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ARTICLES: W.M.M. Schüpbach, D. Maltête, J. L. Houeto, S. Tezenas du Montcel, L. Mallet, M. L. Welter, M. Gargiulo, C. Béhar, A. M. Bonnet, V. Czernecki, B. Pidoux, S. Navarro, D. Dormont, P. Cornu, and Y. Agid Neurosurgery at an earlier stage of Parkinson disease: A randomized, controlled trial Neurology 2007; 68: 267-271 [Abstract] [Full text] [PDF]

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Yves Agid, W.M.M. Schüpbach, MD ; D. Maltête, MD ; J.L. Houeto, MD   (8 May 2007)

Neurosurgery at an earlier stage of Parkinson disease

Richard J. Beukers, Martijn Weisfelt, Rob M.A. de Bie   (8 May 2007)

Reply from the Authors 8 May 2007
Yves Agid, Centre d Investigation Clinique, Inserm U 679 47 Bd de l hopital 75651 Paris CEDEX 13, France, W.M.M. Schüpbach, MD ; D. Maltête, MD ; J.L. Houeto, MD Send Correspondence to journal: Re: Reply from the Authors agid{at}ccr.jussieu.fr Yves Agid, et al.	We thank Drs de Bie, Beukers, and Weisfelt for commenting on our article on subthalamic nucleus stimulation (STN-S) at an earlier stage of Parkinson disease (PD). [1] They draw attention to behavioral and psychosocial problems encountered in STN-S. [2) We agree that STN-S is not without risks. However, it is a powerful treatment improving motor signs and quality of life (QoL). We have previously addressed the issue of behavioral and psychosocial problems in STN-S. [3, 6] de Bie et al question the validity of the self-rating of QoL because of possible cognitive or behavioral adverse effects after neurosurgery and due to a placebo effect. Extensive neuropsychological testing did not reveal cognitive decline in our patients. We did not perform the same assessments as Smeding et al and cannot exclude subtle alterations in certain specialized cognitive tests.[2] However, any cognitive deterioration can be expected to result in worse QoL, especially in the domain of the part of the PDQ-39 referring to cognition. This was not the case in our study. de Bie et al write that all ten of our surgically treated patients had psychiatric problems. This is not correct. Because transient postoperative hypomania and depression sequentially occurred in one patient, only 7 out of 10 patients operated on had postoperative psychiatric problems compared to 5 out of 10 non-operated patients (depression [n=3], hypomania [n=2]). Most psychiatric problems had been resolved by the end of the study. Therefore, we do not think that transient hypomania interfered with QoL self-rating 18 months after surgery. Similarly, the long time between surgery and the final assessment makes a placebo effect unlikely. Motor symptoms “on” medication rated during levodopa challenge were similar in both treatment groups. Yet, QoL improved among surgically treated patients, likely due to the improvement of motor fluctuations and dyskinesias (UPDRS IV). de Bie et al wish to know whether off-time was reduced with stimulation. Indeed, assessment of UPDRS item 39 shows a significant off-time reduction among surgically treated patients. Our study was a pilot trial providing evidence in favor of STN-S in early stage PD (less than 10 years duration). As strict inclusion criteria were applied, our patients represent a highly selected population. We agree that the issue is not settled yet and our findings need to be confirmed; we are currently undertaking a large randomized controlled multicenter study in Germany and France (EARLYSTIM trial) to assess QoL in patients with early stage PD and STN-S. References 6. Houeto JL, Mesnage V, Mallet L, et al. Behavioural disorders, Parkinson's disease and subthalamic stimulation. J Neurol Neurosurg Psychiatry 2002;72:701-707. Disclosure: The authors report no conflicts of interest.
Neurosurgery at an earlier stage of Parkinson disease 8 May 2007
Richard J. Beukers, Academic Medical Center PO box 22660, 1100 DD, Amsterdam, The Netherlands, Martijn Weisfelt, Rob M.A. de Bie Send Correspondence to journal: Re: Neurosurgery at an earlier stage of Parkinson disease r.m.debie{at}amc.uva.nl Richard J. Beukers, et al.	We compliment Schüpbach et al who report the results of a randomized controlled trial for the use of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients at an early stage of Parkinson disease (PD). [1] There are some concerns that we would like addressed. First, previous studies have shown STN-DBS to be associated with adverse effects on cognition, mood and behavior. [2] An evaluation of STN-DBS effects on social adjustment showed that 10 of 29 patients (35%) had a new psychiatric disorder following surgery. [3] Marital conflicts occurred in 17 of 24 couples, and only nine of 16 patients went back to work after surgery. These adverse effects are only briefly addressed in the present paper, even though all 10 surgically treated patients developed transient (n=9) or permanent (n=1) psychiatric problems. Second, the primary outcome was quality of life assessed with the Parkinson Disease Questionnaire (PDQ-39). This is a self-report scale, therefore the results may be affected by the large proportion of patients with adverse affective — often euphoria — or cognitive effects. [4] Because patients were aware of the treatment allocation, a large part of the measured effect could have been due to the placebo effect which can be very strong for quality of life measurements in PD. [5] Motor symptoms and activities of daily living were assessed after withdrawal of dopaminergic medication (off-phase) and after administration of levodopa (on-phase). Patients in the surgical group were only rated during stimulation. In previous studies evaluating STN-DBS in advanced PD, where off-periods are unavoidable, this approach seems reasonable. However, in the earlier stages of the disease, optimizing medical treatment is expected to reduce off-time. Therefore, the duration of off-time should be taken into account when comparing surgery with pharmacological treatment in early PD. In the present study the severity of parkinsonian motor disability on medication was similar in the medical and surgical groups throughout the study. [1] PD is a heterogeneous disorder and rate of disease progression can vary greatly between patients. The use of STN-DBS at an early stage of PD will subject patients to unnecessary risks. In our opinion it is open to discussion whether a beneficial effect on group level warrants the risk of severe surgical complications and neurobehavioral side effects for the individual patient. References 1. Schüpbach W, Maltete D, Houeto J et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized controlled trial. Neurology 2007;68:267-271. 2. Smeding HM, Speelman JD, de Koning-Haanstra M et al. Neuropsychological effects of bilateral STN stimulation in Parkinson disease: A controlled study. Neurology 2006;66:1830-1862. 3. Schupbach M, Gargiulo M Welter ML et al. Neurosurgery in Parkinson disease: A distressed mind in a repaired body? Neurology 2006;66(12):1811-1816. 4. Gronchi-Perrin A, Viollier S, Ghika J, et al. Does subthalamic nucleus deep brain stimulation really improve quality of life in Parkinson’s disease. Mov Disord 2006;21:1465-1468. 5. McRae C, Cherin E, Yamazaki TG, et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 2004;61:412-420. The authors have nothing to disclose.