2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency.

Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance.

Clustering of prostate cancer healthcare pathways in the French National Healthcare database.

Background: Healthcare pathways of patients with prostate cancer are heterogeneous and complex to apprehend using traditional descriptive statistics. Clustering and visualization methods can enhance their characterization.

Methods: Patients with prostate cancer in 2014 were identified in the French National Healthcare database (-SNDS) and their data were extracted with up to 5 years of history and 4 years of follow-up.

Blazar Constraints on Neutrino-Dark Matter Scattering.

Neutrino emission in coincidence with gamma rays has been observed from the blazar TXS 0506+056 by the IceCube telescope. Neutrinos from the blazar had to pass through a dense spike of dark matter (DM) surrounding the central black hole. The observation of such a neutrino implies new upper bounds on the neutrino-DM scattering cross section as a function of DM mass.

Imbalance between alpha-1-antitrypsin and interleukin 6 is associated with in-hospital mortality and thrombosis during COVID-19.

Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19.

Structural, Microstructural, and Metabolic Alterations in Primary Progressive Aphasia Variants.

Neuroimaging studies have described the brain alterations in primary progressive aphasia (PPA) variants (semantic, logopenic, nonfluent/agrammatic). However, few studies combined T1, FDG-PET, and diffusion MRI techniques to study atrophy, hypometabolism, and tract alterations across the three PPA main variants. We therefore explored a large early-stage cohort of semantic, logopenic and nonfluent/agrammatic variants ( = 86) and of 23 matched healthy controls with anatomical MRI (cortical thickness), FDG PET (metabolism) and diffusion MRI (white matter tracts analyses), aiming at identifying cortical and sub-cortical brain alterations, and confronting these alterations across imaging modalities and aphasia variants.

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias.

Objective: To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown.

Methods: We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities.

Cognitive complaint in early Parkinson's disease: A pilot study.

Background: Subjective cognitive complaint (SCC) is a criterion recommended by the Movement Disorder Society (MDS) task force for the diagnosis of mild cognitive impairment (MCI). Until now there were few specific tools for detecting SCC in PD. We sought to develop a new tool to assess SCC specifically dedicated for PD.

Familiarity and recollection vs representational models of medial temporal lobe structures: A single-case study.

Although it is known that medial temporal lobe (MTL) structures support declarative memory, the fact these structures have different architectonics and circuitry suggests they may also play different functional roles. Selective lesions of MTL structures offer an opportunity to understand these roles. We report, in this study, on JMG, a patient who presents highly unusual lesions that completely affected all MTL structures except for the right hippocampus and parts of neighbouring medial parahippocampal cortex.

Case report of Lewy body disease mimicking Creutzfeldt-Jakob disease in a 44-year-old man.

Background: Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease.

Case Presentation: We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations.

Pauses During Autobiographical Discourse Reflect Episodic Memory Processes in Early Alzheimer's Disease.

There is a large body of research on discourse production in Alzheimer's disease (AD). Some studies have focused on pause production, revealing that patients make extensive use of pauses during speech. This has been attributed to lexical retrieval difficulties, but pausing may also reflect other forms of cognitive impairment as it increases with cognitive load.

Proper name anomia with preserved lexical and semantic knowledge after left anterior temporal lesion: a two-way convergence defect.

This article describes the case of a patient who, following herpes simplex encephalitis (HSE), retained the ability to access rich conceptual semantic information for familiar people whom he was no longer able to name. Moreover, this patient presented the very rare combination of name production and name comprehension deficits for different categories of proper names (persons and acronyms). Indeed, besides his difficulty to retrieve proper names, SL presented a severe deficit in understanding and identifying them.

Neuropsychological outcome after carbon monoxide exposure following a storm: a case-control study.

Background: The cognitive consequences of carbon monoxide (CO) poisoning are well described. However, most studies have been carried out without an ad-hoc group of control subjects. The main aim of this study was to evaluate cognitive and psychiatric outcome after CO exposure during the storm Klaus in the South West of France (January 2009) in a homogeneous group of patients compared to a group of 1:1 paired controls.

A case of logopenic primary progressive aphasia with C9ORF72 expansion and cortical florbetapir binding.

We report the case of a 65-year-old woman, clinically diagnosed with the logopenic variant of primary progressive aphasia (PPA), and carrier of C9ORF72 expansion, despite cerebrospinal fluid biomarkers suggesting Alzheimer's disease (AD). She underwent structural MRI, metabolic PET, and amyloid PET imaging using florbetapir. Comparison with healthy controls revealed widespread hypometabolism, left sided cortical atrophy, and an increased cortical amyloid load.

Cortical florbetapir-PET amyloid load in prodromal Alzheimer's disease patients.

Background: Florbetapir (AV-45) has been shown to be a reliable tool to assess amyloid load in patients with Alzheimer's disease (AD) at demential stages. Longitudinal studies also suggest that AV-45 has the ability to bind amyloid in the early stages of AD. In this study, we investigated AV-45 binding and its relation with cognitive performance in a group of patients at the prodromal stage of Alzheimer's disease, recruited according to strict inclusion criteria.

C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing.

Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion.

[Early diagnosis of Alzheimer's disease].

Introduction: Diagnosis of Alzheimer's disease (AD) remains difficult to establish, and can only be considered as certain thanks to anatomopathological evidence, or genetic mutations. Current diagnostic criteria rely on innovative imaging and biological tools, in order to detect pathological cues from very early stages, and with best sensibility and sensitivity.

State Of Art: Advances in neuro-imaging enabled the development of different tools to help establishing the diagnosis, such as cerebral atrophy assessment on magnetic resonance imaging (MRI), and cerebral metabolism study on positron emission tomography (PET).

MR, (18)F-FDG, and (18)F-AV45 PET correlate with AD PSEN1 original phenotype.

We report the case of a 37-year-old man suffering from insidious visual agnosia and spastic paraparesis due to a PSEN1 mutation. His mother was diagnosed with Alzheimer disease after a biopsy. He was assessed by multimodal neuroimaging, including new in vivo positron emission tomography amyloid imaging (F-AV45).

The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers.

We describe 56 novel autosomal dominant early-onset Alzheimer disease (ADEOAD) families with PSEN1, PSEN2, and AβPP mutations or duplications, raising the total of families with mutations on known genes to 111 (74 PSEN1, 8 PSEN2, 16 AβPP, and 13 AβPP duplications) in the French series. In 33 additional families (23% of the series), the genetic determinism remained uncharacterized after this screening. Cerebrospinal fluid (CSF) biomarker levels were obtained for patients of 58 families (42 with known mutations and 16 without genetic characterization).

A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease.

Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases.

Amyloid imaging with AV45 ((18)F-florbetapir) in a cognitively normal AβPP duplication carrier.

We report the case of a 62-year-old asymptomatic carrier of AβPP gene duplication. He was investigated by MRI and the amyloid ligand (18)F-AV45, and compared to Alzheimer's disease patients (n = 11) and healthy controls (n = 11). The neuropsychological examination was normal.

Neuropsychological outcome after a first symptomatic ischaemic stroke with 'good recovery'.

Background: Neuropsychological impairment after stroke when no motor, sensory or language deficits are left remains understudied. The primary aim of this study was to assess neuropsychological outcome in a specific population of patients after a first symptomatic stroke without previous cognitive decline and with a good motor, linguistic, and functional recovery (i.e.

Memantine in behavioral variant frontotemporal dementia: negative results.

We tested the efficacy and tolerability of one-year treatment with memantine (10 mg bid) in behavioral variant frontotemporal dementia (bvFTD). BvFTD patients aged 45 to 75 years, with a Mini-Mental Status Examination (MMSE) score ≥19, were enrolled in a national, randomized, double-blind, placebo-controlled (DBPC), Phase II trial. The primary endpoint was the CIBIC-Plus (Clinician's Interview-Based Impression of Change Plus Caregiver Input).