Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Retrograde thoracic spinal cord stimulation paddle placement for complex persistent spinal pain syndrome type 2.

BACKGROUND: Spinal cord stimulation (SCS) is a cost-effective option for treating refractory persistent spinal pain syndrome type-2 (PSPS-2). For patients with extensive spine instrumentation including the thoraco-lumbar junction, percutaneous placement of SCS leads is usually not an option being paddle leads typically implanted anterograde. Paddle lead placement will be particularly challenging in more complex cases when the instrumentation covers the targeted level. To overcome this barrier, we studied using a retrograde approach to reach the sweet spot, facilitate the placement, and reduce associated risks. OBJECTIVES: To study the use of retrograde SCS paddle as a placement method to optimize the spinal cord target and reduce the risks of conventional placement in complex cases. STUDY DESIGN: Case series and technical note. METHODS: We present three cases of thoracic retrograde SCS paddle lead placement cases, detailing patient selection, operative technique, and outcome. All the cases had extensive instrumentation to the thoraco-lumbar spine, and one had additional spinal canal stenosis. The surgical procedure entailed a retrograde midthoracic inter-laminar approach, flavectomy, and caudal placement of the paddle lead with intraoperative neurophysiologic monitoring (IONM) guidance for functional midline determination. RESULTS: All the cases had a successful lead placement over the sweet spot without complications. The same approach was used to decompress a focal spinal stenosis in one case. One case had significantly improved pain and hence underwent a pulse generator implant. The other cases had non-satisfactory pain control and were explanted. LIMITATIONS: These case description could guide technical procedural steps, however, a larger number of such cases would be needed to describe further technical nuances. CONCLUSIONS: We demonstrated that placing SCS paddle leads via retrograde midthoracic approach with IONM guidance is safe. This procedure should be an option for SCS paddle implants in patients with posterior spinal fusion encompassing the intended targeted spinal stimulation level.

Safety Analysis of a New Portable Electrical Drill With a Smart Autostop Mechanism for Bedside Cranial Procedures.

BACKGROUND AND OBJECTIVES: Bedside procedures are often helpful for neurosurgical patients, especially in neurocritical care. Portable drills with technological advancements may bring more safety and efficiency to the bedside. In this study, we compared the safety and efficiency of a new cordless electric drill with smart autostop ("HD"-Hubly Cranial Drill, Hubly Surgical) with those of a well-established standard traditional electrical neurosurgical perforator ("ST"). METHODS: A cadaveric study was conducted using both drills to perform several burr holes in the fronto-temporo-parietal region of the skull. An evaluation was performed on the number of dura plunges, and complete burr hole success rates were compared. RESULTS: A total of 174 craniotomies using the HD and 36 burr holes using the ST perforator were performed. Despite significantly exceeding intended drill bit tolerance by multiple uses of a single-use disposable HD, autostop engaged in 100% of the 174 craniotomies and before violating dura in 99.4% of the 174 craniotomies, with the single dura penetration occurring on craniotomy no. 128 after the single-use drill bit had significantly dulled beyond its single-use tolerance. Autostop engaged before dura penetration for 100% of the 36 burr holes drilled with the ST perforator ( P = .610). All the perforations were complete using the HD after resuming drilling. An autostop mechanism in a cranial drill is not commonly available for portable bedside perforators. In the operating room, most use a mechanical method to stop the rotation after losing bone resistance. This new drill uses an electrical mechanism (smart autostop) to stop drilling, making it a single-use cranial drill with advanced features for safety and efficiency at the bedside. CONCLUSION: There was no difference in the safety and efficacy of the new cordless electric drill with smart autostop when performing craniotomies compared with a traditional well-established electric cranial perforator with mechanical autostop on a cadaveric model.

Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown. METHODS: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed. RESULTS: Engel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year. CONCLUSIONS: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

Chronic subdural hematoma drainage using anti-thrombotic catheter technique.

Background: Burr hole evacuation is a well-established treatment for symptomatic cases with chronic subdural hematoma (cSDH). Routinely postoperative catheter is left in the subdural space to drain the residual blood. Drainage obstruction is commonly seen, and it can be related to suboptimal treatment. Methods: Two groups of patients submitted to cSDH surgery were evaluated in a retrospective non-randomized trial, one group that had conventional subdural drainage (CD group, n â€‹= â€‹20) and another group that used an anti-thrombotic catheter (AT group, n â€‹= â€‹14). We compared the obstruction rate, amount of drainage and complications. Statistical analyses were done using SPSS (v.28.0). Results: For AT and CD groups respectively (median â€‹± â€‹IQR), the age was 68.23 â€‹± â€‹26.0 and 70.94 â€‹± â€‹21.5 (p â€‹> â€‹0.05); preoperative hematoma width was 18.3 â€‹± â€‹11.0 â€‹mm and 20.7 â€‹± â€‹11.7 â€‹mm and midline shift was 13.0 â€‹± â€‹9.2 and 5.2 â€‹± â€‹8.0 â€‹mm (p â€‹= â€‹0.49). Postoperative hematoma width was 12.7 â€‹± â€‹9.2 â€‹mm and 10.8 â€‹± â€‹9.0 â€‹mm (p â€‹< â€‹0.001 intra-groups compared to preoperative) and MLS was 5.2 â€‹± â€‹8.0 â€‹mm and 1.5 â€‹± â€‹4.3 â€‹mm (p â€‹< â€‹0.05 intra-groups). There were no complications related to the procedure including infection, bleed worsening and edema. No proximal obstruction was observed on the AT, but 8/20 (40%) presented proximal obstruction on the CD group (p â€‹= â€‹0.006). Daily drainage rates and length of drainage were higher in AT compared to CD: 4.0 â€‹± â€‹1.25 days vs. 3.0 â€‹± â€‹1.0 days (p â€‹< â€‹0.001) and 69.86 â€‹± â€‹106.54 vs. 35.00 â€‹± â€‹59.67 â€‹mL/day (p â€‹= â€‹0.074). Symptomatic recurrence demanding surgery occurred in two patients of CD group (10%) and none in AT group (p â€‹= â€‹0.230), after adjusting for MMA embolization, there was still no difference between groups (p â€‹= â€‹0.121). Conclusion: The anti-thrombotic catheter for cSDH drainage presented significant less proximal obstruction than the conventional one and higher daily drainage rates. Both methods demonstrated to safe and effective for draining cSDH.

Covert Tracking to Visual Stimuli in Comatose Patients With Traumatic Brain Injury.

OBJECTIVES: This study investigated video eye tracking (VET) in comatose patients with traumatic brain injury (TBI). METHODS: We recruited healthy participants and unresponsive patients with TBI. We surveyed the patients' clinicians on whether the patient was tracking and performed the Coma Recovery Scale-Revised (CRS-R). We recorded eye movements in response to motion of a finger, a face, a mirror, and an optokinetic stimulus using VET glasses. Patients were classified as covert tracking (tracking on VET alone) and overt tracking (VET and clinical examination). The ability to obey commands was evaluated at 6-month follow-up. RESULTS: We recruited 20 healthy participants and 10 patients with TBI. The use of VET was feasible in all participants and patients. Two patients demonstrated covert tracking (CRS-R of 6 and 8), 2 demonstrated overt tracking (CRS-R of 22 and 11), and 6 patients had no tracking (CRS-R of 8, 6, 5, 7, 6, and 7). Five of 56 (9%) tracking assessments were missed on clinical examination. All patients with tracking recovered consciousness at follow-up, whereas only 2 of 6 patients without tracking recovered at follow-up. DISCUSSION: VET is a feasible method to measure covert tracking. Future studies are needed to confirm the prognostic value of covert tracking.

Neurologic Outcomes for Octogenarians Undergoing Emergent Surgery for Traumatic Acute Subdural Hematoma.

BACKGROUND: Determining the appropriate surgical indications for obtunded octogenarians with traumatic acute subdural hematoma (aSDH) has been challenging. We sought to determine which easily available data would be useful adjuncts to assist in early and quick decision-making. METHODS: We performed a single-center, retrospective review of patients aged ≥80 years with confirmed traumatic aSDH who had undergone emergent surgery. The clinical measurements included the Karnofsky performance scale score, Charlson comorbidity index, Glasgow coma scale (GCS), and abbreviated injury score. The radiographic measurements included the Rotterdam computed tomography score, aSDH thickness, midline shift, and optic nerve sheath diameter (ONSD). The neurologic outcomes were defined using the extended Glasgow outcome scale-extended (GOS-E) at hospital discharge and 3-month follow-up. The Pearson correlation coefficient was used to compare the ONSD with all clinical, radiographic, and outcome variables. Multivariate logistic regression was used to assess the relationship between the discharge and 3-month GOS-E scores between all clinical and radiographic variables. RESULTS: A total of 17 patients met the inclusion criteria. The mean age was 82.5 ± 1.6 years (range, 80-85 years), and the mean GCS score was 11.2 ± 4.1 (range, 4-15). The mean discharge and 3-month GOS-E scores were 3.4 ± 2.6 (range, 1-8) and 2.3 ± 2.1 (range, 1-7), respectively. We found significant negative correlations between the ONSD and the GCS score (r = -0.62; P < 0.01) and the ONSD and discharge GOS-E score (r = -0.49; P = 0.05). Multivariate analysis revealed a significant association between the abbreviated injury score and the discharge GOS-E score (P = 0.05). CONCLUSIONS: Octogenarians sustaining aSDH and requiring emergent surgery have poor outcomes. More data are needed to determine whether the ONSD can be a useful adjunct tool to predict the efficacy of emergent surgery.

Simple wound closure compared with surgery for civilian cranial gunshot wounds.

OBJECTIVE: A carefully selected subset of civilian cranial gunshot wound (CGSW) patients may be treated with simple wound closure (SWC) as a proactive therapy, but the appropriate clinical scenario for using this strategy is unknown. The aim of this study was to compare SWC and surgery patients in terms of their neurological outcomes and complications, including infections, seizures, and reoperations. METHODS: This was a single-center, retrospective review of the prospectively maintained institutional traumatic brain injury and trauma registries. Included were adults who sustained an acute CGSW defined as suspected or confirmed dural penetration. Excluded were nonfirearm penetrating injuries, patients with an initial Glasgow Coma Scale (GCS) score of 3, patients with an initial GCS score of 4 and nonreactive pupils, and patients who died within 48 hours of presentation. RESULTS: A total of 67 patients were included; 17 (25.4%) were treated with SWC and 50 (74.6%) were treated with surgery. The SWC group had a lower incidence of radiographic mass effect (3/17 [17.6%] SWC vs 31/50 [62%] surgery; absolute difference 44.4, 95% CI -71.9 to 16.8; p = 0.002) and lower incidence of involvement of the frontal sinus (0/17 [0%] SWC vs 14/50 [28%] surgery; absolute difference 28, 95% CI -50.4 to 5.6; p = 0.01). There were no differences in the frequency of Glasgow Outcome Scale-Extended scores ≥ 5 between the SWC and surgery groups at 30 days (4/11 [36.4%] SWC vs 12/35 [34.3%] surgery; OR 1.1, 95% CI 0.3-4.5; p > 0.99), 60 days (2/7 [28.6%] SWC vs 8/26 [30.8%] surgery; OR 0.9, 95% CI 0.3-3.4; p > 0.99), and 90 days (3/8 [37.5%] SWC vs 12/26 [46.2%] surgery; OR 0.7, 95% CI 0.1-3.6; p > 0.99). There were no differences in the incidence of infections (1/17 [5.9%] SWC vs 6/50 [12%] surgery; OR 0.5, 95% CI 0.1-4.1; p = 0.67), CSF fistulas (2/11 [11.6%] SWC vs 3/50 [6%] surgery; OR 2.1, 95% CI 0.3-13.7; p = 0.60), seizures (3/17 [17.6%] SWC vs 9/50 [18%] surgery; OR 1, 95% CI 0.2-4.1; p > 0.99), and reoperations (3/17 [17.6%] SWC vs 4/50 [8%] surgery; OR 2.5, 95% CI 0.5-12.4; p = 0.36) between the SWC and surgery groups. CONCLUSIONS: There were important clinically relevant differences between the SWC and surgery groups. SWC can be considered a safe and efficacious proactive therapy in a carefully selected subset of civilian CGSW patients.

Robotic-assisted stereotactic percutaneous balloon compression for trigeminal neuralgia treatment.

Trigeminal neuralgia (TN) is a facial pain disorder that can be a source of significant disability. Percutaneous balloon compression (PBC) has low cost, high efficacy, and minimal invasiveness. Complications can occur due to the balloon inflation or the needle placement itself. In this paper, we describe for the first time the clinical use of robotic-assistance to perform a PBC for TN, presenting our experience in two patients. The stereotactic planning targeted the foramen ovale (FO) establishing a safe and seamless needle trajectory. This yielded a streamlined, single pass needle placement and eliminated the need to "search" for the FO. There were no immediate complications and post-operatively both patients improved their symptoms. Robotic assistance is potentially a useful tool to reduce needle placement related complications, radiation exposure and PBC learning curve.

Design-development of an at-home modular brain-computer interface (BCI) platform in a case study of cervical spinal cord injury.

OBJECTIVE: The objective of this study was to develop a portable and modular brain-computer interface (BCI) software platform independent of input and output devices. We implemented this platform in a case study of a subject with cervical spinal cord injury (C5 ASIA A). BACKGROUND: BCIs can restore independence for individuals with paralysis by using brain signals to control prosthetics or trigger functional electrical stimulation. Though several studies have successfully implemented this technology in the laboratory and the home, portability, device configuration, and caregiver setup remain challenges that limit deployment to the home environment. Portability is essential for transitioning BCI from the laboratory to the home. METHODS: The BCI platform implementation consisted of an Activa PC + S generator with two subdural four-contact electrodes implanted over the dominant left hand-arm region of the sensorimotor cortex, a minicomputer fixed to the back of the subject's wheelchair, a custom mobile phone application, and a mechanical glove as the end effector. To quantify the performance for this at-home implementation of the BCI, we quantified system setup time at home, chronic (14-month) decoding accuracy, hardware and software profiling, and Bluetooth communication latency between the App and the minicomputer. We created a dataset of motor-imagery labeled signals to train a binary motor imagery classifier on a remote computer for online, at-home use. RESULTS: Average bluetooth data transmission delay between the minicomputer and mobile App was 23 ± 0.014 ms. The average setup time for the subject's caregiver was 5.6 ± 0.83 min. The average times to acquire and decode neural signals and to send those decoded signals to the end-effector were respectively 404.1 ms and 1.02 ms. The 14-month median accuracy of the trained motor imagery classifier was 87.5 ± 4.71% without retraining. CONCLUSIONS: The study presents the feasibility of an at-home BCI system that subjects can seamlessly operate using a friendly mobile user interface, which does not require daily calibration nor the presence of a technical person for at-home setup. The study also describes the portability of the BCI system and the ability to plug-and-play multiple end effectors, providing the end-user the flexibility to choose the end effector to accomplish specific motor tasks for daily needs. Trial registration ClinicalTrials.gov: NCT02564419. First posted on 9/30/2015.

Traumatic brain injury and subsequent brain tumor development: a systematic review of the literature.

The role of prior head trauma in stimulating brain tumor development has been previously described in the literature but continues to be debated. The goal of this study was to conduct a systematic review interrogating the contemporary literature to delineate any possible relationship between traumatic brain injury and brain tumor development. A systematic review exploring development of post-TBI brain tumor was conducted by searching electronic databases. Abstracts from articles were read and selected for full-text review according to criteria previously established in the scientific literature. Relevant full-text articles were divided into case reports and single-arm studies and epidemiological studies. Of 1070 resultant articles, 18 case reports and single-arm studies (level of evidence of IV and V) with 45 patients were included. The most common cause of TBI was traffic accidents. The average period between TBI and subsequent tumor diagnosis was 12.8 years. Meningiomas represented the largest share of tumors, followed by gliomas. Most post-TBI brain tumors developed in the frontal and temporal lobes. Fifteen epidemiological studies were also interrogated from a variety of countries (level of evidence of III). Case-control studies were more common than cohort studies. There were 9 of 15 studies proposed a possible relationship between history of head trauma and development of brain tumor. The relationship between head trauma and neoplastic growth continues to be heavily debated. There are certainly case reports and epidemiological studies in the literature that suggest a correlational relationship between the two. However, there is no concrete evidence of a causal relationship between TBI and brain tumors. More research is needed to definitively delineate the extent of any such relationship.

Clinical complications of surviving gunshot wounds to the head in children and adolescents: the Miami experience.

BACKGROUND: Gunshot wounds (GSWs) to the head in the pediatric population are both rare and devastating, with the clinical course of pediatric survivors poorly understood. Correspondingly, the aim of this study was to summarize the clinical complications clinicians can expect of survivors of GSW to the head in children and adolescents in hospital and after discharge. METHODS: A retrospective review of our Level 1 trauma center database between 2011 and 2021 was performed. Clinical data was extracted for those patients aged ≤ 18 years old who survived initial hospitalization with at least one documented follow-up. Categorical data were then compared using Chi-squared test. RESULTS: A total of 19 pediatric survivors of GSW to the head satisfied all selection criteria with an average age was 15.3 years. The majority of cases were isolated head injuries (63%), with an average Glasgow Coma Score (GCS) of 11.9. Bullet trajectory was intraparenchymal in 11 (58%) cases and extraparenchymal in 8 (42%) cases, with 15 (79%) patients treated by surgical intervention. A total of 13 (68%) patients experienced a complication during their hospitalization, with the most common being sympathetic hypertension and endocrinologic salt wasting, each occurring in 5 (26%) patients. With respect to complication categories, the intraparenchymal patients experienced statistically more complications than extraparenchymal patients that were infectious (54% vs 0%, P = 0.01) and sympathetic (45% vs 0%, P = 0.03) in nature. However, with respect to overall neurologic (P = 0.24), endocrinologic (P = 0.24), and traumatic (P = 0.24) complications, their incidences were statistically comparable. All patients were successfully discharged on average post-injury day 22 with an average GCS of 14.0. Mean follow-up for the cohort was 42.6 months, with an average GCS of 14.3. A total of 6 (32%) patients experienced a complication relatable to their initial GSW injury after discharge. The most common individual complication was new-onset seizures in 3 (16%) patients. CONCLUSIONS: Survivors of pediatric GSW to the head can experience multi-systemic complications during both initial hospitalization and afterwards, and bullet trajectory involving the parenchyma may be associated with specific complications more than others. Dedicated inpatient management and outpatient follow-up involving surveillance for complications across all systems, not just neurological, are recommended to ensure patients receive the best care possible.

Burr Hole Hematoma Evacuation of Large Subdural Component Using Recombinant Tissue-Type Plasminogen Activator and a Novel Catheter: Case Report.

The large acute component in a chronic subdural hematoma (cSDH) typically requires a craniotomy. Open surgery can be associated with increased morbidity and is not always possible due to systemic conditions. We present the case of a 58-year-old patient who presented with a Glasgow Coma Scale (GCS) of three fixed pupils, but remaining brainstem reflexes were present. Brain CT showed a large mixed subdural left chronic hematoma, with a predominant acute component, with a 26mm midline shift. The patient was hemodynamically unstable and coagulopathic; thus, emergency bedside burr hole evacuation was done. An "anti-thrombotic catheter" was left in the subdural space as a postoperative drain. Postoperatively, GCS improved, and CT presented a residual 12.7mm midline shift due to the acute bleeding component. Recombinant tissue-type plasminogen activator (r-tPA) solution was repeatedly administered using the catheter for two days, and it continued to drain for 10 more days with no additional dose. The patient presented clinical and radiological improvement with the dissolution of the acute component. This case is the first description of local subdural use of r-tPA to treat the acute component of cSDH with success associated with an anti-thrombotic catheter.

Machine learning to predict passenger mortality and hospital length of stay following motor vehicle collision.

OBJECTIVE: Motor vehicle collisions (MVCs) account for 1.35 million deaths and cost $518 billion US dollars each year worldwide, disproportionately affecting young patients and low-income nations. The ability to successfully anticipate clinical outcomes will help physicians form effective management strategies and counsel families with greater accuracy. The authors aimed to train several classifiers, including a neural network model, to accurately predict MVC outcomes. METHODS: A prospectively maintained database at a single institution's level I trauma center was queried to identify all patients involved in MVCs over a 20-year period, generating a final study sample of 16,287 patients from 1998 to 2017. Patients were categorized by in-hospital mortality (during admission) and length of stay (LOS), if admitted. All models included age (years), Glasgow Coma Scale (GCS) score, and Injury Severity Score (ISS). The in-hospital mortality and hospital LOS models further included time to admission. RESULTS: After comparing a variety of machine learning classifiers, a neural network most effectively predicted the target features. In isolated testing phases, the neural network models returned reliable, highly accurate predictions: the in-hospital mortality model performed with 92% sensitivity, 90% specificity, and a 0.98 area under the receiver operating characteristic curve (AUROC), and the LOS model performed with 2.23 days mean absolute error after optimization. CONCLUSIONS: The neural network models in this study predicted mortality and hospital LOS with high accuracy from the relatively few clinical variables available in real time. Multicenter prospective validation is ultimately required to assess the generalizability of these findings. These next steps are currently in preparation.

Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.

OBJECTIVE: Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. METHODS: Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. RESULTS: Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). SIGNIFICANCE: LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.

Inhibition of glial D-serine release rescues synaptic damage after brain injury.

Synaptic damage is one of the most prevalent pathophysiological responses to traumatic CNS injury and underlies much of the associated cognitive dysfunction; however, it is poorly understood. The D-amino acid, D-serine, serves as the primary co-agonist at synaptic NMDA receptors (NDMARs) and is a critical mediator of NMDAR-dependent transmission and synaptic plasticity. In physiological conditions, D-serine is produced and released by neurons from the enzymatic conversion of L-serine by serine racemase (SRR). However, under inflammatory conditions, glial cells become a major source of D-serine. Here, we report that D-serine synthesized by reactive glia plays a critical role in synaptic damage after traumatic brain injury (TBI) and identify the therapeutic potential of inhibiting glial D-serine release though the transporter Slc1a4 (ASCT1). Furthermore, using cell-specific genetic strategies and pharmacology, we demonstrate that TBI-induced synaptic damage and memory impairment requires D-serine synthesis and release from both reactive astrocytes and microglia. Analysis of the murine cortex and acutely resected human TBI brain also show increased SRR and Slc1a4 levels. Together, these findings support a novel role for glial D-serine in acute pathological dysfunction following brain trauma, whereby these reactive cells provide the excess co-agonist levels necessary to initiate NMDAR-mediated synaptic damage.

Brain-Computer interface control of stepping from invasive electrocorticography upper-limb motor imagery in a patient with quadriplegia.

Introduction: Most spinal cord injuries (SCI) result in lower extremities paralysis, thus diminishing ambulation. Using brain-computer interfaces (BCI), patients may regain leg control using neural signals that actuate assistive devices. Here, we present a case of a subject with cervical SCI with an implanted electrocorticography (ECoG) device and determined whether the system is capable of motor-imagery-initiated walking in an assistive ambulator. Methods: A 24-year-old male subject with cervical SCI (C5 ASIA A) was implanted before the study with an ECoG sensing device over the sensorimotor hand region of the brain. The subject used motor-imagery (MI) to train decoders to classify sensorimotor rhythms. Fifteen sessions of closed-loop trials followed in which the subject ambulated for one hour on a robotic-assisted weight-supported treadmill one to three times per week. We evaluated the stability of the best-performing decoder over time to initiate walking on the treadmill by decoding upper-limb (UL) MI. Results: An online bagged trees classifier performed best with an accuracy of 84.15% averaged across 9 weeks. Decoder accuracy remained stable following throughout closed-loop data collection. Discussion: These results demonstrate that decoding UL MI is a feasible control signal for use in lower-limb motor control. Invasive BCI systems designed for upper-extremity motor control can be extended for controlling systems beyond upper extremity control alone. Importantly, the decoders used were able to use the invasive signal over several weeks to accurately classify MI from the invasive signal. More work is needed to determine the long-term consequence between UL MI and the resulting lower-limb control.

MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson's Disease Patient With Levodopa-Resistant Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) is a debilitating motor deficit in a subset of Parkinson's Disease (PD) patients that is poorly responsive to levodopa or deep brain stimulation (DBS) of established PD targets. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN), to address FOG was based on its observed neuropathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region (MLR). Initial reports of PPN DBS were met with enthusiasm; however, subsequent studies reported mixed results. A closer review of the MLR basic science literature, suggests that the closely related cuneiform nucleus (CnF), dorsal to the PPN, may be a superior site to promote gait. Although suspected to have a conserved role in the control of gait in humans, deliberate stimulation of a homolog to the CnF in humans using directional DBS electrodes has not been attempted. METHODS: As part of an open-label Phase 1 clinical study, one PD patient with predominantly axial symptoms and severe FOG refractory to levodopa therapy was implanted with directional DBS electrodes (Boston Science Vercise CartesiaTM) targeting the CnF bilaterally. Since the CnF is a poorly defined reticular nucleus, targeting was guided both by diffusion tensor imaging (DTI) tractography and anatomical landmarks. Intraoperative stimulation and microelectrode recordings were performed near the targets with leg EMG surface recordings in the subject. RESULTS: Post-operative imaging revealed accurate targeting of both leads to the designated CnF. Intraoperative stimulation near the target at low thresholds in the awake patient evoked involuntary electromyography (EMG) oscillations in the legs with a peak power at the stimulation frequency, similar to observations with CnF DBS in animals. Oscillopsia was the primary side effect evoked at higher currents, especially when directed posterolaterally. Directional DBS could mitigate oscillopsia. CONCLUSION: DTI-based targeting and intraoperative stimulation to evoke limb EMG activity may be useful methods to help target the CnF accurately and safely in patients. Long term follow-up and detailed gait testing of patients undergoing CnF stimulation will be necessary to confirm the effects on FOG. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04218526.

Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson's disease: study protocol for a prospective, pilot trial.

BACKGROUND: Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of Parkinson's disease (PD) patients that is poorly responsive to standard levodopa therapy or deep brain stimulation (DBS) of established PD targets such as the subthalamic nucleus and the globus pallidus interna. The proposal of a DBS target in the midbrain, known as the pedunculopontine nucleus (PPN) to address FOG, was based on its observed pathology in PD and its hypothesized involvement in locomotor control as a part of the mesencephalic locomotor region, a functionally defined area of the midbrain that elicits locomotion in both intact animals and decerebrate animal preparations with electrical stimulation. Initial reports of PPN DBS were met with much enthusiasm; however, subsequent studies produced mixed results, and recent meta-analysis results have been far less convincing than initially expected. A closer review of the extensive mesencephalic locomotor region (MLR) preclinical literature, including recent optogenetics studies, strongly suggests that the closely related cuneiform nucleus (CnF), just dorsal to the PPN, may be a superior target to promote gait initiation. METHODS: We will conduct a prospective, open-label, single-arm pilot study to assess safety and feasibility of CnF DBS in PD patients with levodopa-refractory FOG. Four patients will receive CnF DBS and have gait assessments with and without DBS during a 6-month follow-up. DISCUSSION: This paper presents the study design and rationale for a pilot study investigating a novel DBS target for gait dysfunction, including targeting considerations. This pilot study is intended to support future larger scale clinical trials investigating this target. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04218526 (registered January 6, 2020).

Deep learning for robust detection of interictal epileptiform discharges.

Objective.Automatic detection of interictal epileptiform discharges (IEDs, short as 'spikes') from an epileptic brain can help predict seizure recurrence and support the diagnosis of epilepsy. Developing fast, reliable and robust detection methods for IEDs based on scalp or intracranial electroencephalogram (iEEG) may facilitate online seizure monitoring and closed-loop neurostimulation.Approach.We developed a new deep learning approach, which employs a long short-term memory network architecture ('IEDnet') and an auxiliary classifier generative adversarial network (AC-GAN), to train on both expert-annotated and augmented spike events from iEEG recordings of epilepsy patients. We validated our IEDnet with two real-world iEEG datasets, and compared IEDnet with the support vector machine (SVM) and random forest (RF) classifiers on their detection performances.Main results.IEDnet achieved excellent cross-validated detection performances in terms of both sensitivity and specificity, and outperformed SVM and RF. Synthetic spike samples augmented by AC-GAN further improved the detection performance. In addition, the performance of IEDnet was robust with respect to the sampling frequency and noise. Furthermore, we demonstrated the cross-institutional generalization ability of IEDnet while testing between two datasets.Significance.IEDnet achieves excellent detection performances in identifying interictal spikes. AC-GAN can produce augmented iEEG samples to improve supervised deep learning.