[Show abstract][Hide abstract] ABSTRACT: Cell outgrowth and migration in the developing nervous system result from guidance cues, whose molecular bases and clinical correlates are only partly known. We describe a patient with brain stem malformation, paroxysmal left sided lacrimation when eating ("crocodile tears") and mirror movements in addition to Wildervanck's cervico-oculo-acusticus (COA) syndrome, which encompasses Klippel-Feil anomaly, congenital hearing loss and Duane's syndrome. The unique symptom constellation has not been reported in that combination before and can be discussed in the context of congenital disordered axonal migration based on dysfunction of signalling pathways. However, mutations in some recently discovered genes, associated with single findings also present in our patient, were not found. Therefore, we suppose that the disturbance of an as yet unknown regulatory factor may explain the congenital malformation syndrome of our patient. In general, only a few human disorders have yet been found to result from defects in axon guidance. Nevertheless, disorders of axon guidance can certainly be regarded as a new category of neurodevelopmental disorders.
Journal of Neurology 09/2011; 259(4):761-3. DOI:10.1007/s00415-011-6239-y · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: L-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI).
We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up.
There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%.
O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.
International journal of radiation oncology, biology, physics 05/2011; 81(4):1049-58. DOI:10.1016/j.ijrobp.2010.07.002 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.
[Show abstract][Hide abstract] ABSTRACT: In this study we attempted to differentiate distinct components of the saccade network, namely cortical ocular motor centers and parieto-occipital brain regions, by means of a "minimal design" approach. Using a blocked design fMRI paradigm we evaluated the BOLD changes in a 2 x 2 factorial design experiment which was performed in complete darkness: while looking straight ahead with eyes open (OPEN) or closed (CLOSED) as well as during the execution of self-initiated horizontal to-and-fro saccades with the eyes open (SACCopen) or closed (SACCclosed). Eye movements were monitored outside the scanner via electro-oculography and during scanning using video-oculography. Unintentional eye-drifts did not differ during OPEN and CLOSED and saccade frequencies, and amplitudes did not vary significantly between the two saccade conditions. The main findings of the functional imaging study were as follows: (1) Saccades with eyes open or closed in complete darkness lead to distinct differences in brain activation patterns. (2) A parieto-occipital brain region including the precuneus, superior parietal lobule, posterior part of the intraparietal sulcus (IPS), and cuneus was relatively deactivated during saccades performed with eyes closed but not during saccades with eyes open or when looking straight ahead. This could indicate a preparatory state for updating spatial information, which is active during saccades with eyes open even without actual visual input. The preparatory state is suppressed when the eyes are closed during the saccades. (3) Selected ocular motor areas, not including the parietal eye field (PEF), show a stronger activation during SACCclosed than during SACCopen. The increased effort involved in performing saccades with eyes closed, perhaps due to the unusualness of the task, may be the cause of this increased activation.
Experimental Brain Research 05/2008; 186(3):419-30. DOI:10.1007/s00221-007-1247-y · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Both ischemic stroke and peripheral arterial thromboembolism have been described as extraintestinal complications of inflammatory bowel disease. Here, we present the first case with direct cooccurrence of ischemic stroke and peripheral thromboembolism in a 39-year-old patient with Crohn's disease. A pathophysiological model explaining this cooccurrence as well as the significance of prothrombotic risk factors ("hypercoaguable state") in the setting of inflammatory bowel disease and stroke are discussed.
Journal of the Neurological Sciences 04/2008; 266(1-2):177-9. DOI:10.1016/j.jns.2007.08.035 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis. In contrast, inhibition of Src significantly reduced brain edema formation, lesion volume, and clinical worsening in cold-induced brain injury without decreasing cytokine/chemokine expression. While brain trauma was associated with increased cerebral VEGF formation, VEGF levels significantly declined during pneumococcal meningitis. Therefore, we conclude that in brain trauma blood-brain barrier tightness is regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema formation and leukocyte function during bacterial meningitis.
[Show abstract][Hide abstract] ABSTRACT: We used BOLD fMRI to study the differential effects of the direction of gaze on the visual and the ocular motor systems. Fixation of a target straight ahead was compared to fixation of a target 10 degrees to the right and 10 degrees to the left from gaze straight ahead, and to eyes open in complete darkness in thirteen healthy volunteers. While retinotopic coordinates remained the same in all fixation conditions, the fixation target shifted with respect to a head-centered frame of reference. During lateral fixation, deactivations in higher-order visual areas (one ventral cluster in the lingual and fusiform gyri and one dorsal cluster in the postero-superior cuneus) and, as a trend, activations in early visual cortical areas were found predominantly in the hemisphere contralateral to the fixation target. We propose that visual processing is performed predominantly in the hemisphere contralateral to gaze direction, even during small gaze shifts into one visual hemifield. The excitability of visual neurons may be modulated depending on eye position to construct a head-centered frame of reference from a retinotopic input, thus allowing perceptual stability of space during eye movements. A further finding was that BOLD signal increases in fronto-parietal ocular motor and attentional structures were more pronounced during lateral than central fixation.
[Show abstract][Hide abstract] ABSTRACT: Using magnetic resonance imaging (MRI), residual tumor cannot be differentiated from nonspecific postoperative changes in operated patients with brain gliomas. The higher specificity and sensitivity of L-(methyl-11C)-labeled methionine positron emissions tomography (MET-PET) in gliomas has been demonstrated in previous studies and is the rationale for the integration of this investigation in gross tumor volume delineation. The goal of this trial was to quantify the affect of MET-PET vs. with MRI in gross tumor volume definition for radiotherapy planning of high-grade gliomas.
The trial included 39 patients with resected malignant gliomas. MRI and MET-PET data were coregistered based on mutual information. The residual tumor volume on MET-PET and the volume of tissue abnormalities on T1-weighted MRI (gadolinium [Gd] enhancement) and T2-weighted MRI (hyperintensity areas) were compared using MET-PET/MRI fusion images.
The MET-PET vs. Gd-enhanced T1-weighted MRI analysis was performed on 39 patients. In 5 patients (13%), MET uptake corresponded exactly with Gd enhancement, and in 29 (74%) of 39 patients, the region of MET uptake was larger than that of the Gd enhancement. In 27 (69%) of the 39 patients, the Gd enhancement area extended beyond the MET enhancement. MET uptake was detected up to 45 mm beyond the Gd enhancement. MET-PET vs. T2-weighted MRI was investigated in 18 patients. MET uptake did not correspond exactly with the hyperintensity areas on T2-weighted MRI in any patient. In 9 (50%) of 18 patients, MET uptake extended beyond the hyperintensity area on the T2-weighted MRI, and in 18 (100%), at least some hyperintensity on the T2-weighted MRI was located outside the MET enhancement area. MET uptake was detected up to 40 mm beyond the hyperintensity area on T2-weighted MRI.
In operated patients with brain gliomas, the size and location of residual MET uptake differs considerably from abnormalities found on postoperative MRI. Because postoperative changes cannot be differentiated from residual tumor by MRI, MET-PET, with a greater specificity for tumor tissue, can help to outline the gross tumor volume with greater accuracy.
International Journal of Radiation OncologyBiologyPhysics 10/2005; 63(1):64-74. DOI:10.1016/j.ijrobp.2005.01.045 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During fixation of a stationary, dim light-emitting diode (LED) in complete darkness, a subtle, apparent motion is perceived which is called autokinesis. This autokinetic illusion increases with increasing fixation time. Eleven healthy subjects were examined by fMRI while fixating an LED in darkness for 35 s. BOLD signal changes of the first and the second half of the fixation period were compared. While the stimulus was the same for both periods, perception differed in that autokinesis was more pronounced in the second half. This second half of the period was associated with bilateral activations in the motion-sensitive middle occipito-temporal area known as MT/V5. Our finding suggests that area MT/V5 is involved in the mediation of autokinesis.
[Show abstract][Hide abstract] ABSTRACT: A patient with unilateral focal cortical dysplasia with a significant impairment of visual motion perception within the contralateral hemifield was examined with fMRI. During hemifield visual motion stimulation primary visual cortex areas were activated contralaterally and deactivated ipsilaterally to the stimulated hemifield. Transcallosal visuo-visual interaction was further evident as bilateral activation in temporo-occipital areas that best correspond to the motion sensitive areas MT/V5. MT/V5 was displaced anteriorly, superiorly, and medially within the dysplastic hemisphere and separated into two distinct activation clusters. During visual motion stimulation the parieto-insular vestibular cortex showed signal decreases that agree with the concept of inhibitory visuo-vestibular interaction. Thus, fMRI is a suitable tool for detecting preserved function and transcallosal connections in patients with focal cortical dysplasia.