Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson's disease (INTREPID): a multicentre, double-blind, randomised, sham-controlled study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. METHODS: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. FINDINGS: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. INTERPRETATION: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. FUNDING: Boston Scientific.

Rapid assessment of gait and speech after subthalamic deep brain stimulation.

BACKGROUND: Describe a rapid assessment for patients with idiopathic Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus reporting worsening speech and/or gait problems. METHODS: We retrospectively reviewed 29 patients that had improvement in gait and/or speech within 30 min after turning stimulation off. Clinical data analyzed include unified PD rating scale motor scores and stimulation parameters before and after adjusting stimulation. All patients received electrode efficacy and side effect threshold testing. Stimulation parameters were adjusted to maximize efficacy, avoid side effects, and maximize battery longevity. RESULTS: Turning stimulation off revealed reversible speech and/or gait stimulation side effects within 30 min. Focusing on six factors revealed stimulation modifications that improved motor symptoms, eliminated stimulation side effects, and reduced battery drain. Primary stimulation parameters modified were cathode selection and pulse width reduction. CONCLUSIONS: Stimulation-induced side effects impacting gait and speech can be identified within 30 min. A systematic evaluation can distinguish disease progression from reversible stimulation side effects and improve motor outcomes over the long term.

Parkinson disease: not just a movement disorder.

Nonmotor symptoms are common in Parkinson disease and can significantly worsen the health and quality of life of the patient and family members. These symptoms can be broadly categorized as sensory, autonomic, cognitive-behavioral, and sleep-related. Clinicians can improve the care of these patients by recognizing and addressing these problems.

Deep brain stimulation and the ethics of protection and caring for the patient with Parkinson's dementia.

Deep brain stimulation (DBS) is an effective neurosurgical treatment for patients with advanced Parkinson's disease (PD) suffering from motor complications that are refractory to further medication management. DBS requires an invasive procedure of implanting brain electrodes while awake, followed by implantation of neurostimulators under general anesthesia. The neurostimulator requires battery monitoring and replacement approximately every 3 to 5 years. These two elements of the technology provide numerous decision points about continuing therapies that can involve ethical choices. Although motor function can be improved with subthalamic nucleus (STN) DBS, the long-term risks of living with implanted hardware should be carefully evaluated for patients with diminishing cognitive capacity. We describe two cases where ethical dilemmas occurred postoperatively as a result of cognitive decline and describe salient ethical dimensions that illustrate the need for a proactive postoperative plan for supervision as a prerequisite for surgery to include neuropsychological testing to predict the likelihood of net benefit to the patient and family beyond just motor improvement.

Gait changes after deep brain stimulation for Parkinson's disease in a patient with cervical myelopathy.

Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment for advanced Parkinson's disease. We present a patient with significant gait problems due to Parkinson's disease (PD) who underwent STN DBS. Gait worsened after surgery despite significant improvement in parkinsonian signs, due to underlying spasticity previously overshadowed by his parkinsonian motor symptoms. This case illustrates an emergence of dysfunction in gait in a patient with otherwise improved function and reinforces the need for an interdisciplinary approach to care of these patients.

Deep brain stimulation hardware complications: the role of electrode impedance and current measurements.

Deep brain stimulation (DBS) is an effective therapy for advanced Parkinson's disease patients. Successful DBS outcomes depend on appropriate patient selection, surgical placement of the lead, intact hardware systems, optimal programming, and medical management. Despite its importance, there is little guidance in reference to hardware monitoring, hardware troubleshooting, and patient management. Technical manuals produced by the hardware manufacturer (Medtronic, Minneapolis, MN) are not presented in an applied clinical format, making impedance and current measurements difficult to interpret when the results are not straightforward. We present four patients with evolving DBS hardware complications that occurred during long-term follow-up, that shaped our clinical protocol for long-term care management and hardware troubleshooting.

Parkinson disease: managing a complex, progressive disease at all stages.

Parkinson disease is a complex neurodegenerative disease with both motor and nonmotor symptoms. Levodopa remains the mainstay of therapy but is associated with motor complications as the disease progresses. A levodopa-sparing strategy may reduce or delay the onset of motor complications. New medical and surgical therapies offer improved control of motor complications in advancing disease. Recognition and treatment of nonmotor symptoms can improve quality of life throughout the course of the disease.

Bilateral subthalamic nucleus stimulation after bilateral pallidotomies in a patient with advanced Parkinson's disease.

A 54-year-old man with advanced Parkinson's disease (PD) presented to our institution in early 2000. He had undergone a right pallidotomy in 1994, a left pallidotomy in 1996, and bilateral subthalamic nucleus (STN) electrode implants in 1999. The patient had cervical myelopathy for which he had undergone neck surgery in 1998. We used the Unified Parkinson's Disease Rating Scale (UPDRS) to evaluate motor performance in four states: combinations of stimulation OFF or ON and medication OFF or ON. There was no significant change in motor UPDRS scores with STN stimulation or with medications. Multiple attempts to optimize stimulation parameters and medication dosages did not result in significant and sustained improvement in activities of daily living or motor performance. To our knowledge, this is the first reported case of bilateral STN stimulation after bilateral pallidotomies. The presence of cervical myelopathy and the limited response to anti-Parkinson medications in this patient underscores the importance of patient selection for functional neurosurgery in PD.