Myogenic and cortical evoked potentials vary as a function of stimulus pulse geometry delivered in the subthalamic nucleus of Parkinson's disease patients.

Introduction: The therapeutic efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) may be limited for some patients by the presence of stimulation-related side effects. Such effects are most often attributed to electrical current spread beyond the target region. Prior computational modeling studies have suggested that changing the degree of asymmetry of the individual phases of the biphasic, stimulus pulse may allow for more selective activation of neural elements in the target region. To the extent that different neural elements contribute to the therapeutic vs. side-effect inducing effects of DBS, such improved selectivity may provide a new parameter for optimizing DBS to increase the therapeutic window. Methods: We investigated the effect of six different pulse geometries on cortical and myogenic evoked potentials in eight patients with PD whose leads were temporarily externalized following STN DBS implant surgery. DBS-cortical evoked potentials were quantified using peak to peak measurements and wavelets and myogenic potentials were quantified using RMS. Results: We found that the slope of the recruitment curves differed significantly as a function of pulse geometry for both the cortical- and myogenic responses. Notably, this effect was observed most frequently when stimulation was delivered using a monopolar, as opposed to a bipolar, configuration. Discussion: Manipulating pulse geometry results in differential physiological effects at both the cortical and neuromuscular level. Exploiting these differences may help to expand DBS' therapeutic window and support the potential for incorporating pulse geometry as an additional parameter for optimizing therapeutic benefit.

Feasibility of Magnetic Resonance-Compatible Accelerometers to Monitor Tremor Fluctuations During Magnetic Resonance-Guided Focused Ultrasound Thalamotomy: Technical Note.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is used to treat essential tremor and tremor-dominant Parkinson disease. Feedback is collected throughout the procedure to verify the location of the target and completeness of response; however, variability in clinical judgments may underestimate or overestimate treatment response. OBJECTIVE: To objectively quantify joint motion after each sonication using accelerometers secured to the contralateral upper extremity in an effort to optimize MRgFUS treatment. METHODS: Before the procedure, 3 accelerometers were secured to the patient's arm, forearm, and index finger. Throughout the procedure, tremor motion was regularly recorded during postural and kinetic tremor testing and individual joint angle measures were modeled. The joint angle from each accelerometer was compared with baseline measurements to assess changes in angles. Subsequent adjustments to the target location and sonication energy were made at the discretion of the neurosurgeon and neuroradiologist. RESULTS: Intraoperative accelerometer measurements of hand tremor from 18 patients provided quantified data regarding joint angle reduction: 87.3%, 94.2%, and 86.7% for signature writing, spiral drawing, and line drawing tests, respectively. Target adjustment based on accelerometer monitoring of the angle at each joint added substantial value toward achieving optimal tremor reduction. CONCLUSION: Real-time accelerometer recordings collected during MRgFUS thalamotomy offered objective quantification of changes in joint angle after each sonication, and these findings were consistent with clinical judgments of tremor response. These results suggest that this technique could be used for fine adjustment of the location of sonication energy and number of sonications to consistently achieve optimal tremor reduction.

The impact of pulse timing on cortical and subthalamic nucleus deep brain stimulation evoked potentials.

The impact of pulse timing is an important factor in our understanding of how to effectively modulate the basal ganglia thalamocortical (BGTC) circuit. Single pulse low-frequency DBS-evoked potentials generated through electrical stimulation of the subthalamic nucleus (STN) provide insight into circuit activation, but how the long-latency components change as a function of pulse timing is not well-understood. We investigated how timing between stimulation pulses delivered in the STN region influence the neural activity in the STN and cortex. DBS leads implanted in the STN of five patients with Parkinson's disease were temporarily externalized, allowing for the delivery of paired pulses with inter-pulse intervals (IPIs) ranging from 0.2 to 10 ms. Neural activation was measured through local field potential (LFP) recordings from the DBS lead and scalp EEG. DBS-evoked potentials were computed using contacts positioned in dorsolateral STN as determined through co-registered post-operative imaging. We quantified the degree to which distinct IPIs influenced the amplitude of evoked responses across frequencies and time using the wavelet transform and power spectral density curves. The beta frequency content of the DBS evoked responses in the STN and scalp EEG increased as a function of pulse-interval timing. Pulse intervals <1.0 ms apart were associated with minimal to no change in the evoked response. IPIs from 1.5 to 3.0 ms yielded a significant increase in the evoked response, while those >4 ms produced modest, but non-significant growth. Beta frequency activity in the scalp EEG and STN LFP response was maximal when IPIs were between 1.5 and 4.0 ms. These results demonstrate that long-latency components of DBS-evoked responses are pre-dominantly in the beta frequency range and that pulse interval timing impacts the level of BGTC circuit activation.

Complications Associated With Ventriculoperitoneal Shunt Surgery for Normal Pressure Hydrocephalus Using Stereotactic Navigation and Abdominal Laparoscopy: A Single-Institution Case Series.

BACKGROUND: Normal pressure hydrocephalus (NPH) is characterized by cerebral ventriculomegaly and the triad of magnetic gait, urinary incontinence, and cognitive impairment. Treatment includes ventriculoperitoneal (VP) shunt surgery. OBJECTIVE: To evaluate complication rates in a cohort of patients undergoing VP shunt surgery with stereotactic proximal catheter navigation and laparoscopic distal catheter placement. METHODS: This study was a retrospective consecutive cohort analysis of 117 patients with NPH undergoing VP shunt placement using both stereotactic navigation and laparoscopy from 2015 to 2020. Patients with obstructive hydrocephalus and those with central nervous system infection, intraventricular hemorrhage, Ommaya reservoirs, or undergoing shunt revision at initial encounter were excluded. Variables included demographics and comorbidities, NPH symptoms, operative details, radiographic outcomes, and rates of complications, readmissions, and reoperations within 1, 3, and 12 months. Impact of demographics and comorbidities on complication rates was assessed using Fisher exact tests. RESULTS: Zero patients required reoperation within 30 days. One intracranial hemorrhage was detected on immediate postoperative head computed tomography. Four patients ultimately required revision: 2 for catheter repositioning to alleviate abdominal pain, 1 ligation for a colectomy, and 1 removal for shunt infection. Patients with cardiac or other neurological comorbidities had higher rates of readmission and complications. Systemic complications totaled 12% in the first 30 days. CONCLUSION: The combination of intraoperative stereotactic navigation and laparoscopic assistance leads to low rates of serious complications and reoperations for VP shunt implantation in patients with NPH. These changes to surgical technique are easy to implement and may reduce the risk for this common operation.

Clinical Intervention Using Focused Ultrasound (FUS) Stimulation of the Brain in Diverse Neurological Disorders.

Various surgical techniques and pharmaceutical treatments have been developed to improve the current technologies of treating brain diseases. Focused ultrasound (FUS) is a new brain stimulation modality that can exert a therapeutic effect on diseased brain cells, with this effect ranging from permanent ablation of the pathological neural circuit to transient excitatory/inhibitory modulation of the neural activity depending on the acoustic energy of choice. With the development of intraoperative imaging technology, FUS has become a clinically available noninvasive neurosurgical option with visual feedback. Over the past 10 years, FUS has shown enormous potential. It can deliver acoustic energy through the physical barrier of the brain and eliminate abnormal brain cells to treat patients with Parkinson's disease and essential tremor. In addition, FUS can help introduce potentially beneficial therapeutics at the exact brain region where they need to be, bypassing the brain's function barrier, which can be applied for a wide range of central nervous system disorders. In this review, we introduce the current FDA-approved clinical applications of FUS, ranging from thermal ablation to blood barrier opening, as well as the emerging applications of FUS in the context of pain control, epilepsy, and neuromodulation. We also discuss the expansion of future applications and challenges. Broadening FUS technologies requires a deep understanding of the effect of ultrasound when targeting various brain structures in diverse disease conditions in the context of skull interface, anatomical structure inside the brain, and pathology.

Safety and effectiveness of the assessment and treatment of idiopathic normal pressure hydrocephalus in the Adult Hydrocephalus Clinical Research Network.

OBJECTIVE: The aim of this study was to describe the processes and outcomes associated with patients at five sites in the Adult Hydrocephalus Clinical Research Network (AHCRN) who had undergone evaluation and treatment for suspected idiopathic normal pressure hydrocephalus (iNPH) and had 1-year postoperative follow-up. METHODS: Subjects with possible iNPH who had been prospectively enrolled in the AHCRN registry between November 19, 2014, and December 31, 2018, were evaluated by CSF drainage via either lumbar puncture or external lumbar drainage, consistent with recommendations of the international iNPH guidelines. Standardized clinical evaluations of gait, cognition, urinary symptoms, depression, and functional outcomes were conducted at baseline, before and after CSF drainage, and at 4-month intervals after shunt surgery. Complications of CSF drainage and shunt surgery were recorded. RESULTS: Seventy-four percent (424/570) of patients with possible iNPH had CSF drainage, and 46% of them (193/424) underwent shunt surgery. The mean change in gait velocity with CSF drainage was 0.18 m/sec in patients who underwent shunt surgery versus 0.08 m/sec in patients who did not. For shunt surgery patients, gait velocity increased by 54% from 0.67 m/sec before CSF drainage to 0.96 m/sec 8-12 months after surgery, and 80% of patients had an increase of at least 0.1 m/sec by the first postoperative visit. Evaluation of cognition, urinary symptoms, depression, and functional outcomes also revealed improvement after shunt surgery. Of 193 patients who had undergone shunt surgery, 176 (91%) had no complications and 17 (9%) had 28 complications. Eleven patients (6%) had 14 serious complications that resulted in the need for surgery or an extended hospital stay. The 30-day reoperation rate was 3%. CONCLUSIONS: Using criteria recommended by the international iNPH guidelines, the authors found that evaluation and treatment of iNPH are safe and effective. Testing with CSF drainage and treatment with shunt surgery are associated with a high rate of sustained improvement and a low rate of complications for iNPH in the 1st year after shunt surgery. Patients who had undergone shunt surgery for iNPH experienced improvement in gait, cognitive function, bladder symptoms, depression, and functional outcome measures. Gait velocity, which is an easily measured, objective, continuous variable, should be used as a standard outcome measure to test a patient's response to CSF drainage and shunt surgery in iNPH.

Cognitive and gait outcomes after primary endoscopic third ventriculostomy in adults with chronic obstructive hydrocephalus.

OBJECTIVE: The object of this study was to determine the short- and long-term efficacy of primary endoscopic third ventriculostomy (ETV) on cognition and gait in adults with chronic obstructive hydrocephalus. METHODS: Patients were prospectively accrued through the Adult Hydrocephalus Clinical Research Network patient registry. Patients with previously untreated congenital or acquired obstructive hydrocephalus were included in this study. Gait velocity was assessed using a 10-m walk test. Global cognition was assessed with the Montreal Cognitive Assessment (MoCA). Only patients with documented pre- and post-ETV gait analysis and/or pre- and post-ETV MoCA were included. RESULTS: A total of 74 patients had undergone primary ETV, 42 of whom were analyzed. The remaining 32 patients were excluded, as they could not complete both pre- and post-ETV assessments. The mean age of the 42 patients, 19 (45.2%) of whom were female, was 51.9 ± 17.1 years (range 19-79 years). Most patients were White (37 [88.1%]), and the remainder were Asian. Surgical complications were minor. Congenital etiologies occurred in 31 patients (73.8%), with aqueductal stenosis in 23 of those patients (54.8%). The remaining 11 patients (26.2%) had acquired cases. The gait short-term follow-up cohort (mean 4.7 ± 4.1 months, 35 patients) had a baseline median gait velocity of 0.9 m/sec (IQR 0.7-1.3 m/sec) and a post-ETV median velocity of 1.3 m/sec (IQR 1.1-1.4 m/sec). Gait velocity significantly improved post-ETV with a median within-patient change of 0.3 m/sec (IQR 0.0-0.6 m/sec, p < 0.001). Gait velocity improvements were sustained in the long term (mean 14 ± 2.8 months, 12 patients) with a baseline median velocity of 0.7 m/sec (IQR 0.6-1.3 m/sec), post-ETV median of 1.3 m/sec (IQR 1.1-1.7 m/sec), and median within-patient change of 0.4 m/sec (IQR 0.2-0.6 m/sec, p < 0.001). The cognitive short-term follow-up cohort (mean 4.6 ± 4.0 months, 38 patients) had a baseline median MoCA total score (MoCA TS) of 24/30 (IQR 23-27) that improved to 26/30 (IQR 24-28) post-ETV. The median within-patient change was +1 point (IQR 0-2 points, p < 0.001). However, this change is not clinically significant. The cognitive long-term follow-up cohort (mean 14 ± 3.1 months, 15 patients) had a baseline median MoCA TS of 23/30 (IQR 22-27), which improved to 26/30 (IQR 25-28) post-ETV. The median within-patient change was +2 points (IQR 1-3 points, p = 0.007), which is both statistically and clinically significant. CONCLUSIONS: Primary ETV can safely improve symptoms of gait and cognitive dysfunction in adults with chronic obstructive hydrocephalus. Gait velocity and global cognition were significantly improved, and the worsening of either was rare following ETV.

Directional Stimulation in Parkinson's Disease and Essential Tremor: The Cleveland Clinic Experience.

OBJECTIVE: To assess use of directional stimulation in Parkinson's disease and essential tremor patients programmed in routine clinical care. MATERIALS AND METHODS: Patients with Parkinson's disease or essential tremor implanted at Cleveland Clinic with a directional deep brain stimulation (DBS) system from November 2017 to October 2019 were included in this retrospective case series. Omnidirectional was compared against directional stimulation using therapeutic current strength, therapeutic window percentage, and total electrical energy delivered as outcome variables. RESULTS: Fifty-seven Parkinson's disease patients (36 males) were implanted in the subthalamic nucleus (105 leads) and 33 essential tremor patients (19 males) were implanted in the ventral intermediate nucleus of the thalamus (52 leads). Seventy-four percent of patients with subthalamic stimulation (65% of leads) and 79% of patients with thalamic stimulation (79% of leads) were programmed with directional stimulation for their stable settings. Forty-six percent of subthalamic leads and 69% of thalamic leads were programmed on single segment activation. There was no correlation between the length of microelectrode trajectory through the STN and use of directional stimulation. CONCLUSIONS: Directional programming was more common than omnidirectional programming. Substantial gains in therapeutic current strength, therapeutic window, and total electrical energy were found in subthalamic and thalamic leads programmed on directional stimulation.

Reduced Risk of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From a United States Claims Database.

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States. Design: Retrospective, contemporaneous cohort study. Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018. Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, of which 3,869 patients had a de novo implant and primary diagnosis of PD or ET. Follow-up of 3 months was available for 3,810 patients, 12 months for 3,561 patients, and 24 months for 1,812 patients. Intervention: Implantation of a modern directional (MD) or traditional omnidirectional (TO) DBS system. Primary and Secondary Outcome Measures: We hypothesized that MD systems would impact complication rates. Reoperation rate was the primary outcome. Associated diagnoses, patient characteristics, and implanting center details served as covariates. Kaplan-Meier analysis was performed to compare rates of event-free survival and regression models were used to determine covariate influences. Results: Patients implanted with modern systems were 36% less likely to require reoperation, largely due to differences in acute reoperations and intracranial lead reoperations. Risk reduction persisted while accounting for practice differences and implanting center experience. Risk reduction was more pronounced in patients with PD. Conclusions: In the first multicenter analysis of device-related complications including modern DBS systems, we found that modern systems are associated with lower reoperation rates. This risk profile should be carefully considered during device selection for patients undergoing DBS for PD or ET. Prospective studies are needed to further investigate underlying causes.

Estimating the Risk of Deep Brain Stimulation in the Modern Era: 2008 to 2020.

BACKGROUND: Deep brain stimulation (DBS) was first approved by the United States Food and Drug Administration in 1997. Although the fundamentals of DBS remain the same, hardware, software, and imaging have evolved significantly. OBJECTIVE: To test our hypothesis that the aggregate complication rate in the medical literature in the past 12 years would be lower than what is often cited based on early experience with DBS surgery. METHODS: PubMed, PsycINFO, and EMBASE were queried for studies from 2008 to 2020 that included patients treated with DBS from 2007 to 2019. This yielded 34 articles that evaluated all complications of DBS surgery, totaling 2249 patients. RESULTS: The overall complication rate in this study was 16.7% per patient. There was found to be a systemic complication rate of 0.89%, intracranial complication rate of 2.7%, neurological complication rate of 4.6%, hardware complication rate of 2.2%, and surgical site complication rate of 3.4%. The infection and erosion rate was 3.0%. CONCLUSION: This review suggests that surgical complication rates have decreased since the first decade after DBS was first FDA approved. Understanding how to minimize complications from the inception of a technique should receive more attention.

Biomarker Optimization of Spinal Cord Stimulation Therapies.

OBJECTIVES: We are in the process of designing and testing an intradural stimulation device that will shorten the distance between the location of the electrode array and the targeted neural tissue, thus improving the efficacy of electrical current delivery. Identifying a biomarker that accurately reflects the response to this intervention is highly valued because of the potential to optimize interventional parameters or predict a response before it is clinically measurable. In this report, we summarize the findings pertaining to the study of biomarkers so that we and others will have an up-to-date reference that critically evaluates the current approaches and select one or several for testing during the development of our device. MATERIALS AND METHODS: We have conducted a broad survey of the existing literature to catalogue the biomarkers that could be coupled to intradural spinal cord stimulation. We describe in detail some of the most promising biomarkers, existing limitations, and suitability to managing chronic pain. RESULTS: Chronic, intractable pain is an all-encompassing condition that is incurable. Many treatments for managing chronic pain are nonspecific in action and intermittently administered; therefore, patients are particularly susceptible to large fluctuations in pain control over the course of a day. The absence of a reliable biomarker challenges assessment of therapeutic efficacy and contributes to either incomplete and inconsistent pain relief or, alternatively, intolerable side effects. Fluctuations in metabolites or inflammatory markers, signals captured during dynamic imaging, and genomics will likely have a role in governing how a device is modulated. CONCLUSIONS: Efforts to identify one or more biomarkers are well underway with some preliminary evidence supporting their efficacy. This has far-reaching implications, including improved outcomes, fewer adverse events, harmonization of treatment and individuals, performance gains, and cost savings. We anticipate that novel biomarkers will be used widely to manage chronic pain.

Extended lumbar drainage in idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: When appropriately selected, a high proportion of patients with suspected idiopathic normal pressure hydrocephalus (iNPH) will respond to cerebrospinal fluid diversion with a shunt. Extended lumbar drainage (ELD) is regarded as the most accurate test for this condition, however, varying estimates of its accuracy are found in the current literature. Here, we review the literature in order to provide summary estimates of sensitivity, specificity, positive- and negative predictive value for this test through meta-analysis of suitably rigorous studies. METHODS: Studies involving a population of NPH patients with predominantly idiopathic aetiology (>80%) in which the intention of the study was to shunt patients regardless of the outcome of ELD were included in the review. Various literature databases were searched to identify diagnostic test accuracy studies addressing ELD in the diagnosis of iNPH. Those studies passing screening and eligibility were assessed using the QUADAS-2 tool and data extracted for bivariate random effects meta-analysis. RESULTS: Four small studies were identified. They showed disparate results concerning diagnostic test accuracy. The summary estimates for sensitivity and specificity were 94% (CI 41-100%) and 85% (CI 33-100%), respectively. The summary estimates of positive and negative predictive value were both 90% (CIs 65-100% and 48-100%, respectively). CONCLUSION: Large, rigorous studies addressing the diagnostic accuracy of ELD are lacking, and little robust evidence exists to support the use of ELD in diagnostic algorithms for iNPH. Therefore, a large cohort study, or ideally an RCT, is needed to determine best practice in selecting patients for shunt surgery.

Long-term outcomes of intrathecal baclofen in ambulatory multiple sclerosis patients: A single-center experience.

BACKGROUND: Intrathecal baclofen (ITB) is traditionally reserved for non-ambulatory patients. OBJECTIVE: To investigate outcomes of ITB in ambulatory multiple sclerosis (MS) patients. METHODS: Changes in outcome measures were estimated by a mixed effect model, while the complication rate was calculated using a logistic regression. Predictors of non-ambulatory status were identified by Cox model. RESULTS: In all, 256 patients received an ITB test injection and 170 underwent ITB surgery. Aggregate Modified Ashworth Scale (MAS) scores for the ambulatory ITB cohort decreased from 13.5 ± 6.96 to 4.54 ± 4.18 at 5 years (p < 0.001). There was no significant change in walking speed 1 year post ITB surgery (0.45 m/second ± 0.30 vs 0.38 m/second ± 0.39, p = 0.80) with 77.8% of patients remaining ambulatory which decreased to 41.7% at year 5. Longer MS disease duration (hazard ratio (HR): 1.04; 95% confidence interval (CI): 1.01-1.07; p = 0.018) and lower hip flexor strength (HR: 0.40; 95% CI: 0.27-0.57; p < 0.001) predicted non-ambulatory status after surgery. Complications were more likely in the ambulatory cohort (odds ratio (OR): 3.30, 95% CI: 2.17-5.02; p = 0.017). CONCLUSION: ITB is effective for ambulatory MS patients without compromising short-term walking speed, although a higher complication rate was observed in this cohort.

Earlier radiosurgery leads to better pain relief and less medication usage for trigeminal neuralgia patients: an international multicenter study.

OBJECTIVE: Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery. METHODS: The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed. RESULTS: Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50-95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I-IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075). CONCLUSIONS: TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.

Predictors of second-sided deep brain stimulation for Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurological movement disorder that is commonly treated with deep brain stimulation (DBS) surgery in advanced stages. The purpose of this study was to investigate factors that affect time to placement of a second-sided DBS lead for PD when a unilateral lead is initially placed for asymmetrical presentation. The decision whether to initially perform unilateral or bilateral DBS is largely based on physician and/or patient preference. METHODS: This study was a retrospective cohort analysis of patients with PD undergoing initial unilateral DBS for asymmetrical disease between January 1999 and December 2017 at the authors' institution. Patients treated with DBS for essential tremor or other conditions were excluded. Variables collected included demographics at surgery, time since diagnosis, Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III), patient-reported quality-of-life outcomes, side of operation, DBS target, intraoperative complications, and date of follow-up. Paired t-tests were used to assess mean changes in UPDRS-III. Cox proportional hazards analysis and the Kaplan-Meier method were used to determine factors associated with time to second lead insertion over 5 years. RESULTS: The final cohort included 105 patients who underwent initial unilateral DBS for asymmetrical PD; 59% of patients had a second-sided lead placed within 5 years with a median time of 34 months. Factors found to be significantly associated with early second-sided DBS included patient age 65 years or younger, globus pallidus internus (GPi) target, and greater off-medication reduction in UPDRS-III score following initial surgery. Older age was also found to be associated with a smaller preoperative UPDRS-III levodopa responsiveness score and with a smaller preoperative to postoperative medication-off UPDRS-III change. CONCLUSIONS: Younger patients, those undergoing GPi-targeted unilateral DBS, and patients who responded better to the initial DBS were more likely to undergo early second-sided lead placement. Therefore, these patients, and patients who are more responsive to medication preoperatively (as a proxy for DBS responsiveness), may benefit from consideration of initial bilateral DBS.

Cortical thickness in visuo-motor areas is related to motor outcomes after STN DBS for Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome. METHODS: Using freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons. RESULTS: Based on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis. CONCLUSIONS: Our data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers.

Deep Brain Stimulation for Pain in the Modern Era: A Systematic Review.

BACKGROUND: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. OBJECTIVE: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. METHODS: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. RESULTS: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores. CONCLUSION: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation.

The clinical spectrum of hydrocephalus in adults: report of the first 517 patients of the Adult Hydrocephalus Clinical Research Network registry.

OBJECTIVE: The authors describe the demographics and clinical characteristics of the first 517 patients enrolled in the Adult Hydrocephalus Clinical Research Network (AHCRN) during its first 2 years. METHODS: Adults ≥ 18 years were nonconsecutively enrolled in a registry at 6 centers. Four categories of adult hydrocephalus were defined: transition (treated before age 18 years), unrecognized congenital (congenital pattern, not treated before age 18 years), acquired (secondary to known risk factors, treated or untreated), and suspected idiopathic normal pressure hydrocephalus (iNPH) (≥ age 65 years, not previously treated). Data include etiology, symptoms, examination findings, neuropsychology screening, comorbidities, treatment, complications, and outcomes. Standard evaluations were administered to all patients by trained examiners, including the Montreal Cognitive Assessment, the Symbol Digit Modalities Test, the Beck Depression Inventory-II, the Overactive Bladder Questionnaire Short Form symptom bother, the 10-Meter Walk Test, the Boon iNPH gait scale, the Lawton Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) questionnaire, the iNPH grading scale, and the modified Rankin Scale. RESULTS: Overall, 517 individuals were enrolled. Age ranged from 18.1 to 90.7 years, with patients in the transition group (32.7 ± 10.0 years) being the youngest and those in the suspected iNPH group (76.5 ± 5.2 years) being the oldest. The proportion of patients in each group was as follows: 16.6% transition, 26.5% unrecognized congenital, 18.2% acquired, and 38.7% suspected iNPH. Excluding the 86 patients in the transition group, who all had received treatment, 79.4% of adults in the remaining 3 groups had not been treated at the time of enrollment. Patients in the suspected iNPH group had the poorest performance in cognitive evaluations, and those in the unrecognized congenital group had the best performance. The same pattern was seen in the Lawton ADL/IADL scores. Gait velocity was lowest in patients in the suspected iNPH group. Categories that had the most comorbidities (suspected iNPH) or etiologies of hydrocephalus that directly cause neurological injury (transition, acquired) had greater degrees of impairment compared to unrecognized congenital, which had the fewest comorbidities or etiologies associated with neurological injury. CONCLUSIONS: The clinical spectrum of hydrocephalus in adults comprises more than iNPH or acquired hydrocephalus. Only 39% of patients had suspected iNPH, whereas 43% had childhood onset (i.e., those in the transition and unrecognized congenital groups). The severity of symptoms and impairment was worsened when the etiology of the hydrocephalus or complications of treatment caused additional neurological injury or when multiple comorbidities were present. However, more than half of patients in the transition, unrecognized congenital, and acquired hydrocephalus groups had minimal or no impairment. Excluding the transition group, nearly 80% of patients in the AHCRN registry were untreated at the time of enrollment. A future goal for the AHCRN is to determine whether patients with unrecognized congenital and acquired hydrocephalus need treatment and which patients in the suspected iNPH cohort actually have possible hydrocephalus and should undergo further diagnostic testing. Future prospective research is needed in the diagnosis, treatment, outcomes, quality of life, and macroeconomics of all categories of adult hydrocephalus.

Contemporary Approaches to Preventing and Treating Infections of Novel Intrathecal Neurostimulation Devices.

INTRODUCTION: Contemporary approaches to surgical site infections have evolved significantly over the last several decades in response to the economic pressures of soaring health care costs and increasing patient expectations of safety. Neurosurgeons face multiple unique challenges when striving to avoid as well as manage surgical implant infections. The tissue compartment, organ system, or joint is characterized by biological factors and physical forces that may not be universally relevant. Such implants, once rare, are now routine. Although the prevention, diagnosis, and treatment of surgical site infections involving neural implants has advanced, guidelines are ever changing, and the incidence still exceeds acceptable levels. We assess the impact of these factors on a new class of implantable neuromodulation devices. METHODS: The available evidence along with practice patterns were examined and organized to establish relevant groupings for continuing evaluation and to propose justifiable recommendations for the treatment of infections that might arise in the case of intradural spinal cord stimulators. RESULTS: Few studies in the modern era have systematically evaluated preventive behaviors that were applied to intradural neural implants alone. We anticipate that future efforts will focus even more on the investigation of modifiable factors along a continuum from bacterially repellant implants to weight management. Early diagnosis could offer the best hope for device salvage but to date has been largely understudied. CONCLUSIONS: Historically, prevention is the cornerstone to infection mitigation. However, immediate diagnosis and hardware salvage have not received the attention deserved, and that approach may be especially important for intradural devices.

Intradural Spinal Cord Stimulation: Performance Modeling of a New Modality.

Introduction: Intradural spinal cord stimulation (SCS) may offer significant therapeutic benefits for those with intractable axial and extremity pain, visceral pain, spasticity, autonomic dysfunction and related disorders. A novel intradural electrical stimulation device, limited by the boundaries of the thecal sac, CSF and spinal cord was developed to test this hypothesis. In order to optimize device function, we have explored finite element modeling (FEM). Methods: COMSOL®Multiphysics Electrical Currents was used to solve for fields and currents over a geometric model of a spinal cord segment. Cathodic and anodic currents are applied to the center and tips of the T-cross component of the electrode array to shape the stimulation field and constrain charge-balanced cathodic pulses to the target area. Results: Currents from the electrode sites can move the effective stimulation zone horizontally across the cord by a linear step method, which can be diversified considerably to gain greater depth of penetration relative to standard epidural SCS. It is also possible to prevent spread of the target area with no off-target action potential. Conclusion: Finite element modeling of a T-shaped intradural spinal cord stimulator predicts significant gains in field depth and current shaping that are beyond the reach of epidural stimulators. Future studies with in vivo models will investigate how this approach should first be tested in humans.