Depression and anxiety following bilateral deep brain stimulation in Parkinson's disease

2012/2013 Maria Inês Gomes da Rocha Couto Depression and anxiety following bilateral deep brain stimulation in Parkinson's disease março, 2013 Mestrado Integrado em Medicina Área: Neurologia Trabalho efetuado sob a Orientação de: Dr. João dos Santos Massano de Carvalho E sob a Coorientação de: Doutor Nuno Miguel de Sousa Lunet Trabalho organizado de acordo com as normas da revista: Movement Disorders: official journal of the Movement Disorder Society Maria Inês Gomes da Rocha Couto Depression and anxiety following bilateral deep brain stimulation in Parkinson's disease março, 2013 Agradeço a título profissional a orientação do Dr. João Massano e a co-orientação do Doutor Nuno Lunet sobretudo na idealização dos sucessivos melhores caminhos a tomar. Agradeço, ainda, à Drª Ana Monteiro e à Drª Ana Oliveira pelo trabalho desenvolvido sem o qual não teria sido possível rever tão a fundo a literatura. Obrigado. À minha irmã, por tudo. À minha irmã, por tudo. À minha irmã, por tudo. E mais houvesse. Obrigado! Pela paciência, conselhos, cafés, maledicências da vida, simples companhia. Sobretudo, por ser eu a felizarda de anteceder um ser tão grande na progénie. Posto isto, aos meus pais pelo gene da procura da batalha mais difícil. É dominante entre nós essa tendência! A trivialidade não faz diferente nem maior nem mais além. E sem isso nada muda. E o estagnado é vazio e sem desafio ao intelecto e às capacidades. À minha avó pela bendita costela, porque afinal se não nos rirmos da vida também não a levamos muito avante nem a sério o suficiente para percebermos as suas ironias. À Vera! Que tanto aturou. E que ajudou ainda mais. Muito obrigado. Pelos cafés, pela última mesa da biblioteca, pelos infindáveis relambórios (e o semáforo verde, e vermelho, e verde, e vermelho...), por alguns dos não muitos sorrisos dos últimos tempos, pelo feitio (haja alguém que compreende que realmente a responsabilidade por vezes enerva!). Obrigado. Todas as palavras de alento de todas as pessoas amigas. Obrigado. 1 Title Depression and anxiety following bilateral deep brain stimulation in Parkinson's disease Authors and affiliations Maria Inês Couto1 1-Department of Clinical Neurosciences and Mental Health, Faculty of Medicine University of Porto, Porto, Portugal Corresponding author Maria Inês Couto Address: Department of Clinical Neurosciences and Mental Health, Faculty of Medicine University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal Phone: +351-963282058 Email: [email protected] Word Count: 2435 Running title Depression and anxiety following DBS in PD Key words Parkinson’s disease; deep brain stimulation; anxiety; depression; systematic review Financial disclosures: Maria Inês Couto declares no conflicts of interest. Funding sources: This work received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. 2 Abstract Background: Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson’s disease (PD), improving motor symptoms, motor complications and quality of life. However, adverse psychiatric outcomes have been reported by several authors, albeit variably and in an unstandardized fashion. We aimed to summarize the published evidence on the outcomes of anxiety and depressive symptoms in PD patients following DBS, through systematic review and meta-analysis. Methods: Pubmed was searched until May 2012 to identify studies that assessed anxiety and depressive symptoms in PD patients who underwent bilateral DBS of the subthalamic nucleus (STN) or globus pallidus internus (GPi). Random effects metaanalyses were conducted for groups of at least three studies that were homogeneous regarding the design and the instruments used. Results: Depression and anxiety improvement is apparent after DBS, more pronounced in the short-term, an effect that seems to wane in later assessments. Concerning depression, STN-DBS shows superiority against medical treatment, but not when compared to eligible for surgery control groups. The opposite is apparent for anxiety, as results favor medical treatment over STN-DBS, and STN-DBS over eligible for surgery control group. Superiority of one target over the other is not evident from the results, but data slightly favors GPi for both outcomes. Conclusions: No clear conclusion can be drawn from this meta-analysis, with the possible exception of depression improvement at short-term following STN-DBS, although with significant heterogeneity of results. Efforts should be carried out to standardize assessment procedures for depression and anxiety in PD patients undergoing DBS. 3 Introduction: Parkinson’s disease (PD) is a frequent, disabling neurodegenerative condition characterized by motor and non-motor symptoms, including cognitive and behavioral1. Deep brain stimulation (DBS) has proved effective in advanced PD, as motor symptoms, fluctuations, disability and quality of life improve in patients carefully selected for the procedure2-4. Recently, the efficacy of DBS has been also demonstrated in PD with early motor complications5, suggesting that the universe of potential surgical candidates is wider than previously established. However, significant concerns have been raised about potential cognitive and psychiatric adverse effects in PD patients following DBS, and some data even suggested that consequences might vary according to the chosen target, namely the subthalamic nucleus (STN) or the globus pallidus internus (GPi)6-8. On the other hand, several studies found no significant adverse psychiatric outcomes following DBS in PD9-11. This issue remains incompletely clarified, as several different assessment methods have been used, and results have been reported under diverse formulas. Data have been reviewed systematically in two previous publications concerning psychiatric outcomes in patients undergoing bilateral DBS, but one study published in 2006 was limited to patients having STN-DBS12, while the other, published in 2007, jointly analyzed results in several pathologies including PD13; in addition, several other studies in PD have been published since then, thus justifying re-appraisal of findings. We aimed at systematically reviewing the literature and summarizing the evidence by meta-analysis, in order to establish state of the art knowledge concerning anxiety and depression following DBS in PD. Methods: PubMed was searched from inception until May 2012, using the search expression “("deep brain stimulation" OR "subthalamic stimulation" OR (stimulation AND (“subthalamic nucleus” OR “globus pallidus”))) AND (parkinson disease OR parkinson’s disease)”, to identify studies that assessed anxiety and depressive symptoms in PD patients who underwent bilateral DBS. A total of 3276 references were screened by one of three reviewers (MIC, AM, AO), following the same exclusion criteria defined a priori, as follows: 1) language other than English, Portuguese and Spanish; 2) non-human data; 3) disorders other than PD; 4) studies not concerning DBS; 5) studies not conveying original data (reviews, systematic reviews, meta-analysis, book chapters, letters to the editor with no original data); 6) case reports; and 7) reports with no data on the outcomes of interest, namely: 7.1) no clinical outcome at all (e.g. image methods for target location); 7.2) clinical outcome other than psychiatric; 7.3) psychiatric outcome not objectively assessed by psychometric instrument. References were then restricted to those reporting on the most relevant DBS targets in PD (STN and GPi), and depression or anxiety only. In addition, study design details were used to exclude studies not enrolling participants consecutively or randomly selected. Duplicate references were eliminated by comparing titles, authors, centers and sample details, and a total of 63 reports3,10,14-74 were considered for the systematic review. The systematic review flow-chart is presented as appendix 1. 4 Quantitative data on depression and anxiety were collected from the eligible studies along with DBS target and follow-up time. Five aspects were considered in order to group and analyze data: 1) Main outcome: depression or anxiety; 2) DBS target: STN and GPi were individually considered, so studies containing indiscriminate information on both targets3,72 have not been analyzed; 3) Follow-up time: three main periods were considered: up to 6 months after surgery (short-term follow-up); between 6 months and 3 years (mid-term follow-up); and more than 3 years (long-term follow-up); within each defined time period we selected the data referring to the longest follow-up for analysis, whenever data was available for different moments after the intervention; 4) Assessment scale(s) employed; 5) Study design: two main types of information were sought: the change of variables of interest with the exposure to the procedure (follow-up studies with preand post-operative data) and the difference between groups concerning the response to DBS (studies with different types of comparators). DBS versus controls and STN-DBS versus GPi-DBS were considered comparisons of interest, so in studies with other comparators, only the information concerning the DBS group was collected. “On” state evaluation was considered in studies reporting “on” versus “off” state comparison. In partial duplicates with patients overlapping but with different assessment scales35,49, follow-up time16,27 or comparison groups73, a selection of relevant data was performed for each one, and only specific duplicated information was excluded. A total of 63 studies assessing depression and/or anxiety following DBS (STN or GPi) in consecutive samples of PD patients were selected for analysis. Forest-plots were used to summarize the findings from all eligible studies and random effects meta-analysis (DerSimonian and Laird method) was performed for groups of at least three comparable studies. The I2 statistic was used to quantify heterogeneity. Original data concerning different strata from the same studies were assumed as different samples, strata being defined by age43, single or multiple recording electrodes40, and center (in one collaborative study)73. The pre to postoperative variation was calculated from “postop score – preop score”. Differences between STN-DBS and the comparison groups were calculated by “STN score – comparator score”. The effect size (ES) and corresponding 95% confidence interval (CI) were extracted whenever provided in the original reports or computed using the published data considering matched and independent samples, respectively (adopted formulas detailed in appendix 2). Test-retest coefficients have been collected for the several psychometric instruments75-86. Results: Nearly all studies (n=62, 98.4%) provided data on depression, and 24 (38.1%) on anxiety assessment scales. STN-DBS was performed in 60 studies (95.2%) and GPiDBS in 9 (14.3%); the overlap between target groups corresponds to STN versus GPi comparison studies. Two additional reports3,72 that did not discriminate data by target were not considered in our analysis. From the remaining 61 references, short-term evaluation was performed in 37 (60.7%), mid-term in 36 (59.0%) and long-term in 5 (8.2%). Data on preto postop variation was available in 57 (93.4%) reports and 16 11 17. Oyama G, Shimo Y, Natori S, et al. Acute effects of bilateral subthalamic stimulation on decision-making in Parkinson's disease. Parkinsonism Relat Disord 2011;17:189-193. 18. Nazzaro JM, Pahwa R, Lyons KE. The impact of bilateral subthalamic stimulation on non-motor symptoms of Parkinson's disease. Parkinsonism Relat Disord 2011;17:606-609. 19. Huebl J, Schoenecker T, Siegert S, et al. Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson's disease. 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Neurology 2012;78:998-1006. 20 Figures legends: Figure 1. Beck Depression Inventory forest-plot (STN-DBS). Beck Depression Inventory results following subthalamic stimulation (STN-DBS) with data grouped and analyzed by follow-up time periods. Effect size and 95% confidence interval are presented for each sample. Overall measure is presented for each time period. Abbreviations: country abbreviations according to ISO 3166-1 decoding table. Figure 2. Depression psychometric scales forest-plot (STN-DBS). Depression assessment results following subthalamic stimulation (STN-DBS) with data grouped and analyzed by psychometric instrument and sorted by ascending follow-up time. Effect size and 95% confidence interval are presented for each sample. Abbreviations: BRMES: Bech-Rafaelsen Melancholia Scale; BSId: Brief Symptom Inventory – depression part; GDS: Geriatric Depression Scale; HADd: Hospital Anxiety and Depression scale – depression part; HDRS: Hamilton Depression Rating Scale; MADRS: Mongomery-Åsberg Depression Rating Scale; POMSd: Profile Of Mood States – depression part; SCL90Rd: Symptom CheckList 90 Revised – depression part; UPDRS I,3: Unified Parkinson’s Disease Rating Scale, Part I, Item 3; Zungd: Zung selfrating depression scale. Country abbreviations according to ISO 3166-1 decoding table. Figure 3. Pallidal stimulation outcomes forest-plot. Depression and anxiety assessment results following pallidal stimulation with data grouped and analyzed by psychometric instrument and sorted by ascending follow-up time. Effect size and 95% confidence interval are presented for each sample. 27 Figure 5: . . . . . . . . . . AMDP-AT Dujardin, 2004 (FR/CA/BE) Drapier, 2006 (FR) BAI Auclair-Ouellet, 2011 (CA) Witt, 2008 (DE/AT) Auclair-Ouellet, 2011 (CA) Lhommee, 2012 (FR) BAS Houeto, 2006 (FR) Houeto, 2006 (FR) BSIa York, 2008 (US) HADa Altug, 2011 (TR) Martinez-Martin, 2002 (ES) Kishore, 2010 (IN) Kishore, 2010 (IN) HAMA Kalteis, 2006 (AT) Kalteis, 2006 (AT) SCL90Ra Kaiser, 2008 (AT) Kaiser, 2008 (AT) STAIs Kaiser, 2008 (AT) York, 2008 (US) Rothlind, 2007 (US) Kaiser, 2008 (AT) Zibetti, 2009 (IT) Zibetti, 2011 (IT) STAIt Kaiser, 2008 (AT) York, 2008 (US) Rothlind, 2007 (US) Kaiser, 2008 (AT) Zibetti, 2009 (IT) Zibetti, 2011 (IT) Zunga Daniele, 2003 (IT) Daniele, 2003 (IT) Fasano, 2010 (IT) ID Study -6.10 (-9.58, -2.62) -2.80 (-7.09, 1.49) -3.57 (-10.84, 3.70) -9.00 (-11.94, -6.06) -4.86 (-8.52, -1.20) -4.70 (-6.60, -2.80) -3.60 (-5.67, -1.53) -5.90 (-7.72, -4.08) -3.30 (-5.67, -0.93) -11.77 (-13.89, -9.65) -4.00 (-4.44, -3.56) 0.70 (0.31, 1.09) 1.60 (1.27, 1.93) -5.40 (-7.13, -3.67) -5.10 (-6.76, -3.44) -0.47 (-0.63, -0.31) -0.37 (-0.56, -0.18) -6.96 (-10.47, -3.45) -1.10 (-6.18, 3.98) -0.10 (-5.33, 5.13) -1.66 (-5.38, 2.06) -0.70 (-3.91, 2.51) -2.00 (-9.30, 5.30) -5.82 (-7.53, -4.11) 1.60 (-0.89, 4.09) 3.40 (0.72, 6.08) 2.00 (0.29, 3.71) 0.10 (-1.36, 1.56) 0.00 (-2.90, 2.90) -4.60 (-10.21, 1.01) -6.70 (-10.66, -2.74) -3.40 (-9.55, 2.75) ES (95% CI) 3 6 6 6 12 12 6 24 6 6 6 36 60 6 12 6 36 6 6 15 36 36 108 6 6 15 36 36 108 6 18 96 (months) Follow-up -6.10 (-9.58, -2.62) -2.80 (-7.09, 1.49) -3.57 (-10.84, 3.70) -9.00 (-11.94, -6.06) -4.86 (-8.52, -1.20) -4.70 (-6.60, -2.80) -3.60 (-5.67, -1.53) -5.90 (-7.72, -4.08) -3.30 (-5.67, -0.93) -11.77 (-13.89, -9.65) -4.00 (-4.44, -3.56) 0.70 (0.31, 1.09) 1.60 (1.27, 1.93) -5.40 (-7.13, -3.67) -5.10 (-6.76, -3.44) -0.47 (-0.63, -0.31) -0.37 (-0.56, -0.18) -6.96 (-10.47, -3.45) -1.10 (-6.18, 3.98) -0.10 (-5.33, 5.13) -1.66 (-5.38, 2.06) -0.70 (-3.91, 2.51) -2.00 (-9.30, 5.30) -5.82 (-7.53, -4.11) 1.60 (-0.89, 4.09) 3.40 (0.72, 6.08) 2.00 (0.29, 3.71) 0.10 (-1.36, 1.56) 0.00 (-2.90, 2.90) -4.60 (-10.21, 1.01) -6.70 (-10.66, -2.74) -3.40 (-9.55, 2.75) ES (95% CI) 3 6 6 6 12 12 6 24 6 6 6 36 60 6 12 6 36 6 6 15 36 36 108 6 6 15 36 36 108 6 18 96 (months) Follow-up 0-15 -10 -5 -2 0 2 5 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 1 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html Movement Disorders Copyright © 2013 Movement Disorders Society Edited By: C. Warren Olanow, MD, FRCPC andJose A. Obeso, MD, PhD Impact Factor: 4.505 ISI Journal Citation Reports © Ranking: 2011: 24/192 (Clinical Neurology) Online ISSN: 1531-8257 Author Guidelines NIH Public Access Mandate For those interested in the Wiley-Blackwell policy on the NIH Public Access Mandate, please visit our policy statement (http://www.wiley.com/go/nihmandate) For additional tools visit Author Resources (http://olabout.wiley.com/WileyCDA/Section/id-404516.html) - an enhanced suite of online tools for Wiley InterScience journal authors, featuring Article Tracking, E-mail Publication Alerts and Customized Research Tools. Copyright transfer agreement (CTA-Consent.pdf) The National Institutes of Health Public Access Initiative (http://www.wiley.com/go/nihmandate) Author Guidelines 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 2 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html MANUSCRIPT SUBMISSION INFORMATION Movement!Disorders is pleased to offer authors!web-based manuscript submission and peer-review "#$$%&''()*(+,-.)/0%$)1,$/+2*)3('(4.5. Authors are required to submit online athttp://mc.manuscriptcentral.com/mds(http://mc.manuscriptcentral.com/mds).All accompanying supplementary material (e.g., videos, appendices) should also be submitted online. Policy Regarding Inappropriate Submissions and Publications The editors, members of the editorial board, and publisher's staff at Movement Disorders take their responsibility seriously to assure that the highest ethical publishing standards are maintained by assisting in safeguarding the medical scientific literature against fraudulent publications. Please note manuscript submissions are now submitted for plagiarism detection through CrossCheck. Wiley-Blackwell policy is based on the 'Guidelines on Good Publication Practice' published by the Committee on Publication Ethics (COPE) and can be found at Author Services. Examples of fraud in scientific research include (but are not limited to): 1) The submission of duplicate publications using similar data (i.e., attesting that work submitted is original when, in fact, it was submitted to or accepted by another journal); 2) Falsification of data, copyright, or information regarding conflict of interest; 3) Submission of work from other sources that was not done by the author and is presented as a new and original (plagiarism); 4) Authorship (allowing one’s name to appear as an author or adding an author to a manuscript) without substantial input or without having agreed to submission of the manuscript. The above examples are not meant to be a comprehensive list of fraudulent publication practices. Rather, it should provide adequate basis for careful consideration of avoidable conflicts and editorial scrutiny regarding inappropriate preparation and submission of manuscripts. Manuscripts that have appeared in publications that are not peer-reviewed, are not registered in Pub Med, or are available only on the internet, will be considered for publication in MDS as long as the Editor is informed and grants approval prior to submission of the manuscript for review. If there are questions as to any issues regarding inappropriate submission, the Editor should be consulted prior to the submission. If a submitted or published manuscript is discovered or suspected to be inappropriate, the authors will be asked for a written explanation. If the rationale provided by the authors remains unsatisfactory in the judgment of the editors, the manuscript will be rejected or retracted. Retractions become a matter of public record and are registered in Pub Med. The provost (or equivalent) of the authors' academic institutions will be informed of inappropriate submissions or publications, and the authors will not be allowed to subsequently submit their research to MDS. The leadership of MDS will also inform the editors and publishers of other journals which have published manuscripts judged to be inappropriately submitted to MDS. Editorial Office Information Jose A. Obeso, MD, PhD! University of Navarra Pamplona, Spain Phone: 34-948-194700, ext. 2038 E-mail:![email protected]!"(+02$3&678(391(1,$40.3/41/.*1+.$:;(+02*)3(5 C. Warren Olanow, MD, FRCPC Mount Sinai School of Medicine New York, New York, USA Phone: 1-212-241-8435 E-mail:![email protected]!"(+02$3&)<32+,3<:;(+02*)3(5 Submit your manuscripts online at!http://mc.manuscriptcentral.com/mds!"#$$%&''()*(+,-.)/0%$)1,$/+2*)3('(4.5. Please note: Manuscripts submitted online are marked as received on the day of submission, evaluated by the Chief Editors, and assigned to associate editors to oversee the review process. Papers that are not determined to be of sufficient clinical/scientific interest, focus, or relevance by at least 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 3 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html two senior editors may be rejected without review. Through your individual Author Center on this website, you can view the status of your manuscript as it progresses through the review process. Notification of the final disposition of each manuscript will be sent by E-mail to the corresponding author on the day of decision. To submit your manuscript online: Go to the!submission website!"#$$%&''()*(+,-.)/0%$)1,$/+2*)3('(4.5!"http://mc.manuscriptcentral.com/mds "#$$%&''()*(+,-.)/0%$)1,$/+2*)3('(4.55 Click on the "Check for Existing Account" button at the bottom of the opening page.!If you do not already have an account, then create one by clicking on the "Create an Account" button.!You will then be able to submit your manuscript. Click on “Author Center.”!Follow the on-screen instructions carefully.!Tables and figures should be uploaded as individual files and not part of the manuscript text.!(You do not need to mail hard copies of your manuscript). At the end of a successful submission, you will see a confirmation screen with your manuscript number, and you will receive a separate E-mail confirmation of manuscript reception by the journal.!If these two messages do not appear, then go into your Author Center and make sure that you have clicked on the “Submit” button or contact technical support at http://mchelp.manuscriptcentral.com/gethelpnow/question.htm "#$$%&''()#12%*(+,-.)/0%$)1,$/+2*)3('61$#12%,37'8-1.$03,*#$(5. Video Submission File size limitations:!Files may be no larger than 50 MB. General Information:When submitting manuscripts online, authors must indicate whether the article has an accompanying video. Video must be submitted with manuscripts online in a digital format. If an article includes video, the upper right corner of the title page of the manuscript must be marked “Video is part of ms.” Video clips should be limited to 90 seconds unless formal approval is obtained from the editorial office. Authors must also supply, as part of the manuscript, a video legend for the video clip. If the author does not have the capacity to generate an electronic video, the author may contact the editorial office for assistance. Content:!Video content should be edited to illustrate the key findings in a concise and informative manner. They should be less than 90 seconds in duration, except for special instances, which must be cleared in advance with the appropriate chief editor. Legends for the video segments should be placed at the end of the article and should concisely and sequentially describe what is seen in the video so that it can be readily understood by the viewer. Do not repeat explanatory material that is already in text. The video should be of high quality (both in content and visibility). The video should be edited to ensure maximal efficiency and make the specific point; particularly, it should demonstrate the features described in the text of the manuscript. In addition, the video should be labelled and should directly follow the sequence and content of the video legend. The use of text and/or special transition effects between the titles, subtitles and video segments is permitted. The video you submit should be the final product that will be published with the article. The Editors reserve the right to request additional video editing by the authors (which may delay publication). Patient Consent:The corresponding author must confirm in the author copyright form (Article V) that he or she has received a signed release form from each patient videotaped authorizing the offline and/or online distribution of this video material. Manuscripts with videos will not be sent out for review until the signed copyright form (Article V) with appropriate documentation is received.!The date of submission will be the date all components of the article arrive at the editorial office. For tips on preparing your video for submission, see the Technical Note by Jog and Grantier on digital video preparation.!This article appears in volume 16, issue 6, and is available to all readers. Cover Letter, Author Copyright Form, and Legal Information Cover Letter.The cover letter should briefly describe the scientific or clinical importance of the manuscript. It must confirm that all authors have read the manuscript, the paper has not been previously published, and it is not under simultaneous consideration by another journal. Also, a statement that no ghost writing by anyone not named on the author list!!must be included (see Editorial in Movement Disorders 2005;20:1536). Identify the corresponding author and provide a complete mailing address, telephone number, and email address for each author where possible. 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 4 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html Author Copyright Form. The author Copyright form includes (1) a statement on authorship responsibility, (2) a statement on financial disclosure, (3) one of two statements on copyright or federal employment, and (4) a statement of acknowledgment. Each of the first three statements must be read and signed by each co-author. The corresponding author must sign the acknowledgment statement (See the copyright form at the top of this page).:5)!!When there is accompanying video or photographs on which patients can be identified, the corresponding author must sign the video consent section (Article V). Group Authorship. The journal does not limit the number of authors for an individual manuscript providing that: a)If there are multiple authors , all authors must meet the full criteria and requirements for authorship; b). If there is group, authorship, one or more individuals are designated as authors or members of a writing group who meet full authorship criteria and who take responsibility for the group. Other members of the group are not authors individually, but may be listed in the acknowledgment section (Flanagin A, Fontanarosa PB, DeAngelis CD. Authorship for research groups. JAMA 2002;288:3166-3168). Documentation of Author Roles.At the end of the manuscript, all authors must be listed, along with their specific roles in the project and manuscript preparation. These should include but not be restricted to: 1. Research project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique; Data Access and Responsibility.For clinical trials sponsored by pharmaceutical companies, authors must state in their letter of submission that (1) they have had full access to the data, (2) they have the right to publish all the data, and (3) they have had the right to obtain independent statistical analyses of the data. For any report containing original data, at least one author should indicate that he or she “takes responsibility for the integrity of the data and the accuracy of the data analysis” (DeAngelis CD, Fontanarosa PB, Flanagan A. Reporting financial conflicts of interest and relationships between investigators and research sponsors. JAMA 2001;286:89-91). Patient Consent.When submitting a patient video or photograph in which a patient can be identified, the corresponding author must provide the Movement Disorders journal with a written confirmation (author copyright form, Article V) that stipulates that authorization signed by the patient has been obtained in compliance with any laws regarding patient authorizations relating to the use or disclosure of protected health information of the jurisdiction(s) to which the patient and the physician are subject including, if applicable, the United States Health Insurance Portability and Accountability Act of 1996 (“HIPAA”).1 Manuscripts including, without limitation, a patient video or photograph will not be reviewed until a signed author's accompanying statement (see Item V) has been received. Copyright.The Movement Disorder Society will hold copyright to all published articles and videos. The copyright transfer agreement form can be downloaded from the top of this page. If you are a government employee, please check the “Government-Owned Work” checkbox. Financial Disclosures.All submissions require two entries that cover financial disclosure of all authors:  Financial disclosure related to research covered in this article:A statement that documents all funding sources and potential conflicts of interest from each author that relate to the research covered in the article submitted must be included on the title page, regardless of date. This material will be printed with the published article.  Full financial disclosure for the previous 12 months:A statement that documents all funding sources, regardless of relationship to the current research in the article, from each author must be attached to the article at the end of the manuscript on the last page. This material will be posted on the journal website and may be printed at the Editors’ discretion. The copyright form that is signed by each author confirms that both of these entries are documented in the submitted material. Expedited Publications (Fast Track) Movement!Disorders will attempt to accommodate authors of manuscripts dealing with extremely topical issues or with findings of great scientific or clinical importance by offering Expedited Review and Publication. Expedited papers will be rapidly reviewed and published within 8 weeks. 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 5 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html Scope Movement!Disorders publishes Full-length Articles, Reviews, Opinion papers/Viewpoints/Hypotheses/Editorials, Brief Reports, and Letters. Case reports in which a definitive pathological or genetic diagnosis has been made can be submitted for publication in the Clinico-Pathological Grand Rounds section of the journal. If the editor determines that the report is appropriate for the Clinico-Pathological Grand Rounds format two referees can be solicited to discuss the case and become co-authors of the report. All articles in Movement Disorders, including letters, can be accompanied by a video when appropriate. Authors who are not perfectly fluent in English should have their manuscript professionally edited before submission. A list of independent suppliers of editing services can be found at!www.blackwellpublishing.com/bauthor/english_language.asp "#$$%&''((()*+,-.(/++%0*+12#134)-56'*,0$#57'/34+12#8+,340,4/),2%9.!:,%,3/2/!,0$#572!-,3!,+25!;13<!,!+12$!5;!+5-,+ =34+12#!16%75>/6/3$!2/7>1-/2!,$!http://www.wiley.co.jp/journals/editcontribute.html "#$$%&''((()(1+/?)-5)@%'@5073,+2'/<1$-53$71*0$/)#$6+9.!All services must be arranged and paid for by the author, and use of one of these services does not guarantee acceptance for publication. In addition, the journal will edit accepted papers to ensure uniformity of language and style. Full-Length Articles:!Full-length articles should present new clinical or scientific data in a field related to movement disorders. The format should include - Structured Abstract!!(up to 250 words with only essential abbreviations (e.g. DNA)). Text; (up to 3000 words exclusive of abstract, legends, and references) Minimize abbreviations. Tables and/or figures – up to 5.. Legends; should be concise and describe results without repeating data in text. Videos; see above. The word count must appear on the title page. Reviews:!Clinical and basic science Reviews are generally published upon request or after agreement with the editors of Movement Disorders. Unsolicited Reviews will also be considered for publication. Reviews can be up to 3600 words. The word count must appear on the title page. Viewpoints, Hypotheses, Editorials: Editorials are solicited by the editors. Hypotheses and viewpoints!related to any aspect of movement disorders may be submitted without solicitation. Viewpoints, Hypotheses/Editorials should be limited to 2000 words and 50 references. The word count must appear on the title page. Brief Reports:!Brief reports are short original clinical or basic science reports related to any aspect of movement disorders. Structured Abstracts up to 150 words, text up to 1500 words, tables and figures up to 2. References should be limited to 40. The word count must appear on the title page. Case reports!are not normally recommended for consideration as a research article or brief report and should be submitted as a letter unless they make a scientifically important point. Letters:!Letters to the Editors should have no more than five authors. Movement disorders permits publication of two types of letters to the editor with no abstract: A)!Letters related to new observations. This section is appropriate for preliminary scientific observations and case presentations that raise a novel clinical or scientific issue. Letters on new observations may be up to 500 words and contain no more than 1 table/figure and 7 references. B)!A letter related to published articles. These may be submitted up to 8 weeks after the paper was published in print. Text length for both letters and replies may be up to 500 words and contain 1 table/figure and up to 5 references. Letters from original authors must be submitted within 4 weeks after request for response. Articles reporting Clinical Trials:!Clinical Trial Reports must be written in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement (Moher D et al., JAMA 2001;285:1987–1991; see also Moher D et al., Lancet 2001;357:1191–1194). Authors should ensure that information on all of the critical design features listed in the CONSORT checklist is reported in the manuscript. A CONSORT flow diagram should be included with the manuscript, clearly outlining the flow of patients through the trial. In addition, a statement is required in the cover letter specifically confirming that there has been no ghost writing by anyone not named on the author list (see Editorial in Movement Disorders 2005;20:1536). The precise financial relationship between a clinical trial sponsor and the authors must be delineated in the manuscript. 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 6 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html Medical Images –Medical Images should have no more than three authors. High quality clinical or scientific photographs, drawings, scans, or other images may be submitted along with a title and a legend that describes what is observed in the image and its clinical, scientific or conceptual significance. One image (could have multiple parts) in color or in black and white may be submitted. The image may be based on an MRI, PET, pathologic specimen or clinical phenomenon, etc. Appropriate consent must be included. 200 words of text are permitted as a legend. The legend should begin with a description of what is in the image and then can go on to describe the clinical or pathologic circumstances relevant to the image. This is an imaging section and while we do want some clinical or pathological detail as appropriate, the focus of this section is on the image. A New Section for Movement Disorders – Most movement disorder specialists were initially attracted to the field by their experience with patients. With all of the advances that have been made in the basic sciences and treatment, clinical phenomenology and accurate diagnosis remain at the heart of the field. Starting with this issue of the journal, we will inaugurate a new section entitled “Clinical Vignettes”, under the direction of Dr. Steven Frucht. Each month we will feature one or two interesting cases that illustrate an important diagnostic, clinical or therapeutic point. These cases may illustrate novel clinical or scientific findings, but could also represent an unusual or informative case. In most instances this will include a video demonstration of the movement disorder. Clinical Vignettes should have no more than five authors. Each case can be accompanied by one figure illustrating a salient feature of the vignette (an image or pathologic slide, for example). Additional information can be added as supplementary material on the web site. Clinical vignettes will frequently be accompanied by a brief editorial commentary. Each case will be limited to 1000 words of text; no abstract; and 10 references. Submissions to this section should be labeled “Clinical Vignettes”. They will be published in the regular print issue and will also be available online. Any questions should be directed to Dr. Steven Frucht at [email protected] (mailto:[email protected]), or to the journal staff. Form of Manuscripts. The text of the manuscript should be in the following sequence: (1) Title page, (2) Abstract, (3) Introduction, (4) Methods, (5) Results, (6) Discussion, (7) Acknowledgment, (8) Authors' Roles, (9) Financial Disclosures of all authors (for the preceding 12 months), (10) References, (11) Video Legend, (12) Figures, and (13) Tables. Pages should be numbered in succession, the title page being number one. Title: Titles should be short, specific, and clear. They should not exceed 100 characters. Do not use abbreviations/acronyms in the title. Title Page:The opening page of each manuscript should include: (1) article title (no abbreviations/acronyms); (2) authors' names and affiliations (indicate the specific affiliation of each author by superscript, Arabic numerals); (3) name, address, telephone and email address of the corresponding author; (4) word count; (5) a running title not exceeding 45 letters and spaces; (6) Key words – up to 5; (7) Financial Disclosure/Conflict of Interest concerning the research related to the manuscript: All information on support and financial issues from all authors relative to the research covered in the submitted manuscript must be disclosed regardless of date. Other financial information unrelated to the current research covering the past year will be documented at the end of the manuscript (see below). (8) Funding sources for study. Structured!Abstract:!We require that authors submit structured abstracts, but will consider unstructured abstracts if requested by the authors prior to submission. The page following the title page of Full-Length Articles, and Reviews, should include an abstract of up to 250 words. The abstract should be structured (background, methods, results, and conclusions) unless not appropriate for a specific article. The page following the title page of a Brief Report,!!should include a structured abstract of up to 150 words. Authors are required to spell out all abbreviations/acronyms in the structured abstract unless this has become accepted in the standard scientific literature (e,g, DNA, MPTP). Introduction: Give a brief description of the background and relevance of the scientific contribution. Methods: Describe the methodology of the study.!For experimental investigation of human or animal subjects, please state in this section that an appropriate institutional review board approved the project. For those investigators who do not have formal ethics review committees, the principles outlined in the “Declaration of Helsinki” should be followed. For investigations in human subjects, state in this section the manner in which informed consent was obtained from the subjects. A letter of consent must accompany all photographs, patient descriptions, and 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 7 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html pedigrees in which a possibility of identification exists. The authors are responsible for ensuring anonymity. Results: No specific regulations. Discussion: No specific regulations. Acknowledgment: No specific regulations. These may be published on line at the discretion of the editor. Author Roles: List all authors along with their specific roles in the project and preparation of the manuscript. These may include but are not restricted to: 1) Research project: A. Conception, B. Organization, C. Execution; 2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3) Manuscript: A. Writing of the first draft, B. Review and Critique. Full Financial Disclosures of all Authors for the Past Year:Information concerning all sources of financial support and funding for the preceding twelve months, regardless of relationship to current manuscript, must be submitted with the following categories suggested. List sources or “none”. Stock Ownership in medically-related fields Intellectual Property Rights Consultancies Expert Testimony Advisory Boards Employment Partnerships Contracts Honoraria Royalties Grants Other References: See “Details of Style” below for the proper formatting of citations and References. Video Legend:No specific regulations but should be concise and reflect the sequence of observations on the video Tables and Figure Legends: Double-space legends of fewer than 40 words for tables and figures. For photomicrographs, include the type of specimen, original magnification, and stain type. Include internal scale-markers on photomicrographs when appropriate. Where applicable, indicate the method used to digitally enhance images. Tables: Tables!should be typed neatly, each on a separate page, with a title above and any notes below. Explain all abbreviations. Do not repeat the same information in tables and figures that is present in text.Tables and figures should be uploaded as individual files and not part of the manuscript text.!(You do not need to mail hard copies of your manuscript).!! Figures and Illustrations: Adapt any figures to an appropriate size of art and letters to make them readable in the printed version. Illustrations in full color are accepted at additional charge from the publisher. In the case of review articles or in special circumstances, color articles may be included at no charge with the permission of the Chief Editor. Any illustration or figure from another publication must be acknowledged in the figure legend, and the copyright holder’s written permission to reprint in print and online edition of Movement Disorders must be submitted to the editors. In addition, figures to illustrate concepts are welcome particularly in review articles, and may be enhanced by a professional artists at no cost to author at the discretion of the Editors. Copyright and Disclosure Forms!The corresponding author should upload one PDF file that includes copyright and disclosure forms for all authors to the Movement Disorders submission site with the revised version of the paper. These forms also can be emailed to [email protected].!"#$%&'()#*+,*(--%.,/#(0,#,1'*%2(3*,324(356 Digital Artwork Preparation For best reproduction, electronic artwork files must be in TIFF or EPS format, at a resolution of 600 dpi or higher, sized to print. Movement Disorders offers!Rapid Inspector!"7''8)993$8%*%128,.'(34.$*#:24.(#9;$8%*<128,.'(39=>%9%1*,?4+286™ to help ensure that your electronic graphics files are suitable for print purposes. This free, stand-alone software application will help you to inspect and verify illustrations right on your computer. Go tohttp://rapidinspector.cadmus.com/wi/index.jsp "7''8)993$8%*%128,.'(34.$*#:24.(#9;$8%*<128,.'(39=>%9%1*,?4+286!and create a new account. 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 8 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html Details of Style No patient identifiers (e.g., patient initials) are to be included in the manuscript or video (e.g., case reports, tables, figures, etc.). Units of measure: Conventional units of measure according to the Systeme International (SI) are preferred. The metric system is preferred for length, area, mass, and volume. Express temperature in degrees Celsius. Drug Names: Use generic names only in referring to drugs, followed in parentheses after first mention by any commonly used generic variant. Abbreviations: Follow the list of abbreviations given in "Uniform Requirements for Manuscripts Submitted to Biomedical Journals" (see section on References). For additional abbreviations, consult the CBE Style Manual (available from the Council of Biology Editors, 9650 Rockville Pike, Bethesda, Maryland 20814, USA) or other standard sources. We encourage authors to minimize the use of abbreviations except where they are routinely employed and the full term would be cumbersome (eg MPTP). Spelling: American spelling is used throughout the Journal. References Movement!Disorders complies with the reference style given in "Uniform Requirements for Manuscripts Submitted to Biomedical Journals". (See Annals of Internal Medicine 1982;96:766-771, or British Medical Journal 1982:284:1766-1770.) References are to be cited in the text by number, and in the list of References they are to be numbered in the order in which they are cited. The reference section should be double-spaced at the end of the text, following the sample formats given below. Provide all authors' names when fewer than seven; when seven or more, list the first three and add et al. Provide article titles and inclusive pages. Accuracy of reference data is the responsibility of the author. For abbreviations of journal names, refer to List of Journals Indexed in Index Medicus (available from the Superintendent of Documents, U.S. Government Printing Office, Washington DC 20402, USA, DHEW Publication No. (NIH) 83-267; ISSN 00933821). Sample References " !Journal article: 1. Krack P, Benzzzouz A, Pollak P, et al. Treatment of tremor in Parkinson’s disease by Subthalamic nucleus stiumulation. Mov Disord 1998; 13: 907-914. " !Book: 2.Fahn S, Jankovic J, editors.!Principles and Practice of Movement Disorders, Philadelphia, Churchill Livingstone, 2010, pp 96. " !Chapter in a book: 3. Olanow CW. Hpyerkinetic Movement Disorders. In: Fauci A, Braunwald E, Kasper D, Hauser S, Longo D, Jameson JL, Loscalzo J. Eds. Harrison’s Textbook of Medicine 17th edition. 2008; p2560-2565.!!!!!!!! Accepted Articles: Materials Required for Publication After acceptance, please check to be sure that you have submitted your signed copyright transfer and author consent form as well as permissions forms (if applicable). Authors using images of their patients, whether in artwork or video format, must submit a copy (signed by the corresponding author) of the copyright transfer and author consent form. A sample form is available to authors on Manuscript Central. Proofs Proofs must be returned within 3 days of receipt; late return may cause a delay in publication of an article. Please check text, tables, legends, and references carefully. To expedite publication, page proofs rather than galleys will be sent electronically to the author, and it may be necessary to charge for alterations other than correction of printing errors. E-mail proof pages to: MD Production Editor, Movement Disorders, John Wiley & Sons, Inc., Wiley-Blackwell, 111 River St., Mail Stop 8-02, Hoboken, NJ 07030-5774, USA. E-mail:[email protected]!#$%&'()*$+,-.)+/0&'1234)$5. For Video Clips or Pictures of Patients (U.S. Contributors Only): The United States Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) According to HIPAA, the following core elements must be included in the consent form: 1. A specific and meaningful description of the information to be used 2. The name of the Physician and/or Hospital allowed to disclose the information 3. That the video clip and/or photograph will be submitted for publication in a peer-reviewed medical journal 13/02/27 15:34Movement Disorders - Author Guidelines - Wiley Online Library Página 9 de 9http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257/homepage/ForAuthors.html 4. That the video clip and/or photograph will eventually be used by the readers of a peer-reviewed medical journal for educational purposes 5. An expiration date that relates to the individual or the purpose of the use or disclosure 6. The individual’s signature and the date the authorization is signed. In addition, the patient’s consent form should include the following: 1. A statement that the Patient has the right to revoke his or her consent in writing 2. A statement regarding whether the Physician has the ability to condition medical treatment on the Patient’s giving such consent 3. A statement that information, once disclosed, may be subject to further disclosure by the recipient journal, in which case confidentiality would no longer be assured. The consenting party must understand, additionally, that in some cases the video might be re-presented elsewhere because the journal has policies that allow permissions and/or use copyrighted materials with other educational organizations. The consenting party must understand that in such a case the signed author’s consent form may be shared with this third party and the consenting party consents to this sharing of information for educational purposes. ! OnlineOpen OnlineOpen is available to authors of primary research articles who wish to make their article available to non-subscribers on publication, or whose funding agency requires grantees to archive the final version of their article. With OnlineOpen, the author, the author's funding agency, or the author's institution pays a fee to ensure that the article is made available to non-subscribers upon publication via Wiley Online Library, as well as deposited in the funding agency's preferred archive. For the full list of terms and conditions, see"##$%&&'()*+,-)(-*)(./0/+12,3&,-)(-*,$*-45-)(-*5$*-67*/38 9"##$%&&'()*+,-)(-*)(./0/+12,3&,-)(-*,$*-45-)(-*5$*-67*/38:. Any authors wishing to send their paper OnlineOpen will be required to complete the payment form available from our website at: "##$8%&&,-)(-*)(./0/+1'()*+12,3&,-)(-*5$*-5/;*/!9"##$8%&&,-)(-*)(./0/+1'()*+12,3&,-)(-*5$*-5/;*/:. Prior to acceptance there is no requirement to inform an Editorial Office that you intend to publish your paper OnlineOpen if you do not wish to. All OnlineOpen articles are treated in the same way as any other article. They go through the journal's standard peer-review process and will be accepted or rejected based on their own merit.