Mechanisms of pure alexia: spatially based impairment, letter identification deficit, or both?

We studied reading performance for words and for isolated letters in a pure alexic patient. She performed reasonably well when naming isolated letters but was slower in reading letters than a control subject when reaction times (RTs) were recorded. When the patient read isolated letters, RTs were slower for a subset of letters that cannot be recognized from their left part alone (e.g. "b", an ambiguous letter, could be read "b" "h" "l" or "k" whereas "a" has no predictable confounders). We observed a significant positive correlation between the RTs for reading a word and the mean RTs for reading each of its composing letters before its uniqueness point (i.e. the point, when reading from the left to the right, where a word cannot be a word other than the one it is). This result suggests that, in our patient, the letter identification deficit can account for the slow, letter-by-letter reading behaviour, insofar as each letter represents a perceptual problem. Our findings can be accounted for by a deficit in the parallel processing of the left and right parts of each letter, compounded with a bias to process first the left part of the letter, and may thus reconcile the hypotheses of spatially-based deficit (Rapp and Caramazza, 1991) and of a perceptual deficit occurring at the letter identification level (Behrmann and Shallice, 1995; Perri et al., 1996)

The anatomy of cerebral achromatopsia: A reappraisal and comparison of two case reports

The anatomy of cerebral achromatopsia: A reappraisal and comparison of two case report

[Presentation of an assessment battery for visual mental imagery and visual perception]

The relationship between visual perception and visual mental imagery are at the center of a lively theoretical debate between those postulating common neurocognitive processes between perception and imagery and those who emphasize the differences between these two entities. Neuropsychology can make an important contribution to this debate, by assessing associations and dissociations between perceptual and imaginal deficits in patients with brain damage. However, currently there is no standardized test battery available for such assessments

Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates with the Huntington's disease mutation in peripheral lymphocytes

e search for peripheral markers of neurodegenerative diseases aims at identifying molecules that could help in monitoring the effects of future therapeutics in easily accessible cells. Here we focused on the involvement of the endocannabinoid system in Huntington's disease (HD). We assayed peripheral lymphocytes from HD patients and healthy controls, and found that the activity of the fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide (AEA), was dramatically decreased (down to less than 10%) in HD compared to healthy subjects. Concomitantly, the endogenous levels of AEA were approximately 6-fold higher in HD versus healthy lymphocytes, while the other elements of the endocannabinoid system were not affected by HD. Low FAAH activity in HD lymphocytes was not due to down-regulation of protein expression, but rather to blockage of enzyme activity by a cytosolic and irreversible inhibitor. Finally, pre-HD patients showed defective FAAH activity, as did the brain of HD patients compared with healthy controls. Taken together, our data indicate that FAAH activity in lymphocytes mirrors some of the metabolic changes which take place in the brain, it is a measurable non-genetic peripheral marker that segregates with the HD mutation, and it might serve as a target to test chemicals active on the widespread toxic effects of the mutant protei

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

Item does not contain fulltextBACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS: Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function1 maart 201

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure

Suicidal ideation in a European Huntington's disease population

Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD. METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis. RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive. LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated. CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines

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

Background: People with Huntington's 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's 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