Social cognition profile in early Huntington disease: Insight from neuropsychological assessment and structural neuroimaging.

Background: Huntington's disease (HD) is traditionally associated with motor, cognitive, and neuropsychiatric symptoms. Recent observations suggest that disturbances in social cognition may feature prominently in HD, potentially contributing to behavioral challenges.

Objective: This study aims to explore the onset and neural mechanisms underlying social cognition disturbances in HD, which are not yet well understood despite increasing recognition of these symptoms.

Two Cases of ROSAH-Like Syndrome Restricted to the Ophthalmologic Presentation.

Purpose: To report the clinical presentation and follow-up, including the optical coherence tomography, angiography and electrophysiology of two individuals from the same family presenting with an isolated retinal dystrophy and optic nerve edema who were diagnosed with ROSAH-like syndrome.

Method: Observational case report of a 55-year-old woman and her 36-year-old son with a genetic analysis of ROSAH, after a long-term follow-up.

Results: Both the mother and her son displayed severe optic nerve infiltration and retinal pigment atrophy with intraocular inflammation, which were not improved by immunosuppressive treatment.

Opa1 and MT-Nd6 mutations induce early mitochondrial changes in the retina and prelaminar optic nerve of hereditary optic neuropathy mouse models.

Hereditary optic neuropathies, including dominant optic atrophy and Leber's hereditary optic neuropathy, are genetic disorders characterized by retinal ganglion cell degeneration leading to vision loss, mainly associated with mitochondrial dysfunction. In this study, we analysed mitochondrial distribution and ultrastructure in the retina and longitudinal optic nerve sections of pre-symptomatic hereditary optic neuropathies mouse models with Opa1 and Nd6 deficiency to identify early mitochondrial changes. Our results show significant mitochondrial fragmentation and increased mitophagy in mice, indicating early mitochondrial changes prior to neuronal loss.

Four- and sixteen-month clinical status of a cohort of patients following hospitalization for COVID-19.

Background And Objectives: Although many symptoms of post-COVID syndrome have been described, a comprehensive evaluation of their prevalence is lacking. We aimed to describe symptoms at 16 months from hospitalization for COVID-19.

Methods: A telephone assessment was performed one year later in a cohort of COVID-19 survivors hospitalized between March and May 2020 and already evaluated four months after discharge.

Upstream open reading frame-introducing variants in patients with primary familial brain calcification.

More than 50% of patients with primary familial brain calcification (PFBC), a rare neurological disorder, remain genetically unexplained. While some causative genes are yet to be identified, variants in non-coding regions of known genes may represent a source of missed diagnoses. We hypothesized that 5'-Untranslated Region (UTR) variants introducing an AUG codon may initiate mRNA translation and result in a loss of function in some of the PFBC genes.

Stochastic Optical Reconstruction Microscopy Imaging of Multiple System Atrophy Inclusions Suggests Stepwise α-Synuclein Aggregation.

Background: The architecture and composition of glial (GCI) and neuronal (NCI) α-synuclein inclusions observed in multiple system atrophy (MSA) remain to be precisely defined to better understand the disease.

Methods: Here, we used stochastic optical reconstruction microscopy (STORM) to characterize the nanoscale organization of glial (GCI) and neuronal (NCI) α-synuclein inclusions in cryopreserved brain sections from MSA patients.

Results: STORM revealed a dense cross-linked internal structure of α-synuclein in all GCI and NCI.

"Ten euros now" temporal discounting in Huntington disease.

Background: When making decisions, one often faces a trade-off between immediate and long-term rewards. In these situations, people may prefer immediate over later rewards, even if immediate rewards are smaller than later ones; a phenomenon known as temporal discounting. In this study, we, for the first time, assessed temporal discounting in three populations: participants with manifest Huntington disease (HD), participants with premanifest HD, and control participants.

Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants.

Although tocilizumab treatment in severe and critical coronavirus disease 2019 (COVID-19) patients has proven its efficacy at the clinical level, there is little evidence supporting the effect of short-term use of interleukin-6 receptor blocking therapy on the B cell sub-populations and the cross-neutralization of SARS-CoV-2 variants in convalescent COVID-19 patients. We performed immunological profiling of 69 tocilizumab-treated and non-treated convalescent COVID-19 patients in total. We observed that SARS-CoV-2-specific IgG1 titers depended on disease severity but not on tocilizumab treatment.

Design and application of a customizable relational DataBase to assess clinicopathological correlations and concomitant pathology in neurodegenerative diseases.

The diagnosis of neurodegenerative diseases is made complex by the heterogenous phenotype of the patients and the regular occurrence of concomitant pathology. Studying clinicopathological correlations in autopsy series is a central approach to improve pathological prediction in clinical practice. However, such method requires a wealth of information, and the use of standard spreadsheet software is hardly suitable.

The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands.

Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form the optic nerves, with a consistent genetic heterogeneity. As part of our diagnostic activity, we retrospectively evaluated the combination of Leber hereditary optic neuropathy mutations testing with the exon sequencing of 87 nuclear genes on 2186 patients referred for suspected hereditary optic neuropathies. The positive diagnosis rate in individuals referred for Leber hereditary optic neuropathy testing was 18% (199/1126 index cases), with 92% (184/199) carrying one of the three main pathogenic variants of mitochondrial DNA (m.

The burden of Huntington's disease: A prospective longitudinal study of patient/caregiver pairs.

Background: Caregiver burden is widely recognized in Huntington's disease, but little is known about the factors determining its evolution over time in the absence of longitudinal studies. Our objective was to identify typical patterns of caregiver burden level and evolution using both patients' and caregivers' characteristics over a one-year period to identify potential levers for alleviation.

Methods: We conducted a prospective multicenter longitudinal study in caregiver/patient pairs in Huntington's disease (NCT02876445) between March 2011 and May 2015.

Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial.

Background: Riluzole has been reported to be beneficial in patients with cerebellar ataxia; however, effectiveness in individual subtypes of disease is unclear due to heterogeneity in participants' causes and stages of disease. Our aim was to test riluzole in a single genetic disease, spinocerebellar ataxia type 2.

Methods: We did a randomised, double-blind, placebo-controlled, multicentre trial (the ATRIL study) at eight national reference centres for rare diseases in France that were part of the Neurogene National Reference Centre for Rare Diseases.

Reperfusion therapy for acute ischemic stroke in older people: An observational real-life study.

Background: While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS.

Methods: Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed.

Dominant mutations are a frequent cause of isolated optic atrophy.

Biallelic mutations in , encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in , among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier.

Improved detection of mitochondrial DNA instability in mitochondrial genome maintenance disorders.

Purpose: Diseases caused by defects in mitochondrial DNA (mtDNA) maintenance machinery, leading to mtDNA deletions, form a specific group of disorders. However, mtDNA deletions also appear during aging, interfering with those resulting from mitochondrial disorders.

Methods: Here, using next-generation sequencing (NGS) data processed by eKLIPse and data mining, we established criteria distinguishing age-related mtDNA rearrangements from those due to mtDNA maintenance defects.

Four-Month Clinical Status of a Cohort of Patients After Hospitalization for COVID-19.

Importance: Little is known about long-term sequelae of COVID-19.

Objective: To describe the consequences at 4 months in patients hospitalized for COVID-19.

Design, Setting, And Participants: In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020.

Evolution in geriatric syndromes and association with survival over 5 years in the GERODIAB cohort of older French diabetic patients.

Purpose: Although one in three patients with diabetes in Western countries is over 70 years-old, geriatric syndromes and their relationship with survival remain seldom studied. The present aim of the GERODIAB study was to examine the evolution of geriatric disorders and their relationship with survival in older type 2 patients with diabetes with initial sufficient autonomy.

Methods: We performed a prospective, observational study over 5 years in patients with diabetes aged 70 years or above.

STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain.

Aims: Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high-resolution imaging approaches is a current challenge in neuroscience.

Methods: To this end, we used a recent super-resolution imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyse human brain sections.

Neocortical morphometry in Huntington's disease: Indication of the coexistence of abnormal neurodevelopmental and neurodegenerative processes.

Huntington's disease (HD) is an inherited, autosomal dominant disorder that is characteristically thought of as a degenerative disorder. Despite cellular and molecular grounds suggesting HD could also impact normal development, there has been scarce systems-level data obtained from in vivo human studies supporting this hypothesis. Sulcus-specific morphometry analysis may help disentangle the contribution of coexisting neurodegenerative and neurodevelopmental processes, but such an approach has never been used in HD.