Minimally Invasive Microsurgical Resection of Primary, Intradural Spinal Tumors is Feasible and Safe: A Consecutive Series of 83 Patients

Minimally Invasive Microsurgical Resection of Primary, Intradural Spinal Tumors is Feasible and... Abstract BACKGROUND To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty followed by microsurgical tumor resection. Recently, however, minimally invasive approaches have been attempted by some. OBJECTIVE To investigate the feasibility and safety of minimally invasive surgery (MIS) for primary intradural spinal tumors. METHODS Medical charts of 83 consecutive patients treated with MIS for intradural spinal tumors were reviewed. Patients were followed up during the study year, 2015, by either routine history/physical examination or by telephone consultation, with a focus on tumor status and surgery-related complications. RESULTS Mean age at surgery was 53.7 yr and 52% were female. There were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 paraganglioma, 1 epidermoid cyst, and 1 hemangiopericytoma. The surgical mortality was 0%. In 87% of cases, gross total resection was achieved. The complication rate was 11%, including 2 cerebrospinal fluid leakages, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. There were no postoperative hematomas, and no cases of deep vein thrombosis or pulmonary embolism. Ninety-three percent of patients were ambulatory and able to work at the time of follow-up. CONCLUSION This study both demonstrates that it is feasible and safe to remove select, primary intradural spinal tumors using MIS, and augments the previous literature in favor of MIS for these tumors. Ependymoma, Feasibility studies, Meningioma, Minimally invasive surgical procedures, Neurilemmoma, Spinal neoplasms, Spine ABBREVIATIONS ABBREVIATIONS CSF cerebrospinal fluid DVT deep vein thrombosis ECOG Eastern Cooperative Oncology Group GTR gross total resection MIS minimally invasive surgery MRI magnetic resonance imaging PE pulmonary embolism STR subtotal resection VAS visual analog score The overall incidence rate of primary intraspinal tumors is 1.0 to 1.5 per 100 000 person-years.1,2 The most common histological types are nerve sheath tumors, followed by meningiomas and ependymomas. Most intraspinal tumors present with local back/neck pain, radicular pain, and/or neurological deficit(s). Microsurgical resection is the primary treatment for symptomatic tumors. When planning surgery for an intraspinal tumor, it is of paramount importance to choose an approach that allows for gross total resection (GTR), while at the same time ensuring minimal complications. To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty, succeeded by microsurgical tumor resection.3-14 The open approach, which requires an extensive skin incision, continuous retraction of the paraspinal muscles, and laminectomy/laminotomy, may contribute to intraoperative and postoperative blood loss, prolonged hospital stay, postoperative complications such as hematoma and infection, greater chance of spinal deformity/vertebral instability, and habitual pain in the operated segment.3-16 Recent progress in minimally invasive surgery (MIS) has resulted in spinal approaches that could potentially reduce tissue trauma and subsequent intra/postoperative blood loss, postoperative pain/discomfort, and length of hospital stay. MIS might also facilitate a swifter return to activities of daily living, and from a health economics standpoint this would appear to be a more cost-efficient treatment. Several institutions have already implemented MIS in the treatment of intraspinal tumors and some small cohort studies have been published.17-23 Additionally, a few case control studies comparing MIS to more traditional open approaches have recently been published.24-27 We recently presented our initial experience with MIS in the resection of select, primary intradural spinal tumors,17 and in this study we present our cumulative experience with the technique, now including 83 patients. The objective of the study is to examine the feasibility and safety of MIS for primary, intradural spinal tumors, with a specific emphasis on resection grade and surgery-related complications. METHODS Ethics The study was approved by The Regional Ethical Committee and the Data Protection Official at Oslo University Hospital. All patients participating in the study gave their informed consent. Patients The Department of Neurosurgery at our hospital has a catchment area of ∼1 million inhabitants for intradural tumor surgery. During the time period January 2007 to June 2015, 83 patients had MIS for a primary intradural spinal tumor; these are the patients included in this study. Retrospective Medical Chart Review All patient charts, including radiology and pathology reports and preoperative, operative, postoperative, and outpatient chart notes, were reviewed retrospectively. The following information was recorded from the charts: sex, patient age at surgery (years), presenting symptom(s), level of tumor location, craniocaudal extension of tumor in millimeter, operating time (skin incision to skin closure, in minutes), grade of tumor resection (GTR or subtotal resection [STR]), determined by postoperative magnetic resonance imaging [MRI]), final histological diagnosis, day of mobilization, day of discharge, peri- and postoperative complications, date of most recent MRI with tumor status. Preoperative Routines An anesthesiologist consulted on all patients prior to surgery. In our hospital, an internist routinely consults on elderly patients (>70 yr) and on polypharmacy patients so that medications and each patient's general medical condition are optimized preoperatively. Patients with heart disease were referred to a cardiologist for echocardiography and cardiovascular stress test, and patients with hematological disorders were referred to a hematologist. Anticoagulant and antiplatelet therapy were discontinued prior to surgery in cases where there was a relative indication for their use: in cases where there was an absolute indication for their use, a hematologist and/or cardiologist was/were consulted. Graduated compression stockings were administered to all patients the day before surgery, and they were continued until full mobilization was achieved. Intraoperative Routines/Techniques Patients were placed in the prone position, either flat or resting on the knees and elbows. A second-generation cephalosporin was given intravenously within 30 min prior to the surgical incision and continued every 180 min until the case was finished or until the maximum dose of 8 g daily was reached. The accurate level was confirmed by lateral fluoroscopy. With the MAST-QUADRANT system (Medtronic Inc, Dublin, Ireland), a 30 to 60 mm skin incision was made 20 to 40 mm lateral to the midline. The paraspinous muscles were then bluntly separated using the MAST-QUADRANT dilators. Dilators were successively placed, one over the other, up to 22 mm. The MAST-QUADRANT retractor was implanted over the dilators and positioned over the bony anatomy. The retractor was then secured in place by a table-mounted flexible arm. The dilators were removed, creating a tubular surgical passageway to the interlaminar spaces and lamina. Medial and lateral retractor blades were also used in order to increase the operative field. Due to the flexible, but fixed arm, the blades could be shifted during surgery in order to optimize the viewing field. With the Caspar system (Aesculap Implant Systems, Center Valley, Pennsylvania), a 30 to 60 mm long skin incision was made 10 to 20 mm lateral to the midline; the approach was medial to the paraspinous muscles. The Caspar specules were inserted according to the manufacturer's instructions (Aesculap Implant Systems).28 After positioning the blades, whether using MAST-QUADRANT (Medtronic Inc) or Caspar (Aesculap Implant Systems), the remainder of the procedure was conducted with the assistance of an operating microscope. A 1-level hemilaminectomy, undercutting of the contralateral lamina, and ventral surface of the spinous process were accomplished utilizing Kerrison punches and a high-speed drill. The ligamentum flavum was incised and resected. Ultrasound (LOGIQ, General Electric, Fairfield, Connecticut) was used to verify tumor location prior to dural opening. If the cranial or caudal extension of the tumor was not adequately exposed using a 1-level hemilaminectomy, an arcotomy of the inferior part of the lamina above or an arcotomy of the superior part of the lamina below was performed. If more than one-third of the lamina above or below had to be removed, it was considered a 2-level hemilaminectomy. The dura was opened in the midline or with a paramedian incision. Stay sutures were then placed to reflect the dural edges. Tumor resection was carried out using traditional microsurgical instrumentation. When tumor resection was finished, the dura was approximated with a 5-0 running suture and then sealed with TachoSil; a collagen matrix coated with fibrinogen and thrombin (TachoSil, Nycomed, Oslo, Norway). Postoperative Routines Postoperatively, patients were monitored in a postanesthesia care unit for 3 to 6 h prior to being transferred to either the neurosurgical floor or to a phase II step-down unit for further monitoring. Low-molecular weight heparin was administered on postoperative day 1. The patients were mobilized either the same day as surgery or on postoperative day 1. Immediate postoperative MRI (within 72 h after surgery) was done on all patients for the purpose of establishing resection grade. Follow-up All 83 patients were followed up with MRI 3 to 6 mo postoperatively, followed by outpatient clinical examination. Further follow-up was done as indicated. Patients were provided with detailed information concerning symptoms/signs of the intraspinal tumor and were told to get in touch with the Department of Neurosurgery immediately should such symptoms/signs occur. Patients with schwannoma and meningeoma whose tumors were removed with GTR and were not associated with the genetic neurofibromatosis disorders (NF1, NF2, Schwannomatosis), who had an uncomplicated postoperative period, and whose 3 to 6 mo postoperative follow-up was satisfactory were not followed up further unless they developed signs/symptoms that could be attributed to the intraspinal tumor. For 17 of 83 patients, all of the desired information could be extracted from the most recent outpatient note, and for the remaining 66 patients, the outpatient notes were supplemented with a telephone consultation during the study year (2015) in order to obtain any information that was lacking from the outpatient notes, particularly pain intensity. The following variables were recorded: time to follow-up was calculated from the surgical date to the most recent outpatient consultation or to telephone consultation, back and radicular pain was graded using visual analog scores (VAS; pain was only graded if present 3 or more days per week the preceding 4 wk),29 current use of analgesics (use was defined as intake of analgesics for back or radicular pain 3 or more days per week the preceding 4 wk), symptom status, date of most recent MRI with tumor status, and Eastern Cooperative Oncology Group performance status (ECOG; “0—fully active, able to carry on all predisease performance without restriction; 1—restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2—ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours; 3—capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4—completely disabled, cannot carry on any self-care, totally confined to bed or chair; and 5—dead”30). Vital status and time of death were procured from the Norwegian Population Registry (Folkeregisteret) July 13, 2015. RESULTS Demographics Eighty-three patients with primary, intradural spinal tumors were included in this study: there were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 epidermoid cyst, 1 paraganglioma, and 1 hemangiopericytoma. Patient characteristics are summarized in Table 1. The mean age at surgery was 53.7 yr (range 19.7-85.9), and 43 patients were female. The most common presenting complaints were back pain and radicular pain. TABLE 1. Patient Characteristics     n (%)  Sex  Female  43 (51.8)    Male  40 (48.2)  Age (years)  <20  1 (1.2)    20-39  20 (24.1)    40-59  30 (36.1)    60-79  27 (32.5)    >80  5 (6.0)  Symptoms and signs  Back pain  58 (69.9)    Radicular pain  61 (73.5)    Sensory deficit  36 (43.4)    →Paresthesia  15 (18.1)    →Reduction/loss  21 (25.3)    Paresis  32 (38.6)    Bladder dysfunction  12 (14.5)  Tumor location  Cervical  9 (10.8)    Thoracal  23 (27.7)    Thoracolumbar junction  5 (6.0)    Lumbar  41 (49.4)    Lumbosacral junction  1 (1.2)    Sacral  4 (4.8)  Histology  Schwannoma  49 (59.0)    Meningioma  18 (21.7)    Ependymoma  10 (12.0)    Neurofibroma  1 (1.2)    Hemangioblastoma  2 (2.4)    Hemangiopericytoma  1 (1.2)    Epidermoid cyst  1 (1.2)    Paraganglioma  1 (1.2)  Resection grade  Grosstotal (GTR)  72 (86.7)    Subtotal (STR)  11 (13.3)  Adjuvant treatment  Radiotherapy  1 (1.2)    Chemotherapy  0 (0)      n (%)  Sex  Female  43 (51.8)    Male  40 (48.2)  Age (years)  <20  1 (1.2)    20-39  20 (24.1)    40-59  30 (36.1)    60-79  27 (32.5)    >80  5 (6.0)  Symptoms and signs  Back pain  58 (69.9)    Radicular pain  61 (73.5)    Sensory deficit  36 (43.4)    →Paresthesia  15 (18.1)    →Reduction/loss  21 (25.3)    Paresis  32 (38.6)    Bladder dysfunction  12 (14.5)  Tumor location  Cervical  9 (10.8)    Thoracal  23 (27.7)    Thoracolumbar junction  5 (6.0)    Lumbar  41 (49.4)    Lumbosacral junction  1 (1.2)    Sacral  4 (4.8)  Histology  Schwannoma  49 (59.0)    Meningioma  18 (21.7)    Ependymoma  10 (12.0)    Neurofibroma  1 (1.2)    Hemangioblastoma  2 (2.4)    Hemangiopericytoma  1 (1.2)    Epidermoid cyst  1 (1.2)    Paraganglioma  1 (1.2)  Resection grade  Grosstotal (GTR)  72 (86.7)    Subtotal (STR)  11 (13.3)  Adjuvant treatment  Radiotherapy  1 (1.2)    Chemotherapy  0 (0)  View Large Primary Treatment Microsurgery was the primary mode of treatment for all 83 patients. There was a gradual increase in patients treated with MIS from 0% of patients treated with MIS prior to 2007 to 84% of patients treated with MIS in 2015. Two patients had MIS in 2007, 1 in 2008, 7 in 2009, 10 in 2010, 10 in 2011, 10 in 2012, 17 in 2013, 13 in 2014, and 13 in 2015, respectively. One-level hemilaminectomy provided sufficient exposure in 62 cases, while 2-level hemilaminectomy was necessary in 21 cases. GTR was accomplished in 72 patients (87%) and STR in 11 patients (13%; Table 2). Median surgical duration was 142 min (range 62-374 min). Mean craniocaudal tumor length was 19.6 mm (range 6-49 mm). Median time to mobilization out of bed was 1 d (range 0-4 d). The median duration of hospital stay after surgery was 3 d (range 0-14 d). Forty-six patients (55%) were discharged to the home, while 37 (45%) were transferred to another medical institution. One patient received adjuvant radiotherapy for a subtotally resected myxopapillary ependymoma. None of the patients received chemotherapy. TABLE 2. Main Cause of STR No  Histology  Cause of STR  1  Hemangiopericytoma  Adherent to/invading spinal cord.  2  Ependymoma  Infiltrating conus medullaris.  3  Schwannoma  Surgery for recurrent tumor.  4  Schwannoma  Surgery for recurrent tumor.  5  Schwannoma  STR initially discovered upon postoperative MRI.  6  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  7  Ependymoma  Surgery for recurrent tumor.  8  Meningioma  Small calcified remnant ventral to the spinal cord, intentionally not removed.  9  Schwannoma  STR initially discovered upon postoperative MRI.  10  Hemangioblastoma  Large tumor infiltrating conus medullaris, GTR regarded as too risky.  11  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  No  Histology  Cause of STR  1  Hemangiopericytoma  Adherent to/invading spinal cord.  2  Ependymoma  Infiltrating conus medullaris.  3  Schwannoma  Surgery for recurrent tumor.  4  Schwannoma  Surgery for recurrent tumor.  5  Schwannoma  STR initially discovered upon postoperative MRI.  6  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  7  Ependymoma  Surgery for recurrent tumor.  8  Meningioma  Small calcified remnant ventral to the spinal cord, intentionally not removed.  9  Schwannoma  STR initially discovered upon postoperative MRI.  10  Hemangioblastoma  Large tumor infiltrating conus medullaris, GTR regarded as too risky.  11  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  View Large Surgical Mortality and Morbidity The surgical mortality (death within 30 d of surgery) was 0%. Nine patients (11%) had a total of 10 surgery-related complications (Table 3). In addition, slight sensory disturbances in the distribution of a single dermatoma were seen in 11 patients following surgery. This was not considered a complication per se, as it is a relatively common and anticipated symptom following intradural schwannoma GTR. The surgery-related complications were as follows: 2 cerebrospinal fluid (CSF) leaks, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. Neurological deterioration consisted of moderate paresis in 2 patients and of mild paresis in 2 patients. A sinus venous thrombosis was the cause of moderate paresis in one of the patients. There were no postoperative hematomas in need of surgical evacuation, and none of the patients were diagnosed with pulmonary embolism (PE) or deep vein thrombosis (DVT). The duration of surgery was slightly longer for patients with surgery-related complications. TABLE 3. Surgery-Related Complications   n (%)a  30-d mortality  0 (0)  Postoperative hematoma  0 (0)  Deep surgical site infection  2 (2.4)  CSF-leakage and pseudomeningocele  3 (3.7)  Neurological deterioration  4 (4.9%)  Sinus vein thrombosis  1 (1.2)  DVT/PE  0 (0)    n (%)a  30-d mortality  0 (0)  Postoperative hematoma  0 (0)  Deep surgical site infection  2 (2.4)  CSF-leakage and pseudomeningocele  3 (3.7)  Neurological deterioration  4 (4.9%)  Sinus vein thrombosis  1 (1.2)  DVT/PE  0 (0)  aA total of 10 complications were registered in 9 patients. View Large Follow-up All but 1 of the patients were available for follow-up. Mean time to follow-up was 26 mo (range 3-88 mo), and 54 (66%) patients were followed up for more than 1 yr. Of the 82 patients, 77 (92.8%) had an ECOG score of 0 to 1 (ambulatory and able to carry out work),30 4 (4.8%) had an ECOG score of 2 (ambulatory and capable of all self-care, but unable to carry out any work activities),30 and 1 (1.2%) had an ECOG score of 3 (capable of only limited self-care; confined to bed or chair more than 50% of waking hours).30 The patients with ECOG scores of 2 and 3 did not deteriorate postoperatively, they had the same ECOG scores preoperatively. Four of the 5 patients with ECOG scores of 2 and 3 had tumors located in the thoracic region, so it appears that thoracic location is a risk factor for a poorer outcome (Table 4). There were no cases of vertebral instability/kyphosis in the operated segment at follow-up. One of the 72 patients treated with GTR developed a recurrence, while 4 of the 11 patients treated with STR experienced growth of residual tumor. One patient died during the study period as a result of metastatic cancer of unknown origin, which was diagnosed approximately 4 yr following removal of the intraspinal tumor. TABLE 4. ECOG 2 and 3 Patients No  Sex  Age  Preoperative symptoms  Tumor location  Histology  Surgical complication  Resection grade  ECOG at Follow-up  1  M  51  Paresis, sensory deficit  Thoracic  Meningioma  None  GTR  3  2  F  63  Paresis, pain  Thoracic  Meningioma  None  GTR  2  3  M  31  Paresis, pain  Thoracic  Schwannoma  None  GTR  2  4  F  30  Sensory deficit, pain  Sacral  Meningioma  None  GTR  2  5  M  55  Paresis, sensory deficit, pain  Thoracic  Schwannoma  None  GTR  2  No  Sex  Age  Preoperative symptoms  Tumor location  Histology  Surgical complication  Resection grade  ECOG at Follow-up  1  M  51  Paresis, sensory deficit  Thoracic  Meningioma  None  GTR  3  2  F  63  Paresis, pain  Thoracic  Meningioma  None  GTR  2  3  M  31  Paresis, pain  Thoracic  Schwannoma  None  GTR  2  4  F  30  Sensory deficit, pain  Sacral  Meningioma  None  GTR  2  5  M  55  Paresis, sensory deficit, pain  Thoracic  Schwannoma  None  GTR  2  View Large DISCUSSION Previous studies indicate that MIS might be beneficial for patients with intraspinal tumors; however, these studies are too small and too preliminary in nature to provide any sort of conclusive evidence. The surgical mortality in the current study of consecutive 83 patients was 0%, GTR was achieved in 87% of cases, and the total complication rate was 11%. At follow-up, 93% of patients were ambulatory and able to work. The results of the current study strongly support the idea that MIS for select, primary intradural spinal tumors is feasible and safe.17-27 Tumor Removal The rate of GTR following open surgery for intradural, extramedullary tumors is reported to be in the range of 64% to 98%,3-6,9-13,24,31,32 whereas the corresponding rate for intramedullary tumors is much lower.9 The rate of GTR following MIS for intradural, extramedullary tumors is reported to be in the range of 68% to 100%.17,19,20,22-24,32 In the current study, GTR was achieved in 87% of cases. Taking this and other studies into account, it appears that MIS provides sufficient access to most intraspinal tumors, such that they can be resected as radically with MIS as with open surgery. Our experience with MIS for intramedullary tumors and filum terminale ependymomas larger than 5 cm in craniocaudal extension, however, is limited and it is therefore not possible to make any presumptions regarding whether MIS is comparable to open surgery for these cases. Surgical Mortality Surgical mortality following open surgery for intradural, extramedullary tumors is reported to be in the range of 0% to 2%,4,5,7,9-13,24,26,32 while surgical mortality following MIS for intradural, extramedullary tumors is reported to be 0%.19,20,22-26,31,32 The surgical mortality was 0%, which is in concordance with previous studies. The aforementioned data strongly suggest that MIS for intraspinal tumors poses a very low perioperative risk of death. Surgical Morbidity In a review of complications following spinal surgery, Nasser et al33 pointed out the lack of standardized reporting systems for such complications. Yadla et al34 have recently published a prospective study regarding early complications following spinal surgery, which revealed a rather high complication rate compared to other studies. They postulate that the aforementioned disparity is due to the fact that many studies report falsely low complication rates as a result of deficient records and recall bias. It can also appear that large, national databases report complication rates in the lower range. In the current study, the surgical morbidity was 11% and the following complications were recorded: CSF leakage, pseudomeningocele, postoperative hematoma, surgical site infection, neurological complications, and DVT/PE. Since this is a retrospective study, it must be kept in mind that complications are always lower when assessed retrospectively. Postoperative Mobilization and CSF Leakage In our department, standard procedure following open spine surgery with durotomy is bed rest for 3 d prior to mobilization, the goal being to reduce postoperative CSF leakage. In this study, median time to mobilization out of bed following surgery was 1 d, which is similar to what others have found.19 Shorter time to mobilization can be beneficial in reducing postoperative DVT and PE. The incidence of CSF leakage following resection of intradural tumors with open surgery is reported to be 1.1% to 38.9%,4,5,9-12,20,24,32 whereas following MIS it is reported to be 0% to 4%.19,20,22-24,32 The incidence of pseudomeningocele following resection of intradural tumors is reported to be 0% to 1.6%.4,5,31 In this series, 2 patients (2.4%) were reoperated as a result of CSF leakage and 1 developed an asymptomatic pseudomeningocele. We believe that the combination of watertight dural closure, the use of TachoSil (Nycomed) and the negligible dead space afforded by MIS are important elements that can help minimize the risk of CSF leakage. In keeping with this, Wong et al32 found a significantly lower risk of CSF leakage following MIS than following open surgery for intradural, extramedullary tumors. Postoperative Hematoma The rate of reoperation due to postoperative hematoma following resection of primary intradural tumors is reported to be in the range of 0% to 2.2%.3-5,22,32 None of the patients in this series developed postoperative hematoma. We hypothesize that the minimal dead space and small skin incisions afforded by MIS could potentially reduce the risk of postoperative hematoma, which would in turn render it a safer treatment option than open surgery. Several studies have shown that MIS approaches to the spine result in less intraoperative blood loss than open approaches do.24,25,32 Surgical Site Infections The reported incidence of surgical site infection and meningitis following resection of primary intradural tumors is reported to be in the range of 0% to 4.3%.3-5,7,9-11,19,22 In the current series, the surgical site infection incidence was 2.4%. MIS of the spine is associated with a lower incidence of surgical site infection than open spine surgery is.35,36 Neurological Function The reported incidence of neurological deterioration following resection of primary, intradural tumors is reported to be in the range of 0% to 27%.3-5,7,13,19,22-25,31,32 One possible explanation for this wide range is the use of different indexing systems for the assessment of neurological function.33,34 If only permanent motor deficits are recorded, the complication rate will be low, whereas it will be much higher if all types of neurological deterioration, including transient deficits and sensory deficits in the distribution of a single dermatoma, are recorded. In a large series of 131 intraspinal schwannoma patients, Halvorsen et al5 reported a 27% complication rate, which included all types of perioperative neurological deterioration. As previously noted, in the current study, slight sensory disturbances in the distribution of a single dermatoma were not regarded as a complication per se since they are a relatively common, anticipated and well-tolerated symptom following intradural schwannoma GTR. In this series, 4 (4.9%) patients experienced neurological deterioration, which is well within the range of that reported for open surgery. At follow-up, 93% of patients were ambulatory and capable of working. This illustrates that the bulk of patients had neurological function consistent with independent living following surgery. Postoperative Length of Hospital Stay In this study, the median duration of hospital admission following surgery was 3 d. Several studies have reported that hospital stay duration and hospital costs following MIS are less than those following open spine surgery.19,25,27,37 In a time of limited healthcare resources with a focus on hospital cost reduction efforts, shorter hospital stay is a compelling argument for the implementation of MIS as standard procedure for the treatment of intraspinal tumors. Vertebral Instability/Spinal Deformity Vertebral instability and spinal deformity secondary to dissection and removal of muscles, ligaments and bony elements are significant disadvantages of open approaches. In some cases, fusion is necessary to correct postlaminectomy deformity and spinal instability. Risk factors for developing spinal deformity following laminectomy are young age, intramedullary tumor, and radiotherapy of the operated segment.14,15,38-41 Millward et al27 have reported a lesser degree of vertebral instability following hemilaminectomy vs laminectomy. There were no cases of postoperative vertebral instability/spinal deformity in the present study suggesting that MIS could reduce the risk of these conditions, which would in turn contribute to reducing health care costs. The material is, however, too small and follow-up too limited to provide any sort of conclusive evidence. Technical Comments The MAST Quadrant (Medtronic Inc) and Caspar (Aesculap Implant Systems) systems were utilized in the present study. We are under the impression that there are other comparable systems on the market that can achieve similar results. Although the technique is easy to learn, experience with microsurgical treatment of lumbar stenosis and spinal intradural tumors is required prior to attempting surgery utilizing the tubular retraction system. The confined surgical corridors can render watertight dural closure challenging. To circumvent this difficulty, the unconventional U-clip, a self-closure tool that can accomplish tissue approximation without surgical knot tying, can be used as an alternative and less challenging method of dural closure42; however, the U-clip could potentially cause artifacts on MRI which would complicate follow-up. We have not utilized U-clips for dural closure thus far. We have minimal experience with MIS for intramedullary tumors and filum terminale ependymomas larger than 5 cm in craniocaudal extension, and can therefore not make any presumptions regarding the feasibility of MIS for these cases. With this exception, we believe MIS to be the preferred approach for primary, intradural spinal tumors. Limitations The study is limited as a result of the retrospective design, the nonrandomized design, and by the small number of events occurring in this population. CONCLUSION This study indicates that it is feasible and safe to remove the majority of primary, intradural spinal tumors with MIS. Our experience with MIS for intramedullary tumors, and filum terminale ependymomas larger than 5 cm in craniocaudal extension, however, is limited and it is therefore not possible to make any presumptions regarding whether MIS is comparable to open surgery for these cases. The surgical mortality was 0%, the surgical morbidity was 11%, GTR was achieved in 87% of cases, and at follow-up 93% of patients were ambulatory and capable of working. Our study adds to previous literature in favor of MIS for select, primary intradural spinal tumors; however, a prospective randomized study should be done in order to evaluate whether this microsurgical approach is superior to the more established posterior, bilateral, macrosurgical approach. 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Google Scholar CrossRef Search ADS PubMed  11. Klekamp J, Samii M. Surgical results for spinal meningiomas. Surg Neurol.  1999; 52( 6): 552- 562. Google Scholar CrossRef Search ADS PubMed  12. Lilleeng B, Helseth E. Resection of symptomatic intraspinal meningiomas. Tidsskr Nor Laegeforen.  2008; 128( 7): 818- 821. Google Scholar PubMed  13. Seppala MT, Haltia MJ, Sankila RJ, Jaaskelainen JE, Heiskanen O. Long-term outcome after removal of spinal schwannoma: a clinicopathological study of 187 cases. J. Neurosurg.  1995; 83( 4): 621- 626. Google Scholar CrossRef Search ADS PubMed  14. Papagelopoulos PJ, Peterson HA, Ebersold MJ, Emmanuel PR, Choudhury SN, Quast LM. Spinal column deformity and instability after lumbar or thoracolumbar laminectomy for intraspinal tumors in children and young adults. Spine . 1997; 22( 4): 442- 451. Google Scholar CrossRef Search ADS PubMed  15. Joaquim AF, Cheng I, Patel AA. Postoperative spinal deformity after treatment of intracanal spine lesions. Spine J . 2012; 12( 11): 1067- 1074. Google Scholar CrossRef Search ADS PubMed  16. Tarnanen S, Neva MH, Kautiainen H et al.   The early changes in trunk muscle strength and disability following lumbar spine fusion. Disabil Rehabil.  2013; 35( 2): 134- 139. Google Scholar CrossRef Search ADS PubMed  17. Dahlberg D, Halvorsen CM, Lied B, Helseth E. Minimally invasive microsurgical resection of primary, intradural spinal tumours using a tubular retraction system. Br J Neurosurg.  2012; 26( 4): 472- 475. Google Scholar CrossRef Search ADS PubMed  18. Tredway TL, Santiago P, Hrubes MR, Song JK, Christie SD, Fessler RG. Minimally invasive resection of intradural-extramedullary spinal neoplasms. Neurosurgery . 2006; 58( 1 suppl): ONS52- ONS58; discussion ONS52-ONS58. Google Scholar PubMed  19. Haji FA, Cenic A, Crevier L, Murty N, Reddy K. Minimally invasive approach for the resection of spinal neoplasm. Spine . 2011; 36( 15): E1018- E1026. Google Scholar CrossRef Search ADS PubMed  20. Iacoangeli M, Gladi M, Di Rienzo A et al.   Minimally invasive surgery for benign intradural extramedullary spinal meningiomas: experience of a single institution in a cohort of elderly patients and review of the literature. Clin Interv Aging.  2012; 7: 557- 564. Google Scholar CrossRef Search ADS PubMed  21. Gandhi RH, German JW. Minimally invasive approach for the treatment of intradural spinal pathology. Neurosurg Focus.  2013; 35( 2): E5. Google Scholar CrossRef Search ADS PubMed  22. Zhu YJ, Ying GY, Chen AQ et al.   Minimally invasive removal of lumbar intradural extramedullary lesions using the interlaminar approach. Neurosurg Focus.  2015; 39( 2): E10. Google Scholar CrossRef Search ADS PubMed  23. Turel MK, D'Souza WP, Rajshekhar V. Hemilaminectomy approach for intradural extramedullary spinal tumors: an analysis of 164 patients. Neurosurg Focus.  2015; 39( 2): E9. Google Scholar CrossRef Search ADS PubMed  24. Raygor KP, Than KD, Chou D, Mummaneni PV. Comparison of minimally invasive transspinous and open approaches for thoracolumbar intradural-extramedullary spinal tumors. Neurosurg. Focus.  2015; 39( 2): E12. Google Scholar CrossRef Search ADS PubMed  25. Lu DC, Chou D, Mummaneni PV. A comparison of mini-open and open approaches for resection of thoracolumbar intradural spinal tumors. J Neurosurg Spine.  2011; 14( 6): 758- 764. Google Scholar CrossRef Search ADS PubMed  26. Zong S, Zeng G, Du L, Fang Y, Gao T, Zhao J. Treatment results in the different surgery of intradural extramedullary tumor of 122 cases. PLoS One . 2014; 9( 11): e111495. Google Scholar CrossRef Search ADS PubMed  27. Millward CP, Bhagawati D, Chan HW, Bestwick J, Brecknell JE. Retrospective observational comparative study of hemilaminectomy versus laminectomy for intraspinal tumour resection; shorter stays, lower analgesic usage and less kyphotic deformity. Br J Neurosurg.  2015; 29( 3): 390- 395. Google Scholar CrossRef Search ADS PubMed  28. Caspar W, Campbell B, Barbier DD, Kretschmmer R, Gotfried Y. The Caspar microsurgical discectomy and comparison with a conventional standard lumbar disc procedure. Neurosurgery . 1991; 28( 1): 78- 86; discussion 86-87. Google Scholar CrossRef Search ADS PubMed  29. Huskisson EC. Measurement of pain. J Rheumatol.  1982; 9( 5): 768- 769. Google Scholar PubMed  30. Oken MM, Creech RH, Tormey DC et al.   Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.  1982; 5( 6): 649- 655. Google Scholar CrossRef Search ADS PubMed  31. Bostrom A, Burgel U, Reinacher P et al.   A less invasive surgical concept for the resection of spinal meningiomas. Acta Neurochir (Wien).  2008; 150( 6): 551- 556; discussion 556. Google Scholar CrossRef Search ADS PubMed  32. Wong AP, Lall RR, Dahdaleh NS et al.   Comparison of open and minimally invasive surgery for intradural-extramedullary spine tumors. Neurosurg Focus.  2015; 39( 2): E11. Google Scholar CrossRef Search ADS PubMed  33. Nasser R, Yadla S, Maltenfort MG et al.   Complications in spine surgery. J Neurosurg Spine.  2010; 13( 2): 144- 157. Google Scholar CrossRef Search ADS PubMed  34. Yadla S, Malone J, Campbell PG et al.   Early complications in spine surgery and relation to preoperative diagnosis: a single-center prospective study. J Neurosurg. Spine.  2010; 13( 3): 360- 366. Google Scholar CrossRef Search ADS PubMed  35. Ee WW, Lau WL, Yeo W, Von Bing Y, Yue WM. Does minimally invasive surgery have a lower risk of surgical site infections compared with open spinal surgery? Clin Orthop Relat Res.  2014; 472( 6): 1718- 1724. Google Scholar PubMed  36. McAfee PC, Garfin SR, Rodgers WB, Allen RT, Phillips F, Kim C. An attempt at clinically defining and assessing minimally invasive surgery compared with traditional "open" spinal surgery. SAS J . 2011; 5( 4): 125- 130. Google Scholar CrossRef Search ADS PubMed  37. Lucio JC, Vanconia RB, Deluzio KJ, Lehmen JA, Rodgers JA, Rodgers W. Economics of less invasive spinal surgery: an analysis of hospital cost differences between open and minimally invasive instrumented spinal fusion procedures during the perioperative period. Risk Manag Healthc Policy . 2012; 5: 65- 74. Google Scholar PubMed  38. de Jonge T, Slullitel H, Dubousset J, Miladi L, Wicart P, Illes T. Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J.  2005; 14( 8): 765- 771. Google Scholar CrossRef Search ADS PubMed  39. McGirt MJ, Garces-Ambrossi GL, Parker SL et al.   Short-term progressive spinal deformity following laminoplasty versus laminectomy for resection of intradural spinal tumors: analysis of 238 patients. Neurosurgery . 2010; 66( 5): 1005- 1012. Google Scholar CrossRef Search ADS PubMed  40. Sciubba DM, Chaichana KL, Woodworth GF, McGirt MJ, Gokaslan ZL, Jallo GI. Factors associated with cervical instability requiring fusion after cervical laminectomy for intradural tumor resection. J Neurosurg Spine.  2008; 8( 5): 413- 419. Google Scholar CrossRef Search ADS PubMed  41. Yao KC, McGirt MJ, Chaichana KL, Constantini S, Jallo GI. Risk factors for progressive spinal deformity following resection of intramedullary spinal cord tumors in children: an analysis of 161 consecutive cases. J Neurosurg.  2007; 107( 6 suppl): 463- 468. Google Scholar PubMed  42. Park P, Leveque JC, La Marca F, Sullivan SE. Dural closure using the U-clip in minimally invasive spinal tumor resection. J Spinal Disord Tech . 2010; 23( 7): 486- 489. Google Scholar CrossRef Search ADS PubMed  Neurosurgery Speaks! Audio abstracts available for this article at www.neurosurgery-online.com. COMMENT The authors report on a series of 83 patients who underwent resection of intradural spinal neoplasms through use of an MIS approach with appropriate dilators and a retractor system. The report a gross total resection in 87% of cases, which is comparable to rates in the literature using an open approach. As the trend continues towards use of minimally invasive approaches to address pathology that once was only thought to be cured through open approaches, this work adds to the body of growing evidence that MIS can offer the ability to accomplish the same operative goals in a safe and feasible manner. Further studies will be required to address whether patients undergoing MIS approaches, specifically for this indication, actually benefit overall in terms of shorter length of hospital stay, less postoperative pain, and/or decreased morbidity. Anthony Frempong-Boadu New York, New York Neurosurgery Speaks (Audio Abstracts) Listen to audio translations of this paper's abstract into select languages by choosing from one of the selections below. Chinese: Kai Wang, MD Department of Neurosurgery, Weihai Central Hospital Weihai, Shandong, China Chinese: Kai Wang, MD Department of Neurosurgery, Weihai Central Hospital Weihai, Shandong, China Close English: Jean-Valery Coumans, MD Department of Neurosurgery, Massachusetts General Hospital Boston, Massachusetts English: Jean-Valery Coumans, MD Department of Neurosurgery, Massachusetts General Hospital Boston, Massachusetts Close French: Michael Bruneau, MD, PhD Department of Neurosurgery, Erasme Hospital Brussels, Belgium French: Michael Bruneau, MD, PhD Department of Neurosurgery, Erasme Hospital Brussels, Belgium Close Italian: Daniele Bongetta, MD Department of Neurosurgery, Fondazione IRCCS Policlinico San Matteo Pavia, Italy Italian: Daniele Bongetta, MD Department of Neurosurgery, Fondazione IRCCS Policlinico San Matteo Pavia, Italy Close Japanese: Toshiaki Hayashi, MD, PhD Department of Neurosurgery, Sendai City Hospital Sendai, Japan Japanese: Toshiaki Hayashi, MD, PhD Department of Neurosurgery, Sendai City Hospital Sendai, Japan Close Korean: Tae Gon Kim, MD Division of Vascular Section, Department of Neurosurgery, Bundang CHA Hospital Seongnam, Republic of Korea Korean: Tae Gon Kim, MD Division of Vascular Section, Department of Neurosurgery, Bundang CHA Hospital Seongnam, Republic of Korea Close Portuguese: Andre Luiz Beer-Furlan, MD Department of Neurological Surgery, Ohio State University Wexner Medical Center Columbus, Ohio Portuguese: Andre Luiz Beer-Furlan, MD Department of Neurological Surgery, Ohio State University Wexner Medical Center Columbus, Ohio Close Russian: Sergei Kim Department of Pediatric Neurosurgery, Novosibirsk Federal Centre of Neurosurgery Novosibirsk, Russia Russian: Sergei Kim Department of Pediatric Neurosurgery, Novosibirsk Federal Centre of Neurosurgery Novosibirsk, Russia Close Spanish: Carlos Alarcon, MD Department of Neurosurgery, Hospital Universitario de Bellvitge Barcelona, Spain Spanish: Carlos Alarcon, MD Department of Neurosurgery, Hospital Universitario de Bellvitge Barcelona, Spain Close Greek: George Georgoulis, MD Department of Neurosurgery, University Hospital of Ioannina Ioannina, Greece Greek: George Georgoulis, MD Department of Neurosurgery, University Hospital of Ioannina Ioannina, Greece Close Copyright © 2017 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Minimally Invasive Microsurgical Resection of Primary, Intradural Spinal Tumors is Feasible and Safe: A Consecutive Series of 83 Patients

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Oxford University Press
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Copyright © 2017 by the Congress of Neurological Surgeons
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0148-396X
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1524-4040
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10.1093/neuros/nyx253
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Abstract

Abstract BACKGROUND To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty followed by microsurgical tumor resection. Recently, however, minimally invasive approaches have been attempted by some. OBJECTIVE To investigate the feasibility and safety of minimally invasive surgery (MIS) for primary intradural spinal tumors. METHODS Medical charts of 83 consecutive patients treated with MIS for intradural spinal tumors were reviewed. Patients were followed up during the study year, 2015, by either routine history/physical examination or by telephone consultation, with a focus on tumor status and surgery-related complications. RESULTS Mean age at surgery was 53.7 yr and 52% were female. There were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 paraganglioma, 1 epidermoid cyst, and 1 hemangiopericytoma. The surgical mortality was 0%. In 87% of cases, gross total resection was achieved. The complication rate was 11%, including 2 cerebrospinal fluid leakages, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. There were no postoperative hematomas, and no cases of deep vein thrombosis or pulmonary embolism. Ninety-three percent of patients were ambulatory and able to work at the time of follow-up. CONCLUSION This study both demonstrates that it is feasible and safe to remove select, primary intradural spinal tumors using MIS, and augments the previous literature in favor of MIS for these tumors. Ependymoma, Feasibility studies, Meningioma, Minimally invasive surgical procedures, Neurilemmoma, Spinal neoplasms, Spine ABBREVIATIONS ABBREVIATIONS CSF cerebrospinal fluid DVT deep vein thrombosis ECOG Eastern Cooperative Oncology Group GTR gross total resection MIS minimally invasive surgery MRI magnetic resonance imaging PE pulmonary embolism STR subtotal resection VAS visual analog score The overall incidence rate of primary intraspinal tumors is 1.0 to 1.5 per 100 000 person-years.1,2 The most common histological types are nerve sheath tumors, followed by meningiomas and ependymomas. Most intraspinal tumors present with local back/neck pain, radicular pain, and/or neurological deficit(s). Microsurgical resection is the primary treatment for symptomatic tumors. When planning surgery for an intraspinal tumor, it is of paramount importance to choose an approach that allows for gross total resection (GTR), while at the same time ensuring minimal complications. To date, the traditional approach to intraspinal tumors has been open laminectomy or laminoplasty, succeeded by microsurgical tumor resection.3-14 The open approach, which requires an extensive skin incision, continuous retraction of the paraspinal muscles, and laminectomy/laminotomy, may contribute to intraoperative and postoperative blood loss, prolonged hospital stay, postoperative complications such as hematoma and infection, greater chance of spinal deformity/vertebral instability, and habitual pain in the operated segment.3-16 Recent progress in minimally invasive surgery (MIS) has resulted in spinal approaches that could potentially reduce tissue trauma and subsequent intra/postoperative blood loss, postoperative pain/discomfort, and length of hospital stay. MIS might also facilitate a swifter return to activities of daily living, and from a health economics standpoint this would appear to be a more cost-efficient treatment. Several institutions have already implemented MIS in the treatment of intraspinal tumors and some small cohort studies have been published.17-23 Additionally, a few case control studies comparing MIS to more traditional open approaches have recently been published.24-27 We recently presented our initial experience with MIS in the resection of select, primary intradural spinal tumors,17 and in this study we present our cumulative experience with the technique, now including 83 patients. The objective of the study is to examine the feasibility and safety of MIS for primary, intradural spinal tumors, with a specific emphasis on resection grade and surgery-related complications. METHODS Ethics The study was approved by The Regional Ethical Committee and the Data Protection Official at Oslo University Hospital. All patients participating in the study gave their informed consent. Patients The Department of Neurosurgery at our hospital has a catchment area of ∼1 million inhabitants for intradural tumor surgery. During the time period January 2007 to June 2015, 83 patients had MIS for a primary intradural spinal tumor; these are the patients included in this study. Retrospective Medical Chart Review All patient charts, including radiology and pathology reports and preoperative, operative, postoperative, and outpatient chart notes, were reviewed retrospectively. The following information was recorded from the charts: sex, patient age at surgery (years), presenting symptom(s), level of tumor location, craniocaudal extension of tumor in millimeter, operating time (skin incision to skin closure, in minutes), grade of tumor resection (GTR or subtotal resection [STR]), determined by postoperative magnetic resonance imaging [MRI]), final histological diagnosis, day of mobilization, day of discharge, peri- and postoperative complications, date of most recent MRI with tumor status. Preoperative Routines An anesthesiologist consulted on all patients prior to surgery. In our hospital, an internist routinely consults on elderly patients (>70 yr) and on polypharmacy patients so that medications and each patient's general medical condition are optimized preoperatively. Patients with heart disease were referred to a cardiologist for echocardiography and cardiovascular stress test, and patients with hematological disorders were referred to a hematologist. Anticoagulant and antiplatelet therapy were discontinued prior to surgery in cases where there was a relative indication for their use: in cases where there was an absolute indication for their use, a hematologist and/or cardiologist was/were consulted. Graduated compression stockings were administered to all patients the day before surgery, and they were continued until full mobilization was achieved. Intraoperative Routines/Techniques Patients were placed in the prone position, either flat or resting on the knees and elbows. A second-generation cephalosporin was given intravenously within 30 min prior to the surgical incision and continued every 180 min until the case was finished or until the maximum dose of 8 g daily was reached. The accurate level was confirmed by lateral fluoroscopy. With the MAST-QUADRANT system (Medtronic Inc, Dublin, Ireland), a 30 to 60 mm skin incision was made 20 to 40 mm lateral to the midline. The paraspinous muscles were then bluntly separated using the MAST-QUADRANT dilators. Dilators were successively placed, one over the other, up to 22 mm. The MAST-QUADRANT retractor was implanted over the dilators and positioned over the bony anatomy. The retractor was then secured in place by a table-mounted flexible arm. The dilators were removed, creating a tubular surgical passageway to the interlaminar spaces and lamina. Medial and lateral retractor blades were also used in order to increase the operative field. Due to the flexible, but fixed arm, the blades could be shifted during surgery in order to optimize the viewing field. With the Caspar system (Aesculap Implant Systems, Center Valley, Pennsylvania), a 30 to 60 mm long skin incision was made 10 to 20 mm lateral to the midline; the approach was medial to the paraspinous muscles. The Caspar specules were inserted according to the manufacturer's instructions (Aesculap Implant Systems).28 After positioning the blades, whether using MAST-QUADRANT (Medtronic Inc) or Caspar (Aesculap Implant Systems), the remainder of the procedure was conducted with the assistance of an operating microscope. A 1-level hemilaminectomy, undercutting of the contralateral lamina, and ventral surface of the spinous process were accomplished utilizing Kerrison punches and a high-speed drill. The ligamentum flavum was incised and resected. Ultrasound (LOGIQ, General Electric, Fairfield, Connecticut) was used to verify tumor location prior to dural opening. If the cranial or caudal extension of the tumor was not adequately exposed using a 1-level hemilaminectomy, an arcotomy of the inferior part of the lamina above or an arcotomy of the superior part of the lamina below was performed. If more than one-third of the lamina above or below had to be removed, it was considered a 2-level hemilaminectomy. The dura was opened in the midline or with a paramedian incision. Stay sutures were then placed to reflect the dural edges. Tumor resection was carried out using traditional microsurgical instrumentation. When tumor resection was finished, the dura was approximated with a 5-0 running suture and then sealed with TachoSil; a collagen matrix coated with fibrinogen and thrombin (TachoSil, Nycomed, Oslo, Norway). Postoperative Routines Postoperatively, patients were monitored in a postanesthesia care unit for 3 to 6 h prior to being transferred to either the neurosurgical floor or to a phase II step-down unit for further monitoring. Low-molecular weight heparin was administered on postoperative day 1. The patients were mobilized either the same day as surgery or on postoperative day 1. Immediate postoperative MRI (within 72 h after surgery) was done on all patients for the purpose of establishing resection grade. Follow-up All 83 patients were followed up with MRI 3 to 6 mo postoperatively, followed by outpatient clinical examination. Further follow-up was done as indicated. Patients were provided with detailed information concerning symptoms/signs of the intraspinal tumor and were told to get in touch with the Department of Neurosurgery immediately should such symptoms/signs occur. Patients with schwannoma and meningeoma whose tumors were removed with GTR and were not associated with the genetic neurofibromatosis disorders (NF1, NF2, Schwannomatosis), who had an uncomplicated postoperative period, and whose 3 to 6 mo postoperative follow-up was satisfactory were not followed up further unless they developed signs/symptoms that could be attributed to the intraspinal tumor. For 17 of 83 patients, all of the desired information could be extracted from the most recent outpatient note, and for the remaining 66 patients, the outpatient notes were supplemented with a telephone consultation during the study year (2015) in order to obtain any information that was lacking from the outpatient notes, particularly pain intensity. The following variables were recorded: time to follow-up was calculated from the surgical date to the most recent outpatient consultation or to telephone consultation, back and radicular pain was graded using visual analog scores (VAS; pain was only graded if present 3 or more days per week the preceding 4 wk),29 current use of analgesics (use was defined as intake of analgesics for back or radicular pain 3 or more days per week the preceding 4 wk), symptom status, date of most recent MRI with tumor status, and Eastern Cooperative Oncology Group performance status (ECOG; “0—fully active, able to carry on all predisease performance without restriction; 1—restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2—ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours; 3—capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4—completely disabled, cannot carry on any self-care, totally confined to bed or chair; and 5—dead”30). Vital status and time of death were procured from the Norwegian Population Registry (Folkeregisteret) July 13, 2015. RESULTS Demographics Eighty-three patients with primary, intradural spinal tumors were included in this study: there were 49 schwannomas, 18 meningeomas, 10 ependymomas, 2 hemangioblastomas, 1 neurofibroma, 1 epidermoid cyst, 1 paraganglioma, and 1 hemangiopericytoma. Patient characteristics are summarized in Table 1. The mean age at surgery was 53.7 yr (range 19.7-85.9), and 43 patients were female. The most common presenting complaints were back pain and radicular pain. TABLE 1. Patient Characteristics     n (%)  Sex  Female  43 (51.8)    Male  40 (48.2)  Age (years)  <20  1 (1.2)    20-39  20 (24.1)    40-59  30 (36.1)    60-79  27 (32.5)    >80  5 (6.0)  Symptoms and signs  Back pain  58 (69.9)    Radicular pain  61 (73.5)    Sensory deficit  36 (43.4)    →Paresthesia  15 (18.1)    →Reduction/loss  21 (25.3)    Paresis  32 (38.6)    Bladder dysfunction  12 (14.5)  Tumor location  Cervical  9 (10.8)    Thoracal  23 (27.7)    Thoracolumbar junction  5 (6.0)    Lumbar  41 (49.4)    Lumbosacral junction  1 (1.2)    Sacral  4 (4.8)  Histology  Schwannoma  49 (59.0)    Meningioma  18 (21.7)    Ependymoma  10 (12.0)    Neurofibroma  1 (1.2)    Hemangioblastoma  2 (2.4)    Hemangiopericytoma  1 (1.2)    Epidermoid cyst  1 (1.2)    Paraganglioma  1 (1.2)  Resection grade  Grosstotal (GTR)  72 (86.7)    Subtotal (STR)  11 (13.3)  Adjuvant treatment  Radiotherapy  1 (1.2)    Chemotherapy  0 (0)      n (%)  Sex  Female  43 (51.8)    Male  40 (48.2)  Age (years)  <20  1 (1.2)    20-39  20 (24.1)    40-59  30 (36.1)    60-79  27 (32.5)    >80  5 (6.0)  Symptoms and signs  Back pain  58 (69.9)    Radicular pain  61 (73.5)    Sensory deficit  36 (43.4)    →Paresthesia  15 (18.1)    →Reduction/loss  21 (25.3)    Paresis  32 (38.6)    Bladder dysfunction  12 (14.5)  Tumor location  Cervical  9 (10.8)    Thoracal  23 (27.7)    Thoracolumbar junction  5 (6.0)    Lumbar  41 (49.4)    Lumbosacral junction  1 (1.2)    Sacral  4 (4.8)  Histology  Schwannoma  49 (59.0)    Meningioma  18 (21.7)    Ependymoma  10 (12.0)    Neurofibroma  1 (1.2)    Hemangioblastoma  2 (2.4)    Hemangiopericytoma  1 (1.2)    Epidermoid cyst  1 (1.2)    Paraganglioma  1 (1.2)  Resection grade  Grosstotal (GTR)  72 (86.7)    Subtotal (STR)  11 (13.3)  Adjuvant treatment  Radiotherapy  1 (1.2)    Chemotherapy  0 (0)  View Large Primary Treatment Microsurgery was the primary mode of treatment for all 83 patients. There was a gradual increase in patients treated with MIS from 0% of patients treated with MIS prior to 2007 to 84% of patients treated with MIS in 2015. Two patients had MIS in 2007, 1 in 2008, 7 in 2009, 10 in 2010, 10 in 2011, 10 in 2012, 17 in 2013, 13 in 2014, and 13 in 2015, respectively. One-level hemilaminectomy provided sufficient exposure in 62 cases, while 2-level hemilaminectomy was necessary in 21 cases. GTR was accomplished in 72 patients (87%) and STR in 11 patients (13%; Table 2). Median surgical duration was 142 min (range 62-374 min). Mean craniocaudal tumor length was 19.6 mm (range 6-49 mm). Median time to mobilization out of bed was 1 d (range 0-4 d). The median duration of hospital stay after surgery was 3 d (range 0-14 d). Forty-six patients (55%) were discharged to the home, while 37 (45%) were transferred to another medical institution. One patient received adjuvant radiotherapy for a subtotally resected myxopapillary ependymoma. None of the patients received chemotherapy. TABLE 2. Main Cause of STR No  Histology  Cause of STR  1  Hemangiopericytoma  Adherent to/invading spinal cord.  2  Ependymoma  Infiltrating conus medullaris.  3  Schwannoma  Surgery for recurrent tumor.  4  Schwannoma  Surgery for recurrent tumor.  5  Schwannoma  STR initially discovered upon postoperative MRI.  6  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  7  Ependymoma  Surgery for recurrent tumor.  8  Meningioma  Small calcified remnant ventral to the spinal cord, intentionally not removed.  9  Schwannoma  STR initially discovered upon postoperative MRI.  10  Hemangioblastoma  Large tumor infiltrating conus medullaris, GTR regarded as too risky.  11  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  No  Histology  Cause of STR  1  Hemangiopericytoma  Adherent to/invading spinal cord.  2  Ependymoma  Infiltrating conus medullaris.  3  Schwannoma  Surgery for recurrent tumor.  4  Schwannoma  Surgery for recurrent tumor.  5  Schwannoma  STR initially discovered upon postoperative MRI.  6  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  7  Ependymoma  Surgery for recurrent tumor.  8  Meningioma  Small calcified remnant ventral to the spinal cord, intentionally not removed.  9  Schwannoma  STR initially discovered upon postoperative MRI.  10  Hemangioblastoma  Large tumor infiltrating conus medullaris, GTR regarded as too risky.  11  Schwannoma  First stage of planned 2-stage removal for dumbbell tumor.  View Large Surgical Mortality and Morbidity The surgical mortality (death within 30 d of surgery) was 0%. Nine patients (11%) had a total of 10 surgery-related complications (Table 3). In addition, slight sensory disturbances in the distribution of a single dermatoma were seen in 11 patients following surgery. This was not considered a complication per se, as it is a relatively common and anticipated symptom following intradural schwannoma GTR. The surgery-related complications were as follows: 2 cerebrospinal fluid (CSF) leaks, 1 asymptomatic pseudomeningocele, 2 superficial surgical site infections, 1 sinus vein thrombosis, and 4 cases of neurological deterioration. Neurological deterioration consisted of moderate paresis in 2 patients and of mild paresis in 2 patients. A sinus venous thrombosis was the cause of moderate paresis in one of the patients. There were no postoperative hematomas in need of surgical evacuation, and none of the patients were diagnosed with pulmonary embolism (PE) or deep vein thrombosis (DVT). The duration of surgery was slightly longer for patients with surgery-related complications. TABLE 3. Surgery-Related Complications   n (%)a  30-d mortality  0 (0)  Postoperative hematoma  0 (0)  Deep surgical site infection  2 (2.4)  CSF-leakage and pseudomeningocele  3 (3.7)  Neurological deterioration  4 (4.9%)  Sinus vein thrombosis  1 (1.2)  DVT/PE  0 (0)    n (%)a  30-d mortality  0 (0)  Postoperative hematoma  0 (0)  Deep surgical site infection  2 (2.4)  CSF-leakage and pseudomeningocele  3 (3.7)  Neurological deterioration  4 (4.9%)  Sinus vein thrombosis  1 (1.2)  DVT/PE  0 (0)  aA total of 10 complications were registered in 9 patients. View Large Follow-up All but 1 of the patients were available for follow-up. Mean time to follow-up was 26 mo (range 3-88 mo), and 54 (66%) patients were followed up for more than 1 yr. Of the 82 patients, 77 (92.8%) had an ECOG score of 0 to 1 (ambulatory and able to carry out work),30 4 (4.8%) had an ECOG score of 2 (ambulatory and capable of all self-care, but unable to carry out any work activities),30 and 1 (1.2%) had an ECOG score of 3 (capable of only limited self-care; confined to bed or chair more than 50% of waking hours).30 The patients with ECOG scores of 2 and 3 did not deteriorate postoperatively, they had the same ECOG scores preoperatively. Four of the 5 patients with ECOG scores of 2 and 3 had tumors located in the thoracic region, so it appears that thoracic location is a risk factor for a poorer outcome (Table 4). There were no cases of vertebral instability/kyphosis in the operated segment at follow-up. One of the 72 patients treated with GTR developed a recurrence, while 4 of the 11 patients treated with STR experienced growth of residual tumor. One patient died during the study period as a result of metastatic cancer of unknown origin, which was diagnosed approximately 4 yr following removal of the intraspinal tumor. TABLE 4. ECOG 2 and 3 Patients No  Sex  Age  Preoperative symptoms  Tumor location  Histology  Surgical complication  Resection grade  ECOG at Follow-up  1  M  51  Paresis, sensory deficit  Thoracic  Meningioma  None  GTR  3  2  F  63  Paresis, pain  Thoracic  Meningioma  None  GTR  2  3  M  31  Paresis, pain  Thoracic  Schwannoma  None  GTR  2  4  F  30  Sensory deficit, pain  Sacral  Meningioma  None  GTR  2  5  M  55  Paresis, sensory deficit, pain  Thoracic  Schwannoma  None  GTR  2  No  Sex  Age  Preoperative symptoms  Tumor location  Histology  Surgical complication  Resection grade  ECOG at Follow-up  1  M  51  Paresis, sensory deficit  Thoracic  Meningioma  None  GTR  3  2  F  63  Paresis, pain  Thoracic  Meningioma  None  GTR  2  3  M  31  Paresis, pain  Thoracic  Schwannoma  None  GTR  2  4  F  30  Sensory deficit, pain  Sacral  Meningioma  None  GTR  2  5  M  55  Paresis, sensory deficit, pain  Thoracic  Schwannoma  None  GTR  2  View Large DISCUSSION Previous studies indicate that MIS might be beneficial for patients with intraspinal tumors; however, these studies are too small and too preliminary in nature to provide any sort of conclusive evidence. The surgical mortality in the current study of consecutive 83 patients was 0%, GTR was achieved in 87% of cases, and the total complication rate was 11%. At follow-up, 93% of patients were ambulatory and able to work. The results of the current study strongly support the idea that MIS for select, primary intradural spinal tumors is feasible and safe.17-27 Tumor Removal The rate of GTR following open surgery for intradural, extramedullary tumors is reported to be in the range of 64% to 98%,3-6,9-13,24,31,32 whereas the corresponding rate for intramedullary tumors is much lower.9 The rate of GTR following MIS for intradural, extramedullary tumors is reported to be in the range of 68% to 100%.17,19,20,22-24,32 In the current study, GTR was achieved in 87% of cases. Taking this and other studies into account, it appears that MIS provides sufficient access to most intraspinal tumors, such that they can be resected as radically with MIS as with open surgery. Our experience with MIS for intramedullary tumors and filum terminale ependymomas larger than 5 cm in craniocaudal extension, however, is limited and it is therefore not possible to make any presumptions regarding whether MIS is comparable to open surgery for these cases. Surgical Mortality Surgical mortality following open surgery for intradural, extramedullary tumors is reported to be in the range of 0% to 2%,4,5,7,9-13,24,26,32 while surgical mortality following MIS for intradural, extramedullary tumors is reported to be 0%.19,20,22-26,31,32 The surgical mortality was 0%, which is in concordance with previous studies. The aforementioned data strongly suggest that MIS for intraspinal tumors poses a very low perioperative risk of death. Surgical Morbidity In a review of complications following spinal surgery, Nasser et al33 pointed out the lack of standardized reporting systems for such complications. Yadla et al34 have recently published a prospective study regarding early complications following spinal surgery, which revealed a rather high complication rate compared to other studies. They postulate that the aforementioned disparity is due to the fact that many studies report falsely low complication rates as a result of deficient records and recall bias. It can also appear that large, national databases report complication rates in the lower range. In the current study, the surgical morbidity was 11% and the following complications were recorded: CSF leakage, pseudomeningocele, postoperative hematoma, surgical site infection, neurological complications, and DVT/PE. Since this is a retrospective study, it must be kept in mind that complications are always lower when assessed retrospectively. Postoperative Mobilization and CSF Leakage In our department, standard procedure following open spine surgery with durotomy is bed rest for 3 d prior to mobilization, the goal being to reduce postoperative CSF leakage. In this study, median time to mobilization out of bed following surgery was 1 d, which is similar to what others have found.19 Shorter time to mobilization can be beneficial in reducing postoperative DVT and PE. The incidence of CSF leakage following resection of intradural tumors with open surgery is reported to be 1.1% to 38.9%,4,5,9-12,20,24,32 whereas following MIS it is reported to be 0% to 4%.19,20,22-24,32 The incidence of pseudomeningocele following resection of intradural tumors is reported to be 0% to 1.6%.4,5,31 In this series, 2 patients (2.4%) were reoperated as a result of CSF leakage and 1 developed an asymptomatic pseudomeningocele. We believe that the combination of watertight dural closure, the use of TachoSil (Nycomed) and the negligible dead space afforded by MIS are important elements that can help minimize the risk of CSF leakage. In keeping with this, Wong et al32 found a significantly lower risk of CSF leakage following MIS than following open surgery for intradural, extramedullary tumors. Postoperative Hematoma The rate of reoperation due to postoperative hematoma following resection of primary intradural tumors is reported to be in the range of 0% to 2.2%.3-5,22,32 None of the patients in this series developed postoperative hematoma. We hypothesize that the minimal dead space and small skin incisions afforded by MIS could potentially reduce the risk of postoperative hematoma, which would in turn render it a safer treatment option than open surgery. Several studies have shown that MIS approaches to the spine result in less intraoperative blood loss than open approaches do.24,25,32 Surgical Site Infections The reported incidence of surgical site infection and meningitis following resection of primary intradural tumors is reported to be in the range of 0% to 4.3%.3-5,7,9-11,19,22 In the current series, the surgical site infection incidence was 2.4%. MIS of the spine is associated with a lower incidence of surgical site infection than open spine surgery is.35,36 Neurological Function The reported incidence of neurological deterioration following resection of primary, intradural tumors is reported to be in the range of 0% to 27%.3-5,7,13,19,22-25,31,32 One possible explanation for this wide range is the use of different indexing systems for the assessment of neurological function.33,34 If only permanent motor deficits are recorded, the complication rate will be low, whereas it will be much higher if all types of neurological deterioration, including transient deficits and sensory deficits in the distribution of a single dermatoma, are recorded. In a large series of 131 intraspinal schwannoma patients, Halvorsen et al5 reported a 27% complication rate, which included all types of perioperative neurological deterioration. As previously noted, in the current study, slight sensory disturbances in the distribution of a single dermatoma were not regarded as a complication per se since they are a relatively common, anticipated and well-tolerated symptom following intradural schwannoma GTR. In this series, 4 (4.9%) patients experienced neurological deterioration, which is well within the range of that reported for open surgery. At follow-up, 93% of patients were ambulatory and capable of working. This illustrates that the bulk of patients had neurological function consistent with independent living following surgery. Postoperative Length of Hospital Stay In this study, the median duration of hospital admission following surgery was 3 d. Several studies have reported that hospital stay duration and hospital costs following MIS are less than those following open spine surgery.19,25,27,37 In a time of limited healthcare resources with a focus on hospital cost reduction efforts, shorter hospital stay is a compelling argument for the implementation of MIS as standard procedure for the treatment of intraspinal tumors. Vertebral Instability/Spinal Deformity Vertebral instability and spinal deformity secondary to dissection and removal of muscles, ligaments and bony elements are significant disadvantages of open approaches. In some cases, fusion is necessary to correct postlaminectomy deformity and spinal instability. Risk factors for developing spinal deformity following laminectomy are young age, intramedullary tumor, and radiotherapy of the operated segment.14,15,38-41 Millward et al27 have reported a lesser degree of vertebral instability following hemilaminectomy vs laminectomy. There were no cases of postoperative vertebral instability/spinal deformity in the present study suggesting that MIS could reduce the risk of these conditions, which would in turn contribute to reducing health care costs. The material is, however, too small and follow-up too limited to provide any sort of conclusive evidence. Technical Comments The MAST Quadrant (Medtronic Inc) and Caspar (Aesculap Implant Systems) systems were utilized in the present study. We are under the impression that there are other comparable systems on the market that can achieve similar results. Although the technique is easy to learn, experience with microsurgical treatment of lumbar stenosis and spinal intradural tumors is required prior to attempting surgery utilizing the tubular retraction system. The confined surgical corridors can render watertight dural closure challenging. To circumvent this difficulty, the unconventional U-clip, a self-closure tool that can accomplish tissue approximation without surgical knot tying, can be used as an alternative and less challenging method of dural closure42; however, the U-clip could potentially cause artifacts on MRI which would complicate follow-up. We have not utilized U-clips for dural closure thus far. We have minimal experience with MIS for intramedullary tumors and filum terminale ependymomas larger than 5 cm in craniocaudal extension, and can therefore not make any presumptions regarding the feasibility of MIS for these cases. With this exception, we believe MIS to be the preferred approach for primary, intradural spinal tumors. Limitations The study is limited as a result of the retrospective design, the nonrandomized design, and by the small number of events occurring in this population. CONCLUSION This study indicates that it is feasible and safe to remove the majority of primary, intradural spinal tumors with MIS. Our experience with MIS for intramedullary tumors, and filum terminale ependymomas larger than 5 cm in craniocaudal extension, however, is limited and it is therefore not possible to make any presumptions regarding whether MIS is comparable to open surgery for these cases. The surgical mortality was 0%, the surgical morbidity was 11%, GTR was achieved in 87% of cases, and at follow-up 93% of patients were ambulatory and capable of working. Our study adds to previous literature in favor of MIS for select, primary intradural spinal tumors; however, a prospective randomized study should be done in order to evaluate whether this microsurgical approach is superior to the more established posterior, bilateral, macrosurgical approach. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Duong LM, McCarthy BJ, McLendon RE et al.   Descriptive epidemiology of malignant and nonmalignant primary spinal cord, spinal meninges, and cauda equina tumors, United States, 2004-2007. Cancer . 2012; 118( 17): 4220- 4227. Google Scholar CrossRef Search ADS PubMed  2. Weber C, Gulati S, Jakola AS et al.   Incidence rates and surgery of primary intraspinal tumors in the era of modern neuroimaging: a national population-based study. Spine . 2014; 39( 16): E967- E973. Google Scholar CrossRef Search ADS PubMed  3. Engelhard HH, Villano JL, Porter KR et al.   Clinical presentation, histology, and treatment in 430 patients with primary tumors of the spinal cord, spinal meninges, or cauda equina. J Neurosurg Spine.  2010; 13( 1): 67- 77. Google Scholar CrossRef Search ADS PubMed  4. 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Lucio JC, Vanconia RB, Deluzio KJ, Lehmen JA, Rodgers JA, Rodgers W. Economics of less invasive spinal surgery: an analysis of hospital cost differences between open and minimally invasive instrumented spinal fusion procedures during the perioperative period. Risk Manag Healthc Policy . 2012; 5: 65- 74. Google Scholar PubMed  38. de Jonge T, Slullitel H, Dubousset J, Miladi L, Wicart P, Illes T. Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours. Eur Spine J.  2005; 14( 8): 765- 771. Google Scholar CrossRef Search ADS PubMed  39. McGirt MJ, Garces-Ambrossi GL, Parker SL et al.   Short-term progressive spinal deformity following laminoplasty versus laminectomy for resection of intradural spinal tumors: analysis of 238 patients. Neurosurgery . 2010; 66( 5): 1005- 1012. Google Scholar CrossRef Search ADS PubMed  40. Sciubba DM, Chaichana KL, Woodworth GF, McGirt MJ, Gokaslan ZL, Jallo GI. Factors associated with cervical instability requiring fusion after cervical laminectomy for intradural tumor resection. J Neurosurg Spine.  2008; 8( 5): 413- 419. Google Scholar CrossRef Search ADS PubMed  41. Yao KC, McGirt MJ, Chaichana KL, Constantini S, Jallo GI. Risk factors for progressive spinal deformity following resection of intramedullary spinal cord tumors in children: an analysis of 161 consecutive cases. J Neurosurg.  2007; 107( 6 suppl): 463- 468. Google Scholar PubMed  42. Park P, Leveque JC, La Marca F, Sullivan SE. Dural closure using the U-clip in minimally invasive spinal tumor resection. J Spinal Disord Tech . 2010; 23( 7): 486- 489. Google Scholar CrossRef Search ADS PubMed  Neurosurgery Speaks! Audio abstracts available for this article at www.neurosurgery-online.com. COMMENT The authors report on a series of 83 patients who underwent resection of intradural spinal neoplasms through use of an MIS approach with appropriate dilators and a retractor system. The report a gross total resection in 87% of cases, which is comparable to rates in the literature using an open approach. As the trend continues towards use of minimally invasive approaches to address pathology that once was only thought to be cured through open approaches, this work adds to the body of growing evidence that MIS can offer the ability to accomplish the same operative goals in a safe and feasible manner. Further studies will be required to address whether patients undergoing MIS approaches, specifically for this indication, actually benefit overall in terms of shorter length of hospital stay, less postoperative pain, and/or decreased morbidity. Anthony Frempong-Boadu New York, New York Neurosurgery Speaks (Audio Abstracts) Listen to audio translations of this paper's abstract into select languages by choosing from one of the selections below. Chinese: Kai Wang, MD Department of Neurosurgery, Weihai Central Hospital Weihai, Shandong, China Chinese: Kai Wang, MD Department of Neurosurgery, Weihai Central Hospital Weihai, Shandong, China Close English: Jean-Valery Coumans, MD Department of Neurosurgery, Massachusetts General Hospital Boston, Massachusetts English: Jean-Valery Coumans, MD Department of Neurosurgery, Massachusetts General Hospital Boston, Massachusetts Close French: Michael Bruneau, MD, PhD Department of Neurosurgery, Erasme Hospital Brussels, Belgium French: Michael Bruneau, MD, PhD Department of Neurosurgery, Erasme Hospital Brussels, Belgium Close Italian: Daniele Bongetta, MD Department of Neurosurgery, Fondazione IRCCS Policlinico San Matteo Pavia, Italy Italian: Daniele Bongetta, MD Department of Neurosurgery, Fondazione IRCCS Policlinico San Matteo Pavia, Italy Close Japanese: Toshiaki Hayashi, MD, PhD Department of Neurosurgery, Sendai City Hospital Sendai, Japan Japanese: Toshiaki Hayashi, MD, PhD Department of Neurosurgery, Sendai City Hospital Sendai, Japan Close Korean: Tae Gon Kim, MD Division of Vascular Section, Department of Neurosurgery, Bundang CHA Hospital Seongnam, Republic of Korea Korean: Tae Gon Kim, MD Division of Vascular Section, Department of Neurosurgery, Bundang CHA Hospital Seongnam, Republic of Korea Close Portuguese: Andre Luiz Beer-Furlan, MD Department of Neurological Surgery, Ohio State University Wexner Medical Center Columbus, Ohio Portuguese: Andre Luiz Beer-Furlan, MD Department of Neurological Surgery, Ohio State University Wexner Medical Center Columbus, Ohio Close Russian: Sergei Kim Department of Pediatric Neurosurgery, Novosibirsk Federal Centre of Neurosurgery Novosibirsk, Russia Russian: Sergei Kim Department of Pediatric Neurosurgery, Novosibirsk Federal Centre of Neurosurgery Novosibirsk, Russia Close Spanish: Carlos Alarcon, MD Department of Neurosurgery, Hospital Universitario de Bellvitge Barcelona, Spain Spanish: Carlos Alarcon, MD Department of Neurosurgery, Hospital Universitario de Bellvitge Barcelona, Spain Close Greek: George Georgoulis, MD Department of Neurosurgery, University Hospital of Ioannina Ioannina, Greece Greek: George Georgoulis, MD Department of Neurosurgery, University Hospital of Ioannina Ioannina, Greece Close Copyright © 2017 by the Congress of Neurological Surgeons

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NeurosurgeryOxford University Press

Published: Mar 1, 2018

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