Neuropathies optiques héréditaires

Les neuropathies optiques héréditaires sont un groupe hétérogène de pathologies affectant les nerfs optiques et qui peuvent se transmettre selon un mode autosomique dominant, autosomique récessif, lié à l’X ou selon une hérédité mitochondriale. Les deux pathologies héréditaires non syndromiques les plus fréquentes (neuropathie optique héréditaire de Leber et l’atrophie optique dominante) ont des manifestations cliniques et des modes de transmission très différents, aboutissant néanmoins à une atrophie optique non spécifique. Au-delà des manifestations purement visuelles, il n’est pas exceptionnel de constater chez des patients atteints, un nombre croissant de manifestations neurologiques associées

Executive functions in clinical and preclinical Alzheimer's disease

Executive functions is an umbrella term describing a wide range of higher order processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Impairment of executive functions is common in neurodegenerative disorders such as Alzheimer\u27s disease. These deficits negatively affect everyday activities and hamper the ability to cope with other cognitive or behavioural disorders. In this paper, we propose a synthesis of the knowledge on executive impairments in clinical and preclinical Alzheimer\u27s disease, mostly leaning on the current studies made in this domain. We made some propositions for neuropsychological assessment of executive functions in preclinical and clinical phases of Alzheimer\u27s disease. We hope that this overview will provide a useful insight into an area that is still insufficiently explored in the field of the neuropsychology of Alzheimer\u27s disease

Theory of Mind and Empathy in Preclinical and Clinical Huntington's Disease

We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington\u27s disease (HD). The relation between ToM performance and executive skills was also examined. 16 preclinical and 23 clinical HD patients, and 39 healthy subjects divided in 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory and Aharon-Peretz, 2007) that examines first and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first-and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared to their controls. Our results are consistent with the idea that impaired affective and cognitive mentalising emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy

Variants Cause Spastic Paraplegia Associated with Cerebral Hypomyelination

Oculodentodigital dysplasia is an autosomal dominant disorder due to variants characterized by dysmorphic features. Neurologic symptoms have been described in some patients but without a clear neuroimaging pattern. To understand the pathophysiology underlying neurologic deficits in oculodentodigital dysplasia, we studied 8 consecutive patients presenting with hereditary spastic paraplegia due to variants. Clinical disease severity was highly variable. Cerebral MR imaging revealed variable white matter abnormalities, consistent with a hypomyelination pattern, and bilateral hypointense signal of the basal ganglia on T2-weighted images and/or magnetic susceptibility sequences, as seen in neurodegeneration with brain iron accumulation diseases. Patients with the more prominent basal ganglia abnormalities were the most disabled ones. This study suggests that -related hereditary spastic paraplegia is a complex neurodegenerative disease affecting both the myelin and the basal ganglia. variants should be considered in patients with hereditary spastic paraplegia presenting with brain hypomyelination, especially if associated with neurodegeneration and a brain iron accumulation pattern

Les troubles visuels au cours de la maladie d’Alzheimer

Principale cause de démence chez le sujet âgé, la maladie d’Alzheimer est caractérisée par l’association de troubles mnésiques, d’un syndrome aphaso-apraxo-agnosique et d’un retentissement fonctionnel. Des symptômes visuels peuvent être présents et parfois dominer le tableau, notamment lors de l’atrophie corticale postérieure, décrite comme la « variante visuelle de la maladie d’Alzheimer ». Les patients et leurs proches rapportent ainsi fréquemment des difficultés de lecture, d’écriture, ou de reconnaissance visuelle. Hormis les agnosies visuelles, d’autres anomalies neuro-ophtalmologiques peuvent expliquer cette symptomatologie : atteinte hémianopsique du champ visuel, neuropathies optiques et mouvements oculaires anormaux. L’objectif de cet article est de faire la liste des troubles visuels retrouvés dans la maladie d’Alzheimer

Longitudinal study of informed consent in innovative therapy research: experience and provisional recommendations from a multicenter trial of intracerebral grafting.

BACKGROUND: There is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders. METHODS: We performed a longitudinal study of the consent of Huntington's disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington's Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington's disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington's disease patients and 16 proxies one year later. RESULTS: The comprehension score was high and similar for Huntington's disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year. CONCLUSIONS: Cognitively impaired patients with Huntington's disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients

Hereditary amyloid neuropathy by transthyretin Val107 mutation in a patient of African origin

International audienc

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

PURPOSE: Huntington's 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 Huntington's 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 Huntington's 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

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

BACKGROUND: People with Huntington\u27s disease (HD) have been observed to have lower rates of cancers. OBJECTIVE: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. METHODS: Data were obtained from the European Huntington\u27s disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. RESULTS: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). CONCLUSIONS: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis