Experimental evidence for a robust, transdiagnostic marker in functional disorders: Erroneous sensorimotor processing in functional dizziness and functional movement disorder.

OBJECTIVE: Recent neuroscientific models suggest that functional bodily symptoms can be attributed to perceptual dysregulation in the central nervous system. Evidence for this hypothesis comes from patients with functional dizziness, who exhibit marked sensorimotor processing deficits during eye-head movement planning and execution. Similar findings in eye-head movement planning in patients with irritable bowel syndrome confirmed that these sensorimotor processing deficits represent a shared, transdiagnostic mechanism. We now examine whether erroneous sensorimotor processing is also at play in functional movement disorder. METHODS: We measured head movements of 10 patients with functional movement disorder (F44.4, ICD-10), 10 patients with functional dizziness (F45.8, ICD-10), and (respectively) 10 healthy controls during an eye-head experiment, where participants performed large gaze shifts under normal, increased, and again normal head moment of inertia. Head oscillations at the end of the gaze shift served as a well-established marker for sensorimotor processing problems. We calculated Bayesian statistics for comparison. RESULTS: Patients with functional movement disorder (Bayes Factor (BF)10 = 5.36, BFincl = 11.16; substantial to strong evidence) as well as patients with functional dizziness (BF10 = 2.27, BFincl = 3.56; anecdotal to substantial evidence) showed increased head oscillations compared to healthy controls, indicating marked deficits in planning and executing movement. CONCLUSION: We replicate earlier experimental findings on erroneous sensorimotor processing in patients with functional dizziness, and show that patients with functional movement disorder show a similar impairment of sensorimotor processing during large gaze shifts. This provides an objectively measurable, transdiagnostic marker for functional disorders, highlighting important implications for diagnosis, treatment, and de-stigmatization.

[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

BACKGROUND: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making. MATERIAL AND METHODS: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis. RESULTS: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents. DISCUSSION: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers.

Reduced tear fluid production in neurological diseases: a cohort study in 708 patients.

BACKGROUND: Tear fluid (TF) production is an important component of normal ocular function. It is regulated by parasympathetic and sympathetic innervation. Because parasympathetic nerve fibers originate in the brainstem, pathology in this brain region may affect TF production. For example, a reduction in TF production has been described in patients with Parkinson's disease (PD). METHODS: TF was collected at one center from 772 individuals, 708 of which were patients with different neurological diseases, and 64 healthy controls. Wetting lengths (WL) were recorded using Schirmer test strips with a collection time of 10 min. RESULTS: WL correlated negatively with age and was significantly reduced in subgroups of patients with neurodegenerative diseases (NDDs) (PD, Amyotrophic lateral sclerosis (ALS), other motor neuron diseases (MNDs)), as well as inflammatory/autoimmune/infectious central nervous system (CNS) diseases and vascular CNS diseases (VCDs), even if corrected for age or sex. While temperature had a significant negative effect on TF production, other environmental factors, such as hours of sunlight and humidity, did not. CONCLUSION: WL was altered in many neurological diseases compared to healthy controls. Most importantly, we observed a reduction of WL in NDDs, independent of age or sex. This study highlights the potential of WL as an easily obtainable parameter and suggests functional alterations in the autonomic innervation in various neurological disorders.

Nationwide Retrospective Analysis of Combinations of Advanced Therapies in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Advanced therapies (ATs; deep brain stimulation [DBS] or pump therapies: continuous subcutaneous apomorphine infusion [CSAI], levodopa/carbidopa intestinal gel [LCIG]) are used in later stages of Parkinson disease (PD). However, decreasing efficacy over time and/or side effects may require an AT change or combination in individual patients. Current knowledge about changing or combining ATs is limited to mostly retrospective and small-scale studies. The nationwide case collection Combinations of Advanced Therapies in PD assessed simultaneous or sequential AT combinations in Germany since 2005 to analyze their clinical outcome, their side effects, and the reasons for AT modifications. METHODS: Data were acquired retrospectively by modular questionnaires in 22 PD centers throughout Germany based on clinical records and comprised general information about the centers/patients, clinical (Mini-Mental Status Test/Montréal Cognitive Assessment, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS], side effects, reasons for AT modification), and therapeutical (ATs with specifications, oral medication) data. Data assessment started with initiation of the second AT. RESULTS: A total of 148 AT modifications in 116 patients were associated with significantly improved objective (median decrease of MDS-UPDRS Part III 4.0 points [p < 0.001], of MDS-UPDRS Part IV 6.0 points [p < 0.001], of MDS-UPDRS Part IV-off-time item 1.0 points [p < 0.001]) and subjective clinical outcome and decreasing side effect rates. Main reasons for an AT modification were insufficient symptom control and side effects of the previous therapy. Subgroup analyses suggest addition of DBS in AT patients with leading dyskinesia, addition of LCIG for leading other cardinal motor symptoms, and addition of LCIG or CSAI for dominant off-time. The most long-lasting therapy-until requiring a modification-was DBS. DISCUSSION: Changing or combining ATs may be beneficial when 1 AT is insufficient in efficacy or side effects. The outcome of an AT combination is comparable with the clinical benefit by introducing the first AT. The added AT should be chosen dependent on dominant clinical symptoms and adverse effects. Furthermore, prospective trials are needed to confirm the results of this exploratory case collection. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, in patients with PD, changing or combining ATs is associated with an improvement in the MDS-UPDRS or subjective symptom reporting.

Parkinson's disease therapy: what lies ahead?

The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics. New formulations of approved drugs and treatment options of motor fluctuations in advanced stages accompanied by telehealth monitoring have improved PD patients care. In addition, continuous improvement in the understanding of PD disease mechanisms resulted in the identification of new pharmacological targets. Applying novel trial designs, targeting of pre-symptomatic disease stages, and the acknowledgment of PD heterogeneity raise hopes to overcome past failures in the development of drugs for disease modification. In this review, we address these recent developments and venture a glimpse into the future of PD therapy in the years to come.

Long-Lasting Impact of the COVID-19 Pandemic on Patients with Parkinson's Disease and Their Relatives.

Background: The coronavirus disease 2019 (COVID-19) pandemic has heavily impacted medical care of patients with Parkinson's disease (PwP). Objective: To assess the longitudinal impact of the COVID-19 pandemic on PwP and their relatives in Germany. Methods: Two online, nationwide, cross-sectional surveys were conducted from December 2020 to March 2021 and from July to September 2021. Results: A total of 342 PwP and 113 relatives participated. Despite partial resumption of social and group activities, healthcare was continuously disrupted during times of loosened restrictions. Respondents' willingness to use telehealth infrastructure increased, yet the availability remained low. PwP reported worsened symptoms and further deterioration during the pandemic, resulting in an increase in new symptoms and relatives' burden. We identified patients at particular risk: young patients and those with long disease duration. Conclusions: The COVID-19 pandemic persistently disrupts the care and quality of life of PwP. Although willingness to use telemedicine services has increased, its availability needs to be improved.

Changes in the peripheral and central auditory performance in the elderly-A cross-sectional study.

Age-related hearing loss (ARHL, formerly presbycusis) is due to a variety of lifetime damages to the auditory system and is characterized by bilateral sensorineural hearing loss, impaired speech understanding in noise and central sound processing deficits. Despite its commonness, the pathogenesis has not been completely clarified yet; especially the existence of an independent central ARHL component still remains controversial. We present the results of a cross-sectional topodiagnostic test battery study which aimed at separating aging- and hearing loss-related effects on all parts of the auditory system by current test procedures. Three groups of 30 participants each underwent extensive topodiagnostic test procedures (otoscopy, tympanometry, questionnaires, pure-tone audiometry, DPOAE threshold measurements, auditory brainstem response, central auditory discrimination tests, and speech-in-noise test). By comparing the results of the normally hearing young (18-26 years) and healthy control group, the normally hearing elderly group (60-80 years) and the hearing-impaired elderly group (60-80 years), we deduced aging and hearing loss-related effects on auditory performance. All measurements indicated a significant deterioration of auditory performance in the elderly, partly associated with aging and partly with age-related hearing loss. Our study thereby contributes to a multifocal concept of ARHL. All parts of the auditory system are impaired by aging, age-related hearing loss, or a combination of both. Further evidence for an independent central ARHL component, not attributable to peripheral hearing loss, is provided by the results of the central auditory discrimination test.