Laurent Cleret de Langavant

Zika Virus Associated with Meningoencephalitis

As Zika virus spreads, the associated clinical syndromes need to be defined. In this report, an 81-year-old man is found to have Zika virus–associated meningoencephalitis.

Feeling of presence in Parkinson's disease

Background A feeling of presence (FP), that is, the vivid sensation that somebody (distinct from oneself) is present nearby, is commonly reported by patients with Parkinsons disease (PD), but its phenomenology has not been described precisely. The objective of this study was to provide a detailed description of FP in PD and to discuss its possible mechanisms. Patients and methods The authors studied 52 non-demented PD patients reporting FP in the preceding month (38 consecutive outpatients and 14 inpatients). FP characteristics were recorded with a structured questionnaire. The outpatients with FP were compared with 78 consecutive outpatients without FP. Results About half the patients said they recognised the ‘identity’ of the presence. More than 75% of patients said the FP were not distressing, were short-lasting, were felt beside and/or behind the patient, and occurred while indoors; most patients checked for a real presence, but their insight was generally preserved. In 31% of cases, the patients had an unformed visual hallucination simultaneously with the FP. A higher daily levodopa-equivalent dose and the presence of visual illusions or hallucinations were independently associated with FP. Discussion Although FP is not a sensory perception, projection of the sensation into the extrapersonal space, along with the frequent co-occurrence of elementary visual hallucinations and the strong association with visual hallucinations or illusions, supports its hallucinatory nature. FP may be viewed as a ‘social’ hallucination, involving an area or network specifically activated when a living being is present, independently of any perceptual clue.

Behavioral and Neural Correlates of Communication via Pointing

Communicative pointing is a human specific gesture which allows sharing information about a visual item with another person. It sets up a three-way relationship between a subject who points, an addressee and an object. Yet psychophysical and neuroimaging studies have focused on non-communicative pointing, which implies a two-way relationship between a subject and an object without the involvement of an addressee, and makes such gesture comparable to touching or grasping. Thus, experimental data on the communicating function of pointing remain scarce. Here, we examine whether the communicative value of pointing modifies both its behavioral and neural correlates by comparing pointing with or without communication. We found that when healthy participants pointed repeatedly at the same object, the communicative interaction with an addressee induced a spatial reshaping of both the pointing trajectories and the endpoint variability. Our finding supports the hypothesis that a change in reference frame occurs when pointing conveys a communicative intention. In addition, measurement of regional cerebral blood flow using H2O15 PET-scan showed that pointing when communicating with an addressee activated the right posterior superior temporal sulcus and the right medial prefrontal cortex, in contrast to pointing without communication. Such a right hemisphere network suggests that the communicative value of pointing is related to processes involved in taking another persons perspective. This study brings to light the need for future studies on communicative pointing and its neural correlates by unraveling the three-way relationship between subject, object and an addressee.

Joint recognition–expression impairment of facial emotions in Huntington's disease despite intact understanding of feelings

Patients with Huntingtons disease (HD), a neurodegenerative disorder that causes major motor impairments, also show cognitive and emotional deficits. While their deficit in recognising emotions has been explored in depth, little is known about their ability to express emotions and understand their feelings. If these faculties were impaired, patients might not only mis-read emotion expressions in others but their own emotions might be mis-interpreted by others as well, or thirdly, they might have difficulties understanding and describing their feelings. We compared the performance of recognition and expression of facial emotions in 13 HD patients with mild motor impairments but without significant bucco-facial abnormalities, and 13 controls matched for age and education. Emotion recognition was investigated in a forced-choice recognition test (FCR), and emotion expression by filming participants while they mimed the six basic emotional facial expressions (anger, disgust, fear, surprise, sadness and joy) to the experimenter. The films were then segmented into 60 stimuli per participant and four external raters performed a FCR on this material. Further, we tested understanding of feelings in self (alexithymia) and others (empathy) using questionnaires. Both recognition and expression were impaired across different emotions in HD compared to controls and recognition and expression scores were correlated. By contrast, alexithymia and empathy scores were very similar in HD and controls. This might suggest that emotion deficits in HD might be tied to the expression itself. Because similar emotion recognition-expression deficits are also found in Parkinsons Disease and vascular lesions of the striatum, our results further confirm the importance of the striatum for emotion recognition and expression, while access to the meaning of feelings relies on a different brain network, and is spared in HD.

The unified huntington's disease rating scale for advanced patients: Validation and follow-up study: Assessment of Advanced-HD Patients

The Unified Huntingtons Disease Rating Scale (UHDRS) adequately measures decline in patients at early and moderate stages of Huntingtons disease (HD). In advanced patients, floor effects hamper the evaluation, thus calling for an adjusted scale. We designed the UHDRS‐For Advanced Patients (UHDRS‐FAP), in order to improve longitudinal assessment of patients at advanced disease stage. Sixty‐nine patients with a Total Functional Capacity (TFC) ≤ 5 were recruited in France and in the Netherlands. Among them, 45 patients were followed longitudinally (mean 1.6 ± 1.2 years) with the UHDRS‐FAP; 30 were also assessed with the UHDRS. Cross‐sectional analyses evaluated psychometric properties and interrater reliability of the scale. Longitudinal analyses evaluated the sensitivity to decline compared to the UHDRS. Internal consistency was higher for motor and cognitive scores than for somatic and behavioral scores (0.84, 0.91, 0.70, and 0.49, respectively). Interrater reliability was ≥ 0.88 in all scores. The somatic score, specific to the UHDRS‐FAP, declined over time, as well as motor and cognitive performance with both scales. Although performance with the 2 scales correlated, the UHDRS‐FAP appeared more sensitive to change and was the only scale that detected decline in patients with a TFC ≤ 1. Neither scale detected a significant decline in behavioral scores. The UHDRS‐FAP is reliable and more sensitive to change than the original UHDRS for cognitive and motor domains. It offers items relevant for daily care. Behavioral scores tended to decline but this may reflect the decline in the communicative abilities of the patients.

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

Purpose: Huntingtons disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. Methods: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntingtons Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. Results: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41±0.17 units per year vs. risperidone and 0.54±0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). Conclusions: Antipsychotics are widely used to treat patients with Huntingtons disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

COMT Val158Met Polymorphism Modulates Huntington's Disease Progression.

Little is known about the genetic factors modulating the progression of Huntington’s disease (HD). Dopamine levels are affected in HD and modulate executive functions, the main cognitive disorder of HD. We investigated whether the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, which influences dopamine (DA) degradation, affects clinical progression in HD. We carried out a prospective longitudinal multicenter study from 1994 to 2011, on 438 HD gene carriers at different stages of the disease (34 pre-manifest; 172 stage 1; 130 stage 2; 80 stage 3; 17 stage 4; and 5 stage 5), according to Total Functional Capacity (TFC) score. We used the Unified Huntington’s Disease Rating Scale to evaluate motor, cognitive, behavioral and functional decline. We genotyped participants for COMT polymorphism (107 Met-homozygous, 114 Val-homozygous and 217 heterozygous). 367 controls of similar ancestry were also genotyped. We compared clinical progression, on each domain, between groups of COMT polymorphisms, using latent-class mixed models accounting for disease duration and number of CAG (cytosine adenine guanine) repeats. We show that HD gene carriers with fewer CAG repeats and with the Val allele in COMT polymorphism displayed slower cognitive decline. The rate of cognitive decline was greater for Met/Met homozygotes, which displayed a better maintenance of cognitive capacity in earlier stages of the disease, but had a worse performance than Val allele carriers later on. COMT polymorphism did not significantly impact functional and behavioral performance. Since COMT polymorphism influences progression in HD, it could be used for stratification in future clinical trials. Moreover, DA treatments based on the specific COMT polymorphism and adapted according to disease duration could potentially slow HD progression.

The prevalence and characteristics of hallucinations, delusions and minor phenomena in a non-demented population sample aged 60 years and over.

Psychotic phenomena can occur in non‐clinical subjects. The goals of this study were to assess the prevalence of delusions, hallucinations and minor ‘psychotic’ phenomena (visual illusions, feeling of presence and passage hallucinations) and to describe the characteristics of the latter in a non‐clinical older population.

How to capitalize on the retest effect in future trials on Huntington's disease

The retest effect—improvement of performance on second exposure to a task—may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington’s disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington’s Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington’s Disease (RIL-HD). All were assessed with the Unified Huntington’s Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required.

The role of the striatum in linguistic selection: Evidence from Huntington’s disease and computational modeling

Though accumulating evidence indicates that the striatum is recruited during language processing, the specific function of this subcortical structure in language remains to be elucidated. To answer this question, we used Huntingtons disease as a model of striatal lesion. We investigated the morphological deficit of 30 early Huntingtons disease patients with a novel linguistic task that can be modeled within an explicit theory of linguistic computation. Behavioral results reflected an impairment in HD patients on the linguistic task. Computational model-based analysis compared the behavioral data to simulated data from two distinct lesion models, a selection deficit model and a grammatical deficit model. This analysis revealed that the impairment derives from an increased randomness in the process of selecting between grammatical alternatives, rather than from a disruption of grammatical knowledge per se. Voxel-based morphometry permitted to correlate this impairment to dorsal striatal degeneration. We thus show that the striatum holds a role in the selection of linguistic alternatives, just as in the selection of motor and cognitive programs.