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Parkinson Disease: HELP
Articles by Heike Stockner
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, H. Stockner wrote the following 18 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community. 2016

Mahlknecht, Philipp / Gasperi, Arno / Willeit, Peter / Kiechl, Stefan / Stockner, Heike / Willeit, Johann / Rungger, Gregorio / Sawires, Martin / Nocker, Michael / Rastner, Verena / Mair, Katherina J / Hotter, Anna / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · King's British Heart Foundation Centre, King's College London, London, United Kingdom. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Werner.Poewe@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Klaus.Seppi@tirol-kliniken.at. ·Mov Disord · Pubmed #27273736.

ABSTRACT: BACKGROUND: Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinson's disease (PD), but to date their predictive value has not yet been tested in population-based cohorts. METHODS: We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable. RESULTS: After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of "probable prodromal PD" status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%). CONCLUSIONS: Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease-prevention trials. © 2016 International Parkinson and Movement Disorder Society.

2 Article Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident Parkinson's disease over 10 years: A prospective population-based study. 2020

Mahlknecht, Philipp / Stockner, Heike / Marini, Kathrin / Gasperi, Arno / Djamshidian, Atbin / Willeit, Peter / Kiechl, Stefan / Willeit, Johann / Rungger, Gregorio / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, United Kingdom. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Klaus.Seppi@tirol-kliniken.at. ·Parkinsonism Relat Disord · Pubmed #31864071.

ABSTRACT: INTRODUCTION: Associations of substantia nigra (SN) hyperechogenicity on transcranial sonography, olfactory dysfunction, and mild parkinsonian signs (MPS) with incident Parkinson's disease (PD) have only been studied over limited periods of follow-up and their long-term predictive properties are unclear. We aimed to prospectively assess the risk for incident PD over 10 years in community-dwelling elderly individuals with these risk markers. METHODS: SN-hyperechogenicity, olfactory function, and MPS were assessed in the prospective population-based Bruneck Study (2005 in-person assessment; n = 574, aged 55-94 years). Cases of incident PD were identified at 5-year and 10-year follow-up visits. We estimated relative risks of baseline markers for incident cases. RESULTS: After excluding 35 cases with PD or secondary parkinsonism at baseline, a total of 20 cases of incident PD were identified from the remaining 539 participants (11 at 5 years and 9 at 10 years). Relative risks for incident PD over the 10-year follow-up period were 7.43 (2.71-20.39), 3.60 (1.48-8.78), and 5.52 (2.43-12.57) for baseline SN-hyperechogenicity, hyposmia, and mild parkinsonian signs, respectively. While risk of hyposmia for incident PD was similar for the two sequential 5-year periods studied, relative risks of SN-hyperechogenicity and MPS were higher for the first five years as compared to later. CONCLUSION: Our findings extend the established risk relationship of SN-hyperechogenicity, hyposmia, and MPS with incident PD beyond 5 years of follow-up.

3 Article Prevalence and Associated Factors of Sarcopenia and Frailty in Parkinson's Disease: A Cross-Sectional Study. 2019

Peball, Marina / Mahlknecht, Philipp / Werkmann, Mario / Marini, Kathrin / Murr, Franziska / Herzmann, Helga / Stockner, Heike / de Marzi, Roberto / Heim, Beatrice / Djamshidian, Atbin / Willeit, Peter / Willeit, Johann / Kiechl, Stefan / Valent, Dora / Krismer, Florian / Wenning, Gregor Karl / Nocker, Michael / Mair, Katherina / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria, klaus.seppi@tirol-kliniken.at. ·Gerontology · Pubmed #30199864.

ABSTRACT: BACKGROUND: Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited. OBJECTIVE: We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life. METHODS: In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency. RESULTS: The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05). CONCLUSIONS: Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them.

4 Article Performance of the Movement Disorders Society criteria for prodromal Parkinson's disease: A population-based 10-year study. 2018

Mahlknecht, Philipp / Gasperi, Arno / Djamshidian, Atbin / Kiechl, Stefan / Stockner, Heike / Willeit, Peter / Willeit, Johann / Rungger, Gregorio / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. ·Mov Disord · Pubmed #29436728.

ABSTRACT: OBJECTIVE: We aimed to identify prodromal Parkinson's disease (PD) and its predictive accuracy for incident PD in an unselected elderly population and to estimate the relevance of this approach for future neuroprotection trials. METHODS: We applied the recently published Movement Disorders Society (MDS) research criteria for prodromal PD to participants of the prospective population-based Bruneck Study of the 2005 assessment (n = 574, ages 55-94 years). Cases of incident PD were identified at 3-year, 5-year, and 10-year follow-up visits. We calculated predictive accuracies of baseline prodromal PD status for incident cases, and, based on them, estimated sample sizes for neuroprotection trials with conversion to PD as the primary outcome. RESULTS: Baseline status of probable prodromal PD (n = 12) had a specificity in predicting incident PD of 98.8% (95% confidence interval, 97.3%-99.5%), a sensitivity of 66.7% (29.6%-90.8%), and a positive predictive value of 40.0% (16.7%-68.8%) over 3 years. Specificity remained stable with increasing follow-up time, sensitivity decreased to 54.6% (28.0%-78.8%) over 5 years and to 35.0% (18.0%-56.8%) over 10 years, whereas positive predictive value rose to 60.0% (31.2%-83.3%) and 77.8% (44.3%-94.7%), respectively. Sample size estimates at 80% power in an intention-to-treat approach ranged from 108 to 540 patients with probable prodromal PD depending on trial duration (3-5 years) and effect size of the agent (30%-50%). CONCLUSIONS: Our findings show that the MDS criteria for prodromal PD yield moderate to high predictive power for incident PD in a community-based setting and may thus be helpful to define target populations of future neuroprotection trials. © 2018 International Parkinson and Movement Disorder Society.

5 Article Consistency of "Probable RBD" Diagnosis with the RBD Screening Questionnaire: A Follow-up Study. 2017

Stefani, Ambra / Mahlknecht, Philipp / Seppi, Klaus / Nocker, Michael / Mair, Katherina J / Hotter, Anna / Stockner, Heike / Willeit, Johann / Kiechl, Stefan / Rungger, Gregor / Gasperi, Arno / Poewe, Werner / Högl, Birgit. ·Department of Neurology Medical University of Innsbruck Innsbruck Austria. · Department of Neurology Hospital of Bruneck Bruneck Italy. ·Mov Disord Clin Pract · Pubmed #30363451.

ABSTRACT: Introduction: The aim of this study was to evaluate the consistency of "probable RBD" diagnosis with the RBD screening questionnaire (RBDSQ) assessed 2 years apart in a population-based study. Methods: Probable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged ≥60 years. Results: A total of 437 participants completed the RBDSQ in 2008 and 2010. There were 29 (6.6%) and 23 (5.3%) participants with probable RBD in 2008 and in 2010, respectively. Only eight (1.8%) screened positive on both occasions. RBDSQ values 2 years apart showed low correlation with each other (Spearman rank coefficient r = 0.348, Conclusions: We found low agreement between the two assessments. Possible explanations are the fluctuation of untreated RBD expression and the poor utility of the RBDSQ to detect RBD in the general population. Until further PSG validation of the RBDSQ in population-based studies, investigators must be aware of the inherent uncertainty of questionnaire-based RBD diagnosis.

6 Article Characterization of patients with longstanding idiopathic REM sleep behavior disorder. 2017

Iranzo, Alex / Stefani, Ambra / Serradell, Monica / Martí, Maria Jose / Lomeña, Francisco / Mahlknecht, Philipp / Stockner, Heike / Gaig, Carles / Fernández-Arcos, Ana / Poewe, Werner / Tolosa, Eduard / Högl, Birgit / Santamaria, Joan / Anonymous7380909. ·From the Neurology Service (A.I., M.S., M.J.M., C.G., A.F.-A., E.T., J.S.) and Nuclear Medicine Service (F.L.), Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Spain · and Department of Neurology (A.S., P.M., H.S., W.P., B.H.), Medical University Innsbruck, Austria. ·Neurology · Pubmed #28615430.

ABSTRACT: OBJECTIVE: To evaluate the presence of prodromal markers of Parkinson disease (PD) in patients with longstanding idiopathic REM sleep behavior disorder (IRBD), a small subgroup of individuals with IRBD with long-term follow-up thought not to be at risk of developing PD. METHODS: Demographic, clinical, and neuroimaging markers of PD were evaluated in 20 patients with polysomnographic-confirmed longstanding IRBD and in 32 matched controls. RESULTS: Patients were 16 men and 4 women with mean age of 72.9 ± 8.6 years and mean follow-up from IRBD diagnosis of 12.1 ± 2.6 years. Patients more often had objective smell loss (35% vs 3.4%, CONCLUSIONS: Prodromal PD markers are common in individuals with longstanding IRBD, suggesting that they are affected by an underlying neurodegenerative process. This observation may be useful for the design of disease-modifying trials to prevent PD onset in IRBD.

7 Article Substantia nigra hyperechogenicity and Parkinson's disease risk in patients with essential tremor. 2016

Sprenger, Fabienne S / Wurster, Isabel / Seppi, Klaus / Stockner, Heike / Scherfler, Christoph / Sojer, Martin / Schmidauer, Christof / Berg, Daniela / Poewe, Werner. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Neurology Center, Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany. ·Mov Disord · Pubmed #26893155.

ABSTRACT: BACKGROUND: Several studies have reported an increased risk for patients with essential tremor to develop Parkinson's disease. In addition, hyperechogenicity in the area of the substantia nigra has been associated with a markedly increased risk for Parkinson's disease. The objective of this study was to evaluate the validity of substantia nigra hyperechogenicity in patients with essential tremor as a risk marker for Parkinson's disease. METHODS: Transcranial sonography was performed in 70 patients suffering from essential tremor. Fifty-four of these patients were available for follow-up after a mean of 6.16 ± 2.05 years and were assessed for the incidence of new-onset Parkinson's disease. RESULTS: The relative risk for developing Parkinson's disease in patients with essential tremor who had hyperechogenicity at baseline versus those without this hyperechogenicity was 7.00 (95% confidence interval, 1.62-30.34; sensitivity, 77.8%; specificity, 75.6%). CONCLUSIONS: Substantia nigra hyperechogenicity is also associated with an increased risk for Parkinson's disease in patients with essential tremor. These findings further support the potential role of this echofeature as a risk marker for Parkinson's disease.

8 Article Probable RBD and association with neurodegenerative disease markers: A population-based study. 2015

Mahlknecht, Philipp / Seppi, Klaus / Frauscher, Birgit / Kiechl, Stefan / Willeit, Johann / Stockner, Heike / Djamshidian, Atbin / Nocker, Michael / Rastner, Verena / Defrancesco, Michaela / Rungger, Gregor / Gasperi, Arno / Poewe, Werner / Högl, Birgit. ·Department of Neurology, Medical University of Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. · Department of Molecular Neuroscience and Reta Lila Weston Institute for Neurological Studies, University of London, London, UK. · Department of Psychiatry, Medical University Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Italy. ·Mov Disord · Pubmed #26208108.

ABSTRACT: BACKGROUND: The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined. METHODS: We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older. RESULTS: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety. CONCLUSIONS: Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD.

9 Article Predictors for mild parkinsonian signs: a prospective population-based study. 2015

Mahlknecht, Philipp / Kiechl, Stefan / Stockner, Heike / Willeit, Johann / Gasperi, Arno / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria; Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. Electronic address: Philipp.Mahlknecht@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Stefan.Kiechl@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Heike.Stockner@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Johann.Willeit@i-med.ac.at. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. Electronic address: Arno.Gasperi@sb-bruneck.it. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Werner.Poewe@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Klaus.Seppi@uki.at. ·Parkinsonism Relat Disord · Pubmed #25585991.

ABSTRACT: OBJECTIVE: Mild parkinsonian signs (MPS) are common in the elderly population and are associated with a wide range of adverse health outcomes, including incident Parkinson's disease (PD). We aimed to prospectively evaluate potential risk factors for incident MPS. METHODS: Participants of the population-based Bruneck Study representative for the general elderly community underwent a baseline assessment of substantia nigra (SN)-echogenicity with transcranial sonography, olfactory function with the Sniffin' Sticks identification test and vascular risk according to the Framingham risk score as well as a baseline and 5-year follow-up neurological examination. MPS were defined according to established criteria based on the entire motor section of the Unified PD Rating Scale. Participants with PD at baseline or follow-up and subjects with MPS at baseline were excluded. A logistic regression analysis adjusted for age and sex was used to detect risk factors for incident MPS in the remaining 393 participants. RESULTS: SN-hyperechogenicity and hyposmia were related to the development of MPS with odds ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among the various motor domains, increased SN-echogenicity predicted the development of bradykinesia and rigidity, whereas diminished olfactory function predicted the development of impaired axial motor function. CONCLUSIONS: In addition to their established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are associated with an increased risk for MPS in the general elderly community.

10 Article Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder. 2014

Iranzo, Alex / Stockner, Heike / Serradell, Mónica / Seppi, Klaus / Valldeoriola, Francesc / Frauscher, Birgit / Molinuevo, José Luis / Vilaseca, Isabel / Mitterling, Thomas / Gaig, Carles / Vilas, Dolores / Santamaria, Joan / Högl, Birgit / Tolosa, Eduard / Poewe, Werner. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. ·Mov Disord · Pubmed #25384461.

ABSTRACT: Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm(2) vs. 0.19 ± 0.07 cm(2) ; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time.

11 Article Risk factors and prodromal markers and the development of Parkinson's disease. 2014

Lerche, Stefanie / Seppi, Klaus / Behnke, Stefanie / Liepelt-Scarfone, Inga / Godau, Jana / Mahlknecht, Philipp / Gaenslen, Alexandra / Brockmann, Kathrin / Srulijes, Karin / Huber, Heiko / Wurster, Isabel / Stockner, Heike / Kiechl, Stefan / Willeit, Johann / Gasperi, Arno / Fassbender, Klaus / Poewe, Werner / Berg, Daniela. ·Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Hoppe Seyler-Strasse 3, 72076, Tübingen, Germany, stefanie.lerche@uni-tuebingen.de. ·J Neurol · Pubmed #24190794.

ABSTRACT: Identification of risk factors and prodromal markers for Parkinson's disease (PD) and the understanding of the point in time of first occurrence is essential for the early detection of incident PD. In this three-center longitudinal, observational study, we evaluated the specific risk for PD associated with single or combinations of risk factors and prodromal markers. In addition, we evaluated which risk factors and prodromal markers emerge at which time before the diagnosis of PD. Of the 1,847 at-baseline PD-free individuals ≥ 50 years, 1,260 underwent the 5-year follow-up assessment. There were 21 cases of incident PD during the study period. Enlarged hyperechogenic substantia nigra was the most frequent baseline sign in individuals developing PD after 3 years (80.0 %) and 5 years (85.7 %) compared to healthy controls (17.5 %) followed by the occurrence of mild parkinsonian signs and hyposmia. Evaluation of the signs at the first follow-up assessment showed that individuals developing PD after two additional years showed the same pattern of signs as individuals who developed PD 3 years after baseline assessment.

12 Article Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease. 2013

Scherfler, Christoph / Esterhammer, Regina / Nocker, Michael / Mahlknecht, Philipp / Stockner, Heike / Warwitz, Boris / Spielberger, Sabine / Pinter, Bernadette / Donnemiller, Eveline / Decristoforo, Clemens / Virgolini, Irene / Schocke, Michael / Poewe, Werner / Seppi, Klaus. ·1 Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. ·Brain · Pubmed #24014521.

ABSTRACT: Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor score (r = -0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson's disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies.

13 Article Substantia nigra hyperechogenicity as a marker for Parkinson's disease: a population-based study. 2013

Mahlknecht, Philipp / Seppi, Klaus / Stockner, Heike / Nocker, Michael / Scherfler, Christoph / Kiechl, Stefan / Willeit, Johann / Schmidauer, Christoph / Gasperi, Arno / Rungger, Gregorio / Poewe, Werner. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. ·Neurodegener Dis · Pubmed #23689066.

ABSTRACT: BACKGROUND: The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. OBJECTIVE: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. METHODS: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. RESULTS: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm(2), TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. CONCLUSION: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community.

14 Article Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease. 2013

Berg, Daniela / Behnke, Stefanie / Seppi, Klaus / Godau, Jana / Lerche, Stefanie / Mahlknecht, Philipp / Liepelt-Scarfone, Inga / Pausch, Christoph / Schneider, Niko / Gaenslen, Alexandra / Brockmann, Kathrin / Srulijes, Karin / Huber, Heiko / Wurster, Isabel / Stockner, Heike / Kiechl, Stefan / Willeit, Johann / Gasperi, Arno / Fassbender, Klaus / Gasser, Thomas / Poewe, Werner. ·Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. daniela.berg@uni-tuebingen.de ·Mov Disord · Pubmed #23115051.

ABSTRACT: BACKGROUND: SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinson's disease (PD). Recently, we reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50 years within 3 years. METHODS: This is the second follow-up of a prospective, longitudinal, three-center observational study after 5 years. Of the initial 1,847 at baseline PD-free participants 50 years or older, 1,271 underwent the 5-year reassessment. RESULTS: Within 5 years, 21 individuals developed incident PD. Participants with SN+ at baseline had a more than 20.6 times increased risk to develop PD in this time span than those without this echo feature. CONCLUSION: We thus confirm our finding of the 3-year follow-up examination in a longer observation time and higher number of individuals with incident PD and suggest SN+ as an important risk marker for PD.

15 Article The PRIPS study: screening battery for subjects at risk for Parkinson's disease. 2013

Berg, D / Godau, J / Seppi, K / Behnke, S / Liepelt-Scarfone, I / Lerche, S / Stockner, H / Gaenslen, A / Mahlknecht, P / Huber, H / Srulijes, K / Klenk, J / Fassbender, K / Maetzler, W / Poewe, W / Anonymous1100733. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Tübingen, Germany. daniela.berg@uni-tuebingen.de ·Eur J Neurol · Pubmed #22852790.

ABSTRACT: BACKGROUND AND PURPOSE: Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD). METHODS: The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+). RESULTS: After 3 years follow-up 11 subjects had developed PD. In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN+. CONCLUSION: With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost-effective screening strategy which might require longer follow-up intervals and application of additional instruments.

16 Article Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease? 2012

Stockner, Heike / Schwingenschuh, Petra / Djamshidian, Atbin / Silveira-Moriyama, Laura / Katschnig, Petra / Seppi, Klaus / Dickson, John / Edwards, Mark J / Lees, Andrew J / Poewe, Werner / Bhatia, Kailash P. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. heike.stockner@i-med.ac.at ·Mov Disord · Pubmed #22744819.

ABSTRACT: BACKGROUND: Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients. METHODS: TCS was performed in 14 patients with SWEDD and 19 PD patients. RESULTS: There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm(2) ), compared to the group of patients with SWEDD (0.13 ± 0.06 cm(2) ; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity (P < 0.001). CONCLUSIONS: We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD.

17 Article Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons. 2011

Berg, Daniela / Seppi, Klaus / Behnke, Stefanie / Liepelt, Inga / Schweitzer, Katherine / Stockner, Heike / Wollenweber, Frank / Gaenslen, Alexandra / Mahlknecht, Philipp / Spiegel, Jörg / Godau, Jana / Huber, Heiko / Srulijes, Karin / Kiechl, Stefan / Bentele, Marianna / Gasperi, Arno / Schubert, Teresa / Hiry, Teresa / Probst, Mareike / Schneider, Vera / Klenk, Jochen / Sawires, Martin / Willeit, Johann / Maetzler, Walter / Fassbender, Klaus / Gasser, Thomas / Poewe, Werner. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center of Neurodegenerative Diseases, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. daniela.berg@uni-tuebingen.de ·Arch Neurol · Pubmed #21747034.

ABSTRACT: OBJECTIVE: To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population. DESIGN: Longitudinal 3-center observational study with 37 months of prospective follow-up. SETTING: Individuals 50 years or older without evidence of PD or any other neurodegenerative disease. PARTICIPANTS: Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment. MAIN OUTCOME MEASURE: Incidence of new-onset PD in relation to baseline transcranial sonography status. RESULTS: There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants. CONCLUSIONS: In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.

18 Minor Is transcranial sonography useful to distinguish drug-induced parkinsonism from Parkinson's disease? 2012

Mahlknecht, Philipp / Stockner, Heike / Kiechl, Stefan / Willeit, Johann / Rastner, Verena / Gasperi, Arno / Rungger, Gregor / Poewe, Werner / Seppi, Klaus. · ·Mov Disord · Pubmed #22692761.

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