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The article discusses a case study of a 58-year-old woman with Spinocerebellar Ataxia Type 12 (SCA12) who underwent deep brain stimulation (DBS) of the posterior subthalamic area (PSA) to treat her intractable action tremor. The patient's tremor significantly improved after DBS, leading to better quality of life and sustained tremor control. The study highlights the short-term effectiveness of DBS in treating SCA12 and suggests that patients with SCA12 and mild cerebellar ataxia may benefit from this treatment. The authors emphasize the need for continued monitoring to assess the long-term outcomes of DBS for SCA12. [Extracted from the article]

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: 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: 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: 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: 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]

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]

Autosomal recessive spinocerebellar ataxia (SCAR) is a rare and complex group of diseases. Revolutionary gene-sequencing techniques, especially next generation sequencing (NGS), have revealed numerous SCAR-causing genes.[2] Previous reports showed mutations in a wide range of genes. In group A, all patients mainly exhibited cerebellar ataxia; four probands with senataxin ( I SETX i ) mutations showed neuropathy, and three with Niemann-Pick disease, type C1 ( I NPC1 i ) mutations complained of cognitive decline. Friedreich's ataxia (FRDA) was reported as the most frequently occurring SCAR, followed by ataxia-telangiectasia or ataxia with oculomotor apraxia,[1] while I ATX i - I SETX i gene mutations were most frequently found in our cohort. [Extracted from the article]

Aims Alzheimer's disease ( AD) and Parkinson's disease ( PD) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine-rich repeat kinase 2 ( LRRK2) have been reported to be responsible for PD, and the location of LRRK2 is within a linkage peak for sporadic AD ( SAD). The aim of this study was to investigate two Asian-specific LRRK2 variants, R1628 P and G2385 R, with the association of Han Chinese SAD. Methods Genotyping of R1628 P and G2385 R was performed by PCR-restriction fragment length polymorphism ( RFLP) analysis in 390 patients with SAD and 545 unrelated age- and sex-matched healthy controls. Results The frequency of the C allele within R1628 P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) ( OR 0.264; 95% CI, 0.088-0.792, P = 0.018). After stratification by the presence of one or two apolipoprotein E ε4 alleles, the protective effect becomes stronger (ε44: OR 0.028; 95% CI, 0.003-0.303, P = 0.003; ε4: OR 0.104; 95% CI, 0.013-0.818, P = 0.031). However, no difference was found in G2385 R variant. Conclusion Our study suggested that R1628 P variant within LRRK2 plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Nowadays, cognitive impairment has been characterized as one of the most vital clinical symptoms in progressive supranuclear palsy (PSP).Based on a relatively large cohort, we aimed to show the cognitive deterioration in different PSP subtypes during 1‐year follow‐up and investigate potential contributors for disease prognosis.One hundred seventeen patients from Progressive Supranuclear Palsy Neuroimage Initiative (PSPNI) cohort underwent neuropsychological tests and 1‐year follow‐up, with 73 diagnosed as PSP‐Richardson syndrome (PSP‐RS) and 44 as PSP‐non‐RS. Patients were divided into normal cognition (PSP‐NC), mild cognitive impairment (PSP‐MCI), and PSP‐dementia. Cognitive impairment and progression rates were compared between PSP‐RS and PSP‐non‐RS, and determinants for MCI conversion to dementia were calculated by multiple cox regression.At baseline, 30.8% of PSP patients were diagnosed as dementia, 53.0% as MCI, and only 16.2% as NC. Compared to PSP‐non‐RS, PSP‐RS suffered more from motor symptoms and cognitive impairment. During follow‐up, PSP‐RS also exhibited faster disease progression in Mini‐Mental State Examination and visuospatial function, with cognitive deterioration in attention and executive function, but retained in language and memory subdomains. Twenty‐seven of 62 PSP‐MCI patients converted to dementia during follow‐up, with the diagnosis of RS subtype as the most significant contributor to conversion (hazard ration = 2.993, 95% confidence interval = 1.451, 5.232, P = 0.009).Patients with PSP‐RS showed more severe cognitive impairment and faster decline longitudinally than patients with PSP‐non‐RS. Additionally, the diagnosis of RS subtype appears to be the most contributed factor for MCI conversion to dementia within just 1‐year follow‐up period. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18F‐AV‐1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB.Our aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the 18F‐Florzolotau positron emission tomography (PET) imaging.This cross‐sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and 18F‐Florzolotau PET imaging were performed. 18F‐Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel‐wise analysis.18F‐Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology.18F‐Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease‐modifying therapies. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: The mutation of TANK‐binding kinase 1 (TBK1) gene has been regarded as a causative gene of frontotemporal dementia (FTD)‐amyotrophic lateral sclerosis (ALS) spectrum disease in recent years. So far, more than 70 TBK1 variants have been identified in patients with FTD‐ALS spectrum. Methods: We reported a Chinese FTD patient carrying TBK1 p.Ile334Thr variant detected by target sequencing and Sanger sequencing. The patient's clinical materials were collected. The transcription and translation levels of TBK1 mutant were investigated in fibroblast by qPCR and western blot. The effects of TBK1 mutant in inflammation pathway and autophagy were detected by luciferase reporter assay and GST pull‐down assay. Results: The patient was diagnosed as behavioral variant FTD (bvFTD) and displayed progressively severe cognitive impairment especially in executive function. A pattern of frontotemporal atrophy and hypometabolism was shown through MRI and PET‐CT. In vitro functional experiments of TBK1 p.Ile334Thr variant demonstrated reduced transcription and translation levels, decreased kinase activity but maintenance of interaction with optineurin. The variant was classified as likely pathogenic according to American College of Medical Genetics and Genomics guideline. Conclusion: We proposed the TBK1 mutation p.Ile334Thr as a likely pathogenic variant in bvFTD which also expanded the clinical spectrum of this variant. It can partially abrogate TBK1 functions and be responsible for FTD‐ALS spectrum diseases through neuroinflammatory pathway. We reported a patient with TBK1 mutation p.Ile334Thr and identify its potential disturbance of neuroinflammatory pathway in vitro. [ABSTRACT FROM AUTHOR]