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The thresholds for considering neurological signs as soft versus significant for ataxia, parkinsonism, dystonia, etc. are critically important in tremor classification and must be studied across movement disorder subspecialties, not simply within a pool of tremor specialists.

Clinical signs leading to diagnostic disagreement were identified with STEA, and STEA should therefore be useful in future studies of diagnostic disagreement. The thresholds for considering neurological signs as soft versus significant for ataxia, parkinsonism, dystonia, etc. are critically important in tremor classification and must be studied across movement disorder subspecialties, not simply within a pool of tremor specialists.

Apathy is a disorder of motivation common to Huntington’s disease (HD). Recent conceptual frameworks suggest that apathy is not unitary but consists of discrete subtypes (“dimensions”). Which of the proposed dimensions are preferentially affected in HD, and how these dimensions evolve with disease progression is unknown.

The Dimensional Apathy Scale (DAS) separates apathy into Executive, Initiation and Emotional subscales. Using the DAS, we aimed to 1) Determine the apathy subtypes prevalent in HD; 2) Compare the DAS against a unitary measure of apathy (Apathy Evaluation Scale, AES); 3) Assess the reliability of self- and observer-ratings; and 4) Determine the relationship between the DAS, and disease burden, total functional capacity (TFC) and the AES.

Fifty pre-manifest, 51 manifest-HD, 87 controls, and 50 HD-observers completed the DAS, AES, and TFC.

Manifest-HD participants had the highest levels of apathy across all dimensions (30.4% on Executive subscale, 34.8% on Initiation subscale, and 15.2% on Emotional subscale), relative to pre-manifest and control participants. click here Self- and observer-ratings on the DAS did not differ. Hierarchical regressions across the entire gene-expanded sample showed that scores on the Initiation subscale correlated with AES scores; higher Executive subscale scores were related to higher disease burden; and Emotional subscale scores with lower total functional capacity.

In this first study of the DAS in HD, manifest-HD participants were more apathetic than pre-manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.

In this first study of the DAS in HD, manifest-HD participants were more apathetic than pre-manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.

Determination of disease onset in Huntington’s disease is made by clinical experience. The diagnostic confidence level is an assessment regarding the certainty about the clinical diagnosis based on motor signs. A level of 4 means the rater has ≥99% confidence motor abnormalities are unequivocal signs of disease. However, it does not state which motor abnormalities are signs of disease and how many must be present.

Our aim is to explore how accurate the diagnostic confidence level is in estimating disease onset using the Enroll-HD data set. For clinical disease onset we use a cut-off total motor score >5 of the Unified Huntington’s Disease Rating Scale. link2 This score is used in the TRACK-HD study, with ≤5 indicating no substantial motor signs in premanifests.

At baseline premanifest participants who converted to manifest (converters) and non-converters were compared for clinical symptoms and diagnostic confidence level. Clinical symptoms and diagnostic confidence levels were longitudinally displayed in converters.

Of 3731 eligible participants, 455 were converters and 3276 non-converters. Baseline diagnostic confidence levels were significantly higher in converters compared to non-converters (

< 0.001). 232 (51%) converters displayed a baseline motor score >5 (mean = 6.7). Converters had significantly more baseline clinical symptoms, and higher disease burden compared to non-converters (

< 0.001). Diagnostic confidence level before disease onset ranged between 1 and 3 in converters.

According to this data the diagnostic confidence level is not an accurate instrument to determine phenoconversion. With trials evaluating disease modifying therapies it is important to develop more reliable diagnostic criteria.

According to this data the diagnostic confidence level is not an accurate instrument to determine phenoconversion. With trials evaluating disease modifying therapies it is important to develop more reliable diagnostic criteria.

Neuroimaging has been used to support a diagnosis of possible multiple system atrophy (MSA). Only blood pressure changes upon standing are included in the second consensus criteria but other autonomic function tests (AFT) are also useful to diagnose widespread and progressive autonomic failure typical of MSA. Additional diagnostic tools are of interest to improve accuracy of MSA diagnosis.

To assess the utility of diagnostic tools beyond brain imaging and AFT in enhancing a laboratory-supported diagnosis of MSA to support the upcoming revision of the consensus criteria.

The International Parkinson and Movement Disorders Society MSA Study Group (MoDiMSA) performed a systematic review of original papers on biomarkers, sleep studies, genetic, neuroendocrine, neurophysiological, neuropsychological and other tests including olfactory testing and acute levodopa challenge test published before August 2019.

Evaluation of history of levodopa responsiveness and olfaction is useful in patients in whom MSA-parkinsonian subtype is suspected. Neuropsychological testing is useful to exclude dementia at time of diagnosis. Applicability of sphincter EMG is limited. When MSA-cerebellar subtype is suspected, a screening for the common causes of adult-onset progressive ataxia is useful, including spinocerebellar ataxias in selected patients. Diagnosing stridor and REM sleep behavior disorder is useful in both MSA subtypes. However, none of these tools are validated in large longitudinal cohorts of postmortem confirmed MSA cases.

Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

Despite limited evidence, additional laboratory work-up of patients with possible MSA beyond imaging and AFT should be considered to optimize the clinical diagnostic accuracy.

In the field of movement disorders, what you see (phenotype) is seldom what you get (genotype). Whereas 1 phenotype was previously associated to 1 gene, the advent of next-generation sequencing (NGS) has facilitated an exponential increase in disease-causing genes and genotype-phenotype correlations, and the “one-phenotype-many-genes” paradigm has become prominent.

To highlight the “one-phenotype-many-genes” paradigm by discussing the main challenges, perspectives on how to address them, and future directions.

We performed a scoping review of the various aspects involved in identifying the underlying molecular cause of a movement disorder phenotype.

The notable challenges are (1) the lack of gold standards, overlap in clinical spectrum of different movement disorders, and variability in the interpretation of classification systems; (2) selecting which patients benefit from genetic tests and the choice of genetic testing; (3) problems in the variant interpretation guidelines; (4) the filtering of variadiagnostic yield. Future directions, including post-NGS phenotyping and cohort analyses enriched by genotype-phenotype integration and gene networks, ought to be pursued to accelerate identification of disease-causing genes and further improve our understanding of disease biology.

Progress in genetics – particularly the advent of next-generation sequencing (NGS) – has enabled an unparalleled gene discovery and revealed unmatched complexity of genotype-phenotype correlations in movement disorders. Among other things, it has emerged that mutations in one and the same gene can cause multiple, often markedly different phenotypes. Consequently, movement disorder specialists have increasingly experienced challenges in clinicogenetic correlations.

To deconstruct biological phenomena and mechanistic bases of phenotypic heterogeneity in monogenic movement disorders and neurodegenerative diseases. To discuss the evolving role of movement disorder specialists in reshaping disease phenotypes in the NGS era.

This scoping review details phenomena contributing to phenotypic heterogeneity and their underlying mechanisms.

Three phenomena contribute to phenotypic heterogeneity, namely incomplete penetrance, variable expressivity and pleiotropy. Their underlying mechanisms, which are often shared unique in its reliance on clinical judgment to accurately define disease phenotypes. This has been reaffirmed by the NGS revolution, which provides ever-growing sequencing data and fuels challenges in variant pathogenicity assertions for such clinically heterogeneous disorders. Deep phenotyping, with characterization and continual updating of “core” phenotypes, and comprehension of determinants of genotype-phenotype complex relationships are crucial for clinicogenetic correlations and have implications for the diagnosis, treatment and counseling.

Peripherally induced movement disorders represent a rare and debated complication of peripheral trauma. link3 It is difficult to determine a causal relationship between peripheral injuries and subsequent movement disorders.

Here, we introduce and characterize four patients with post-surgical scar-associated movement disorders, a peripherally-induced rippling movement disorder confined to the muscles just under a long surgical incision scar, appearing weeks to months after surgery. This novel ‘scar dancing’ syndrome does not spread to adjacent muscles and persists during sleep.

Scar dancing syndrome expands the phenotypic spectrum of peripherally induced movement disorders, in which movement disorder is confined to a long surgical incision site.

Scar dancing syndrome expands the phenotypic spectrum of peripherally induced movement disorders, in which movement disorder is confined to a long surgical incision site.The islets of Langerhans constitute the endocrine pancreas which regulates blood glucose homeostasis and their dysfunction results in diabetes. Each of the pancreatic islets constitutes an entire micro-organ with intricate cell to cell interactions and that is well vascularized and innervated. An important therapeutic advantage in islet transplant is that pancreatic islets maintain their organ integrity when isolated and transplanted to patients with severe diabetes. Once transplanted, the islet micro-organs actively contribute to their own vascularization and start to function immediately. Hence, in terms of organ transplantation, the application of pancreatic islets will be a decisive clinical tool for future diabetes care (credit Tilo Moede).Significance Signal contamination is a major hurdle in functional near-infrared spectroscopy (fNIRS) of the human head as the NIR signal is contaminated with the changes corresponding to superficial tissue, therefore occluding the functional information originating from the cerebral region. For continuous wave, this is generally handled through linear regression of the shortest source-detector (SD) distance intensity measurement from all of the signals. Although phase measurements utilizing frequency domain (FD) provide deeper tissue sampling, the use of the shortest SD distance phase measurement for regression of superficial signal contamination can lead to misleading results, therefore suppressing cortical signals. Aim An approach for FD fNIRS that utilizes a short-separation intensity signal directly to regress both intensity and phase measurements, providing a better regression of superficial signal contamination from both data-types, is proposed. Approach Simulated data from realistic models of the human head are used, and signal regression using both intensity and phase-based components of the FD fNIRS is evaluated.