Biomedical subjects
Thomas Nägele
Publications and source records attributed to Thomas Nägele.
Risk factors for early recurrent cerebral ischemia before treatment of symptomatic carotid stenosis.
BACKGROUND AND PURPOSE: In patients with a recently symptomatic carotid stenosis, surgical or interventional treatment is often delayed for weeks to months. Because therapy should be instituted as early as possible in patients at highest risk for recurrent ischemia, the aim of this study was to identify these individuals using clinical data and serial diffusion-weighted imaging (DWI). METHODS: One hundred thirty-one patients (98 male; mean age 68+/-9 years) who had been referred to our department within 14 days (median; interquartile range, 4 to 36 days) after experiencing an ischemic event caused by a carotid stenosis were followed-up until carotid angioplasty and stenting. Risk factors predicting recurrent transient ischemic attack, stroke, or new DWI lesions were examined. RESULTS: During a median follow-up period of 7 days (interquartile range, 5 to 13 days) no patient experienced a stroke, 4 patients (3.1%) developed a hemispherical transient ischemic attack, and in 15 patients (12%) new asymptomatic DWI lesions were present in the territory of the treated artery. Multivariable regression analysis revealed that motor symptoms (odds ratio, 5.6; 95% CI, 1.2 to 26.3; P<0.05) or the presence of a contralateral carotid occlusion (odds ratio, 4.6; 95% CI, 1.0 to 20.4; P<0.05) were significant independent predictors of further cerebral ischemic events before carotid angioplasty and stenting. CONCLUSIONS: In patients with a recently symptomatic carotid stenosis, the risk of early recurrent ischemia is highest in those with motor symptoms and in those with a contralateral carotid occlusion. In these high-risk patients urgent preventive treatment might be warranted.
Incidence of new brain lesions after carotid stenting with and without cerebral protection.
BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) may be a useful tool to evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during carotid angioplasty and stenting (CAS). The goals of this study were (1) to compare the frequency, number, and size of new DWI lesions after unprotected and protected CAS; and (2) to determine the clinical significance of these lesions. METHODS: DWI was performed immediately before and within 48 hours after unprotected or protected CAS. Clinical outcome measures were stroke and death within 30 days. RESULTS: The proportion of patients with any new ipsilateral DWI lesion (49% versus 67%; P<0.05) as well as the number of new ipsilateral DWI lesions (median=0; interquartile range [IQR]=0 to 3 versus median=1; IQR=0 to 4; P<0.05) were significantly lower after protected (n=139) than unprotected (n=67) CAS. The great majority of these lesions were asymptomatic and less than 10 mm in diameter. Although there were no significant differences in clinical outcome between patients treated and not treated with protection devices (7.5% versus 4.3%, not significant), the number of new DWI lesions was significantly higher in patients who developed a stroke (median=7.5; IQR=1.5 to 17) than in patients who did not (median=0; IQR=1 to 3.25; P<0.01). CONCLUSIONS: The use of cerebral protection devices significantly reduces the incidence of new DWI lesions after CAS of which the majority are asymptomatic and less than 10 mm in diameter. The frequent occurrence of these lesions and their close correlation with the clinical outcome indicates that DWI could become a sensitive surrogate end point in future randomized trials of unprotected versus protected CAS.
Visualization and quantification of disease progression in multiple system atrophy.
To visualize and quantify disease progression in multiple system atrophy (MSA) from cerebellar type (MSA-C), we combined two magnetic resonance imaging (MRI) techniques, voxel-based morphometry (VBM) and 3D-based volumetry. Patients suffering from MSA-C (n = 14) were imaged twice with an interval of 2.0 +/- 0.2 years. We first applied VBM to map brain morphology changes between MSA patients and controls and to identify brain areas that showed a significant amount of atrophy. Using 3D-based volumetry, we confirmed that in MSA-C patients, the brainstem including medulla and pons, vermis and cerebellar hemispheres, caudate nucleus and putamen showed significant atrophy compared with controls. Next, we used 3D-based volumetry to analyze the atrophy rates. Atrophy rates in patients with MSA were significantly different from controls for putamen (-11.4% +/- 2.6%/year), vermis (-12.3% +/- 2.9%/year), and cerebellar hemispheres (-6.6% +/- 1.1%/year). The results show that 3D-based MRI volumetry is a tool that allows the disease progression of MSA to be followed over a time period of 2 years and suggest that it may serve as a surrogate marker in clinical trials to measure disease progression.
Statin therapy at carotid angioplasty and stent placement: effect on procedure-related stroke, myocardial infarction, and death.
PURPOSE: To retrospectively determine if preprocedural statin treatment is associated with a reduction of cardiovascular events after carotid angioplasty and stent placement (CAS) in patients with symptomatic carotid stenosis. MATERIALS AND METHODS: A study resulting in a prospective database was approved by the institutional ethics review board; written informed consent was obtained. The approval and informed consent included future retrospective analysis. Consecutive patients (n = 180) from the prospective database underwent CAS for high-grade symptomatic carotid disease. The frequency of cardiovascular complications (composite of stroke, myocardial infarction, and death within 30 days after CAS) between 127 patients without preprocedural statin treatment and that of 53 patients with preprocedural statin treatment at CAS were compared with chi2 and multivariate logistic regression analysis. RESULTS: The overall 30-day myocardial infarction rate was two of 180 (1%) patients, the minor stroke rate was 16 of 180 (9%) patients, the major stroke rate was one of 180 (0.5%) patients, and the death rate was two of 180 (1%) patients. The incidence of cardiovascular events (composite of stroke, myocardial infarction, and death within 30 days after CAS) was significantly different between patients with preprocedural treatment (4%) and those without preprocedural statin treatment (15%) (P < .05). These higher complication rates among patients without preprocedural statin treatment were not mediated by adjustment for age, sex, other baseline characteristics, degree of carotid stenosis, use of cerebral protection devices, or the year in which CAS was performed. CONCLUSION: Preprocedural statin therapy appears to reduce the incidence of stroke, myocardial infarction, and death within 30 days after CAS. Future prospective randomized trials are warranted to further assess this potential protective effect of statin drugs during carotid interventions.
Prospective comparison of the impact on treatment decisions of whole-body magnetic resonance imaging and computed tomography in patients with metastatic malignant melanoma.
Patient management and treatment strategies for metastatic melanoma depend largely on the stage of metastatic disease. The aim of this study was to compare contrast-enhanced whole-body magnetic resonance imaging (wbMRI) and whole-body computed tomography (wbCT) to detect distant metastases for staging. A total of 43 patients (41 with completed wbCT and wbMRI examination) with known American Joint Committee on Cancer (AJCC) stage III-IV malignant melanoma were examined and 775 metastases were identified by both methods. Whole-body CT was able to detect 522 metastases, whereas wbMRI found 730 metastases. Whole-body CT identified 188 pulmonary metastases, compared with 143 metastases detected by wbMRI. In kidneys, adrenal glands and lymph nodes, respectively, wbCT and wbMRI detected the same number of lesions. Whole-body MRI detected more metastases than wbCT in liver (detection rate 122/199), spleen (26/54), subcutaneous tissue (39/61), muscle (4/11), bone marrow (23/132) and brain (15/25). Therapy was modified as a consequence of wbMRI findings in 10/41 (24%) patients. In conclusion, wbMRI detected clearly more malignant melanoma metastases in most organ systems with the exception of lung metastases. More accurate and complete staging by wbMRI has an impact on treatment strategy in about one-quarter of the patients.
Atherosclerotic disease: whole-body cardiovascular imaging with MR system with 32 receiver channels and total-body surface coil technology--initial clinical results.
In this prospective study, the feasibility of a comprehensive cardiovascular imaging protocol with a dedicated whole-body 1.5-T magnetic resonance (MR) imager with 32 receiver channels in 34 patients with peripheral arterial occlusive disease was evaluated. Informed consent and institutional review board approval were obtained. Three-dimensional MR angiographic data sets were acquired with adapted injection protocol. Cardiac functional imaging and delayed-enhancement imaging were performed, as were fluid-attenuated inversion-recovery imaging of the brain and time-of-flight MR angiography of the intracranial blood vessels. Sensitivity and specificity for depiction of significant vascular stenosis (> 70%) were 96%, with conventional digital subtraction angiography as the standard. Substantial microangiopathic tissue alterations (n = 4) and/or cerebral infarction (n = 4) were diagnosed in seven patients. In seven patients, subendocardial or transmural delayed enhancement was detected in corresponding regions, indicating prior myocardial infarction. Previously unknown findings diagnosed with MR imaging required midterm follow-up or therapy in 24 patients, whereas change of therapy or immediate treatment was necessary in three. For patients suspected of having systemic atherosclerotic disease, comprehensive risk assessment is feasible within 30 minutes.
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.
Normalized perfusion MRI to identify common areas of dysfunction: patients with basal ganglia neglect.
Perfusion-weighted imaging (PWI) is used to identify brain regions that are receiving enough blood supply to remain structurally intact, but not enough to function normally. Previous observations suggest that spatial neglect due to subcortical stroke can be explained by dysfunction of cortical areas rather than through the neuronal loss in the subcortical structures itself. The present study aimed to identify the dysfunctional cortical regions induced by basal ganglia stroke in patients with spatial neglect. In a patient group with stroke lesions centring on the basal ganglia, we examined the common area(s) of structurally intact but dysfunctional cortical tissue by using spatial normalization of PWI maps as well as symmetric voxel-wise inter-hemispheric comparisons. These new techniques allow comparison of the structurally intact but abnormally perfused areas of different individuals in the same stereotaxic space, and at the same time avoid problems due to regional perfusion differences and to possible observer-dependent biases. We found that strokes centring on the right basal ganglia which provoke spatial neglect induce abnormal perfusion in a circumscribed area of intact cortex that typically involves those three regions that have previously been described to provoke spatial neglect when damaged directly by cortical infarction: the superior temporal gyrus, the inferior parietal lobule and the inferior frontal gyrus. The data suggest that spatial neglect following a right basal ganglia lesion typically is caused by the dysfunction of (part of) these specific cortical areas.
Awareness of the functioning of one's own limbs mediated by the insular cortex?
Normally, we are aware of the current functions of our arms and legs. However, this self-evident status may change dramatically after brain damage. Some patients with "anosognosia" typically are convinced that their limbs function normally, although they have obvious motor defects after stroke. Such patients may experience their own paretic limbs as strange or as not belonging to them and may even attribute ownership to another person and try to push their paralyzed limb out of bed. These odd beliefs have been attributed to disturbances somewhere in the right hemisphere. Here, we use lesion mapping in 27 stroke patients to show that the right posterior insula is commonly damaged in patients with anosognosia for hemiplegia/hemiparesis but is significantly less involved in hemiplegic/hemiparetic patients without anosognosia. The function of the posterior insular cortex has been controversially discussed. Recent neuroimaging results in healthy subjects revealed specific involvement of this area in the subject's feeling of being versus not being involved in a movement. Our finding corresponds with this observation and suggests that the insular cortex is integral to self-awareness and to one's beliefs about the functioning of body parts.
Clinical predictors of transient ischemic attack, stroke, or death within 30 days of carotid angioplasty and stenting.
BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) is currently being assessed in the treatment of severe carotid stenosis. However, little data are available concerning patient-related factors affecting the risk of CAS. The purpose of this study was to identify potential clinical risk factors for the development of postprocedural deficits after CAS. METHODS: The clinical characteristics of 299 patients (217 men, 82 women; mean age 69+/-9 years) who underwent CAS for asymptomatic (n=129, 43%) or symptomatic (n=170, 57%) stenoses and the combined 30-day complication rates (any transient ischemic attack [TIA], minor stroke, major stroke, or death) were analyzed with logistic regression analysis. RESULTS: The overall 30-day TIA rate was 3.7%; the minor stroke rate was 5.3%, the major stroke rate was 0.7%, and the death rate was 0.7%. Although patients presenting with a hemispherical TIA or minor stroke had a significantly higher risk than asymptomatic patients (odds ratio [OR] 5.69; 95% confidence interval [CI], 2.03 to 19.57; P<0.001), the complication rates between patients presenting with a retinal TIA and asymptomatic patients was comparable (OR, 1.42; 95% CI, 0.13 to 9.09; P=0.6). Multivariate regression analysis revealed advanced age (OR, 1.06; 95% CI, 1 to 1.11; P<0.05), stroke (OR, 8; 95% CI, 2.6 to 24.4; P<0.01) or hemispherical TIA (OR, 4.7; 95% CI, 1.6 to 13.3) as presenting symptoms as independent clinical predictors of the combined 30-day outcome measures any TIA, stroke, or death. CONCLUSIONS: Aside from advanced age and symptom status, the type of presenting event predicts postprocedural complications after CAS. When evaluating the outcome of CAS and comparing this treatment modality to surgery, patients should be stratified according to their presenting event.
UKT-04 trial of continuous metronomic low-dose chemotherapy with methotrexate and cyclophosphamide for recurrent glioblastoma.
Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Continuous oral low-dose chemotherapy with methotrexate (MTX) and cyclophosphamide (CPM) has modest activity in heavily pretreated patients with breast cancer. We explored the efficacy of 100 mg CPM daily and 5 mg MTX twice weekly in relapsed glioblastoma. Ten patients, 22-59 years old, with a Karnofsky score of 50% or higher who had failed at least two chemotherapies were accrued. No toxicity was observed. No patient showed a complete or partial response. Five of 10 patients progressed within 2 months of therapy. Another five patients progressed after 3-4.5 months. The median time to progression was 2.5 months. The median overall survival after start of MTX/CPM was 6.9 months (range 0.5-18.8 months). Since the progression-free survival rate at 6 months was 0%, the trial was prematurely closed.
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.
Disseminating anaplastic brainstem oligodendroglioma associated with allelic loss in the tumor suppressor candidate region D19S246 of chromosome 19 mimicking an inflammatory central nervous system disease in a 9-year-old boy.
We report the case of a 9-year-old boy clinically presenting with severe headache, vomiting, head retroflexion, nystagmus, and ataxia. Magnetic resonance imaging showed brainstem enlargement leading to the diagnosis of an inflammatory process. In addition, the clinical picture, a monocytic cerebrospinal fluid pleocytosis with elevated protein and lactate and serum IgM antibodies to Mycoplasma pneumoniae favored this diagnosis. Subsequently, corticosteroid treatment rapidly improved clinical symptoms, and lesions declined in subsequent neuroradiological examinations. However, 2 months later, fulminant disease progression led to brain death. Final neuroradiological examination favored meningoencephalitis. The autopsy revealed brain swelling and brainstem softening with a superficial gelatinous mass extending along the spinal cord. Finally, a disseminating anaplastic oligodendroglioma with allelic loss of the D19S246 tumor suppressor candidate locus of chromosome 19 was diagnosed. To our knowledge, this is the first case of a disseminating anaplastic brainstem oligodendroglioma associated with this specific allelic loss occurring in childhood.
Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease*.
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Fast whole-body assessment of metastatic disease using a novel magnetic resonance imaging system: initial experiences.
OBJECTIVE: The objective of this study was to investigate the clinical use of a novel whole-body magnetic resonance imaging (MRI) system for comprehensive assessment of tumor spread in clinical routine. MATERIAL AND METHODS: Sixty-five patients with different tumors with known metastatic disease and 6 healthy volunteers were included. High-resolution MRI from head to toe was performed using multiple phased-array surface coil elements, 24 independent receiver channels, and an integrated parallel acquisition technique (iPAT). A total room time of less than 60 minutes was required. Whole-body MRI and conventional spiral computed tomography (CT) were independently evaluated and compared in terms of feasibility, location/number of detected metastases, and therapeutic relevance. RESULTS: Whole-body MRI was successfully performed in 68 of 71 subjects. Compared with CT, more metastases were detected by MRI in 11 of 63 patients (17%), particularly in brain, liver, spleen, lymph nodes, bone marrow, muscle, and subcutaneous fat tissue. According to these findings, therapy had to be modified in 6 of 63 patients (10%). CONCLUSIONS: High-resolution whole-body MRI is feasible in clinical routine within 1 single examination and offers great potential for fast assessment of individual tumor spread and total tumor burden.
3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy.
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a disorder of leucine metabolism that usually presents with recurrent episodes of life-threatening hypoglycemia during early childhood. We report on a 36-year-old woman with seizures, recurrent metabolic disturbances, and severe leukoencephalopathy. The diagnosis was made by analysis of amino acids in urine and serum and was confirmed by demonstration of the deficient enzyme in cultured skin fibroblasts. The patient improved clinically on oral L-carnitine substitution. This treatable condition can remain unrecognized in adults and should be considered a potential cause of leukoencephalopathy.
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.