A Pilot Study Assessing the Effects of Pallidal Deep Brain Stimulation on Sleep Quality and Polysomnography in Parkinson's Patients.

OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention to treat poorly controlled motor symptoms in Parkinson's disease (PD). Both surgical targets (the subthalamic nucleus and globus pallidus) have proven equally efficacious in treating motor symptoms but unique differences may exist in effects on nonmotor symptoms. Sleep dysfunction, a common disabling symptom in PD, has only been examined directly in the subthalamic target, demonstrating some beneficial changes in sleep quality. We aimed to explore sleep changes after pallidal stimulation; hypothesizing similar benefits would be seen. METHODS: We performed a prospective nonblinded clinical trial evaluating sleep in five PD patients already slated for pallidal DBS pre and six months postimplantation using validated sleep surveys and polysomnograms (PSGs). Surveys included the Epworth sleepiness scale, PD sleep scale, Insomnia severity index (ISI), and RLS severity scale. RESULTS: Most patients had notable improvements in sleep quality as measured by PSG metrics such as sleep efficiency and latency to sleep but they did not reach statistical significance. Most surveys reflected an improvement as well with the ISI scale showing the most promising trend post pallidal DBS (14.4 ± 7.02 vs. 9.0 ± 2.55; p = 0.07). CONCLUSION: In this small pilot trial, pallidal DBS failed to demonstrate statistically significant improvements in sleep metrics postimplantation but did reveal improving trends in several PSG measures including sleep efficiency and latency to sleep onset as well as sleep survey scores. A larger, blinded clinical trial is needed to more definitively determine whether pallidal DBS may benefit sleep.

The Impact of Pallidal and Subthalamic Deep Brain Stimulation on Urologic Function in Parkinson's Disease.

OBJECTIVE: Deep Brain Stimulation (DBS) is an established adjunctive surgical intervention for treating Parkinson's disease (PD) motor symptoms. Both surgical targets, the globus pallidus interna (GPi) and subthalamic nucleus (STN), appear equally beneficial when treating motor symptoms but effects on nonmotor symptoms are not clear. Lower urinary tract symptoms (LUTS) are a common PD complaint. Given prior data in STN-DBS, we aimed to further explore potential benefits in LUTS in both targets. METHODS: We performed a prospective, nonblinded clinical trial evaluating LUTS in PD patients in both targets pre and post DBS using validated urologic surveys. Participants were already slated for DBS and target selection predetermined before study entry. LUTS was evaluated using: the American Urological Association (AUA-SI), Quality of Life score (QOL), Overactive Bladder 8 Questionnaire (OAB-q), and Sexual Health Inventory for Men (SHIM). RESULTS: Of 33 participants, 20 underwent STN DBS and 13 had GPi DBS. Patients demonstrated moderate baseline LUTS. The urologic QOL score significantly improved post DBS (3.24 ± 1.77vs. 2.52 ± 1.30; p = 0.03). Analyzed by target, only the STN showed significant change in QOL (3.20 ± 1.61 vs 2.25 ± 1.33; p = 0.04). There were no other significant differences in urologic scores post DBS noted in either target. CONCLUSION: In PD patients with moderate LUTS, there were notable improvements in QOL for LUTS post DBS in the total sample and STN target. There may be differences in DBS effects on LUTS between targets but this will require further larger, blinded studies.

Generalized motor inhibitory deficit in Parkinson's disease patients who freeze.

Freezing of gait is a disabling symptom of Parkinson's disease (PD) that involves failure to initiate and continue motor activity appropriately. PD disrupts fronto-basal ganglia circuitries that also implement the inhibition of responses, leading to the hypothesis that freezing of gait may involve fundamental changes in both initiation and inhibition of motor actions. We asked whether PD patients who show freezing of gait show selective deficits in their ability to inhibit upper and lower extremity reactions. We compared older healthy controls, older PD controls without freezing of gait, and older PD participants with freezing of gait, in stop-signal tasks that measured the initiation (go trials) and inhibition (stop trials) of both hand and foot responses. When only go trials were presented, all three groups showed similar initiation speeds across lower and upper extremity responses. When stop-signal trials were introduced, both PD groups slowed their reactions nearly twice as much as healthy controls. While this adjustment helped PD controls stop their actions as quickly as healthy controls, PD patients with freezing showed significantly delayed inhibitory control of both upper and lower extremities. When anticipating the need to stop their actions urgently, PD patients show greater adjustments (i.e., slowing) to reaction speed than healthy controls. Despite these proactive adjustments, PD patients who freeze show marked impairments in inhibiting both upper and lower extremity responses, suggesting that freezing may involve a fundamental disruption to the brain's inhibitory control system.

Rescue Procedures after Suboptimal Deep Brain Stimulation Outcomes in Common Movement Disorders.

Deep brain stimulation (DBS) is a unique, functional neurosurgical therapy indicated for medication refractory movement disorders as well as some psychiatric diseases. Multicontact electrodes are placed in "deep" structures within the brain with targets varying depending on the surgical indication. An implanted programmable pulse generator supplies the electrodes with a chronic, high frequency electrical current that clinically mimics the effects of ablative lesioning techniques. DBS's efficacy has been well established for its movement disorder indications (Parkinson's disease, essential tremor, and dystonia). However, clinical outcomes are sometimes suboptimal, even in the absence of common, potentially reversible complications such as hardware complications, infection, poor electrode placement, and poor programming parameters. This review highlights some of the rescue procedures that have been explored in suboptimal DBS cases for Parkinson's disease, essential tremor, and dystonia. To date, the data is limited and difficult to generalize, but a large majority of published reports demonstrate positive results. The decision to proceed with such treatments should be made on a case by case basis. Larger studies are needed to clearly establish the benefit of rescue procedures and to establish for which patient populations they may be most appropriate.

Dysrhythmia of timed movements in Parkinson's disease and freezing of gait.

A well-established motor timing paradigm, the Synchronization-Continuation Task (SCT), quantifies how accurately participants can time finger tapping to a rhythmic auditory beat (synchronization phase) then maintain this rhythm after the external auditory cue is extinguished, where performance depends on an internal representation of the beat (continuation phase). In this study, we investigated the hypothesis that Parkinson's disease (PD) patients with clinical symptoms of freezing of gait (FOG) exhibit exaggerated motor timing deficits. We predicted that dysrhythmia is exacerbated when finger tapping is stopped temporarily and then reinitiated under the guidance of an internal representation of the beat. Healthy controls and PD patients with and without FOG performed the SCT with and without the insertion of a 7-s cessation of motor tapping between synchronization and continuation phases. With no interruption between synchronization and continuation phases, PD patients, especially those with FOG, showed pronounced motor timing hastening at the slowest inter-stimulus intervals during the continuation phase. The introduction of a gap prior to the continuation phase had a beneficial effect for healthy controls and PD patients without FOG, although patients with FOG continued to show pronounced and persistent motor timing hastening. Ratings of freezing of gait severity across the entire sample of PD tracked closely with the magnitude of hastening during the continuation phase. These results suggest that PD is accompanied by a unique dysrhythmia of measured movements, with FOG reflecting a particularly pronounced disruption to internal rhythmic timing.

Advances in the mechanisms of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder. Despite fairly typical clinical and pathologic features, the etiology remains unknown. Many cellular mechanisms such as oxidative stress, mitochondrial dysfunction, lysosomal dysfunction, neuroinflammatory changes, and the formation of pathologic inclusions have been proposed as potential causes. Potential links between environmental and genetic changes appear to predispose individuals to develop Parkinson's disease. Considering these observations, albeit with different levels of evidence, it is becoming more probable that Parkinson's disease is a heterogeneous disorder or a syndrome that arises from the contribution of many different factors.