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The article discusses the case of a 58-year-old woman with Spinocerebellar Ataxia Type 12 (SCA12) who underwent bilateral deep brain stimulation of the posterior subthalamic area (PSA) to alleviate intractable action tremors. The patient's tremors significantly improved post-surgery, leading to better quality of life and reduced tremor amplitudes. The study highlights the effectiveness of deep brain stimulation in treating medication-resistant tremors in patients with SCA12, emphasizing the need for continued monitoring to assess long-term outcomes. [Extracted from the article]

A comprehensive model for deep dynamics in Asia has been developed from the data on the evolution of melting anomalies in the context of lithospheric plate motions, interactions, orogeny, and rifting. The key components of our model are the primary (transition layer) and secondary (upper mantle) melting anomalies (Gobi, Baikal, and North Transbaikalia; and Hangay, Sayan, and Vitim, respectively). It is inferred that the primary melting anomalies originated at the beginning of the latest geodynamic stage (ca. 90 Ma) as a result of the transition layer distortion by lower mantle flows. Such primary anomalies were caused by avalanche collapses of the slab material that had been stagnated under the closed fragments of the Solonker, Ural-Mongolian paleooceans and the Mongol-Okhotsk Bay of Paleopacific. The secondary melting anomalies occurred due to the Early-Middle Miocene structural reorganization in the Pacific-Asian and Indo-Asian interaction zones. The primary melting anomalies governed the spatial distribution of forces and processes of the latest geodynamic stage. The secondary melting anomalies resulted from the lithospheric motions relative to the primary anomalies and provided for the development of orogeny and rifting. The Baikal-Mongolian corridor of asthenospheric flows was limited by the lateral zones of convergent interactions between India and Asia in the southwest, and North America and Asia in the northeast. In these lateral zones, Late Phanerozoic paleoslabs and ascending mantle fluxes were revealed in the transition layer, as well as in the upper mantle, without any destruction by the asthenospheric flows.

Introduction: Respiratory dysfunction in patients with Parkinson's disease (PD) could present in the early stage and worsen in the late stages. These changes could be a factor affecting the ability of daily living and quality of life of patients with PD. The primary objective of this study was to assess the respiratory function and its association with motor function in patients with different stages of PD. Methods: This was a cross-sectional study conducted at the Huashan Hospital of Fudan University in Shanghai, China. The study included 65 patients diagnosed with PD (the Hoehn and Yahr scale between 1 and 4) and 20 healthy individuals of similar age, gender, weight, and height. The ventilatory function was assessed using the spirometry. Motor function was evaluated using subscale III of the United Parkinson's disease rating scale (UPDRS-III). After confirming the normality of data distribution, we performed one-way ANOVA with a Tukey's post hoc test. Results: Compared with the healthy individuals, there was no statistical significance in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) in the H&Y 1 group and H&Y 2 group (p > 0.05) but reduced peak expiratory flow (PEF) in the H&Y 2 group (p = 0.002). Reduced FVC, FEV1, and PEF was seen in the H&Y 3 group (p = 0.002, p = 0.001, and p = 0.0001, respectively). Reduced FVC, FEV1, PEF, and FEF25–75% was seen in the H&Y 4 group (p = 0.001, p = 0.0001, p = 0.0001, and p = 0.025, respectively). The correlation analysis revealed that there was a significant negative correlation between FVC and UPDRS-III scores (r = −0.248, p = 0.046), disease duration (r = −0.276, p = 0.026), H&Y scale (r = −0.415, p = 0.001). FEV1 was negatively correlated with UPDRS-III scores (r = −0.277, p = 0.025), disease duration (r = −0.291, p = 0.019), H&Y scale (r = −0.434, p = 0.0001). FEF25–75% was negatively correlated with disease duration (r = −0.247, p = 0.047), H&Y scale (r = −0.278, p = 0.025). Conclusion: Our findings revealed that respiratory impairment is present in moderate and advanced PD patients, and directly related to the severity of the disease. It is important to conduct respiratory function test in the clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. Methods: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. Results: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. Conclusions: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains. [ABSTRACT FROM AUTHOR]

Background: Recent development in tau‐sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18F‐florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease‐level differences exist with other neurodegenerative tauopathies is still unanswered. Objective: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18F‐florzolotau PET imaging and to examine whether differences with other tauopathies exist. Methods: 18F‐florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy–Richardson's syndrome (PSP‐RS). Cerebrospinal fluid (CSF) levels of β‐amyloid biomarkers were quantified in all patients with CBS. 18F‐florzolotau uptake was quantitatively assessed using standardized uptake value ratios. Results: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18F‐florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18F‐florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP‐RS. An asymmetric pattern of 18F‐florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. Conclusions: In vivo 18F‐florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: The self-reported quality of life (QoL) should be carefully listened to in progressive supranuclear palsy (PSP) from the patient-centered perspective. However, there was still a lack of short QoL measurement tool in atypical parkinsonism. Objective: We aimed to test whether the short Parkinson's Disease Questionnaire-8 (PDQ-8) was effective in assessing QoL in PSP, comparing with Progressive Supranuclear Palsy Quality of Life Scale (PSP-QoL) and Parkinson's Disease Questionnaire-39 (PDQ-39). Methods: 132 patients with clinical diagnosed PSP, including PSP-Richardson syndrome (RS) subtype (n = 71) and PSP-non-RS subtype (n = 61) were recruited for clinical evaluation including QoL assessment. The detailed QoL profiles and possibility of using PDQ-8 were systemically analyzed. The determinants to the QoL were then calculated by multivariate linear regression analysis. Results: The PSP-QoL total score summary index (SI) was 22.8 (10.1, 41.1), while the PDQ-8 and PDQ-39 total SI score were 28.1 (12.5, 46.9) and 29.5 (15.4, 49.4). Mobility, activities of daily life, cognition and communication were the main affected QoL subdomains (median SI: 40.0, 31.3, 25.0 and 25.0 respectively). PSP-RS subtype showed more severe damage physically (p<0.001) and mentally (p = 0.002) compared to other subtypes. More importantly, the strong relevance of PDQ-8 and recommended PSP QoL tools were confirmed (p<0.001). In addition, disease severity, depression and daytime sleepiness were proved to be critical determinants for QoL in PSP. Conclusions: PDQ-8 could be an easy, reliable, and valid tool to evaluate QoL in patients with PSP. Besides motor symptoms, more attention should be paid to non-motor impairment such as depression in PSP. [ABSTRACT FROM AUTHOR]

Background: 18 F-APN-1607 is a novel tau PET tracer characterized by high binding affinity for 3- and 4-repeat tau deposits. Whether 18 F-APN-1607 PET imaging is clinically useful in PSP remains unclear.Objectives: The objective of this study was to investigate the clinical utility of 18 F-APN-1607 PET in the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP.Methods: We enrolled 3 groups consisting of patients with PSP (n = 20), patients with α-synucleinopathies (MSA with predominant parkinsonism, n = 7; PD, n = 10), and age- and sex-matched healthy controls (n = 13). The binding patterns of 18 F-APN-1607 in PET/CT imaging were investigated. Regional standardized uptake ratios were compared across groups and examined in relation to their utility in the differential diagnosis of PSP versus α-synucleinopathies. Finally, the relationships between clinical severity scores and 18 F-APN-1607 uptake were investigated after adjustment for age, sex, and disease duration.Results: Compared with healthy controls, patients with PSP showed increased 18 F-APN-1607 binding in several subcortical regions, including the striatum, putamen, globus pallidus, thalamus, subthalamic nucleus, midbrain, tegmentum, substantia nigra, pontine base, red nucleus, raphe nuclei, and locus coeruleus. We identified specific regions that were capable of distinguishing PSP from α-synucleinopathies. The severity of PSP was positively correlated with the amount of 18 F-APN-1607 uptake in the subthalamic nucleus, midbrain, substantia nigra, red nucleus, pontine base, and raphe nuclei.Conclusions: 18 F-APN-1607 PET imaging holds promise for the diagnosis, differential diagnosis, and assessment of disease severity in patients with PSP. © 2021 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Previous studies with a limited sample size suggested more severe dopaminergic transporter (DAT) lesions in the striatum of progressive supranuclear palsy (PSP) than those in Parkinson's disease (PD) and multiple system atrophy–parkinsonism (MSA‐P). However, few studies had taken various subtypes of PSP into consideration, making the reanalysis of DAT imaging in larger PSP cohort with various subtypes in need. Objectives: To compare the dopaminergic lesion patterns of PSP with MSA‐P and PD, and to explore the specific striatal subregional patterns of different PSP subtypes. Methods: 11C‐CFT positron emission tomography (PET) imaging was conducted in 83 PSP patients consisting of different subtypes, 61 patients with PD, 41 patients with MSA‐P, and 43 healthy volunteers. Demographic and clinical data were compared by the chi‐squared test or one‐way analysis of variance. A generalized linear model was used to examine intergroup differences in tracer uptake values after adjusting for age, disease duration, and disease severity. Areas under the receiver operating characteristic curve were calculated to assess the diagnostic accuracy of subregional DAT binding patterns. Results: The patients with PSP presented more severe DAT loss in the striatum than in PD and MSA‐P, especially in caudate. In PSP, the subregional lesion was still more severe in putamen than in caudate, similar to that in PD and MSA‐P. Among detailed subtypes, no significant difference was detected. Conclusion: The dopaminergic lesions were more severe in PSP, and no difference was detected among subtypes. [ABSTRACT FROM AUTHOR]

Background: Anecdotal evidence suggests that patients diagnosed with the parkinsonian subtype of multiple system atrophy (MSA-P) may show uptake of the second-generation tau positron emission tomography (PET) tracer 18 F-Florzolotau (previously known as 18 F-APN-1607) in the putamen.Objectives: This study systematically investigated the localization and magnitude of 18 F-Florzolotau uptake in a relatively large cohort of patients with MSA-P.Methods: 18 F-Florzolotau PET imaging was performed in 31 patients with MSA-P, 24 patients with Parkinson's disease (PD), and 20 age-matched healthy controls. 18 F-Florzolotau signal in the striatum was analyzed by visual inspection and classified as either positive or negative. Regional 18 F-Florzolotau binding was also expressed as standardized uptake value ratio (SUVR) to assess whether it was associated with core symptoms of MSA-P after adjustment for potential confounders.Results: By visual inspection and semiquantitative SUVR comparisons, patients with MSA-P showed elevated 18 F-Florzolotau uptake in the putamen, globus pallidus, and dentate-a finding that was not observed in PD. This increased signal was significantly associated with the core symptoms of MSA-P. In addition, patients with MSA-P with cerebellar ataxia showed an elevated 18 F-Florzolotau uptake in the cerebellar dentate.Conclusions: 18 F-Florzolotau tau PET imaging findings may reflect the clinical severity of MSA-P and can potentially discriminate between this condition and PD. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients.Methods: Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition.Results: At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027).Conclusion: Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal lobar degeneration with tauopathy caused by MAPT (microtubule‐associated protein tau) mutations is a highly heterogenous disorder. The ability to visualize and longitudinally monitor tau deposits may be beneficial to understand disease pathophysiology and predict clinical trajectories. Objective: The aim of this study was to investigate the cross‐sectional and longitudinal 18F‐APN‐1607 positron emission tomography/computed tomography (PET/CT) imaging findings in MAPT mutation carriers. Methods: Seven carriers of MAPT mutations (six within exon 10 and one outside of exon 10) and 15 healthy control subjects were included. All participants underwent 18F‐APN‐1607 PET/CT at baseline. Three carriers of exon 10 mutations received follow‐up 18F‐APN‐1607 PET/CT scans. Standardized uptake value ratio (SUVR) maps were obtained using the cerebellar gray matter as the reference region. SUVR values observed in MAPT mutation carriers were normalized to data from healthy control subjects. A regional SUVR z score ≥ 2 was used as the criterion to define positive 18F‐APN‐1607 PET/CT findings. Results: Although the seven study patients had heterogenous clinical phenotypes, all showed a significant 18F‐APN‐1607 uptake characterized by high‐contrast signals. However, the anatomical localization of tau deposits differed in patients with distinct clinical symptoms. Follow‐up imaging data, which were available for three patients, demonstrated worsening trends in patterns of tau accumulation over time, which were paralleled by a significant clinical deterioration. Conclusions: Our data represent a promising step in understanding the usefulness of 18F‐APN‐1607 PET/CT imaging for detecting tau accumulation in MAPT mutation carriers. Our preliminary follow‐up data also suggest the potential value of 18F‐APN‐1607 PET/CT for monitoring the longitudinal trajectories of frontotemporal lobar degeneration caused by MAPT mutations. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Mutations in Presenilin-1 (PSEN1) have been found to be associated with very early onset Alzheimer's disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic distribution of PSEN1 mutations. [ABSTRACT FROM AUTHOR]

Objective: Little is known about the disease progression of Parkinson's disease patients with subjective cognitive complaint (PD‐SCC). This longitudinal cohort study aims to compare the progression of clinical features and quality of life (QoL) in PD patients with normal cognition (NC), SCC, and mild cognitive impairment (MCI). Methods: A total of 383 PD patients were enrolled, including 189 PD‐NC patients, 59 PD‐SCC patients, and 135 PD‐MCI patients, with 1–7 years of follow‐up. Linear mixed models were applied to evaluate longitudinal changes in motor symptoms, nonmotor features (cognitive impairment, depression, and excessive daytime sleepiness), and QoL in PD. Results: At baseline, PD‐SCC patients had lower Beck Depression Inventory (BDI) scores and Parkinson's Disease Questionnaire‐39 (PDQ‐39) scores than PD‐NC patients (all p < 0.05). Longitudinal analyses revealed that the PD‐SCC group exhibited faster progression in terms of BDI scores (p = 0.042) and PDQ‐39 scores (p = 0.035) than the PD‐NC group. The PD‐MCI group exhibited faster progression rates in the Epworth Sleepiness Scale scores (p = 0.001) and PDQ‐39 scores (p = 0.005) than the PD‐NC group. In addition, the PD‐SCC group exhibited a greater reduction in attention (Trail Making Test Part A, p = 0.047) and executive function (Stroop Color‐Word Test, p = 0.037) than the PD‐NC group. Interpretation: PD‐SCC patients exhibited faster deterioration of depression and QoL than PD‐NC patients, and SCC may be an indicator of initial attention and executive function decline in PD. Our findings provided a more accurate prognosis in PD‐SCC patients. [ABSTRACT FROM AUTHOR]

Abstract Background TARDBP mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between TARDBP mutations and Chinese patients with ALS. Methods 71 SALS patients and 5 FALS families with non-SOD1 mutations were screened for TARDBP mutations via direct sequencing. Results A novel heterozygous variation, Ser292Asn (875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c). Conclusions The present data have extended the spectrum of TARDBP mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET). Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis. Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391–0.8609]. Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin -related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin -related PD patients. Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited (n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD- Parkin) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed. Results: PD- Parkin patients had a younger AOO (p = 0.003) and longer disease duration (p = 0.005). After adjustment for AOO and disease duration, more dystonia (p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety (p = 0.015) and sleep disorders (p = 0.005) in Non-motor symptoms questionnaire, were found in PD- Parkin comparing with GU-EOPD. PD- Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores (p = 0.005) and ESS scores (p = 0.047) were significant determinants of QoL in PD-Parkin. Conclusion: Newly diagnosed PD- Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations. [ABSTRACT FROM AUTHOR]