Search

Objective: Huntington's Disease (HD) is an inherited neurodegenerative disease caused by the mutation of the Htt gene, impacting all aspects of living and functioning. Among cognitive disabilities, spatial capacities are impaired, but their monitoring remains scarce as limited by lengthy experts' assessments. Language offers an alternative medium to evaluate patients' performance in HD. Yet, its capacities to assess HD's spatial abilities are unknown. Here, we aimed to bring proof-of-concept that HD's spatial deficits can be assessed through speech., Methods: We developed the Spatial Description Model to graphically represent spatial relations described during the Cookie Theft Picture (CTP) task. We increased the sensitivity of our model by using only sentences with spatial terms, unlike previous studies in Alzheimer's disease. 78 carriers of the mutant Htt, including 56 manifest and 22 premanifest individuals, as well as 25 healthy controls were included from the BIOHD & (NCT01412125) & Repair-HD (NCT03119246) cohorts. The convergence and divergence of the model were validated using the SelfCog battery., Results: Our Spatial Description Model was the only one among the four assessed approaches, revealing that individuals with manifest HD expressed fewer spatial relations and engaged in less spatial exploration compared to healthy controls. Their graphs correlated with both visuospatial and language SelfCog performances, but not with motor, executive nor memory functions., Conclusions: We provide the proof-of-concept using our Spatial Description Model that language can grasp HD patient's spatial disturbances. By adding spatial capabilities to the panel of functions tested by the language, it paves the way for eventual remote clinical application., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The unified model of time processing suggests that the striatum is a central structure involved in all tasks that require the processing of temporal durations. Patients with Huntington's disease exhibit striatal degeneration and a deficit in time perception in interval timing tasks (i.e. for duration ranging from hundreds of milliseconds to minutes), but whether this deficit extends to time production remains unclear. In this study, we investigated whether symptomatic patients (HD, N = 101) or presymptomatic gene carriers (Pre-HD, N = 31) of Huntington's disease had a deficit in time production for durations between 4 and 10 s compared to healthy controls and whether this deficit developed over a year for patients. We found a clear deficit in temporal production for HD patients, whereas Pre-HD performed similarly to Controls. For HD patients and Pre-HD participants, task performance was correlated with grey matter volume in the amygdala and caudate, bilaterally. These results confirm that the striatum is involved in interval timing not only in perception but also in production, in accordance with the unified model of time processing. Furthermore, exploratory factor analyses on our data indicated that temporal production was associated with clinical assessments of psychomotor and executive functions. Finally, when retested twelve months later, the deficit of HD patients remained stable, although striatal degeneration was more pronounced. Thus, the simple, short and language-independent temporal production task may be a useful clinical tool to detect striatal degeneration in patients in early stages of Huntington's disease. However, its usefulness to detect presymptomatic stages or for monitoring the evolution of HD over a year seems limited., Competing Interests: Declaration of competing interest Laurie Lemoine, Marine Lunven, Nicolas Fraisse, Katia Youssov, Blanche Bapst, Graça Morgado and Vincent de Gardelle declare no conflict of interest. AC Bachoud-Lévi: Expert for Roch between 2020 and 2021 and PI on various academic grants. David Craufurd: Advisory Boards (F Hoffman-La Roche, Lundbeck, Novartis UK)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.

Objective: The objective of this article is to review anatomical, histological and physiological muscle changes following below-knee amputation., Materials and Methods: We searched the PubMed and Reedoc databases for studies evaluating modifications of the below-knee stump and changes over time in its anatomy, volume and histology. We also looked at postamputation modifications in gait and balance., Results: Below-knee amputees show muscular atrophy on both the amputated side and nonamputated side, with fewer and smaller muscle fibres (particularly slow-twitch fibres). This amyotrophy varies in magnitude and distribution and can reach about 25% for the quadriceps (predominantly on the medial side), but is nonsignificant for the hamstrings. This amyotrophy results from the anatomical consequences of the surgical act. The loss of one or more of a muscle's insertions or reimplantation into a nonphysiological site prompts greater atrophy. Changes in muscle activation patterns also lead to atrophy. The hamstrings replace the triceps as the main muscles for propulsion and the remaining stump muscles contract so as to ensure a good fit with the prosthesis. The below-knee amputee must adapt to a new muscular state: gait symmetry is altered, energy expenditure for walking is higher and training is needed in order to achieve optimal balance control.