Palliative care and Parkinson's disease : meeting summary and recommendations for clinical research

Introduction: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson’s disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. Methods: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson’s Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. Results: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. Conclusions: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers

Remote telemedicine evaluation of deep brain stimulation candidacy: Retrospective cohort analysis.

ObjectiveTo determine whether initial presurgical evaluation of deep brain stimulation (DBS) candidacy with video telemedicine (VTEL) can reliably predict surgical candidacy (patients who will eventually undergo DBS surgery) and decrease resource utilization when compared to an in-person evaluation.MethodsIn this retrospective, cohort analysis, all out-of-state referrals to the San Francisco Veterans Affairs from 2008 to 2013 for DBS therapy were reviewed and their surgical outcomes were assessed until 2017. Patients were designated as good, borderline, or poor surgical candidates after initial evaluation, and their rates of undergoing DBS were recorded. An assessment of patient travel costs was performed.ResultsThere were 60 out-of-state DBS referrals identified out of the 148 initial presurgical DBS evaluations completed for surgical treatment of dystonia, essential tremor, or Parkinson disease; 24 patients underwent in-person consultation and 36 patients underwent evaluation via VTEL. There was no difference between the rates of undergoing surgical treatment with DBS based on surgical candidacy for patients in the in-person and VTEL cohorts. Patients who underwent initial presurgical screening via VTEL saved time and money.ConclusionsVTEL can be used to facilitate presurgical screening for DBS and saves costs

Pallidal Deep-Brain Stimulation Disrupts Pallidal Beta Oscillations and Coherence with Primary Motor Cortex in Parkinson's Disease.

In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13-20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4-8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression

Clinical outcomes of PD patients having bilateral STN DBS using high-field interventional MR-imaging for lead placement

ObjectiveRecently, an iMRI-guided technique for implanting DBS electrodes without MER was developed at our center. Here we report the clinical outcomes of PD patients undergoing STN DBS surgery using this surgical approach.MethodsConsecutive PD patients undergoing bilateral STN DBS using this method were prospectively studied. Severity of PD was determined using the UPDRS scores, Hoehn and Yahr staging score, stand-sit-walk testing, and the dyskinesia rating scale. The primary outcome measure was the change in UPDRS III off medication score at 6 months. DBS stimulation parameters, adverse events, levodopa equivalent daily dose (LEDD), and DBS lead locations were also recorded. Seventeen advanced PD patients (9M/8F) were enrolled from 2007 to 2009.ResultsThe mean UPDRS III off medication score improved from 44.5 to 22.5 (49.4%) at 6 months (p=0.001). Other secondary outcome measures (UPDRS II, III on medication, and IV) significantly improved as well (p<0.01). LEDD decreased by an average of 24.7% (p=0.003). Average stimulation parameters were: 2.9V, 66.4μs, 154Hz.ConclusionThis pilot study demonstrates that STN DBS leads placed using the iMRI-guided method results in significantly improved outcomes in PD symptoms, and these outcomes are similar to what has been reported using traditional frame-based, MER-guided stereotactic methods

Subthalamic Nucleus Neurons Are Synchronized to Primary Motor Cortex Local Field Potentials in Parkinson's Disease

In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200 Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower-frequency rhythm (phase-amplitude coupling), such that "waves" of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge

Pallidal Deep-Brain Stimulation Disrupts Pallidal Beta Oscillations and Coherence with Primary Motor Cortex in Parkinson's Disease.

In Parkinson's disease (PD), subthalamic nucleus beta band oscillations are decreased by therapeutic deep-brain stimulation (DBS) and this has been proposed as important to the mechanism of therapy. The globus pallidus is a common alternative target for PD with similar motor benefits as subthalamic DBS, but effects of pallidal stimulation in PD are not well studied, and effects of pallidal DBS on cortical function in PD are unknown. Here, in 20 PD and 14 isolated dystonia human patients of both genders undergoing pallidal DBS lead implantation, we recorded local field potentials from the globus pallidus and in a subset of these, recorded simultaneous sensorimotor cortex ECoG potentials. PD patients had elevated resting pallidal low beta band (13-20 Hz) power compared with dystonia patients, whereas dystonia patients had elevated resting pallidal theta band (4-8 Hz) power compared with PD. We show that this results in disease-specific patterns of interaction between the pallidum and motor cortex: PD patients demonstrated relatively elevated phase coherence with the motor cortex in the beta band and this was reduced by therapeutic pallidal DBS. Dystonia patients had greater theta band phase coherence. Our results support the hypothesis that specific motor phenomenology observed in movement disorders are associated with elevated network oscillations in specific frequency bands, and that DBS in movement disorders acts in general by disrupting elevated synchronization between basal ganglia output and motor cortex.SIGNIFICANCE STATEMENT Perturbations in synchronized oscillatory activity in brain networks are increasingly recognized as important features in movement disorders. The globus pallidus is a commonly used target for deep-brain stimulation (DBS) in Parkinson's disease (PD), however, the effects of pallidal DBS on basal ganglia and cortical oscillations are unknown. Using invasive intraoperative recordings in patients with PD and isolated dystonia, we found disease-specific patterns of elevated oscillatory synchronization within the pallidum and in coherence between pallidum and motor cortex. Therapeutic pallidal DBS in PD suppresses these elevated synchronizations, reducing the influence of diseased basal ganglia on cortical physiology. We propose a general mechanism for DBS therapy in movement disorders: functional disconnection of basal ganglia output and motor cortex by coherence suppression

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease.

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease.

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons

Patient Experience with Rechargeable Implantable Pulse Generator Deep Brain Stimulation for Movement Disorders.

Background/aimsNonrechargeable deep brain stimulation implantable pulse generators (IPGs) for movement disorders require surgical replacement every few years due to battery depletion. Rechargeable IPGs reduce frequency of replacement surgeries and inherent risks of complications but require frequent recharging. Here, we evaluate patient experience with rechargeable IPGs and define predictive characteristics for higher satisfaction.MethodsWe contacted all patients implanted with rechargeable IPGs at a single center in a survey-based study. We analyzed patient satisfaction with respect to age, diagnosis, target, charging duration, and body mass index. We tabulated hardware-related adverse events.ResultsDystonia patients had significantly higher satisfaction than Parkinson's disease patients in recharging, display, programmer, and training domains. Common positive responses were "fewer surgeries" and "small size." Common negative responses were "difficulty finding the right position to recharge" and "need to recharge every day." Hardware-related adverse events occurred in 21 of 59 participants.ConclusionPatient experience with rechargeable IPGs was largely positive; however, frustrations with recharging and adverse events were common. Dystonia diagnosis was most predictive of high satisfaction across multiple categories, potentially related to expected long disease duration with need for numerous IPG replacements