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Parkinson Disease: HELP
Articles by Jens Volkmann
Based on 74 articles published since 2008

Between 2008 and 2019, J. Volkmann wrote the following 74 articles about Parkinson Disease.
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 Guideline [Deep brain stimulation for Parkinson's disease. Consensus recommendations of the German Deep Brain Stimulation Association]. 2009

Hilker, R / Benecke, R / Deuschl, G / Fogel, W / Kupsch, A / Schrader, C / Sixel-Döring, F / Timmermann, L / Volkmann, J / Lange, M / Anonymous2770626. ·Zentrum der Neurologie und Neurochirurgie, Klinik für Neurologie, Goethe-Universität, Frankfurt am Main. ·Nervenarzt · Pubmed #19360386.

ABSTRACT: Deep brain stimulation (DBS) has been shown to be effective for levodopa-responsive symptoms and tremor in Parkinson's disease (PD). The subthalamic nucleus (STN) is the preferred target for most patients suffering from late stage motor complications of the disorder. STN DBS is superior to best medical treatment concerning the control of motor fluctuations and the increase of on-time without dyskinesias. In contrast to DBS of the internal pallidum (GPi), STN stimulation also permits a reduction of the dopaminergic medication. Long-term data demonstrated sustained effectiveness of STN DBS despite progressive disease. DBS of the thalamic ventral intermediate nucleus (VIM) is an alternative target in older PD patients with severe PD tremor refractory to medication. In order to minimize potential risks and side effects, the use of DBS needs careful adherence to inclusion and exclusion criteria for eligible PD patients. This paper summarizes the current consensus recommendations of the German Deep Brain Stimulation Association for DBS in 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 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.

5 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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 Review Proprioception and motor control in Parkinson's disease. 2009

Konczak, Jürgen / Corcos, Daniel M / Horak, Fay / Poizner, Howard / Shapiro, Mark / Tuite, Paul / Volkmann, Jens / Maschke, Matthias. ·School of Kinesiology, University of Minnesota, Minneapolis, MN 55455, USA. jkonczak@umn.edu ·J Mot Behav · Pubmed #19592360.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder that leads to a progressive decline in motor function. Growing evidence indicates that PD patients also experience an array of sensory problems that negatively impact motor function. This is especially true for proprioceptive deficits, which profoundly degrade motor performance. This review specifically address the relation between proprioception and motor impairments in PD. It is structured around 4 themes: (a) It examines whether the sensitivity of kinaesthetic perception, which is based on proprioceptive inputs, is actually altered in PD. (b) It discusses whether failed processes of proprioceptive-motor integration are central to the motor problems in PD. (c) It presents recent findings focusing on the link between the proprioception and the balance problems in PD. And (d) it discusses the current state of knowledge of how levodopa medication and deep brain stimulation affect proprioceptive and motor function in PD. The authors conclude that a failure to evaluate and to map proprioceptive information onto voluntary and reflexive motor commands is an integral part of the observed motor symptoms in PD.

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 Clinical Trial Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson's disease. 2009

Volkmann, Jens / Albanese, Alberto / Kulisevsky, Jaime / Tornqvist, Aana-Lena / Houeto, Jean-Luc / Pidoux, Bernard / Bonnet, Anne-Marie / Mendes, Alexandre / Benabid, Alim-Louis / Fraix, Valerie / Van Blercom, Nadege / Xie, Jing / Obeso, José / Rodriguez-Oroz, Maria Cruz / Guridi, Jurge / Schnitzler, Alfons / Timmermann, Lars / Gironell, Alexandre A / Molet, Juan / Pascual-Sedano, Benta / Rehncrona, Stig / Moro, Elena / Lang, Anthony C / Lozano, Andres M / Bentivoglio, Anna Rita / Scerrati, Massimo / Contarino, Maria Fiorella / Romito, Luigi / Janssens, Marc / Agid, Yves. ·Neurologische Klinik der Christian-Albrechts-Universität, Kiel, Germany. j.volkmann@neurologie.uni-kiel.de ·Mov Disord · Pubmed #19412954.

ABSTRACT: We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time.

17 Clinical Trial Influence of subthalamic deep brain stimulation versus levodopa on motor perseverations in Parkinson's disease. 2009

Herzog, Jan / Möller, Bettina / Witt, Karsten / Pinsker, Marcus O / Deuschl, Günther / Volkmann, Jens. ·Department of Neurology, Christian-Albrechts-University, Schittenhelmstr. 10, Kiel, Germany. ·Mov Disord · Pubmed #19412937.

ABSTRACT: Patients with Parkinson's disease (PD) show impairment in generating random motor sequences reflecting a higher order motor deficit in set-shifting and suppression of perseverative behavior. The impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on motor perseverations has not yet been elucidated. In 35 patients with PD, we evaluated the effect of STN-DBS and levodopa on motor perseverations using the Vienna perseveration task. The task was performed 6 months after implantation of stimulation electrodes in the following three conditions: Stimulation off/medication off (Stim OFF/Med OFF), Stim ON/Med OFF, and Stim OFF/Med ON. Perseverations were measured by redundancy of second order (R(2)) with higher values indicating more severe perseverations. ANCOVA analysis revealed that influence of STN-DBS on R(2) significantly depended on R(2) severity during Stim OFF/Med OFF (F = 4.69, P = 0.035). Accordingly, we classified patients with PD into two groups based on the R(2) value during off treatment. In patients with mild perseveration (R(2) < 35) neither STN-DBS nor levodopa changed perseverations. By contrast, in patients with severe perseveration (R(2) > 35), STN-DBS significantly reduced R(2) by 9.7 +/- 2.6 (P < 0.001) whereas levodopa had no impact (R(2) reduction 3.7 +/- 1.6, P = 0.081). This demonstrates that STN-DBS, by reducing motor perseveration, influences higher order aspects of motor behavior of patients with PD.

18 Clinical Trial Effect of cabergoline on parkinsonian tremor assessed by long-term actigraphy. 2009

Binder, Sabine / Deuschl, Gunther / Volkmann, Jens. ·Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstrasse 10, Kiel, Germany. ·Eur Neurol · Pubmed #19092251.

ABSTRACT: BACKGROUND: Tremor is one of the cardinal symptoms in Parkinson's disease, but only few clinical studies have focussed on its therapy as the primary endpoint. One reason is the substantial fluctuation of tremor severity over time, which is difficult to capture and may render momentary clinical assessments unreliable. METHODS: We evaluated the usefulness of a novel wrist-worn actigraph allowing long-term recordings of tremor in a pilot study, in which we assessed the therapeutic effect of cabergoline on tremor in 10 patients with tremor-dominant Parkinson's disease. Clinical data were obtained by using the Unified Parkinson's Disease Rating Scale (UPDRS Part III, item 20) and simultaneously a patient's tremor diary. RESULTS: We found a significant reduction in UPDRS motor and tremor scores, in tremor duration and tremor amplitude by actigraphy and diaries. Furthermore, we found significant correlations between actigraphy measurements and patient ratings of tremor intensity and occurrence in diaries. CONCLUSION: Long-term actigraphy is a reliable method to assess tremor occurrence and severity and may be used to document antitremor effects in clinical studies.

19 Clinical Trial Neuropsychological and psychiatric changes after deep brain stimulation for Parkinson's disease: a randomised, multicentre study. 2008

Witt, Karsten / Daniels, Christine / Reiff, Julia / 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. ·Christian-Albrechts-University, Kiel, Germany. ·Lancet Neurol · Pubmed #18538636.

ABSTRACT: BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. METHODS: 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. FINDINGS: 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohen's d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. INTERPRETATION: DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. FUNDING: German Federal Ministry of Education and Research (01GI0201).

20 Article Phase matters: A role for the subthalamic network during gait. 2018

Arnulfo, Gabriele / Pozzi, Nicolò Gabriele / Palmisano, Chiara / Leporini, Alice / Canessa, Andrea / Brumberg, Joachim / Pezzoli, Gianni / Matthies, Cordula / Volkmann, Jens / Isaias, Ioannis Ugo. ·Department of Neurology, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. · 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. · Fondazione Europea di Ricerca Biomedica (FERB Onlus), Cernusco s/N (Milan), Italy. · Department of Nuclear Medicine, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. · Centro Parkinson ASST G. Pini-CTO, Milan, Italy. · Department of Neurosurgery, University Hospital and Julius-Maximillian-University, Wuerzburg, Germany. ·PLoS One · Pubmed #29874298.

ABSTRACT: The role of the subthalamic nucleus in human locomotion is unclear although relevant, given the troublesome management of gait disturbances with subthalamic deep brain stimulation in patients with Parkinson's disease. We investigated the subthalamic activity and inter-hemispheric connectivity during walking in eight freely-moving subjects with Parkinson's disease and bilateral deep brain stimulation. In particular, we compared the subthalamic power spectral densities and coherence, amplitude cross-correlation and phase locking value between resting state, upright standing, and steady forward walking. We observed a phase locking value drop in the β-frequency band (≈13-35Hz) during walking with respect to resting and standing. This modulation was not accompanied by specific changes in subthalamic power spectral densities, which was not related to gait phases or to striatal dopamine loss measured with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon computed tomography. We speculate that the subthalamic inter-hemispheric desynchronization in the β-frequency band reflects the information processing of each body side separately, which may support linear walking. This study also suggests that in some cases (i.e. gait) the brain signal, which could allow feedback-controlled stimulation, might derive from network activity.

21 Article Subthalamotomy for Parkinson's disease: back to the future? 2018

Volkmann, Jens. ·Julius-Maximilians-University, Würzburg, Germany. Electronic address: volkmann_j@ukw.de. ·Lancet Neurol · Pubmed #29203154.

ABSTRACT: -- No abstract --

22 Article Pulse duration settings in subthalamic stimulation for Parkinson's disease. 2018

Steigerwald, Frank / Timmermann, Lars / Kühn, Andrea / Schnitzler, Alfons / Reich, Martin M / Kirsch, Anna Dalal / Barbe, Michael Thomas / Visser-Vandewalle, Veerle / Hübl, Julius / van Riesen, Christoph / Groiss, Stefan Jun / Moldovan, Alexia-Sabine / Lin, Sherry / Carcieri, Stephen / Manola, Ljubomir / Volkmann, Jens. ·Department of Neurology, Universitätsklinikum Würzburg, Würzburg, Germany. · Departments of Neurology and Functional & Stereotactic Neurosurgery, Universitätsklinikum Köln, Köln, Germany. · Department of Neurology, Charité, University Medicine Berlin, Germany. · Department of Neurology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany. · Boston Scientific Neuromodulation, Valencia, California, USA. · Boston Scientific Neuromodulation, Diegem, Belgium. ·Mov Disord · Pubmed #29165837.

ABSTRACT: BACKGROUND: Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations. METHODS: A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side-effect thresholds and unified PD rating scale (UPDRS) III were measured in meds-off (primary outcome). The therapeutic window was the difference between patients' efficacy and side effect thresholds. RESULTS: The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). INTERPRETATION: Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation-related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

23 Article Frontal Lobe Connectivity and Network Community Characteristics are Associated with the Outcome of Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson's Disease. 2018

Koirala, Nabin / Fleischer, Vinzenz / Glaser, Martin / Zeuner, Kirsten E / Deuschl, Günther / Volkmann, Jens / Muthuraman, Muthuraman / Groppa, Sergiu. ·Department of Neurology, Johannes Gutenberg University, 55131, Mainz, Germany. · Department of Neurosurgery, Johannes Gutenberg University, 55131, Mainz, Germany. · Department of Neurology, University of Kiel, 24105, Kiel, Germany. · Department of Neurology, University of Würzburg, 97080, Würzburg, Germany. · Department of Neurology, Johannes Gutenberg University, 55131, Mainz, Germany. segroppa@uni-mainz.de. ·Brain Topogr · Pubmed #28986718.

ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is nowadays an evidence-based state of the art therapy option for motor and non-motor symptoms in patients with Parkinson's disease (PD). However, the exact anatomical regions of the cerebral network that are targeted by STN-DBS have not been precisely described and no definitive pre-intervention predictors of the clinical response exist. In this study, we test the hypothesis that the clinical effectiveness of STN-DBS depends on the connectivity profile of the targeted brain networks. Therefore, we used diffusion-weighted imaging (DWI) and probabilistic tractography to reconstruct the anatomical networks and the graph theoretical framework to quantify the connectivity profile. DWI was obtained pre-operatively from 15 PD patients who underwent DBS (mean age = 67.87 ± 7.88, 11 males, H&Y score = 3.5 ± 0.8) using a 3T MRI scanner (Philips Achieva). The pre-operative connectivity properties of a network encompassing frontal, prefrontal cortex and cingulate gyrus were directly linked to the postoperative clinical outcome. Eccentricity as a topological-characteristic of the network defining how cerebral regions are embedded in relation to distant sites correlated inversely with the applied voltage at the active electrode for optimal clinical response. We found that network topology and pre-operative connectivity patterns have direct influence on the clinical response to DBS and may serve as important and independent predictors of the postoperative clinical outcome.

24 Article Connectivity Predicts deep brain stimulation outcome in Parkinson disease. 2017

Horn, Andreas / Reich, Martin / Vorwerk, Johannes / Li, Ningfei / Wenzel, Gregor / Fang, Qianqian / Schmitz-Hübsch, Tanja / Nickl, Robert / Kupsch, Andreas / Volkmann, Jens / Kühn, Andrea A / Fox, Michael D. ·Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. · Department of Neurology, Movement Disorder and Neuromodulation Unit, Charité-Universitätsmedizin, Berlin, Germany. · Department of Neurology, Würzburg University Hospital, Würzburg, Germany. · Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah. · Institute of Software Engineering and Theoretical Computer Science, Neural Information Processing Group, Berlin Technical University, Berlin, Germany. · Department of Bioengineering, Northeastern University, Boston, MA. · NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany. · Department of Neurosurgery, Würzburg University Hospital, Würzburg, Germany. · Clinic of Neurology and Stereotactic Neurosurgery, Otto von Guericke University, Magdeburg, Germany. · Neurology Moves, Berlin, Germany. · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA. ·Ann Neurol · Pubmed #28586141.

ABSTRACT: OBJECTIVE: The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. METHODS: A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. RESULTS: In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p < 0.001). This same connectivity profile predicted response in an independent patient cohort (p < 0.01). Structural and functional connectivity were independent predictors of clinical improvement (p < 0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. INTERPRETATION: Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. Ann Neurol 2017;82:67-78.

25 Article Subthalamic nucleus deep brain stimulation is neuroprotective in the A53T α-synuclein Parkinson's disease rat model. 2017

Musacchio, Thomas / Rebenstorff, Maike / Fluri, Felix / Brotchie, Jonathan M / Volkmann, Jens / Koprich, James B / Ip, Chi Wang. ·Department of Neurology, University Hospital of Würzburg, Würzburg, Germany. · The Krembil Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada. ·Ann Neurol · Pubmed #28470693.

ABSTRACT: OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective symptomatic therapy for motor deficits in Parkinson's disease (PD). An additional, disease-modifying effect has been suspected from studies in toxin-based PD animal models, but these models do not reflect the molecular pathology and progressive nature of PD that would be required to evaluate a disease-modifying action. Defining a disease-modifying effect could radically change the way in which DBS is used in PD. METHODS: We applied STN-DBS in an adeno-associated virus (AAV) 1/2-driven human mutated A53T α-synuclein (aSyn)-overexpressing PD rat model (AAV1/2-A53T-aSyn). Rats were injected unilaterally, in the substantia nigra (SN), with AAV1/2-A53T-aSyn or control vector. Three weeks later, after behavioral and nigrostriatal dopaminergic deficits had developed, rats underwent STN-DBS electrode implantation ipsilateral to the vector-injected SN. Stimulation lasted for 3 weeks. Control groups remained OFF stimulation. Animals were sacrificed at 6 weeks. RESULTS: Motor performance in the single pellet reaching task was impaired in the AAV1/2-A53T-aSyn-injected stim-OFF group, 6 weeks after AAV1/2-A53T-aSyn injection, compared to preoperative levels (-82%; p < 0.01). Deficits were reversed in AAV1/2-A53T-aSyn, stim-ON rats after 3 weeks of active stimulation, compared to the AAV1/2-A53T-aSyn stim-OFF rats (an increase of ∼400%; p < 0.05), demonstrating a beneficial effect of DBS. This motor improvement was maintained when the stimulation was turned off and was accompanied by a higher number of tyrosine hydroxylase INTERPRETATION: Our data support the putative neuroprotective and disease-modifying effect of STN-DBS in a mechanistically relevant model of PD. Ann Neurol 2017;81:825-836.