Thalamic Atrophy in Huntington's Disease Co-varies with Cognitive Performance: A Morphometric MRI Analysis

The pattern of motor, behavioral and cognitive symptoms in Huntington's disease (HD) implicates dysfunction of basal-ganglia-thalamo-cortical circuits. This study explored if cognitive performance in HD is correlated with localized cerebral changes. Psychomotor functions were investigated by verbal fluency, Stroop color word and Digit Symbol tests in 44 HD patients and 22 controls. Three-dimensional magnetic resonance imaging (MRI) data were analyzed with regard to regional gray matter changes by use of the observer-independent whole-brain-based approach of voxel-based morphometry (VBM). Using statistical parametric mapping, the MRI data of the HD patients were analyzed in an ANCOVA including the individual results of the neuropsychological tests. Besides striatal areas, symmetrical regional atrophy of the thalamus was found to co-vary significantly with cognitive performance (P < 0.001, corrected for multiple comparisons). In particular, thalamic subnuclei projecting to prefrontal areas (dorsomedial subnucleus) and connected to the striatum (centromedian/parafascicular and ventrolateral nuclear complex) displayed volume loss, in agreement with neuropathological studies. These results suggest that thalamic degeneration contributes in an important way to the impairment of executive function in early HD. Patients who are impaired in executive tests display structural double lesions of the basal-ganglia-thalamo-cortical circuitry both at the striatal and at the thalamic leve

MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

Neuropathological studies revealed the propagation of amyotrophic lateral sclerosis (ALS) in a sequence of four separate disease-related regional patterns. Diffusion tensor imaging (DTI)-based analysis was established for the individual mapping of sequential disease spreading in ALS as the in vivo transfer to neuroimaging. The aim of this review is to summarize cross-sectional and longitudinal results of these technical approaches in ALS as an in vivo tool to image ALS propagation stages. This concept was also applied to restricted phenotypes of ALS, e.g., lower motor neuron disease (LMND) or primary lateral sclerosis (PLS). In summary, the regional disease patterns in the course of ALS have been successfully mapped by DTI in vivo both cross-sectionally and longitudinally so that this technique might have the potential as a read-out in clinical trials

Analysis and Visualization of 3D Motion Data for UPDRS Rating of Patients with Parkinson's Disease

Remote monitoring of Parkinson's Disease (PD) patients with inertia sensors is a relevant method for a better assessment of symptoms. We present a new approach for symptom quantification based on motion data: the automatic Unified Parkinson Disease Rating Scale (UPDRS) classification in combination with an animated 3D avatar giving the neurologist the impression of having the patient live in front of him. In this study we compared the UPDRS ratings of the pronation-supination task derived from: (a) an examination based on video recordings as a clinical reference;(b) an automatically classified UPDRS;and (c) a UPDRS rating from the assessment of the animated 3D avatar. Data were recorded using Magnetic, Angular Rate, Gravity (MARG) sensors with 15 subjects performing a pronation- supination movement of the hand. After preprocessing, the data were classified with a J48 classifier and animated as a 3D avatar. Video recording of the movements, as well as the 3D avatar, were examined by movement disorder specialists and rated by UPDRS. The mean agreement between the ratings based on video and (b) the automatically classified UPDRS is 0.48 and with (c) the 3D avatar it is 0.47. The 3D avatar is similarly suitable for assessing the UPDRS as video recordings for the examined task and will be further developed by the research team

Changes in cortical activation during mirror reading before and after training: an fMRI study of procedural learning

The neural correlates of procedural learning were studied using functional magnetic resonance imaging (fMRI) and the mirror reading paradigm. The aim of the study was to investigate a presumed learning-related change of activation in cortical areas that are involved in the performance of a nonmotor skill. Changes in cortical blood oxygenation contrast were recorded in 10 healthy subjects while they alternatively read visually presented single mirror script words and normal script words. Responses in naive subjects were compared to those acquired after training of mirror script reading. The acquisition volume included the motor and premotor cortex, the parietal lobe and the occipital lobe including its inferior aspects. Striate and extrastriate visual areas, associative parietal cortex and the premotor cortex were bilaterally active during normal and mirror script reading. Significantly stronger activation during mirror reading was seen in BA7 and 40 (parietal associative cortex) and in BA6 (corresponding to the frontal eye fields). Simultaneous eye movement recordings indicated that activation in BA6 was related to processing components other than saccade frequency. After training, BA6 and BA7 exhibited a decrease of activation during mirror reading that significantly exceeded nonspecific changes observed in the normal script control condition. The present findings confirm the hypothesis of practice-related decrease of activation in task-related cortical areas during nonmotor procedural learning

Diffusion tensor imaging and tractwise fractional anisotropy statistics: quantitative analysis in white matter pathology

<p>Abstract</p> <p>Background</p> <p>Information on anatomical connectivity in the brain by measurements of the diffusion of water in white matter tracts lead to quantification of local tract directionality and integrity.</p> <p>Methods</p> <p>The combination of connectivity mapping (fibre tracking, FT) with quantitative diffusion fractional anisotropy (FA) mapping resulted in the approach of results based on group-averaged data, named tractwise FA statistics (TFAS). The task of this study was to apply these methods to group-averaged data from different subjects to quantify differences between normal subjects and subjects with defined alterations of the corpus callosum (CC).</p> <p>Results</p> <p>TFAS exhibited a significant FA reduction especially in the CC, in agreement with region of interest (ROI)-based analyses.</p> <p>Conclusion</p> <p>In summary, the applicability of the TFAS approach to diffusion tensor imaging studies of normal and pathologically altered brains was demonstrated.</p

Electrophysiological Assessment of the Deltoid Muscle after Minimally Invasive Treatment of Proximal Humerus Fractures - A Clinical Observation

The minimal anterolateral acromial approach offers a less invasive access to the proximal humerus. Functional impairment following this procedure may be caused by paresis of the deltoid muscle as a result of iatrogenic injury to the axillary nerve. It was addressed whether electromyography (EMG) of the deltoid muscle gives evidence for an axillary nerve lesion in association with the minimal anterolateral acromial approach

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications:A UK Cost-Effectiveness Analysis

International audienceBackground: Parkinson’s disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective.Methods: We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty.Results: Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values.Conclusion: These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications

Two histological methods for recognition and study of cortical microinfarcts in thick sections

Cortical microinfarcts are the most widespread form of brain infarction but frequently remain undetected by standard neuroimaging protocols. Moreover, microinfarcts are only partially detectable in hematoxylin-eosin-stained (H and E) 4-10 µm paraffin sections at routine neuropathological examination. In this short report, we provide two staining protocols for visualizing cortical microinfarcts in 100-300 µm sections. For low-power microscopy, the first protocol combines aldehyde fuchsine staining for detection of lipofuscin granules and macrophages with Darrow red counterstaining for Nissl material. The second protocol combines collagen IV immunohistochemistry with aldehyde fuchsine/Darrow red or with erythrosin-phosphotungstic acid-aniline blue staining for detailed study of the capillary network. In the first protocol, microinfarcts are recognizable as radially-oriented funnel-like accumulations of aldehyde fuchsine-positive macrophages. The second protocol recognizes microinfarcts and alterations of the capillary network, at whose center accumulations of dead neurons and aldehyde fuchsine-positive macrophages cluster. In addition, the second protocol permits visualization of abnormalities within the capillary network associated with more recent microinfarcts. Both protocols can be useful for comparing MRI datasets with cortical microinfarcts in corresponding whole brain sections of 100-300 µm thickness