[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.

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.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives: To judge the long-term outcome of patients with STN-DBS. Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson's disease and atypical Parkinsonian syndromes.

The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard.

High-Resolution Mapping of Strain Partitioning and Relaxation in InGaN/GaN Nanowire Heterostructures.

Growing an Inx Ga1- x N/GaN (InGaN/GaN) multi-quantum well (MQW) heterostructure in nanowire (NW) form is expected to overcome limitations inherent in light-emitting diodes (LEDs) based on the conventional planar heterostructure. The epitaxial strain induced in InGaN/GaN MQW heterostructure can be relaxed through the sidewalls of NW, which is beneficial to LEDs because a much larger misfit strain with higher indium concentration can be accommodated with reduced piezoelectric polarization fields. The strain relaxation, however, renders highly complex strain distribution within the NW heterostructure. Here the authors show that complementary strain mapping using scanning transmission electron microscopy and dark-field inline holography can comprehend the strain distribution within the axial In0.3 Ga0.7 N/GaN MQW heterostructure embedded in GaN NW by providing the strain maps which can cover the entire NW and fine details near the sidewalls. With the quantitative evaluation by 3D finite element modelling, it is confirmed that the observed complex strain distribution is induced by the strain relaxation leading to the strain partitioning between InGaN quantum disk, GaN quantum well, and the surrounding epitaxial GaN shell. The authors further show that the strain maps provide the strain tensor components which are crucial for accurate assessment of the strain-induced piezoelectric fields in NW LEDs.

[Treatment practice of patients with Parkinson's disease in Saxony : A secondary data-based analysis of utilization in the observation period 2011-2019]. / Versorgungssituation von Parkinson-Patienten in Sachsen : Eine sekundärdatenbasierte Analyse der Inanspruchnahme im Beobachtungszeitraum 2011 bis 2019.

BACKGROUND: The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson's disease (PwP), a status quo analysis of current care practice is required. OBJECTIVE: To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019? MATERIAL AND METHODS: The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder. RESULTS: Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4­fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson's disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist. DISCUSSION: The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care.

Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson's Disease.

Identification of individual risk factors for motor complications in Parkinson's disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOB CC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089-0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039-0.520]; p=0.003) than MAOB TT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD.

SARS-CoV-2 rapid antigen testing in the healthcare sector: A clinical prediction model for identifying false negative results.

OBJECTIVES: SARS-CoV-2 rapid antigen tests (RAT) provide fast identification of infectious patients when RT-PCR results are not immediately available. We aimed to develop a prediction model for identification of false negative (FN) RAT results. METHODS: In this multicenter trial, patients with documented paired results of RAT and RT-PCR between October 1st 2020 and January 31st 2021 were retrospectively analyzed regarding clinical findings. Variables included demographics, laboratory values and specific symptoms. Three different models were evaluated using Bayesian logistic regression. RESULTS: The initial dataset contained 4,076 patients. Overall sensitivity and specificity of RAT was 62.3% and 97.6%. 2,997 cases with negative RAT results (FN: 120; true negative: 2,877; reference: RT-PCR) underwent further evaluation after removal of cases with missing data. The best-performing model for predicting FN RAT results containing 10 variables yielded an area under the curve of 0.971. Sensitivity, specificity, PPV and NPV for 0.09 as cut-off value (probability for FN RAT) were 0.85, 0.99, 0.7 and 0.99. CONCLUSION: FN RAT results can be accurately identified through ten routinely available variables. Implementation of a prediction model in addition to RAT testing in clinical care can provide decision guidance for initiating appropriate hygiene measures and therefore helps avoiding nosocomial infections.

Association of history of cerebrovascular disease with severity of COVID-19.

OBJECTIVE: To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). METHODS: In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran's Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. RESULTS: Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52-2.81; p < 0.0001]. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22-1.71; p < 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83-4.24; p < 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75-2.7; p < 0.0001). CONCLUSION: A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19  suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Parkinson Network Eastern Saxony (PANOS): Reaching Consensus for a Regional Intersectoral Integrated Care Concept for Patients with Parkinson's Disease in the Region of Eastern Saxony, Germany.

As integrated care is recognized as crucial to meet the challenges of chronic conditions such as Parkinson's disease (PD), integrated care networks have emerged internationally and throughout Germany. One of these networks is the Parkinson Network Eastern Saxony (PANOS). PANOS aims to deliver timely and equal care to PD patients with a collaborative intersectoral structured care pathway. Additional components encompass personalized case management, an electronic health record, and communicative and educative measures. To reach an intersectoral consensus of the future collaboration in PANOS, a structured consensus process was conducted in three sequential workshops. Community-based physicians, PD specialists, therapists, scientists and representatives of regulatory authorities and statutory health insurances were asked to rate core pathway-elements and supporting technological, personal and communicative measures. For the majority of core elements/planned measures, a consensus was reached, defined as an agreement by >75% of participants. Additionally, six representatives from all partners involved in the network-design independently assessed PANOS based on the Development Model for Integrated Care (DMIC), a validated model addressing the comprehensiveness and maturity of integrated care concepts. The results show that PANOS is currently in an early maturation state but has the potential to comprehensively represent the DMIC if all planned activities are implemented successfully. Despite the favorable high level of consensus regarding the PANOS concept and despite its potential to become a balanced integrated care concept according to the DMIC, its full implementation remains a considerable challenge.

Specialized Staff for the Care of People with Parkinson's Disease in Germany: An Overview.

Access to specialized care is essential for people with Parkinson´s disease (PD). Given the growing number of people with PD and the lack of general practitioners and neurologists, particularly in rural areas in Germany, specialized PD staff (PDS), such as PD nurse specialists and Parkinson Assistants (PASS), will play an increasingly important role in the care of people with PD over the coming years. PDS have several tasks, such as having a role as an educator or adviser for other health professionals or an advocate for people with PD to represent and justify their needs. PD nurse specialists have been established for a long time in the Netherlands, England, the USA, and Scandinavia. In contrast, in Germany, distinct PDS models and projects have been established. However, these projects and models show substantial heterogeneity in terms of access requirements, education, theoretical and practical skills, principal workplace (inpatient vs. outpatient), and reimbursement. This review provides an overview of the existing forms and regional models for PDS in Germany. PDS reimbursement concepts must be established that will foster an implementation throughout Germany. Additionally, development of professional roles in nursing and more specialized care in Germany is needed.

[The role of inhibitors of COMT and MAO-B in the therapy of Parkinson's disease]. / Grundlagen und Stellenwert der COMT- und MAO-B-Inhibitoren in der Therapie des idiopathischen Parkinson-Syndroms.

Inhibitors of COMT and MAO-B are well established in the pharmacotherapy of Parkinson's disease (PD). MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Both classes of compounds prolong the response duration of levodopa and optimise its clinical benefit. As a result, the ON-times are prolonged significantly. In the past, MAO-B inhibitors were also adminstered for neuroprotection; however, despite convincing scientific reasoning in support of neuroprotective effects, these could not be substantiated in clinical studies performed so far.

Recommendations for Standards of Network Care for Patients with Parkinson's Disease in Germany.

Although our understanding of Parkinson´s disease (PD) has improved and effective treatments are available, caring for people with PD remains a challenge. The large heterogeneity in terms of motor symptoms, nonmotor symptoms, and disease progression makes tailored individual therapy and individual timing of treatment necessary. On the other hand, only limited resources are available for a growing number of patients, and the high quality of treatment cannot be guaranteed across the board. At this point, networks can help to make better use of resources and improve care. The working group PD Networks and Integrated Care, part of the German Parkinson Society, is entrusted to convene clinicians, therapists, nurses, researchers, and patients to promote the development of PD networks. This article summarizes the work carried out by the working group PD Networks and Integrated Care in the development of standards of network care for patients with PD in Germany.

[Parkinson Networks in Germany: Future or Utopia?] / Parkinson-Netzwerke in Deutschland: Zukunft oder Utopie?

BACKGROUND: Parkinson's disease requires a close interaction between different care partners from the point of diagnosis in order to provide the best possible care for patients. However, the treatment reality shows that there are often still significant gaps in care. In recent years it has been recognised that the formation of networks can contribute to improving the care of Parkinson's patients. OBJECTIVES: To present the current status of the development of Parkinson's networks in Germany, the available evidence and the future of Parkinson's networks. MATERIAL AND METHODS: Experiences from existing networks in Germany were systematically recorded on the basis of personal reports and publications. The existing national and international evidence was summarised, and critical success factors and hurdles were analysed. In addition, possible future scenarios were developed. RESULTS: There are many integrated approaches to improve the care of Parkinson's patients. However, this is usually subject to the initiative at individual locations, without binding conditions being created for this by the legislator or the funding agencies outside of model projects. DISCUSSION: It must be noted that it is currently very difficult to implement a problem-free and cost-efficient development of intersectoral network structures within the existing possibilities of the German health care system. The high personal commitment of individual actors currently forms the basis of existing regional networks. An overarching health policy concept is needed to further promote the content and infrastructure of Parkinson's disease networks.

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

Putaminal Dopamine Turnover in de novo Parkinson's Disease Predicts Later Neuropsychiatric Fluctuations but Not Other Major Health Outcomes.

BACKGROUND AND OBJECTIVE: To investigate the predictive value of striatal dopamine turnover in patients with de novo Parkinson's disease (PD) for later occurrence of major non-motor health outcomes. METHODS: This retrospective, observer-blinded cohort study followed up 29 patients with de novo PD for a median of 10.7 years, who completed 18Fluorodopa PET imaging to measure striatal effective distribution volume ratio (EDVR, inverse of dopamine turnover) prior to antiparkinsonian treatment. Outcomes were assessed with a battery of non-motor, health-related quality-of-life and non-motor fluctuation (WOQ-19) measures and survival. RESULTS: During follow-up, 52% of patients developed wearing-off, 43% neuropsychiatric fluctuations, 35% sensory fluctuations, 32% dementia, 46% depression, 30% psychosis, and PD-related mortality was 26%. Patients with wearing-off and neuropsychiatric fluctuations showed significantly lower baseline EDVR (higher dopamine turnover) in the putamen but not in the caudate nucleus than those without these fluctuations. Consistently, baseline EDVR in the putamen predicted development of wearing-off and neuropsychiatric fluctuations with a lower risk with higher EDVR (lower dopamine turnover), whereas EDVR in caudate nucleus did not correlate with these fluctuations. No relationships were observed between baseline PET measures and the presence of other major health outcomes including survival. CONCLUSIONS: Lower putaminal dopamine turnover in de novo PD is associated with reduced risk for later neuropsychiatric fluctuations comprising a disease-intrinsic predisposing factor for their development, similar as reported for levodopa-induced motor complications. Striatal (putaminal/caudate) dopamine turnover is not predictive for other long-term major health outcomes. These results should be treated as hypothesis generating and require confirmation.

Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.

OBJECTIVE: The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). METHODS: This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. RESULTS: Patients carrying the MAOBCC/(C)/CT genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. CONCLUSIONS: The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Impairment in Respiratory Function Contributes to Olfactory Impairment in Amyotrophic Lateral Sclerosis.

BACKGROUND: Nonmotor symptoms are very common in neurodegenerative diseases. In patients suffering from amyotrophic lateral sclerosis (ALS), olfactory dysfunction was first reported more than 20 years ago; however, its pathophysiological correlates and further implications remain elusive. METHODS: In this so far largest case-control study, we analyzed olfactory performance with the "Sniffin' Sticks," a validated olfactory testing kit used in clinical routine. This test kit was designed to investigate different qualities of olfaction including odor threshold, odor discrimination, and odor identification. RESULTS: ALS patients were mildly but significantly impaired in TDI score, the composite of the three subtests (ALS 27.7 ± 7.9, Controls 32.3 ± 5.8). In contrast to Parkinson's disease, ALS patients did not show impaired performance in the suprathreshold tests identification and discrimination. However, the odor threshold was markedly decreased (ALS 6.0 ± 3.4, Controls 8.77 ± 3.6). This pattern of olfactory loss resembles sinonasal diseases, where olfactory dysfunction results from impeded odorant transmission to the olfactory cleft. The evaluation of medical history and clinical data of ALS patients showed that patients with perception of dyspnea (TDI 25.7 ± 8.0) performed significantly worse in olfactory testing compared to those who did not (TDI 30.0 ± 7.4). In line with that, we found that in patients with preserved respiratory function (vital capacity >70% of index value), olfactory performance did not differ from healthy controls. CONCLUSION: These findings suggest that the mild impairment of olfaction in patients suffering from ALS should at least partly be considered as a consequence of impaired respiratory function, and odor threshold might be a marker of respiratory dysfunction in ALS.

Subthalamic nucleus stimulation and levodopa modulate cardiovascular autonomic function in Parkinson's disease.

We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six Parkinson's disease patients with bilateral subthalamic nucleus stimulation in a stable state were tested under stimulation off and dopaminergic medication off (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and stimulation on and medication (levodopa) on (ON-ON) conditions by recording continuously blood pressure, ECG, and respiration at rest, during metronomic deep breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses were performed by trigonometric regressive spectral analysis. Subthalamic nucleus stimulation and levodopa had multiple influences. (1) Systolic blood pressure during tilt-up was reduced by subthalamic nucleus stimulation, and then further by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different effects on sympathetic and parasympathetic regulations in Parkinson's disease. (3) Levodopa decreased baroreflex sensitivity and RR interval only in the orthostatic hypotension group, and had opposite effects on the non-orthostatic hypotension group. These findings indicate that subthalamic nucleus stimulation and levodopa have different effects on cardiovascular autonomic function in Parkinson's disease, which are modulated by the presence of orthostatic hypotension as well.