Search

OBJECTIVE The aim of this study was to investigate the impact of the US-Mexico border wall height extension on traumatic brain injuries (TBIs) and related costs. METHODS In this retrospective cohort study, patients who presented to the UC San Diego Health Trauma Center for injuries from falling at the border wall between 2016 and 2021 were considered. Patients in the pre–height extension period (January 2016–May 2018) were compared with those in the post–height extension period (January 2020–December 2021). Demographic characteristics, clinical data, and hospital charges were analyzed. RESULTS A total of 383 patients were identified: 51 (0 TBIs, 68.6% male) in the pre–height extension cohort and 332 (14 TBIs, 77.1% male) in the post–height extension cohort, with mean ages of 33.5 and 31.5 years, respectively. There was an increase in the average number of TBIs per month (0.0 to 0.34) and operative TBIs per month (0.0 to 0.12). TBIs were associated with increased Injury Severity Score (8.8 vs 24.2, p < 0.001), median (IQR) hospital length of stay (5.0 [2–11] vs 8.5 [4–45] days, p = 0.03), and median (IQR) hospital charges ($163,490 [$86,369–$277,918] vs $243,658 [$136,769–$1,127,920], p = 0.04). TBIs were normalized for changing migration rates on the basis of Customs and Border Protection apprehensions. CONCLUSIONS This heightened risk of intracranial injury among vulnerable immigrant populations poses ethical and economic concerns to be addressed regarding border wall infrastructure.

One of the challenges in clinical translation of cell-replacement therapies is the definition of optimal cell generation and storage/recovery protocols which would permit a rapid preparation of cell-treatment products for patient administration. Besides, the availability of injection devices that are simple to use is critical for potential future dissemination of any spinally targeted cell-replacement therapy into general medical practice. Here, we compared the engraftment properties of established human-induced pluripotent stem cells (hiPSCs)-derived neural precursor cell (NPCs) line once cells were harvested fresh from the cell culture or previously frozen and then grafted into striata or spinal cord of the immunodeficient rat. A newly developed human spinal injection device equipped with a spinal cord pulsation-cancelation magnetic needle was also tested for its safety in an adult immunosuppressed pig. Previously frozen NPCs showed similar post-grafting survival and differentiation profile as was seen for freshly harvested cells. Testing of human injection device showed acceptable safety with no detectable surgical procedure or spinal NPCs injection-related side effects.

Intraoperative neuromonitoring (IONM) is a widely used practice in spine surgery for early detection and minimization of neurological injury. IONM is most commonly conducted by indirectly recording motor and somatosensory evoked potentials from either muscles or the scalp, which requires large-amplitude electrical stimulation and provides limited spatiotemporal information. IONM may inform of inadvertent events during neurosurgery after they occur, but it does not guide safe surgical procedures when the anatomy of the diseased spinal cord is distorted. To overcome these limitations and to increase our understanding of human spinal cord neurophysiology, we applied a microelectrode array with hundreds of channels to the exposed spinal cord during surgery and resolved spatiotemporal dynamics with high definition. We used this method to construct two-dimensional maps of responsive channels and define with submillimeter precision the electrophysiological midline of the spinal cord. The high sensitivity of our microelectrode array allowed us to record both epidural and subdural responses at stimulation currents that are well below those used clinically and to resolve postoperative evoked potentials when IONM could not. Together, these advances highlight the potential of our microelectrode arrays to capture previously unexplored spinal cord neural activity and its spatiotemporal dynamics at high resolution, offering better electrophysiological markers that can transform IONM.

Background The recent San Diego–Mexico border wall height extension has resulted in an increased injury risk for unauthorized immigrants falling from greater heights. However, the effects of the border wall extension on frequency and morbidity of spinal injuries and related economic costs have yet to be highlighted. Methods We retrospectively compared two cohorts who presented to the UC San Diego Health Trauma Center for border wall falls: pre-height extension (12 patients; January 2016–May 2018), and post-height extension (102 patients; January 2020–December 2021). Patients presented during border wall construction (June 2018–December 2019) were excluded. Demographics, clinical data and hospital costs were collected. Spinal injuries were normalized using Customs and Border Protection apprehensions. Costs were adjusted for inflation using the 2021 medical care price index. Results The increase in spine injuries per month (0.8–4.25) and operative spine injuries per month (0.3– 1.7) was statistically significant (P Conclusion The data support that the recent San Diego–Mexico border wall extension is correlated with more frequent, severe and costly spinal injuries. This current infrastructure should be re-evaluated as border-related injuries represent a humanitarian and public health crisis.

Spinal cord injury (SCI) can permanently impair motor and sensory function and has a devastating cost to patients and the United States healthcare system. Stem cell transplantation for treatment of SCI is a new technique aimed at creating biological functional recovery. Operative techniques in stem cell transplantation for SCI are varied. We review various clinical treatment paradigms, surgical techniques and technical considerations important in SCI treatment. The NCBI PubMed database was queried for “SCI” and “stem cell” with a filter placed for “clinical trials”. Thirty-nine articles resulted from the search and 29 were included and evaluated by study authors. A total of 10 articles were excluded (9 not SCI focused or transplantation focused, 1 canine model). Key considerations for stem cell transplantation include method of delivery (intravenous, intrathecal, intramedullary, or excision and engraftment), time course of treatment, number of treatments and time from injury until treatment. There are no phase III clinical trials yet, but decreased time from injury to treatment and a greater number of stem cell injections both seem to increase the chance of functional recovery.

The critical requirements in developing clinical-grade human-induced pluripotent stem cells–derived neural precursors (hiPSCs-NPCs) are defined by expandability, genetic stability, predictable in vivo post-grafting differentiation, and acceptable safety profile. Here, we report on the use of manual-selection protocol for generating expandable and stable human NPCs from induced pluripotent stem cells. The hiPSCs were generated by the reprogramming of peripheral blood mononuclear cells with Sendai-virus (SeV) vector encoding Yamanaka factors. After induction of neural rosettes, morphologically defined NPC colonies were manually harvested, re-plated, and expanded for up to 20 passages. Established NPCs showed normal karyotype, expression of typical NPCs markers at the proliferative stage, and ability to generate functional, calcium oscillating GABAergic or glutamatergic neurons after in vitro differentiation. Grafted NPCs into the striatum or spinal cord of immunodeficient rats showed progressive maturation and expression of early and late human-specific neuronal and glial markers at 2 or 6 months post-grafting. No tumor formation was seen in NPCs-grafted brain or spinal cord samples. These data demonstrate the effective use of in vitro manual-selection protocol to generate safe and expandable NPCs from hiPSCs cells. This protocol has the potential to be used to generate GMP (Good Manufacturing Practice)-grade NPCs from hiPSCs for future clinical use.

BACKGROUND Thoracic epidural capillary hemangioma is exceedingly rare, with only a few reported cases. The typical presentation usually includes chronic, progressive symptoms of spinal cord compression in middle-aged adults. To the authors’ knowledge, this case is the first report in the literature of acute traumatic capillary hemangioma rupture. OBSERVATIONS A 22-year-old male presented with worsening lower extremity weakness and paresthesias after a fall onto his spine. Imaging showed no evidence of spinal fracture but revealed an expanding hematoma over 24 hours. Removal of the lesion demonstrated a ruptured capillary hemangioma. LESSONS This unique case highlights a rare occurrence of traumatic rupture of a previously unknown asymptomatic thoracic capillary hemangioma in a young adult.

INTRODUCTION Deep brain stimulation (DBS) is an important treatment modality for movement disorders. Its role in tasks and processes of higher cortical function continues to increase in importance and relevance. This systematic review investigates the impact of DBS on measures of impulsivity. EVIDENCE ACQUISITION A total of 45 studies were collated from PubMed (30 prospective, 8 animal, 4 questionnaire-based, and 3 computational models), excluding case reports and review articles. Two areas extensively studied are the subthalamic nucleus (STN) and nucleus accumbens (NAc). EVIDENCE SYNTHESIS While both are part of the basal ganglia, the STN and NAc have extensive connections to the prefrontal cortex, cingulate cortex, and limbic system. Therefore, understanding cause and treatment of impulsivity requires understanding motor pathways, learning, memory, and emotional processing. DBS of the STN and NAc shell can increase objective measures of impulsivity, as measured by reaction times or reward-based learning, independent from patient insight. The ability for DBS to treat impulse control disorders, and also cause and/or worsen impulsivity in Parkinson's disease, may be explained by the affected closely-related neuroanatomical areas with discrete and sometimes opposing functions. CONCLUSIONS As newer, more refined DBS technology emerges, large-scale prospective studies specifically aimed at treatment of impulsivity disorders are needed.

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further α-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers. Injection of AAV–shRNA below the pial surface of the spinal cord prevents onset or ameliorates progression in a mouse model of ALS, and achieves widespread delivery to the spinal cord and brain motor centers in adult pigs and non-human primates.

Cervical disc arthroplasty (CDA) is a recent alternative to anterior cervical discectomy and fusion (ACDF) in patients suffering cervical disc herniation and degeneration. To date, a systematic analysis of their comparative advantages and risks following elective surgery remains elusive.Adult patients undergoing elective CDA or ACDF were extracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2011-2014. A total of 19,369 patients were matched 1:1 by age, sex, functional status, charlson comorbidity index, ASA classification, BMI classification, and number of vertebral levels operated on during surgery. This matching process led to a final sample of 588 subjects (294 CDA, 294 ACDF). Multivariable regression was performed for five outcome measures: operation time, early complications, reoperation rates, hospital length of stay (HLOS), and discharge destination. Mean differences (B), odds ratios (OR) and associated 95% confidence intervals (CI) are reported.Compared to ACDF, CDA was associated with decreased mean operation time (B=-18.78-min, 95% CI [-29.13, -8.42]; p0.001), decreased HLOS (B=-0.44-days [-0.77, -0.11]; p=0.009), and increased likelihood of discharge to home (OR=5.39 [1.14-25.43]; p=0.033). No differences in reoperation rates and complications were found.In a matched cohort analysis, CDA performs comparably to ACDF and is associated with decreased operation time and HLOS, and increased likelihood of discharge to home, without differences in 30-day complications or reoperation rates. Future prospective studies are warranted.

OBJECTIVE Normative data exists for stimulus-evoked pedicle screw electromyography (EMG) current thresholds in the lumbar spine, and is routinely referenced during spine surgeries to detect a screw breach, prevent injury of neural elements, and ensure the most biomechanically sound instrumentation construct. To date, similar normative data for cervical lateral mass screws is limited, thus the utility of lateral mass screw testing remains unclear. To address this disparity, in this study the authors describe cumulative lateral mass screw stimulation threshold data in patients undergoing posterior cervical instrumentation with lateral mass screws. These data are correlated with screw placement on postoperative imaging, and a novel correlation is discovered with direct clinical implications. METHODS Using a ball-tip probe, 154 lateral mass screws in 21 patients were electrically tested intraoperatively. In each case, for each screw, the lowest (or threshold) current at which the first polyphasic stimulus-evoked EMG response was reproducibly observed by a neurophysiologist was recorded. All patients underwent postoperative CT. Screw position within the lateral mass was first measured in the axial and sagittal planes for each lateral mass screw using the CT images. Screw placement was also evaluated by 2 independent physicians, blinded to current threshold data, on a binary scale of acceptability. The predictive capacity of screw EMG threshold data was evaluated via multivariable regression analyses and receiver operating characteristic (ROC) analyses. Predictive capacity was examined with respect to screw position within the lateral mass, as well as screw acceptability. RESULTS Lateral mass screw EMG thresholds did not appear to differ significantly for screws considered “acceptable” versus “unacceptable” according to the radiographic criteria. Accordingly, ROC analysis confirmed that EMG current threshold data were of minimal utility in predicting screw radiographic acceptability. However, EMG threshold was significantly predictive of screw medial distance from the spinal canal. A screw stimulating below 7.5 mA correctly identified a screw as being within 2 mm of the spinal canal with 75% sensitivity and 92% specificity (positive predictive value 20%, negative predictive value 99.3%), independent of its distance relative to other lateral mass landmarks. EMG current threshold was not significantly predictive of screw deviation in the superior or inferior directions, and was inversely predictive of screw deviations in the lateral direction. CONCLUSIONS In the context of uncertainty regarding the utility of cervical lateral mass EMG current threshold data, this study found that EMG current thresholds correspond significantly, and exclusively, with screw distance from the spinal canal. This association appears independent of other criteria for screw misplacement. As such, the authors recommend that EMG current thresholds be referenced in the case of a suspected medial breach as an effective means to rule out screw placement too medial to the spinal canal.

Objective To review the literature of spinal cord injury and stem cell therapy for large animal models and incorporate those results into an understanding of stem cell therapy for human cord injury. Methods Review of the literature. Results Eleven canine studies were identified and 3 sub-human primate studies were identified showing variable results. Conclusions Stem cell therapy is a promising therapeutic option for patients with spinal cord injury; however, the technology has many un-answered questions and further research is needed.

Objective To examine the relative incidence of newly recorded diagnosis of depression after spinal surgery as a proxy for the risk of post–spinal surgery depression. Patients and Methods We used the longitudinal California Office of Statewide Health Planning and Development database (January 1, 2000, through December 31, 2010) to identify patients who underwent spinal surgery during these years. Patients with documented depression before surgery were excluded. Risk of new postoperative depression was determined via the incidence of newly recorded depression on any hospitalization subsequent to surgery. For comparison, this risk was also determined for patients hospitalized during the same time period for coronary artery bypass grafting, hysterectomy, cholecystectomy, chronic obstructive pulmonary disease, congestive heart failure exacerbation, or uncomplicated vaginal delivery. Results Our review identified 1,078,639 patients. Relative to the uncomplicated vaginal delivery cohort, the adjusted hazard ratios (HRs) for newly recorded depression within 5 years after the admission of interest were 5.05 for spinal surgery (95% CI, 4.79-5.33), 2.33 for coronary artery bypass grafting (95% CI, 2.15-2.54), 3.04 for hysterectomy (95% CI, 2.88-3.21), 2.51 for cholecystectomy (95% CI, 2.35-2.69), 2.44 for congestive heart failure exacerbation (95% CI, 2.28-2.61), and 3.04 for chronic obstructive pulmonary disease (95% CI, 2.83-3.26). Among patients who underwent spinal surgery, this risk of postoperative depression was highest for patients who underwent fusion surgery (HR, 1.28; 95% CI, 1.22-1.36) or had undergone multiple spinal operations (HR, 1.22; 95% CI, 1.16-1.29) during the analyzed period. Conclusion Patients who undergo spinal surgery have a higher risk for postoperative depression than patients treated for other surgical or medical conditions known to be associated with depression.

Dorsal thoracic arachnoid webs are rare clinical entities caused by a thickened intradural extramedullary band of arachnoid tissue that compresses the spinal cord, and often present with progressive back pain, paresthesias, and lower extremity weakness. In this report, we review the radiographic features of the “Scalpel Sign” and describe the case of a 47-year-old male that failed conservative therapy and was found to have dorsal thoracic arachnoid web. The patient underwent laminectomy and microsurgical release of the compressing arachnoid band. Postoperatively, the patient had complete resolution of his pain. Intraoperatively, the somatosensory evoked potentials were improved once the band was released. The prompt diagnosis of dorsal arachnoid webs remains critical because surgical treatment arrests and potentially reverses the pathology.

Neural precursor cells (NSCs) hold great potential to treat a variety of neurodegenerative diseases and injuries to the spinal cord. However, current delivery techniques require an invasive approach in which an injection needle is advanced into the spinal parenchyma to deliver cells of interest. As such, this approach is associated with an inherent risk of spinal injury, as well as a limited delivery of cells into multiple spinal segments. Here, we characterize the use of a novel cell delivery technique that employs single bolus cell injections into the spinal subpial space. In immunodeficient rats, two subpial injections of human NSCs were performed in the cervical and lumbar spinal cord, respectively. The survival, distribution, and phenotype of transplanted cells were assessed 6‐8 months after injection. Immunofluorescence staining and mRNA sequencing analysis demonstrated a near‐complete occupation of the spinal cord by injected cells, in which transplanted human NSCs (hNSCs) preferentially acquired glial phenotypes, expressing oligodendrocyte (Olig2, APC) or astrocyte (GFAP) markers. In the outermost layer of the spinal cord, injected hNSCs differentiated into glia limitans‐forming astrocytes and expressed human‐specific superoxide dismutase and laminin. All animals showed normal neurological function for the duration of the analysis. These data show that the subpial cell delivery technique is highly effective in populating the entire spinal cord with injected NSCs, and has a potential for clinical use in cell replacement therapies for the treatment of ALS, multiple sclerosis, or spinal cord injury., Migration and functional maturation of subpially injected human neural precursor cells (hNSCs) in immunodeficient rats: after injection, cells migrate into the spinal parenchyma across the glia limitans. A subpopulation of cells differentiate into astrocytes, incorporate into glia limitans and express functional markers characteristic if glia limitans‐forming astrocytes, including superoxide dismutase (SOD) and laminin. The other population of injected cells continues to migrate into the spinal parenchyma.

Ultrasound-accelerated thrombolysis (USAT) is advocated in pulmonary embolism (PE) based on the hypothesis that adjunctive ultrasound provides superior clinical efficacy compared to standard catheter-directed thrombolysis (CDT). This retrospective study was designed to compare outcomes between the two modalities. We analyzed patients with computed tomography-diagnosed PE at our institution treated with either USAT or standard CDT. Efficacy parameters assessed included invasive pulmonary artery systolic pressure (PASP; pre- and 24 hours post-treatment), non-invasive right-to-left ventricle (RV/LV) ratio (pre- and post-treatment), and general clinical outcomes (length-of-stay, significant bleeding, and mortality). We analyzed 98 cases (62 USAT and 36 CDT), in whom massive PE was diagnosed in 7%, intermediate/high risk in 81%, and intermediate/low risk in 12%. Overall, 92% had bilateral clot and 40% saddle embolus. At 24 hours, PASP decreased similarly in both groups (CDT Δ14.7 mmHg, USAT Δ10.8 mmHg; p = 0.14). Post-treatment, CDT showed similar improvement in the RV/LV ratio (CDT Δ0.58 vs USAT Δ0.45; p = 0.07), despite the baseline ratio being greater in the CDT group, indicating more severe RV strain (1.56 ± 0.36 vs 1.40 ± 0.29; p = 0.01). Intensive care unit and hospital length-of-stays were similar in both groups. A trend toward lesser significant bleeding rates in the CDT group (8.3% vs 12.9%, p = 0.74) as well as improved survival-to-discharge (97.2% vs 91.9%, p = 0.66) was observed. Compared to USAT, standard CDT achieves similar beneficial effects on hemodynamics, RV/LV ratios, and clinical outcomes. These observations suggest that salutary clinical results may be achieved without the need for very expensive devices.

BACKGROUND Laminectomy with excision of spinal neoplasms is commonly performed. The current study examines risk profiles associated with elective laminectomies of benign, malignant primary, and secondary/metastatic neoplasms of the thoracic spine. METHODS Adult patients undergoing elective thoracic laminectomy and excision of spinal neoplasm were abstracted from ACS-NSQIP years 2011-2014. Patients were classified into three cohorts: benign primary, malignant primary, secondary/metastatic. Univariate and multivariable analyses compared operation time, early complications, hospital length of stay (HLOS), and discharge destination across cohorts. RESULTS One-hundred sixty patients were included, aged 58.0±14.8-years. Mean operation time was 209.23±101.52 minutes and cohorts did not differ significantly on multivariable analysis. Mean HLOS was 6.10±7.14 days and did not differ by cohort. Early complications were observed in 15.6% of patients; secondary/metastatic patients associated with increased odds of >1 unit of blood transfusion, but not overall complications. Failure to be discharged home occurred in 31.8% of patients (benign primary: 30.0%, malignant primary: 66.6%, secondary/metastatic: 10.5%; P

BackgroundOperative management of lower back pain often necessitates anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF). Specific pathoanatomic advantages and indications exist for both approaches, and few studies to date have characterized comparative early outcomes.MethodsAdult patients undergoing elective ALIF or TLIF operations were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) years 2011-2014. Univariate analyses were performed by surgery cohort for each outcome and adjusted for demographic/clinical variables (age ≥ 65, sex, race, body mass index, American Society of Anesthesiologists physical classification score, functional status, inpatient/outpatient status, smoking, hypertension, Charlson Comorbidity Index) using multivariable regression. Means, standard errors, mean differences (B), odds ratios (ORs), and associated 95% confidence intervals (CIs) are reported. Significance was assessed at P < .05.ResultsOf 8263 subjects (ALIF: 4325, TLIF: 3938), ALIF subjects were younger, less obese, less physically impaired, and had significantly lower rates of hypertension, diabetes, coagulopathy, and previous cardiac surgery. On multivariable analysis, ALIF associated with shorter operative time (B = -11.80 minutes, 95% CI [-16.48, -7.12]; P < .001). Transforaminal lumbar interbody fusion was associated with increased incidence of urinary tract infections (UTIs; OR = 1.57, 95% CI [1.10, 2.26]; P = .013) and of blood transfusions (OR = 1.19, 95% CI [1.04, 1.37]; P = .012). Multivariate analysis also demonstrated TLIF associated with shorter hospital length of stay (B = -0.27 days, 95% CI [-0.54, -0.01]; P = .041), and fewer cases of pneumonia (OR = 0.55, 95% CI [0.32, 0.94]; P = .029) and prolonged ventilator dependency (OR = 0.33, 95% CI [0.12, 0.84]; P = .021).ConclusionsComparatively, ALIF patients experienced decreased operative time and decreased incidence of postoperative UTIs and blood transfusions. Anterior lumbar interbody fusion patients were more likely to suffer postoperative pulmonary complications and longer hospital stays. Our data support the notion that both anterior and transforaminal surgical approaches perform comparably in context of 30-day perioperative outcomes.

The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)–mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.

Introduction: Rural and low-resource areas have diminished capacity to care for neurosurgical patients due to lack of infrastructure, healthcare investment, and training programs. This review summarizes the range of rural neurosurgical procedures, novel mechanisms for delivering care, rapid training programs, and outcome differences across international rural neurosurgical practice. Methods: A comprehensive literature search was performed for English language manuscripts with keywords “rural” and “neurosurgery” using the National Library of Medicine PubMed database (01/1971–06/2017). Twenty-four articles focusing on rural non-neurosurgical practice were included. Results: Time to care and/or surgery and shortage of trained personnel remain the strongest risk factors for mortality and poor outcome. Telemedicine consults to regional centers with neurosurgery housestaff have potential for increased timeliness of diagnosis/triage, improved time to surgery, and reductions in unnecessary transfers in remote areas. Mobile neurosurgery teams have been deployed with success in nations with large transport distances precluding initial transfers. Common neurosurgical procedures involve trauma mechanisms; accordingly, training programs for nonneurosurgery medical personnel on basic assessment and operative techniques have been successful in resource-deficient settings where neurosurgeons are unavailable. Conclusions: Protracted transport times, lack of resources/training, and difficulty retaining specialists are barriers to successful outcomes. Advances in telemedicine, mobile neurosurgery, and training programs for urgent operative techniques have been implemented efficaciously. Development of guidelines for paired partnerships between rural centers and academic hospitals, supplying surplus technology to rural areas, and rapid training of qualified local surgical personnel can create sustainable feed-forward programs for trainees and infrastructural solutions to address challenges in rural neurosurgery.

The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent transgene expression through the spinal parenchyma (white and gray matter) in subpially-injected spinal segments has been demonstrated. Because of the wide range of transgenic mouse models of neurodegenerative diseases, there is a strong desire for the development of a potent central nervous system (CNS)-targeted vector delivery technique in adult mice. Accordingly, the present study describes the development of a spinal subpial vector delivery device and technique to permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar 1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 µL; 1.2 x 10(13) genome copies (gc)) encoding green fluorescent protein (GFP) was then injected subpially. After injections, neurological function (motor and sensory) was assessed periodically, and animals were perfusion-fixed 14 days after AAV9 delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal cord sections showed transgene expression throughout the entire spinal cord, in both gray and white matter. In addition, intense retrogradely-mediated GFP expression was seen in the descending motor axons and neurons in the motor cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was noted in any animals. These data show that the subpial vector delivery technique can successfully be used in adult mice, without causing procedure-related spinal cord injury, and is associated with highly potent transgene expression throughout the spinal neuraxis.

Intramedullary spinal cord hematomas are a rare neurosurgical pathological entity typically arising from vascular and neoplastic lesions. Endometriosis is an extremely rare cause of intramedullary spinal cord hematoma, with only 5 previously reported cases in the literature. Endometriosis is characterized by ectopic endometrial tissue, typically located in the female pelvic cavity, that causes a cyclical pain syndrome, bleeding, and infertility. In the rare case of intramedullary endometriosis of the spinal cord, symptoms include cyclical lower-extremity radiculopathies and voiding difficulties, and can acutely cause cauda equina syndrome. The authors report a case of endometriosis of the conus medullaris, the first to include radiological, intraoperative, and histopathological imaging. A brief review of the literature is also presented, with discussion including etiological theories surrounding intramedullary endometriosis.

When positioning patients with meningocele and meningomyelocele, it is standard practice to avoid direct pressure on the lesions. That caution is intended to prevent injury to neural elements within the lesion and violation of the cerebrospinal fluid space. We herein report an additional hazard of direct intraoperative pressure on such lesions. An adult patient with a lumbosacral pseudomeningocele sustained a cerebral ischemic injury as a consequence of direct pressure on the lesion during general anesthesia. A 32-yr-old male with spina bifida and a pseudomeningocele related to recent lumbar surgery underwent a urologic procedure in the lithotomy position. Because the lesion was recognized to lie to the left of the midline, cushioning was placed under the patient’s left hip and buttock. The patient was slow to awaken and has sustained significant long-term cognitive deficits. Imaging is consistent with a diffuse cerebral ischemic insult. In retrospect, the size and leftward extent of the pseudomeningocele were not appreciated preoperatively, and in spite of the care taken, intraoperative pressure was placed on the lesion. This report cautions that intraoperative pressure related to positioning patients with extra-axial lesions containing cerebrospinal fluid (CSF), e.g., meningoceles and pseudomeningoceles, can result in increases in CSF pressure and thereby a reduction in cerebral perfusion pressure sufficient to result in cerebral ischemia.

An important component for successful translation of cell replacement-based therapies into clinical practice is the utilization of large animal models to conduct efficacy and/or safety cell dosing studies. Over the past few decades, several large animal models (dog, cat, nonhuman primate) were developed and employed in cell replacement studies; however, none of these models appears to provide a readily available platform to conduct effective and large-scale preclinical studies. In recent years, numerous pig models of neurodegenerative disorders were developed using both a transgenic approach as well as invasive surgical techniques. The pig model (naive noninjured animals) was recently used successfully to define the safety and optimal dosing of human spinal stem cells after grafting into the central nervous system (CNS) in immunosuppressed animals. The data from these studies were used in the design of a human clinical protocol used in amyotrophic lateral sclerosis (ALS) patients in a Phase I clinical trial. In addition, a highly inbred (complete major histocompatibility complex [MHC] match) strain of miniature pigs is available which permits the design of comparable MHC combinations between the donor cells and the graft recipient as used in human patients. Jointly, these studies show that the pig model can represent an effective large animal model to be used in preclinical cell replacement modeling. This review summarizes the available pig models of neurodegenerative disorders and the use of some of these models in cell replacement studies. The challenges and potential future directions in more effective use of the pig neurodegenerative models are also discussed. J. Comp. Neurol. 522:2784–2801, 2014. © 2014 Wiley Periodicals, Inc.

The immune cell composition of the tumor microenvironment can be a decisive factor for tumor pathogenesis. Gliomas are tumors that develop from the glial cells of the brain and spinal cord and make up to 30% of all brain tumors. In gliomas, microglia and infiltrating macrophages can comprise up to 30 to 50% of total tumor-associated cells. Increased CD68 staining, a marker of microglia/macrophages, in adult gliomas is positively associated with histologic tumor grade. Despite the accumulated evidence substantiating a critical role for microglia and infiltrating macrophages in gliomagenesis, little is known is about the molecular mechanisms driving microglial contribution to tumor growth and whether microglia/macrophages are therapeutic targets in both low- and high-grade gliomas. Despite microglia sharing common properties with other tissue-resident macrophages, they express hundreds of genes at higher levels compared to other tissue-resident macrophages, many of which are influenced by the brain micro-environment. Additionally, engraftment of bone-marrow derived cells into the central nervous system fails to produce microglia identical to yolk sac-derived microglia at the transcriptional level. Hence, in any inflammatory context, including cancer, an interesting question arises: how does each population contribute to the pathogenesis and/or resolution of inflammation? To elucidate the role(s) of microglia/macrophages in gliomas, we isolated the myeloid fraction from primary pediatric and adult low-grade and high-grade gliomas using flow cytometry. By integrating bulk and single-cell transcriptome analysis, we find significant inter- and intratumoral heterogeneity within the myeloid population. Additionally, we find evidence for tumor environment-dependent gene change. In combination with ongoing comparative analysis of the corresponding epigenetic landscapes of the myeloid populations, we seek to decipher how the tumor microenvironment reprograms the transcription factor network in microglia/macrophages to generate tumor-promoting cells. Citation Format: Claudia Z. Han, Sascha H. Duttke, Zhengyu Ouyang, Sebastian Preissl, Johannes C.M. Schlachetzki, Alexander Nott, Conor Fitzpatrick, Carolyn O'Connor, Nicole G. Coufal, Mihir Gupta, David D. Gonda, Michael L. Levy, Ben-Haim Sharona, Barba David, Joseph D. Ciacci, Alexander A. Khalessi, Clark C. Chen, Bing Ren, Christopher K. Glass. Dissecting the myeloid lineage in human gliomas [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A078.

In previous studies, we have demonstrated that spinal grafting of human or rat fetal spinal neural precursors leads to amelioration of spasticity and improvement in ambulatory function in rats with spinal ischemic injury. In the current study, we characterize the survival and maturation of three different human embryonic stem (ES) cell line-derived neural precursors (hNPCs) once grafted into ischemia-injured lumbar spinal cord in rats or in naive immunosuppressed minipigs. Proliferating HUES-2, HUES-7, or HUES-9 colonies were induced to form embryoid bodies. During the nestin-positive stage, the rosettes were removed and CD184+/CD271-/CD44-/CD24+population of ES-hNPCs FAC-sorted and expanded. Male Sprague–Dawley rats with spinal ischemic injury or naive immunosuppressed Gottingen–Minnesota minipigs received 10 bilateral injections of ES-NPCs into the L2–L5 gray matter. After cell grafting, animals survived for 2 weeks to 4.5 months, and the presence of grafted cells was confirmed after staining spinal cord sections with a combination of human-specific (hNUMA, HO14, hNSE, hSYN) or nonspecific (DCX, MAP2, CHAT, GFAP, APC) antibodies. In the majority of grafted animals, hNUMA-positive grafted cells were identified. At 2–4 weeks after grafting, double-labeled hNUMA/ DCX-immunoreactive neurons were seen with extensive DCX+processes. At survival intervals of 4–8 weeks, hNSE+neurons and expression of hSYN was identified. Some hSYN-positive terminals formed putative synapses with the host neurons. Quantitative analysis of hNUMA+cells at 2 months after grafting showed comparable cell survival for all three cell lines. In the presence of low-level immunosuppression, no grafted cell survival was seen at 4.5 months after grafting. Spinal grafting of proliferating pluripotent HUES-7 cells led to consistent teratoma formation at 2–6 weeks after cell transplantation. These data show that ES-derived, FAC-sorted NPCs can represent an effective source of human NPCs to be used in CNS cell replacement therapies.

STUDY DESIGN This was a retrospective study of patients with Chiari I (CM I) and Chiari II (CM II) malformations, tethered cord syndrome, and syringomyelia examining the effect of neurosurgery on scoliosis. OBJECTIVE The aim of this study was to determine the factors affecting spinal deformity progression in patients with diseases of the neural axis following neurosurgical management. SUMMARY OF BACKGROUND DATA There have been attempts to explain which factors influence the spinal deformity in diseases of the neural axis with varying results. Debate still exists as to the effectiveness of neurosurgery in curve stabilization. METHODS The medical records for patients treated over the past 10 years were reviewed. The spinal deformity surgical group consisted of patients who received surgery or progressed to surgical range (50°) and the nonsurgical group those who did not undergo fusion. RESULTS Fifteen patients (eight females and seven males) with scoliosis who underwent neurosurgical intervention were identified. Ten had tethered cord, six CM II, four CM I, and 11 syrinx. Average age at the time of neurosurgery was 7 ± 4 years (range 0.7-14 yrs). Following neurosurgery, no patients experienced improvement in their curves (defined as >10° decrease in Cobb angle), eight patients experienced stabilization ( 10° increase). The group that went on to spinal deformity surgery possessed larger curves before neurosurgery (mean 42°, range 20°-63°) than the nonsurgical group (19°, range 15°-26°; P = 0.004). CM II patients had the greatest magnitude of curve progression, mean of 49°, compared with patients with CM I (6°) or tether cord without CM I or II (11°, P = 0.01). CONCLUSION Neurosurgical intervention may prevent curve progression in patients with scoliosis and Cobb angles

Low back pain (LBP) is a common medical problem with high morbidity and healthcare costs. The optimal management strategy, including the role of surgical intervention, remains controversial. The Spine Patient Outcomes Research Trials were randomized controlled studies conducted to assess the effectiveness of surgery for three of the most common conditions implicated in LBP: Intervertebral disc herniation, degenerative spondylolisthesis, and spinal stenosis. Despite challenges in data interpretation related to patient cross over, these studies support the efficacy of surgery as treatment for these three common conditions.

Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Here, we demonstrate that the spinal pia membrane represents the primary barrier limiting effective AAV9 penetration into the spinal parenchyma after intrathecal AAV9 delivery. We develop a novel subpial AAV9 delivery technique and AAV9-dextran formulation. We use these in adult rats and pigs to show (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 delivery. Thus, subpial delivery of AAV9 enables gene-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients.

The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4–9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mm-diameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. During recovery, motor and sensory function were periodically monitored. After survival, the animals were perfusion fixed and the extent of local SCI was analyzed by (1) post-mortem MRI analysis of dissected spinal cords, (2) qualitative and quantitative analysis of axonal survival at the epicenter of injury, and (3) defining the presence of local inflammatory changes, astrocytosis, and schwannosis. Following 2.5-kg spinal cord compression the animals demonstrated a near complete loss of motor and sensory function with no recovery over the next 4–9 months. Those that underwent spinal cord compression with 2 kg force developed an incomplete injury with progressive partial neurological recovery characterized by a restricted ability to stand and walk. Animals injured with a spinal compression force of 1.5 kg showed near normal ambulation 10 days after injury. In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.

To describe our clinical experience using a unique single-isocenter technique for frameless intensity-modulated stereotactic radiosurgery (IM-SRS) to treat multiple brain metastases.Twenty-six patients with a median of 5 metastases (range, 2-13) underwent optically guided frameless IM-SRS using a single, centrally located isocenter. Median prescription dose was 18 Gy (range, 14-25). Follow-up magnetic resonance imaging (MRI) and clinical examination occurred every 2-4 months.Median follow-up for all patients was 3.3 months (range, 0.2-21.3), with 20 of 26 patients (77%) followed up until their death. For the remaining 6 patients alive at the time of analysis, median follow-up was 14.6 months (range, 9.3-18.0). Total treatment time ranged from 9.0 to 38.9 minutes (median, 21.0). Actuarial 6- and 12-month overall survivals were 50% (95% confidence interval [C.I.], 31-70%) and 38% (95% C.I., 19-56%), respectively. Actuarial 6- and 12-month local control (LC) rates were 97% (95% C.I., 93-100%) and 83% (95% C.I., 71-96%), respectively. Tumorsor=1.5 cm had a better 6-month LC than those1.5 cm (98% vs. 90%, p = 0.008). New intracranial metastatic disease occurring outside of the treatment volume was observed in 7 patients. Gradeor=3 toxicity occurred in 2 patients (8%).Frameless IM-SRS using a single-isocenter approach for treating multiple intracranial metastases can produce clinical outcomes that compare favorably with those of conventional SRS in a much shorter treatment time (40 minutes). Given its faster treatment time, this technique is appealing to both patients and personnel in busy clinics.

Summary We tested the feasibility and safety of human-spinal-cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury (SCI). In this clinical trial, four subjects with T2–T12 SCI received treatment consisting of removal of spinal instrumentation, laminectomy, and durotomy, followed by six midline bilateral stereotactic injections of NSI-566 cells. All subjects tolerated the procedure well and there have been no serious adverse events to date (18–27 months post-grafting). In two subjects, one to two levels of neurological improvement were detected using ISNCSCI motor and sensory scores. Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting.

Joseph Ciacci1, Allen Ho1,2, Christopher P Ames3, Rahul Jandial41Division of Neurosurgery, University of California, San Diego, La Jolla, California, USA; 2Del E Webb Neurosciences, Aging and Stem Cell Research Center, The Burnham Institute for Medical Research, La Jolla, California, USA; 3Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; 4Division of Neurosurgery, Department of Surgery, City of Hope Cancer Center, Duarte, CA, USAAbstract: Intervertebral disc degeneration remains a pervasive and intractable disease arising from a combination of aging and stress on the back and spine. The growing field of regenerative medicine brings the promise of stem cells in the treatment of disc disease. Scientists and physicians hope to employ stem cells not only to stop, but also reverse degeneration. However, there are many important outstanding issues, including the hostile avascular, apoptotic physiological environment of the intervertebral disc, and the difficulty of obtaining mesenchymal stem cells, and directing them towards chondrocytic differentiation and integration within the nucleus pulposus of the disc. Given the recent advances in minimally invasive spine surgery, and developing body of work on stem cell manipulation and transplantation, stem cells are uniquely poised to bring about large-scale improvements in treatment and outcomes for degenerative disc disease. In this review we will first discuss the cellular and molecular factors influencing degeneration, and then examine the efficacy and difficulties of stem cell transplantation.Keywords: intervertebral disc degeneration, stem cells, disc disease, mesenchymal stem cells, stem cell transplantation

To compare cost of percutaneous cryoablation vs open and robot-assisted partial nephrectomy of T1a renal masses from the hospital perspective.We retrospectively compared cost, clinical and tumor data of 37 percutaneous cryoablations to 26 open and 102 robot-assisted partial nephrectomies. Total cost was the sum of direct and indirect cost of procedural and periprocedural variables. Clinical data included demographics, Charlson Comorbidity Index (CCI), hospitalization time, complication rate, ICU admission rate, and 30-day readmission rates. Tumor data included size, RENAL nephrometry score, and malignancy rate. Student's t-test was used for continuous variables and Fisher's exact or chi-square tests for categorical data.Mean total cost was lower for percutaneous cryoablation than open or robot-assisted partial nephrectomy: $6067 vs $11392 or $11830 (p0.0001) with lower cost of procedure room: $1516 vs $3272 or $3254 (p0.0001), room and board: $95 vs $1907 or $1106 (p0.0001), anesthesia: $684 vs $1223 or $1468 (p0.0001), and laboratory/pathology fees: $205 vs $804 or $720 (p0.0001). Supply and device cost was higher than open: $2596 vs $1352 (p0.0001), but lower than robot-assisted partial nephrectomy: $3207 (p=0.002). Mean hospitalization times were lower for percutaneous cryoablation (p0.0001), while age and CCI were higher (p0.0001). No differences in tumor size, nephrometry score, malignancy rate complication, ICU, or 30-day readmission rates were observed.Percutaneous cryoablation can be performed at significantly lower cost than open and robotic partial nephrectomies for similar masses.

Traumatic retrolisthesis of the lumbar spine is a rare clinical entity. Only a few case reports have shown retrolisthesis of the fractured fragment over the inferior vertebral body. Fracture dislocations of the spine are unstable injuries that require operative fixation to restore alignment and prevent progressive deformity. We present the case of a traumatic L5-S1 fracture dislocation with retrolisthesis of the L5 vertebral body over the superior aspect of S1 managed with anterior, middle, and posterior column reconstruction. The patient presented with paraplegia and bowel and bladder incontinence. Retrolisthesis fracture dislocations injuries are rare, and as such, there are no guidelines regarding their management. In our case, we performed an L5 vertebrectomy with anterior, middle, and posterior column reconstruction via a posterior approach using a lumbosacral-pelvic construct. The patient did not regain function in his distal lower extremities postoperatively.

INTRODUCTION:We conducted a retrospective cohort analysis of early outcomes after elective anterior cervical discectomy and fusion (ACDF) vs cervical artificial disc replacement (C-ADR) using the National Surgical Quality Improvement Program database. Risk factors associated with operation time, hos

Objective: Cervical spine fusion is the preferred treatment modality for a variety of degenerative and/or myelopathic disorders. Surgeons select between two approaches (anterior or posterior cervical fusion [ACF; PCF]) based on pathoanatomical features and spinal levels involved. Complications and outcome profiles between the approaches following elective surgery have not been systematically investigated. Methods: Adult patients undergoing elective ACF or PCF were extracted from the American College of Surgeons National Surgical Quality Improvement Program years 2011–2014. Five hundred twenty-eight patients (264 ACF and 264 PCF) were matched 1:1 by age, sex, functional status, vertebral levels operated, and the American Society of Anesthesiologists classification. Multivariable regression was performed by surgical approach for operation time, complications, hospital length of stay (HLOS), and discharge destination, controlling for body mass index and comorbidities. Mean differences (B), odds ratios (ORs), and 95% confidence intervals (CIs) are reported. Results: Compared to ACF, PCF was associated with increased odds of blood transfusions >1 unit (OR = 4.31, 95% CI [1.18–15.75]; P = 0.027) and failure to discharge to home (OR = 3.68 [2.17–6.25]; P < 0.001), and increased mean HLOS (B = 1.72 days [1.19–2.26]; P < 0.001). No differences in operation time, other complications, or reoperation rates were found by surgical approach. Conclusions: In a matched cohort analysis by age, sex, functional and physical status, and vertebral levels, elective PCF is associated with increased HLOS and increased likelihood of failing to discharge to home compared to ACF without increased risk of 30-day complications. Increased blood transfusion volume is noted for patients undergoing PCF. Future prospective studies are warranted.

STUDY DESIGN Cross-sectional analysis of the American College of Surgeons' National Surgical Quality Improvement Program database between 2005 and 2011. OBJECTIVE To determine whether differences exist in 30-day rate of return to the operating room, mortality, and other perioperative outcomes for spinal fusion by specialty. SUMMARY OF BACKGROUND DATA Although both neurosurgeons and orthopedic surgeons perform spinal fusions, it is unclear whether surgeon specialty impacts perioperative outcomes. METHODS Unadjusted bivariate analysis was performed to determine whether outcomes differed by surgeon specialty. A Bonferroni correction was applied to account for multiple comparisons. For outcomes with a statistically significant association, further multivariate analysis was performed. RESULTS A total of 9719 patients receiving a spinal fusion were identified. Of them, 54.0% had their operation completed by a neurosurgeon. Orthopedic surgeons had practices with a greater percentage of lumbar spine cases (76.0% vs. 65.0%, P < 0.001). There was not a statistically significant difference in the number of levels fused or operative technique used between specialties. There was no difference in the majority of perioperative outcomes between orthopedic surgeons and neurosurgeons including death, rate of return to the operating room, and other complications associated with significant morbidity. On unadjusted analysis, it was found that neurosurgeons were associated with a decreased incidence of operations requiring blood transfusion relative to orthopedic surgeons (8.3% vs. 14.6%, P < 0.001). This trend persisted on multivariate analysis controlling for preoperative hematocrit, history of bleeding disorder, anatomical location of the operation, number of levels fused, operative technique, demographics, and comorbidities (odds ratio, 0.49; 95% confidence interval, 0.43-0.57). CONCLUSION Spine surgeons, regardless of specialty, seem to achieve equivalent outcomes on measured metrics of mortality, 30-day readmission, and surgical site infection. Observed differences in blood transfusion rates by specialty were noted, but the cause of this difference is unclear and warrants further investigation to assess the impact of this difference, if any, on patient outcomes and cost. LEVEL OF EVIDENCE 3.

Objective The aim of this study was to determine whether there are differences in pituitary apoplexy and subclinical apoplexy secondary to adenoma hemorrhage in the adolescent population with regard to symptomatology, neuroimaging features, pathology, and outcomes compared with adults. Methods A retrospective series of 9 consecutive patients with a diagnosis of pituitary hemorrhage who were surgically treated at Rady's Children's Hospital San Diego, between 2008 and 2013 were evaluated for clinical, endocrine, neuroradiographic, and pathologic features in association with clinical outcomes. Results Nine patients (6 girls, age 14−21 years) presented to our institution with headache (9/9), nausea (3/9), dizziness (4/9), and visual disturbances (6/9) in the setting of a sellar hemorrhagic tumor on magnetic resonance imaging (MRI). Three patients presented with apoplexy and 6 with subclinical apoplexy. Duration of symptoms ranged from 3 days to 1 year. MRI revealed hemorrhage (9/9), rim enhancement (6/9), sphenoid sinus mucosal thickening (2/9), mass effect on the optic chiasm (8/9), and sellar remodeling (9/9). The percentage of hemorrhage preoperatively observed on MRI ranged from 50% to greater than 95%. On presentation, hyperprolactinemia was recorded in 7 patients, 6 of whom had galactorrhea and/or amenorrhea. Open transsphenoidal decompression was performed in 8/9 patients; 7 of 9 were diagnosed with prolactinoma. Biopsy specimens revealed 10%−90% hemorrhage and no infarction in any of the cases. All patients treated showed improvement of symptoms after surgery (average follow-up, 28.2 months). Postoperative complications included transient diabetes insipidus (n = 5), persistent cerebrospinal fluid rhinorrhea (n = 3), and meningitis (n = 1). Five patients had long-term endocrine sequelae of hyperprolactinemia requiring ongoing medical treatment. Conclusions Pituitary hemorrhage resulting in apoplexy or subclinical apoplexy in adolescents may represent a distinct entity with a more indolent symptomatology and more favorable neurologic and endocrine outcome compared with adults that is worthy of further validation in a multi-institutional cohort.