The eye-tracking study aimed at assessing spatial biases in visual exploration in patients after acute right MCA (middle cerebral artery) stroke. Patients affected by unilateral neglect show less ...functional recovery and experience severe difficulties in everyday life. Thus, accurate diagnosis is essential, and specific treatment is required. Early assessment is of high importance as rehabilitative interventions are more effective when applied soon after stroke. Previous research has shown that deficits may be overlooked when classical paper-and-pencil tasks are used for diagnosis. Conversely, eye-tracking allows direct monitoring of visual exploration patterns. We hypothesized that the analysis of eye-tracking provides more sensitive measures for spatial exploration deficits after right middle cerebral artery stroke. Twenty-two patients with right MCA stroke (median 5 days after stroke) and 28 healthy controls were included. Lesions were confirmed by MRI/CCT. Groups performed comparably in the Mini-Mental State Examination (patients and controls median 29) and in a screening of executive functions. Eleven patients scored at ceiling in neglect screening tasks, 11 showed minimal to severe signs of unilateral visual neglect. An overlap plot based on MRI and CCT imaging showed lesions in the temporo-parieto-frontal cortex, basal ganglia, and adjacent white matter tracts. Visual exploration was evaluated in two eye-tracking tasks, one assessing free visual exploration of photographs, the other visual search using symbols and letters. An index of fixation asymmetries proved to be a sensitive measure of spatial exploration deficits. Both patient groups showed a marked exploration bias to the right when looking at complex photographs. A single case analysis confirmed that also most of those patients who showed no neglect in screening tasks performed outside the range of controls in free exploration. The analysis of patients' scoring at ceiling in neglect screening tasks is of special interest, as possible deficits may be overlooked and thus remain untreated. Our findings are in line with other studies suggesting considerable limitations of laboratory screening procedures to fully appreciate the occurrence of neglect symptoms. Future investigations are needed to explore the predictive value of the eye-tracking index and its validity in everyday situations.
Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour ...lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM.
Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed.
259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006).
Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.
Objective
To investigate cognitive flexibility in premanifest and manifest Huntington's disease (HD).
Background
HD is an autosomal dominant neurodegenerative disease characterized by motor, ...cognitive, and behavioral abnormalities with typical motor symptoms. In this study, we wanted to assess decision making in premanifest (pre‐HD) and manifest HD patients.
Methods
A total of 77 non‐demented subjects including 29 pre‐HD, 22 manifest HD patients, and 26 healthy controls (HC) were included. We stratified the pre‐HD group based on their estimated years to disease onset into a far (FAR, n = 13) and a near (NEAR, n = 16) group. Furthermore, participants performed the Montreal cognitive assessment battery (MoCA), the trail making task part A and B (TMT A, TMT B), the Symbol digit modalities test (SDMT), and the beads task.
Results
In the beads task, HD patients gathered less information than all other groups (all p‐values < .001). Furthermore, the NEAR group gathered less information than the FAR group (p < .001) and HC (p = .001). There was no difference between the HC and the FAR group (p = 1.0). In the TMT and the SDMT, HD patients were slower than all other groups (all p‐values < .01) but there were no other significant differences.
Conclusions
Decision making with a higher degree of uncertainty may be an early neuropsychological sign to indicate the disease process prior to reaching criteria for motor diagnosis of HD.
In this study, we assessed decision making in manifest Huntington's disease (HD) and premanifest HD patients. We could show that jumping to conclusions is an early marker of cognitive dysfunction in premanifest HD patients prior to reaching criteria for the motor diagnosis of HD.
The synthetic tetrahydrocannabinol-analog nabilone improved non-motor symptoms (NMS) in Parkinson's disease (PD) patients in a placebo-controlled, double-blind, parallel-group, randomized withdrawal ...trial with enriched enrollment (NMS-Nab-study). This was a single-center open-label extension study to assess the long-term safety and efficacy of nabilone for NMS in PD. To be eligible for this study, patients had to be treatment responders during the previous NMS-Nab-trial and complete its double-blind phase without experiencing a drug-related serious/severe/moderate adverse event (AE). Patients were re-introduced to nabilone during an up-titration phase until their overall NMS burden improved. Nabilone was continued for six months with clinic visits every 3 months. Evaluation of AEs was based on self-report and clinical assessment. Twenty-two patients participated in the NMS-Nab2-study (age-median 68.33 y, 52% females, disease duration-median 7.42 y). Nabilone was well tolerated with concentration difficulties as the most common treatment-related AE (possibly/not related n = 1 each). One in two drop-outs discontinued because of an AE for which a prohibited concomitant medication needed to be introduced (night-time sleep problems). Efficacy evaluation showed a significant and lasting improvement in NMS burden according to the CGI-I (79% at V3). Nabilone improved overall sleep (NMSS Domain-2: -8.26 points; 95%CI -13.82 to -2.71; p = 0.004; ES = -0.72), night-time sleep problems (MDS-UPDRS-1.7: -1.42 points; 95 CI -2.16 to -0.68; p = 0.002; ES = -0.92), and overall pain (KPPS Total Score: -8.00 points; 95%CI -15.05 to -0.95; p = 0.046; ES -0.55 and MDS-UPDRS-1.9: -0.74 points; 95%CI -1.21 to -0.26; p = 0.008; ES = -0.74). This study demonstrates continuous long-term safety and efficacy in PD patients responding early to nabilone without intolerable side effects.
Increasing evidence suggests persistent cognitive dysfunction after COVID‐19. In this cross‐sectional study, frontal lobe function was assessed 12 months after the acute phase of the disease, using ...tailored eye tracking assessments. Individuals who recovered from COVID‐19 made significantly more errors in all eye tracking tasks compared to age/sex‐matched healthy controls. Furthermore, patients who were treated as inpatients performed worse compared to outpatients and controls. Our results show impaired inhibitory cortical control in individuals who recovered from COVID‐19. The association between disease severity and its sequelae may contribute to a better understanding of post‐COVID‐19 cognitive function.
Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters ...could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs.
A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics.
Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all
< 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively).
CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.
Augmentation (AUG) in patients with restless legs syndrome (RLS) can be associated with impulse control disorder (ICD) symptoms, such as compulsive sexual behavior, gambling disorder or compulsive ...shopping. In this study, we wanted to assess whether RLS patients with AUG differ in decision making from those patients who have augmentation and in addition ICD symptoms (AUG + ICD) in a post hoc analysis of a patient cohort assessed in a previous study.
In total, 40 RLS patients with augmentation (19 AUG + ICD, 21 AUG without ICDs) were included. RLS diagnosis, severity, and diagnosis of augmentation were made by sleep disorder specialists. ICD symptoms were assessed using semi-structured interviews. All patients performed the beads task, which is an information sampling task where participants must decide from which of the two cups colored beads were drawn. Results were compared to 21 healthy controls (HC).
There was no difference in information sampling or irrational decision making between AUG and AUG + ICD patients (
= 0.67 and
= 1.00, respectively). Both patient groups drew less beads and made more irrational decisions than HC (all
-values < 0.03, respectively).
Our results suggest that augmentation itself is associated with poorer decision making even in the absence of ICD symptoms. Further studies are necessary to explore whether rapid and hasty decision making are a harbinger of augmentation in RLS.
The topic of the therapeutic use of cannabinoids in Parkinson's disease (PD) is broadly discussed and frequently comes up in the outpatient clinic. So far, there are only a few randomized clinical ...trials assessing the effects of cannabinoids in PD. We are able to demonstrate a reduction in non-motor symptom (NMS) burden after the administration of nabilone. As impairment of attention and working memory have been described earlier as possible side effects, we assess cognitive performance using saccadic paradigms measured by an eye tracker. We do not observe a significant difference in any of the saccadic paradigms between PD patients on placebo versus those treated with nabilone. We, therefore, conclude that top-down inhibitory control is not affected by the tetrahydrocannabinol analogue. Nabilone did not significantly worsen cognitive performance and appears to be safe to use in selected PD patients who suffer from disabling NMS.
Objective
To assess emotional processing and alexithymia in patients with restless legs syndrome (RLS) with augmentation versus those who never had augmentation.
Methods
We recruited 26 patients who ...had a history of augmentation (AUG), either current or past, 27 RLS patients treated with dopamine agonists who never had augmentation (RLS controls), and 21 healthy controls (HC). All participants were screened for impulse control disorders (ICDs). Alexithymia was assessed by means of the Toronto Alexithymia Scale – 20 (TAS‐20). Facial emotion recognition was tested through an eye‐tracking task. Furthermore, all participants performed neuropsychological tests assessing global cognitive status, impulsivity, anxiety, and depression.
Results
ICD symptoms occurred more frequently in AUG patients than in RLS controls (P = 0.047). Patients with AUG scored higher on the TAS‐20 (P = 0.007) and the attentional subdomain of an impulsivity scale (BIS‐11; P = 0.015) compared to HC. Patients with AUG also performed worse on the facial emotion recognition task relative to RLS controls (P = 0.009) and HC (P = 0.003). We found a group difference for the time to first fixation and the fixation count in the mouth region (P = 0.019 and P = 0.021, respectively). There were no other differences in the eye tracking examination.
Interpretation
This study showed evidence of poorer emotional processing in patients who had augmentation compared to RLS patients without augmentation and healthy controls. The altered exploration pattern of faces and the higher alexithymia scores suggest abnormalities in emotion processing in patients with augmentation.
•Two different antisaccade tasks were applied to investigate cognition, affect, and HRV.•We induced sadness and emotional arousal compared to a neutral control group.•Higher HRV reactivity predicted ...inhibitory control performance in the sadness group only.•Lower error rates were related to higher HRV reactivity.•Negative affect moderated the effect of HRV reactivity on inhibition of emotional stimuli.
Higher negative affectivity has an association with decreased executive function and cognitive control. Heart rate variability (HRV) serves as an index of cardiac vagal regulation differences in the autonomic nervous system for both cognition and emotion. The current study investigates this association using a classic as well as emotional antisaccade paradigm to study inhibitory control performance. Ninety participants completed affective questionnaires (Beck Depression Inventory-II, and Mood Scale), a 6-minute baseline electrocardiogram, and two different antisaccade tasks. After the baseline, subjects were presented with a video sequence with either neutral, sad, or emotionally arousing content. By subtracting the baseline from the video sequence, we computed HRV reactivity and tested whether the reactivity score could predict inhibitory control performance. We hypothesized that this would be the case in both the sadness and arousal group, but not in the neutral one. Furthermore, we awaited significant performance differences between experimental groups. Contrary to our assumption, inhibitory control performance did not differ between experimental groups. Moreover, there was no significant relation between affective measures and task performance. Nevertheless, cardiovascular reactivity in terms of HRV was predictive of error rates in both antisaccade tasks in the sadness group. We could find this effect neither in the neutral nor in the arousal group. In addition, BDI scores moderated the effect in the emotional task. Results indicate that emotional reactivity to a sad video stimulus as indexed by HRV as well as the interaction with current emotional state predict inhibitory control performance.
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