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Background Aims Methods Results Conclusions Differentiating idiopathic Parkinson disease (iPD) from other causes of tremor and parkinsonism based on clinical grounds can be challenging, particularly early in the course of disease or in the case of atypical clinical presentations. 18F‐fluorodopa (F‐DOPA) is a positron emission tomography (PET) radioligand that can be used to demonstrate the presence and pattern of striatal presynaptic dopaminergic deficit and, thus, assist in the diagnosis of iPD and related disorders.To determine the clinical utility of F‐DOPA PET in an Australian movement disorder clinic setting.Retrospective cohort study of movement disorder clinic patients referred for F‐DOPA PET by four movement disorder neurologists over a 10‐year period to a single Australian nuclear medicine centre. Results of F‐DOPA PET scans were correlated with changes in provisional diagnosis and management in the short term following review of F‐DOPA PET results.A total of 105 F‐DOPA PET scan results and patient records were examined. In this cohort, provisional clinical diagnosis was altered in 37.9% of patients, and changes to clinical management were made in 48.4% of patients in the short term following review of F‐DOPA PET results. Changes in both diagnosis and management were more common following a normal F‐DOPA PET scan result (42.4% and 53.0% respectively) than a scan consistent with iPD (23.5% and 32.4% respectively).There was significant change in provisional clinical diagnosis and management in the short term following review of F‐DOPA PET results indicating significant clinical utility of F‐DOPA PET in the Australian movement disorder clinic setting. [ABSTRACT FROM AUTHOR]

The hereditary cerebellar ataxias (HCAs) are rare, progressive neurologic disorders caused by variants in many different genes. Inheritance may follow autosomal dominant, autosomal recessive, X-linked or mitochondrial patterns. The list of genes associated with adult-onset cerebellar ataxia is continuously growing, with several new genes discovered in the last few years. This includes short-tandem repeat (STR) expansions in RFC1, causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), FGF14-GAA causing spinocerebellar ataxia type 27B (SCA27B), and THAP11. In addition, the genetic basis for SCA4, has recently been identified as a STR expansion in ZFHX3. Given the large and growing number of genes, and different gene variant types, the approach to diagnostic testing for adult-onset HCA can be complex. Testing methods include targeted evaluation of STR expansions (e.g. SCAs, Friedreich ataxia, fragile X-associated tremor/ataxia syndrome, dentatorubral-pallidoluysian atrophy), next generation sequencing for conventional variants, which may include targeted gene panels, whole exome, or whole genome sequencing, followed by various potential additional tests. This review proposes a diagnostic approach for clinical testing, highlights the challenges with current testing technologies, and discusses future advances which may overcome these limitations. Implementing long-read sequencing has the potential to transform the diagnostic approach in HCA, with the overall aim to improve the diagnostic yield. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 57-year-old Han Chinese male with dopa-responsive dystonia (DRD) caused by a large inversion affecting the GCH1 gene. The patient experienced abnormal head posturing and gait disturbance following a head injury at age 10. Despite not having an identifiable disease-causing variant through conventional gene sequencing, the patient responded well to low-dose levodopa treatment. The study highlights the importance of using whole genome sequencing, nanopore long-read sequencing, and optical genome mapping to detect and confirm complex structural variants in patients with DRD. [Extracted from the article]

Currently, pathogenic variants in more than 500 different genes are known to cause various movement disorders. The increasing accessibility and reducing cost of genetic testing has resulted in increasing clinical use of genetic testing for the diagnosis of movement disorders. However, the optimal use case(s) for genetic testing at a patient level remain ill-defined. Here, we review the utility of genetic testing in patients with movement disorders and also highlight current challenges and limitations that need to be considered when making decisions about genetic testing in clinical practice. Highlights: The utility of genetic testing extends across multiple clinical and non-clinical domains. Here we review different aspects of the utility of genetic testing for movement disorders and the numerous associated challenges and limitations. These factors should be weighed on a case-by-case basis when requesting genetic tests in clinical practice. [ABSTRACT FROM AUTHOR]

Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. There is no disease-modifying treatment currently available. Therefore, standardized, validated outcome measures to facilitate clinical trials are urgently needed. We performed a scoping review of outcome measures and biomarkers for HSP to provide recommendations for future studies and identify areas for further research. We searched Embase, Medline, Scopus, Web of Science, and the Central Cochrane database. Seventy studies met the inclusion criteria, and eighty-three outcome measures were identified. The Spastic Paraplegia Rating Scale (SPRS) was the most widely used (27 studies), followed by the modified Ashworth Scale (18 studies) and magnetic resonance imaging (17 studies). Patient-reported outcome measures (PROMs) were infrequently used to assess treatment outcomes (28% of interventional studies). Diffusion tensor imaging, gait analysis and neurofilament light chain levels were the most promising biomarkers in terms of being able to differentiate patients from controls and correlate with clinical disease severity. Overall, we found variability and inconsistencies in use of outcome measures with a paucity of longitudinal data. We highlight the need for (1) a standardized set of core outcome measures, (2) validation of existing biomarkers, and (3) inclusion of PROMs in HSP clinical trials. [ABSTRACT FROM AUTHOR]

The DES gene encodes desmin, a key intermediate filament of skeletal, cardiac and smooth muscle. Pathogenic DES variants produce a range of skeletal and cardiac muscle disorders collectively known as the desminopathies. We report three desminopathy cases which highlight the phenotypic heterogeneity of this disorder and discuss various factors that may contribute to the clinical dierences seen between patients with dierent desmin variants and also between family members with the same varian. [ABSTRACT FROM AUTHOR]