Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

Postoperative shunt failure following hemispherectomy in pediatric patients with pre-existing hydrocephalus.

OBJECTIVE: The risk of hydrocephalus following hemispherectomy for drug resistant epilepsy (DRE) remains high. Patients with pre-existing hydrocephalus pose a postoperative challenge, as maintaining existing shunt patency is necessary but lacks a clearly defined strategy. This study examines the incidence and predictors of shunt failure in pediatric hemispherectomy patients with pre-existing ventricular shunts. METHODS: We performed a retrospective chart review at our center to identify pediatric patients diagnosed with DRE who were treated with ventricular shunt prior to their first hemispherectomy surgery. Demographic and perioperative data were obtained including shunt history, hydrocephalus etiology, epilepsy duration, surgical technique, and postoperative outcomes. Univariate analysis was performed using Fisher's exact test and Pearson correlation, with Bonferroni correction to a = 0.00625 and a = 0.01, respectively. RESULTS: Five of nineteen (26.3%) patients identified with ventriculoperitoneal shunting prior to hemispherectomy experienced postoperative shunt malfunction. All 5 of these patients underwent at least 1 shunt revision prior to hemispherectomy, with a significant association between pre- and post-hemispherectomy shunt revisions. There was no significant association between post-hemispherectomy shunt failure and valve type, intraoperative shunt alteration, postoperative external ventricular drain placement, hemispherectomy revision, lateralization of shunt relative to resection, postoperative complications, or postoperative aseptic meningitis. There was no significant correlation between number of post-hemispherectomy shunt revisions and age at shunt placement, age at hemispherectomy, epilepsy duration, or shunt duration prior to hemispherectomy. CONCLUSIONS: Earlier shunt revision surgery may portend a subsequent need for shunt revision following hemispherectomy. These findings may guide neurosurgeons in counseling patients with pre-existing ventricular shunts prior to hemispherectomy surgery.

Beyond seizure freedom: Dissecting long-term seizure control after surgical resection for drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy. METHODS: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up. RESULTS: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively. SIGNIFICANCE: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

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.

Disparities in the nationwide distribution of epilepsy centers.

BACKGROUND: Prior studies in the field of epilepsy surgical disparities have examined barriers in undergoing epilepsy surgical resections in disadvantaged populations involving trust in health providers, education level, social support, and fear of treatment. Few studies have analyzed the geographical locations of specialized epilepsy centers and their role in nationwide epilepsy surgical access and disparities. OBJECTIVE: To better visualize the locations of epilepsy level IV centers in the United States with respect to epilepsy prevalence and socioeconomic disadvantage. METHODS: We created heat maps of the United States to visualize geographical locations of level IV epilepsy centers with respect to the 2015 state-wide epilepsy prevalence and 2017 county-wide Area Deprivation Index (ADI) scores, a composite measure of socioeconomic disadvantage. Univariate logistic regression was used to test for associations between the presence or absence of epilepsy centers and socioeconomic disadvantage. RESULTS: We found eight states within the United States without any level IV epilepsy centers. In states with level IV centers, centers were clustered in populated and metropolitan regions. Disadvantaged counties (with increased ADI scores) were less likely to have level IV centers compared to counties that were less disadvantaged (lower ADI scores) (p < 0.00001). CONCLUSION: Further work is required to remedy the decreased access to specialized epilepsy care due to geographical disparities, and to better understand its contribution to overall disparities affecting epilepsy surgery referrals.

The Need for Digital Health Solutions in Deep Brain Stimulation for Parkinson's Disease in the Time of COVID-19 and Beyond.

OBJECTIVES: Deep brain stimulation (DBS) is a well-established therapy for the management of patients with advanced Parkinson's disease and other movement disorders. Patients implanted with DBS require life-long management of the medical device as well as medications. Patients are often challenged to frequently visit the specialized DBS centers and such challenges are aggravated depending on geography, socioeconomic factors, and support systems. We discuss the need for digital health solutions to overcome these barriers to better and safely take care of patients, especially in the current COVID-19 pandemic. MATERIALS AND METHODS: A review of the literature was conducted for technology and logistics necessary in forming a digital health program. RESULTS: Digital health encounters can take place in both a synchronous and asynchronous manner. Factors involving patients include cognitive capacity, physical safety, physical capacity, connectivity, and technological security. Physician factors include examining the patient, system diagnostics, and adjusting stimulation or medications. Technology is focused on bridging the gap between patient and physician through integrating the DBS lead, implantable pulse generator (IPG), programmer, novel devices/applications to grade motor function, and teleconference modalities. CONCLUSIONS: For patients with Parkinson's disease, digital health has the potential to drastically change the landscape after DBS surgery. Furthermore, technology is fundamental in connectivity, diagnostic evaluation, and security in order to create stable and useful patient-focused care.

MR-guided laser interstitial thermal therapy in the treatment of recurrent intracranial meningiomas.

OBJECTIVE: Recurrent meningiomas can prove problematic for treatment, especially if anaplastic, as options are limited primarily to surgery and radiation therapy. Laser interstitial thermal therapy (LITT) is a minimally invasive technique for achieving immediate cytoreduction. This study seeks to determine the utility of LITT in the setting of recurrent meningiomas. MATERIALS AND METHODS: Patients undergoing LITT for tumor treatment at our institution between November 2014 and February 2016 were identified. Those with biopsy-confirmed meningiomas were reviewed with attention to ablation volume, survival, demographic data, and complications. Data from imaging performed at set intervals post-operatively were available for all. RESULTS: Four patients were identified, three of whom had successful treatment with a total of four ablations. The one case that did not result in a successful ablation was due to problems with stereotactic placing of the laser catheter. One patient had a grade 1 meningioma, with the other two being Grade 3. Immediate ablation volumes averaged 75% of preoperative tumor volume and increased to 97% at 2 weeks before dropping to 65% at 3 months. One patient had acute hemiparesis with speech difficulty, which resolved after 6 months. At date of last follow-up, two of three had progression at an average of nine weeks, and one had no progression at 28 weeks. CONCLUSION: LITT appeared to be a potentially viable treatment for recurrent meningiomas. Ablation volumes increased over time, but not beyond the initial meningioma volume. Larger studies are needed to better determine complications and outcomes. Lasers Surg. Med. 51:245-250, 2019. © 2018 Wiley Periodicals, Inc.

Surgical Neuromodulation of Tinnitus: A Review of Current Therapies and Future Applications.

INTRODUCTION: Tinnitus is the conscious perception of an auditory sensation in the absence of external stimulus. Proposed theories are based on neuroplastic changes that occur due to sensory deprivation. The authors review the relevant literature on functional imaging and neuromodulation of tinnitus and describe potential targets for deep brain stimulation (DBS). MATERIALS AND METHODS: A MEDLINE keyword and Medical Subject Heading term literature search was performed using PubMed for tinnitus, neuromodulation, DBS, transcranial magnetic stimulation, epidural electrode stimulation, intradural electrode stimulation, functional imaging, and connectivity. Data from these reports were extracted and reviewed. RESULTS: Multiple imaging studies are employed to understand the pathophysiology of tinnitus. Abnormal regions and altered connectivity implicated in tinnitus include auditory pathway and limbic structures. Neuromodulation attempts to correct this hyperexcitable state by disrupting these aberrant oscillations and returning activity to baseline. Applied treatment modalities include transcranial magnetic stimulation, epidural/intradural electrode stimulation, and DBS. More recently, modulation of autonomic pathways through vagus nerve stimulation and paired auditory sounds has demonstrated tinnitus improvement via plasticity changes. CONCLUSIONS: DBS shows much promise as a therapeutic option for tinnitus. Stimulation of the auditory pathway, particularly the medial geniculate body, could counteract thalamocortical dysrhythmias and reduce gamma activity implicated in the tinnitus percept. Stimulation of the limbic pathway could decrease attention to and perception of tinnitus. Additional studies, focusing on the involvement of thalamic and limbic structures in the pathophysiology of tinnitus, are needed to support the use of DBS.

The safety of magnetic resonance imaging-guided laser interstitial thermal therapy for cerebral radiation necrosis.

Cerebral radiation necrosis (CRN) is a known complication of radiation therapy. Treatment options are limited and include steroids, bevacizumab, and surgery. This study seeks to determine the safety of laser interstitial thermal therapy (LITT) for CRN and identify the pattern of post-ablation volume change over time. Patients undergoing LITT for tumor treatment at Henry Ford Hospital between November 2013 and January 2016 with biopsy-confirmed CRN were prospectively collected and retrospectively reviewed with attention to ablation volume, survival, demographic data, steroid dose, and complications. Imaging occurred at set intervals beginning pre-ablation. Ten patients with 11 ablations were evaluated. Four patients had a primary diagnosis of high-grade glioma, while six had metastatic lesions. An average of 86% of CRN volume was ablated. Ablation volume increased to 430% of initial CRN volume at 1-2 weeks before decreasing to 69% after 6 months. No patient had a decline in baseline neurological examination while in the hospital. Four patients developed delayed neurological deficits likely due to post-operative edema, of which three improved back to baseline. The 6-month survival was 77.8% and the 1-year survival was 64.8% based on Kaplan-Meier curve estimates. In this study, LITT was a relatively safe treatment for CRN, providing both a diagnostic and therapeutic solution for refractory patients. Significant increase in ablation volume was noted at 1-2 months, gradually decreasing in size to less than the original volume by 6 months. Further studies are needed to better define the role of LITT in the treatment of CRN.

A Multivariate Approach to Quantifying Risk Factors Impacting Stereotactic Robotic-Guided Stereoelectroencephalography.

BACKGROUND AND OBJECTIVES: Stereoelectroencephalography (SEEG) is an important method for invasive monitoring to establish surgical candidacy in approximately half of refractory epilepsy patients. Identifying factors affecting lead placement can mitigate potential surgical risks. This study applies multivariate analyses to identify perioperative factors affecting stereotactic electrode placement. METHODS: We collected registration and accuracy data for consecutive patients undergoing SEEG implantation between May 2022 and November 2023. Stereotactic robotic guidance, using intraoperative imaging and a novel frame-based fiducial, was used for planning and SEEG implantation. Entry-point (EE), target-point (TE), and angular errors were measured, and statistical univariate and multivariate linear regression analyses were performed. RESULTS: Twenty-seven refractory epilepsy patients (aged 15-57 years) undergoing SEEG were reviewed. Sixteen patients had unilateral implantation (10 left-sided, 6 right-sided); 11 patients underwent bilateral implantation. The mean number of electrodes per patient was 18 (SD = 3) with an average registration mean error of 0.768 mm (SD = 0.108). Overall, 486 electrodes were reviewed. Univariate analysis showed significant correlations of lead error with skull thickness (EE: P = .003; TE: P = .012); entry angle (EE: P < .001; TE: P < .001; angular error: P = .030); lead length (TE: P = .020); and order of electrode implantation (EE: P = .003; TE: P = .001). Three multiple linear regression models were used. All models featured predictors of implantation region (157 temporal, 241 frontal, 79 parietal, 9 occipital); skull thickness (mean = 5.80 mm, SD = 2.97 mm); order (range: 1-23); and entry angle in degrees (mean = 75.47, SD = 11.66). EE and TE error models additionally incorporated lead length (mean = 44.08 mm, SD = 13.90 mm) as a predictor. Implantation region and entry angle were significant predictors of error (P ≤ .05). CONCLUSION: Our study identified 2 primary predictors of SEEG lead error, region of implantation and entry angle, with nonsignificant contributions from lead length or order of electrode placement. Future considerations for SEEG may consider varying regional approaches and angles for more optimal accuracy in lead placement.

Disconnective hemispherotomy: technique and operative highlights.

Hemispherectomy is an effective procedure used in the treatment of drug-resistant hemispheric epilepsy, especially in the pediatric population. A number of resective and disconnective techniques are used, and selection of surgical strategy is paramount to achieving successful results. Notably, disconnective (or functional) hemispherotomy maximizes the benefits of safe, surgical disconnection while minimizing hemispheric tissue resection, thereby avoiding some of the perioperative factors contributing to morbidity in traditional anatomical hemispherectomy procedures. In this video, the authors outline the principal surgical steps of disconnective hemispherotomy and highlight important technical factors leading to optimal outcomes in patients with refractory, oftentimes catastrophic, hemispheric epilepsy. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2436.

Validation and Safety Profile of a Novel, Noninvasive Fiducial Attachment for Stereotactic Robotic-Guided Stereoelectroencephalography: A Case Series.

BACKGROUND AND OBJECTIVES: We developed, tested, and validated a novel, noninvasive, Leksell G frame-based fiducial attachment, for use in stereotactic registration for stereoelectroencephalography (sEEG). Use of the device increased the number of fixed reference points available for registration, while obviating the need for additional scalp incisions. We report here on our experience and safety profile of using the device. METHODS: We collected registration data using the fiducial device across 25 adult and pediatric patients with epilepsy consecutively undergoing robotic-guided sEEG for invasive epilepsy monitoring, treated between May 2022 and July 2023. ROSA One Brain was used for trajectory planning and electrode implantation. Postoperative clinical and radiographic data were computed and quantified, including mean registration error for all patients. Entry point, target point (TP), and angular errors were measured. Descriptive statistics and correlation coefficients for error were calculated. RESULTS: Twenty-five patients underwent robotic-guided sEEG implantation (11 patients, bilateral; 10 patients, left unilateral; 4 patients, right). The mean number of electrodes per patient was 18 ± 3. The average mean registration error was 0.77 ± 0.11 mm. All patients were implanted with Ad-Tech depth electrodes. No clinically relevant complications were reported. Analysis of trajectory error was performed on 446 electrodes. The median entry point error was 1.03 mm (IQR 0.69-1.54). The median TP error was 2.26 mm (IQR 1.63-2.93). The mean angular error was 0.03 radians (IQR 0.02-0.05). There was no significant correlation between root mean square error and lead error. Root mean square error did not appreciably change over time, nor were there any significant changes in average angular, entry point, or TP error metrics. CONCLUSION: A novel, noninvasive, Leksell G frame-based fiducial attachment was developed, tested, and validated, facilitating O-arm-based stereotactic registration for sEEG. This simple innovation maintained an excellent accuracy and safety profile for sEEG procedures in epilepsy patients, with the added advantages of providing additional reference points for stereotactic registration, without requiring additional scalp incisions.

Predictive factors of hydrocephalus development in pediatric patients undergoing hemispherectomy for intractable epilepsy.

OBJECTIVE: Hemispherectomy surgery is an effective procedure for pediatric patients with intractable hemispheric epilepsy. Hydrocephalus is a well-documented complication of hemispherectomy contributing substantially to patient morbidity. Despite some clinical and operative factors demonstrating an association with hydrocephalus development, the true mechanism of disease is incompletely understood. The aim of this study was to investigate a range of clinical and surgical factors that may contribute to hydrocephalus to enhance understanding of the development of this complication and to aid the clinician in optimizing peri- and postoperative surgical management. METHODS: A retrospective chart review was conducted on all pediatric patients younger than 21 years who underwent hemispherectomy surgery at the Cleveland Clinic between 2002 and 2016. Data collected for each patient included general demographic information, neurological and surgical history, surgical technique, pathological analysis, presence and duration of perioperative CSF diversion, CSF laboratory values obtained while an external ventricular drain (EVD) was in place, length of hospital stay, postoperative aseptic meningitis, and in-hospital surgical complications (including perioperative stroke, hematoma formation, wound breakdown, and/or infection). Outcomes data included hemispherectomy revision and Engel grade at last follow-up (based on the Engel Epilepsy Surgery Outcome Scale). RESULTS: Data were collected for 204 pediatric patients who underwent hemispherectomy at the authors' institution. Twenty-eight patients (14%) developed hydrocephalus requiring CSF diversion. Of these 28 patients, 13 patients (46%) presented with hydrocephalus during the postoperative period (within 90 days), while the remaining 15 patients (54%) presented later (beyond 90 days after surgery). Multivariate analysis revealed postoperative aseptic meningitis (OR 7.0, p = 0.001), anatomical hemispherectomy surgical technique (OR 16.3 for functional/disconnective hemispherectomy and OR 7.6 for modified anatomical, p = 0.004), male sex (OR 4.2, p = 0.012), and surgical complications (OR 3.8, p = 0.031) were associated with an increased risk of hydrocephalus development, while seizure freedom (OR 0.3, p = 0.038) was associated with a decreased risk of hydrocephalus. CONCLUSIONS: Hydrocephalus remains a prominent complication following hemispherectomy, presenting both in the postoperative period and months to years after surgery. Aseptic meningitis, anatomical hemispherectomy surgical technique, male sex, and surgical complications show an association with an increased rate of hydrocephalus development while seizure freedom postsurgery is associated with a decreased risk of subsequent hydrocephalus. These findings speak to the multifactorial nature of hydrocephalus development and should be considered in the management of pediatric patients undergoing hemispherectomy for medically intractable epilepsy.

The Rate and Risk Factors of Deep Brain Stimulation-Associated Complications: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) is an established neurosurgical treatment of a variety of neurological disorders. DBS is considered a safe and effective neurosurgical procedure; however, surgical complications are inevitable, and clinical outcomes may vary. The aim of this study was to describe DBS complications at a large clinical center in the United States and to investigate the relationship between patients' baseline characteristics, surgical technique, and operative complications. METHODS: We identified all patients who underwent DBS lead implantation at our center between 1st January 2012 and 1st January 2020. We extracted relevant information regarding patient demographics, surgical details, clinical complications, and clinical outcomes from the electronic medical records. RESULTS: A total of 859 leads were implanted in 481 patients (153 men, 328 women). The mean patient age at the time of the surgery was 65 years, with the mean disease duration of 13.3 years. There were no mortalities and 57 readmissions within 30 days (mean = 14.2 days). The most common complications included pneumocephalus (n = 661), edema (n = 78), altered mental state (n = 35), implantable pulse generator discomfort (n = 34), hemorrhage (n = 26), and infection (n = 23). Most notably, the use of general anesthesia, hypertension, heart disease, and depression were associated with significantly longer postoperative stay. High preoperative body mass index was associated with higher rates of surgery-related infections and lead revision/explantation. The intraoperative mean arterial pressure, anesthesia type, and frame apparatus were all important predictors of postoperative pneumocephalus. CONCLUSION: In this report, we described the rates and types of complications associated with DBS surgery at a large neurosurgical center in the United States. The novel insights highlighted in this study present an opportunity to further improve the clinical outcomes and patient selection in DBS surgery.

Radiofrequency ablation during stereoelectroencephalography: from diagnostic tool to therapeutic intervention. Illustrative case.

BACKGROUND: Radiofrequency thermocoagulation (RFTC) during intracranial stereoelectroencephalography (sEEG) was first described as a safe technique for creating lesions of epileptic foci in 2004. Since that time, the method has been applied as a diagnostic and/or palliative intervention. Although widely practiced in European epilepsy surgical programs, the technique has not been popularized in the United States given the lack of Food and Drug Administration (FDA)-approved technologies permitting safe usage of in situ sEEG electrodes for this purpose. OBSERVATIONS: The authors present a case report of a young female patient with refractory left neocortical temporal lobe epilepsy undergoing sEEG electrode implantation, who underwent sEEG-guided RFTC via a stereotactic temperature-sensing pallidotomy probe. Although used as a diagnostic step in her workup, the patient has remained seizure-free for nearly 18 months. LESSONS: The use of in situ sEEG electrodes for RFTC remains limited in the United States. In this context, this case highlights a safe alternative and temporizing approach to performing diagnostic sEEG-guided RFTC, using a temperature-sensing pallidotomy probe to create small, precise stereotactic lesions. The authors caution careful consideration of this technique as a temporary work-around solution while also highlighting the rising need for new FDA-approved technologies for safe RFTC through in situ temperature-sensing sEEG electrodes.

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.

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.

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.

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.

Alterations in cerebral oxidative metabolism following traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) generates regional alterations in cerebral metabolism, leading to the potential evolution of persistent metabolic dysfunction. In the case of penetrating, firearm-related TBI, the pathophysiological mechanisms underlying these acute-phase metabolic derangements are not entirely understood-hindering the potential effectiveness of therapeutic intervention. The use of cerebral microdialysis to monitor biochemical alterations that occur, post-TBI, provides critical insight into the events that perpetuate neurological deterioration. METHODS: Cerebral microdialysis was used to monitor alterations in the brain tissue chemistry of a 22-year-old female patient who sustained a penetrating gunshot wound to the head. Extracellular glucose, lactate, pyruvate, and lactate pyruvate ratio (LPR) were monitored over the course of the first-week post-injury. RESULTS: Analysis of the microdialysate revealed sustained elevations in LPR with peaks in excess of those seen in patients who have sustained permanent ischemic injury. This interval of persistently elevated LPR was followed by a spontaneous reduction of values, to levels below the defined threshold for metabolic crisis, over a period of several days. CONCLUSIONS: Microdialysis studies may significantly improve the understanding of the metabolic alterations that occur in patients who sustain a variety of forms of neurotrauma. Ultimately, monitoring these variations in brain tissue chemistry will improve the insight into the neuropathological mechanisms underlying penetrating traumatic brain injury, and enhance the therapeutic approach of these patients.