Background

Parkinson's disease (PD) can have a significant impact on sleep. Deep brain stimulation (DBS) is an effective treatment for motor features of PD, but less is understood about the impact DBS may have on sleep architecture and various sleep issues commonly seen in PD.

Objective

To review the impact of DBS on various sleep issues in PD.

Methods

We reviewed the literature regarding the impact of DBS on sleep patterns, nocturnal motor and non-motor symptoms, and sleep disorders in PD.

Results

Objective sleep measures on polysomnography (PSG), including sleep latency and wake after sleep onset improve after subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS. Subjective sleep measures, nocturnal motor symptoms, and some non-motor symptoms (nocturia) also may improve. Current evidence suggests STN DBS has no impact on Rapid Eye Movement Behavior Disorder (RBD), while STN DBS may improve symptoms of Restless Legs Syndrome (RLS). There are no studies that have evaluated the impact of GPi DBS on RBD, while it is unclear if GPi has an effect on RLS in PD.

Conclusion

DBS therapy at either site appears to improve objective and subjective sleep parameters in patients with PD. Most likely, the improvement of motor and some non-motor nocturnal symptoms leads to an increase in total sleep time by up to an hour, as well as reduction of sleep fragmentation. DBS most likely has no impact on RBD, while there is evidence that STN DBS appears to help reduce RLS severity. Further studies are needed.

Background

Post-hypoxic myoclonus (PHM) is characterized by generalized myoclonus after hypoxic brain injury. Myoclonus is often functionally impairing and refractory to medical therapies. Deep brain stimulation (DBS) has been used to treat myoclonus-dystonia, but few cases of PHM have been described.

Case report

A 33-year-old woman developed severe, refractory generalized myoclonus after cardiopulmonary arrest from drowning. We performed MRI-guided asleep bilateral pallidal DBS placement, resulting in improvement in action myoclonus at one year.

Discussion

Our case contributes to growing evidence for DBS for PHM. Interventional MRI guided DBS technique can be used for safe and accurate lead placement.

Highlights

We report a case of a patient who developed post-hypoxic myoclonus after cardiopulmonary arrest from drowning, who later underwent deep brain stimulation to treat refractory myoclonus. This is the first case to describe asleep, interventional MRI-guided technique for implanting DBS leads in post-hypoxic myoclonus.

In 2016, the American Academy of Neurology (AAN) published practice guidelines for botulinum toxin (BoNT) in the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. This article, focusing on dystonia, provides context for these guidelines through literature review. Studies that led to Food and Drug Administration (FDA) approval of each toxin for dystonia indications are reviewed, in addition to several studies highlighted by the AAN guidelines. The AAN guidelines for the use of BoNT in dystonia are compared with those of the European Federation of the Neurological Societies (EFNS), and common off-label uses for BoNT in dystonia are discussed. Toxins not currently FDA-approved for the treatment of dystonia are additionally reviewed. In the future, additional toxins may become FDA-approved for the treatment of dystonia given expanding research in this area.

Importance

Isolated dystonia and Parkinson disease (PD) are disorders of the basal gangliothalamocortical network. They have largely distinct clinical profiles, but both disorders respond to deep brain stimulation (DBS) in the same subcortical targets using similar stimulation paradigms, suggesting pathophysiologic overlap. We hypothesized that, similar to PD, isolated dystonia is associated with elevated cortical neuronal synchronization.

Objective

To investigate the electrophysiologic characteristics of the sensorimotor cortex arm-related area using a temporary subdural electrode strip in patients with isolated dystonia and PD undergoing DBS implantation in the awake state.

Design, setting, and participants

An observational study recruited patients scheduled for DBS at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center. Data were collected from May 1, 2008, through April 1, 2015. Findings are reported for 22 patients with isolated cervical or segmental dystonia (8 with [DYST-ARM] and 14 without [DYST] arm symptoms) and 14 patients with akinetic rigid PD. Data were analyzed from November 1, 2014, through May 1, 2015.

Main outcomes and measures

Cortical local field potentials, power spectral density, and phase-amplitude coupling (PAC).

Results

Among our 3 groups that together included 36 patients, cortical PAC was present in primary motor and premotor arm-related areas for all groups, but the DYST group was less likely to exhibit increased PAC (P = .008). Similar to what has been shown for patients with PD, subthalamic DBS reversibly decreased PAC in a subset of patients with dystonia who were studied before and during intraoperative test stimulation (n = 4). At rest, broadband gamma (50-200 Hz) power in the primary motor cortex was greater in the DYST-ARM and PD groups compared with the DYST group, whereas alpha (8-13 Hz) and beta (13-30 Hz) power was comparable in all 3 groups. During movement, the DYST-ARM group had impaired beta and low gamma desynchronization in the primary motor cortex.

Conclusions and relevance

Isolated dystonia and PD have physiologic overlap with respect to high levels of motor cortex synchronization and reduction of cortical synchronization by subthalamic DBS, providing an explanation for their similar therapeutic response to basal ganglia stimulation.

Background

Blepharospasm can be present as an isolated dystonia or in conjunction with other forms of cranial dystonia, causing significant disability.

Case report

We report a case of a 69-year-old male with craniocervical dystonia, manifesting primarily as incapacitating blepharospasm refractory to medical treatments. He underwent bilateral globus pallidus (GP) deep brain stimulation (DBS) with complete resolution of his blepharospasm and sustained benefit at 12 months postoperatively.

Discussion

This case illustrates successful treatment of blepharospasm with pallidal stimulation. GP-DBS should be considered a reasonable therapeutic option for intractable blepharospasm.

The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop.

Background

The cerebellum's role in dystonia is increasingly recognized. Dystonia can be a disabling and refractory condition; deep brain stimulation can help many patients, but it is traditionally less effective in acquired dystonia. New surgical targets would be instrumental in providing treatment options and understanding dystonia further.

Objective

To evaluate the efficacy of deep brain stimulation of the cerebellum in acquired dystonia.

Methods

We report our management of a 37-year-old woman with severe left arm and leg dystonia, a complication of an ischemic stroke in childhood. She had already had 2 thalamotomies with only transient benefit. These procedures, in addition to her initial stroke that had damaged the basal ganglia, left traditional deep brain stimulation targets unavailable.

Results

After implantation of bilateral deep cerebellar nuclei, dystonia improved with a 40% reduction in severity on scales and subjective reports of improved posturing, gait, and pain. This improvement has been maintained for almost 2 years after implantation.

Conclusion

Cerebellar stimulation has potential for therapeutic benefit in acquired dystonia and should be further explored.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.SIGNIFICANCE STATEMENT This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.