLinked to original sources
PubMed2005

Risk factors for periprocedural complications in carotid artery stenting without filter protection: A serial diffusion-weighted MRI study.

INTRODUCTION: In high-grade stenosis, carotid artery stenting (CAS) may be chosen as an alternative to carotid surgery. Ischemic periprocedural complications may be documented best with diffusion-weighted MRI (DWMRI). In this prospective study serial DW-MRI and color-coded duplex sonography (CCDS) were used to identify carotid stenosis, which is associated with an increased risk of ischemic events due to CAS. METHODS: High resolution DW-MRI were performed in 74 out of 77 patients before and after CAS. All MRI scans were analyzed in a blinded manner. With CCDS each carotid stenosis was evaluated according to the grade, length, echo properties and plaque surface. RESULTS: In 42 out of 74 patients (56.8 %) a total of 188 new procedure- related DWI-lesions could be detected, while in 32 patients MRI-controls remained normal. Of the lesions 79.25 % had a size < 1 cm. In one major and two minor strokes due to CAS (total complication rate 3.9 %) corresponding territorial infarcts could be demonstrated. A highly significant correlation was found between the length of the stenosis and the incidence of new DWI-lesions (p = 0.0141). In contrast, neither the grade of ICA stenosis nor the sonographic plaque morphology or plaque surface correlated with the number of DWI-lesion in postinterventional scans. CONCLUSIONS: The length-and not the degree-of an ICA stenosis seems to be the most decisive sonographic factor for estimating the periprocedural risk of embolism. DWI-lesions are much more frequent than clinical complications and may represent an important surrogate marker for improving the techniques of carotid artery stenting, especially comparing the benefit of different mechanical protection devices.

Aged↗
PubMed2005

Posterior thalamic hemorrhage induces "pusher syndrome".

BACKGROUND: Recent findings argue for a pathway in humans for sensing the orientation of gravity and controlling upright body posture, separate from the one for orientation perception of the visual world. Stroke patients with contraversive pushing were shown to experience their body as oriented upright when actually tilted about 20 degrees to the ipsilesional side, in spite of normal visual-vestibular functioning. A recent study suggested the involvement of posterolateral thalamus typically associated with the disorder. OBJECTIVE: To evaluate the relationship between pushing behavior and thalamic function. METHODS: Over a 3-year period the authors prospectively investigated 40 patients with left- or right-sided thalamic strokes. RESULTS: Twenty-eight percent showed contraversive pushing. The authors found a strong relationship between etiology, vascular territory, lesion size, and neurologic disorders associated with contraversive pushing. Pusher patients had larger lesions that typically were caused by hemorrhage (vs infarcts) located in the posterior thalamus (vs anterior thalamic lesions in those patients without pushing behavior). A paresis of the contralesional extremities was more frequent and more severe in pusher patients. Further, these patients showed more additional spatial neglect with right thalamic lesions, while they tended to be more aphasic with left thalamic lesions. CONCLUSIONS: Posterior thalamus seems to be fundamentally involved in our control of upright body posture. Higher pressure, swelling, and other secondary pathologic processes associated with posterior thalamic hemorrhage (vs thalamic infarction) may provoke contraversive pushing in combination with additional neurologic symptoms.

Aged↗
PubMed2005

NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

Antimetabolites, Antineoplastic↗
PubMed2005

Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients.

To avoid an unnecessary extend of surgery in primary central nervous system lymphoma (PCNSL), the diagnosis should be suspected after MRI. Pre-treatment MRI examinations of 100 immunologically competent patients with biopsy-proven PCNSL were evaluated. All patients had T2- and T1-weighted images with contrast enhancement. Diffusion-weighted MRI (DW-MRI) was available in 15, proton-MR-spectroscopy (1H-MRS) in four patients. The number of lesions ranged from one (n=65 patients) to eight (n=1) with a mean of 1.7. The most frequent locations were the cerebral hemispheres (n=66), the basal ganglia (n=27) and the corpus callosum (n=24). In the 65 patients with a solitary lesion, hemispheric lesions were most frequent (n=23) followed by corpus callosum (n=18). Contrast enhancement was found in all but one patient. 1H-MRS revealed a uniformly pathologic pattern of metabolite concentrations in all patients. Characteristic imaging features of PCNSL are contrast-enhancing lesions with a diameter of at least 15 mm in contact with the subarachnoid space. DW-MRI and proton spectroscopy may aid in differential diagnosis.

Adult↗
PubMed2005

Minor inflammation after surgical evacuation compared with fibrinolytic therapy of experimental intracerebral hemorrhages.

OBJECTIVES: Toxic components released from the intracerebral blood clot, such as thrombin and hemoglobin, potentially trigger brain edema formation and therefore favor an early evacuation of the clot. Despite a significant reduction in hematoma size in our porcine model of hematoma induction by injecting autologous blood ICP-controlled into the right frontal white matter with subsequent fibrinolysis using recombinant tissue-plasminogen activator (rt-PA) and aspiration of the liquefied clot (n = 9), local rt-PA promoted delayed perihematomatous edema formation and invoked a substantial inflammatory reaction compared with controls (n = 11). METHODS: We therefore modified our formerly developed porcine model of intracerebral hemorrhage in removing the hematoma by open craniotomy and suction of the clot in seven animals. The residual hematoma size and extent of perifocal edema were evaluated over 10 days on planimetry of the MRI data, and correlated to the histopathological changes of edema and inflammation found at autopsy. RESULTS: The edema volume on day 4 was significantly less in the surgical group compared with the lysis group (p < 0.03). On day 10, however, the difference in edema size was not statistically significant compared with the lysis group (p < 0.07) and the control group (p < 0.09). The inflammatory response was minor compared with the lysis and control group. DISCUSSION: In conclusion, despite a significant reduction in hematoma size by surgical removal of the clot, only the inflammatory response, but not the extent of delayed edema can be positively influenced.

Analysis of Variance↗
PubMed2004

Leptomeningeal metastasis: survival and prognostic factors in 155 patients.

In this single-center retrospective study, 155 consecutive patients with leptomeningeal metastasis (LM) were analyzed for the prognostic role of patient- and therapy-related variables. Ten percent of the patients received radiotherapy alone, 32% had chemotherapy alone, 31% received radiochemotherapy, 17% had supportive therapy only, and 10% were not evaluable for therapy. Chemotherapy was systemic (17%), combined systemic and intrathecal (10%), or intrathecal only (35%). Clinical improvement was noted in 41% of the patients. Overall median survival time (MST) was 4.8 months. Survival varied considerably depending on the type of primary tumor in this largest published cohort of LM patients. Univariate Cox regression analysis revealed that age >60 and elevated cerebrospinal fluid (CSF) albumin or lactate levels were therapy-independent predictors of poor survival in the entire cohort as well as in the subgroup of patients with systemic primary tumors (n=105). The assessment of three therapy-independent parameters allows to group LM patients into groups of low, intermediate, and high risk of poor survival. Moreover, the application of systemic chemotherapy was a positive prognostic factor in patients with subarachnoid lesions detected by neuroimaging (RR 1.94, p=0.001) or with extra-CNS tumor deposits (RR 1.52, p=0.05). The results of this study suggest that systemic chemotherapy alone or in combination with other therapeutic modalities may improve outcome in patients with subarachnoid tumor cell deposits detectable by neuroimaging.

Adolescent↗
PubMed2004

The anatomy of spatial neglect based on voxelwise statistical analysis: a study of 140 patients.

A major challenge for any anatomical study of spatial neglect in neurological patients is that human lesions vary tremendously in extent and location between individuals. Approaches to this problem used in previous studies were to focus on subgroups of patients that are more homogeneous either with respect to the branch territory affected by the stroke or with respect to existing additional neurological symptoms (e.g. additional visual field defects). It could be argued that such strategies might bias the conclusions on the critical substrate associated with spatial neglect. The present study thus addressed the high variability inherent in naturally occurring lesions by using an unselected, but very large sample size and by comparing a neglect group with a non-neglect group using voxelwise statistical testing. We investigated an unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes. Seventy-eight had spatial neglect, 62 did not show the disorder. The incidence of visual field defects was comparable in both groups. For assessing lesion location, in a first step, we used conventional lesion density plots together with subtraction analysis. Moreover, due to the large size of the sample voxelwise statistical testing was possible to objectively estimate which brain regions are more frequently compromised in neglect patients relative to patients without neglect. The results demonstrate that the right superior temporal cortex, the insula and subcortically putamen and caudate nucleus are the neural structures damaged significantly more often in patients with spatial neglect.

Adult↗
PubMed2004

Diffusion-weighted MRI of spinal cord infarction--high resolution imaging and time course of diffusion abnormality.

Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted (DW) MRI has been established as a highly sensitive technique for assessing acute cerebral ischemia, its role in spinal cord infarction remains to be determined. The purpose of this study is to present the signal characteristics of acute spinal cord ischemia using DWMRI within the first two days and after one week. MRI including DW imaging (DWI) was performed in three patients with acute spinal cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated after one week in two patients. Two initial scans included EPI DW sequences in transverse and sagittal orientation. The remaining examinations were performed with an optimised high-spatial resolution DWI sequence in the transverse plane. The diagnosis of spinal cord ischemia was established by imaging, clinical history and CSF analysis. T2 signal abnormality and restricted diffusion was demonstrated in all initial examinations. Transverse DW sequences had the highest sensitivity. The spinal infarctions were mainly located in the centre of the spinal cord and the grey matter. Contrast enhancement was absent. After one week, the restricted diffusion had normalised (pseudo normalisation) whereas the T2 signal changes had become more prominent. Restricted diffusion in the course of spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a diffusion abnormality can be found after few hours, it does not last for longer than one week. At this time, the establishment of the diagnosis has to rely mainly on T2-weighted images with additional post contrast T1-weighted images being useful.

Adult↗
PubMed2004

Intracranial metastatic esthesioneuroblastoma responsive to temozolomide.

Successful management of a heavily pretreated 58-year-old woman with metastatic esthesioneuoblastoma using temozolomide is reported. There is no standard treatment of this tumors with extra- and intracranial manifestations. The response, long term stability and high quality of life using temozolomide for this tumor entity should be recognized.

Antineoplastic Agents, Alkylating↗
PubMed2003

The cortical substrate of visual extinction.

Neuroimaging studies investigated the attentional systems of the human brain revealing two networks, one for voluntary allocation of attention and another for stimulus-driven attentional processes. Whereas lesions of the latter system were supposed to lead to spatial neglect, we show that such lesions rather are typical for the occurrence of visual extinction. Extinction describes the inability of brain-damaged patients to detect a contralesional target in the presence of a competing ipsilesional stimulus. In a sample of consecutively admitted patients with right hemisphere stroke, we found dissociable cortical substrates for spatial neglect and visual extinction. There was a surprising congruency between the typical lesion site in patients with extinction and the activation clusters found in previous neuroimaging studies of healthy subjects. The results show that the temporo-parietal junction (TPJ), considered to be a crucial part of the stimulus-driven attentional network, is the neural substrate of visual extinction.

Aged↗
PubMed2003

The long-term effect of recombinant tissue-plasminogen-activator (rt-PA) on edema formation in a large-animal model of intracerebral hemorrhage.

Hematoma puncture, fibrinolysis, and aspiration of the liquefied clot is a promising new treatment strategy for large intracerebral hemorrhages (ICH). Characteristics of the cellular injury and neuronal and glial cell death associated with ICH and the administration of fibrinolytic agents still need to be defined. We developed a porcine model to study the histopathological effects of recombinant tissue-Plasminogen-Activator (rt-PA) on perihematomatous cell integrity. In 20 pigs, lobar hematomas were induced by intracranial pressure (ICP)-controlled injections of 7.6 +/- 1.6 ml of autologous blood into the white matter of the right frontal hemisphere. In nine animals, the clots were lysed with rt-PA, thereby facilitating aspiration 2 h after hematoma induction. In 11 control pigs, the hematoma resorption followed its natural course. The rate of hematoma reduction and edema formation over 10 days was evaluated on planimetry of the MRI data and correlated to the histopathological changes found at autopsy. Although rt-PA significantly accelerated clot resolution compared to controls (p < 0.02), the increase of perihematomatous edema volume within 10 days was not significantly ameliorated in rt-PA-treated animals compared to controls on MRI. The extent of inflammatory infiltrates on histology was more pronounced in animals treated with rt-PA. In conclusion, despite significant reduction in the size of the hematoma clot liquefication with rt-PA and aspiration invokes a substantial inflammatory response when studied after 10 days and does not result in a reduction of the perihematomatous edema.

Animals↗
PubMed2002

German Cancer Society Neuro-Oncology Working Group NOA-03 multicenter trial of single-agent high-dose methotrexate for primary central nervous system lymphoma.

The prospective multicenter NOA-03 trial, conducted by the Neuro-Oncology Working Group (NOA) of the German Cancer Society, was initiated to define the feasibility and efficacy of single-agent high-dose methotrexate therapy without concomitant radiotherapy in immunocompetent patients with primary central nervous system lymphoma. Thirty-seven patients (median age, 60 years) received 179 biweekly courses of 8 g/m2 methotrexate. Response was assessed after 3 and 6 courses. We had planned to enter 105 patients into the trial. Since fewer than the projected 18 of 37 patients achieved a complete response after an intermediate analysis, the trial was closed. In intention-to-treat analysis, 11 of 37 patients (29.7%) achieved complete response, whereas 14 of 37 patients (37.8%) were found to have progressive disease. The median relapse-free survival among complete response patients was 13.7 months. Multivariate logistic regression analysis revealed that corticosteroid application during the first methotrexate course was associated with complete response. The regimen was well tolerated, but, unlike previously reported results, the activity of high-dose methotrexate was only moderate.

Adult↗
PubMed2002

Gliomatosis cerebri: molecular pathology and clinical course.

Gliomatosis cerebri is a rare, diffusely growing neuroepithelial tumor characterized by extensive brain infiltration involving more than two cerebral lobes. Among 13 patients with gliomatosis cerebri (median age, 46 years), biopsies showed features of diffuse astrocytoma (n = 4), oligoastrocytoma (n = 1), anaplastic astrocytoma (n = 5), anaplastic oligoastrocytoma (n = 1), or glioblastoma (n = 2). Molecular genetic investigation showed TP53 mutations in three of seven tumors and both PTEN mutation and epidermal growth factor receptor overexpression in one tumor. Amplification of CDK4 or MDM2 or homozygous deletion of CDKN2A was not detected. Three of 10 patients receiving radiotherapy showed a partial response (one patient) or had stable disease (two patients) lasting for more than 1 year. Four of six patients treated with procarbazine, carmustine, vincristine chemotherapy demonstrated partial remission (one patient), minor response (two patients), or stable disease (one patient). Median survival time from diagnosis was 14 months (range, 4-91+ months). Infratentorial involvement was associated with shorter survival. We conclude that (1) the molecular genetic alterations in gliomatosis cerebri resemble those in diffuse astrocytomas; (2) the prognosis of gliomatosis cerebri is variable but for at least 50% of patients as poor as for glioblastoma; and (3) some patients respond to radiotherapy and/or procarbazine, carmustine, vincristine chemotherapy.

Adult↗
PubMed2002

MRI characteristics of acute and subacute brainstem and thalamic infarctions: value of T2- and diffusion-weighted sequences.

MRI including diffusion-weighted sequences (DW-MRI) has demonstrated its high sensitivity for acute supratentorial ischemic lesions. In this study we examined the sensitivity of different MRI sequences for the detection of acute brainstem and isolated thalamic infarctions. Diffusion- and T2-weighted MRI of 45 consecutive patients with signs and symptoms of infratentorial and thalamic infarction between 6/1997 and 1/2000 were analysed. The time between the onset of symptoms and the first MRI varied between 2 hours to 7 days with a median of 2 days. MRI repeats were performed in 4 patients in whom the clinical brainstem infarction had not been detected initially. Lesion detectability and size were evaluated for different brainstem and thalamic localizations. An acute brainstem or thalamic infarction as defined by the clinical condition could be identified in all patients by comparison of DW-MRI and T2-weighted images. Pons in farctions were the largest, followed by midbrain and thalamic lesions. Medulla oblongata infarctions were small in comparison. Pons, mid-brain and thalamic infarctions were reliably identified beginning 12 hours after the onset of symptoms. In contrast, detectability of medulla oblongata infarctions varied within the first 24 hours and their overall visibility was worse than that of other brainstem infarctions corresponding to their small size. However, regardless of loca tion, none of the 3 infarctions examined within the first 5 hours after the onset of symptoms could be identified. These lesions were demonstrated in follow-up examinations. In conclusion, pontine, midbrain and thalamic infarctions can reliably be visualized by a combination of DW-MRI and T2-weighted images beginning 12 hours after the ischemic attack. However, sensitivity seems to be lower earlier than 12 hours after ischemia and for medulla oblongata lesions.

Acute Disease↗
PubMed2002

Diffusion-weighted MRI in patients with symptomatic internal carotid artery disease.

Beside the early detection of ischemia, there is an increasing body of evidence that diffusion-weighted imaging (DWI) can provide important information on stroke etiology. Against the background of an increased use of magnetic resonance angiography in patients being evaluated for carotid endarterectomy (CEA), the question arises if the additional performance of a DWI scan could also yield clinically relevant findings in these patients. In a prospective observational study we analysed the DWI data of 107 patients with high-grade symptomatic carotid artery disease (CAD) being evaluated for CEA. While no patient with a retinal TIA (n = 29) exhibited a DWI lesion, nineteen of the 42 patients with a hemisphere TIA and all patients with a minor stroke (n = 36) showed DWI lesion(s). In patients with TIAs the occurrence of DWI abnormalities was significantly more frequent in patients with long lasting TIAs. The majority of patients had multiple DWI lesions suggestive of acute large-artery thromboembolism as a common morphological phenotype of stroke. The finding of a similar lesion pattern in 4 patients with additional pre-existing atrial fibrillation suggested a symptomatic carotid stenosis. In contrast, unexpected bihemisphere lesions suggested cardioembolism in two patients with a normal circle of Willis and instigated thorough cardiac investigations. In both instances 24-h Holter monitoring revealed intermittent atrial fibrillation, so that a CEA was not performed. In conclusion, we demonstrate a common DWI lesion pattern in patients with symptomatic high-grade CAD eligible for CEA. In patients with known concomitant cardiac disorders the finding of this typical lesion pattern may support the diagnosis of a symptomatic CAD. In contrast, the additional performance of DWI can also reveal an unexpected cardiac source of embolism in some patients, which can substantially influence their further clinical management.

Aged↗