Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2–6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3–6 months. In contrast, bilateral STN-DBS at 130–185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.

The peduncolopontine nucleus modulates locomotor activity and dysfunction in this nucleus may be responsible for the gait and postural impairments seen in Parkinson's disease and other movement disorders. We report the first surgical exploration and implantation of deep brain stimulating electrodes of the peduncolopontine nucleus area in two Parkinson's disease patients to examine the safety and the potential benefit of chronic electrical stimulation at this site. Under local anesthesia, the peduncolopontine nucleus was approached from a coronal burr hole using a trajectory that was 78–80° and 62–64° on the coronal and sagittal planes. Microrecordings helped to identify neurons in peduncolopontine nucleus and the adjacent substantia nigra pars reticulata. Chronic deep brain stimulating electrodes were implanted within the peduncolopontine nucleus in a manner similar to that practiced with deep brain stimulating surgery at other targets. Peduncolopontine nucleus neurons were characterized by small and broad multiunits (230 μV, 2.5 ms, 14.6 Hz). Caudal to this area, neurons firing at higher frequency, approximately 70 Hz, characteristic of nigral neuronal discharges, were encountered, followed by 2 mm of cells similar to those recorded in the dorsal peduncolopontine nucleus area. After deep brain stimulating electrodes implantation, acute intraoperative stimulation (up to 3 V) was performed with two stimulation frequencies in each session. Stimulation at 80 Hz has little discernable effect. On the other hand, stimulation at 10 Hz fostered a subjective feeling of ‘well-being’ and a time-locked amelioration of the clinical scores. These findings demonstrate that the stereotactic approach of peduncolopontine nucleus is safe. The target may reliably be identified by microrecordings. Low-frequency stimulation may produce acute improvements in motor function.

Objective: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. Methods: In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. Results: Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged “on-time” duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. Conclusions: These data demonstrate a reversible Helicobacter pylori (HP)–induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics.