Showing papers by "Gereon R. Fink published in 2017"

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

Abstract: Neurodegenerative brain changes can affect the functional connectivity strength between nodes of the default-mode network (DMN), which may underlie changes in cognitive performance. It remains unclear how the functional connectivity strength of DMN nodes differs from healthy to pathological aging and whether these changes are cognitively relevant. We used resting-state functional magnetic resonance imaging to investigate the functional connectivity strength across five DMN nodes in 25 healthy controls (HC), 28 subjective cognitive decline (SCD) participants, and 25 prodromal Alzheimer's disease (AD) patients. After identifying the ventral medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), retrosplenial cortex (RSC), inferior parietal lobule, and the hippocampus we investigated the functional strength between DMN nodes using temporal network modeling. Functional coupling of the vmPFC and PCC in prodromal AD patients was disrupted. This vmPFC-PCC coupling correlated positively with memory performance in prodromal AD. Furthermore, the hippocampus de-coupled from posterior DMN nodes in SCD and prodromal AD patients. There was no coupling between the hippocampus and the anterior DMN. Additional mediation analyses indicated that the RSC enables communication between the hippocampus and DMN regions in HC but none of the other two groups. These results suggest an anterior-posterior disconnection and a hippocampal de-coupling from posterior DMN nodes with disease progression. Hippocampal de-coupling already occurring in SCD may provide valuable information for the development of a functional biomarker.

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

Abstract: 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. 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 (TBRmean, TBRmax) 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). The diagnostic accuracy of 18F–FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBRmean and TBRmax of 18F–FET PET uptake (0.80, 0.83) and for TBRmean and TBRmax 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. 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.

Photopenic defects on O-(2-[18F]-fluoroethyl)-L-tyrosine PET: clinical relevance in glioma patients.

Abstract: BACKGROUND O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET has a sensitivity of more than 90% to detect gliomas. In the remaining small fraction of gliomas without increased tracer uptake, some tumors even show photopenic defects whose clinical significance is unclear. METHODS Glioma patients with a negative FET PET scan prior to neuropathological confirmation were identified retrospectively. Gliomas were rated visually as (i) having indifferent FET uptake or (ii) photopenic, if FET uptake was below background activity. FET uptake in the area of signal hyperintensity on the T2/fluid attenuated inversion recovery-weighted MRI was evaluated by mean standardized uptake value (SUV) and mean tumor-to-brain ratio (TBR). The progression-free survival (PFS) of photopenic gliomas was compared with that of gliomas with indifferent FET uptake. RESULTS Of 100 FET-negative gliomas, 40 cases with photopenic defects were identified. Fifteen of these 40 cases (38%) had World Health Organization (WHO) grades III and IV gliomas. FET uptake in photopenic gliomas was significantly decreased compared with both the healthy-appearing brain tissue (SUV, 0.89 ± 0.26 vs 1.08 ± 0.23; P < 0.001) and gliomas with indifferent FET uptake (TBR, 0.82 ± 0.09 vs 0.96 ± 0.13; P < 0.001). Irrespective of the applied treatment, isocitrate dehydrogenase (IDH)-mutated WHO grade II diffuse astrocytoma patients with indifferent FET uptake (n = 25) had a significantly longer PFS than patients with IDH-mutated diffuse astrocytomas (WHO grade II) with photopenic defects (n = 11) (51 vs 24 mo; P = 0.027). The multivariate survival analysis indicated that photopenic defects predict an unfavorable PFS (P = 0.009). CONCLUSION Photopenic gliomas in negative FET PET scans should be managed more actively, as they seem to have a higher risk of harboring a higher-grade glioma and an unfavorable outcome.

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3

Abstract: This work was produced as part of the activities of FAPESP Research, Disseminations and Innovation Center for Neuromathematics (grant 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0).

Disruption of the right temporoparietal junction impairs probabilistic belief updating

Abstract: Generating and updating probabilistic models of the environment is a fundamental modus operandi of the human brain. Although crucial for various cognitive functions, the neural mechanisms of these inference processes remain to be elucidated. Here, we show the causal involvement of the right temporoparietal junction (rTPJ) in updating probabilistic beliefs and we provide new insights into the chronometry of the process by combining online transcranial magnetic stimulation (TMS) with computational modeling of behavioral responses. Female and male participants performed a modified location-cueing paradigm, where false information about the percentage of cue validity (%CV) was provided in half of the experimental blocks to prompt updating of prior expectations. Online double-pulse TMS over rTPJ 300 ms (but not 50 ms) after target appearance selectively decreased participants' updating of false prior beliefs concerning %CV, reflected in a decreased learning rate of a Rescorla-Wagner model. Online TMS over rTPJ also impacted on participants' explicit beliefs, causing them to overestimate %CV. These results confirm the involvement of rTPJ in updating of probabilistic beliefs, thereby advancing our understanding of this area's function during cognitive processing.SIGNIFICANCE STATEMENT Contemporary views propose that the brain maintains probabilistic models of the world to minimize surprise about sensory inputs. Here, we provide evidence that the right temporoparietal junction (rTPJ) is causally involved in this process. Because neuroimaging has suggested that rTPJ is implicated in divergent cognitive domains, the demonstration of an involvement in updating internal models provides a novel unifying explanation for these findings. We used computational modeling to characterize how participants change their beliefs after new observations. By interfering with rTPJ activity through online transcranial magnetic stimulation, we showed that participants were less able to update prior beliefs with TMS delivered at 300 ms after target onset.

An fMRI study into emotional processing in Parkinson's disease: Does increased medial prefrontal activation compensate for striatal dysfunction?

Abstract: Background Apart from a progressive decline of motor functions, Parkinson’s disease (PD) is also characterized by non-motor symptoms, including disturbed processing of emotions. This study aims at assessing emotional processing and its neurobiological correlates in PD with the focus on how medicated Parkinson patients may achieve normal emotional responsiveness despite basal ganglia dysfunction. Methods Nineteen medicated patients with mild to moderate PD (without dementia or depression) and 19 matched healthy controls passively viewed positive, negative, and neutral pictures in an event-related blood oxygen level-dependent functional magnetic resonance imaging study (BOLD-fMRI). Individual subjective ratings of valence and arousal levels for these pictures were obtained right after the scanning. Results Parkinson patients showed similar valence and arousal ratings as controls, denoting intact emotional processing at the behavioral level. Yet, Parkinson patients showed decreased bilateral putaminal activation and increased activation in the right dorsomedial prefrontal cortex (PFC), compared to controls, both most pronounced for highly arousing emotional stimuli. Conclusions Our findings revealed for the first time a possible compensatory neural mechanism in Parkinson patients during emotional processing. The increased medial PFC activity may have modulated emotional responsiveness in patients via top-down cognitive control, therewith restoring emotional processing at the behavioral level, despite striatal dysfunction. These results may impact upon current treatment strategies of affective disorders in PD as patients may benefit from this intact or even compensatory influence of prefrontal areas when therapeutic strategies are applied that rely on cognitive control to modulate disturbed processing of emotions.

Spatial Attention, Motor Intention, and Bayesian Cue Predictability in the Human Brain.

Abstract: Predictions about upcoming events influence how we perceive and respond to our environment. There is increasing evidence that predictions may be generated based upon previous observations following Bayesian principles, but little is known about the underlying cortical mechanisms and their specificity for different cognitive subsystems. The present study aimed at identifying common and distinct neural signatures of predictive processing in the spatial attentional and motor intentional system. Twenty-three female and male healthy human volunteers performed two probabilistic cueing tasks with either spatial or motor cues while lying in the fMRI scanner. In these tasks, the percentage of cue validity changed unpredictably over time. Trialwise estimates of cue predictability were derived from a Bayesian observer model of behavioral responses. These estimates were included as parametric regressors for analyzing the BOLD time series. Parametric effects of cue predictability in valid and invalid trials were considered to reflect belief updating by precision-weighted prediction errors. The brain areas exhibiting predictability-dependent effects dissociated between the spatial attention and motor intention task, with the right temporoparietal cortex being involved during spatial attention and the left angular gyrus and anterior cingulate cortex during motor intention. Connectivity analyses revealed that all three areas showed predictability-dependent coupling with the right hippocampus. These results suggest that precision-weighted prediction errors of stimulus locations and motor responses are encoded in distinct brain regions, but that crosstalk with the hippocampus may be necessary to integrate new trialwise outcomes in both cognitive systems. SIGNIFICANCE STATEMENT The brain is able to infer the environments9 statistical structure and responds strongly to expectancy violations. In the spatial attentional domain, it has been shown that parts of the attentional networks are sensitive to the predictability of stimuli. It remains unknown, however, whether these effects are ubiquitous or if they are specific for different cognitive systems. The present study compared the influence of model-derived cue predictability on brain activity in the spatial attentional and motor intentional system. We identified areas with distinct predictability-dependent activation for spatial attention and motor intention, but also common connectivity changes of these regions with the hippocampus. These findings provide novel insights into the generality and specificity of predictive processing signatures in the human brain.

Age-related changes in oscillatory power affect motor action.

Abstract: With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum) as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC). This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

New onset status epilepticus in older patients: Clinical characteristics and outcome

Abstract: Purpose We here evaluated (1) the differential characteristics of status epilepticus (SE) in older (≥60 years) compared to younger adults (18–59 years). In particular, we were interested in (2) the proportion and characteristics of new onset SE in patients with no history of epilepsy (NOSE) in older compared to younger adults, and (3) predictive parameters for clinical outcome in older subjects with NOSE. Methods We performed a monocentric retrospective analysis of all adult patients (≥18years) admitted with SE to our tertiary care centre over a period of 10 years (2006–2015) to evaluate clinical characteristics and short-time outcome at discharge. Results One-hundred-thirty-five patients with SE were included in the study. Mean age at onset was 64 years (range 21–90), eighty-seven of the patients (64%) were older than 60 years. In 76 patients (56%), SE occurred as NOSE, sixty-seven percent of them were aged ≥60 years. There was no age-dependent predominance for NOSE. NOSE was not a relevant outcome predictor, especially regarding age-related subgroups. Older patients with NOSE had less frequently general tonic clonic SE (GTCSE; p=0.001) and were more often female (p=0.01). Regarding outcome parameters and risk factors in older patients with NOSE, unfavourable outcome was associated with infections during in-hospital treatment (0.04), extended stay in ICU (p=0.001), and generally in hospital (p Conclusion In our cohort, older patients represented the predominant subgroup in patients with SE. Older patients suffered more often from non-convulsive semiology and had a less favourable short-time outcome. NOSE was not a predictive outcome parameter in older patients. Data suggest that avoiding infections should have a priority because higher infection rates were associated with unfavourable outcome.

Frontostriatal contribution to the interplay of flexibility and stability in serial prediction

Abstract: Surprising events may be relevant or irrelevant for behavior, requiring either flexible adjustment or stabilization of our model of the world and according response strategies. Cognitive flexibility and stability in response to environmental demands have been described as separable cognitive states, associated with activity of striatal and lateral prefrontal regions, respectively. It so far remains unclear, however, whether these two states act in an antagonistic fashion and which neural mechanisms mediate the selection of respective responses, on the one hand, and a transition between these states, on the other. In this study, we tested whether the functional dichotomy between striatal and prefrontal activity applies for the separate functions of updating in response to changes in the environment, i.e., switches and shielding in response to chance occurrences of events violating expectations, i.e., drifts of current predictions. We measured brain activity using fMRI while 20 healthy participants performed a task that required to serially predict upcoming items. Switches between predictable sequences had to be indicated via button press while sequence omissions drifts had to be ignored. We further varied the probability of switches and drifts to assess the neural network supporting the transition between flexible and stable cognitive states as a function of recent performance history in response to environmental demands. Flexible switching between models was associated with activation in medial pFC BA 9 and BA 10, whereas stable maintenance of the internal model corresponded to activation in the lateral pFC BA 6 and inferior frontal gyrus. Our findings extend previous studies on the interplay of flexibility and stability, suggesting that different prefrontal regions are activated by different types of prediction errors, dependent on their behavioral requirements. Furthermore, we found that striatal activation in response to switches and drifts was modulated by participants' successful behavior toward these events, suggesting the striatum to be responsible for response selections following unpredicted stimuli. Finally, we observed that the dopaminergic midbrain modulates the transition between different cognitive states, thresholded by participants' individual performance history in response to temporal environmental demands.

Spatiotopic updating of visual feature information.

Abstract: Saccades shift the retina with high-speed motion. In order to compensate for the sudden displacement, the visuomotor system needs to combine saccade-related information and visual metrics. Many neurons in oculomotor but also in visual areas shift their receptive field shortly before the execution of a saccade (Duhamel, Colby, & Goldberg, 1992; Nakamura & Colby, 2002). These shifts supposedly enable the binding of information from before and after the saccade. It is a matter of current debate whether these shifts are merely location based (i.e., involve remapping of abstract spatial coordinates) or also comprise information about visual features. We have recently presented fMRI evidence for a feature-based remapping mechanism in visual areas V3, V4, and VO (Zimmermann, Weidner, Abdollahi, & Fink, 2016). In particular, we found fMRI adaptation in cortical regions representing a stimulus' retinotopic as well as its spatiotopic position. Here, we asked whether spatiotopic adaptation exists independently from retinotopic adaptation and which type of information is behaviorally more relevant after saccade execution. We first adapted at the saccade target location only and found a spatiotopic tilt aftereffect. Then, we simultaneously adapted both the fixation and the saccade target location but with opposite tilt orientations. As a result, adaptation from the fixation location was carried retinotopically to the saccade target position. The opposite tilt orientation at the retinotopic location altered the effects induced by spatiotopic adaptation. More precisely, it cancelled out spatiotopic adaptation at the saccade target location. We conclude that retinotopic and spatiotopic visual adaptation are independent effects.

Neural correlates underlying the attentional spotlight in human parietal cortex independent of task difficulty

Abstract: Changes in the size of the attentional focus and task difficulty often co-vary. Nevertheless, the neural processes underlying the attentional spotlight process and task difficulty are likely to differ from each other. To differentiate between the two, we parametrically varied the size of the attentional focus in a novel behavioral paradigm while keeping visual processing difficulty either constant or not. A behavioral control experiment proved that the present behavioral paradigm could indeed effectively manipulate the size of the attentional focus per se, rather than affecting purely perceptual processes or surface processing. Imaging results showed that neural activity in a dorsal frontoparietal network, including right superior parietal cortex (SPL), was positively correlated with the size of the attentional spotlight, irrespective of whether task difficulty was constant or varied across different sizes of attentional focus. In contrast, neural activity in the ventral frontoparietal network, including the right inferior parietal cortex (IPL), was positively correlated with increasing task difficulty. Data suggest that sub-regions in parietal cortex are differentially involved in the attentional spotlight process and task difficulty: while SPL was involved in the attentional spotlight process independent of task difficulty, IPL was involved in the effect of task difficulty independent of the attentional spotlight process. Hum Brain Mapp 38:4996-5018, 2017. © 2017 Wiley Periodicals, Inc.

Incomplete Large Vessel Occlusions in Mechanical Thrombectomy: An Independent Predictor of Favorable Outcome in Ischemic Stroke.

Abstract: Background and Purpose: Cerebral large vessel occlusion (LVO) in acute ischemic stroke (AIS) may be complete (CLVO) or incomplete (ILVO). The influence of ILVO on clinical outcome after mechanical thrombectomy (MT) remains unclear. We investigated primarily the clinical outcome in patients with AIS due to ILVO or CLVO. Methods: Five hundred three consecutive AIS patients with LVO treated with stent-retriever or direct aspiration-based MT between 2010 and 2016 were analyzed. The primary endpoint was favorable clinical outcome (modified Rankin Scale ≤2) at 90 days; secondary endpoints were periprocedural parameters. Results: Forty-nine patients (11.3%) with a median National Institutes of Health Stroke Scale (NIHSS) of 11 presented with ILVO and the remainder presented with CLVO and median NIHSS of 15 (p < 0.001). The median groin puncture-to-reperfusion time was 30 vs. 67 min, respectively (p < 0.001). Successful reperfusion was reached in 47 out of 49 ILVO (95.9%) vs. 298 out of 381 CLVO (78.2%; p < 0.005) with less retrieval maneuvers (1.7 ± 2.2 vs. 3.0 ± 2.5; p < 0.001). The favorable outcome at 90 days was 81% in patients with ILVO vs. 29.1% in CLVO (p < 0.001); respective all-cause mortality rates were 6.4 vs. 28.5% (p < 0.001). Periprocedural complications (6.9%) occurred exclusively in CLVO patients (p < 0.05). ILVO was associated with favorable clinical outcome independent of age and NIHSS in multivariate logistic regression both in the anterior (OR 3.6; 95% CI 1.8-6.9; p < 0.001) and posterior circulation (OR 3.5; 95% CI 1.8-6.9; p < 0.001). Conclusions: AIS due to ILVO is frequent and is associated with a nearly threefold higher chance of favorable clinical outcome at 90 days, independent of age and initial NIHSS compared to CLVO.

Lymphocyte antigens targetable by monoclonal antibodies in non-systemic vasculitic neuropathy

Abstract: Objective To identify the most relevant antigens for monoclonal antibodies in lymphocytic infiltrates in non-systemic vasculitic neuropathy (NSVN). Background Current immunosuppressive treatment for NSVN is insufficient. Monoclonal antibodies might be a treatment option, but the expression profile for targetable antigens on lymphocytic infiltrates in NSVN is unknown. Methods Sural nerve biopsies from a cohort of patients with NSVN were immunohistochemically studied for the expression of potential candidate antigens in perivascular and intramural lymphocytic infiltrates and correlated with neurological and electrophysiological parameters. 20 patients with treatment naive NSVN and 5 patients with idiopathic axonal neuropathy were included. Results The CD52, BAFF and CD49d antigens were expressed in epineurial, perivascular or intramural lymphocytes of all (20/20) patients. CD52 was most prominently expressed in 21.49% of all inflammatory infiltrates. BAFF and CD49d were detected in 11.25% and 10.99% of these lymphocytes, respectively. The CD20, CD25 and CD126 antigens were found less frequently and at low levels only (CD20: 10/20 patients, 5.84% of lymphocytes; CD25: 17/20 patients, 5.22% of lymphocytes; CD126: 3/20 patients, 0.15% of lymphocytes). Conclusion This is the first study in NSVN that identifies antigens expressed by pathogenic lymphocytes, which are potential targets for future monoclonal antibody treatment. Our data suggest that NSVN is amenable to monoclonal antibodies and, moreover, that targeting CD52 may be particularly promising. Our results strongly warrant future clinical trials in NSVN with monoclonal antibodies.

New Structures in Neurology: Palliative Care for Neurological Patients

Abstract: Although patients with incurable neurological diseases suffer from a variety of distressing symptoms and may die from their neurological condition and associated complications, palliative and hospice care for these patients to date remains rare. Initial estimates indicate that on average 10% of all patients suffering from a neurological disease need palliative and hospice care. However, within German neurology departments, only few physicians (on average 1.3/department) and nurses (on average 2.2./department) are specialized in palliative and hospice care and only about 3% of patients cared for in palliative or hospice care structures suffer from neurological diseases (in contrast to the approximately 80% of patients suffering from oncological diseases). This rather low number is due to the gradual increase in the awareness of palliative and hospice care needs for neurological patients and a currently predominant supply of oncological patients in palliative and hospice care structures that are primarily aimed at these patients. Correspondingly, the special aspects of neurological patients are currently not adequately addressed in the palliative training curricula of healthcare professionals. Rather, patients with advanced neurological conditions are medically cared for by general practitioners and by the existing inpatient and outpatient neurology structures, which may also offer sub-specialty services. Consequently, adequate care for severely affected neurological patients becomes difficult as soon as these patients are hardly able to visit these structures because home-based specialist treatment is currently rendered and financed only to a limited degree. Novel yet to date rare approaches, mostly of international origin, suggest that these patients may benefit from specialized home-based services, combining neurological and palliative care expertise. At present, data that characterizes the situation of neuro-palliative care in Germany remains scarce. In addition to the already known supply gaps (e. g., low rate of neurologists trained in palliative medicine as well as of nurses working in neurology trained in palliative care, lack of consideration of the specific (care) needs of neurological patients in general and specialized palliative and hospice care structures, few available home-based outpatient specialists) research is a prerequisite to identify current gaps in palliative care of neurological patients in more detail and how these might be overcome in the future.

Brain Glucose Metabolism in Parry-Romberg Syndrome.

Abstract: Parry-Romberg syndrome is a rare disorder characterized by a progressive facial hemiatrophy of the skin, subcutaneous tissue, musculature, bone, and cartilage. It is often associated with neurological symptoms such as trigeminal neuropathy, paresthesia of the face, migraine, and seizures and can be paired with ocular problems and ipsilateral progressive body atrophy. Here, we present a young woman with progressive facial hemiatrophy, who was referred for FDG-PET/CT. Hypometabolism was observed in the left cingulate and postcentral gyrus, left cerebellum, and right basal ganglia. Hypometabolism may be observed before anatomical changes and therefore facilitate early diagnosis.

Palliativmedizinische Versorgung neurologischer Patienten

Abstract: Obwohl Patienten mit unheilbar neurologischen Erkrankungen oftmals unter belastenden Symptomen leiden und an ihren Erkrankungen und damit einhergehenden Komplikationen versterben konnen, werden diese bislang noch zu selten unter palliativmedizinischen/hospizlichen Gesichtspunkten behandelt. Erste Schatzungen sehen bei durchschnittlich 10 % der neurologischen Patienten Bedarf fur eine palliativmedizinische/hospizliche Versorgung. Gleichwohl gibt es innerhalb neurologischer Abteilungen nur wenige Arzte (im Durchschnitt 1,3/Abteilung) bzw. Pflegekrafte (im Durchschnitt 2,2/Abteilung), die auf diesem Gebiet weitergebildet sind, und nur ca. 3 % der Patienten, die in spezialisierten palliativmedizinischen/hospizlichen Strukturen versorgt werden, leiden unter neurologischen Grunderkrankungen (im Gegensatz zu Patienten mit onkologischen Grunderkrankungen, ca. 80 %). Fur diese niedrige Zahl verantwortlich ist neben einem erst allmahlich wachsenden Bewusstsein fur palliativmedizinische/hospizliche Bedarfe neurologisch Erkrankter eine derzeit uberwiegende Versorgung onkologischer Patienten in Palliativ-/Hospizstrukturen, die entsprechend primar auf letztere Patienten ausgerichtet sind. Passend dazu werden die besonderen Aspekte der Palliativversorgung neurologischer Patienten in den palliativen Aus- und Weiterbildungscurricula der Gesundheitsberufe derzeit nicht ausreichend berucksichtigt. Fortgeschritten neurologisch erkrankte Patienten sind deswegen neben der hausarztlichen Grundversorgung oft darauf angewiesen, dass sie weiter facharztlich, ggf. auch in Spezialsprechstunden/-kliniken versorgt werden. Eine bedarfsgerechte Versorgung schwer betroffener neurologischer Patienten wird hierdurch erschwert, insbesondere wenn sie nur schwerlich in der Lage sind, diese stationaren und ambulanten Einrichtungen aufzusuchen, da hausliche facharztliche Behandlung derzeit nur eingeschrankt durchgefuhrt und finanziert wird. Erste noch wenig beforschte Ansatze, zumeist internationaler Herkunft, legen nahe, dass gerade diese Patienten von einer spezialisierten, hauslich-orientierten neurologisch-palliativmedizinischen Versorgung profitieren konnten. In Deutschland gibt es hierzu jedoch bislang kaum Daten. Uber die bislang bekannten Versorgungsdefizite (z. B. niedrige Rate an palliativmedizinisch weitergebildeten Neurologen oder Fachpflegekraften im neurologischen Bereich mit Palliative-Care-Weiterbildung, fehlende Berucksichtigung der spezifischen Versorgungsbedarfe und besonderen Bedurfnisse neuropalliativer Patienten in den Angeboten der allgemeinen und spezialisierten Palliativ- und Hospizversorgung, kaum vorhandene aufsuchende ambulante facharztliche Tatigkeit) hinaus besteht ein hoher Forschungsbedarf, wie neurologische Patienten mit palliativen Bedarfen im deutschen Gesundheitssystem aktuell im Detail versorgt werden, welche Versorgungslucken bestehen und wie bedarfsgerechte, adaquate Versorgungsstrukturen fur schwer betroffene neurologische Patienten geschaffen werden konnen.

Retraction Statement. Paper ‘Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial' by Sato et al. Cerebrovasc Dis 2005;20:187-192

Abstract: We wish to retract the paper entitled ‘Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial’ [Cerebrovasc Dis 2005;20:187–192] by Y. Sato, J. Iwamoto, T. Kanoko and K. Satoh as a result of concerns about data integrity and scientific misconduct which have been brought to our attention. For further information see also http://retractionwatch.com/2016/11/09/analysis-casts-doubt-on-bone-researchers-body-of-work/. M.G. Hennerici, Editor-in-Chief M. Fatar, Managing Editor Published online: September 23, 2017

„Therapierefraktäre Polymyositis“ – stimmt die Diagnose?

Abstract: Wir berichten uber eine 32-jahrige Patientin mit einer progredienten proximal betonten Tetraparese und deutlich erhohten CK-Werten (bis 80000 U/l) Bei Nachweis von entzundlichen Veranderungen in der Muskelbiopsie wurde unter Annahme einer Polymyositis eine immunsuppressive Therapie erfolglos durchgefuhrt In der humangenetischen Diagnostik konnte eine bisher nicht bekannte homozygote Mutation im Dysferlin-Gen nachgewiesen werden Auch degenerative Erkrankungen (Muskeldystrophien), wie z B eine Dysferlinopathie, konnen mit ausgepragten entzundlichen Veranderungen einhergehen