Rapport d'étape évaluation de la stimulation cérébrale profonde dans la maladie de parkinson idiopathique - Progress report : evaluation of deep brain stimulation in idiopathic Parkinson’s disease - Summary

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Posted on Jun 01 2002 A summary statement in English will be available in due course. Posted on Jun 01 2002

Sujets

• Neurochirurgie
• Gériatrie
• Maladie neurodégénérative

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• Publié par: haute-autorite-sante-accreditation-medecins
• Publié le: 01 juin 2002
• Nombre de lectures: 18
• Licence : En savoir +
  Paternité, pas d'utilisation commerciale, partage des conditions initiales à l'identique
• Langue: English

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                  PROGRESS REPORT : EVALUATION OF DEEP BRAIN STIMULATION IN IDIOPATHIC PARKINSON’S DISEASE        J UNE 2002                                        S ERVICE EVALUATION DES TECHNOLOGIES  

J UNE 2002   Progress report: evaluation of deep brain stimulation in idiopathic Parkinson’s disease  

    I NDOOICTUNRT       Medicine today is seeing very rapid development of new technologies for the prevention, diagnosis and treatment of disease. Decision-makers in the health service and health care professionals have to make choices and define strategies on the basis of criteria of safety, efficacy and benefit.   The National Agency for Accreditation and Evaluation in Health (ANAES) evaluates these

strategies, produces a summary of available information and disseminates conclusions to all

partners involved in health care. Its role is to provide assistance with the individual and collective decision-making process:

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it informs the public authorities about the state-of-the-art in science, its implications for medicine, organisation and financing, and its impact on matters of public health; it helps health care establishments provide the best response to patients’ needs in order to improve health care; it helps health professionals define and implement the best strategies for diagnosis and treatment, in conformity with the criteria to be met.

  This document fulfils this mission. The technological and economic information it contains has been independently produced using rigorous scientific methods and comes from a review of the international literature and from consultation with experts.    

  Professor Yves Matillon Executive Director

BACKGROUND    High- frequency deep brain stimulation is a form of functional surgery which was pioneered in the late 1980s. One or two electrodes are implanted in target nuclei in the brain, where they emit high frequency electrical impulses to interfere with abnormal electrical signal sequences. The three targets used at present are the ventral intermediate nucleus of the thalamus (VIM), the globus pallidus internus (Gpi) and the subthalamic nucleus (STN). The technique is an alternative to lesional surgery, which destroys these nuclei.   Deep brain stimulation is indicated in a small population of patients with Parkinson's disease for whom standard treatment has failed. It is an emerging technique that changes the prospects for treating this disease, but its efficacy and safety have still to be evaluated.   ANAES has produced a progress report on deep brain stimulation at the request of the French Hospital and Care Organisation Directorate (DHOS). Efficacy, safety and surgical technique were studied for the procedure, but not cost nor arrangements for care. 

  METHODS    The French- and English- language clinical literature on deep brain stimulation in patients with Parkinson’s disease was reviewed (from 1996 to 2002). The results of this critical appraisal of the literature were submitted to a multidisciplinary working group, and discussed with them during a joint meeting. Comments on the report produced by the working group were solicited from a second expert group of peer-reviewers.

  RESULTS    Critical appraisal of the literature   Selection and design of the clinical trials Ten clinical trials were identified: - Three were randomised controlled clinical trials. Two of them compared lesional surgery with deep brain stimulation, and one compared unilateral with bilateral stimulation; - Two non-randomised trials compared stimulation of the Gpi and STN; - Five were case series studying one or more target nuclei. Three review papers addressed surgery in Parkinson's disease, while a fourth dealt specifically with deep brain stimulation. The clinical trials were poorly designed: - Only one randomised controlled trial described the hypothesis being tested, and calculated how many patients were needed to test this hypothesis; - Populations studied varied according to the trial. Patient selection criteria were disparate and rarely given in any detail; - Surgical procedures were specific to each centre, even in the multicentre trials ; - There were many different endpoints, mostly clinical scores, some of which had been adapted for local use. The primary endpoint was defined in only one trial; - Descriptions of the evaluation conditions (number of assessors, presence of blinding) were often vague, and they differed from trial to trial; - Efficacy and safety results were not always reported. More specifically, adverse events were not reported in detail, and they were not ordered by severity; - Patient follow- up did not exceed one year.

Population to be treated   The consensus conference on Parkinson's disease held by ANAES in 2000 decided that the indications of deep brain stimulation are very restricted. Patients have to be suffering from severe Parkinson's disease which no longer responds to medical treatment, but must retain good sensitivity to levodopa therapy. They have to be physically and mentally fit enough for surgery. It is estimated that every year there are between 500 and 1000 new patients who might benefit from deep brain stimulation. An ongoing epidemiological study should give a precise figure.   Efficacy and safety   The lack of properly designed trials hampers the assessment of the efficacy and safety of deep brain stimulation. We cannot draw conclusions from existing clinical trials on the theoretical advantages of stimulation, i.e. its efficacy compared with lesional surgery or with optimum medical therapy, the possibility of bilateral stimulation without increasing the complications, and its reversibility. The real efficacy of deep brain stimulation is not known. Results of clinical trials suggest that stimulation of the Gpi or STN is effective in the short-term against the symptoms of the disease. Stimulation of the VIM is only effective against tremor. At this stage of development it is impossible to predict whether the effects will persist in the long-term, or to decide on the best target (Gpi, STN). Safety assessment had to be based on incomplete descriptive trials. There is a problem with under-reporting of serious events during clinical trials. Three types of adverse events have been reported due to (i) surgery (haemorrhage), (ii) medical device (infection, dysfunction) and (iii) stimulation parameters. Further studies are needed to investigate the complications caused by stimulation, which affect the patient’s functional, cognitive or behavioural status.   A complex, location-specific surgical procedure   Deep brain stimulation is a form of stereotactic surgery involving a complex sequence of diagnostic and therapeutic actions. Surgery has to be carried out in a hospital with appropriate high-technology equipment and an experienced multidisciplinary team with the right skills. The literature review revealed - and the experts agreed - that the surgical procedure is specific to each centre. No clinical trials have assessed how surgical technique impacts on clinical results.   Opinion of the working group   The experts unanimously agreed that deep brain stimulation is effective, in view of the amplitude of the therapeutic effect they observed in their own practice. In France, the STN is tending to become the preferred target. The experts recognised that adverse events are not reported in sufficient detail, and that they need to be graded by severity. The complications need to be investigated further, particularly behavioural and metabolic disorders. At the current stage of development of the technique, the experts fe lt that surgeons should remain free to choose from the various surgical options in use so long as the technique is effective and has a low level of morbidity, and that they should find ways of collecting this information.    

CONCLUSIONS    According to the current state-of-the-art, deep brain stimulation is feasible. However, the benefit-risk ratio of this form of treatment has not yet been properly assessed in the indications proposed.   At this stage, expert centres need to be involved in evaluating the technique, so that they can provide the safety and efficacy information required, which is essential to any assessment of the further development of the procedure.     PERSPECTIVES   

Cohort study   The first priority is to carry out a longitudinal prospective cohort study with the participation of all centres, in order to observe, as closely as possible, the results of current practices. Because the questions to be answered are complex, the study needs to be very precisely defined and its objectives have to be stated clearly. The design should allow very careful patient selection. The primary endpoint should be an assessment of motor performance in daily life. A quality-of- life scale should be an important secondary endpoint. The study should also record the main elements of the surgical technique in each centre so that any differences can be identified and assessed. Finally, there needs to be a rigorous search for adverse events so they can be listed and quantified.   Clinical trial   Properly designed clinical trials are needed to assess this new technique. Future trials should be multicentre, randomised controlled trials, including enough patients to test the research hypothesis and, if possible, should comprise blinded assessment and long-term follow-up. Serious adverse events need to be evaluated thoroughly. As such trials are difficult to carry out, objectives need to be prioritised beforehand and rigorous follow- up is imperative.   A first randomised controlled clinical trial comparing deep brain stimulation with optimum medical therapy is needed. After the indication for surgery has been confirmed, patients could be randomised into two groups, one of which would undergo surgery immediately while the other would have surgery postponed for a year. This would allow both treatment groups to be studied during that year.   If the benefit of deep brain stimulation is confirmed, trials will be needed to determine the best target (Gpi or STN), and the best surgical technique.   Medical device vigilance   The fact that there have been few medical device vigilance reports, and from only a few centres, suggests under-reporting. Teams need to become more aware and involved as medical device vigilance incidents complement adverse events collected during clinical trials.    

Participating centres   Until there is enough data to determine a benefit-risk ratio, the technique should only be performed by specialist teams who have mastered both the procedure and the management of Parkinson's disease, and who will be involved in evaluating the technique.     The full report (in French) can be downloaded from the ANAES website:   http://www.anaes.fr  or http://www.sante.fr          THE POSITIONS AND RECOMMENDATIONS EXPRESSED IN THIS DOCUMENT ARE THOSE OF ANAES, AND NONE OF THE EXPERTS CONSULTED IS REGARDED AS INDIVIDUALLY RESPONSIBLE FOR THEM.        

Neurosurgeon  Neurosurgeon  Neurologist  Neurosurgeon  CEDIT 1   Neurologist  Neurologist  AFSSAPS 2    Pharmacologist/neurologist  Neurologist 

Working group :   Professor Serge Blond Lille Professor Alim Louis Benabid Grenoble Professor Emmanuel Broussolle Lyon Professor Philippe Cornu Paris Annick Courtay Paris Professor Philippe Damier Nantes Professor Patrick Davous Argenteuil Pascal di Donato Saint-Denis Professor Olivier Rascol Toulouse Professor François Viallet Aix-en-Provence       Peer review group:   Dr. Frédérique Brudon Neurologist Villeurbanne Professor Gilles-Louis Defer Neurologist Caen Professor Roger Gil Neurologist Poitiers Dr. Sylvie Gillier General practitioner Strasbourg Professor Jean-Jacques Lemaire Neurosurgeon Clermont-Ferrand Professor Philippe Paquis Neurosurgeon Nice Professor Jean-François Payen Intensivist Grenoble Professor Alain Rougier Neurochirurgie Bordeaux Professor Christine Tranchant Neurologist Strasbourg Dr. Georges Zöllner Radiologist Strasbourg     The clinical literature analysis was carried out and the report produced by Dr. Marie -Claude Hittinger, under the supervision of Dr. Bertrand Xerri, Head of the Technology Assessment Department . Documentary research was carried out by Nathalie Dunia, assisted by Sylvie Lascols . Secretarial services were provided by Hélène Robert-Rouillac .   We would like to thank the members of ANAES’ Scientific Council who kindly reread this document and provided useful criticism and, in particular, Paul Landais, who acted as rapporteur.          

                                                  1  Comité d'Evaluation et de Diffusion des Innovations Technologiques- the French Assistance Publique - Hôpitaux de echnol tion Committee  2  Agence Française de     P S a é r c is u   r ( it A é P   - S H an P i ) t   a T ire des o P g ro y d E u v it a s l   u d a e Santé- Agency for Health Product Safety