Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.

Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

Background and Objectives: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores. Methods: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication. Results: Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04-1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10-6). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04-1.23). Discussion: ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk models.

Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review. / La estimulación cerebral profunda en el trastorno obsesivo-compulsivo refractario al tratamiento: una revisión sistemática.

INTRODUCTION: At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. METHOD: We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. RESULTS: The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. CONCLUSIONS: The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit.

A Rare PSEN1 (Leu85Pro) Mutation Causing Alzheimer's Disease in a 29-Year-Old Woman Presenting as Corticobasal Syndrome.

Dementia is not just a disease of old age. Early-onset dementia affects people younger than 65 and its differential diagnosis is broader than in older people. Nevertheless, although young people are considerably more liable to develop a rare form of dementia, Alzheimer's disease (AD) remains the most common diagnosis. The aim of this article is to report on an early-onset AD patient associated with the rare pathogenic variant PSEN1 (Leu85Pro) presenting as a possible corticobasal syndrome with asymmetric limb apraxia, parkinsonian signs, and myoclonus.