ABSTRACT
There is ample behavioral evidence that others' mere presence can affect any behavior in human and non-human animals, generally facilitating the expression of mastered responses while impairing the acquisition of novel ones. Much less is known about i) how the brain orchestrates the modulation of such a wide array of behaviors by others' presence and ii) when these neural underpinnings mature during development. To address these issues, fMRI data were collected in children and adults alternately observed and unobserved by a familiar peer. Subjects performed a numerosity comparison task and a phonological comparison task. While the former involves number-processing brain areas, the latter involves language-processing areas. Consistent with previous behavioral findings, adults' and children's performance improved in both tasks when observed by a peer. Across all participants, task-specific brain regions showed no reliable change in activity under peer observation. Rather, we found task-independent changes in domain-general brain regions typically involved in mentalizing, reward, and attention. Bayesian analyses singled out the attention network as the exception to the close child-adult resemblance of peer observation neural substrates. These findings suggest that i) social facilitation of some human education-related skills is primarily orchestrated by domain-general brain networks, rather than by task-selective substrates, and ii) apart from attention, peer presence neural processing is largely mature in children.
Subject(s)
Brain , Cognition , Animals , Adult , Humans , Bayes Theorem , Cognition/physiology , Brain/physiology , Brain Mapping , Language , Magnetic Resonance ImagingABSTRACT
AIM: KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants. METHODS: We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles. RESULTS: VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman's Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%. CONCLUSION: This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation.
Subject(s)
Autism Spectrum Disorder , Brain Diseases , Epilepsy , Intellectual Disability , Adaptation, Psychological , Adolescent , Adult , Autism Spectrum Disorder/complications , Autism Spectrum Disorder/epidemiology , Autism Spectrum Disorder/genetics , Brain Diseases/complications , Brain Diseases/epidemiology , Brain Diseases/genetics , Child , Child, Preschool , Epilepsy/genetics , Humans , Intellectual Disability/epidemiology , Intellectual Disability/genetics , Intellectual Disability/psychology , Shab Potassium Channels/genetics , Young AdultABSTRACT
PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Autism Spectrum Disorder , Autistic Disorder , Intellectual Disability , Adult , Attention Deficit Disorder with Hyperactivity/genetics , Autism Spectrum Disorder/genetics , Autistic Disorder/genetics , Humans , Intellectual Disability/genetics , Regulatory Factor X Transcription Factors , Transcription Factors/geneticsABSTRACT
BACKGROUND: Pathogenic variants of the AUTS2 (Autism Susceptibility candidate 2) gene predispose to intellectual disability, autism spectrum disorder, attention deficit hyperactivity disorder, facial dysmorphism and short stature. This phenotype is therefore associated with neurocognitive disturbances and social cognition, indicating potential functional maladjustment in the affected subjects, and a potentially significant impact on quality of life. Although many isolated cases have been reported in the literature, to date no families have been described. This case reports on a family (three generations) with a frameshift variant in the AUTS2 gene. CASE PRESENTATION: The proband is 13 years old with short stature, dysmorphic features, moderate intellectual disability and autism spectrum disorder. His mother is 49 years old and also has short stature and similar dysmorphic features. She does not have autism disorder but presents an erotomaniac delusion. Her cognitive performance is heterogeneous. The two aunts are also of short stature. The 50-year-old aunt has isolated social cognition disorders. The 45-year-old aunt has severe cognitive impairment and autism spectrum disorder. The molecular analysis of the three sisters and the proband shows the same AUTS2 heterozygous duplication leading to a frame shift expected to produce a premature stop codon, p.(Met593Tyrfs*85). Previously reported isolated cases revealed phenotypic and cognitive impairment variability. In this case report, these variabilities are present within the same family, presenting the same variant. CONCLUSIONS: The possibility of a phenotypic spectrum within the same family highlights the need for joint psychiatry and genetics research.
Subject(s)
Autism Spectrum Disorder , Intellectual Disability , Adolescent , Autism Spectrum Disorder/genetics , Cytoskeletal Proteins/genetics , Female , Humans , Intellectual Disability/genetics , Middle Aged , Phenotype , Quality of Life , Transcription Factors/geneticsABSTRACT
Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the α subunit of the delayed rectifier voltage-dependent potassium channel Kv 2.1. We review the 37 previously reported patients carrying 29 distinct KCNB1 variants and significantly expand the mutational spectrum describing 18 novel variants from 27 unreported patients. Most variants occur de novo and mainly consist of missense variants located on the voltage sensor and the pore domain of Kv 2.1. We also report the first inherited variant (p.Arg583*). KCNB1-related encephalopathies encompass a wide spectrum of neurodevelopmental disorders with predominant language difficulties and behavioral impairment. Eighty-five percent of patients developed epilepsies with variable syndromes and prognosis. Truncating variants in the C-terminal domain are associated with a less-severe epileptic phenotype. Overall, this report provides an up-to-date review of the mutational and clinical spectrum of KCNB1, strengthening its place as a causal gene in DEEs and emphasizing the need for further functional studies to unravel the underlying mechanisms.
Subject(s)
Epilepsy/diagnosis , Epilepsy/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , Shab Potassium Channels/genetics , Alleles , Genetic Association Studies/methods , Genotype , Humans , Phenotype , Shab Potassium Channels/chemistry , Shab Potassium Channels/metabolism , Structure-Activity RelationshipABSTRACT
PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved. METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types ofSOX5 alterations. Functional consequences of selected substitutions were investigated. RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated. CONCLUSIONS: This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.
Subject(s)
DNA-Binding Proteins/genetics , Intellectual Disability/genetics , Neurodevelopmental Disorders/genetics , SOXD Transcription Factors/genetics , Adolescent , Adult , Animals , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Haploinsufficiency/genetics , Humans , Infant , Intellectual Disability/diagnosis , Intellectual Disability/pathology , Language Development Disorders/diagnosis , Language Development Disorders/genetics , Language Development Disorders/pathology , Male , Mutation, Missense/genetics , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/pathology , Pedigree , Phenotype , Young AdultABSTRACT
BACKGROUND: The role of deleterious copy number variations in schizophrenia is well established while data regarding pathogenic variations remain scarce. We report for the first time a case of schizophrenia in a child with a pathogenic mutation of the chromodomain helicase DNA binding protein 2 (CHD2) gene. CASE PRESENTATION: The proband was the second child of unrelated parents. Anxiety and sleep disorders appeared at the age of 10 months. He presented febrile seizures and, at the age of 8, two generalized tonic-clonic seizures. At the age of 10, emotional withdrawal emerged, along with a flat affect, disorganization and paranoid ideation, without seizures. He began to talk and giggle with self. Eventually, the patient presented daily auditory and visual hallucinations. The diagnosis of childhood onset schizophrenia (DSM V) was then evoked. Brain imaging was unremarkable. Wakefulness electroencephalography showed a normal background and some bilateral spike-wave discharges that did not explain the psychosis features. A comparative genomic hybridization array (180 K, Agilent, Santa Clara, CA, USA) revealed an 867-kb 16p13.3 duplication, interpreted as a variant of unknown significance confirmed by a quantitative PCR that also showed its maternal inheritance. Risperidone (1,5 mg per day), led to clinical improvement. At the age of 11, an explosive relapse of epilepsy occurred with daily seizures of various types. The sequencing of a panel for monogenic epileptic disorders and Sanger sequencing revealed a de novo pathogenic heterozygous transition in CHD2 (NM_001271.3: c.4003G > T). CONCLUSIONS: This case underlines that schizophrenia may be, sometimes, underpinned by a Mendelian disease. It addresses the question of systematic genetic investigations in the presence of warning signs such as a childhood onset of the schizophrenia or a resistant epilepsy. It points that, in the absence of pathogenic copy number variation, the investigations should also include a search for pathogenic variations, which means that some of the patients with schizophrenia should benefit from Next Generation Sequencing tools. Last but not least, CHD2 encodes a member of the chromodomain helicase DNA-binding (CHD) family involved in chromatin remodeling. This observation adds schizophrenia to the phenotypic spectrum of chromodomain remodeling disorders, which may lead to innovative therapeutic approaches.
Subject(s)
DNA Copy Number Variations/genetics , DNA-Binding Proteins/genetics , Schizophrenia/genetics , Brain/metabolism , Brain/pathology , Child , Chromatin/genetics , Chromatin Assembly and Disassembly/genetics , Electroencephalography , Female , Heterozygote , Humans , Male , Mutation , Phenotype , Schizophrenia/physiopathology , Seizures, Febrile/genetics , Seizures, Febrile/pathologyABSTRACT
OBJECTIVE: We aimed to delineate the phenotypic spectrum and long-term outcome of individuals with KCNB1 encephalopathy. METHODS: We collected genetic, clinical, electroencephalographic, and imaging data of individuals with KCNB1 pathogenic variants recruited through an international collaboration, with the support of the family association "KCNB1 France." Patients were classified as having developmental and epileptic encephalopathy (DEE) or developmental encephalopathy (DE). In addition, we reviewed published cases and provided the long-term outcome in patients older than 12 years from our series and from literature. RESULTS: Our series included 36 patients (21 males, median age = 10 years, range = 1.6 months-34 years). Twenty patients (56%) had DEE with infantile onset seizures (seizure onset = 10 months, range = 10 days-3.5 years), whereas 16 (33%) had DE with late onset epilepsy in 10 (seizure onset = 5 years, range = 18 months-25 years) and without epilepsy in six. Cognitive impairment was more severe in individuals with DEE compared to those with DE. Analysis of 73 individuals with KCNB1 pathogenic variants (36 from our series and 37 published individuals in nine reports) showed developmental delay in all with severe to profound intellectual disability in 67% (n = 41/61) and autistic features in 56% (n = 32/57). Long-term outcome in 22 individuals older than 12 years (14 in our series and eight published individuals) showed poor cognitive, psychiatric, and behavioral outcome. Epilepsy course was variable. Missense variants were associated with more frequent and more severe epilepsy compared to truncating variants. SIGNIFICANCE: Our study describes the phenotypic spectrum of KCNB1 encephalopathy, which varies from severe DEE to DE with or without epilepsy. Although cognitive impairment is worse in patients with DEE, long-term outcome is poor for most and missense variants are associated with more severe epilepsy outcome. Further understanding of disease mechanisms should facilitate the development of targeted therapies, much needed to improve the neurodevelopmental prognosis.
Subject(s)
Brain Diseases/diagnostic imaging , Brain Diseases/genetics , Epilepsy/diagnostic imaging , Epilepsy/genetics , Genetic Variation/genetics , Shab Potassium Channels/genetics , Adolescent , Adult , Brain Diseases/physiopathology , Child , Child, Preschool , Cohort Studies , Electroencephalography/trends , Epilepsy/physiopathology , Female , Humans , Infant , Male , Retrospective Studies , Time Factors , Treatment Outcome , Young AdultABSTRACT
Smith-Magenis syndrome (SMS), linked to Retinoic Acid Induced (RAI1) haploinsufficiency, is a unique model of the inversion of circadian melatonin secretion. In this regard, this model is a formidable approach to better understand circadian melatonin secretion cycle disorders and the role of the RAI1 gene in this cycle. Sleep-wake cycle disorders in SMS include sleep maintenance disorders with a phase advance and intense sleepiness around noon. These disorders have been linked to a general disturbance of sleep-wake rhythm and coexist with inverted secretion of melatonin. The exact mechanism underlying the inversion of circadian melatonin secretion in SMS has rarely been discussed. We suggest three hypotheses that could account for the inversion of circadian melatonin secretion and discuss them. First, inversion of the circadian melatonin secretion rhythm could be linked to alterations in light signal transduction. Second, this inversion could imply global misalignment of the circadian system. Third, the inversion is not linked to a global circadian clock shift but rather to a specific impairment in the melatonin secretion pathway between the suprachiasmatic nuclei (SCN) and pinealocytes. The development of diurnal SMS animal models that produce melatonin appears to be an indispensable step to further understand the molecular basis of the circadian melatonin secretion rhythm.
Subject(s)
Disease Susceptibility , Melatonin/biosynthesis , Smith-Magenis Syndrome/etiology , Smith-Magenis Syndrome/metabolism , Animals , Chromosome Mapping , Circadian Rhythm , Genetic Predisposition to Disease , Humans , Quantitative Trait Loci , Quantitative Trait, Heritable , Smith-Magenis Syndrome/diagnosisABSTRACT
BACKGROUND: Comorbid psychiatric disorders are frequent in children with intellectual disability (ID). Given the limitations of drugs treatments, cognitive remediation could be a promising tool to reduce these challenging behaviors but evidence is still scarce. Our group recently developed the «COGNITUS & MOI¼ program that is designed to train the attentional and visuospatial skills in children with ID. This study investigates the efficiency of the «COGNITUS & MOI¼ program in this condition. METHODS: Children (age: 6.00-13.11) with mild to moderate ID and behavioral problems, will benefit from a therapy during a 16 week randomized controlled trial. One group will be randomly treated with the «COGNITUS & MOI¼ program and the other with a motor skill and video viewing intervention. All participants will undergo a behavioral, functional and neurocognitive assessment at baseline, post-intervention, and 6-month follow-up. Primary outcome will be the change from the baseline of the score on the "hyperactivity - noncompliance" subscale of the Aberrant Behavior Checklist. DISCUSSION: If the results are conclusive, the «COGNITUS & MOI¼ program could be added to the therapeutic arsenal against challenging behavior in children with ID. TRIAL REGISTRATION: ClinicalTrials NCT02797418 . Date registered: 8th of June 2016.
Subject(s)
Cognitive Remediation/methods , Intellectual Disability/therapy , Problem Behavior/psychology , Adolescent , Attention , Child , Computers , Female , Humans , Intellectual Disability/psychology , Male , Randomized Controlled Trials as Topic , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Sex chromosome aneuploidies occur in approximately one in 420 live births. The most frequent abnormalities are 45,X (Turner syndrome), 47,XXX (triple X), 47,XXY (Klinefelter syndrome), and 47,XYY. The prevalence of males with more than one extra sex chromosome (e.g. 48,XXYY or 48,XXXY) is less common. However, the literature provides little information about the cognitive and behavioural phenotype and the natural history of the disease. We report the clinical, neurocognitive, social cognitive and psychiatric characterization of a patient with 49,XYYYY syndrome. CASE PRESENTATION: The patient presented with a complex phenotype including a particular cognitive profile with intellectual deficiency and autism spectrum disorder (ASD) with limited interests. Moreover, social anxiety disorder with selective mutism and separation anxiety disorder were observed (DSM-5 criteria, MINI Assessment). CONCLUSION: It is now admitted that 49,XYYYY has unique medical, neurodevelopmental and behavioural characteristics. Interestingly, ASD is more common in groups with Y chromosome aneuploidy. This clinical report suggests that understanding the cognitive and social functioning of these patients may provide new insights into possible therapeutic strategies, as cognitive remediation or social cognitive training.
Subject(s)
Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/psychology , Chromosomes, Human, Y/genetics , Adult , Humans , Male , Phenotype , Tetrasomy , Turner SyndromeABSTRACT
BACKGROUND: Deletions or duplications of chromosome 19 are rare and there is no previous report in the literature of a ring chromosome derived from proximal 19p. Copy Number Variants (CNVs) responsible for complex phenotypes with Social Communication Disorder (SCD), may contribute to improve knowledge about the distinction between intellectual deficiency and autism spectrum disorders. CASE PRESENTATION: We report the clinical and cytogenetic characterization of a patient (male, 33 years-old, first child of healthy Portuguese non-consanguineous parents) presenting with a complex phenotype including SCD without intellectual deficiency and carrying a mosaic supernumerary ring chromosome 19p. Microarray-Based Comparative Genomic Hybridization and Fluorescence in situ Hybridization were performed. Genetic analysis showed a large mosaic interstitial duplication 19p13.12p12 of the short arm of chromosome 19, spanning 8.35 Mb. Our data suggested a putative association between psychosocial dysfunction and mosaic pure trisomy 19p13.2p12. CONCLUSION: This clinical report demonstrated the need to analyze more discreet trait-based subsets of complex phenotypes to improve the ability to detect genetic effects. To address this question and the broader issue of deciphering the yet unknown genetic contributors to complex phenotype with SCD, we suggest performing systematic psychological and psychiatric assessments in patients with chromosomal abnormalities.
Subject(s)
Chromosomes, Human, Pair 19/genetics , Communication Disorders/genetics , Trisomy , Adult , Communication Disorders/pathology , Humans , Male , Mosaicism , Phenotype , Ring ChromosomesABSTRACT
Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26). Three groups of actionable SF were rendered: predisposition to late-onset actionable diseases; genetic counseling; pharmacogenomics. Participants expressed strong interest in obtaining SF and a high satisfaction level when a SF is reported. The medical actionability of the SF reinforced parents' sense of taking action for their child and was seen as an opportunity. While we observed no serious psychological concerns, we showed that these results could have psychological consequences, in particular for late-onset actionable diseases SF, within families already dealing with rare diseases. This study shows that participants remain in favor of accessing SF despite the potential psychological, care, and lifestyle impacts, which are difficult to anticipate. The establishment of a management protocol, including the support of a multidisciplinary team, would be necessary if national policy allows the reporting of these data.
Subject(s)
Denervation/methods , Dopamine/metabolism , Galactosemias/pathology , Brain/diagnostic imaging , Brain/drug effects , Fluorine Radioisotopes/pharmacokinetics , Galactosemias/diagnostic imaging , Humans , Male , Middle Aged , Tomography, Emission-Computed, Single-Photon , Tropanes/pharmacokineticsABSTRACT
Alterations in cognitive functions in Parkinson's disease (PD) have been reported even in mild stages of the disease. These functions may play a role in complex daily activities, such as driving. This article provides an overview on the relationships between cognitive functions and driving behavior in PD in driving simulator and on-road studies. The role of attention, executive functions, visual memory, visuospatial construction and information processing speed is discussed. In driving simulator studies, driving performances were correlated with several neuropsychological measures, especially those of Trail Making Test (TMT), Brixton and Symbol Digit Modalities Test. In on-road studies, TMT, Useful Field Of View and Block Design tests appear as good predictors of driving performances. Most of these tests are also relevant to driving in Alzheimer's disease and traumatic brain injury.
Subject(s)
Automobile Driving , Cognition Disorders/physiopathology , Parkinson Disease/physiopathology , Alzheimer Disease/complications , Alzheimer Disease/physiopathology , Attention , Brain Injuries/complications , Brain Injuries/physiopathology , Cognition Disorders/etiology , Executive Function , Humans , Neuropsychological Tests , Parkinson Disease/complications , Psychomotor Performance , Stroke/complications , Stroke/physiopathologyABSTRACT
Slowness of movement initiation is a cardinal motor feature of Parkinson's disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 µg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson's disease.
Subject(s)
Parkinson Disease , Clonidine/pharmacology , Clonidine/therapeutic use , Humans , Magnetic Resonance Imaging , Movement/physiology , Norepinephrine , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapyABSTRACT
The Almirall European Headache Awards (AEHA) were organized in conjunction with the European Headache Federation. The awards were held in 2009, aiming to share clinical experience and best practice in headache-related disease management. 56 unusual and challenging cases of headache from 5 European countries (Belgium, France, Italy, Portugal and Spain) were judged by a Scientific Committee including expert representatives from participating countries, acting as reviewers. Three cases were selected from each country. The 15 resulting cases were presented to the Scientific Committee in Madrid, Spain in November 2009 and awards were given to the top 5 presentations. This article presents details of these cases, including the award winning entries. They have been categorized into four main groups: (a) headaches in rare syndromes; (b) secondary headaches to infectious/autoimmune causes or post-trauma/mass occupation; (c) headache in unresolved cases; and (d) other relevant cases. First prize was awarded to a case involving a 55-year-old male with familial thrombocytopenia and a unilateral neuralgiform headache secondary to trigeminal vascular contact, and which was successfully treated with carbamazepine. Conclusions from the meeting include: rare syndromes do occur and require appropriate treatment to improve outcomes; concomitant diseases may impair adequate diagnosis and should be investigated; physicians should be cautious and treat possible serious underlying disease, whilst accurately clarifying the correct diagnosis; neurological examination and complementary tests may be required; consideration should be given to possible rare medication events; and some cases may remain without a clear cause or diagnosis and symptoms should be treated whilst investigations continue.
Subject(s)
Diagnostic Errors/prevention & control , Diagnostic Techniques, Neurological/standards , Headache Disorders/diagnosis , Headache Disorders/etiology , Rare Diseases/complications , Rare Diseases/diagnosis , Adolescent , Adult , Causality , Comorbidity , Diagnosis, Differential , Europe , Female , Headache Disorders/physiopathology , Humans , Male , Middle Aged , Predictive Value of Tests , Rare Diseases/physiopathology , SyndromeABSTRACT
A large body of evidence suggests that math learning in children is built upon innate mechanisms for representing numerical quantities in the intraparietal sulcus (IPS). Learning math, however, is about more than processing quantitative information. It is also about understanding relations between quantities and making inferences based on these relations. Consistent with this idea, recent behavioral studies suggest that the ability to process transitive relations (A > B, B > C, therefore A > C) may contribute to math skills in children. Here we used fMRI coupled with a longitudinal design to determine whether the neural processing of transitive relations in children could predict their current and future math skills. At baseline (T1), children (n = 31) processed transitive relations in an MRI scanner. Math skills were measured at T1 and again 1.5 years later (T2). Using a machine learning approach with cross-validation, we found that activity associated with the representation of transitive relations in the IPS predicted math calculation skills at both T1 and T2. Our study highlights the potential of neurobiological measures of transitive reasoning for forecasting math skills in children, providing additional evidence for a link between this type of reasoning and math learning.
Subject(s)
Parietal Lobe , Problem Solving , Child , Humans , Magnetic Resonance Imaging , MathematicsABSTRACT
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVM). Of these, spinal AVM is a rare manifestation that concerns mainly children. In this report, we describe two cases of spinal AVM revealed by acute paraparesis due to subarachnoid hemorrhage in children with HHT and reviewed the literature on spinal arteriovenous malformations in HHT. In most of the cases reported, the clinical presentation was acute in the pediatric population and insidious during adulthood. The prognosis of spinal AVM mainly depends on the presence or not of medullar signs and symptoms and on the delay before treatment. In conclusion, any child with a family history of HHT should be considered at risk for spinal AVM in order to improve management of such complications and to decrease the risk of neurological sequellae.
Subject(s)
Arteriovenous Fistula/complications , Arteriovenous Fistula/genetics , Paraplegia/etiology , Spinal Cord/blood supply , Telangiectasia, Hereditary Hemorrhagic/complications , Acute Disease , Arteriovenous Fistula/diagnosis , Arteriovenous Fistula/therapy , Child , Chromosome Aberrations , Diagnosis, Differential , Embolization, Therapeutic , Follow-Up Studies , Genes, Dominant , Humans , Infant , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Neurologic Examination , Spinal Cord/pathology , Spinal Cord Ischemia/diagnosis , Spinal Cord Ischemia/genetics , Spinal Cord Ischemia/therapy , Spinal Cord Vascular Diseases/diagnosis , Spinal Cord Vascular Diseases/genetics , Spinal Cord Vascular Diseases/therapy , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/therapyABSTRACT
AIM: Social cognitive impairments are core features in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia (SCZ). Indeed, adults with 22q.11.2 DS often have poorer social competence as well as poorer performance on measures of social cognitive skills (emotion recognition and theory of mind, ToM) compared with typically developing people. However, studies comparing specific social cognitive components in 22q11.2DS and SCZ have not yet been widely conducted. METHODS: In this study we compared performances of 22q11.2DS and SCZ on both facial emotion recognition and ToM. Patients with 22q11.2DS (n = 18) and matched SCZ patients were recruited. After neuropsychological testing, the facial emotion recognition test assessed the patients' ability to recognize six basic, universal emotions (joy, anger, sadness, fear, disgust, and contempt). The Versailles-situational intentional reading evaluated ToM with six scenes from movies showing characters in complex interactions (involving hints, lies, and indirect speech). RESULTS: We show that 22q11.2DS exhibited significantly lower performance in emotion recognition than SCZ patients did, especially for disgust, contempt, and fear. This impairment seems to be a core cognitive phenotype in 22q11.2DS, regardless of the presence of SCZ symptoms. Concerning ToM, our results may highlight the same impairment level in 22q11.2DS and SCZ but require to be replicated in a larger cohort. CONCLUSION: Our results document the existence of threshold social cognitive deficits distinguishing 22q11.2DS from SCZ.