Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA. METHODS: The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study's initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment. RESULTS: Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists. CONCLUSIONS: The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated. TRIAL REGISTRATION: NCT04539964; August 31, 2020.

Vacuum-assisted scalp repositioning: a novel temporizing approach to acute sinking skin flap syndrome. Illustrative cases.

BACKGROUND: This report describes the use of a novel approach to address acute sinking skin flap syndrome (SSFS), a postcraniectomy complication arising from brain dysfunction beneath the skull defect. The authors present a case series of two patients, emphasizing the prospective application of an external plaster cast in tandem with a vacuum-assisted closure (VAC) device (wound VAC) to promptly reposition the scalp and relieve brain compression. OBSERVATIONS: Following intervention, one patient showed immediate neurological improvement, with complete resolution of symptoms within hours. Conversely, the second patient developed nonconvulsive status epilepticus. Computed tomography scans postintervention validated the successful scalp repositioning and mass effect resolution in both instances. This temporary approach proved successful in one patient with moderate symptoms, serving as a bridge to cranioplasty. LESSONS: The integration of an external plaster cast and wound VAC offers a cost-effective and prompt solution for patients with acute SSFS pending cranioplasty. Appropriate patient selection and heightened caution for those with severe symptoms should be exercised.

Baseline frailty status, not advanced patient age, predicts epilepsy surgery outcomes: An analysis of 696 patients from the NSQIP database.

OBJECTIVE: Preoperative risk stratification of patients undergoing epilepsy surgery remains challenging. Recently, the efforts to look beyond age alone as an outcomes predictor has resulted in the development of measures of physiological reserve, or 'frailty indices.' The most frequently cited index in neurosurgery is the 11-item or 5-item modified frailty index (mFI11 or mFI-5). The present study aimed to use a large national registry to evaluate the effect of frailty (as measured by mFI-5 versus age on postoperative outcomes of patients undergoing epilepsy surgery. METHODS: The National Surgical Quality Improvement Program (NSQIP) database, overseen by the American College of Surgeons (ACS), was used to extract data for patients undergoing epilepsy surgery from 2015 to 2019. Univariate and multivariate analyses for age and mFI-5 were performed for the following 30-day outcomes of extended length of hospital stay (eLOS) and non-home discharge (NHD). The effect sizes were summarized by odds ratio and associated 95 % confidence intervals. Receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC), was used to quantify the discrimination. RESULTS: Univariate and multivariate analyses demonstrated that frailty statuses from mFI-5, not age, were significantly predictive of eLOS and NHD. On ROC curve analysis, mFI-5 was a stronger predictor of eLOS (C = 0.59, 95 % CI 0.54-0.64, p < 0.001) and NHD (C = 0.69, 95 % CI 0.64-0.76, p < 0.001) than age (C = 0.53, 95 % CI 0.48-0.58, p = 0.21 and C = 0.53, 95 % CI 0.46-0.59, p = 0.44, respectively). CONCLUSION: Frailty, not age, is an independent risk factor for poor postoperative outcomes, particularly eLOS and NHD, in patients undergoing epilepsy surgery. Usage of mFI-5 for preoperative risk stratification of epilepsy surgery patients can help in prognostication.

Frailty Measured by the Risk Analysis Index Predicts Nonhome Discharge and Mortality After Resection in Refractory Epilepsy: Analysis of 1236 Patients From a Prospective Surgical Registry, 2012 to 2020.

BACKGROUND: Risk stratification of epilepsy surgery patients remains difficult. The Risk Analysis Index (RAI) is a frailty measurement that augments preoperative risk stratification. OBJECTIVE: To evaluate RAI's discriminative threshold for nonhome discharge disposition (NHD) and mortality (or discharge to hospice within 30 days of operation) in epilepsy surgery patients. METHODS: Patients were queried from the American College of Surgeons-National Surgical Quality Improvement Program database (2012-2020) using diagnosis/procedure codes. Linear-by-linear trend tests assessed RAI's relationship with NHD and mortality. Discriminatory accuracy was assessed by C-statistics (95% CI) in receiver operating characteristic curve analysis. RESULTS: Epilepsy resections (N = 1236) were grouped into temporal lobe (60.4%, N = 747) and nontemporal lobe (39.6%, N = 489) procedures. Patients were stratified by RAI tier: 76.5% robust (RAI 0-20), 16.2% normal (RAI 21-30), 6.6% frail (RAI 31-40), and 0.8% severely frail (RAI 41 and above). The NHD rate was 18.0% (N = 222) and positively associated with increasing RAI tier: 12.5% robust, 34.0% normal, 38.3% frail, and 50.0% severely frail ( P < .001). RAI had robust predictive discrimination for NHD in overall cohort (C-statistic 0.71), temporal lobe (C-statistic 0.70), and nontemporal lobe (C-statistic 0.71) cohorts. The mortality rate was 2.7% (N = 33) and significantly associated with RAI frailty: 1.1% robust, 8.0% normal, 6.2% frail, and 20.0% severely frail ( P < .001). RAI had excellent predictive discrimination for mortality in overall cohort (C-statistic 0.78), temporal lobe (C-statistic 0.80), and nontemporal lobe (C-statistic 0.74) cohorts. CONCLUSION: The RAI frailty score predicts mortality and NHD after epilepsy surgery. This is accomplished with a user-friendly calculator: https://nsgyfrailtyoutcomeslab.shinyapps.io/epilepsy/ .

Neuroinvasive Onchocerca lupi Infection in a Ten-Year-Old Girl.

The nematode Onchocerca lupi is an emerging human pathogen. Though its life cycle is not well studied, it likely infects humans after a bite from a black fly vector, which in turn acquires infective microfilariae from an infected canid. These microfilariae mature into an infective larval stage within the fly. Among six reported cases in the United States, five involved children, and all occurred in the southwest. In this report, we present a case of O. lupi infection with cervical spine invasion in a healthy 10-year-old girl. She presented with five months of neurological symptoms from a rural and medically underserved area, highlighting a need for clinical vigilance in such settings for this emerging infectious threat in the American southwest.

An In Vitro Study of Magnetic Field Interference with an Electronic Shunt Programmer.

BACKGROUND: Programmable shunts play a valuable role in the treatment of hydrocephalus. However, the use of magnets in programming these valves has caused obstacles in today's magnetized world. Previous studies have reported problems with magnetic toys and electronics unintentionally reprogramming shunt valves. This study investigated how an Apple Watch can interfere with the Codman CERTAS Plus electronic programmer. METHODS: In this in vitro study, we tested the magnetic field emitted by Apple Watch Series 3, 4, 5, and 6 using an electromagnetic field tester at distances of 0-50 mm. We conducted 20 trials of shunt programming and shunt setting reading with and without each watch. RESULTS: All 4 watches generated significant magnetic fields. Maximum magnetic fields were Series 3, 165.73 millitesla (mT); Series 4, 144.91 mT; Series 5, 131.09 mT; and Series 6, 130.68 mT. All 4 watches interfered with the programmer's ability to correctly read and program the valve setting. CONCLUSIONS: The Codman CERTAS Plus electronic programmer detects the magnetic field emitted from an Apple Watch and mistakes it for the valve, rendering programming difficult. These smartwatches and similar electronic devices should be kept away from the programmer and not worn by health care providers to avoid inappropriate readings and setting changes.

Trends in United States pediatric neurosurgical practice during the COVID-19 pandemic.

There is minimal information on COVID-19 pandemic's national impact on pediatric neurosurgical operative volumes. In this study, using a national database, TriNetX, we compared the overall and seasonal trends of pediatric neurosurgical procedure volumes in the United States during the pandemic to pre-pandemic periods. In the United States, the incidence of COVID-19 began to rise in September 2020 and reached its maximum peak between December 2020 and January 2021. During this time, there was an inverse relationship between pediatric neurosurgical operative volumes and the incidence of COVID-19 cases. From March 2020 to May 2021, there was a significant decrease in the number of pediatric shunt (-11.7% mean change, p = 0.006), epilepsy (-16.6%, p < 0.001), and neurosurgical trauma (-13.8%, p < 0.001) surgeries compared to pre-pandemic years. The seasonal analysis also yielded a broad decrease in most subcategories in spring 2020 with significant decreases in pediatric spine, epilepsy, and trauma cases. To the best of our knowledge, this is the first study to report a national decline in pediatric shunt, epilepsy, and neurosurgical trauma operative volumes during the pandemic. This could be due to fear-related changes in health-seeking behavior as well as underdiagnosis during the COVID-19 pandemic.

Impact of insurance status, hospital ownership type, and children's hospital designation on outcomes for pediatric neurosurgery patients following spasticity procedures in the USA.

PURPOSE: This study aims to examine the relationship between insurance status, hospital ownership type, and children's hospital designation with outcomes for pediatric patients undergoing neurosurgical treatment for spasticity. METHODS: This retrospective cohort study utilized the Healthcare Cost and Utilization Project Kids' Inpatient Database and included 11,916 pediatric patients (≤ 17 years of age) who underwent neurosurgical treatment for spasticity between 2006 and 2012 using ICD-9-CM procedure codes. RESULTS: Uninsured patients had a significantly shorter hospital length of stay compared to Medicaid patients (-1.42 days, P = 0.030) as did privately insured patients (-0.74 days; P = 0.035). Discharge disposition and inpatient mortality rate were not associated with insurance status. There were no significant associations with hospital ownership type. Free-standing children's hospitals retained patients significantly longer compared to non-children's hospitals (+1.48 days; P = 0.012) and had a significantly higher likelihood of favorable discharge disposition (P = 0.004). Mortality rate was not associated with children's hospital designation. CONCLUSION: Pediatric patients undergoing neurosurgical treatment for spasticity were more likely to stay in the hospital longer if they were insured by Medicaid or treated in a free-standing children's hospital. In addition, patients in free standing children's hospitals were more likely to be discharged with a favorable disposition.

Necessity of brain imaging in COVID-19 infected patients presenting with acute neurological deficits.

BACKGROUND: Patients undergoing cardiopulmonary stabilization in the intensive care unit for novel coronavirus (COVID-19) are often sedated, placing timely assessment of a neurological decline at risk. CASE DESCRIPTION: Here, we present two cases of COVID-19 infected young patients transferred to our facility in a cardio-pulmonary crisis, with a poor neurological exam. While there was significant delay in obtaining brain imaging in the first patient, the second patient had timely recognition of her ischemic infarct, underwent emergent surgery, and is now doing well. CONCLUSIONS: These cases highlight the importance of early head imaging in COVID-19 patients with a poor neurological exam. While lungs remain the primary target of COVID-19, these cases alert the medical community to suspect involvement of the central nervous system, since there may be life-saving surgical interventions available.

Tenosynovial Giant Cell Tumor in an Infant.

In this report, the authors describe a child presenting at 6 months old with a rapidly expanding extracranial left temporal mass concerning for malignancy. The mass was successfully treated at 16 months with radical surgical excision. The patient was found to have a tenosynovial giant cell tumor, diffuse type, completely encased by the temporalis muscle. To our knowledge, this is the first report of a case of diffuse type tenosynovial giant cell tumor in the temporalis muscle, without articular involvement, presenting in an infant.

Successful Novel Treatment of a Paraspinal Primitive Neuroectodermal Tumor with Predominantly Glial Differentiation: A 3-Year Follow-Up After Surgery, Intensity-Modulated Radiation Therapy and Oral Temozolomide.

BACKGROUND: Paraspinal masses are a relatively uncommon but diverse group of lesions that can be neoplastic or non-neoplastic. Peripheral primitive neuroectodermal tumors of the lumbar paraspinal region with diffuse and strong glial differentiation have never been reported before. CASE DESCRIPTION: We report a primary paraspinal primitive neuroectodermal tumor with overwhelming glial differentiation in a 23-year-old female patient who presented with intractable right lower extremity pain. The patient underwent a 2-staged operation with gross total resection of the mass followed by intensity-modulated radiation therapy and oral temozolomide, a regimen employed for high-grade intracranial gliomas. Serial imaging revealed no evidence of recurrence after 3 years. CONCLUSIONS: Although these lesions appear to be exceptionally rare, an approach similar to that of intracranial high-grade glial tumors was effective in our experience. Our patient had no evidence of recurrence at 3-year follow-up.

Calcified Middle Cranial Fossa Mass.

A 21-year-old male presented for evaluation of transient loss of consciousness and was found to have a hyperdense mass in the left middle fossa. He underwent craniotomy for tumor resection. Intra- and extradural invasion was noted. Gross total resection was achieved. Pathology demonstrated a densely cellular neoplasm with predominately spindle cell morphology in a collagen-containing stroma, areas of vascular proliferation, focal mineralization, and regions of cartilage formation. High mitotic index and regions of necrosis were seen. Based on the final diagnosis of osteosarcoma, the patient was referred for chemotherapy and radiation. Intracranial osteosarcoma is a nonmeningiomatous mesenchymal tumor. Most osteosarcomas are meningeal-based and supratentorial. Presentation depends on tumor location and may include focal neurologic deficits, cranial neuropathy, seizures, or symptoms of increased intracranial pressure. Given the relative rarity of intracranial osteosarcoma, there are no established guidelines for treatment, and therapy is guided by experience with systemic osteosarcoma. Gross total resection is recommended whenever feasible. Both chemotherapy and radiation therapy are used as adjuvant therapy. Regardless of treatment, osteosarcoma remains a highly aggressive malignancy with a poor prognosis. Morbidity and mortality may be the result of local recurrence or development of pulmonary or skeletal metastasis.

Neurosurgical Emergencies in Sports Neurology.

PURPOSE OF REVIEW: Athletic neurosurgical emergencies are injuries that can lead to mortality or significant morbidity and require immediate recognition and treatment. This review article discusses the epidemiology of sports-related traumatic brain injury (TBI) with an attempt to quantify the incidence of neurosurgical emergencies in sports. Emergencies such as intracranial hemorrhage, second impact syndrome, vascular injuries, and seizures are discussed. RECENT FINDINGS: The incidence of sports-related TBI presenting to level I or II trauma centers in the USA is about 10 in 100,000 population per year. About 14 % of the adult sports-related TBIs and 13 % of the pediatric sports-related TBIs were moderate or severe in nature. Patients presenting with headache and neck pain should prompt further investigation for cervical spine and vascular injuries. CT angiography is becoming the modality of choice to screen for blunt cerebrovascular injuries. The treatment of these injuries remains controversial. High-quality evidence in sports-related TBI is lacking. Further research is required to help guide management of this increasingly prevalent condition. The role of prevention and education should also not be underestimated.

Borden-Shucart Type I dural arteriovenous fistulas: clinical course including risk of conversion to higher-grade fistulas.

OBJECT: The goal of this study was to determine the clinical course of Borden-Shucart Type I cranial dural arteriovenous fistulas (DAVFs) and to calculate the annual rate of conversion of these lesions to more aggressive fistulas that have cortical venous drainage (CVD). METHODS: A retrospective chart review was conducted of all patients harboring DAVFs who were seen at the authors' institution between 1997 and 2009. Twenty-three patients with Type I DAVFs who had available clinical follow-up were identified. Angiographic and clinical data from these patients were reviewed. Neurological outcome and status of presenting symptoms were assessed during long-term follow-up. RESULTS: Of the 23 patients, 13 underwent endovascular treatment for intolerable tinnitus or ophthalmological symptoms, and 10 did not undergo treatment. Three untreated patients died of unrelated causes. In those who were treated, complete DAVF obliteration was achieved in 4 patients, and palliative reduction in DAVF flow was achieved in 9 patients. Of the 19 patients without radiographic cure, no patient developed intracranial hemorrhage or nonhemorrhagic neurological deficits (NHNDs), and no patient died of DAVF-related causes over a mean follow-up of 5.6 years. One patient experienced a spontaneous, asymptomatic obliteration of a partially treated DAVF in late follow-up, and 2 patients experienced a symptomatic conversion of their DAVF to a higher-grade fistula with CVD in late follow-up. The annual rate of conversion to a higher-grade DAVF based on Kaplan-Meier cumulative event-free survival analysis was 1.0%. The annual rate of intracranial hemorrhage, NHND, and DAVF-related death was 0.0%. CONCLUSIONS: A small number of Type I DAVFs will convert to more aggressive DAVFs with CVD over time. This conversion to a higher-grade DAVF is typically heralded by a change in patient symptoms. Follow-up vascular imaging is important, particularly in the setting of recurrent or new symptoms.

Cranial dural arteriovenous fistulae: asymptomatic cortical venous drainage portends less aggressive clinical course.

OBJECTIVE: Cranial dural arteriovenous fistulae (dAVF) with cortical venous drainage (CVD) (Borden Types 2 and 3) are reported to carry a 15% annual risk of intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND). The purpose of this study was to compare the clinical course of Type 2 and 3 dAVFs that present with ICH or NHND with those that do not. METHODS: Twenty-eight patients with Type 2 or 3 dAVFs were retrospectively evaluated. CVD was classified as asymptomatic (aCVD) if patients presented incidentally or with pulsatile tinnitus or orbital phenomena. CVD was classified as symptomatic (sCVD) if patients presented with ICH or NHND. Occurrence of new ICH or new or worsening NHND between diagnosis and disconnection of CVD or last follow-up (if not disconnected) was noted. Overall frequency of events was compared using Fisher's exact test. Cumulative, event-free survival was compared using Kaplan-Meier analysis with log-rank testing. RESULTS: Of 17 patients with aCVD, 1 (5.9%) developed ICH and none experienced NHND or death during the median 31.4-month follow-up period. Of 11 patients with sCVD, 2 (18.2%) developed ICH and 3 (27.3%) experienced new or worsened NHND over the median 9.7-month follow-up period. One of these patients subsequently died. Overall frequency of ICH or NHND was significantly lower in patients with aCVD versus sCVD (P = 0.022). Respective annual event rates were 1.4 versus 19.0%. aCVD patients had significantly higher cumulative event-free survival (P = 0.0016). CONCLUSION: Cranial dAVFs with aCVD may have a less aggressive clinical course than those with sCVD.

Spontaneous isolated convexity subarachnoid hemorrhage: presentation, radiological findings, differential diagnosis, and clinical course.

OBJECT: The clinical characteristics and overall outcome in patients with spontaneous isolated convexity subarachnoid hemorrhage (SAH) are not well described in the literature. The purpose of this study was to examine the mode of presentation, common origins, radiographic findings, and clinical course in a large case series of such patients. METHODS: A retrospective single-center chart review of all patients in whom nontraumatic primary convexity SAH was diagnosed between 2002 and 2007 was performed. Twenty patients were identified and analyzed for presenting symptoms, radiological and laboratory findings, hospital course, and outcome. RESULTS: There were 15 women and 5 men in our series, and the mean age was 52 years (range 18-86 years). The most common presenting symptom was headache, with 15 patients experiencing it as a chief complaint. Other frequent manifestations included altered mental status (8 patients), focal neurological deficits (7), and seizure (4 patients). An underlying cause of the hemorrhage was identified in 13 cases, whereas the remainder went unresolved. Of the known causes, 5 were due to posterior reversible encephalopathy syndrome, 3 were caused by thrombocytopenia or anticoagulation, and the remainder were isolated cases of lupus vasculitis, drug-induced vasculopathy, postpartum cerebral angiopathy, hypertensive microangiopathy, and Call-Fleming syndrome. All patients with unknown disease origins had favorable outcomes, whereas 8 of 13 patients with an identifiable underlying disorder experienced favorable outcomes. CONCLUSIONS: Spontaneous isolated convexity SAH is rarely caused by aneurysm rupture, has a distinct mode of presentation, and generally carries a more favorable prognosis than that of aneurysmal SAH.