Background In many patients with idiopathic Parkinson's disease,treatment with levodopa is complicated by fluctuations betweenan "off" period (also referred to as "off medication"), whenthe medication is not working and the motor symptoms of parkinsonismare present, and an "on" period, when the medication is causingimproved mobility (also referred to as "on medication"), oftenaccompanied by debilitating dyskinesias. In animal models ofParkinson's disease, there is overactivity in the subthalamicnucleus, and electrical stimulation of the subthalamic nucleusimproves parkinsonism. We therefore sought to determine theefficacy and safety of electrical stimulation of the subthalamicnucleus in patients with Parkinson's disease.
Methods We studied 24 patients with idiopathic Parkinson's diseasein whom electrodes were implanted bilaterally in the subthalamicnucleus under stereotactic guidance with imaging and electrophysiologictesting of the location. Twenty were followed for at least 12months. Clinical evaluations included the Unified Parkinson'sDisease Rating Scale, a dyskinesia scale, and timed tests conductedbefore and after surgery, when patients were off and on medications.
Results After one year of electrical stimulation of the subthalamicnucleus, the patients' scores for activities of daily livingand motor examination scores (Unified Parkinson's Disease RatingScale parts II and III, respectively) off medication improvedby 60 percent (P<0.001). The subscores improved for limbakinesia, rigidity, tremor, and gait. In the testing done onmedication, the scores on part III improved by 10 percent (P<0.005).The mean dose of dopaminergic drugs was reduced by half. Thecognitive-performance scores remained unchanged, but one patienthad paralysis and aphasia after an intracerebral hematoma duringthe implantation procedure.
Conclusions Electrical stimulation of the subthalamic nucleusis an effective treatment for advanced Parkinson's disease.The severity of symptoms off medication decreases, and the doseof levodopa can be reduced, with a consequent reduction in dyskinesias.
Source Information
From the Department of Clinical and Biologic Neurosciences, Joseph Fourier University, Grenoble, France (P.L., P.K., P.P., A.B., C.A., D.H., A.-L.B.); the Medical Research Council Human Movement and Balance Unit, Queen Square, London (P.L.); and the Neurology Department, University of Kiel, Kiel, Germany (P.K.).
Address reprint requests to Dr. Pollak at the Department of Clinical and Biologic Neurosciences, Joseph Fourier University, B.P. 217, 38043 Grenoble CEDEX 9, France.
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Lagrange, E., Krack, P., Moro, E., Ardouin, C., Van Blercom, N., Chabardes, S., Benabid, A.L., Pollak, P.
(2002). Bilateral subthalamic nucleus stimulation improves health-related quality of life in PD. Neurology
59: 1976-1978
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Mesnage, V, Houeto, J-L, Welter, M-L, Agid, Y, Pidoux, B, Dormont, D, Cornu, P
(2002). Parkinson's disease: neurosurgery at an earlier stage?. J. Neurol. Neurosurg. Psychiatry
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Bejjani, B.P., Houeto, J.L., Hariz, M., Yelnik, J., Mesnage, V., Bonnet, A.M., Pidoux, B., Dormont, D., Cornu, P., Agid, Y.
(2002). Aggressive behavior induced by intraoperative stimulation in the triangle of Sano. Neurology
59: 1425-1427
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Finelli, D. A., Rezai, A. R., Ruggieri, P. M., Tkach, J. A., Nyenhuis, J. A., Hrdlicka, G., Sharan, A., Gonzalez-Martinez, J., Stypulkowski, P. H., Shellock, F. G.
(2002). MR Imaging-Related Heating of Deep Brain Stimulation Electrodes: In Vitro Study. Am. J. Neuroradiol.
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Moro, E., Esselink, R. J. A., Benabid, A. L., Pollak, P.
(2002). Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation. Brain
125: 2408-2417
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Kleiner-Fisman, G., Saint-Cyr, J.A., Miyasaki, J., Lozano, A., Lang, A.E., Vingerhoets, F.J. G., Villemure, J.G., Ghika, J.
(2002). Subthalamic DBS replaces levodopa in Parkinson's disease. Neurology
59: 1293-1294
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Loher, T J, Burgunder, J-M, Weber, S, Sommerhalder, R, Krauss, J K
(2002). Effect of chronic pallidal deep brain stimulation on off period dystonia and sensory symptoms in advanced Parkinson's disease. J. Neurol. Neurosurg. Psychiatry
73: 395-399
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Charles, P.D., Van Blercom, N., Krack, P., Lee, S.L., Xie, J., Besson, G., Benabid, A.-L., Pollak, P.
(2002). Predictors of effective bilateral subthalamic nucleus stimulation for PD. Neurology
59: 932-934
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Dauper, J., Peschel, T., Schrader, C., Kohlmetz, C., Joppich, G., Nager, W., Dengler, R., Rollnik, J. D.
(2002). Effects of subthalamic nucleus (STN) stimulation on motor cortex excitability. Neurology
59: 700-706
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Moro, E., Esselink, R. J.A., Xie, J., Hommel, M., Benabid, A. L., Pollak, P.
(2002). The impact on Parkinson's disease of electrical parameter settings in STN stimulation. Neurology
59: 706-713
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Rocchi, L, Chiari, L, Horak, F B
(2002). Effects of deep brain stimulation and levodopa on postural sway in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry
73: 267-274
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Vesper, J, Chabardes, S, Fraix, V, Sunde, N, Ostergaard, K
(2002). Dual channel deep brain stimulation system (Kinetra) for Parkinson's disease and essential tremor: a prospective multicentre open label clinical study. J. Neurol. Neurosurg. Psychiatry
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Cunic, D., Roshan, L., Khan, F. I., Lozano, A. M., Lang, A. E., Chen, R.
(2002). Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson's disease. Neurology
58: 1665-1672
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Houeto, J L, Mesnage, V, Mallet, L, Pillon, B, Gargiulo, M, du Moncel, S T., Bonnet, A M, Pidoux, B, Dormont, D, Cornu, P, Agid, Y
(2002). Behavioural disorders, Parkinson's disease and subthalamic stimulation. J. Neurol. Neurosurg. Psychiatry
72: 701-707
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Pogarell, O, Gasser, T, van Hilten, J J, Spieker, S, Pollentier, S, Meier, D, Oertel, W H
(2002). Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study. J. Neurol. Neurosurg. Psychiatry
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Romito, L. M.A., Scerrati, M., Contarino, M. F., Bentivoglio, A. R., Tonali, P., Albanese, A.
(2002). Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease. Neurology
58: 1546-1550
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Bejjani, B-P, Arnulf, I, Houeto, J-L, Milea, D, Demeret, S, Pidoux, B, Damier, P, Cornu, P, Dormont, D, Agid, Y
(2002). Concurrent excitatory and inhibitory effects of high frequency stimulation: an oculomotor study. J. Neurol. Neurosurg. Psychiatry
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