Medical, surgical, and physical treatments for Parkinson's disease.

Although dopamine replacement therapy remains a core component of Parkinson's disease treatment, the onset of motor fluctuations and dyskinetic movements might require a range of medical and surgical approaches from a multidisciplinary team, and important new approaches in the delivery of dopamine replacement are becoming available. The more challenging, wide range of non-motor symptoms can also have a major impact on the quality of life of a patient with Parkinson's disease, and requires careful multidisciplinary management using evidence-based knowledge, as well as appropriately tailored strategies according to the individual patient's needs. Disease-modifying therapies are urgently needed to prevent the development of the most disabling refractory symptoms, including gait and balance difficulties, cognitive impairment and dementia, and speech and swallowing impairments. In the third paper in this Series, we present the latest evidence supporting the optimal treatment of Parkinson's disease, and describe an expert approach to many aspects of treatment choice where an evidence base is insufficient.

Pain in monogenic Parkinson's disease: a comprehensive review.

Pain, a challenging symptom experienced by individuals diagnosed with Parkinson's disease (PD), still lacks a comprehensive understanding of its underlying pathophysiological mechanisms. A systematic investigation of its prevalence and impact on the quality of life in patients affected by monogenic forms of PD has yet to be undertaken. This comprehensive review aims to provide an overview of the association between pain and monogenic forms of PD, specifically focusing on pathogenic variants in SNCA, PRKN, PINK1, PARK7, LRRK2, GBA1, VPS35, ATP13A2, DNAJC6, FBXO7, and SYNJ1. Sixty-three articles discussing pain associated with monogenic PD were identified and analyzed. The included studies exhibited significant heterogeneity in design, sample size, and pain outcome measures. Nonetheless, the findings of this review suggest that patients with monogenic PD may experience specific types of pain depending on the pathogenic variant present, distinguishing them from non-carriers. For instance, individuals with SNCA pathogenic variants have reported painful dystonia, lower extremity pain, dorsal pain, and upper back pain. However, these observations are primarily based on case reports with unclear prevalence. Painful lower limb dystonia and lower back pain are prominent symptoms in PRKN carriers. A continual correlation has been noted between LRRK2 mutations and the emergence of pain, though the conflicting research outcomes pose challenges in reaching definitive conclusions. Individuals with PINK1 mutation carriers also frequently report experiencing pain. Pain has been frequently reported as an initial symptom and the most troublesome one in GBA1-PD patients compared to those with idiopathic PD. The evidence regarding pain in ATP13A2, PARK7, VPS35, DNAJC6, FBXO7, and SYNJ1pathogenic variants is limited and insufficient. The potential linkage between genetic profiles and pain outcomes holds promising clinical implications, allowing for the potential stratification of patients in clinical trials and the development of personalized treatments for pain in monogenic PD. In conclusion, this review underscores the need for further research to unravel the intricate relationship between pain and monogenic forms of PD. Standardized methodologies, larger sample sizes, and longitudinal studies are essential to elucidate the underlying mechanisms and develop targeted therapeutic interventions for pain management in individuals with monogenic PD.

Patient experiences of virtual care across specialist neuroscience and psychiatry clinics related to the second wave of the COVID-19 pandemic in Calgary, Alberta.

Purpose: The emergence of the COVID-19 (SARS-CoV-2) pandemic has led to public health restrictions and a shift towards virtual care and telehealth. The aim of this study was to explore barriers and facilitators of virtual care from the perspective of neurological and psychiatric patients. Methods: One-on-one interviews were conducted remotely using telephone and online video teleconferencing. There was a total of 57 participants, and a thematic content analysis was conducted using NVivo software. Results: The two main themes were (1) virtual health service delivery and (2) virtual physician/patient interaction, with subthemes around how virtual care improved accessibility of care for patients and improved patient-centered care; how privacy and technical issues impact patients using virtual care; and the need for relationality and connection between health care providers and patients while using virtual care. Conclusions: This study showed that virtual care can increase accessibility and efficiency for patients and providers, indicating its potential for ongoing use in the delivery of clinical care. Virtual care was found to be an acceptable mode of healthcare delivery from the perspective of patients; however, there is a continued need for relationship-building between care providers and patients.

The Pain in Dystonia Scale (PIDS)-Development and Validation in Cervical Dystonia.

BACKGROUND: A better understanding of pain in adult-onset idiopathic dystonia (AOID) is needed to implement effective therapeutic strategies. OBJECTIVE: To develop a new rating instrument for pain in AOID and validate it in cervical dystonia (CD). METHODS: Development and validation of the Pain in Dystonia Scale (PIDS) comprised three phases. In phase 1, international experts and participants with AOID generated and evaluated the preliminary items for content validity. In phase 2, the PIDS was drafted and revised by the experts, followed by cognitive interviews to ensure self-administration suitability. In phase 3, the PIDS psychometric properties were assessed in 85 participants with CD and retested in 40 participants. RESULTS: The final version of PIDS evaluates pain severity (by body-part), functional impact, and external modulating factors. Test-retest reliability showed a high-correlation coefficient for the total score (0.9, P < 0.001), and intraclass correlation coefficients were 0.7 or higher for all items in all body-parts subscores. The overall PIDS severity score showed high internal consistency (Cronbach's α, 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the Toronto Western Spasmodic Torticollis Rating Scale pain subscale (0.8, P < 0.001) and the Brief Pain Inventory-short form items related to pain at time of the assessment (0.7, P < 0.001) and impact of pain on daily functioning (0.7, P < 0.001). CONCLUSION: The PIDS is the first specific questionnaire developed to evaluate pain in all patients with AOID, here, demonstrating high-level psychometric properties in people with CD. Future work will validate PIDS in other forms of AOID. © 2023 International Parkinson and Movement Disorder Society.

Demographics and Clinical Characteristics of Autosomal Dominant Spinocerebellar Ataxia in Canada.

Background: Autosomal dominant (AD) spinocerebellar ataxias (SCAs) encompass a large group of rare disorders, which occurs in individuals of different ethnic backgrounds. To date, demographics, and clinical descriptions of AD SCA in Canada are lacking. Methods: A retrospective chart review of patients with a genetically confirmed diagnosis of AD SCAs was performed at five tertiary centers across Canada in the provinces of Quebec, Alberta, and Ontario. Demographic, genetic, and clinical information were collected and analyzed. Results: A total of 203 patients with AD SCA were identified. Weighted estimated prevalence of AD SCA in three large Canadian provinces was calculated (2.25 cases per 100.000) which is in keeping with the figures documented worldwide. We found that the distribution of the most common SCA differed when comparing provinces. The most prevalent SCA diagnosis in Ontario was SCA3 (49%), while the most prevalent SCA diagnosis in Alberta and Quebec was SCA2 in 26% and 47%, respectively. SCA6 was the third most prevalent SCA subtype in Quebec (14%), which was not seen as commonly in other provinces. SCA1 was uncommonly seen in both Alberta and Quebec, despite being common in Ontario. Conclusions: In this largest Canadian study, we describe the prevalence, distribution, and clinical characteristics of AD SCA. We found that the distribution of the most common SCA differed in the three provinces studied. This finding reflects the heterogenous nature of the Canadian population.

Rapid Eye Movement Sleep Behavior Disorder in Parkinson's Disease: A Survey-Based Study.

OBJECTIVE: To characterize Parkinson's disease (PD) symptoms based on the presence, onset time, and severity of rapid eye movement sleep behavior disorder (RBD) and their association with impulse control disorders (ICD). BACKGROUND: RBD is a frequent non-motor symptom in PD, usually described as prodromal. The severity of RBD according to the start time and its relationship with ICD in PD needs further clarification. METHODS: A survey-based study was performed to determine the presence of RBD symptoms, their severity, and the temporal relationship with the PD onset. The survey included RBD1Q, the Mayo Sleep, and the RBDQ-HK questionnaires and questions about clinical characteristics, including ICD. Only PD patients with care partners spending night hours in the same room were included. RESULTS: 410 PD patients were included: 206 with RBD (50.2%) and 204 non-RBD (49.8%). The PD-RBD patients were younger and their daily levodopa dose was higher than the non-RBD group. Most of these patients developed RBD symptoms after the onset of clinical PD were younger at motor symptom onset and had higher scores in the hallucinations and psychosis subsection of MDS-UPDRS-I. RBD group had a more severe non-motor phenotype, including more ICD than those without RBD, mainly due to higher compulsive eating. CONCLUSIONS: In our study, most patients recognized RBD symptoms after the onset of the PD motor symptoms and the clinical features of PD with and without RBD were distinctive, supporting the hypothesis that PD-RBD might represent a variant pattern of neurodegeneration.

Health Care Utilization in the Last Year of Life in Parkinson Disease and Other Neurodegenerative Movement Disorders.

Background and Objectives: Neurodegenerative movement disorders are rising in prevalence and are associated with high health care utilization. Generally, health care resources are disproportionately expended in the last year of life. Health care utilization by those with neurodegenerative movement disorders in the last year of life is not well-understood. The goal of this study was to assess the utilization of acute care in the last year of life among individuals with neurodegenerative movement disorders and determine whether outpatient neurology or palliative care affected acute care utilization and place of death. Methods: We conducted a retrospective cross-sectional study including health system administrative data in Alberta, Canada, from 2011 to 2017. Administrative data were used to determine place of death and quantify emergency department (ED) visits, hospitalizations, intensive care unit admissions, and outpatient generalist and specialist visits. Diagnoses were classified by 10th revision of the International Classification of Diseases codes. Stata 16v was used for statistical analyses. Results: Among 1439 individuals (60% male), Parkinson disease (n = 1226), progressive supranuclear palsy (n = 78), multiple system atrophy (n = 47), and Huntington disease (n = 58) were the most common diagnoses. The most frequent place of death was in hospital (45.9%), followed by long-term care (36.3%), home (7.9%), and residential hospice (4.0%). Most (64.2%) had >1 ED visit, and 14.4% had >3 emergency department visits. Fifty-five percent had >1 hospitalization, and 23.3% spent >30 days in hospital. Few (2.6%) were admitted to ICU. Only 37.2% and 8.8% accessed outpatient neurologist and specialist palliative care services, respectively. Multivariate logistic regression found the odds of dying at home was higher for those who received outpatient palliative consultation (OR, 2.49, 95% confidence interval [CI], 1.48-4.21, p < 0.001) and were with a longer duration of home care support (OR, 1.0007, 95% CI, 1.0004-1.0009, p < 0.001). Discussion: There are high rates of in-hospital death and acute care utilization in the year before death among those with neurodegenerative movement disorders. Most did not access specialist palliative or neurologic care in the last year of life. Outpatient palliative care and home care services were associated with increased odds of dying at home. Our results indicate the need for further research into the causes, costs, and potential modifiers to inform public health planning.

What neurologists wish palliative care physicians knew.

As the incidence of neurologic (particularly neurodegenerative) diseases continues to rise, so too will the palliative needs in this patient population. To appropriately care for these patients and families, neurologists and palliative care providers will need to strengthen collaboration. Palliative care providers not formally trained in neurology may feel ill-equipped to manage some of the distinct neuropalliative care needs of these patients. Here, we provide insights into the unique characteristics of patients with neurologic disease and emphasize the relevance of the palliative care skillset in this population to aid the collaboration between palliative care providers and neurologists.

A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity.

Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.

Treatment-related fluctuations in Guillain-Barré syndrome​: clinical features and predictors of recurrence / Fluctuaciones relacionadas al tratamiento en el Síndrome de Guillain-Barré: características clínicas y predictores de recurrencia

ABSTRACT Background: A treatment-related fluctuation (TRF) in a patient with Guillain-Barré syndrome (GBS) is defined as clinical deterioration within two months of symptom onset following previous stabilization or improvements with treatment. Objective: To investigate the clinical characteristics and factors that could increase the risk of relapse of GBS in patients with and without TRFs. Methods: Retrospective review of medical records of patients (>18 years) with GBS evaluated between January/2006 and July/2019. Demographic and clinical characteristics, ancillary studies, treatment received, and the clinical course of patients with and without TRFs were analyzed. Results: Overall, 124 cases of GBS were included; seven (5.6%) presented TRFs. GBS-TRF cases were triggered more frequently by infectious mononucleosis (28.57 vs. 8.55%; p=0.01). GBS-TRF were initially treated with plasmapheresis more frequently than those without TRF (14.29 vs. 1.70%; p=0.0349). Combined treatment (71.43 vs. 4.27%; p<0.001) and corticosteroids (42.86 vs. 1.71%; p<0.001) were more commonly used in the GBS-TRF group. GBS-TRF patients presented a higher median initial disability score (4 vs. 2; p=0.01). Conclusions: Patients with GBS triggered by infectious mononucleosis and a high degree of initial disability have higher chances of developing TRFs. Although patients with TRF were treated with plasmapheresis more often, the total number was too low to suggest a link between plasma exchange and TRF.

RESUMEN Antecedentes: Una fluctuación relacionada al tratamiento (FRT) en un paciente con síndrome de Guillain-Barré (SGB) se define como un deterioro clínico dentro de los dos meses posteriores al inicio de los síntomas después de una estabilización previa o mejoría con el tratamiento. Objetivo: Investigar las características clínicas y los factores que podrían incrementar el riesgo de recaída, comparando pacientes con SGB, con y sin FRT. Métodos: Revisión retrospectiva de historias clínicas de pacientes (>18 años) con SGB evaluados entre enero/2006 y julio/2019. Se analizaron las características demográficas y clínicas, los estudios complementarios, el tratamiento recibido y la evolución clínica de los pacientes con y sin FRT. Resultados: Se incluyeron 124 casos de SGB en el total; 7 (5,6%) presentaron FRT. Los casos de SGB con FRT se desencadenaron con mayor frecuencia por mononucleosis infecciosa (28,57 vs. 8,55%; p=0,01). Los casos de SGB con FRT se trataron inicialmente con plasmaféresis con más frecuencia que aquellos sin FRT (14,29 vs. 1,70%; p=0,0349). El tratamiento combinado (71,43 vs. 4,27%; p<0,001) y los corticosteroides (42,86 vs. 1,71%; p<0,001) se utilizaron con mayor frecuencia en el grupo de SGB con FRT. Los pacientes con FRT presentaron una escala de discapacidad inicial mediana más alta (4 vs. 2; p=0,01). Conclusiones: Aquellos SGB desencadenados por mononucleosis infecciosa y un alto grado de discapacidad inicial tienen una mayor probabilidad de desarrollar FRT. Aunque los pacientes con FRT fueron tratados con plasmaféresis con mayor frecuencia, el número total fue demasiado bajo para sugerir un vínculo entre la plasmaféresis y FRT.

Treatment-related fluctuations in Guillain-Barré syndrome​: clinical features and predictors of recurrence.

BACKGROUND: A treatment-related fluctuation (TRF) in a patient with Guillain-Barré syndrome (GBS) is defined as clinical deterioration within two months of symptom onset following previous stabilization or improvements with treatment. OBJECTIVE: To investigate the clinical characteristics and factors that could increase the risk of relapse of GBS in patients with and without TRFs. METHODS: Retrospective review of medical records of patients (>18 years) with GBS evaluated between January/2006 and July/2019. Demographic and clinical characteristics, ancillary studies, treatment received, and the clinical course of patients with and without TRFs were analyzed. RESULTS: Overall, 124 cases of GBS were included; seven (5.6%) presented TRFs. GBS-TRF cases were triggered more frequently by infectious mononucleosis (28.57 vs. 8.55%; p=0.01). GBS-TRF were initially treated with plasmapheresis more frequently than those without TRF (14.29 vs. 1.70%; p=0.0349). Combined treatment (71.43 vs. 4.27%; p<0.001) and corticosteroids (42.86 vs. 1.71%; p<0.001) were more commonly used in the GBS-TRF group. GBS-TRF patients presented a higher median initial disability score (4 vs. 2; p=0.01). CONCLUSIONS: Patients with GBS triggered by infectious mononucleosis and a high degree of initial disability have higher chances of developing TRFs. Although patients with TRF were treated with plasmapheresis more often, the total number was too low to suggest a link between plasma exchange and TRF.

Field studies on the deterioration of microplastic films from ultra-thin compostable bags in soil.

In recent years, some countries have replaced single-use plastic bags with bags manufactured from compostable plastic film that can be used for collecting food wastes and composted together with the waste. Because industrial compost contains undeteriorated fragments of these bags, application to field soil is a potential source of small-sized residues from these bags. This study was undertaken to examine deterioration of these compostable film microplastics (CFMPs) in field soil at three different localities in Italy. Deterioration of CFMPs did not exceed 5.7% surface area reduction during the 12-month experimental period in two sites located in Northern Italy. More deterioration was observed in the Southern site, with 7.2% surface area reduction. Deterioration was significantly increased when fields were amended with industrial compost (up to 9.6%), but not with home compost. Up to 92.9% of the recovered CFMPs were associated with the soil fungus Aspergillus flavus, with 20.1%-71.2% aflatoxin-producing isolates. Application of industrial compost resulted in a significant increase in the percentage of CFMPs associated with A. flavus. This observation provides an argument for government regulation of accumulation of CFMPs and elevation of hazardous fungi levels in agricultural soils that receive industrial compost.

Effects of the COVID-19 Pandemic on Parkinson's Disease: a Single-Centered Qualitative Study.

BACKGROUND: The public health measure restrictions across the world due to COVID-19 have inadvertently impacted the routines for people with Parkinson's disease (PD) and their care partners not only in terms of compromised neurological clinical care but also drastically changing the way of life to minimize the risk of becoming infected. This study explores initial PD patients' lived experiences to observe how quality of life and health care has been affected at the start of the COVID-19 pandemic and provide insight into the importance of patient engagement and virtual care. METHODS: Twenty-two virtual, in-depth semi-structured interviews with persons diagnosed with PD who usually attend a Movement Disorders specialty clinic in Calgary, Alberta, were completed between April 28 and May 13, 2020, and the care partners that wished to participate. Interviews were recorded and transcribed, after which transcripts were analyzed and coded into relevant themes using NVivo 12. RESULTS: Impacts from the public health measures and COVID-19 results into three main themes: (1) Impacts of COVID-19 on PD Clinical Care; (2) Activities of Daily Living; (3) Attitudes and Perceptions. Participants reported worsening in motor and nonmotor symptoms and had to accommodate to clinical care via virtual means which were associated with limitations and suggestions for improvement of remote care. CONCLUSION: This study provides a unique opportunity for researchers to better understand the lived experiences of PD patients in all aspects of their life suggesting that innovative means are needed for facilitating virtual health care medicine and increased social interaction.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Response to Thalamic Ventralis Intermedius Nucleus Deep Brain Stimulation in Essential Tremor vs. Essential Tremor-Plus.

Introduction: Essential tremor (ET) is a tremor syndrome characterized by bilateral, upper limb action tremor. Essential tremor-plus (ET-plus) describes ET patients with additional neurologic signs. It is unknown whether there is a difference in response to treatment with ventralis intermedius nucleus deep brain stimulation (VIM DBS) in patients with ET and ET-plus. Due to potential variability in underlying etiology in ET-plus, there is a concern that ET-plus patients may have worse outcomes. The aim of this study was to identify whether patients with ET-plus have worse tremor outcomes after VIM DBS than patients with ET. Methods: This is a retrospective chart and video review evaluating VIM DBS outcomes by comparing changes from baseline in the Fahn-Tolosa-Marin Tremor Rating Scale Part B (FTM-B) for the treated limb between patients with ET and ET-plus at follow-up examinations. Patients were re-classified as having ET or ET-plus using pre-operative examination videos by two independent movement disorders neurologists blinded to patient characteristics. As a secondary outcome, we evaluated for correlations and potential predictors of treatment response. Results: Twenty-six patients were included: 13 with ET, 13 with ET-plus. There were no significant differences in the change in FTM-B scores between the ET and ET-plus patients at each follow-up examination. None of the included patients developed new symptoms compatible with dystonia, parkinsonism or gait disturbances. Conclusions: Patients with ET-plus had tremor improvement from VIM DBS, with no differences when compared to those with ET, without emergence of postoperative neurological issues. Patients with ET-plus should still be considered good candidates for VIM DBS for treatment of tremor.

Antidepressants Effects on Pain in Parkinson Disease: A Systematic Review.

OBJECTIVE: Pain in Parkinson disease (PD) is complex as this symptom can be multifactorial in origin because deficits in dopaminergic but also other neurotransmitters are involved. Pain and depression are increasingly recognized to have clinical importance for the quality of life of people living with PD. This systematic review aims to summarize the existing evidence on the potential benefit of using prescribed antidepressants for decreasing or controlling pain associated with PD. METHODS: PubMed databases were searched for relevant studies using keywords and our exclusion/inclusion criteria and targeting only randomized placebo-controlled trials for antidepressants in PD. RESULTS: After screening 108 articles, only 3 focused articles were analyzed. Two of the included studies reported were on nortriptyline and paroxetine antidepressants. Unfortunately, included studies did not align in their outcome measures and did not directly compare the drug groups against each other or the placebo. Therefore, the complex nature of the unaligned outcome measures is inadequate for interpreting the efficacy of antidepressants in treating pain symptoms in PD. The third study focused solely on observing the effects of duloxetine but showed no favorable effects of this drug on pain. CONCLUSIONS: Prospective studies with a direct comparison of antidepressants and placebo should be conducted, focusing on pain-related scales and questions to understand further the role of antidepressants in treating pain in PD.

Non-motor complications in late stage Parkinson's disease: recognition, management and unmet needs.

Introduction: The burden of non-motor symptoms (NMS) is a major determinant of health-related quality of life in Parkinson's disease (PD), particularly at its late stage.Areas covered: The late stage is usually defined as the period from unstable advanced to the palliative stage, characterized by a combination of emerging treatment-resistant axial motor symptoms (freezing of gait, postural instability, falls and dysphagia), as well as both non-dopaminergic and dopaminergic NMS: cognitive decline, neuropsychiatric symptoms, aspects of dysautonomia, pain and sleep disturbances (insomnia and excessive day-time sleepiness). Here, the authors summarize the current knowledge on NMS dominating the late stage of PD and propose a pragmatic and clinically focused approach for their recognition and treatment.Expert opinion: The NMS progression pattern is complex and remains under-researched. While dopamine-dependent NMS may improve with dopamine replacement therapy, non-dopamine dependent NMS worsen progressively and culminate at the late stages of PD. Furthermore, some PD specific features could interact negatively with other comorbidities, multiple medication use and frailty - the evaluation of these aspects is important in the creation of personalized management plans in the late stage of PD.

Heart rate variability and falls in Huntington's disease.

PURPOSE: Persons with Huntington's disease (HD) have a high incidence of falls. Autonomic nervous system dysfunction has been reported even in early stages of this disease. To date, there has been no analysis of the relationship between heart rate variability (HRV) and falls in this patient population. The aim of the study reported here was to evaluate the relationship between HRV and falls in persons with HD. METHODS: Huntington's disease patients enrolled in a prospective study on fear of falling and falls were assessed using short-term HRV analyses and blood pressure measures in both the resting and standing states. Time-frequency domains and nonlinear parameters were calculated. Data on falls, the risk of falling (RoF) and disease-specific scales were collected at baseline and at the end of the 6-month follow-up. RESULTS: Of the 24 HD patients who were invited to participate in the study, 20 completed the baseline analysis and 18 completed the 6-month follow-up. At baseline, seven (35%) HD patients reported at least one fall (single fallers) and 13 (65%) reported ≥ 2 falls (recurrent fallers) in the previous 12 months. At baseline, recurrent fallers had lower RMSSD (root mean square of successive RR interval differences) in the resting state (RMSSD-resting), higher LF/HF (low/high frequency) ratio in both states and higher DFA-α1 parameter (detrended fluctuation analyses over the short term) in both states. This association was similar at the 6-month follow-up for recurrent fallers, who showed lower RMSSD-resting and higher LF/HF ratio in the standing state (LF/HF-standing) than single fallers. Significant correlations were found between the number of falls, RMSSD-resting and LF/HF-standing. No differences were found between recurrent and single fallers for any blood pressure measures. CONCLUSIONS: The observed HRV pattern is consistent with a higher sympathetic prevalence associated with a higher RoF. Reduced parasympathetic HRV values in this patient population predict being a recurrent faller at 6 months of follow-up, independently of orthostatic phenomena.