Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the HΨ Patients with a lower H&Y stage may be more affected if they have a greater NMS burden

Papel del factor activador plaquetario en la patogenia de la encefalitis alérgica experimental de la rata Lewis

Tesis inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 22 de Marzo de 1991

Non-Motor Symptoms in PLA2G6-Associated Dystonia-Parkinsonism: A Case Report and Literature Review

PLA2G6-dystonia-parkinsonism (PLAN-DP) is characterized by levodopa responsive parkinsonism and dystonia. While neuropsychiatric symptoms and early cognitive decline are also common in this entity there is little information regarding other non-motor symptoms (NMS). Here, we describe a 26-year-old patient with PLAN-DP whose motor symptoms were preceded by mild cognitive impairment and anxiety, and who developed many other NMS as the disease evolved. Furthermore, we reviewed the NMS described in all the PLAN-DP patients published to date. A total of 50 patients with PLAN-DP were identified, 42 of whom developed NMS and in 23 of these cases, NMS preceded the motor symptoms of the disease. Neuropsychiatric symptoms dominated the premotor phase of this condition and cognitive impairment/dementia was the most prevalent NMS. Other NMS were reported infrequently like sleep disorders, autonomic symptoms, pain and hyposmia, and mostly as the disease evolved. NMS are very frequent in PLAN-DP and they may appear before diagnosis or during the course of the disease. Neuropsychiatric symptoms and cognitive decline are the most frequent NMS. The appearance of neuropsychiatric symptoms like depression, anxiety or personality changes prior to a diagnosis of parkinsonism in younger individuals might suggest the presence of PLA2G6 gene mutations

Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is usually associated with dystonia, which is typically severe and progressive over time. Pallidal stimulation (GPi DBS) has been carried out in selected cases of PKAN with drug-resistant dystonia with variable results. We report a 30-month follow-up study of a 30-year-old woman with PKAN-related dystonia treated with GPi DBS. Postoperatively, the benefit quickly became evident, as the patient exhibited a marked improvement in her dystonia, including her writing difficulty. This result has been maintained up to the present. GPi DBS should be considered in dystonic PKAN patients provided fixed contractures and/or pyramidal symptoms are not present

A genetic analysis of a Spanish population with early onset Parkinson’s disease

Introduction Both recessive and dominant genetic forms of Parkinson’s disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson’s disease in a cohort from central Spain. Methods/patients We analyzed a cohort of 117 unrelated patients with early onset Parkinson’s disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson’s disease and other Parkinsonisms and CNV screening. Results Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes. Conclusions Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson’s disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson’s disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson’s disease

Trunk Range of Motion Is Related to Axial Rigidity, Functional Mobility and Quality of Life in Parkinson’s Disease: An Exploratory Study

Background: People with Parkinson’s disease (PD) present deficits of the active range of motion (ROM), prominently in their trunk. However, if these deficits are associated with axial rigidity, the functional mobility or health related quality of life (HRQoL), remains unknown. The aim of this paper is to study the relationship between axial ROM and axial rigidity, the functional mobility and HRQoL in patients with mild to moderate PD. Methods: An exploratory study was conducted. Non-probabilistic sampling of consecutive cases was used. Active trunk ROM was assessed by a universal goniometer. A Biodex System isokinetic dynamometer was used to measure the rigidity of the trunk. Functional mobility was determined by the Get Up and Go (GUG) test, and HRQoL was assessed with the PDQ-39 and EuroQol-5D questionnaires. Results: Thirty-six mild to moderate patients with PD were evaluated. Significant correlations were observed between trunk extensors rigidity and trunk flexion and extension ROM. Significant correlations were observed between trunk flexion, extension and rotation ROM and GUG. Moreover, significant correlations were observed between trunk ROM for flexion, extension and rotations (both sides) and PDQ-39 total score. However, these correlations were considered poor. Conclusions: Trunk ROM for flexion and extension movements, measured by a universal goniometer, were correlated with axial extensors rigidity, evaluated by a technological device at 30°/s and 45°/s, and functional mobility. Moreover, trunk ROM for trunk flexion, extension and rotations were correlated with HRQoL in patients with mild to moderate PD

A circuit‐based approach to modulate hypersexuality in Parkinson's disease

2023 Acuerdos transformativos CRUEAim: Impulse‐control disorder is a common neuropsychiatric complication in Parkinson's disease (PD) under dopamine replacement therapy. Prior studies tested the balance between enhanced desire towards reward and cognitive control deficits, hypothesized to be biased towards the former in impulse control disorders. We provide evidence for this hypothesis by measuring behavioral and neural patterns behind the influence of sexual desire over response inhibition and tools towards functional restoration using repetitive transcranial stimulation in patients with hypersexuality as predominant impulsive disorder. Methods: The effect of sexual cues on inhibition was measured with a novel erotic stop‐signal task under on and off dopaminergic medication. Task‐related functional and anatomical connectivity models were estimated in 16 hypersexual and 17 nonhypersexual patients with PD as well as in 17 healthy controls. Additionally, excitatory neuromodulation using intermittent theta‐burst stimulation (sham‐controlled) was applied over the pre‐supplementary motor area in 20 additional hypersexual patients with PD aiming to improve response inhibition. Results: Compared with their nonhypersexual peers, patients with hypersexuality recruited caudate, pre‐supplementary motor area, ventral tegmental area, and anterior cingulate cortex while on medication. Reduced connectivity was found between pre‐supplementary motor area and caudate nucleus in hypersexual compared with nonhypersexual patients (while medicated), a result paralleled by compensatory enhanced anatomical connectivity. Furthermore, stimulation over the pre‐supplementary motor area improved response inhibition in hypersexual patients with PD when exposed to sexual cues. Conclusion: This study, therefore, has identified a specific fronto‐striatal and mesolimbic circuitry underlying uncontrolled sexual responses in medicated patients with PD where cortical neuromodulation halts its expression.Ministerio de Ciencia, Innovación y UniversidadesInstituto de Salud Carlos IIIFundación Jesús de Gangoiti BarreraDepto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpubAPC financiada por la UC

A genetic analysis of a Spanish population with early onset Parkinson’s disease

[Introduction] Both recessive and dominant genetic forms of Parkinson’s disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson’s disease in a cohort from central Spain.[Methods/patients] We analyzed a cohort of 117 unrelated patients with early onset Parkinson’s disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson’s disease and other Parkinsonisms and CNV screening.[Results] Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes.[Conclusions] Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson’s disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson’s disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson’s disease.This study was supported by grants from the Spanish Ministry of Economy and Competitiveness [PI14/01823, PI16/01575, PI18/01898] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña. Pilar Gómez-Garre was supported by the "Miguel Servet" (from ISCIII-FEDER) and “Nicolás Monardes” (from Andalusian Ministry of Health) programs. Silvia Jesús Maestre was supported by the "Juan Rodés" program (from ISCIII-FEDER). Cristina Tejera was supported by VPPI-US from the Universidad de Sevilla