"Ten euros now" temporal discounting in Huntington disease.

BACKGROUND: When making decisions, one often faces a trade-off between immediate and long-term rewards. In these situations, people may prefer immediate over later rewards, even if immediate rewards are smaller than later ones; a phenomenon known as temporal discounting. In this study, we, for the first time, assessed temporal discounting in three populations: participants with manifest Huntington disease (HD), participants with premanifest HD, and control participants. METHODS: Using the temporal discounting task, we invited participants to choose between small immediate amount of money vs. delayed, but larger amount of money (e.g., "Which do you prefer: you get 10 euros right now or 50 euros in a month?"). We also measured inhibition in order to test if it impacts discounting performance. RESULTS: Analysis demonstrated higher temporal discounting (i.e., a preference for the immediate rewards) in participants with manifest HD compared to those with premanifest HD or control participants, but no significant differences were observed in participants with premanifest HD and control participants. Analysis also demonstrated significant correlations between temporal discounting and scores on an inhibition test in participants with manifest HD, but not in those with premanifest HD or in control participants. DISCUSSION: We suggest that, when making decisions, patients with manifest HD may have difficulties with suppressing the temptation of smaller, but immediate, rewards.

Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study.

OBJECTIVES: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis. MATERIAL AND METHODS: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0. RESULTS: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0-4.0)) compared to SM patients (2.0, (1.0-3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01-1.95, p = 0.046). CONCLUSION: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.

Cyclosporine A does not prevent second-eye involvement in Leber's hereditary optic neuropathy.

BACKRGROUND: Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber's hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2.5 mg/kg/day, were examined at three-month intervals for a year. The primary endpoint was the best corrected visual acuity in the unaffected eye; the secondary endpoints were the best corrected visual acuity in the first eye affected, the mean visual field defect on automated perimetry, the thickness of the perifoveal retinal ganglion cell inner plexiform layer, and the thickness of the peripapillary retinal nerve fiber layer in both eyes. RESULTS: Among the 24 patients referred to our institution with genetically confirmed LHON, between July 2011 and April 2014, only five patients, four males and one female, fulfilled the inclusion criteria. Age at enrolment ranged from 19 to 42 years (mean: 27.2 years; median: 26 years), four patients harbored the m.11778G > A pathogenic variant, and one the m.14484 T > C pathogenic variant. The time-interval between the onset of symptoms and inclusion in the study ranged from 7 to 17 weeks (mean: 11.8 weeks; median: 9 weeks). Despite treatment with oral cyclosporine A, all patients eventually experienced bilateral eye involvement, occurring within 11-65 weeks after the initiation of treatment. Over the study time period, the average best corrected visual acuity worsened in the first eye affected; by the end of the study, both eyes were equally affected. CONCLUSIONS: Oral cyclosporine, at 2.5 mg/kg/day, did not prevent second-eye involvement in patients with strictly unilateral Leber's hereditary optic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02176733 . Registrated June 25, 2014.

Dissociation between decision-making under risk and decision-making under ambiguity in premanifest and manifest Huntington's disease.

We investigated decision-making under ambiguity (DM-UA) and decision making under risk (DM-UR) in individuals with premanifest and manifest Huntington's disease (HD). Twenty individuals with premanifest HD and 23 individuals with manifest HD, on one hand, and 39 healthy individuals divided into two control groups, on the other, undertook a modified version of the Iowa Gambling Task (IGT), an adaptation of a DM-UA task, and a modified version of the Game of Dice Task (GDT), an adaptation of a DM-UR task. Participants also filled in a questionnaire of impulsivity and responded to cognitive tests specifically designed to assess executive functions. Compared to controls, individuals with premanifest HD were unimpaired in performing executive tests as well as in decision-making tasks, except for the Stroop task. In contrast, individuals with manifest HD were impaired in both the IGT and executive tasks, but not in the GDT. No sign of impulsivity was observed in individuals with premanifest or manifest HD. Our results suggest that the progression of HD impairs DM-UA without affecting DM-UR, and indicate that decision-making abilities are preserved during the premanifest stage of HD.

A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease.

BACKGROUND: Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. METHODS: Ninety-six patients with early-stage Huntington's disease were randomized to 1200 mg delayed-release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed-effects model for repeated measures was used to assess treatment effect, expressed as the least-squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. RESULTS: At 18 months, the treatment effect was not statistically significant - least-squares mean difference, -1.5 ± 1.71 (P = 0.385) - although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. CONCLUSIONS: Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society.

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's disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054-67) 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 with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing 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.

The most appropriate primary outcomes to design clinical trials on Huntington's disease: meta-analyses of cohort studies and randomized placebo-controlled trials.

Huntington's disease (HD) is a rare multifactorial neurodegenerative disease. Both its natural course and any placebo effect are poorly known. All are obstacles to design randomized controlled trials (RCTs). We conducted meta-analyses of RCTs and cohorts on all parameters of the Unified Huntington's Disease Rating Scale to determine the most appropriate outcomes and to minimize the number of patients required to design RCTs in HD. Twenty-four RCTs were included, involving 838 patients with a mean age of 50.0 ± 2.3 years and a mean total functional capacity (TFC) score of 9.8 ± 0.6. Nineteen cohorts were included involving 1939 patients with a mean age of 48.9 ± 2.3 years and a mean TFC of 10.1 ± 0.7. Significant deterioration was observed in RCTs for all scores except behavioral score. Effect sizes were comparable between RCTs and cohorts for each test except that there was a significant difference for TFC. The weighted mean deterioration per year on the TFC scale was -0.5 (0.2) in RCTs and -0.8 (0.2) in cohorts. The lowest number of patients required per group in a RCT was for TFC (19 per group), whereas 30 patients would be required per group for the total motor score (TMS). For cognition, the verbal fluency test required the smallest number of patients: 104 per group. In conclusion, TMS and TFC are the most appropriate outcomes to design RCTs on HD likewise the verbal fluency test for cognition. Our results suggest an effect of placebo administration on the total functional capacity.

Association between caffeine intake and age at onset in Huntington's disease.

Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.

Analysis of clinical patterns and underlying epileptogenic zones of hypermotor seizures.

BACKGROUND: Hypermotor seizures (HMS) are characterized by complex movements involving the proximal segment of the limbs and trunk. Although they are primarily reported in mesial frontal or orbitofrontal epilepsies, they have also been described in patients with temporal or insular epilepsies, questioning the localizing value of HMS in patients contemplating epilepsy surgery. Furthermore, HMS can include different forms of HM behaviors. Whether these clinical variations may be systematized and may reflect different locations of the epileptogenic zone (EZ) has not been evaluated yet. METHODS: We have retrospectively analyzed ictal signs and intracerebral EEG data in 11 patients presenting with HMS who became seizure free following epilepsy surgery with a minimum follow-up of 24 months. Clinical phenomena were reviewed blinded to seizure onset zone. RESULTS: Two types of HMS could be distinguished in this population: HMS1, observed in six patients, mainly consisted of marked agitation that either included body rocking, kicking, or boxing, associated with a facial expression of fear. HMS2, observed in the five other patients, mainly consisted of mild agitation that included either horizontal movements or rotation of trunk and pelvis while lying on the bed, usually associated with tonic/dystonic posturing. SEEG findings showed that the EZ associated with HMS1 was mainly centered on the ventromesial frontal cortex. Conversely, HMS2 was primarily associated with an EZ localized within the mesial premotor cortex. CONCLUSIONS: Although these findings remain to be confirmed by larger studies, they may help optimize the placement of intracerebral electrodes in patients contemplating epilepsy surgery.