Are dopa-responsive dystonia and Parkinson’s disease related disorders? A case report

Objectivel-Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by an excellent response to low dosages of levodopa. DRD patients may also develop Parkinsonism which resembles idiopathic Parkinson’s disease. In classical DRD no changes in the dopaminergic uptake have been observed.MethodsA 65-year old woman presented with clinically remarkably slowly progressing Parkinson’s disease (PD) without any dystonic signs and excellent response to dopaminergic medications. We obtained a [¹²³I] FP-CIT-SPECT (DaTSCAN?) in order to elucidate a striatal dopaminergic deficit.ResultsWe found a reduced uptake in the [¹²³I] FP-CIT-SPECT (DaTSCAN?) contralateral to the more affected body side. Additionally, the patient showed a heterozygous deletion of the GHC1 gene.ConclusionsPatients with mild parkinsonian symptoms, excellent response to low dosages of dopaminergic drugs and a reduced dopamine-transporter uptake in [¹²³I] FP-CIT-SPECT might more commonly be GCH1 mutation carriers than has previously been supposed. PD patients with a positive family history of DRD and combination of these clinical symptoms should be offered genetic counselling and testing for GCH1.     

Development of a methodological approach for the characterization of bioaerosols in exhaust air from pig fattening farms with MALDI-TOF mass spectrometry

In this paper, we evaluated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a cultivation-independent, routinely applicable approach to identify microbial fractions in bioaerosol emission samples. We developed a streamlined protocol in line with the German state-of-the-art impingement sampling guideline. Following isokinetic sampling, a fast and reliable pre-treatment methodology involving a series of cascade filtration steps was implemented, which produced fractions for spectrometric measurement devoid of interfering substances. We sampled the exhaust air from eight pig fattening farms around western Germany, which yielded two sets of samples for both method development and validation. For method development, in total 65 bacterial isolates were produced directly from the exhaust air samples, taxonomically classified by 16S rRNA-Gene sequencing, and subjected to MALDI-TOF analysis. In this way, we could assign fingerprint biomarkers to classified bacterial genera or even species to build up a preliminary reference database. For verification of the novel methodology and application of the reference database, we subjected the second set of exhaust air samples to the developed protocol. Here, 18 out of 21 bacterial species deposited in the database were successfully retrieved, including organisms classified in risk group 2, which might be used to evaluate the pathogenic potential of sampled exhaust air. Overall, this study pursues an entirely new approach to rapidly analyze airborne microbial fractions.     

Increased cortisol levels in cognitively challenging situations are beneficial in young but not older subjects

Rationale  Adaptation to stressful situations changes with increasing age. This is also reflected in age-related differences in effects of acute stress on, e.g., episodic memory. Less is known about age-related differences of the cognitive effects of individual stress responses to challenging situations. Objective  To investigate the influence of the individual cortisol response (as a marker for the individual stress level) on behavioral and neural measures during a challenging memory paradigm. Materials and methods  Twenty young and 12 older subjects were scanned using functional magnetic resonance imaging during encoding and retrieval of spatial contextual information. Salivary cortisol levels were measured before and after scanning. Results  A multiple regression analysis of behavioral data showed an interaction effect of age and cortisol response on memory for the items and their spatial context during retrieval due to increased accuracy with increasing cortisol responses in young compared to old subjects. During encoding, this was reflected in a positive effect of the cortisol response on prefrontal activity in young but not in older subjects. During retrieval, there was a negative effect of the cortisol response on brain activity in the hippocampus and prefrontal regions in older but not in young subjects. Conclusions  The data suggest an increased efficiency to encode items and their context with increasing cortisol responses in young subjects, and a decreased efficiency to retrieve information with increasing cortisol responses in older subjects. We conclude that neuroendocrine responses are differentially associated with behavioral and neural measures in cognitively challenging situations in young and older volunteers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast

Volumetric imaging of dynamic processes with microscopic resolution holds a huge potential in biomedical research and clinical diagnosis. Using supercontinuum light sources and high numerical aperture (NA) objectives, optical coherence tomography (OCT) achieves microscopic resolution and is well suited for imaging cellular and subcellular structures of biological tissues. Currently, the imaging speed of microscopic OCT (mOCT) is limited by the line-scan rate of the spectrometer camera and ranges from 30 to 250 kHz. This is not fast enough for volumetric imaging of dynamic processes in vivo and limits endoscopic application. Using a novel CMOS camera, we demonstrate fast 3-dimensional OCT imaging with 600,000 A-scans/s at 1.8 µm axial and 1.1 µm lateral resolution. The improved speed is used for imaging of ciliary motion and particle transport in ex vivo mouse trachea. Furthermore, we demonstrate dynamic contrast OCT by evaluating the recorded volumes rather than en face planes or B-scans. High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mOCT in vivo. With further increase in imaging speed and integration in flexible endoscopes, volumetric mOCT may be used to complement or partly replace biopsies.     

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS.

Comparison of <Superscript>18</Superscript>F-FET PET and perfusion-weighted MRI for glioma grading: a hybrid PET/MR study

Purpose

Both perfusion-weighted MR imaging (PWI) and O-(2-¹⁸F-fluoroethyl)-L-tyrosine PET (¹⁸F–FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of ¹⁸F–FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner.

Methods

Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with ¹⁸F–FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBR_mean, TBR_max) were calculated. In addition, Time-to-Peak (TTP) and slopes of time–activity curves were calculated for ¹⁸F–FET PET. Diagnostic accuracies of ¹⁸F–FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC).

Results

The diagnostic accuracy of ¹⁸F–FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBR_mean and TBR_max of ¹⁸F–FET PET uptake (0.80, 0.83) and for TBR_mean and TBR_max of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 ± 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy.

Conclusions

Both ¹⁸F–FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by ¹⁸F–FET PET and PWI is based on different pathophysiological phenomena.

     

Early signs of VCP-related frontotemporal dementia: a neuropsychological,FDG-PET and fMRI study

Journal of Neurology -