ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Correction: Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

OBJECTIVE: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. METHODS: The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. RESULTS: The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. CONCLUSIONS: Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study.

OBJECTIVE: Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS: TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher's exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS: The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS: Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Decision tree-based machine learning analysis of intraoperative vasopressor use to optimize neurological improvement in acute spinal cord injury.

OBJECTIVE: Previous work has shown that maintaining mean arterial pressures (MAPs) between 76 and 104 mm Hg intraoperatively is associated with improved neurological function at discharge in patients with acute spinal cord injury (SCI). However, whether temporary fluctuations in MAPs outside of this range can be tolerated without impairment of recovery is unknown. This retrospective study builds on previous work by implementing machine learning to derive clinically actionable thresholds for intraoperative MAP management guided by neurological outcomes. METHODS: Seventy-four surgically treated patients were retrospectively analyzed as part of a longitudinal study assessing outcomes following SCI. Each patient underwent intraoperative hemodynamic monitoring with recordings at 5-minute intervals for a cumulative 28,594 minutes, resulting in 5718 unique data points for each parameter. The type of vasopressor used, dose, drug-related complications, average intraoperative MAP, and time spent in an extreme MAP range (< 76 mm Hg or > 104 mm Hg) were collected. Outcomes were evaluated by measuring the change in American Spinal Injury Association Impairment Scale (AIS) grade over the course of acute hospitalization. Features most predictive of an improvement in AIS grade were determined statistically by generating random forests with 10,000 iterations. Recursive partitioning was used to establish clinically intuitive thresholds for the top features. RESULTS: At discharge, a significant improvement in AIS grade was noted by an average of 0.71 levels (p = 0.002). The hemodynamic parameters most important in predicting improvement were the amount of time intraoperative MAPs were in extreme ranges and the average intraoperative MAP. Patients with average intraoperative MAPs between 80 and 96 mm Hg throughout surgery had improved AIS grades at discharge. All patients with average intraoperative MAP > 96.3 mm Hg had no improvement. A threshold of 93 minutes spent in an extreme MAP range was identified after which the chance of neurological improvement significantly declined. Finally, the use of dopamine as compared to norepinephrine was associated with higher rates of significant cardiovascular complications (50% vs 25%, p < 0.001). CONCLUSIONS: An average intraoperative MAP value between 80 and 96 mm Hg was associated with improved outcome, corroborating previous results and supporting the clinical verifiability of the model. Additionally, an accumulated time of 93 minutes or longer outside of the MAP range of 76-104 mm Hg is associated with worse neurological function at discharge among patients undergoing emergency surgical intervention for acute SCI.

Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.

Trigger point injection for post-mastectomy pain: a simple intervention with high rate of long-term relief.

Post-mastectomy pain syndrome (PMPS) is a common and often debilitating condition. The syndrome is defined by chest wall pain unresponsive to standard pain medications and the presence of exquisite point tenderness along the inframammary fold at the site of the T4 and T5 cutaneous intercostal nerve branches as they exit from the chest wall. Pressure at the site triggers and reproduces the patient's spontaneous or motion-evoked pain. The likely pathogenesis is neuroma formation after injury to the T4 and T5 intercostal nerves during breast surgery. We assessed the rate of long-term resolution of post-mastectomy pain after trigger point injections (2 mL of 1:1 mixture of 0.5% bupivacaine and 4 mg/mL dexamethasone) to relieve neuropathic pain in a prospective single-arm cohort study. Fifty-two women (aged 31-92) who underwent partial mastectomy with reduction mammoplasty or mastectomy with or without reconstruction, and who presented with PMPS were enrolled at the University of California San Francisco Breast Care Center from August 2010 through April 2018. The primary outcome was a long-term resolution of pain, defined as significant or complete relief of pain for greater than 3 months. A total of 91 trigger points were treated with mean follow-up 43.9 months with a 91.2% (83/91) success rate. Among those with a long-term resolution of pain, 60 trigger points (72.3%) required a single injection to achieve long-lasting relief. Perineural infiltration with bupivacaine and dexamethasone is a safe, simple, and effective treatment for PMPS presenting as trigger point pain along the inframammary fold.

Telemedicine in Neurosurgery: Standardizing the Spinal Physical Examination Using A Modified Delphi Method.

OBJECTIVE: The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations. METHODS: We identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized. RESULTS: After the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol. CONCLUSION: The resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.

Diagnostic blood RNA profiles for human acute spinal cord injury.

Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI): an overview of initial enrollment and demographics.

OBJECTIVE: Traumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI). METHODS: Data were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury. RESULTS: One hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed. CONCLUSIONS: The authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

Diagnostic Challenges in Primary Sacral Tumors and the Yield of Computed Tomography-Guided Needle Biopsy in the Modern Era.

OBJECTIVE: Primary sacral tumors pose unique challenges because of their complex radiographic appearances, diverse pathologic entities, and dramatically different treatment paradigms based on tumor type. Magnetic resonance imaging and computed tomography (CT) can provide valuable information; however, sacral lesions can possess unique radiographic features and pose diagnostic dilemmas. CT-guided percutaneous needle biopsy is a critical component of the diagnostic workup. However, limited data are available on its efficacy for primary sacral tumors. METHODS: The data from patients with newly diagnosed primary sacral lesions during a 12-year period at our hospital were analyzed. The preoperative magnetic resonance imaging findings, biopsy results, and pathological data for patients who required surgery were analyzed. Unique cases in which the final pathologic result was unexpected from the preoperative imaging findings have been highlighted. RESULTS: Of 38 patients who underwent percutaneous needle biopsy, diagnostic tissue was obtained on the first attempt for 31 (82%). Five of the remaining 7 obtained diagnostic tissue on the second attempt, yielding 95% diagnosis, with only two requiring open biopsies. In 2 patients with diagnostic tissue on CT-guided biopsy, an open biopsy was still recommended because of the clinical scenario. In both patients, the open biopsy results matched those of the CT-guided biopsy. For the 18 patients who required surgery, we found 100% correlation between the percutaneous needle biopsy findings and the final pathological diagnosis. No biopsy-induced complications or extraspinal tumor seeding occurred. CONCLUSIONS: CT-guided biopsy is a safe and effective technique. It represents a critical component of the diagnostic algorithm, given the diverse pathological findings of primary sacral lesions and dramatic differences in treatment.

Clinical Implementation of Novel Spinal Cord Perfusion Pressure Protocol in Acute Traumatic Spinal Cord Injury at U.S. Level I Trauma Center: TRACK-SCI Study.

OBJECTIVE: We sought to report the safety of implementation of a novel standard of care protocol using spinal cord perfusion pressure (SCPP) maintenance for managing traumatic spinal cord injury (SCI) in lieu of mean arterial pressure goals at a U.S. Level I trauma center. METHODS: Starting in December 2017, blunt SCI patients presenting <24 hours after injury with admission American Spinal Injury Association Impairment Scale (AIS) A-C (or AIS D at neurosurgeon discretion) received lumbar subarachnoid drain (LSAD) placement for SCPP monitoring in the intensive care unit and were included in the TRACK-SCI (Transforming Research and Clinical Knowledge in Spinal Cord Injury) data registry. This SCPP protocol comprises standard care at our institution. SCPPs were monitored for 5 days (goal ≥65 mm Hg) achieved through intravenous fluids and vasopressor support. AISs were assessed at admission and day 7. RESULTS: Fifteen patients enrolled to date were aged 60.5 ± 17 years. Injury levels were 93.3% (cervical) and 6.7% (thoracic). Admission AIS was 20.0%/20.0%/26.7%/33.3% for A/B/C/D. All patients maintained mean SCPP ≥65 mm Hg during monitoring. Fourteen of 15 cases required surgical decompression and stabilization with time to surgery 8.8 ± 7.1 hours (71.4% <12 hours). At day 7, 33.3% overall and 50% of initial AIS A-C had an improved AIS. Length of stay was 14.7 ± 8.3 days. None had LSAD-related complications. There were 7 respiratory complications. One patient expired after transfer to comfort care. CONCLUSIONS: In our initial experience of 15 patients with acute SCI, standardized SCPP goal-directed care based on LSAD monitoring for 5 days was feasible. There were no SCPP-related complications. This is the first report of SCPP implementation as clinical standard of care in acute SCI.

Neurological outcomes and surgical complications in 221 spinal nerve sheath tumors.

OBJECTIVE Among all primary spinal neoplasms, approximately two-thirds are intradural extramedullary lesions; nerve sheath tumors, mainly neurofibromas and schwannomas, comprise approximately half of them. Given the rarity of these lesions, reports of surgical complications are limited. The aim of this study was to identify the rates of new or worsening neurological deficits and surgical complications associated with the resection of spinal nerve sheath tumors and the potential factors related to these outcomes. METHODS Patients were identified through a search of an institutional neuropathology database and a separate review of current procedural terminology (CPT) codes. Age, sex, clinical presentation, presence of neurofibromatosis (NF), tumor type, tumor location, extent of resection characterized as gross total or subtotal, use of intraoperative neuromonitoring, surgical complications, presence of neurological deficit, and clinical follow-up were recorded. RESULTS Two hundred twenty-one tumors in 199 patients with a mean age of 45 years were identified. Fifty-three tumors were neurofibromas; 163, schwannomas; and 5, malignant peripheral nerve sheath tumors (MPNSTs). There were 70 complications in 221 cases, a rate of 32%, which included 34 new or worsening sensory symptoms (15%), 12 new or worsening motor deficits (5%), 10 CSF leaks or pseudomeningoceles (4%), 11 wound infections (5%), 5 cases of spinal deformity (2%), and 6 others (2 spinal epidural hematomas, 1 nonoperative cranial subdural hematoma, 1 deep venous thrombosis, 1 case of urinary retention, and 1 recurrent laryngeal nerve injury). Complications were more common in cervical (36%) and lumbosacral (38%) tumors than in thoracic (18%) lesions (p = 0.021). Intradural and dumbbell lesions were associated with higher rates of CSF leakage, pseudomeningocele, and wound infection. Complications were present in 18 neurofibromas (34%), 50 schwannomas (31%), and 2 MPNSTs (40%); the differences in frequency were not significant (p = 0.834). Higher complication rates were observed in patients with NF than in patients without (38% vs 30%, p = 0.189), although rates were higher in NF Type 2 than in Type 1 (64% vs 31%). There was no difference in the use of intraoperative neuromonitoring when comparing cases with surgical complications and those without (67% vs 69%, p = 0.797). However, the use of neuromonitoring was associated with a significantly higher rate of gross-total resection (79% vs 66%, p = 0.022). CONCLUSIONS Resection is a safe and effective treatment for spinal nerve sheath tumors. Approximately 30% of patients developed a postoperative complication, most commonly new or worsening sensory deficits. This rate probably represents an inevitable complication of nerve sheath tumor surgery given the intimacy of these lesions with functional neural elements.

Comparative Sensitivity of Intraoperative Motor Evoked Potential Monitoring in Predicting Postoperative Neurologic Deficits: Nondegenerative versus Degenerative Myelopathy.

STUDY DESIGN: Retrospective review. OBJECTIVE: Intraoperative motor evoked potential (MEP) monitoring in spine surgery may assist surgeons in taking corrective measures to prevent neurologic deficits. The efficacy of monitoring MEPs intraoperatively in patients with myelopathy from nondegenerative causes has not been quantified. We compared the sensitivity and specificity of intraoperative MEP monitoring in patients with myelopathy caused by nondegenerative processes to patients with degenerative cervicothoracic spondylotic myelopathy (CSM). METHODS: We retrospectively reviewed our myelopathy surgical cases during a 1-year period to identify patients with degenerative CSM and CSM of nondegenerative causes and collected data on intraoperative MEP changes and postoperative new deficits. Categorical variables were analyzed by Fisher exact test. Receiver operator curves assessed intraoperative MEP monitoring performance in the two groups. RESULTS: In all, 144 patients were identified: 102 had degenerative CSM and 42 had CSM of nondegenerative causes (24 extra-axial tumors, 12 infectious processes, 5 traumatic fractures, and 1 rheumatoid arthritis). For degenerative CSM, there were 11 intraoperative MEP alerts and 7 new deficits (p < 0.001). The corresponding sensitivity was 71% and the specificity was 94%. In the nondegenerative group, there were 11 intraoperative MEP alerts and 3 deficits, which was not significant (p > 0.99). The sensitivity (33%) and specificity (74%) were lower. Among patients with degenerative CSM, the model performed well for predicting postoperative deficits (area under the curve [AUC] 0.826), which appeared better than the nondegenerative group, although it did not reach statistical significance (AUC 0.538, p = 0.16). CONCLUSIONS: Based on this large retrospective analysis, intraoperative MEP monitoring in surgery for nondegenerative CSM cases appears to be less sensitive to cord injury and less predictive of postoperative deficits when compared with degenerative CSM cases.

Results of Spinal Fusion After Spinal Nerve Sheath Tumor Resection.

INTRODUCTION: Intradural extramedullary spine tumors, approximately one-half of which are peripheral nerve sheath tumors (PNSTs), comprise two-thirds of primary spinal neoplasms. Given the rarity of PNSTs and the restricted indications for adding fusion to laminectomy for tumor resection, analyses of spinal fusion outcomes are limited. METHODS: Demographics, clinical presentation, tumor characteristics, extent of resection, spinal fusion, complications, and clinical follow-up were recorded retrospectively. RESULTS: A total of 221 tumors in 199 patients were identified (53 neurofibromas, 163 schwannomas, 5 malignant PNSTs); 78 patients underwent fusion (70 instrumented; 8 noninstrumented). Fusion rates were higher for extradural versus intradural lesions (60% vs. 29%; P = 0.001) and for tumors involving the cervicothoracic junction (88% vs. 31%, P < 0.001). There was no difference in fusion rates based on pathology. Rates of new or worsening sensory (19% in fusion vs. 13% in nonfused) or motor deficits (8% in fused vs. 4% in nonfused), wound infection (3% in fused vs. 6% in nonfused) and cerebrospinal fluid (CSF) leak or pseudomeningocele (6% in fused vs. 4% in nonfused) were not statistically different. There were 10 fusion-related complications: 6 adjacent segment disease, 3 implant failures, and 1 pseudoarthrosis. Mean time from surgery to last follow-up was 32 months. CONCLUSIONS: In this cohort, PNSTs in the cervical spine, spanning the cervicothoracic junction, and extradural tumors were associated with higher rates of spinal fusion. Fusion was not associated with new or worsening motor/sensory deficits, CSF leak, pseudomeningocele, wound infection, or spinal deformity. Overall, spinal fusions were well tolerated and did not increase the risk of postoperative complications.

Microsurgical Fenestration and Paraspinal Muscle Pedicle Flaps for the Treatment of Symptomatic Sacral Tarlov Cysts.

OBJECTIVE: Sacral Tarlov cysts are rare causes of sciatic and sacrococcygeal pain and neurologic deficits. Although several microsurgical treatments have been described, the optimal treatment has yet to be determined. We describe our initial experience with symptomatic lesions combining 1) cyst fenestration and imbrication and 2) filling the epidural space using vascularized paraspinous muscle flaps rotated into the cystic cavity. METHODS: We retrospectively reviewed all consecutive cases of symptomatic giant sacral Tarlov cysts treated with microsurgery at our institution between 2003 and 2011. The main outcome measure was self-reported symptom relief. Postoperative imaging, surgical complications, and subsequent treatments were also recorded. RESULTS: Thirty-five patients were treated. Mean age was 52 years. All patients presented with a chief complaint of sacral-perineal pain. The mean cyst size was 3.6 cm (largest diameter). Follow-up beyond the initial hospital stay was available in 86% (median 8 months). Ninety-three percent reported improvement in pain at some point during the postoperative course but 50% of those developed recurrent pain symptoms. Postoperative imaging was available in 69% of the patients in whom 92% showed complete obliteration (25%) or reduction in cyst size (67%). CONCLUSIONS: The combination of microsurgical cyst fenestration and the use of vascularized muscle pedicle flaps to fill the cystic cavity and the epidural space results in obliteration or reduction in size of the majority of cysts and is associated with initial improvement in pain in most patients. However, delayed recurrence of pain was common with this technique.

Neurogenic thoracic outlet syndrome: current diagnostic criteria and advances in MRI diagnostics.

Neurogenic thoracic outlet syndrome (nTOS) is caused by compression of the brachial plexus as it traverses from the thoracic outlet to the axilla. Diagnosing nTOS can be difficult because of overlap with other complex pain and entrapment syndromes. An nTOS diagnosis is made based on patient history, physical exam, electrodiagnostic studies, and, more recently, interpretation of MR neurograms with tractography. Advances in high-resolution MRI and tractography can confirm an nTOS diagnosis and identify the location of nerve compression, allowing tailored surgical decompression. In this report, the authors review the current diagnostic criteria, present an update on advances in MRI, and provide case examples demonstrating how MR neurography (MRN) can aid in diagnosing nTOS. The authors conclude that improved high-resolution MRN and tractography are valuable tools for identifying the source of nerve compression in patients with nTOS and can augment current diagnostic modalities for this syndrome.

Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors.

OBJECT Intradural extramedullary spine tumors represent two-thirds of all primary spine neoplasms. Approximately half of these are peripheral nerve sheath tumors, mainly neurofibromas and schwannomas. Given the rarity of this disease and, thus, the limited analyses of clinical outcomes, the authors examined the association of tumor location, extent of resection, and neurofibromatosis (NF) status with clinical outcomes. METHODS Patients were identified through a search of the University of California, San Francisco, neuropathology database and a separate review of current procedural terminology codes. Data recorded included patient age, patient sex, clinical presentation, presence of NF, tumor type, tumor location, extent of resection (gross-total resection [GTR] or subtotal resection [STR]), and clinical follow-up. RESULTS Of 221 tumors in 199 patients (mean age 45 years), 53 were neurofibromas, 163 were schwannomas, and 5 were malignant peripheral nerve sheath tumors. The most common presenting symptom was spinal pain (76%), followed by weakness (36%) and sensory abnormalities (34%). Mean symptom duration was 16 months. In terms of spinal location, neurofibromas were more common in the cervical spine (74% vs 27%, p < 0.001), and schwannomas were more common in the thoracic and lumbosacral spine (73% vs 26%, p < 0.001). Rates of GTR were lower for neurofibromas than schwannomas (51% vs 83%, p < 0.001), regardless of location. Rates of GTR were lower for cervical (54%) than thoracic (90%) and lumbosacral (86%) lesions (p < 0.001). NF was associated with lower rates of GTR among all tumors (43% vs 86%, p < 0.001). The mean follow-up time was 32 months. Recurrence/progression was more common for neurofibromas than schwannomas (17% vs 7%, p = 0.03), although the mean time to recurrence/progression did not differ according to tumor type (45 vs 53 months, p = 0.63). As expected, GTR was associated with lower recurrence rates (4% vs 22%, p < 0.001). According to multivariate analysis, cervical location (OR 0.239, 95% CI 0.110-0.520) and presence of NF (OR 0.166, 95% CI 0.054-0.507) were associated with lower rates of GTR. In a separate model, only GTR (OR 0.141, 95% CI 0.046-0.429) was associated with tumor recurrence. CONCLUSIONS Resection is an effective treatment for spinal nerve sheath tumors. Neurofibromas were found more commonly in the cervical spine than in other regions of the spine and were associated with higher rates of recurrence and lower rates of GTR than other tumor types, particularly in patients with NF Types 1 or 2. According to multivariate analysis, both cervical location and presence of NF were associated with lower rates of GTR. According to a second multivariate model, the only variable associated with tumor recurrence was extent of resection. Maximal safe resection remains ideal for these lesions; however, patients with cervical tumors or NF should be counseled about their increased risk for recurrence.

Surgical outcomes in spinal cord ependymomas and the importance of extent of resection in children and young adults.

OBJECT: Ependymomas are a common type of CNS tumor in children, although only 13% originate from the spinal cord. Aside from location and extent of resection, the factors that affect outcome are not well understood. METHODS: The authors performed a search of an institutional neuropathology database to identify all patients with spinal cord ependymomas treated over the past 20 years. Data on patient age, sex, clinical presentation, symptom duration, tumor location, extent of resection, use of radiation therapy, surgical complications, presence of tumor recurrence, duration of follow-up, and residual symptoms were collected. Pediatric patients were defined as those 21 years of age or younger at diagnosis. The extent of resection was defined by the findings of the postoperative MR images. RESULTS: A total of 24 pediatric patients with spinal cord ependymomas were identified with the following pathological subtypes: 14 classic (Grade II), 8 myxopapillary (Grade I), and 2 anaplastic (Grade III) ependymomas. Both anaplastic ependymomas originated in the intracranial compartment and spread to the spinal cord at recurrence. The mean follow-up duration for patients with classic and myxopapillary ependymomas was 63 and 45 months, respectively. Seven patients with classic ependymomas underwent gross-total resection (GTR), while 4 received subtotal resection (STR), 2 received STR as well as radiation therapy, and 1 received radiation therapy alone. All but 1 patient with myxopapillary ependymomas underwent GTR. Three recurrences were identified in the Grade II group at 45, 48, and 228 months. A single recurrence was identified in the Grade I group at 71 months. The mean progression-free survival (PFS) was 58 months in the Grade II group and 45 months in the Grade I group. CONCLUSIONS: Extent of resection is an important prognostic factor in all pediatric spinal cord ependymomas, particularly Grade II ependymomas. These data suggest that achieving GTR is more difficult in the upper spinal cord, making tumor location another important factor. Although classified as Grade I lesions, myxopapillary ependymomas had similar outcomes when compared with classic (Grade II) ependymomas, particularly with respect to PFS. Long-term complications or new neurological deficits were rare. Among patients with long-term follow-up, those who underwent GTR had a recurrence rate of 20% compared with 40% among those with STR or biopsy only, suggesting that extent of resection is perhaps a more important prognostic factor than histological grade in predicting PFS, which has been suggested by other data in the literature. Given the relative paucity of these lesions, collaborative multiinstitutional studies are needed, and such efforts should also focus on molecular and genetic analysis to refine the current classification system.

Intraoperative neuromonitoring with MEPs and prediction of postoperative neurological deficits in patients undergoing surgery for cervical and cervicothoracic myelopathy.

OBJECT: The use of intraoperative neurophysiological monitoring (IONM) in surgical decompression surgery for myelopathy may assist the surgeon in taking corrective measures to reduce or prevent permanent neurological deficits. We evaluated the efficacy of IONM in cervical and cervicothoracic spondylotic myelopathy (CSM) cases. METHODS: The authors retrospectively reviewed 140 cases involving patients who underwent surgery for CSM utilizing IONM during 2011 at the University of California, San Francisco. Data on preoperative clinical variables, intraoperative changes in transcranial motor evoked potentials (MEPs), and postoperative new neurological deficits were collected. Associations between categorical variables were analyzed with the Fisher exact test. RESULTS: Of the 140 patients, 16 (11%) had significant intraoperative decreases in MEPs. In 8 of these cases, the MEP signal did not return to baseline values by the end of the operation. There were 8 (6%) postoperative deficits, of which 6 were C-5 palsies and 2 were paraparesis. Six of the patients with postoperative deficits had demonstrated persistent MEP signal change on IONM. There was a significant association between persistent MEP changes and postoperative deficits (p < 0.001). The sensitivity of intraoperative MEP monitoring was 75%, the specificity 98%, the positive predictive value 75%, and the negative predictive value 98%. Due to higher rates of false negatives, the sensitivity decreased to 60% in the subgroup of patients with vascular disease comorbidity. The sensitivity increased to 100% in elderly patients and in patients with preoperative motor deficits. The sensitivity and positive predictive value of deltoid and biceps MEP changes in predicting C-5 palsy were 67% and 67%, respectively. CONCLUSIONS: The authors found a correlation between decreased intraoperative MEPs and postoperative new neurological deficits in patients with CSM. Sensitivity varies based on patient comorbidities, age, and preoperative neurological function. Monitoring of MEPs is a useful adjunct for CSM cases, and the authors have developed a checklist to standardize their responses to intraoperative MEP changes.