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Biomedical subjects

Wilhelm Küker

Publications and source records attributed to Wilhelm Küker.

17 recordsLinked to original sources
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↗
PubMed2002

Neonatal cerebral infarction diagnosed by diffusion-weighted MRI: pseudonormalization occurs early.

BACKGROUND: Seizures in the neonatal period may be the single symptom of acute ischemic cerebral infarction. It may be difficult to establish the diagnosis in the acute phase by the use of ultrasound, CT, and conventional MRI because of the high water content of the immature brain. Diffusion-weighted (DW) MRI is a very sensitive and fast imaging modality to visualize acute ischemic stroke in infants even before conventional MR images become abnormal. Signal abnormality in DW MRI, however, seems to follow a different time course than in older patients. CASE DESCRIPTION: DW MRI became falsely negative 1 week after stroke (pseudonormalization) in 2 newborn patients during persistence of signal abnormalities on turbo spin-echo images, whereas the so-called pseudonormalization in adults normally occurs within 10 to 14 days. CONCLUSIONS: T2-weighted sequences should supplement DW images to reliably detect subacute ischemic infarctions in the neonatal period.

Cerebral Arteries↗
PubMed2002

Complete asymptomatic thrombosis and resorption of a congenital giant intracranial aneurysm.

Intracranial aneurysms in infants are rare, but are associated with a high risk of rupture and subarachnoid hemorrhage. The authors report a case of an incidentally diagnosed, probably congenital, asymptomatic giant aneurysm of the posterior communicating artery in a 9-month-old girl, which completely thrombosed following a diagnostic superselective angiography without any neuropathological incident. Follow-up magnetic resonance imaging revealed that the aneurysm decreased further in size and was largely resorbed within 3 years after the initial finding. In single cases the natural history of congenital giant aneurysms may be better than previously assumed.

Cerebral Angiography↗
PubMed2002

Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation.

OBJECT: Fibrinolysis therapy accomplished using tissue plasminogen activator (tPA) and aspiration is considered to be a viable alternative to microsurgery and medical therapy for the treatment of deep-seated spontaneous intracerebral hematomas (SICHs). Tissue plasminogen activator is a mediator of thrombin- and ischemia-related delayed edema. Because both thrombin release and ischemia occur after SICH, the authors planned to investigate the effect of fibrinolytic therapy on hematoma and delayed edema volume. METHODS: A spherical hematoma was created in the frontal white matter of 18 pigs. In the tPA-treated group (nine pigs), a mean of 1.55 ml tPA was injected into the clot and the resulting liquefied blood was aspirated. Magnetic resonance (MR) imaging was performed on Days 0 (after surgery), 4, and 10, and the volumes of hematoma and edema were determined. In the animals not treated with tPA (untreated group; nine pigs), the volume of hematoma dropped from 1.43+/-0.42 ml on Day 0 to 0.85+/-0.28 ml on Day 10. In the tPA-treated group, the volume of hematoma was reduced from 1.51 +/- 0.28 ml on Day 0 to 0.52 +/- 0.39 ml on Day 10. In comparison with the untreated group, the reduction in hematoma volume was significantly accelerated (p = 0.02). In the untreated group, perihematomal edema increased from 0.32 +/- 0.61 ml to 1.73 +/- 0.73 ml on Day 4, before dropping to 1.17 +/- 0.92 ml on Day 10. In the tPA-treated group, the volume of the edema increased from 0.09 +/- 0.21 ml on Day 0 to 1.93 +/- 0.79 ml on Day 4, and further to 3.34 +/- 3.21 ml on Day 10. The increase in edema volume was significantly more pronounced in the tPA-treated group (p = 0.04). CONCLUSIONS: Despite a significantly accelerated reduction in hematoma volume, the development of delayed perifocal edema was intensified by fibrinolytic therapy, which is probably related to the function of tPA as a mediator of edema formation after thrombin release and ischemia. Further experimental and clinical investigations are required to establish the future role of fibrinolysis in the management of SICH.

Animals↗
PubMed2001

Congenital disorder of glycosylation type Ia: benign clinical course in a new genetic variant.

The congenital disorders of glycosylation (CDG) are autosomal recessive disorders of N-glycans processing. Several different subtypes have been identified in recent years. Cerebellar atrophy is a characteristic finding in subtype Ia. We report clinical, imaging and genetic findings in a patient with a particularly benign clinical course, who had a normal CT at the age of 9 months and a new, previously undescribed, combination of mutations of the PMM gene locus on chromosome 16p13 (647,691). The 691 mutation has been described only in severe cases so far. This could indicate that genotype-phenotype correlation is lower than expected.

Brain↗