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Parkinson Disease: HELP
Articles by Jens Volkmann
Based on 89 articles published since 2010
(Why 89 articles?)

Between 2010 and 2020, J. Volkmann wrote the following 89 articles about Parkinson Disease.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program. 2015

Odin, P / Ray Chaudhuri, K / Slevin, J T / Volkmann, J / Dietrichs, E / Martinez-Martin, P / Krauss, J K / Henriksen, T / Katzenschlager, R / Antonini, A / Rascol, O / Poewe, W / Anonymous2260838. ·Department of Neurology, Lund University Hospital, 221 85 Lund, Sweden; Klinikum-Bremerhaven, D-27574 Bremerhaven, Germany. Electronic address: per.odin@med.lu.se. · King's College London, and National Parkinson Foundation Centre of Excellence, Dept of Neurology, King's College Hospital, London, UK. · Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 740 South Limestone Street, Lexington, KY 40536-0284, USA. · Department of Neurology, University Hospital of Würzburg, 97080 Würzburg, Germany. · Department of Neurology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway. · National Center for Epidemiology and CIBERNED, ISCIII, Avenida Monforte de Lemos 5, 28029 Madrid, Spain. · Department of Neurosurgery, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. · University Hospital of Bispebjerg, Bispebjerg Bakke 23, 2400 København, NV, Denmark. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Sozialmedizinisches Zentrum Ost - Donauspital, 1220 Wien Langobardenstraße 122, Austria. · Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. · Clinical Investigation Center 1436 and Department of Clinical Pharmacology, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France; Clinical Investigation Center 1436 and Department of Neurosciences, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France. · Innsbruck Medical University/University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. ·Parkinsonism Relat Disord · Pubmed #26233582.

ABSTRACT: Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS.

2 Review Management of Advanced Therapies in Parkinson's Disease Patients in Times of Humanitarian Crisis: The COVID-19 Experience. 2020

Fasano, Alfonso / Antonini, Angelo / Katzenschlager, Regina / Krack, Paul / Odin, Per / Evans, Andrew H / Foltynie, Thomas / Volkmann, Jens / Merello, Marcelo. ·Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, University Health Network, Division of Neurology University of Toronto Toronto Ontario Canada. · Krembil Brain Institute Toronto Ontario Canada. · The Center for Advancing Neurotechnological Innovation to Application Toronto Ontario Canada. · Department of Neuroscience University of Padua Padua Italy. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders Donauspital Vienna Austria. · Department of Neurology, Center for Parkinson's Disease and Movement Disorders Inselspital, Bern University Hospital, University of Bern Bern Switzerland. · Division of Neurology, Department of Clinical Sciences Lund Lund University Lund Sweden. · Department of Neurology the Royal Melbourne Hospital Victoria Australia. · Department of Clinical & Movement Neurosciences University College London Institute of Neurology, Queen Square London United Kingdom. · Neurologischen Klinik Universitätsklinikum Würzburg Würzburg Germany. · Movement Disorders Section Fleni Buenos Aires Argentina. · Consejo Nacional de Investigaciones Científicas y Técnicas Buenos Aires Argentina. ·Mov Disord Clin Pract · Pubmed #32373652.

ABSTRACT: Background: Although the COVID-19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID-19. Objective: To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future. Conclusion: Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD.

3 Review Parkinson disease. 2017

Poewe, Werner / Seppi, Klaus / Tanner, Caroline M / Halliday, Glenda M / Brundin, Patrik / Volkmann, Jens / Schrag, Anette-Eleonore / Lang, Anthony E. ·Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. · Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, California, USA. · Department of Neurology, University of California - San Francisco, San Francisco, California, USA. · Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. · Faculty of Medicine, University of New South Wales &Neuroscience Research Australia, Sydney, New South Wales, Australia. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA. · Department of Neurology, University Hospital of Würzburg, Würzburg, Germany. · Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK. · Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. ·Nat Rev Dis Primers · Pubmed #28332488.

ABSTRACT: Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

4 Review Innovations in deep brain stimulation methodology. 2017

Kühn, Andrea A / Volkmann, Jens. ·Department of Neurology, Charité, Berlin, Germany. · Department of Neurology, University Hospital of Würzburg, Würzburg, Germany. ·Mov Disord · Pubmed #27400763.

ABSTRACT: Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. © 2016 International Parkinson and Movement Disorder Society.

5 Review Deep brain stimulation for gait and postural symptoms in Parkinson's disease. 2013

Pötter-Nerger, Monika / Volkmann, Jens. ·Department of Neurology, University Hospital Eppendorf, Hamburg, Germany. ·Mov Disord · Pubmed #24132849.

ABSTRACT: In patients with Parkinson's disease, gait and balance difficulties have emerged as some of the main therapeutic concerns. During earlier stages of the disease, the dopamine-responsive aspects of gait disorder can be treated initially with dopaminergic drugs or deep brain stimulation. However, certain temporal aspects of parkinsonian gait disorder remain therapeutically resistant in both the short term and the long term. In this review, we summarize the effects of deep brain stimulation on gait and postural symptoms in the five currently available targets (subthalamic nucleus, globus pallidus, ventralis intermedius thalamic nucleus, pedunculopontine nucleus, and substantia nigra) and describe programming strategies for patients who are mainly disabled by gait problems.

6 Review Postoperative management of deep brain stimulation in Parkinson's disease. 2013

Castrioto, Anna / Volkmann, Jens / Krack, Paul. ·Movement Disorder Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Joseph Fourier University, and INSERM, Unit 836, Grenoble Institut des Neurosciences, Grenoble, France. ·Handb Clin Neurol · Pubmed #24112890.

ABSTRACT: Deep brain stimulation has become an established treatment for advanced Parkinson's disease. Its postoperative management is a delicate phase, dedicated to finding the optimal balance between stimulation and dopaminergic treatment. Postoperative management can be divided into an acute phase, aimed at the selection of the best stimulation contact, and a stabilization phase, aimed at the progressive adjustment of stimulation parameters and medications. A good knowledge of the electrophysiological anatomy of the target and surrounding structures, of the potential consequences of dopaminergic treatment modifications, and of the time course and interactions between stimulation and medication effects is mandatory for optimal outcome. This chapter focuses on the main strategies for the acute and chronic management of stimulation parameters and medication in the three main nuclei targeted in Parkinson's disease, namely the subthalamic nucleus, the ventral intermediate thalamic nucleus, and the internal part of the globus pallidus.

7 Review Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review. 2013

Volkmann, Jens / Albanese, Alberto / Antonini, Angelo / Chaudhuri, K Ray / Clarke, Carl E / de Bie, Rob M A / Deuschl, Günther / Eggert, Karla / Houeto, Jean-Luc / Kulisevsky, Jaime / Nyholm, Dag / Odin, Per / Østergaard, Karen / Poewe, Werner / Pollak, Pierre / Rabey, Jose Martin / Rascol, Olivier / Ruzicka, Evzen / Samuel, Michael / Speelman, Hans / Sydow, Olof / Valldeoriola, Francesc / van der Linden, Chris / Oertel, Wolfgang. ·Department of Neurology, University Clinic of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany, volkmann_j@klinik.uni-wuerzburg.de. ·J Neurol · Pubmed #23287972.

ABSTRACT: Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

8 Review Factors associated with neuropsychiatric side effects after STN-DBS in Parkinson's disease. 2012

Witt, Karsten / Daniels, Christine / Volkmann, Jens. ·Department of Neurology, Christian-Albrechts University, Kiel, Germany. k.witt@neurologie.uni-kiel.de ·Parkinsonism Relat Disord · Pubmed #22166423.

ABSTRACT: Neurostimulation of the subthalamic nucleus is an established treatment for advanced Parkinson's disease, and it might be the second milestone in treatment of Parkinson's disease after the introduction of L-dopa and dopamine agonists. However there are cognitive and psychiatric adverse effects have attracted increasing attention. In this context the subthalamic nucleus (STN) and the stimulation of the STN has been highlighted. The STN is part of the basal ganglia that are considered as part of distributed cortico-subcortical networks, which are involved in the selection, facilitation and inhibition of movements, emotions, behaviors and thoughts. Within this conception of the basal ganglia as a global "Go-/No-go-system" the STN is viewed as a central regulator. Those behavioral or cognitive effects of STN high frequency stimulation which can be modulated by changes in stimulation are therefore likely reflecting the intrinsic role of the STN in non-motor domains. However, there is insufficient knowledge about which proportion of Neuropsychiatric effects directly relates to such a modulation of the intrinsic basal ganglia state or which individual susceptibility factors may contribute to their clinical presentation. In this review the role of the preoperative factors and also the relevance of the intraoperative and postoperative management is analyzed.

9 Review Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. 2011

Bronstein, Jeff M / Tagliati, Michele / Alterman, Ron L / Lozano, Andres M / Volkmann, Jens / Stefani, Alessandro / Horak, Fay B / Okun, Michael S / Foote, Kelly D / Krack, Paul / Pahwa, Rajesh / Henderson, Jaimie M / Hariz, Marwan I / Bakay, Roy A / Rezai, Ali / Marks, William J / Moro, Elena / Vitek, Jerrold L / Weaver, Frances M / Gross, Robert E / DeLong, Mahlon R. ·University of California, Los Angeles, School of Medicine, Department of Neurology, 710 Westwood Plaza, Los Angeles, CA 90095, USA. jbronste@ucla.edu ·Arch Neurol · Pubmed #20937936.

ABSTRACT: OBJECTIVE: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). DATA SOURCES AND STUDY SELECTION: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. DATA EXTRACTION AND SYNTHESIS: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. CONCLUSIONS: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients.

10 Review Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease. 2010

Volkmann, Jens / Daniels, Christine / Witt, Karsten. ·Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany. j.volkmann@neurologie.uni-kiel.de ·Nat Rev Neurol · Pubmed #20680036.

ABSTRACT: Neurostimulation of the subthalamic nucleus (STN) is an established treatment for motor symptoms in advanced Parkinson disease (PD), although concerns exist regarding the safety of this therapy in terms of cognitive and psychiatric adverse effects. The basal ganglia are considered to be part of distributed cortico-subcortical networks that are involved in the selection, facilitation and inhibition of movements, emotions, behaviors and thoughts. The STN has a central role in these networks, probably providing a global 'no-go' signal. The behavioral and cognitive effects observed following STN high-frequency stimulation (HFS) probably reflect the intrinsic role of this nucleus in nonmotor functional domains. Nevertheless, postoperative behavioral changes are seldom caused by such stimulation alone. PD is a progressive neurodegenerative disorder with motor, cognitive, behavioral and autonomic symptoms. The pattern of neurodegeneration and expression of these symptoms are highly variable across individuals. The preoperative neuropsychiatric state can be further complicated by sensitization phenomena resulting from long-term dopaminergic treatment, which include impulse control disorders, punding, and addictive behaviors (dopamine dysregulation syndrome). Finally, personality traits, the social environment, culture and learned behaviors might be important determinants explaining why behavioral symptoms differ between patients after surgery. Here, we summarize the neuropsychiatric changes observed after STN HFS and try to disentangle their various etiologies.

11 Review [Deep brain stimulation for treatment of dystonia and tremor]. 2010

Timmermann, L / Volkmann, J. ·Klinik und Poliklinik für Neurologie, Universitätsklinikum Köln, Joseph-Stelzmann-Strasse 9, Köln, Germany. lars.timmermann@uk-koeln.de ·Nervenarzt · Pubmed #20495777.

ABSTRACT: Deep brain stimulation (DBS) is a safe and successful therapeutic option for patients with dystonia and tremor syndrome who do not respond sufficiently to conservative therapies. The most common target of DBS in patients with dystonia is the internal region of the globus pallidus (GPI). DBS of the GPI leads to long-lasting and remarkable improvement of dystonic movements in about 80% of patients. Recently it could be shown that not only patients with idiopathic dystonia but also patients with secondary dystonia can benefit from DBS although to a somewhat lesser extent. In patients with tremor syndromes, such as essential tremor, tremor-dominant Parkinson's disease or tremor in multiple sclerosis (MS) the intermediate ventral nucleus of the thalamus (VIM) as well as the subthalamic region proved to be promising targets for DBS electrodes. Especially in patients with essential tremor VIM-DBS leads to an often acute reduction of the tremor syndrome. In long-term observations, however, patients with essential tremor showed some tolerability to VIM-DBS leading to a slow increase of stimulation parameters to maintain a stable effect. VIM-DBS in patients with Parkinson's disease is rare and is reserved for elderly patients with pronounced tremor syndrome and little disease progression. Controlled studies and data on DBS in MS tremor are lacking and data are sparse and heterogeneous. Therefore, VIM-DBS in MS tremor patients has to be evaluated individually with caution. In summary patients with tremor syndromes as well as dystonia who cannot be adequately controlled with conservative therapy are good candidates for deep brain stimulation, a therapeutic option with moderate complications and risks and very good outcome for most patients.

12 Clinical Trial Opposite effects of l-dopa and DBS-STN on saccadic eye movements in advanced Parkinson's disease. 2017

Dec-Ćwiek, Małgorzata / Tutaj, Marcin / Gracies, Jean-Michel / Volkmann, Jens / Rudzińska, Monika / Słowik, Agnieszka / Szczudlik, Andrzej. ·Department of Neurology, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: malgorzatadec@yahoo.co.uk. · Department of Neurology, Jagiellonian University, Medical College, Kraków, Poland. · Department of Neurorehabilitation, EA BIOTN, Henri Mondor Hospital, Créteil, France. · Department of Neurology, Julius-Maximilians-University Würzburg, Würzburg, Germany. · Department of Neurology, Medical University of Silesia, Faculty of Medicine, Katowice, Poland. ·Neurol Neurochir Pol · Pubmed #28669542.

ABSTRACT: OBJECTIVE: To assess the effects of l-dopa and deep brain stimulation of the subthalamic nucleus (DBS-STN) on saccadic eye movements in patients with Parkinson's disease (PD). METHODS: Visually and internally guided horizontal saccades were evaluated using a saccadometer in 64 patients with advanced PD and 48 healthy controls. Forty-four pharmacologically treated patients were assessed in their "med-off" (OFF) and "med-on" (ON) status, whereas 20 DBS-STN treated patients were assessed in their "med-off, stim-off" (OFF) and "med-off, stim-on" (ON) status. RESULTS: In all PD patients the saccades in the OFF status were delayed, slower and smaller (p<0.01) than in controls. In pharmacologically treated patients all studied parameters showed tendency to worsen in the ON status as compared to the OFF status. In contrast, activating DBS-STN showed tendency to improve all studied parameters. Comparison of the studied saccade parameters between the ON status of DBS-STN treated patients, ON status of the pharmacologically treated patients and the controls showed that 73% of these parameters in the DBS-STN treated patients were similar as in the controls. While in the pharmacologically treated patients only 26% of these parameters were similar as in the controls. CONCLUSION: This prospective study comparing the influence of l-dopa and DBS-STN on saccades in advanced PD showed contrasting results between these two treatments; the majority of the studied parameters in patients on DBS-STN were similar as in the controls.

13 Clinical Trial EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease. 2015

Martinez-Martin, Pablo / Reddy, Prashanth / Katzenschlager, Regina / Antonini, Angelo / Todorova, Antoniya / Odin, Per / Henriksen, Tove / Martin, Anne / Calandrella, Daniela / Rizos, Alexandra / Bryndum, Narissah / Glad, Arne / Dafsari, Haidar Salimi / Timmermann, Lars / Ebersbach, Georg / Kramberger, Milica G / Samuel, Michael / Wenzel, Karoline / Tomantschger, Volker / Storch, Alexander / Reichmann, Heinz / Pirtosek, Zvezdan / Trost, Maja / Svenningsson, Per / Palhagen, Sven / Volkmann, Jens / Chaudhuri, K Ray. ·National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain. ·Mov Disord · Pubmed #25382161.

ABSTRACT: Subcutaneous apomorphine infusion (Apo) and intrajejunal levodopa infusion (IJLI) are two treatment options for patients with advanced Parkinson's disease (PD) and refractory motor complications, with varying cost of treatment. There are no multicenter studies comparing the effects of the two strategies. This open-label, prospective, observational, 6-month, multicenter study compared 43 patients on Apo (48.8% males, age 62.3 ± 10.6 years; disease duration: 14 ± 4.4 years; median H & Y stage 3; interquartile range [IQR]: 3-4) and 44 on IJLI (56.8% males, age 62.7 ± 9.1 years; disease duration: 16.1 ± 6.7 years; median H & Y stage 4; IQR, 3-4). Cohen's effect sizes (≥0.8 considered as large) were "large" with both therapies with respect to total motor, nonmotor, and quality-of-life scores. The Non-Motor Symptoms Scale (NMSS) with Apo showed moderate improvement, whereas sleep/fatigue, gastrointestinal, urinary, and sexual dimensions of the NMSS showed significantly higher improvement with IJLI. Seventy-five percent on IJLI improved in their quality-of-life and nonmotor symptoms (NMS), whereas in the Apo group, a similar proportion improved in quality of life, but 40% in NMS. Adverse effects included peritonitis with IJLI and skin nodules on Apo. Based on this open-label, nonrandomized, comparative study, we report that, in advanced Parkinson's patients, both IJLI and Apo infusion therapy appear to provide a robust improvement in motor symptoms, motor complications, quality-of-life, and some NMS. Controlled, randomized studies are required.

14 Clinical Trial Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. 2010

Daniels, Christine / Krack, Paul / Volkmann, Jens / Pinsker, Markus O / Krause, Martin / Tronnier, Volker / Kloss, Manja / Schnitzler, Alfons / Wojtecki, Lars / Bötzel, Kai / Danek, Adrian / Hilker, Rüdiger / Sturm, Volker / Kupsch, Andreas / Karner, Elfriede / Deuschl, Günther / Witt, Karsten. ·Department of Neurology, Christian-Albrechts-University, Kiel, Germany. ·Mov Disord · Pubmed #20589868.

ABSTRACT: A slight decline in cognitive functions and especially in executive functioning after deep brain stimulation (DBS) of the nucleus subthalamicus (STN) in patients with Parkinson's disease (PD) has been described. This study evaluated baseline parameters that contribute to a deterioration of cognitive functioning after DBS. We analyzed data from the neuropsychological protocol in a randomized controlled study comparing DBS with best medical treatment (BMT). Change scores were calculated for the cognitive domains "global cognitive functioning," "memory," "working memory," "attention," and "executive function." These domain-specific change scores were correlated with previously defined preoperative parameters. Compared with the BMT group (63 patients), the STN-DBS group (60 patients) showed a significant decline only in the domain executive function 6 months after DBS, which was significantly correlated with age, levodopa-equivalence dosage (LED) and axial subscore of the UPDRS in the off-medication state at baseline. Multiple regression analysis showed that these three factors explained, however, only about 23% of the variance. Patients with higher age, higher baseline LED, and/or higher axial subscore of the UPDRS at baseline have an increased risk for worsening of executive function after STN-DBS. High scores of these factors might reflect an advanced stage of disease progression. As these baseline factors explained the variance of the change score executive function only to a minor proportion, other factors including the surgical procedure, the exact placement of the electrode or postsurgical management might be more relevant for a decline in executive functioning after STN-DBS.

15 Clinical Trial Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease. 2010

Moro, Elena / Lozano, Andres M / Pollak, Pierre / Agid, Yves / Rehncrona, Stig / Volkmann, Jens / Kulisevsky, Jaime / Obeso, Jose A / Albanese, Alberto / Hariz, Marwan I / Quinn, Niall P / Speelman, Jans D / Benabid, Alim L / Fraix, Valerie / Mendes, Alexandre / Welter, Marie-Laure / Houeto, Jean-Luc / Cornu, Philippe / Dormont, Didier / Tornqvist, Annalena L / Ekberg, Ron / Schnitzler, Alfons / Timmermann, Lars / Wojtecki, Lars / Gironell, Andres / Rodriguez-Oroz, Maria C / Guridi, Jorge / Bentivoglio, Anna R / Contarino, Maria F / Romito, Luigi / Scerrati, Massimo / Janssens, Marc / Lang, Anthony E. ·Toronto Western Hospital, Movement Disorders Center, University of Toronto and University Health Network, Toronto, Ontario, Canada. elena.moro@uhn.on.ca ·Mov Disord · Pubmed #20213817.

ABSTRACT: We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-five STN patients and 16 GPi patients were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN, P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with off-stimulation, regardless of the sequence of stimulation. In open assessment, both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN, P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS in advanced PD. Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group.

16 Article A New Stimulation Mode for Deep Brain Stimulation in Parkinson's Disease: Theta Burst Stimulation. 2020

Horn, Martin A / Gulberti, Alessandro / Gülke, Eileen / Buhmann, Carsten / Gerloff, Christian / Moll, Christian K E / Hamel, Wolfgang / Volkmann, Jens / Pötter-Nerger, Monika. ·University Medical Center Hamburg-Eppendorf, Department of Neurology, Hamburg, Germany. · University Medical Center Hamburg-Eppendorf, Department of Neurophysiology and Pathophysiology, Hamburg, Germany. · University Medical Center Hamburg-Eppendorf, Department of Neurosurgery, Hamburg, Germany. · University Hospital Würzburg, Department of Neurology, Würzburg, Germany. ·Mov Disord · Pubmed #32357269.

ABSTRACT: BACKGROUND AND OBJECTIVES: The purpose of this study was to assess efficacy and safety of a new patterned theta burst stimulation algorithm of DBS with the aim of expanding the therapeutic window and clinical benefit in PD. METHODS: In this single-center, randomized, double-blind, clinical short-term trial, unilateral conventional subthalamic DBS was compared with unilateral patterned stimulation algorithms with intraburst high- or low-frequency theta burst stimulation in 17 PD patients. RESULTS: There were no serious adverse events with theta burst stimulation. During monopolar review, conventional subthalamic DBS and high-frequency theta burst stimulation were comparable, but low-frequency theta burst stimulation differed by requiring higher stimulation amplitudes for symptom reduction, but a larger therapeutic window. High- and low-frequency theta burst stimulation with adapted stimulation amplitude were effective in PD symptom reduction with differential effects on akinesia and tremor, depending on the theta burst stimulation mode. CONCLUSIONS: Theta burst stimulation is a safe and effective stimulation mode with potential future application opportunities. © 2020 International Parkinson and Movement Disorder Society.

17 Article Gait Initiation in Parkinson's Disease: Impact of Dopamine Depletion and Initial Stance Condition. 2020

Palmisano, Chiara / Brandt, Gregor / Vissani, Matteo / Pozzi, Nicoló G / Canessa, Andrea / Brumberg, Joachim / Marotta, Giorgio / Volkmann, Jens / Mazzoni, Alberto / Pezzoli, Gianni / Frigo, Carlo A / Isaias, Ioannis U. ·Department of Neurology, University Hospital Würzburg and The Julius Maximilian University of Würzburg, Würzburg, Germany. · MBMC Lab, Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy. · Translational Neural Engineering Area, The Biorobotics Institute, Scuola Superiore Sant'Anna, Pontedera, Italy. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Nuclear Medicine, University Hospital Würzburg and The Julius Maximilian University of Würzburg, Würzburg, Germany. · Department of Nuclear Medicine, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. · Centro Parkinson, ASST G. Pini-CTO, Milan, Italy. ·Front Bioeng Biotechnol · Pubmed #32211390.

ABSTRACT: Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson's disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment.

18 Article Freezing of gait in Parkinson's disease reflects a sudden derangement of locomotor network dynamics. 2019

Pozzi, Nicoló G / Canessa, Andrea / Palmisano, Chiara / Brumberg, Joachim / Steigerwald, Frank / Reich, Martin M / Minafra, Brigida / Pacchetti, Claudio / Pezzoli, Gianni / Volkmann, Jens / Isaias, Ioannis U. ·Department of Neurology, University Hospital and Julius Maximilian University, Würzburg, Germany. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, Genoa, Italy. · Department of Electronics, Information and Bioengineering, MBMC Lab, Politecnico di Milano, Milan, Italy. · Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany. · Parkinson and Movement Disorder Unit, IRCCS Mondino Foundation, Pavia, Italy. · Centro Parkinson ASST G. Pini-CTO, Milan, Italy. ·Brain · Pubmed #31505548.

ABSTRACT: Freezing of gait is a disabling symptom of Parkinson's disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson's disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4-13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson's disease and suggests that freezing of gait is a 'circuitopathy' related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson's disease should aim at directly targeting derangements of neural network dynamics.

19 Article Levodopa Modulates Functional Connectivity in the Upper Beta Band Between Subthalamic Nucleus and Muscle Activity in Tonic and Phasic Motor Activity Patterns in Parkinson's Disease. 2019

Ramirez Pasos, Uri E / Steigerwald, Frank / Reich, Martin M / Matthies, Cordula / Volkmann, Jens / Reese, René. ·Department of Neurology, University Hospital Würzburg, Würzburg, Germany. · Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany. · Department of Neurology, University of Rostock, Rostock, Germany. ·Front Hum Neurosci · Pubmed #31312129.


20 Article The aggregation state of α-synuclein deposits in dermal nerve fibers of patients with Parkinson's disease resembles that in the brain. 2019

Kuzkina, A / Schulmeyer, L / Monoranu, C-M / Volkmann, J / Sommer, C / Doppler, K. ·Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. Electronic address: kuzkina_a@ukw.de. · Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. ·Parkinsonism Relat Disord · Pubmed #30902527.

ABSTRACT: INTRODUCTION: Phosphorylated α-synuclein (p-α-syn) can be detected in dermal nerve fibers of patients with Parkinson's disease (PD) and multiple system atrophy (MSA). Here we investigated whether p-α-syn in the cutaneous nerve fibers represents misfolded aggregated protein. METHODS: Using immunofluorescence with conformation specific antibodies and digestion with proteinase K (PK), we studied skin biopsies from a cohort of patients with early stage PD (Hoehn and Yahr I/II, n=27), MSA with predominant parkinsonism (MSA-P, n=8) and normal controls (n=21). RESULTS: We could show that α-synuclein (α-syn) found in the dermal nerve fibers in PD and MSA-P is not only phosphorylated but represents PK resistant and truncated aggregated protein. Comparison with a post mortem midbrain sample revealed a similar staining pattern of pathologic α-syn lesions in the PD brain. CONCLUSION: Immunostaining of nerve fibers with different conformation specific antibodies and digestion with PK gave comparable results between midbrain and skin sections, showing that cutaneous nerve deposits of α-syn are structurally similar to Lewy pathology in the brain and are highly specific for synucleinopathy.

21 Article Sit-to-walk performance in Parkinson's disease: A comparison between faller and non-faller patients. 2019

Palmisano, Chiara / Brandt, Gregor / Pozzi, Nicoló Gabriele / Leporini, Alice / Maltese, Virginia / Canessa, Andrea / Volkmann, Jens / Pezzoli, Gianni / Frigo, Carlo Albino / Isaias, Ioannis Ugo. ·Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany; Department of Electronic, Information and Bioengineering, MBMC Lab, Politecnico di Milano, via Colombo 40, 20133 Milan, Italy. · Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. · Department of Informatics, Bioengineering, Robotics and System Engineering, University of Genoa, via all'Opera Pia 13a, 16145 Genoa, Italy; Fondazione Europea di Ricerca Biomedica (FERB Onlus), Via Uboldo 18, 20063 Cernusco s/N, Milan, Italy. · Centro Parkinson ASST G. Pini-CTO, via Bignami 1, 20126 Milan, Italy. · Department of Electronic, Information and Bioengineering, MBMC Lab, Politecnico di Milano, via Colombo 40, 20133 Milan, Italy. · Department of Neurology, University Hospital and Julius-Maximilian-University, Josef-Schneider-Str. 11, 97080 Würzburg, Germany; Centro Parkinson ASST G. Pini-CTO, via Bignami 1, 20126 Milan, Italy. Electronic address: Isaias_I@ukw.de. ·Clin Biomech (Bristol, Avon) · Pubmed #30889433.

ABSTRACT: BACKGROUND: Falls are one of the main concerns in people with Parkinson's disease, leading to poor quality of life and increased mortality. The sit-to-walk movement is the most frequent postural transition task during daily life and is highly demanding in terms of balance maintenance and muscular strength. METHODS: With the aim of identifying biomechanical variables of high risk of falling, we investigated the sit-to-walk task performed by 9 Parkinson's disease patients with at least one fall episode in the six months preceding this study, 15 Parkinson's disease patients without previous falls, and 20 healthy controls. Motor performance was evaluated with an optoelectronic system and two dynamometric force plates after overnight suspension of all dopaminergic drugs and one hour after consumption of a standard dose of levodopa/benserazide. FINDINGS: Poor trunk movements critically influenced the execution of the sit-to-walk movement in patients with a history of falling. The peak velocity of the trunk in the anterior-posterior direction discriminated faller from non-faller patients, with high specificity and sensitivity in both the medication-off and -on state. INTERPRETATION: Our results confirm the difficulties in merging consecutive motor tasks in patients with Parkinson's disease. Trunk movements during the sit-to-walk can provide valuable measurements to monitor and possibly predict the risk of falling.

22 Article Rescuing Suboptimal Outcomes of Subthalamic Deep Brain Stimulation in Parkinson Disease by Surgical Lead Revision. 2019

Nickl, Robert C / Reich, Martin M / Pozzi, Nicoló Gabriele / Fricke, Patrick / Lange, Florian / Roothans, Jonas / Volkmann, Jens / Matthies, Cordula. ·Department of Neurosurgery, Julius-Maximilians-University Hospital, Wue-rzburg, Germany. · Department of Neurology, Julius-Maximilians-University Hospital, Wuerzburg, Germany. ·Neurosurgery · Pubmed #30839077.

ABSTRACT: BACKGROUND: Clinical trials have established subthalamic deep-brain-stimulation (STN-DBS) as a highly effective treatment for motor symptoms of Parkinson disease (PD), but in clinical practice outcomes are variable. Experienced centers are confronted with an increasing number of patients with partially "failed" STN-DBS, in whom motor benefit doesn't meet expectations. These patients require a complex multidisciplinary and standardized workup to identify the likely cause. OBJECTIVE: To describe outcomes in a series of PD patients undergoing lead revision for suboptimal motor benefit after STN-DBS surgery and characterize selection criteria for surgical revision. METHODS: We investigated 9 PD patients with STN-DBS, who had unsatisfactory outcomes despite intensive neurological management. Surgical revision was considered if the ratio of DBS vs levodopa-induced improvement of UPDRS-III (DBS-rr) was below 75% and the electrodes were found outside the dorsolateral STN. RESULTS: Fifteen electrodes were replaced via stereotactic revision surgery into the dorsolateral STN without any adverse effects. Median displacement distance was 4.1 mm (range 1.6-8.42 mm). Motor symptoms significantly improved (38.2 ± 6.6 to 15.5 ± 7.9 points, P < .001); DBS-rr increased from 64% to 190%. CONCLUSION: Patients with persistent OFFmotor symptoms after STN-DBS should be screened for levodopa-responsiveness, which can serve as a benchmark for best achievable motor benefit. Even small horizontal deviations of the lead from the optimal position within the dorsolateral STN can cause stimulation responses, which are markedly inferior to the levodopa response. Patients with an image confirmed lead displacement and preserved levodopa response are candidates for lead revision and can expect significant motor improvement from appropriate lead replacement.

23 Article Development of evidence-based quality indicators for deep brain stimulation in patients with Parkinson's disease and first year experience of implementation of a nation-wide registry. 2019

Haas, Kirsten / Stangl, Stephanie / Steigerwald, Frank / Matthies, Cordula / Gruber, Doreen / Kühn, Andrea A / Krauss, Joachim K / Sixel-Döring, Friederike / von Eckardstein, Kajetan / Deuschl, Günther / Classen, Joseph / Winkler, Dirk / Voges, Jürgen / Galazky, Imke / Oertel, Wolfgang / Ceballos-Baumann, Andres O / Lange, Max / Gharabaghi, Alireza / Weiss, Daniel T / Volkmann, Jens / Heuschmann, Peter U. ·Institute for Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany. · Department of Neurology, University of Würzburg, Würzburg, Germany. · Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany. · Kliniken Beelitz, Movement Disorder Clinic, Beelitz-Heilstätten, Germany. · Department of Neurology, Movement Disorders and Neuromodulation Unit, Charité - University Medicine (CCM), Berlin, Germany. · Department of Neurosurgery, Medical School Hannover, Hannover, Germany. · Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurology, Philipps-University Marburg, Germany. · Department of Neurosurgery, University Medicine Göttingen, Georg-August University, Göttingen, Germany. · Department of Neurology, Christian-Albrecht-University, Kiel, Germany. · Department of Neurology, University of Leipzig, Leipzig, Germany. · Faculty of Medicine, Department of Neurosurgery, University Clinic of Leipzig, Leipzig, Germany. · Leibniz Institute for Neurobiology, Magdeburg, Germany; Department of Stereotactic Neurosurgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. · Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany. · Department of Neurology, Philipps-University Marburg, Germany. · Schön Klinik München Schwabing, Department of Neurology, Technische Universität München, München, Germany. · Department of Neurosurgery, University of Regensburg, Medical Center, Regensburg, Germany. · Division of Functional and Restorative Neurosurgery, Department of Neurosurgery, University of Tuebingen, Centre for Integrative Neuroscience (CIN), University of Tuebingen, Tuebingen, Germany. · Centre of Neurology, Department for Neurodegenerative Diseases, and Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Germany. · Department of Neurology, University of Würzburg, Würzburg, Germany. Electronic address: Volkmann_J@ukw.de. · Institute for Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Comprehensive Heart Failure Center, University Würzburg, Clincial Trial Center Würzburg, University Hospital Würzburg, Germany. ·Parkinsonism Relat Disord · Pubmed #30772278.

ABSTRACT: INTRODUCTION: Deep Brain Stimulation (DBS) is a complex, invasive and cost-intensive therapy that requires a high level of expertise. To date, data on quality of DBS in clinical routine in the German health care system are lacking. METHODS: The development of evidence-based QIs for DBS in PD patients was performed following a standardized process by a multidisciplinary board between 2014 and 2016. The process was initiated by the German Parkinson Society and followed international recommendations for developing QIs including: a systematic literature search; an appraisal of the published evidence; a consensus-based selection of the QI set; and a pilot study to assess the feasibility in implementing the QIs in clinical routine. RESULTS: A set of 28 QIs for determining the quality of DBS in PD was established by the board covering different dimensions of health care quality (structure, process, and outcome) in different treatment phases of DBS care (pre-operative, peri-operative, and post-operative). Implementation in clinical practice was tested in a pilot study comprising three hospitals delivering DBS care. The feasibility of the QI set was evaluated positively by the participating physicians and hospitals. Mean time to document one patient was 25 min. The German-wide implementation of the defined indicator set within a dedicated quality registry (QualiPa) started in June 2016. CONCLUSION: QIs are a necessary requirement to monitor hospital performance in DBS care. The evidence-based approach to develop the proposed indicator set is expected to assure transparency, acceptance and long-term applicability of the QI set in Germany.

24 Article Abnormal α-synuclein deposits in skin nerves: intra- and inter-laboratory reproducibility. 2019

Donadio, V / Doppler, K / Incensi, A / Kuzkina, A / Janzen, A / Mayer, G / Volkmann, J / Rizzo, G / Antelmi, E / Plazzi, G / Sommer, C / Liguori, R / Oertel, W H. ·IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy. · Department of Neurology, University Hospital Würzburg, Würzburg, Germany. · Philipps University, Marburg, Germany. ·Eur J Neurol · Pubmed #30770596.

ABSTRACT: BACKGROUND AND PURPOSE: Visualization of phosphorylated α-synuclein at serine 129 (p-syn) in skin nerves is a promising test for the in vivo diagnosis of synucleinopathies. Here the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna). METHODS: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. Skin biopsy was performed at the C7 paravertebral spine region and distal skin sites (thigh or leg). The analysis was standardized in both laboratories and carried out blinded on a single skin section double stained with antibodies to p-syn and the pan-axonal marker protein gene product 9.5. Fifty skin sections were randomly selected for the analysis: 25 from C7 and 25 from distal sites. Differently classified sections were re-evaluated to understand the reasons for the discrepancy. RESULTS: The intra-laboratory analysis showed an excellent reproducibility both in Würzburg (concordance of classification 100% of sections; K = 1; P < 0.001) and Bologna (96% of sections; K = 0.92; P < 0.001). Inter-laboratory analysis showed reproducibility in 45 sections (90%; K = 0.8; P < 0.001) and a different classification in five sections, which was mainly due to fragmented skin samples or weak fluorescent signals. CONCLUSIONS: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.

25 Article Quality of life predicts outcome of deep brain stimulation in early Parkinson disease. 2019

Schuepbach, W M Michael / Tonder, Lisa / Schnitzler, Alfons / Krack, Paul / Rau, Joern / Hartmann, Andreas / Hälbig, Thomas D / Pineau, Fanny / Falk, Andrea / Paschen, Laura / Paschen, Stephen / Volkmann, Jens / Dafsari, Haidar S / Barbe, Michael T / Fink, Gereon R / Kühn, Andrea / Kupsch, Andreas / Schneider, Gerd-H / Seigneuret, Eric / Fraix, Valerie / Kistner, Andrea / Chaynes, P Patrick / Ory-Magne, Fabienne / Brefel-Courbon, Christine / Vesper, Jan / Wojtecki, Lars / Derrey, Stéphane / Maltête, David / Damier, Philippe / Derkinderen, Pascal / Sixel-Döring, Friederike / Trenkwalder, Claudia / Gharabaghi, Alireza / Wächter, Tobias / Weiss, Daniel / Pinsker, Marcus O / Regis, Jean-Marie / Witjas, Tatiana / Thobois, Stephane / Mertens, Patrick / Knudsen, Karina / Schade-Brittinger, Carmen / Houeto, Jean-Luc / Agid, Yves / Vidailhet, Marie / Timmermann, Lars / Deuschl, Günther / Anonymous1351117. ·From the Département de Neurologie (W.M.M.S., A.H., T.D.H., F.P., Y.A., M.V.), Hôpital Pitié-Salpêtrière, Centre d'Investigation Clinique 1422, Institut du Cerveau et de la Moelle Epinière, Institut National de Santé et en Recherche Médicale, Assistance Publique Hôpitaux de Paris, France · Institute of Neurology (W.M.M.S.), Konolfingen · Department of Neurology (W.M.M.S.), University Hospital Bern and University of Bern, Switzerland · Medtronic (L.T.), Minneapolis, MN · Institute of Clinical Neuroscience & Medical Psychology and Department of Neurology (A.D., L.W.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany · Movement Disorder Unit, Neurology (P.K.), CHU Grenoble Alpes · Grenoble Institut des Neurosciences (P.K., V.F., A. Kistner), University Grenoble Alpes · Inserm U1216 (P.K., V.F., A. Kistner), Grenoble, France · Department of Clinical Neurosciences (Neurology) (P.K.), Faculty of Medicine, University of Geneva, Switzerland · Coordinating Center for clinical trials of the Philipps University of Marburg (J.R., C.S.-B.) · Neurochirurgische Klinik im Neurozentrum (A.F., L.P., S.P., J. Volkmann, K.K., G.D.),Christian-Albrechts-Universität Kiel · Neurologische Klinik und Poliklinik (J. Volkmann), Universitätsklinikum Würzburg · Department of Neurology (H.S.D., M.T.B., G.R.F., L.T.), University Hospital Cologne · Research Centre Jülich (G.R.F.) · Klinik für Neurologie (T.D.H., A. Kühn, A. Kupsch) and Klinik für Neurochirurgie (G.-H.S.), Campus Virchow, Charité-Universitätsmedizin Berlin · Praxis Kupsch (A. Kupsch), Berlin, Germany · Service de Neurochirurgie (E.S.) and Service de Neurologie (V.F.), Hôpital Michallon, Centre Hospitalo-Universitaire, Grenoble · Departments of Neurosurgery (P.P.C.), Neurology (F.O.-M., C.B.-C.), and Clinical Pharmacology (C.B.-C.), University Hospital of Toulouse · ToNIC (F.O.-M., C.B.-C.), Toulouse Neuroimaging Center, University of Toulouse, Inserm, UPS, France · Department of Neurosurgery (J. Vesper), Universitätsklinikum Düsseldorf, Germany · Departments of Neurosurgery (S.D.) and Neurology (D.M.), Rouen University Hospital and University of Rouen · INSERM U1239 (D.M.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan · Service de Neurologie (P. Damier, P. Derkinderen), CHU Nantes, Hôpital Laënnec, France · Paracelsus-Elena-Klinik Kassel (F.S.-D., C.T.) · Department of Neurosurgery (C.T.), University Medical Center Göttingen · Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience (A.G.), Tübingen · Abteilung für Neurologie (T.W.), Reha-Zentrum Bad Gögging, Passauer Wolf · Department for Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (D.W.), University of Tübingen · Division of Stereotactic and Functional Neurosurgery (M.O.P.), University Medical Center Freiburg, Germany · Departments of Functional and Stereotactic Neurosurgery and Radiosurgery (J.-.M.R.) and Neurology (T.W.), Timone University Hospital, INSERM, Marseille · Institut des Sciences Cognitives Marc Jeannerod (S.T.), CNRS, UMR 5229, Université de Lyon · Centre Expert Parkinson (S.T.), Service de Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron · Department of Neurosurgery (P.M.), University Hospital of Neurology and Neurosurgery, Hospices Civils de Lyon, Université de Lyon · Department of Neurology (J.-L.H.), INSERM-1402, Centre Hospitalier Universitaire de Poitiers, University of Poitiers, France · and Universitätsklinikum Giessen und Marburg (L.T.), Marburg Campus, Germany. ·Neurology · Pubmed #30737338.

ABSTRACT: OBJECTIVE: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications. METHODS: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI. RESULTS: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups ( CONCLUSION: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS. CLINICALTRIALSGOV IDENTIFIER: NCT00354133.