Based on the principle that alimentary-derived amino acids compete for absorption of l-dopa, the use of a low-protein diet has been advocated as a means of controlling the motor fluctuations (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 advanced disease who have persisted with this diet have reported improvement in their symptoms or an enhanced effect of l-dopa. A novel observation by Pierantozzi and colleagues has been that the absorption of l-dopa may be influenced by the presence of gastric Helicobacter pylori infection and that eradication of the organism was associated with longer “on” time.
Until recently, success with l-dopa had entirely replaced the use of the ablative surgical therapy pioneered by
Cooper 50 years ago. The surgical approaches involved the placement of lesions in the globus pallidus, ventrolateral thalamus, or subthalamic nucleus, contralateral to the side of the body chiefly 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 surgical therapy in Cooper’s patients were postural imbalance and instability, paroxysmal akinesia, bladder and bowel disturbances, dystonia, and speech difficulties. These remain the most resistant symptoms with modern surgical techniques as well.
Through the work of Leskell and others as described by Laitinen, this mode of therapy has evolved into stereotactically guided procedures and advanced by the technique of implanted electrodes with an electrical stimulator implanted in the chest wall (deep brain stimulation, DBS). For the treatment of Parkinson disease, the electrodes are placed in the posterior and ventral (medial) parts of the subthalamic nucleus or in the internal segment of the globus pallidus. Most patients who have DBS experience enhanced responsiveness to l-dopa and a reduction of drug-induced dyskinesias. Bilateral stimulation of the subthalamic nucleus has produced improvement in most features of the disease, including in bradykinesia, that is lost after several years, but as mentioned, there is generally little benefit for impaired gait and balance (Limousin et al; Weaver et al, who conducted a more extensive study but for only 6 months). A study by the Deep-Brain Stimulation for
Parkinson’s Disease Group demonstrated at least short-term benefit in motor fluctuations after the bilateral implantation of stimulating electrodes in the subthalamic nuclei and the durability of this effect with continued DBS in subsequent studies ranged from 2 to 7 years.
The ideal candidates for DBS are those in whom, after several years, there is a failure of medications to adequately relieve symptoms but especially if there are unmanageable dyskinesias that result from l-dopa. Restated, the typical patient who will derive benefit from deep-brain stimulation is one who, to maintain mobility, requires a dose of l-dopa that produces unacceptable dyskinesias and who is constantly cycling between on and off periods. A randomized, blinded trial by Deuschl and colleagues confirmed this effect and demonstrated an overall improvement in the quality of life at 6 months. The benefit with bilateral stimulation of the globus pallidus has been essentially equivalent to results from subthalamic stimulation (Follett et al). Dystonia, when present as part of the native disease or as a result of medication, may also benefit from this treatment, perhaps more so with pallidal stimulation. The effect on nonmotor symptoms such as pain are less predictable but our patients have not noticed much improvement unless the pain was due to dystonia. A small series reported by Cury and coworkers came to essentially the same conclusion.