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Given the inconsistent results in the past, there is an ongoing debate whether and how deep brain stimulation in the subthalamic nucleus modifies cognitive control processes like response inhibition in persons with Parkinson’s disease. In this study, we examined how the location of the stimulation volume within the subthalamic nucleus affects the performance in an antisaccade task but also how its structural connectivity is related to response inhibition. Antisaccade error rates and latencies were collected in 14 participants on and off deep brain stimulation in a randomized order. Stimulation volumes were computed based on patient-specific lead localizations using preoperative MRI and postoperative CT scans. Structural connectivity of the stimulation volumes with pre-defined cortical oculomotor control regions as well as whole-brain connectivity was estimated using a normative connectome. We showed that the detrimental effect of deep brain stimulation on response inhibition, measured as antisaccade error rate, depended upon the magnitude of the intersection of volumes of activated tissue with the non-motor subregion of the subthalamic nucleus and on its structural connectivity with regions of the prefrontal oculomotor network including bilateral frontal eye fields and right anterior cingulate cortex. Our results corroborate previous recommendations for avoidance of stimulation in the ventromedial non-motor subregion of the subthalamic nucleus which connects to the prefrontal cortex to prevent stimulation-induced impulsivity. Furthermore, antisaccades were initiated faster with deep brain stimulation when the stimulation volume was connected to fibres passing the subthalamic nucleus laterally and projecting onto the prefrontal cortex, indicating that improvement of voluntary saccade generation with deep brain stimulation may be an off-target effect driven by stimulation of corticotectal fibres directly projecting from the frontal and supplementary eye fields onto brainstem gaze control areas. Taken together, these findings could help implement individualized circuit-based deep brain stimulation strategies that avoid impulsive side effects while improving voluntary oculomotor control.

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence. Introduction: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. Methods: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. Results: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. Conclusion: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Introduction Gaucher disease (GD) is a monogenic, lysosomal storage disorder, classified according to the presence of acute (type 2), chronic (type 3), or no (type 1) neurological manifestations. The Norrbottnian subtype of neuronopathic GD type 3 (GD3) is relatively frequent in the northern part of Sweden. It exhibits a wide range of neurological symptoms but is characterized by extended life expectancy compared to GD3 in other countries. The aim of our study was to describe the cognitive profile of adult patients with Norrbottnian GD3. Materials and Methods Ten patients with GD3 (five males and five females) underwent neurocognitive testing with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RBANS consists of different short tests that assess Immediate Memory, Visuospatial and Constructional function, Language, Attention, and Delayed Memory. General neurological symptoms of the patients were assessed with the modified severity scoring tool. Results Patients (median age 41.5 range 24–57) performed lower than average in all cognitive domains. The overall index score was low (median 58.5, Interquartile range [IQR] 25.5), with the most profound deficit in attention (median 57, IQR 32.5) and immediate memory (median 76.5, IQR 13). Higher scores were found in language (median 83, IQR 21.5), delayed memory (median 81, IQR 41), and visuospatial/constructional function (median 86, IQR 32.35). Conclusion Norrbottnian GD3 patients showed a unique neurocognitive profile with low overall performance, mostly derived from low scores in attention and memory domains whereas language and visuospatial/constructional ability were relatively spared.

Saccade performance has been reported to be altered in Parkinson's disease (PD), however, with a large variability between studies as both motor and cognitive impairment interfere with oculomotor control. The aim of this study was to identify different patterns in saccade alterations in PD using a data-driven approach and to explore their relationship with cognitive phenotypes. Sixty-one participants with PD and 25 controls performed eye-tracking (horizontal and vertical prosaccades, antisaccades) and neuropsychological testing. Hierarchical cluster analysis was applied to the eye-tracking data to subsequently compare the clusters based on demographical, clinical and cognitive characteristics. The three identified clusters of saccade alterations differed in cognitive profiles from healthy controls, but not in PD-related motor symptoms or demographics. The rate of directive errors in the antisaccade task was increased in clusters 1 and 2. Further, cluster 1 was defined by a general disinhibition of reflexive saccades and executive dysfunction in the neuropsychological evaluation. In cluster 2, prolonged saccade latencies and hypometria were accompanied by multidomain cognitive impairment. The cluster 3 showed increased antisaccade latency and vertical hypometria despite lack of evidence for cognitive impairment. Our results suggest that there may be at least two opposing patterns of saccade alterations associated with cognitive impairment in PD, which may explain some of the contradictory results of previous studies.

Postural instability marks one of the most disabling features of Parkinson's disease (PD), but it only reveals itself after affected brain areas have already been significantly damaged. Thus there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their center of pressure and their full-body motion, from which we also extracted the center of mass. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants' bodies. Patients exhibited significantly higher sway amplitudes as compared with the control subjects. However, their sway was phase locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by phase locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase locking (PL) across the body revealed a shift of the highest PL values from the upper body toward the hip region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired motor control, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.

The usefulness of eye-tracking tasks as potential biomarkers for motor or cognitive disease burden in Parkinson’s disease (PD) has been subject of debate for many years. Several studies suggest that the performance in the antisaccade task may be altered in patients with PD and associated with motor disease severity or executive dysfunction. In this meta-analysis, random effects models were used to synthesize the existing evidence on antisaccade error rates and latency in PD. Furthermore, meta-regressions were performed to assess the role of motor and cognitive disease severity, dopaminergic medication and methodological factors. Additionally, the impact of acute levodopa administration and activation of deep brain stimulation was evaluated in two separate sub-analyses. This meta-analysis confirms that antisaccade latency and error rate are significantly increased in PD. Disease duration, Unified Parkinson’s disease rating scale score and Hoehn and Yahr stage mediate the effect of PD on antisaccade latency with higher motor burden being associated with increased antisaccade latency. Acute administration of levodopa had no significant effects on antisaccade performance in a small number of eligible studies. Deep brain stimulation in the subthalamic nucleus, on the other hand, may alter the speed accuracy trade-off supporting an increase of impulsivity following deep brain stimulation in PD. According to the results of the meta-analysis, antisaccade latency may provide a potential marker for disease severity and progression in PD which needs further confirmation in longitudinal studies. Supplementary Information The online version contains supplementary material available at 10.1007/s11065-021-09489-1.

Background Paraduodenal pancreatitis (PDP) is a particular form of chronic pancreatitis (CP) occurring in and around the duodenal wall. Despite its low prevalence, this rare condition presents a significant challenge in clinical practice. Methods We retrospectively analysed the electronic medical charts of all patients with a diagnosis of chronic pancreatitis and identified those with PDP, between January 1999 and December 2020. Results There were 35 patients diagnosed with PDP (86% males and 14% females); median age of 56 ± 11 (range 38–80). Alcohol overconsumption was reported in 81% and smoking in 90% of patients. Abdominal pain was the leading symptom (71%), followed by weight loss, nausea and vomiting, jaundice, and diarrhoea. In 23 patients (66%), recurrent acute pancreatitis attacks were noted. Focal duodenal wall thickening was present in 34 patients (97%), cystic lesions in 80%, pancreatic duct dilatation in 54% and common bile duct dilatation in 46%. Endoscopic treatment was performed on nine patients (26%) and five patients (14%) underwent surgery. Complete symptom relief was reported in 12 patients (34%), partial symptom relief in three (9%), there was no improvement in five (14%), data were not available in three (9%) and 12 (34%) patients died before data analysis. Conclusions PDP is a rare form of pancreatitis, most commonly occurring in the 5th or 6th decade of life, with a predominance in males and patients with a history of smoking and high alcohol consumption. Focal thickening and cystic lesions of the duodenal wall are the most common imaging findings, followed by pancreatic duct and common bile duct dilatation. A minority of patients requires surgery.

Postural instability marks one of the most disabling features of Parkinson’s disease (PD), but only reveals itself after affected brain areas have already been significantly damaged. Thus, there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their centre of pressure and their full-body motion. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants’ bodies. Patients exhibited significantly higher sway amplitudes as compared to the control subjects. However, their sway was phase-locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by – most likely reflexively - phase-locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase-locking (PL) across the body revealed a shift of the highest PL-values from the upper body towards the hip-region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired neuromuscular stability, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease.New & NoteworthyA better understanding of visuomotor control in Parkinson’s disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patient’s quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage to have an impaired muscular stability but intact visuomotor control.

Parkinsons disease (PD) is associated with functional changes in the neural activity within the brains sensorimotor network, which in turn are related to the characteristic motor symptoms in PD. The functional changes in PD are particularly prominent in terms of oscillatory neuronal activity in the characteristic sensorimotor alpha and beta rhythms. However, summaries in terms of alpha or beta power do not capture the full range of the complex dynamic nature of the signals from the somatosensory cortex. This raises the question of how to quantify and summarise the functional changes in such oscillatory features in a manner that captures the relevant disease- and symptom-related neural activity. We investigated the role of spontaneous cortical somatosensory activity in the electrophysiological alpha and beta bands among a cohort of early- to mid-stage PD patients (N=78) and age- and gender-matched healthy controls (N=60) using source reconstructed resting-state magnetoencephalography (MEG) recordings. We quantified the oscillatory features of the neural time series by its oscillatory alpha power, beta power, and 1/f broadband characteristics using power spectral density, and additionally by characterising "burst" properties in the signals. We examined the relationship between the signal features and disease state, age, sex, and cortical thickness. Using multiple regression, we examined the relative contribution of the oscillatory features on the clinical manifestation of motor symptoms in the PD group. Our results show that PD patients differ from healthy controls on several of the oscillatory features, showing higher beta-band power, higher burst amplitude, and steeper 1/f broadband characteristics compared to healthy controls, as well as a steeper age-related decrease in the bursts rate. While there was a high degree of correlation between some of the oscillatory features, several features also appeared functionally separated, showing independent feature-to-symptom relationships. For instance, oscillatory beta power increased with the severity of midline function symptoms, while burst rate decreased with the severity of bradykinesia. Our study shows that quantification of distinct features within the oscillatory sensorimotor neural time series in PD captures different underlying mechanisms related to disease progression and symptom severity, which in turn has a potential for a more individualised and precision-based approach to assessing functional neural changes in PD.

In Deutschland leben mindestens 300000 Menschen mit einem idiopathischen Parkinson-Syndrom. Aufgrund des demografischen Wandels ist mit einer stetig steigenden Zahl Betroffener zu rechnen. In diesem Beitrag werden die evidenzbasierte Diagnostik und Therapie des idiopathischen Parkinson-Syndroms dargestellt. Insbesondere soll ein Überblick über die neuen Erkenntnisse und Entwicklungen der letzten Jahre gegeben werden.

Previous studies provide partly contradictory results about the characteristics of saccades in PD and the possible effects of levodopa, which may be attributed to different study design regarding disease stages, medication state or cognitive functioning. We studied horizontal and vertical visually guided saccades (VGS) and antisaccades (AS) in 40 patients with PD with and without postural instability in On and Off medication state as well as in 20 healthy controls (HC). Motor and cognitive performance were assessed using UPDRS, Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). The PD group showed decreased VGS amplitudes and increased vertical VGS and AS latencies. Only relatively few studies had assessed vertical saccades in PD so far. However, our results indicate that vertical saccadic amplitude may be a supportive marker in diagnosing PD since upwards gain demonstrated an AUC of 0.85 for the discrimination of PD and HC. Only more advanced patients in Hoehn & Yahr stage 3 executed higher numbers of AS errors than HC. Since the AS error rate correlated with FAB and MoCA scores, AS performance seems to reflect cognitive ability in PD. Furthermore, the correlation of AS latency with the UPDRS axial subscore promotes the recently highlighted connection between postural control and executive function in PD. Levodopa did not alter saccade amplitudes and had opposing effects on the initiation of VGS and AS: Levodopa intake prolonged VGS latency, but decreased AS latency. Possible mechanisms by which levodopa may be capable of partially reversing the impaired balance between voluntary and reflexive cortical saccade initiation of PD are discussed.

Chronic pancreatitis is a progressive inflammatory disease of the pancreas potentially giving rise to several complications. For this reason, patients need long-term care and treatment by medical, interventional, and sometimes surgical measures. This article reviews current state-of-the-art strategies and guidelines for treating chronic pancreatitis with conventional and endoscopic measures.

Background: Patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic ductal adenocarcinoma (PDAC). We present data on PDAC in one of the most extensive European single-centre cohort studies of patients with CP. Methods: Retrospective analysis of prospectively collected data of patients with CP was performed. Aetiology of CP was determined according to the M-ANNHEIM classification system and only patients with definite CP &gt, 18 years at data analysis were included. The final dataset included 581 patients with definite CP diagnosed between 2003 and 2018. Results: At CP diagnosis, there were 371 (63.9%) males and 210 (36.1%) females (median age 57 years, range 2&ndash, 86). During 3423 person-years of observation, six pancreatic cancers were diagnosed (0.2% year). The mean time between diagnosis of CP and the occurrence of PDAC was 5.0 years (range 2.7&ndash, 8.6). None of the cancer patients had a family history of PDAC. Diabetes mellitus (DM) was present in five of six (83.3%) patients with PDAC: in three patients before and in two after CP diagnosis. Clinical/laboratory signs of pancreatic exocrine insufficiency (PEI) were present in five of six (83.3%) patients with PDAC: in two at diagnosis of CP and in three after diagnosis. The mean survival time was 4 months after the diagnosis of PDAC (range 0.5&ndash, 13). PDAC occurred significantly more often (p &lt, 0.001) in two groups of patients without previous acute pancreatitis (AP): 2 of 20 patients (10%) with low body mass index (BMI) and PEI and in 3 of 10 (30%) patients with high BMI and DM at diagnosis of CP. Conclusions: Patients with CP have a high risk of developing PDAC, although risk is low in absolute terms. Our data suggest the possibility of defining subgroups of patients with a particularly elevated risk of PDAC. Such a possibility would open a path to personalised decision making on initiation of PDAC surveillance of patients with no previous episode of AP, (i) with low BMI and PEI, or (ii) elevated BMI and DM.

Deficits in response inhibition are a central feature of the highly prevalent dysexecutive syndrome found in Parkinson's disease (PD). Such deficits are related to a range of common clinically relevant symptoms including cognitive impairment as well as impulsive and compulsive behaviors. In this study, we explored the cortical dynamics underlying response inhibition during the mental preparation for the antisaccade task by recording magnetoencephalography (MEG) and eye-movements in 21 non-demented patients with early to mid-stage Parkinson's disease and 21 age-matched healthy control participants (HC). During the pre-stimulus preparatory period for antisaccades we observed: Taken together, the results indicate that alterations in pre-stimulus prefrontal alpha and beta activity hinder proactive response inhibition and in turn result in higher error rates and prolonged response latencies in PD.

Background: Chronic pancreatitis is a long-standing, inflammatory condition of the pancreas that leads to the progressive damage and loss of function of pancreatic parenchyma and to the development of possible locoregional and systemic medical complications. Materials and methods: In this review, we tried to summarize the current evidence on non-surgical treatment trying to suggest a practical approach to the management of chronic pancreatitis. Results: Besides the unclear pathophysiological mechanism and a poorly unknown epidemiology, chronic pancreatitis is a complex syndrome that displays different possible challenges for physicians. Despite being traditionally considered as a benign disease, chronic pancreatitis encompasses 10-year mortality rates which are superior to the ones reported for some of the most common cancers. Conclusions: Chronic pancreatitis encompasses the management of multiple and complex medical co-morbidities that needs to be understood and addressed in a multidisciplinary specialist context.

Background and study aims Conventional endoscopic retrograde cholangiopancreatography (ERCP) is hampered by two-dimensional visualization, post-procedural adverse events (AEs), and exposure to ionizing radiation. Bimodal ERCP might mitigate these challenges, but no reports of its use are available to date. The aim of this study was to explore the feasibility of bimodal ERCP, while investigating its potential clinical yield. Patients and methods This was a retrospective observational study of patients that underwent bimodal ERCP in a single tertiary academic referral center. Thirteen patients undergoing conventional ERCP had a previously T2-weighted isotropic 3 D TSE MRCP sequence aligned and fused with the two-dimensional image generated from the fluoroscopy c-arm unit in real time. Results Over a 2-month period, 13 patients with a mean age of 54 underwent bimodal ERCP for bile duct stricture (61.5 %), complex cholelithiasis (7.7 %) and ductal leakage (30.1 %). Bimodal ERCP was feasible in all 13 cases, and image quality was assessed as “good” in 11 patients (84.6 %). Bimodal ERCP aided in visualizing the lesion of interest (76.9 %), assisted in understanding the 3 D anatomy of the biliopancreatic ductal system (61.5 %), and aided in finding a favorable position for the c-arm (38.4 %) for subsequent therapeutic intervention. Conclusions This first report on bimodal ERCP proves its feasibility and suggests that it may assist in increasing both the diagnostic and therapeutic yield of ERCP, while at the same time decreasing AEs during and after ERCP. Its main application might lie in treatment of complex intrahepatic disease.

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