Abstract Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods ...Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD PCA-AD, Lewy body disease PCA-LBD, corticobasal degeneration PCA-CBD, prion disease PCA-prion) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work.
Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main ...cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
Some students have neurodevelopmental disorders that might affect their academic and professional careers if they are not identified and addressed by specific pedagogic adaptations. The objective of ...this work was to describe medical teachers' opinions of students with neurodevelopmental disorders and their management of these students.
An anonymous cross-sectional electronic survey was performed to describe medical teachers' opinions about the impact of neurodevelopmental disorders on the student's life and on the medical teachers' management. aThe survey was created, including visual analogic scales and free text, to assess teachers' opinions from identification and assessment of neurodevelopemental burden on students and teachers, to their own knowledge about neurodevelopemental disorders and the specific pedagogic management available. The survey was sent to 175 medical teachers in 2019, of whom 67 responded. Quantitative descriptive statistics and qualitative analysis of free text were reported.
Many medical teachers report having encountered students who might have had neurodevelopmental disorders (dyspraxia 33%; dyslexia 46%; autism spectrum disorders 68%; attention deficit hyperactivity disorders 75%). Impact on students and on teachers was considered as important (mean VAS score for impact over 60/100 for all syndromes except for dyspraxia). Medical teachers' self-reported knowledge about neurodevelopmental disorders (mean VAS score 43.9/100) and available pedagogical adaptations (mean VAS score 19.0/100) was limited. The teachers were concerned about ethical issues (mean VAS score 72.2/100) but were interested in receiving specialized training (mean VAS score 64.4/100).
Medical teachers feel unprepared to manage students with neurodevelopmental disorders. They would be interested in specific training and procedures about the pedagogic management of these students.
Introduction
The Balloon Analog Risk Task (BART), a computerized behavioral paradigm, is one of the most common tools used to assess the risk-taking propensity of an individual. Since its initial ...behavioral version, the BART has been adapted to neuroimaging technique to explore brain networks of risk-taking behavior. However, while there are a variety of paradigms adapted to neuroimaging to date, no consensus has been reached on the best paradigm with the appropriate parameters to study the brain during risk-taking assessed by the BART. In this review of the literature, we aimed to identify the most appropriate BART parameters to adapt the initial paradigm to neuroimaging and increase the reliability of this tool.
Methods
A systematic review focused on the BART versions adapted to neuroimaging was performed in accordance with PRISMA guidelines.
Results
A total of 105 articles with 6,879 subjects identified from the PubMed database met the inclusion criteria. The BART was adapted in four neuroimaging techniques, mostly in functional magnetic resonance imaging or electroencephalography settings.
Discussion
First, to adapt the BART to neuroimaging, a delay was included between each trial, the total number of inflations was reduced between 12 and 30 pumps, and the number of trials was increased between 80 and 100 balloons, enabling us to respect the recording constraints of neuroimaging. Second, explicit feedback about the balloon burst limited the decisions under ambiguity associated with the first trials. Third, employing an outcome index that provides more informative measures than the standard average pump score, along with a model incorporating an exponential monotonic increase in explosion probability and a maximum explosion probability between 50 and 75%, can yield a reliable estimation of risk profile. Additionally, enhancing participant motivation can be achieved by increasing the reward in line with the risk level and implementing payment based on their performance in the BART. Although there is no universal adaptation of the BART to neuroimaging, and depending on the objectives of a study, an adjustment of parameters optimizes its evaluation and clinical utility in assessing risk-taking.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a strong clinical, genetic, and pathological connection but association of ALS with Alzheimer's disease (AD) is seldom reported. ...We report a series of 5 cases of AD associated with ALS. Our patients presented with cognitive deterioration with episodic memory impairment meeting criteria for AD. ALS occurred subsequently in all cases and its phenotype was not homogenous. Amyloid process was confirmed in four cases with cerebrospinal fluid biomarkers. One case underwent postmortem exam, demonstrating hallmarks lesions of both diseases. This series highlights that ALS-AD phenotype could be a specific underexplored entity.
Apathy is commonly defined as a loss of motivation leading to a reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, is ...one of the most prevalent neuropsychiatric features of Parkinson's disease (PD). It has been established that the prevalence of apathy increases as PD progresses. However, the pathophysiology and anatomic substrate of this syndrome remain unclear. Apathy seems to be underpinned by impaired anatomical structures that link the prefrontal cortex with the limbic system. It can be encountered in the prodromal stage of the disease and in fluctuating PD patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, apathy may be considered as a disorder of motivation that embodies amotivational behavioral syndrome, is underpinned by combined dopaminergic and serotonergic denervation and is dopa-responsive. In contrast, in advanced PD patients, apathy may be considered as cognitive apathy that announces cognitive decline and PD dementia, is underpinned by diffuse neurotransmitter system dysfunction and Lewy pathology spreading and is no longer dopa-responsive. In this review, we discuss the clinical patterns of apathy and their treatment, the neurobiological basis of apathy, the potential role of the anatomical structures involved and the pathways in motivational and cognitive apathy.
In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a "psychodynamic" lesion. Numerous advances in neuroimaging have ...permitted identification of the neural underpinnings of this disorder.
Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology.
This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of "dynamic lesion".
Microduplications of the 17q21.31 chromosomal region encompassing the
MAPT
gene, which encodes the Tau protein, were identified in patients with a progressive disorder initially characterized by ...severe memory impairment with or without behavioral changes that can clinically mimic Alzheimer disease. The unique neuropathological report showed a primary tauopathy, which could not be unanimously classified in a given known subtype, showing both 4R- and 3R-tau inclusions, mainly within temporal cortical subregions and basal ganglia, without amyloid deposits. Recently, two subjects harboring the same duplication were reported with an atypical extrapyramidal syndrome and gait disorder. To decipher the phenotypic spectrum associated with
MAPT
duplications, we studied ten carriers from nine families, including two novel unrelated probands, gathering clinical (
n
= 10), cerebrospinal fluid (
n
= 6), MRI (
n
= 8), dopamine transporter scan (
n
= 4), functional (
n
= 5), amyloid (
n
= 3) and Tau-tracer (
n
= 2) PET imaging data as well as neuropathological examination (
n
= 4). Ages at onset ranged from 37 to 57 years, with prominent episodic memory impairment in 8/10 patients, associated with behavioral changes in four, while two patients showed atypical extrapyramidal syndrome with gait disorder at presentation, including one with associated cognitive deficits. Amyloid imaging was negative but Tau imaging showed significant deposits mainly in both mesiotemporal cortex. Dopaminergic denervation was found in 4/4 patients, including three without extrapyramidal symptoms. Neuropathological examination exclusively showed Tau-immunoreactive lesions. Distribution, aspect and 4R/3R tau aggregates composition suggested a spectrum from predominantly 3R, mainly cortical deposits well correlating with cognitive and behavioral changes, to predominantly 4R deposits, mainly in the basal ganglia and midbrain, in patients with prominent extrapyramidal syndrome. Finally, we performed in vitro seeding experiments in HEK-biosensor cells. Morphological features of aggregates induced by homogenates of three
MAPT
duplication carriers showed dense/granular ratios graduating between those induced by homogenates of a Pick disease and a progressive supranuclear palsy cases. These results suggest that
MAPT
duplication causes a primary tauopathy associated with diverse clinical and neuropathological features.
Alzheimer's disease leads to an alteration of decision-making abilities which may increase risk-taking behaviours, particularly associated anosognosia. Anticipating the progression of the disease ...raises a number of questions, particularly in relation to aging in place. Our qualitative study aimed to identify the arguments used by older patients with Alzheimer's disease when choosing a place to age. The study included 22 older adults, living at home, and diagnosed as mild dementia. The patients' arguments in favour of ageing in place were based mainly on the preservation of internal security, through the familiarity of places and relations as well as the maintenance of their independence and their lifestyle habits, allowing stability in their daily lives. Despite the identification of memory loss, the associated risks were minimized or hidden from the reflection on the choice of the place to age.
Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative ...frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.
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