Search

IntroductionBoth 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/patientsWe 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.ResultsTwenty-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.ConclusionsOur 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.

Abstract Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients.

Background and objective: Staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (Motor; Non-motor; Cognition; Dependency) and five stages, correlated with disease severity, patients' quality of life and caregivers' strain and burden. Our aim was to apply the MNCD classification in advanced PD patients treated with device-aided therapy (DAT). Patients and Methods: A multicenter observational retrospective study of the first patients to start the levodopa-entacapone-carbidopa intestinal gel (LECIG) in Spain was performed (LECIPARK study). The MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) were collected by the neurologist at V0 (before starting LECIG) and V2 (follow-up visit). Wilcoxon's signed rank and Marginal Homogeneity tests were applied to compare changes from V0 to V2. Results: Sixty-seven PD patients (58.2% males; 69.9 ± 9.3 years old) with a mean disease duration of 14.4 ± 6.5 years were included. The mean treatment duration (V2) was 172.9 ± 105.2 days. At V0, patients were classified as in stage 2 (35.8%), 3 (46.3%) or 4 (17.9%). The frequency of patients in stage 4 decreased to 9% at V2 (p = 0.001). The MNCD total score decreased from 6.27 ± 1.94 at V0 to 5.21 ± 2.23 (p < 0.0001). From V0 to V2, the motor (M; p < 0.0001) and non-motor symptom (N; p < 0.0001) burden decreased, and autonomy for the activities of daily living (D; p = 0.005) improved. Conclusions: The MNCD classification could be useful to classify advanced PD patients and to monitor the response to a DAT. [ABSTRACT FROM AUTHOR]

Background: Myofascial trigger points (TrPs) are hypersensitive points located in a tight band of muscle that, when palpated, produce not only local pain but also referred (distant) pain. The role of TrPs in patients with cervical dystonia (CD) has not been investigated. Objective: To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain. Methods: Thirty‐one patients (74.2% women; age: 61.2 years, SD: 10.1 years) participated. TrPs were explored in the sternocleidomastoid, upper trapezius, splenius capitis, levator scapulae, anterior scalene, suboccipital, and infraspinatus muscles. Clinical features of CD were documented as well as the presence of pain. The severity of dystonia and its consequences were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results: The mean number of TrPs for each patient was 12 (SD:3), with no differences between patients with pain (n = 20) and those without pain (n = 11). Active TrPs were only found in patients with pain (mean: 7.5, SD:4). Latent TrPs were found in both groups but were more prevalent (P < 0.001) in patients without pain (mean: 11, SD:3.5) than in those with pain (mean: 5, SD:3.5). The number of active TrPs or latent TrPs was positively associated with the TWSTRS disability subscale and the TWSTRS total score. The number of active, but not latent, TrPs was associated with worse scores on the TWSTRS pain subscale. Conclusion: Active TrPs were present in patients with CD reporting pain, while latent TrPs were present in all CD patients, irrespective of their pain status. The numbers of active/latent TrPs were associated with disability. TrPs could act as pain generators in CD and also contribute to the involuntary muscle contractions characteristic of dystonia. [ABSTRACT FROM AUTHOR]

Background: This exploratory study evaluated the presence of sensitization-associated and neuropathic-like symptoms and identified their association with pressure sensitivity, pain, and disability in patients with cervical dystonia (CD). Methods: Thirty-one patients with CD (74.2% women, age: 61.2 years, SD 10.1) participated. Data collected included clinical variables, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI), as well as widespread pressure pain thresholds (PPTs). Results: Patients with CD with pain (n = 20, 64.5%) showed higher scores on the TWSTRS disability subscale and the CSI (p < 0.001), and lower PPTs (p < 0.05). Fifteen patients (15/31, 48%) showed sensitization-associated symptoms (CSI ≥ 40), whereas five of the patients with pain (5/20, 25%) exhibited neuropathic-like symptoms (S-LANSS ≥ 12). The CSI and S-LANSS were positively associated with the TWSTRS, HADS-A and HADS-D, and negatively associated with PPTs. HADS-D and S-LANSS explained 72.5% of the variance of the CSI (r2: 0.725), whereas CSI explained 42.3% of the variance of the S-LANSS (r2: 0.423). Conclusions: Pain is an important source of disability in CD, and may be a consequence of different mechanisms, including sensitization. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosing progressive primary aphasia (PPA) and its variants is of great clinical importance, and fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a useful diagnostic technique. The purpose of this study was to evaluate interobserver variability in the interpretation of FDG PET images in PPA as well as the diagnostic sensitivity and specificity of the technique. We also aimed to compare visual and statistical analyses of these images. Methods: There were 10 raters who analysed 44 FDG PET scans from 33 PPA patients and 11 controls. Five raters analysed the images visually, while the other five used maps created using Statistical Parametric Mapping software. Two spatial normalization procedures were performed: global mean normalization and cerebellar normalization. Clinical diagnosis was considered the gold standard. Results: Inter-rater concordance was moderate for visual analysis (Fleiss' kappa 0.568) and substantial for statistical analysis (kappa 0.756-0.881). Agreement was good for all three variants of PPA except for the nonfluent/agrammatic variant studied with visual analysis. The sensitivity and specificity of each rater's diagnosis of PPA was high, averaging 87.8 and 89.9 % for visual analysis and 96.9 and 90.9 % for statistical analysis using global mean normalization, respectively. In cerebellar normalization, sensitivity was 88.9 % and specificity 100 %. Conclusion: FDG PET demonstrated high diagnostic accuracy for the diagnosis of PPA and its variants. Inter-rater concordance was higher for statistical analysis, especially for the nonfluent/agrammatic variant. These data support the use of FDG PET to evaluate patients with PPA and show that statistical analysis methods are particularly useful for identifying the nonfluent/agrammatic variant of PPA. [ABSTRACT FROM AUTHOR]

Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients. [ABSTRACT FROM AUTHOR]

Background and objective: Parkinson's disease (PD) is a clinically heterogeneous disorder in which the symptoms and prognosis can be very different among patients. We propose a new simple classification to identify key symptoms and staging in PD. Patients and Methods: Sixteen movement disorders specialists from Spain participated in this project. The classification was consensually approved after a discussion and review process from June to October 2021. The TNM classification and the National Institutes of Health Stroke Scale (NIHSS) were considered as models in the design. Results: The classification was named MNCD and included 4 major axes: (1) motor symptoms; (2) non-motor symptoms; (3) cognition; (4) dependency for activities of daily living (ADL). Motor axis included 4 sub-axes: (1) motor fluctuations; (2) dyskinesia; (3) axial symptoms; (4) tremor. Four other sub-axes were included in the non-motor axis: (1) neuropsychiatric symptoms; (2) autonomic dysfunction; (3) sleep disturbances and fatigue; (4) pain and sensory disorders. According to the MNCD, 5 stages were considered, from stage 1 (no disabling motor or non-motor symptoms with normal cognition and independency for ADL) to 5 (dementia and dependency for basic ADL). Conclusions: A new simple classification of PD is proposed. The MNCD classification includes 4 major axes and 5 stages to identify key symptoms and monitor the evolution of the disease in patients with PD. It is necessary to apply this proof of concept in a properly designed study. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Levodopa–entacapone–carbidopa intestinal gel (LECIG) infusion is a recently developed device‐aided therapy for advanced Parkinson disease (PD) patients. The aim of this study was to report real‐world evidence about the effectiveness, tolerability, and safety of LECIG in PD patients.A multicenter observational retrospective study of the first patients who initiated LECIG in Spain was performed. All neurologists with an experience of at least two patients treated until 30 March 2024 were invited to participate. Data about effectiveness and safety from the medical records (V0, pre‐LECIG; V1, initiation of LECIG; V2, post‐LECIG follow‐up) with a total of 246 variables were collected.Seventy‐three PD patients (61.6% males, 70.1 ± 9.1 years old) from 21 Spanish centers with a mean disease duration of 14.4 ± 6.3 years (range = 5–31) were included. Twenty‐six patients (35.6%) were switched directly from levodopa–carbidopa intestinal gel. The mean exposure to LECIG was 177.3 ± 110.5 days (range = 7–476). The mean daily OFF time decreased from 5.2 ± 3 (pre‐LECIG) to 1.9 ± 1.8 (post‐LECIG; n = 66, p < 0.0001). Global improvement was observed in >85% of the patients. No significant change was detected in the levodopa equivalent daily dose from V0 to V2. Only 7% received 24‐h infusion, and 24.7% required more than one cartridge per day at V2. Thirty‐four patients (46.6%) had at least one adverse event related to LECIG and/or the device system. Five patients (6.8%) discontinued LECIG.LECIG was safe and effective in advanced PD patients. [ABSTRACT FROM AUTHOR]

In recent years we have witnessed a growing tendency to opt for the use of dopamine agonists (DA) as treatment for Parkinson's disease (PD), with the aim of delaying as far as possible the development of fluctuations and dyskinesias. Yet, levodopa continues to be the most effective antiparkinson drug and is probably the one that improves the greatest number of symptoms of the disease. This article reports on the results of a comprehensive review of the literature dealing with the benefits and risks of levodopa treatment in patients with PD which was conducted by a group of expert neurologists and members of the Spanish Neurology Society's Movement Disorder Group. The main conclusion reached in this article is that levodopa continues to be the most effective treatment for PD. Although the risk and incidence of developing dyskinesias remains at a lower level in the group initially treated with DA, the number of patients who develop disabling dyskinesias is very low in all the studies and is similar for DA and for levodopa. Scores on the quality of life scales are also similar in the two groups, which casts some doubt on the impact that these motor complications have on the quality of life of patients with PD. In view of these findings, we should consider whether there is any real justification for depriving patients of the good control of their symptoms offered by levodopa owing to the fear of developing dyskinesias or mild motor fluctuations that are not really going to have any negative effect on their quality of life. There is also the possibility of their developing severe side effects, which are more frequent with the use of DA.