FROM EXPERIMENTATION TO THE SURGICAL TREATMENT OF PARKINSON'S DISEASE: PRELUDE OR SUITE IN BASAL GANGLIA RESEARCH? CHRISTIAN E. GROSS 1 *, THOMAS BORAUD, DOMINIQUE GUEHL, BERNARD BIOULAC and ERWAN BEZARD Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Universite de Bordeaux 2, 146 rue Leo Saignat, 33076, Bordeaux Cedex, France (Received 26 February 1999) AbstractÐParkinson's disease remains one of the greatest challenges facing those who work in the ®eld of neurological research. Although the development of levodopa treatment revolutionised management of this debilitating diseases, no eective long-term therapy has yet been found. With recent advances in the understanding of basal ganglia physiopathology and the experimental demonstration of the ecacy of certain surgical procedures, there is a renewed interest in the surgical approach. This paper provides a chronological overview of the history of parkinsonian surgery and discusses the principal surgical options at our disposal today. These take three main forms: ablation (thalamotomy, pallidotomy and subthalamotomy); cell graft and gene therapy (mainly in the striatum); and deep brain stimulation (of the thalamus, globus pallidus pars internalis and the subthalamic nucleus). Our knowledge of basal ganglia function and our conception of how motor information is processed by this network have evolved parallel to the development of surgical techniques. Recent results from both clinical and experimental studies underline the complexity of the physio- pathological mechanisms which generate parkinsonian symptomatology and lead us to question our assumption that each class of clinical signs (tremor, akinesia, rigidity, levodopa-induced dyskinesias ... ) is produced by a speci®c and separate mechanism. In the same way, comparison of the electrophysiological and biochemical eects of the dierent tech- niques induced in brain function vary considerably. This complex world of interaction and interconnection is a labyrinth that we are still far from compre- hending in its entirety. All the more reason, in consequence, for extending experimental investigation into the impact of any new therapy before proposing its clinical application. # 1999 Elsevier Science Ltd. All rights reserved CONTENTS 1. Introduction 510 2. Surgical ablation 510 2.1. The prestereotactic era 510 2.2. The ®rst stereotactic era 511 3. Grafting 514 3.1. Adrenal and mesencephalic transplants 514 3.2. What have we learnt from grafting? 516 3.3. Future trends 517 4. The comeback of surgical ablation 518 5. Deep brain stimulation 521 5.1. Stimulation of the thalamus 521 5.2. Stimulation of the STN and GPi 522 5.3. What have we learnt from DBS? 522 6. Concluding remarks 525 Acknowledgements 526 References 526 Progress in Neurobiology Vol. 59, pp. 509 to 532, 1999 # 1999 Elsevier Science Ltd. All rights reserved Printed in Great Britain 0301-0082/99/$ - see front matter PII: S0301-0082(99)00015-5 www.elsevier.com/locate/pneurobio 1 christian.gross@umr5543.u-bordeaux2.fr * Corresponding author. 509