Role of Epileptic Activity in Older Adults With Delirium, a Prospective Continuous EEG Study

Background/Objectives: Delirium occurs in up to 50 % of hospitalized old patients and is associated with increased morbidity and mortality. Acute medical conditions favor delirium, but the pathophysiology is unclear. Preliminary evidence from retrospective and prospective studies suggests that a substantial minority of old patients with unexplained delirium have non-convulsive seizures or status epilepticus (NCSE). Yet, seeking epileptic activity only in unexplained cases of delirium might result in misinterpretation of its actual prevalence. We aimed to systematically investigate the role of epileptic activity in all older patients with delirium regardless of the underlying etiology.Design, Setting: Prospective observational study in a tertiary medical center. Adults >65 years with delirium underwent at least 24 h of continuous electro-encephalographic monitoring (cEEG). Background patterns and ictal and interictal epileptic discharges were identified, as well as clinical and biological characteristics.Participants: Fifty patients were included in the study.Results: NCSE was found in 6 (12%) patients and interictal discharges in 15 (30%). There was no difference in the prevalence of epileptic activity rates between delirium associated with an acute medical condition and delirium of unknown etiology.Conclusion: Epileptic activity may play a substantial role in the pathophysiology of delirium by altering brain functioning and neuronal metabolism. No clinical or biological marker was found to distinguish delirious patients with or without epileptic activity, underlining the importance of cEEG in this context

Genotype–phenotype correlation in PRKN- associated Parkinson’s disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials

Genotype-phenotype correlation in PRKN-associated Parkinson's disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson's disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p &lt; 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials

La nature de trouble de compréhension des phrases dans la maladie de Huntington

Pas de résumé françaisIn this thesis, we investigated troubles of sentence processing in Huntington’s disease (HD) at earlystage, which represents a model of damage mainly confined to the striatum. The role of striatalstructures in sentence processing is agreed upon, but its nature is still controversial. Most studieshave reported a role of the striatum for complex sentences or more controlled processes withinsentence processing, but the interpretation of this pattern differs according to two main views.Some authors have proposed that striatal structures have a linguistic function restricted to somesub-processes of sentence processing, while others claim that the deficits detected depend on themodulation that executive function exerts on language and sentence processing. Here, we aimed atfilling the gap between these approaches by using a psycholinguistic perspective to investigate onthe one hand the role of executive functions, in particular, working memory, in sentenceprocessing, and on the other hand the nature of the linguistic discrepancies reported in associationto striatal lesions. We thus built experimental paradigms that allow dissociating fine-grainedlinguistic variations in healthy subjects, and transferred them to HD patients. The profile ofimpairment detected in our experiments showed that working memory and other sources ofcomplexity can interfere with sentence processing by decreasing accuracy, but an impairment ofspecific syntactic processes occurs when working memory is controlled for. The pattern of the finegrainedsyntactic impairment detected is consistent with a dissociation between more frequent/lesscontrolled (default) and less frequent/more controlled (non-default) procedures in sentenceprocessing. Additionally, we detected that this deficit occurs despite the fact that HD patients arestill able to process syntactic information, suggesting that striatal structures spare syntacticrepresentations while they are involved in correctly applying syntactic procedures in non-defaultcontexts. We propose that this pattern is explained by a role of striatal structures in selectingbetween competing alternatives during sentence processing, which results in an inability to adapt tothe sentence context for non-default procedures. This parallels the role of striatal structures for selecting between competing alternatives in order to adapt to the changing environment, as reportedin motor control and in other domains of cognition. Although the domain specificity of striatalinvolvement in language cannot be demonstrated, it is highly compatible with the results obtainedin this thesis. Hence, linguistic functions might be modulated by distinct cortico-striatal circuits: onthe one hand by selecting linguistic representations as a function of the context, and on the otherhand, by modulating performance in language through executive functions. The frameworkemerging from this work thus helps conciliating apparently incongruent findings reported in theliterature. Yet, future research should better characterize anatomo-functional correlates of thisproposa

The Nature of Sentence Processing Impairment in Huntington's Disease at Early Stage

Pas de résumé françaisIn this thesis, we investigated troubles of sentence processing in Huntington s disease (HD) at earlystage, which represents a model of damage mainly confined to the striatum. The role of striatalstructures in sentence processing is agreed upon, but its nature is still controversial. Most studieshave reported a role of the striatum for complex sentences or more controlled processes withinsentence processing, but the interpretation of this pattern differs according to two main views.Some authors have proposed that striatal structures have a linguistic function restricted to somesub-processes of sentence processing, while others claim that the deficits detected depend on themodulation that executive function exerts on language and sentence processing. Here, we aimed atfilling the gap between these approaches by using a psycholinguistic perspective to investigate onthe one hand the role of executive functions, in particular, working memory, in sentenceprocessing, and on the other hand the nature of the linguistic discrepancies reported in associationto striatal lesions. We thus built experimental paradigms that allow dissociating fine-grainedlinguistic variations in healthy subjects, and transferred them to HD patients. The profile ofimpairment detected in our experiments showed that working memory and other sources ofcomplexity can interfere with sentence processing by decreasing accuracy, but an impairment ofspecific syntactic processes occurs when working memory is controlled for. The pattern of the finegrainedsyntactic impairment detected is consistent with a dissociation between more frequent/lesscontrolled (default) and less frequent/more controlled (non-default) procedures in sentenceprocessing. Additionally, we detected that this deficit occurs despite the fact that HD patients arestill able to process syntactic information, suggesting that striatal structures spare syntacticrepresentations while they are involved in correctly applying syntactic procedures in non-defaultcontexts. We propose that this pattern is explained by a role of striatal structures in selectingbetween competing alternatives during sentence processing, which results in an inability to adapt tothe sentence context for non-default procedures. This parallels the role of striatal structures for selecting between competing alternatives in order to adapt to the changing environment, as reportedin motor control and in other domains of cognition. Although the domain specificity of striatalinvolvement in language cannot be demonstrated, it is highly compatible with the results obtainedin this thesis. Hence, linguistic functions might be modulated by distinct cortico-striatal circuits: onthe one hand by selecting linguistic representations as a function of the context, and on the otherhand, by modulating performance in language through executive functions. The frameworkemerging from this work thus helps conciliating apparently incongruent findings reported in theliterature. Yet, future research should better characterize anatomo-functional correlates of thisproposalPARIS-EST-Université (770839901) / SudocPARIS12-Bib. électronique (940280011) / SudocSudocFranceF

Formal Topologies on the Set of First-Order Formulae

this paper that the question has a simple negative answer. This raised further natural questions on what can be said about the points of these two topologies; we give some answers. The observation that topological models for first-order theories can expressed in the framework of locales appears, for instance, in Fourman and Grayson [6], where the analogy between points of a locale and models of a theory is emphasised; the identification of formal points with Henkin sets, gives a precise form to this analogy. We replace the use of locales by formal topology, which can be expressed in a predicative framework such as Martin-Lof&apos;s type theory. Proof-theoretic issues are also considered by Dragalin [4], who presents a topological completeness proof using only finitary inductive definitions. Palmgren and Moerdijk [10] is also concerned with constructions of models: using sheaf semantics, they obtain a stronger conservativity result than the one in [3]. We will first investigate the difference between the Dedekind-MacNeille cover and the inductive cover. It easy to see that \Delta DM is stronger than \Delta I , that is, OE \Delta I U implies OE \Delta DM U , but the converse does not hold in general. The notion of point is not primitive in formal topology and therefore it is natural to require that a formal topology has some notion of positivity defined on the basic neighbourhoods; that a neighbourhood is positive then corresponds to, in ordinary point based topology, that it is inhabited by some point. We will show several negative results on positivity, both for the inductive topology and the Dedekind-MacNeille topology. The points of an inductive topology correspond to Henkin sets, but the Dedekind-MacNeille topology has, in general, no points. Our reasoning is constructi..

Cas clinique: encephalite limbique paranéoplasique avec troubles mnésiques isolés

info:eu-repo/semantics/publishe

Structural priming in sentence comprehension: A single prime is enough

Experiencing a syntactic structure affects how we process subsequent instances of that structure. This phenomenon, called structural priming, is observed both in language production and in language comprehension. However, while abstract syntactic structures can be primed independent of lexical overlap in sentence production, evidence for structural priming in comprehension is more elusive. In addition, when structural priming in comprehension is found, it can often be accounted for in terms of participants' explicit expectations. Participants may use the structural repetition over several sentences and build expectations, which create a priming effect. Here, we use a new experimental paradigm to investigate structural priming in sentence comprehension independent of lexical overlap and of participants' expectations. We use an outcome dependent variable instead of commonly used online measures, which allows us to more directly compare these effects with those found in sentence production studies. We test priming effects in syntactically homogeneous and heterogeneous conditions on a sentence-picture matching task that forces participants to fully parse the sentences. We observe that, while participants learn the structural regularity in the homogeneous condition, structural priming is also found in the heterogeneous condition, in which participants do not expect any particular structure. In fact, we find that a single prime is enough to trigger priming. Our results indicate that±like in sentence production-structural priming can be observed in sentence comprehension without lexical repetition and independent of participants' expectation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe