Philipp Mahlknecht

Innsbruck Medical University

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Werner Poewe

Innsbruck Medical University

Klaus Seppi

Innsbruck Medical University

Stefan Kiechl

Innsbruck Medical University

Heike Stockner

Innsbruck Medical University

Atbin Djamshidian

Innsbruck Medical University

Johann Willeit

Innsbruck Medical University

Christoph Scherfler

Innsbruck Medical University

Beatrice Heim

Universität Innsbruck

Arno Gasperi

Krankenhaus Bruneck

Gregor K. Wenning

Innsbruck Medical University

Cooperative Institutions

John Wiley & Sons (United States)

260

Innsbruck Medical University

154

Universität Innsbruck

136

University College London

National Hospital for Neurology and Neurosurgery

Centre for Movement Disorders

University Hospital Innsbruck

Medical University of Vienna

German Center for Neurodegenerative Diseases

University of Lübeck

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Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease

Movement Disorders (2016)

Philipp Mahlknecht Raimund Pechlaner Sanne Boesveldt D. Volc Bernardette Pinter

The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD.Odor identification with the 16-item Sniffin' Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts.Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve ≥0.90; sensitivities ≥83.3%; specificities ≥82.0%) and from non-PD patients (areas under the curve ≥0.91; sensitivities ≥84.1%; specificities ≥84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%).Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Identification

10.1002/mds.26637

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Citations (60)

Neurological outcome and quality of life 3 months after COVID‐19: A prospective observational cohort study

European Journal of Neurology (2021)

Verena Rass Ronny Beer Alois Josef Schiefecker Mario Kofler Anna Lindner

To assess neurological manifestations and health-related quality of life (QoL) 3 months after COVID-19.In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist-5) 3 months after disease onset.Of 135 consecutive COVID-19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain-Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3-month follow-up. Self-reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow-up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively.Despite recovery from the acute infection, neurological symptoms were prevalent at the 3-month follow-up. Above all, smelling disorders were persistent in a large proportion of patients.

Depression

Hyposmia

Neurological examination

10.1111/ene.14803

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Citations (163)

Faculty Opinions recommendation of Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2014)

Werner Poewe Philipp Mahlknecht

Inosine

10.3410/f.718234420.793489521

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Citations (1)

Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease

Movement Disorders (2017)

Philipp Mahlknecht Harith Akram Dejan Georgiev Elina Tripoliti Joseph Candelario

ABSTRACT Background: Subthalamic deep brain stimulation (STN‐DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract. Objectives: To assess the relevance of pyramidal tract activation with STN‐DBS in PD. Methods: In a multimodal, blinded study in 20 STN‐DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography. Results: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a “lateral‐type” speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility. Conclusions: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society

Subthalamic Nucleus

Pyramidal tracts

10.1002/mds.27042

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Citations (57)

Supplementary Material for: Associations of Gait Disorders and Recurrent Falls in Older People: A Prospective Population-Based Study

Figshare (2021)

Kathrin Marini Philipp Mahlknecht Oliver Schorr Melanie Baumgartner Roberto deMarzi

Background: Recurrent falls represent a major source of serious adverse health outcomes in the general older population. Gait impairment has been linked to recurrent falls, but there are only limited long-term data on this association. Objectives: The objective of the study was to investigate the association of gait disorders (GDs) and gait tests with future falls in an existing longitudinal population-based cohort. Method: The study was performed in participants of the Bruneck Study cohort 2010 aged 60–97 years, with prospective 5-year follow-up. At baseline, participants underwent a clinical gait assessment (to determine neurological and non-neurological GDs according to an established classification) and were also evaluated by quantitative and semiquantitative gait tests (Hauser Index, Tinetti balance and gait test, and gait speed). Logistic regression analysis adjusted for age and sex was used to determine the relationship of baseline variables with incident recurrent falls at 5-year follow-up. Results: Of 328 included participants, 22 (6.7%) reported recurrent falls at follow-up. Baseline presence of GDs was associated with recurrent falls at follow-up (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.6–11.1; p = 0.004), and this effect was largely driven by neurological GDs (OR 5.5; 95% CI 1.7–17.4; p = 0.004). All 3 simple gait tests were predictive for incident falls (Hauser Index, p = 0.002; Tinetti test, p = 0.006; and gait speed, p < 0.001). Conclusions: Clinical assessment of GDs and gait tests both had independent significant predictive value for recurrent falls over a 5-year follow-up period. This highlights the potential of such assessments for early fall risk screening and timely implementation of fall-preventive measures.

10.6084/m9.figshare.17696834

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Disability Milestones and Death in Parkinson's Disease under Subthalamic Neurostimulation

Movement Disorders Clinical Practice (2023)

Philipp Mahlknecht Wilhelm Eisner Werner Poewe

10.1002/mdc3.13841

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Citations (1)

Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease

Brain (2013)

Christoph Scherfler Regina Esterhammer Michael Nocker Philipp Mahlknecht Heike Stockner

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-[18F] 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-[18F] 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-[18F] 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-[18F] 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-[18F] 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-[18F] 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.

Basal ganglia disease

Basal (medicine)

10.1093/brain/awt234

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Citations (58)

Predictors of Neurodegeneration in Idiopathic REM sleep behavior disorder: a multicenter cohort study (CCI.003)

Neurology (2018)

Ronald B. Postuma Álex Iranzo Joshua Shulman Raffaele Manni Wolfgang H. Oertel

April 23, 2018April 10, 2018Free AccessPredictors of Neurodegeneration in Idiopathic REM sleep behavior disorder: a multicenter cohort study (CCI.003)Ronald Postuma, Alex Iranzo, Michele Hu, Raffaele Manni, Wolfgang Oertel, Bradley Boeve, Birgit Hogl, … Show All … , Isabelle Arnulf, Dario Arnaldi, Valerie Cochen De Cock, Brit Mollenhauer, Monica Puligheddu, Karel Sonka, Ki-Young Jung, Aleksandar Videnovic, Federica Provini, Yves Dauvilliers, Simon Lewis, Anna Heidbreder, Dieter Kunz, Milena Pavlova, Jacques Montplaisir, Benjamin Dawson, Amelie Pelletier, Jean-Francois Gagnon, Joan Santamaria, Thomas R. Barber, Michele Terzaghi, Annette Janzen, Erik St-Louis, Ambra Stefani, Flavio Nobili, Friedriecke Sixel-Doring, Petr Dusek, Pietro Cortelli, Kaylena Martens, Veronique Latreille, Charles Gaig, Claudia Trenkwalder, Philip Mahlknecht, and Evi Holzknecht Show FewerAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement)https://doi.org/10.1212/WNL.90.15_supplement.CCI.003 Letters to the Editor

10.1212/wnl.90.15_supplement.cci.003

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Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia

Proceedings of the National Academy of Sciences (2022)

Andreas Horn Martin M. Reich Siobhán Ewert Ningfei Li Bassam Al‐Fatly

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network.

Cervical dystonia

Subthalamic Nucleus

Movement Disorders

10.1073/pnas.2114985119

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Citations (43)

Front & Back Matter

Neurodegenerative Diseases (2013)

Nikolaus R. McFarland Thomas C. Burdett Cody A. Desjardins Matthew P. Frosch Michael A. Schwarzschild

10.1159/000356485

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Citations (0)