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dose of L-dopa and utilize more frequent doses during the 24-h day; combining it with a dopamine agonist or a long-acting preparation may be helpful Sometimes temporarily withdrawing L-dopa and at the same time substituting other medications may reduce the on-off phenomenon Based on the notion that alimentary-derived amino acids antagonize the clinical effects of L-dopa, the use of a low-protein diet has been advocated as a means of controlling the motor uctuations described above (Pincus and Barry) Symptoms can sometimes be reduced by the simple expedient of eliminating dietary protein from breakfast and lunch Moreover, this dietary regimen may permit the patient to reduce slightly the total daily dose of L-dopa Such dietary manipulation is worth trying in appropriate patients; it is not harmful, and most of our patients with advance disease who have persisted with this diet have reported improvement in their symptoms or an enhanced effect of L-dopa Surgical Measures Until recently, success with L-dopa had practically replaced the use of the ablative surgical therapy pioneered by Cooper This involved the stereotactic placement of lesions in either the globus pallidus, ventrolateral thalamus, or subthalamic nucleus, contralateral to the side of the body chie y affected The best results were obtained in relatively young patients, in whom unilateral tremor or rigidity rather than akinesia were predominant The symptoms that responded least well to operation (and indeed to treatment with L-dopa) in Cooper s patients were postural imbalance and instability, paroxysmal akinesia, bladder and bowel disturbances, dystonia, and speech dif culties In the last two decades, through the work of Laitinen and others, this mode of therapy has been revived and advanced by the newer technique of implanted electrical stimulators Both the ablative approach and the implantation of electrodes involve the placement, under precise stereotactic control, of a lesion or a wire in the posterior and ventral (medial) part of the subthalamic nucleus or the globus pallidus Improvement of parkinsonian symptoms is reliably effected, particularly on the side opposite the procedure Also, there is in most patients an enhanced responsiveness to L-dopa and a reduction of drug-induced dyskinesias In patients who have been studied for more than a few years after the unilateral ablative procedure, the bene cial effects on dyskinesias contralateral to the operation are sustained to some extent, but not in the ipsilateral limbs The improvement in off-state bradykinesia is lost after 2 or so years and any betterment in axial rigidity and imbalance abates in many patients within a year of operation, as reported by Gregory and by Lang et al In a randomized trial comparing pallidotomy to continued medical treatment of patients with dyskinesias, bradykinesia, or severe uctuations in response to L-dopa, de Bie and colleagues demonstrated a clear improvement in motor function after surgery, while the group treated with medication continued to worsen These improvements are in part due to the ability to reduce the dose of L-dopa Most groups have abandoned the pallidum as a surgical target in favor of the subthalamic nucleus The technique of high-frequency electrical stimulation has given probably better results than surgical ablation It is now used almost exclusively In particular, stimulation of the subthalamic nucleus has produced improvement in all features of the disease but least of all in gait and balance (Limousin et al) A study by The Deep-Brain Stimulation for Parkinson s Disease Group has demonstrated at least short-term bene t in motor uctuations after the bilateral implantation of stimulating electrodes in both subthalamic nuclei, but the durability of this effect is not known The patients.

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