No Evidence of Early Developmental Delay in Juvenile-Onset Huntington's Disease Patients.

Background: Previous studies suggest that early developmental delay is a common feature of Juvenile-Onset Huntington's disease (JOHD), with highest incidence in those with very high CAG repeats (> 80). However, all reports of developmental delay in JOHD are exclusively based on retrospective review of medical charts. Comprehensive assessment of birth history metrics may provide better insight into the question of early life development in JOHD.

Mutant Huntingtin Drives Development of an Advantageous Brain Early in Life: Evidence in Support of Antagonistic Pleiotropy.

Objective: Huntington's disease (HD) is a neurodegenerative disease caused by a triplet repeat expansion within the gene huntingtin (HTT). Antagonistic pleiotropy is a theory of aging that posits that some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging-related processes. Antagonistic pleiotropy theory may explain a positive evolutionary pressure toward functionally advantageous brain development that is vulnerable to rapid degeneration.

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls.

Assisted annotation in Deep LOGISMOS: Simultaneous multi-compartment 3D MRI segmentation of calf muscles.

Background: Automated segmentation of individual calf muscle compartments in 3D MR images is gaining importance in diagnosing muscle disease, monitoring its progression, and prediction of the disease course. Although deep convolutional neural networks have ushered in a revolution in medical image segmentation, achieving clinically acceptable results is a challenging task and the availability of sufficiently large annotated datasets still limits their applicability.

Purpose: In this paper, we present a novel approach combing deep learning and graph optimization in the paradigm of assisted annotation for solving general segmentation problems in 3D, 4D, and generally n-D with limited annotation cost.

Longitudinal Clinical and Biological Characteristics in Juvenile-Onset Huntington's Disease.

Background: Juvenile-onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) characterized by symptom onset before the age of 21 years. Observational data in this cohort is lacking.

Objectives: Quantify measures of disease progression for use in clinical trials of patients with JOHD.

The S-Factor, a New Measure of Disease Severity in Spinocerebellar Ataxia: Findings and Implications.

Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders, but there is no metric that predicts disease severity over time. We hypothesized that by developing a new metric, the Severity Factor (S-Factor) using immutable disease parameters, it would be possible to capture disease severity independent of clinical rating scales. Extracting data from the CRC-SCA and READISCA natural history studies, we calculated the S-Factor for 438 participants with symptomatic SCA1, SCA2, SCA3, or SCA6, as follows: ((length of CAG repeat expansion - maximum normal repeat length) /maximum normal repeat length) × (current age - age at disease onset) × 10).

Behavioral features in child and adolescent huntingtin gene-mutation carriers.

Introduction: We compared neuropsychiatric symptoms between child and adolescent huntingtin gene-mutation carriers and noncarriers. Given previous evidence of atypical striatal development in carriers, we also assessed the relationship between neuropsychiatric traits and striatal development.

Methods: Participants between 6 and 18 years old were recruited from families affected by Huntington's disease and tested for the huntingtin gene expansion.

Neurofilament Light Protein as a Potential Blood Biomarker for Huntington's Disease in Children.

Background: Juvenile-onset Huntington's disease (JOHD) is a rare and particularly devastating form of Huntington's disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD.

Methods: We performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies.

Blood-Based Markers of Neuronal Injury in Adult-Onset Myotonic Dystrophy Type 1.

Introduction: The present study had four aims. First, neuronal injury markers, including neurofilament light (NF-L), total tau, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1), were compared between individuals with and without adult-onset myotonic dystrophy type 1 (DM1). Second, the impact of age and CTG repeat on brain injury markers was evaluated.

Global and Regional White Matter Fractional Anisotropy in Children with Chronic Kidney Disease.

Objective: To investigate the associations between neurocognition and white matter integrity in children with chronic kidney disease (CKD).

Study Design: This cross-sectional study included 17 boys (age 6-16 years) with a diagnosis of mild to moderate (stages 1-3, nondialysis/nontransplant) CKD because of congenital anomalies of the kidney and urinary tract and 20 typically developing community controls. Participants underwent 3T neuroimaging and diffusion-weighted magnetic resonance imaging to assess white matter fractional anisotropy.

Cognitive Deficits, Apathy, and Hypersomnolence Represent the Core Brain Symptoms of Adult-Onset Myotonic Dystrophy Type 1.

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, and is primarily characterized by muscle weakness and myotonia, yet some of the most disabling symptoms of the disease are cognitive and behavioral. Here we evaluated several of these non-motor symptoms from a cross-sectional time-point in one of the largest longitudinal studies to date, including full-scale intelligence quotient, depression, anxiety, apathy, sleep, and cerebral white matter fractional anisotropy in a group of 39 adult-onset myotonic dystrophy type 1 participants (27 female) compared to 79 unaffected control participants (46 female). We show that intelligence quotient was significantly associated with depression ( < 0.

Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease.

Background: Neurofilament light-chain (NfL) protein is a blood-based marker of neuroaxonal injury. We sought to (1) compare plasma NfL levels in children with chronic kidney disease (CKD) and healthy peers, (2) characterize the relationship between NfL level and kidney function, and (3) evaluate NfL as a predictor of abnormal brain structure in CKD.

Methods: Sixteen children with CKD due to congenital kidney anomalies and 23 typically developing peers were included.

Association of CAG Repeat Length in the Huntington Gene With Cognitive Performance in Young Adults.

Objective: To investigate the relationships between CAG repeat length in the huntingtin gene and cognitive performance in participants above and below the disease threshold for Huntington disease (HD), we performed a cross-sectional analysis of the Enroll-HD database.

Methods: We analyzed data from young, developing adults (≤30 years of age) without a history of depression, apathy, or cognitive deficits. We included participants with and without the gene expansion (CAG ≥36) for HD.

White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden.

Deficits in white matter (WM) integrity and motor symptoms are among the most robust and reproducible features of myotonic dystrophy type 1 (DM1). In the present study, we investigate whether WM integrity, obtained from diffusion-weighted MRI, corresponds to quantifiable motor outcomes (e.g.

DMPK mRNA Expression in Human Brain Tissue Throughout the Lifespan.

Objective: Myotonic dystrophy is a multisystem disorder caused by a trinucleotide repeat expansion on the myotonic dystrophy protein kinase () gene. To determine whether wildtype DMPK expression patterns vary as a function of age, we analyzed DMPK expression in the brain from 99 donors ranging from 5 postconceptional weeks to 80 years old.

Methods: We used the BrainSpan messenger RNA sequencing and the Yale Microarray data sets, which included brain tissue samples from 42 and 57 donors, respectively.

Brainstem and striatal volume changes are detectable in under 1 year and predict motor decline in spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 is a progressive neurodegenerative, movement disorder. With potential therapies on the horizon, it is critical to identify biomarkers that (i) differentiate between unaffected and spinocerebellar ataxia Type 1-affected individuals; (ii) track disease progression; and (iii) are directly related to clinical changes of the patient. Magnetic resonance imaging of volumetric changes in the brain may be a suitable source of biomarkers for spinocerebellar ataxia Type 1.

Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities.

Background: The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI).

Methods: The sample age range was 6-16 years.

Encoding of facial expressions in individuals with adult-onset myotonic dystrophy type 1.

Emotional issues are often reported among individuals with myotonic dystrophy type 1 (DM1) and some studies have suggested that deficits in ability to quickly encode emotions may contribute to these problems. However, poor performance on emotion encoding tasks could also be explained by a more general cognitive deficit (Full Scale IQ [FSIQ]), rather than a specific deficit in emotional processing. Since individuals with DM1 are known to exhibit difficulties in general cognitive abilities, it is important to account for FSIQ when evaluating emotion encoding.

Abnormal Brain Development in Huntington' Disease Is Recapitulated in the zQ175 Knock-In Mouse Model.

Emerging cellular and molecular studies are providing compelling evidence that altered brain development contributes to the pathogenesis of Huntington's disease (HD). There has been lacking longitudinal system-level data obtained from HD models supporting this hypothesis. Our human MRI study in children and adolescents with HD indicates that striatal development differs between the HD and control groups, with initial hypertrophy and more rapid volume decline in HD group.

Variant repeats within the CTG expansion protect function in myotonic dystrophy type 1.

Objective: We tested the hypothesis that variant repeat interruptions (RIs) within the CTG repeat tract lead to milder symptoms compared with pure repeats (PRs) in myotonic dystrophy type 1 (DM1).

Methods: We evaluated motor, neurocognitive, and behavioral outcomes in a group of 6 participants with DM1 with RI compared with a case-matched sample of 12 participants with DM1 with PR and a case-matched sample of 12 unaffected healthy comparison participants (UA).

Results: In every measure, the RI participants were intermediate between UA and PR participants.

Procedural and declarative memory brain systems in developmental language disorder (DLD).

The aim of the current study was to examine microstructural differences in white matter relevant to procedural and declarative memory between adolescents/young adults with and without Developmental Language Disorder (DLD) using diffusion tensor imaging (DTI). The findings showed atypical age-related changes in white matter structures in the corticostriatal system, in the corticocerebellar system, and in the medial temporal region in individuals with DLD. Results highlight the importance of considering the age factor in research on DLD.

Cognitive function and its relationship with brain structure in myotonic dystrophy type 1.

Studies have shown relationships between white matter abnormalities and cognitive dysfunction in myotonic dystrophy type 1 (DM1), but comprehensive analysis of potential structure-function relationships are lacking. Fifty adult-onset DM1 individuals (33 female) and 68 unaffected adults (45 female) completed the Wechsler Adult Intelligence Scale-IV (WAIS-IV) to determine the levels and patterns of intellectual functioning. Neuroimages were acquired with a 3T scanner and were processed with BrainsTools.