Voxel-based morphometry (VBM) has proved a powerful method to detect subtle changes of gray matter (GM) at the group level but the role of VBM for the detection of GM changes in single subjects, ...especially in those with suspected neurodegenerative disorder, remains uncertain. Here, we performed single subject analyses in 22 patients in early stages of Huntington disease (HD), a neurodegenerative disorder with a well-known and characteristic pattern of GM loss.
We applied an ANCOVA with age and gender as covariates and corrected for multiple statistical tests by false discovery rate (P < 0.05). Each patient was compared to 133 healthy controls. The same procedure was applied to 22 of the controls matched for age and gender in a pair-wise manner.
Our analyses yielded biologically plausible results in HD patients in which GM decrease within the caudate nucleus could be identified in 15 of the 16 most affected patients while GM decrease was found in only 1 control subject. Lowering the size of the control group yielded comparable results with 99 and 66 control subjects whereas sensitivity decreased with 33 control subjects.
Our pilot study demonstrates a potential role of VBM for the detection of cerebral GM changes in single subjects with suspected neurodegenerative disorder.
1. The present study was carried out to determine the effects of feeding ensiled alfalfa leaves (ALS) as an alternative protein source to laying hens under the terms of an organic diet. Due to the ...occurrence of unexpected negative health effects and undesirable egg yolk pigmentation in the test groups the trial was prematurely stopped and further analysis was conducted to evaluate the responsible substances.
2. Body weights of the test groups decreased significantly already in week 2 of the trial. Performance variables dropped. Olive green pigmented egg yolks were found in groups fed diets containing ALS. Severe comb necrosis occurred in the experimental group receiving the highest level of ALS (20%) combined with the option of free-range access and therefore natural light exposure.
3. The noxious agent found in ALS, blood serum and egg yolk was the photosensitising chlorophyll derivate pheophorbid a (PPBa), deriving from a strong depletion of chlorophyll contained in the alfalfa leaves. PPBa caused the olive-green pigmentation found in yolks and led to photosensitivity in groups with the highest level of ALS in the diet in combination with light exposure.
4. By aiming for high protein and amino acid levels, harvesting and processing have, unintentionally and initially unnoticed, led to a strong accumulation of phototoxic PPBa. From these results it is strongly advised not to include ensiled alfalfa leaves as a protein source in organic laying hen diets.
Transcranial magnetic stimulation of the motor cortex was performed in 10 normal subjects and 10 patients with radiographical abnormalities of the corpus callosum. Seven patients had a complete or ...partial agenesis or hypoplasia of the corpus callosum, two had a thin corpus callosum due to hydrocephalus or white matter degeneration and one had a circumscript contusion lesion of the corpus callosum. The patients served as a clinical model to investigate transcallosal influences on excitatory and inhibitory effects of motor cortex stimulation and to assess the potential diagnostic use of interhemispheric conduction studies and the contribution of interhemispheric interaction on transcranially elicited contralateral excitatory and inhibitory motor responses. Stimulation over one motor cortex suppressed tonic voluntary electromyographic activity in ipsilateral hand muscles in all subjects with preserved anterior half of the trunk of the corpus callosum. Since this suppression was lacking or had a delayed onset latency in patients with absence or abnormalities of the anterior half of the trunk of the corpus callosum it can be concluded that it is due to a transcallosal inhibition (Ti) of the opposite motor cortex mediated by fibres passing through this part of the corpus callosum. In normal subjects Ti had an mean onset latency of 36.1 +/- 3.5 ms (SD) and a duration of 24.5 +/- 3.9 ms. The calculated mean transcallosal conduction time was 13 ms. The threshold of Ti recorded in muscles ipsilateral to stimulation tended to be higher than the one for eliciting excitatory contralateral motor responses (56 +/- 6% versus 46 +/- 10% maximum stimulator output). Cortical thresholds (at rest) for contralateral excitatory hand motor responses were higher in patients with developmental abnormalities of the corpus callosum than in normals (66 +/- 17% versus 46 +/- 10% maximum stimulator output), which probably reflects also a facilitatory transcallosal interaction of both motor cortices in normals. In contrast, facilitation of cortically elicited motor responses in one hand by strong contraction of the other hand was the same in the patients with agenesis of the corpus callosum and normals, which suggests that this facilitatory spread takes place on a spinal rather than on a cortical level. Central motor latencies and amplitudes of contralateral hand motor responses were the same in patients with developmental abnormalities of the corpus callosum and normals (6.1 +/- 0.7 ms versus 6.3 +/- 0.7 ms and 6.7 +/- 2.4 mV versus 6.6 +/- 2.9 mV) so that callosal transfers do not seem to influence corticospinal conduction properties.
We used PET scans with the tracers 18Ffluorodeoxyglucose (FDG) and 11Craclopride (RACLO) to study glucose metabolism and dopamine D2 receptor binding in the caudate nucleus and putamen of 18 carriers ...of the Huntington's disease gene mutation (10 asymptomatic subjects and eight untreated symptomatic Huntington's disease patients in an early disease stage). We also performed MR1 scans and measured the bicaudate ratio (BCR) in the same subjects. Data were compared with those from nine mutation-negative members of Huntington's disease families and separate groups of age matched controls. The PET scans were repeated 1.5–3 years later in six of the asymptomatic gene carriers. Symptomatic Huntington's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR. Asymptomatic mutation carriers revealed significant hypometabolism in the caudate nucleus and putamen. The RACLO binding was significantly decreased in the putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO, correlated significantly with BCR increases in both symptomatic and asymptomatic gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases were also significantly associated with the CAG repeat number but not with the individual's age. Discriminant function analysis correctly classified clinical and genetic status in 24 of 27 subjects on the basis of their striatal PET values (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were classified/grouped together with mutation-negative subjects, indicating that these individuals had normal striatal RACLO and FDG uptake. Follow-up PET data from gene-positive subjects showed a significant reduction in the mean striatal RACLO binding of 6.3% per year. Striatal glucose metabolism revealed an overall non significant 2.3% decrease per year These data indicate that asymptomatic Huntington's disease mutation carriers may show normal neuronal function for a long period of life. These findings also suggest that it may be possible to predict when an asymptomatic gene carrier will develop clinical symptoms from serial PET measurements of striatal function.
In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution ...of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.
For three detector components of the KASCADE-Grande experiment, WEB based online event displays have been implemented. They provide, in a fast and simplified way, actual information about energy ...deposits and arrival times of measured events, and the overall detector status. Besides the aspect of being able to show air shower events to interested people wherever there is an internet access available, these event displays are an easy and highly useful tool for controlling and maintaining tasks from remote places. The event displays are designed as client-server applications, with the server running as independent part of the local data acquisition. Simplified event data are distributed via socket connections directly to the java applets acting as clients. These clients can run in any common browser on any computer anywhere on the planet.
Prompted by the observation of decreased glucose metabolism in the striate and extrastriate visual cortex in a patient with opsoclonus, we studied the influence of involuntary eye movements on visual ...cortex activity. Repeated measurements of cerebral blood flow (CBF) by PET were performed in 12 healthy volunteers using H2(15)O-bolus technique after ear canal irrigation with ice cold or warm (44 degrees C) water with the subjects eyes closed. In addition to blood flow increases in areas involved in central vestibular processing, statistical subtraction analysis revealed a nearly symmetrical, bilateral, highly significant decrease in the occipital cortex covering Brodmann areas 17, 18, and 19 after ice water stimulation of either ears. Region of interest analysis revealed in all subjects a mean decrease in regional CBF (rCBF) of 12.8% (range 4.6-21.0%) in these areas. A similar but less pronounced effect (mean rCBF decrease in visual cortex 4.8%, range 1.1-11.5%) was observed after warm water irrigation. The observations suggest that deactivation of the visual cortex is induced by involuntary ocular oscillations. This deactivation is not dependent on changes of the retinal input (eyes closed). The physiological significance of this hitherto unknown phenomenon may be the protection from inadequate visual input (oscillopsia) during involuntary ocular oscillations.
The KASCADE-Grande experiment has significantly contributed to the current knowledge about the energy spectrum and composition of cosmic rays for energies between the knee and the ankle. Meanwhile, ...post-LHC versions of the hadronic interaction models are available and used to interpret the entire data set of KASCADE-Grande. In addition, a new, combined analysis of both arrays, KASCADE and Grande, was developed significantly increasing the accuracy of the shower observables. First results of the new analysis with the entire data set of the KASCADE-Grande experiment will be the focus of this contribution.
According to the excitotoxicity hypothesis, neurotoxicity due to glutamate is regarded as potential factor in the progredient neurodegeneration of Huntington's disease (HD). Memantine, as a glutamate ...receptor antagonist, should counteract this mechanism. Its effectiveness (up to 30 mg/day) with regard to retardation of progression was thus examined in 27 HD patients in a two year, open and multicentre trial. The results suggest that memantine treatment of HD may be useful in terms of retardation of the progression of the disorder.
PDF
