Lesser-Known Aspects of Deep Brain Stimulation for Parkinson's Disease: Programming Sessions, Hardware Surgeries, Residential Care Admissions, and Deaths.

OBJECTIVE: The long-term treatment burden, duration of community living, and survival of patients with Parkinson's disease (PD) after deep brain stimulation (DBS) implantation are unclear. This study aims to determine the frequency of programming, repeat hardware surgeries (of the intracranial electrode, implantable pulse generator [IPG], and extension-cable), and the timings of residential care and death in patients with PD treated with DBS. MATERIALS AND METHODS: In this cross-sectional, population-based study, individual-level data were collected from the Australian government covering a 15-year period (2002-2016) on 1849 patients with PD followed from DBS implantation. RESULTS: The mean DBS implantation age was 62.6 years and mean follow-up 5.0 years. Mean annual programming rates were 6.9 in the first year and 2.8 in subsequent years. 51.4% of patients required repeat hardware surgery. 11.3% of patients had repeat intracranial electrode surgery (including an overall 1.1% of patients who were completely explanted). 47.6% of patients had repeat IPG/extension-cable surgery including for presumed battery depletion. 6.2% of patients had early repeat IPG/extension-cable surgery (within one year of any previous such surgery). Thirty-day postoperative mortality was 0.3% after initial DBS implantation and 0.6% after any repeat hardware surgery. 25.3% of patients were admitted into residential care and 17.4% died. The median interval to residential care and death was 10.2 years and 11.4 years, respectively. Age more than 65 years was associated with fewer repeat hardware surgeries for presumed complications (any repeat surgery of electrodes, extension-cables, and early IPG surgery) and greater rates of residential care admission and death. CONCLUSIONS: Data from a large cohort of patients with PD treated with DBS found that the median life span after surgery is ten years. Repeat hardware surgery, including of the intracranial electrodes, is common. These findings support development of technologies to reduce therapy burden such as enhanced surgical navigation, hardware miniaturization, and improved battery efficiency.

Electrically evoked and spontaneous neural activity in the subthalamic nucleus under general anesthesia.

OBJECTIVE: Deep brain stimulation (DBS) surgery is commonly performed with the patient awake to facilitate assessments of electrode positioning. However, awake neurosurgery can be a barrier to patients receiving DBS. Electrode implantation can be performed with the patient under general anesthesia (GA) using intraoperative imaging, although such techniques are not widely available. Electrophysiological features can also aid in the identification of target neural regions and provide functional evidence of electrode placement. Here we assess the presence and positional variation under GA of spontaneous beta and high-frequency oscillation (HFO) activity, and evoked resonant neural activity (ERNA), a novel evoked response localized to the subthalamic nucleus. METHODS: ERNA, beta, and HFO were intraoperatively recorded from DBS leads comprising four individual electrodes immediately after bilateral awake implantation into the subthalamic nucleus of 21 patients with Parkinson's disease (42 hemispheres) and after subsequent GA induction deep enough to perform pulse generator implantation. The main anesthetic agent was either propofol (10 patients) or sevoflurane (11 patients). RESULTS: GA reduced the amplitude of ERNA, beta, and HFO activity (p < 0.001); however, ERNA amplitudes remained large in comparison to spontaneous local field potentials. Notably, a moderately strong correlation between awake ERNA amplitude and electrode distance to an "ideal" therapeutic target within dorsal STN was preserved under GA (awake: ρ = -0.73, adjusted p value [padj] < 0.001; GA: ρ = -0.69, padj < 0.001). In contrast, correlations were diminished under GA for beta (awake: ρ = -0.45, padj < 0.001; GA: ρ = -0.13, padj = 0.12) and HFO (awake: ρ = -0.69, padj < 0.001; GA: ρ = -0.33, padj < 0.001). The largest ERNA occurred at the same electrode (awake vs GA) for 35/42 hemispheres (83.3%) and corresponded closely to the electrode selected by the clinician for chronic therapy at 12 months (awake ERNA 77.5%, GA ERNA 82.5%). The largest beta amplitude occurred at the same electrode (awake vs GA) for only 17/42 (40.5%) hemispheres and 21/42 (50%) for HFO. The electrode measuring the largest awake beta and HFO amplitudes corresponded to the electrode selected by the clinician for chronic therapy at 12 months in 60% and 70% of hemispheres, respectively. However, this correspondence diminished substantially under GA (beta 20%, HFO 35%). CONCLUSIONS: ERNA is a robust electrophysiological signal localized to the dorsal subthalamic nucleus subregion that is largely preserved under GA, indicating it could feasibly guide electrode implantation, either alone or in complementary use with existing methods.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome.

OBJECTIVE: We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. METHODS: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. RESULTS: GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5-0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3 Hz) frequency band. For alpha (8-12 Hz) and beta (13-30 Hz) frequencies, PTE was greatest 1-0.5 seconds before GPFA onset. SIGNIFICANCE: Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG-functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

Subthalamic nucleus deep brain stimulation evokes resonant neural activity.

Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027-1031.

Intraoperative definition of bottom-of-sulcus dysplasia using intraoperative ultrasound and single depth electrode recording - A technical note.

Bottom of sulcus dysplasias (BOSDs) are localized focal cortical dysplasias (FCDs) centred on the bottom of a sulcus that can be highly epileptogenic, but difficult to delineate intraoperatively. We report on a patient with refractory epilepsy due to a BOSD, successfully resected with the aid of a multimodal surgical approach using neuronavigation based on MRI and PET, intraoperative ultrasound (iUS) and electrocorticography (ECoG) using depth electrodes. The lesion could be visualized on iUS showing an increase in echogenicity at the grey-white matter junction. IUS demonstrated the position of the depth electrode in relation to the lesion. Depth electrode recording showed almost continuous spiking. Thus, intraoperative imaging and electrophysiology helped confirm the exact location of the lesion. Post-resection ultrasound demonstrated the extent of the resection and depth electrode recording did not show any epileptiform activity. Thus, both techniques helped assess completeness of resection. The patient has been seizure free since surgery. Using a multimodal approach including iUS and ECoG is a helpful adjunct in surgery for BOSD and may improve seizure outcome.

Surgery for temporal lobe epilepsy associated with mesial temporal sclerosis in the older patient: a long-term follow-up.

PURPOSE: To assess the outcomes from temporal lobectomy for hippocampal sclerosis in patients 50 years or older. Controversy exists as to the suitability of older patients for epilepsy surgery, with most of the previous studies demonstrating a correlation between increasing age and poor outcome. However, the inclusion of temporal lobe epilepsy of multiple etiologies has confounded many previous studies of this age group. METHODS: Twenty-one patients aged 50 years or older (mean 54.9 years) at the time of surgery were included in the study group. All patients had a pathologic diagnosis of hippocampal sclerosis. A retrospective analysis was performed comparing seizure outcomes following a standardized anterior temporal lobectomy with those from 103 patients younger than 50 (mean age 34.7 years) operated upon over the same time period. The mean follow-up period for the study was 9.57 years. RESULTS: Twenty of the 21 patients in the older group (95.2%) had a satisfactory seizure outcome (Engel classes I and II) compared with 90.3% of the younger patients. There was no statistically significant difference in the outcomes between the two groups (p = 0.719). Across both groups of patients combined, there was no significant difference between the mean age in the patients with a satisfactory seizure outcome compared to those with an unsatisfactory outcome (38.3 vs. 34.7 years, p = 0.213). DISCUSSION: Patients 50 years or older with intractable seizures from hippocampal sclerosis have seizure outcomes following temporal lobectomy that are comparable to young patients over the long term. Older patients should not be denied treatment on the basis of age.

Submuscular transposition of the ulnar nerve: review of safety, efficacy and correlation with neurophysiological outcome.

OBJECTIVE: The surgical management of ulnar nerve entrapment at the elbow is a controversial topic, with each surgeon believing his/her technique to be the best. The authors routinely perform submuscular transposition (SMT) of the ulnar nerve to treat entrapment neuropathy at the elbow. The aims of this review are (1) to review the results of SMT with respect to safety and complications, (2) to compare the efficacy of SMT with other studies previously published, and (3) to compare the clinical results with the neurophysiological outcome. METHODS: A retrospective review of patients who underwent SMT for ulnar nerve entrapment between April 2000 and May 2003 was performed. Forty-five ulnar nerves in 44 patients were operated, of which 40 nerves were first time operation (primary group), and 5 nerves had previously undergone a simple decompressive procedure elsewhere (redo group). All patients were graded using the Louisiana State University Medical Centre (LSUMC) system for grading of ulnar nerve entrapment. Pre- and post-operative nerve conduction studies were performed, and these results compared to clinical recovery post-operatively. RESULTS: For the primary group, function improved by one grade in 32.5%, two grades in 37.5% and three grades in 12.5% of patients. There was no change in 17.5%, and no patient deteriorated post-operatively. In the redo group there was improvement of at least one grade in 60% of patients. When clinical improvement was compared with electrophysiological improvement, no clear correlation was demonstrated. CONCLUSION: Submuscular transposition of the ulnar nerve is a safe, effective treatment for ulnar nerve entrapment at the elbow. When performed by trained peripheral nerve surgeons, good results are achievable for both primary and redo surgery.