Distinctive Pattern of Metal Deposition in Neurologic Wilson Disease: Insights From 7T Susceptibility-Weighted Imaging.

BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.

Iron deposition in subcortical nuclei of Parkinson's disease: A meta-analysis of quantitative iron-sensitive magnetic resonance imaging studies.

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2* and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata (P <0.001) and compacta (P <0.001), SN (P <0.001), red nucleus (RN, P <0.001), globus pallidus (P <0.001), putamen (PUT, P = 0.009), and thalamus (P = 0.046) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT (P <0.001), RN (P = 0.003), SN (P = 0.017), and caudate nucleus (P = 0.027) than MSA patients, and lower iron content in RN (P = 0.001), PUT (P <0.001), globus pallidus (P = 0.004), SN (P = 0.015), and caudate nucleus (P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.84). CONCLUSION: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION: PROSPERO; CRD42022344413.

Validation of the brief version of the Susceptibility to Persuasion-II scale and evaluation of measurement invariance across age and gender in the Canadian general population.

Measurement tools that can assess personality traits rendering people more susceptible to engagement with and compliance in scams can help identify at-risk populations. The brief, 30-item version of the Susceptibility to Persuasion-II (StP-II-B) scale is a recently developed instrument for assessing 10 personality traits that play a role in scam compliance; however, psychometric evidence supporting the use of this scale is limited. This study aimed to validate the StP-II-B by examining its internal consistency reliability, factor structure, as well as age- and gender-related measurement invariance with a sample of 1287 Canadians aged 16 years and older. Confirmatory factor analysis supported a 10-factor structure identified in previous research. Good internal consistency reliability was obtained for each of the 10 subscales. This 10-factor structure was found to be invariant across age and gender at configural, metric, and scalar levels, suggesting that the StP-II-B was conceptualized in the same way across age and gender and that meaningful comparisons of factor scores could be made. Age and gender differences were found in most factors, with younger individuals and men scoring higher than older individuals and women. This study supports the use of the StP-II-B as a valid and reliable scale for measuring personality traits associated with scam compliance in the Canadian general population and offers insights into age and gender cohorts that may be at higher risk of scam victimization.

The Role of Diet in Parkinson's Disease.

The aim of this review is to examine the intersection of Parkinson's disease (PD) with nutrition, to identify best nutritional practices based on current evidence, and to identify gaps in the evidence and suggest future directions. Epidemiological work has linked various dietary patterns and food groups to changes in PD risk; however, fewer studies have evaluated the role of various diets, dietary components, and supplements in the management of established PD. There is substantial interest in exploring the role of diet-related interventions in both symptomatic management and potential disease modification. In this paper, we evaluate the utility of several dietary patterns, including the Mediterranean (MeDi), Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), Alternative Healthy Eating Index (AHEI), vegan/vegetarian, and ketogenic diet in persons with PD. Additionally, we provide an overview of the evidence relating several individual food groups and nutritional supplements to PD risk, symptoms and progression.

Microstructural and functional alterations of the ventral pallidum are associated with levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND AND PURPOSE: The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa-induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD-LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). METHODS: Thirty-one PD-LID patients, 39 PD patients without LID (PD-nLID), and 28 healthy controls (HCs) underwent T1-weighted MRI, quantitative susceptibility mapping, multi-shell diffusion MRI, and resting-state functional MRI (rs-fMRI). Different measures characterizing the VP were obtained using a region-of-interest-based approach. RESULTS: The left VP in the PD-LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD-nLID and HC groups. Rs-MRI revealed that, compared with the PD-nLID group, the PD-LID group in the medication 'off' state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. CONCLUSION: Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum-VP-mediodorsal thalamus-cortex network may be associated with pathophysiological mechanisms of PD-LID.

Dopaminergic versus anticholinergic treatment effects on physiologic complexity of hand tremor in Parkinson's disease: A randomized crossover study.

AIMS: Parkinsonian tremor (PT) is regulated by numerous neurophysiological components across multiple temporospatial scales. The dynamics of tremor fluctuation are thus highly complex. This study aimed to explore the effects of different medications on tremor complexity, and how the underlying factors contribute to such tremor complexity. METHODS: In this study, 66 participants received a 2-mg dose of benzhexol or a pre-determined dose of levodopa at two study visits in a randomized order. Before and after taking the medications, tremor fluctuation was recorded using surface electromyography electrodes and accelerometers in resting, posture, and weighting conditions with and without a concurrent cognitive task. Tremor complexity was quantified using multiscale entropy. RESULTS: Tremor complexity in resting (p = 0.002) and postural condition (p < 0.0001) was lower when participants were performing a cognitive task compared to a task-free condition. After taking levodopa and benzhexol, participants had increased (p = 0.02-0.03) and decreased (p = 0.03) tremor complexity compared to pre-medication state, respectively. Tremor complexity and its changes as induced by medications were significantly correlated with clinical ratings and their changes (ß = -0.23 to -0.39; p = 0.002-0.04), respectively. CONCLUSION: Tremor complexity may be a promising marker to capture the pathophysiology underlying the development of PT, aiding the characterization of the effects medications have on PT regulation.

Demographic and psychometric predictors associated with engagement in risk-associated alternative healthcare behaviours.

This paper builds on prior work exploring the use of risk-associated alternative healthcare (RAAH) in Canada. RAAH uptake was surveyed to explore the characteristics of adult RAAH users and the value of established psychometric instruments previously used in alternative healthcare studies in predicting RAAH behaviours: the Control Beliefs Inventory (CBI), the Reward Responsiveness Behavioural Activation System (RBAS) scale, the Positive Attitudes to Science (PAS) scale, the Satisfaction with Orthodox Medicine (SOM) scale, and the brief version of the Susceptibility to Persuasion-II (StP-II-B) scale. Findings suggest RAAH is influenced by gender, age, income, education, employment, chronic illness status, and ethnicity. Engagement in some form of RAAH was common (around 40%) and the most common types of RAAH use reported were physical manipulation and herbal/nutritional supplement use. Other higher-risk AH activities (such as use of toxins and physically invasive procedures) were also reported by about 5% of respondents. The StP-II-B and PAS instruments were predictive of the likelihood of engagement in RAAH behaviours, as illustrated by higher risk tolerance, desire for novelty, positive attitude to advertising and social influence, and positive beliefs about science. The CBI, RBAS, and SOM instruments were not predictive overall. However, the CBI and SOM instruments were predictive of engagement with physical manipulative RAAH activities, while the RBAS was predictive of herbal/nutritional RAAH engagement. These findings can help inform health professionals' understanding of public health-seeking behaviours with respect to risk.