Effective inhaler therapy requires correct handling of the inhaler, including being able to prepare the inhaler for use. Motor function impairment and cognitive disabilities, may impose problems on patients with Parkinson's disease when they have to prepare medication, such as inhalers, for use. The aim of the present study was to examine whether Parkinson's patients are able to correctly prepare the Cyclops inhaler for use. At first, 12 patients, 6 in an off state and 6 in an on state, were asked to open 5 inhalers with ascending peel resistance of the cover foil. It was investigated up to which peel resistance they were able to successfully pull the foil from the inhaler. For the second part of the study, 48 participants, 24 on and 24 off, were asked to open 2 pouches and the 2 inhalers selected in part 1. For pouch 1, 70.8% of the patients in an on state and 58.3% in an off state were able to open the pouch correctly. For pouch 2, this was 79.2% and 75.0%, respectively. Both Cyclops inhalers were opened correctly by 95.8% of the participants in the on state and 91.7% of the participants in the off state.

Objectives: Disease patterns (DP) derived from the scaled subprofile model, a principal component analysis based method (SSM/PCA), have been used to successfully identify Alzheimer’s disease (AD) patients based on 18F-FDG PET scans. In the current study, a similar approach was explored with parametric images derived from pharmacokinetic analysis of 11C-Pittsbough Compound B (PIB) to generate DPs based on different imaging characteristics of the disease. Methods: Pharmacokinetic modeling using the simplified reference tissue model 2 was applied to the dynamic PIB-PET scans of 30 subjects (15 AD and 15 healthy controls). Parametric images of binding potential (BPND) and relative influx of tracer (R1) were used to construct metric-specific DPs. Then Z-scores were assigned to the images based on its similarities with these DPs. Moreover, the subjects were classified based on a specific threshold derived from receiver-operator characteristic curves. Finally, a set of 32 different subjects diagnosed with AD (n = 4), Lewy body dementia (DLB) (n = 5), frontal temporal dementia (FTD) (n = 5), or mild cognitive impairment (MCI) with (+) (n = 11) or without (-) (n = 7) deposits of amyloid-β plaques, were tested against the DPs. Results: Visual inspection of the DPs generated for each method were in line with previous studies: a higher binding (BPND images) and hypoperfusion (R1) were observed in multiple gray matter regions of AD, as compared to healthy subjects. The Z-score threshold for classifying AD patients based on BPND and R1 parametric maps were, respectively, 4.3 (area under the curve (AUC) = 1) and 1.3 (AUC = 0.9). Figure 1 shows the distribution of the Z-scores of the testing subjects. The AD group, as expected, presented an average value above the threshold, of 6.9 ± 6.8 (mean ± SD) for the BPND and 2.0 ± 1.7 for the R1. Meanwhile, the MCI- and DLB groups both presented mean Z-scores smaller than the thresholds (for the DLB group, BPND was of 0.7 ± 1.0 and R1 was 1.0 ± 0.8, and for the MCI-, 0.7 ± 3.1 and 0.8 ± 1.2 respectively). The MCI+ group presented a similar BPND pattern as the AD subjects, with a mean of 14.4 ± 7.2, but the same did not apply to the R1, with a mean of 0.6 ± 0.6. Interestingly, an opposite effect was observed in the FTD group, with high R1 Z-scores (2.1 ± 1.4), and low BPND (–0.4 ± 0.2). Conclusions: Pharmacokinetic modeling of dynamic PIB-PET scans provide high-quality parametric maps, such as BPND and R1, that provide complimentary information. These images can be used as input for a SSM/PCA analysis, resulting in DPs that demonstrate different characteristic of AD patients when compared to healthy subjects. The multiparametric combination of these parametric images showed to be effective for a better discrimination of AD from other dementias.

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3). Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [F-18]-Fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy. Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (rho = 0.72; P = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (rho = 0.51; P = 0.04, uncorrected for multiple comparisons). Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.

A reduction in goal-directed behavior, or apathy, occurs in neurological and psychiatric disorders, though its neural substrates remain unclear. Deficits in circuits connecting the prefrontal cortex to subcortical regions are considered to underlie apathy. Although apathy is empirically associated with widespread changes in these regions, studies across disorders also link apathy with the lateral parietal cortex. Such variety in regional involvement is consistent with the established role of prefrontal and subcortical regions in models of goal-directed behavior, and with the suggestion of subtypes of apathy. However, these models do not provide a basis for the involvement of the lateral parietal cortex with apathy. Here, we review the association between lateral parietal cortex dysfunction and apathy across disorders and analyze the putative cognitive functions that may link this region with goal-directed behavior. We suggest that neural processes in the angular and supramarginal gyri of the inferior parietal lobule may provide an interface enabling the transformation of internal goals to external actions through intentional initiation of action interrelated with mechanisms of primary sensorimotor transformation. Consequently, we propose that impairment in this process of embedding intended action in a ‘body schema’ facilitating adequate recruitment of an effector system, is the likely mechanism underlying the association between the lateral parietal cortex and apathy. Considering the evidence, we propose a revised neurocognitive model of apathy where deficient internal initiation of behavior mediated by the inferior parietal lobule may be sufficient, though not necessary, to reduce goal-directed behavior, and may constitute a volitional subtype of apathy.

BACKGROUND We describe the phenomenon of crossed cerebellar diaschisis (CCD) in four subjects diagnosed with Alzheimer's disease (AD) according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, in combination with 18F-FDG PET and 11C-PiB PET imaging. METHODS 18F-FDG PET showed a pattern of cerebral metabolism with relative decrease most prominent in the frontal-parietal cortex of the left hemisphere and crossed hypometabolism of the right cerebellum. 11C-PiB PET showed symmetrical amyloid accumulation, but a lower relative tracer delivery (a surrogate of relative cerebral blood flow) in the left hemisphere. CCD is the phenomenon of unilateral cerebellar hypometabolism as a remote effect of supratentorial dysfunction of the brain in the contralateral hemisphere. The mechanism implies the involvement of the cortico-ponto-cerebellar fibers. The pathophysiology is thought to have a functional or reversible basis but can also reflect in secondary morphologic change. CCD is a well-recognized phenomenon, since the development of new imaging techniques, although scarcely described in neurodegenerative dementias. RESULTS To our knowledge this is the first report describing CCD in AD subjects with documentation of both 18F-FDG PET and 11C-PiB PET imaging. CCD in our subjects was explained on a functional basis due to neurodegenerative pathology in the left hemisphere. There was no structural lesion and the symmetric amyloid accumulation did not correspond with the unilateral metabolic impairment. CONCLUSION This suggests that CCD might be caused by non-amyloid neurodegeneration. The pathophysiological mechanism, clinical relevance and therapeutic implications of CCD and the role of the cerebellum in AD need further investigation.

Background: Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown. Methods: We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)). Results: Poor inter-rater agreement was found for phenotype and stimulus sensitivity (κ = –0.05), moderate agreement for localization (κ = 0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC) = 0.64) and almost perfect agreement for the UMRS (ICC = 0.82). Discussion: Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.

The delay associated with cerebral processing time implies a lack of real-time representation of changes in the observed environment. To bridge this gap for motor actions in a dynamical environment, the brain uses predictions of the most plausible future reality based on previously provided information. To optimise these predictions, adjustments to actual experiences are necessary. This requires a perceptual memory buffer. In our study we gained more insight how the brain treats (real-time) information by comparing cerebral activations related to judging past-, present- and future locations of a moving ball, respectively. Eighteen healthy subjects made these estimations while fMRI data was obtained. All three conditions evoked bilateral dorsal-parietal and premotor activations, while judgment of the location of the ball at the moment of judgment showed increased bilateral posterior hippocampus activation relative to making both future and past judgments at the one-second time-sale. Since the condition of such 'real-time' judgments implied undistracted observation of the ball's actual movements, the associated hippocampal activation is consistent with the concept that the hippocampus participates in a top-down exerted sensory gating mechanism. In this way, it may play a role in novelty (saliency) detection.

We investigated simple directional hand movements based on different degrees of muscle co-activity, at behavioral and cerebral level in healthy subjects and Parkinson's disease (PD) patients. We compared "singular" movements, dominated by the activity of one agonist muscle, to "composite" movements, requiring conjoint activity of multiple muscles, in a center-out (right hand) step-tracking task. Behavioral parameters were obtained by EMG and kinematic recordings. fMRI was used to investigate differences in underlying brain activations between PD patients (N = 12) and healthy (age-matched) subjects (N = 18). In healthy subjects, composite movements recruited the striatum and cortical areas comprising bilaterally the supplementary motor area and premotor cortex, contralateral medial prefrontal cortex, primary motor cortex, primary visual cortex, and ipsilateral superior parietal cortex. Contrarily, the ipsilateral cerebellum was more involved in singular movements. This striking dichotomy between striatal and cortical recruitment vs. cerebellar involvement was considered to reflect the complementary roles of these areas in motor control, in which the basal ganglia are involved in movement selection and the cerebellum in movement optimization. Compared to healthy subjects, PD patients showed decreased activation of the striatum and cortical areas in composite movement, while performing worse at behavioral level. This implies that PD patients are especially impaired on tasks requiring highly tuned muscle co-activity. Singular movement, on the other hand, was characterized by a combination of increased activation of the ipsilateral parietal cortex and left cerebellum. As singular movement performance was only slightly compromised, we interpret this as a reflection of increased visuospatial processing, possibly as a compensational mechanism.

Background: To deal with processing-time in the nervous system, visuomotor control requires anticipation. An index for such anticipation is provided by the 'flash-lag illusion' in which moving objects are perceived ahead of static objects while actually being in the same place. We investigated the neurophysiological relation between visuomotor anticipation and motor velocity in Parkinson's disease (PD) and controls.Methods: Motor velocity was assessed by the number of keystrokes in 30s ('kinesia score') and visuomotor anticipation in a behavioural flash-lag paradigm while electroencephalography data was obtained. PD patients (n = 24) were divided in a 'PDslow' and a 'PDfast' group based on kinesia score.Results: The PDslow group had a lower kinesia score than controls (resp. 40.3 +/- 1.7 and 64.9 +/- 4.6, p < 0.001). The flash-lag illusion was weaker in the PDslow group than in controls (resp. fractions 0.32 +/- 0.04 and 0.50 +/- 0.09 of the responses indicating perceived lagging, p = 0.03). Furthermore, the magnitude of the flash-lag illusion correlated with the kinesia score (cc = 0.45, p = 0.02). Finally, electroencephalography background frequency was lower in the PDslow group than in controls (resp 8.24 +/- 0.24 and 9.1 +/- 032 Hz, p = 0.01) and background frequency correlated with the kinesia score (cc = 0.58, p = 0.001).Conclusions: The decreased flash-lag illusion and lower electroencephalography background frequency in more bradykinetic PD patients provides support for disturbed visuomotor anticipations, putatively caused by reduced, sub-cortically mediated, network efficiency. This suggests a link between anticipation in early-stage visual motion processing and motor preparation. (C) 2015 Elsevier Ltd. All rights reserved.

The supplementary motor area (SMA) syndrome is a characteristic neurosurgical syndrome that can occur after unilateral resection of the SMA. Clinical symptoms may vary from none to a global akinesia, predominantly on the contralateral side, with preserved muscle strength and mutism. A remarkable feature is that these symptoms completely resolve within weeks to months, leaving only a disturbance in alternating bimanual movements. In this review we give an overview of the old and new insights from the SMA syndrome and extrapolate these findings to seemingly unrelated diseases and symptoms such as Parkinson's disease (PD) and tics. Furthermore, we integrate findings from lesion, stimulation and functional imaging studies to provide insight in the motor function of the SMA.

A young woman known with end-stage heart failure and renal and liver abnormalities underwent cardiopulmonary resuscitation. Seven hours after administration of 1.2mg/kg of rocuronium, acceleromyography still showed a complete neuromuscular block. After administration of rocuronium-antagonist sugammadex (16mg/kg), she could promptly move upon commands. Several of the published risk factors for block prolongation were present in our patient. To our knowledge, this is the first time that sugammadex reversed an extremely prolonged rocuronium-induced neuromuscular block. This case underscores the importance of recognizing neuromuscular block prolongation in ICU patients. In such instances testing for the presence of residual paralysis and the administration of sugammadex as a novel direct antagonist for rocuronium should be considered.