Neurosurgery Blog


Daily bibliographic review of the Neurosurgery Department. La Fe University Hospital. Valencia, Spain

An assessment of the most reliable method to estimate the sagittal alignment of the cervical spine

J Neurosurg Spine 26:572–576, 2017

Although there is increasing recognition of the importance of cervical spinal sagittal balance, there is a lack of consensus as to the optimal method to accurately assess the cervical sagittal alignment. Cervical alignment is important for surgical decision making. Sagittal balance of the cervical spine is generally assessed using one of two methods; namely, measuring the angle between C-2 and C-7, and drawing a line between C-2 and C-7. Here, the best method to assess sagittal alignment of the cervical spine is investigated.

METHODS Data from 138 patients enrolled in a randomized controlled trial (Procon) were analyzed. Two investigators independently measured the angle between C-2 and C-7 by using Harrison’s posterior tangent method, and also estimated the shape of the sagittal curve by using a modified Toyama method. The mean angles of each quantitative assessment of the sagittal alignment were calculated and the results were compared. The interrater reliability for both methods was estimated using Cronbach’s alpha.

RESULTS For both methods the interrater reliability was high: for the posterior tangent method it was 0.907 and for the modified Toyama technique it was 0.984. For a lordotic cervical spine, defined by the modified Toyama method, the mean angle (defined by Harrison’s posterior tangent method) was 23.4° ± 9.9° (range 0.4°–52.4°), for a kyphotic cervical spine it was -2.2° ± 9.2° (range -16.1° to 16.9°), and for a straight cervical spine it was 10.5° ± 8.2° (range -11° to 36°).

CONCLUSIONS An absolute measurement of the angle between C-2 and C-7 does not unequivocally define the sagittal cervical alignment. As can be seen from the minimum and maximum values, even a positive angle between C-2 and C-7 could be present in a kyphotic spine. For this purpose, the modified Toyama method (drawing a line from the posterior inferior part of the vertebral body of C-2 to the posterior upper part of the vertebral body of C-7 without any measurements) is a better tool for a global assessment of cervical sagittal alignment. Clinical trial registration no.: ISRCTN41681847 (

How to predict return to work after lumbar discectomy

How to predict return to work after lumbar discectomy- answers from the NeuroPoint-SD registry

J Neurosurg Spine 25:181–186, 2016

To date, the factors that predict whether a patient returns to work after lumbar discectomy are poorly understood. Information on postoperative work status is important in analyzing the cost-effectiveness of the procedure.

Methods An observational prospective cohort study was completed at 13 academic and community sites (Neuro- Point–Spinal Disorders [NeuroPoint-SD] registry). Patients undergoing single-level lumbar discectomy were included. Variables assessed included age, sex, body mass index (BMI), SF-36 physical function score, Oswestry Disability Index (ODI) score, presence of diabetes, smoking status, systemic illness, workers’ compensation status, and preoperative work status. The primary outcome was working status within 3 months after surgery. Stepwise logistic regression analysis was performed to determine which factors were predictive of return to work at 3 months following discectomy.

Results There were 127 patients (of 148 total) with data collected 3 months postoperatively. The patients’ average age at the time of surgery was 46 ± 1 years, and 66.9% of patients were working 3 months postoperatively. Statistical analyses demonstrated that the patients more likely to return to work were those of younger age (44.5 years vs 50.5 years, p = 0.008), males (55.3% vs 28.6%, p = 0.005), those with higher preoperative SF-36 physical function scores (44.0 vs 30.3, p = 0.002), those with lower preoperative ODI scores (43.8 vs 52.6, p = 0.01), nonsmokers (83.5% vs 66.7%, p = 0.03), and those who were working preoperatively (91.8% vs 26.2%, p < 0.0001). When controlling for patients who were working preoperatively (105 patients), only age was a statistically significant predictor of postoperative return to work (44.1 years vs 51.1 years, p = 0.049).

Conclusions In this cohort of lumbar discectomy patients, preoperative working status was the strongest predictor of postoperative working status 3 months after surgery. Younger age was also a predictor. Factors not influencing return to work in the logistic regression analysis included sex, BMI, SF-36 physical function score, ODI score, presence of diabetes, smoking status, and systemic illness. Clinical trial registration no.: 01220921 (

Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury

Neurosurgery 78:436–447, 2016

In our previous report, 3 of 10 patients with spinal cord injury who were injected with autologous mesenchymal stem cells (MSCs) showed motor improvement in the upper extremities and in activities of daily living.

OBJECTIVE: To report on the results of a phase III clinical trial of autologous MSCs therapy.

METHODS: Patients were selected based on the following criteria: chronic American Spinal Injury Association B status patients who had more than 12 months of cervical injury, and no neurological changes during the recent 3 months of vigorous rehabilitation. We injected 1.6 x10(7) autologous MSCs into the intramedullary area at the injured level and 3.2 x 10(7) autologous MSCs into the subdural space. Outcome data were collected over 6 months regarding neurological examination, magnetic resonance imaging with diffusion tensor imaging, and electrophysiological analyses.

RESULTS: Among the 16 patients, only 2 showed improvement in neurological status (unilateral right C8 segment from grade 1 to grade 3 in 1 patient and bilateral C6 from grade 3 to grade 4 and unilateral right C8 from grade 0 to grade 1 in 1 patient). Both patients with neurological improvement showed the appearance of continuity in the spinal cord tract by diffusion tensor imaging. There were no adverse effects associated with MSCs injection.

CONCLUSION: Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary.

Effects of methylene blue on postoperative low-back pain and functional outcomes after lumbar open discectomy: a triple-blind, randomized placebo-controlled trial

Surgical technique and effectiveness of microendoscopic discectomy for large uncontained lumbar disc herniations

J Neurosurg Spine 24:7–15, 2016

Despite advances in surgical and anesthesiology techniques, many patients continue to experience postoperative pain after lumbar disc operations. This study aims to investigate the effects of methylene blue (MB) on preventing postoperative low-back pain (LBP) with or without radicular pain and improving the quality of life (QOL) in patients undergoing lumbar open discectomy.

Methods This is a prospective, randomized, triple-blind, placebo-controlled clinical trial, which was conducted at Shiraz University of Medical Sciences between July 2011 to January 2012. Of a total of 130 patients, 115 were eligible for participation; 56 received 1 ml of MB solution at a concentration of 0.5% (MB group) and 59 received an equivalent volume of normal saline (control group). Primary outcomes were the control of LBP with or without radicular pain, which was evaluated preoperatively and at 24 hours and 3 months after surgery with the use of a visual analog scale (VAS), and the improvement of QOL, which was assessed preoperatively and 3 months postoperatively by means of the Persian translation of the Oswestry Disability Index questionnaire.

Results The mean VAS scores for LBP were significantly lower in the MB group compared with the control group at 24 hours (1.25 ± 0.97 vs 2.80 ± 0.69, p < 0.001) and 3 months (1.02 ± 1.29 vs 2.07 ± 1.10, p = 0.019) after treatment. The mean radicular pain scores decreased significantly in the 2 groups at 24 hours after surgery, but the mean radicular pain score was significantly lower in the MB-treated patients than the control group. However, the difference between radicular pain scores in the MB group (1 ± 1.1) and the control group (1.2 ± 1) was not statistically significant (p = 0.64). The reduction in LBP was greater in the MB group than the control group (8.11 ± 1.74 vs 6.07 ± 1.52, p = 0.023, CI 95% –1.37 to –0.10). The functional QOL improved significantly 3 months after the operation in both groups (p < 0.001). Moderate disability occurred more frequently in the control group than in the MB group (14.5% vs 7.7%, p = 0.004). No toxicity, adverse effects, or complications were found in the group of patients treated with MB injection.

Conclusions A single dose of MB (1 ml 0.5%) for coating the dura and surrounding tissues (facet and muscle) shows promising results in terms of safety, reduction of postoperative pain, and functional outcome compared with placebo.

Minimally invasive lateral fusion for adjacent disease

Minimally invasive lateral interbody fusion for the treatment of rostral adjacent-segment lumbar degenerative stenosis without supplemental pedicle screw fixation

J Neurosurg Spine 21:861–866, 2014

Adjacent-segment degeneration and stenosis are common in patients who have undergone previous lumbar fusion. Treatment typically involves a revision posterior approach, which requires management of postoperative scar tissue and previously implanted instrumentation. A minimally invasive lateral approach allows the surgeon to potentially reduce the risk of these hazards. The technique relies on indirect decompression to treat central and foraminal stenosis and placement of a graft with a large surface area to promote robust fusion and stability in concert with the surrounding tensioned ligaments. The goal in this study was to determine if lateral interbody fusion without supplemental pedicle screws is effective in treating adjacent-segment disease.

Methods. For a 30-month study period at two institutions, the authors obtained all cases of lumbar fusion with new back and leg pain due to adjacent-segment stenosis and spondylosis failing conservative measures. All patients had undergone minimally invasive lateral interbody fusion from the side of greater leg pain without supplemental pedicle screw fixation. Patients were excluded from the study if they had undergone surgery for a nondegenerative etiology such as infection or trauma. They were also excluded if the intervention involved supplemental posterior instrumented fusion with transpedicular screws. Postoperative metrics included numeric pain scale (NPS) scores for leg and back pain. All patients underwent dynamic radiographs and CT scanning to assess stability and fusion after surgery.

Results. During the 30-month study period, 21 patients (43% female) were successfully treated using minimally invasive lateral interbody fusion without the need for subsequent posterior transpedicular fixation. The mean patient age was 61 years (range 37–87 years). Four patients had two adjacent levels fused, while the remainder had single-level surgery. All patients underwent surgery without conversion to a traditional open technique, and recombinant human bone morphogenetic protein–2 was used in the interbody space in all cases. The mean follow-up was 23.6 months. The mean operative time was 86 minutes, and the mean blood loss was 93 ml. There were no major intraoperative complications, but one patient underwent subsequent direct decompression in a delayed fashion. The leg pain NPS score improved from a mean of 6.3 to 1.9 (p < 0.01), and the back pain NPS score improved from a mean of 7.5 to 2.9 (p < 0.01). Intervertebral settling averaged 1.7 mm. All patients had bridging bone on CT scanning at the last follow-up, indicating solid bony fusion.

Conclusions. Adjacent-segment stenosis and spondylosis can be treated with a number of different operative techniques. Lateral interbody fusion provides an attractive alternative with reduced blood loss and complications, as there is no need to re-explore a previous laminectomy site. In this limited series a minimally invasive lateral approach provided high fusion rates when performed with osteobiological adjuvants.

Intraspinal Stem Cell Transplantation in Amyotrophic Lateral Sclerosis

Intraspinal Stem Cell Transplantation in Amyotrophic Lateral Sclerosis

Neurosurgery 74:77–87, 2014

The first US Food and Drug Administration approved clinical trial for a stem cell-based treatment of amyotrophic lateral sclerosis has now been completed.

OBJECTIVE: Primary aims assessed the safety of a direct microinjection-based technique and the toxicity of neural stem cell transplantation to the ventral horn of the cervical and thoracolumbar spinal cord. Results from thoracolumbar-only microinjection groups have been previously published. Cervical and cervical plus thoracolumbar microinjection group perioperative morbidity results are presented.

METHODS: Eighteen microinjection procedures (n = 12 thoracolumbar [T10/11], n = 6 cervical [C3-5]) delivered NSI-566RSC (Neuralstem, Inc), a human neural stem cell, to 15 patients in 5 cohorts. Each injection series comprised 5 injections of 10 mL at 4-mm intervals. The patients in group A (n = 6) were nonambulatory and received unilateral (n = 3) or bilateral (n = 3) thoracolumbar microinjections. The patients in groups B to E were ambulatory and received either unilateral (group B, n = 3) or bilateral (group C, n = 3) thoracolumbarmicroinjection. Group D and E patients received unilateral cervical (group D, n = 3) or cervical plus bilateral thoracolumbar microinjection (group E, n = 3).

RESULTS: Unilateral cervical (group D, n = 3) and cervical plus thoracolumbar (group E, n = 3) microinjections to the ventral horn have been completed in ambulatory patients. One patient developed a postoperative kyphotic deformity prompting completion of a laminoplasty in subsequent patients. Another required reoperation for wound dehiscence and infection. The solitary patient with bulbar amyotrophic lateral sclerosis required perioperative reintubation.

CONCLUSION: Delivery of a cellular payload to the cervical or thoracolumbar spinal cord was well tolerated by the spinal cord in this vulnerable population. This encouraging finding supports consideration of this delivery approach for neurodegenerative, oncologic, and traumatic spinal cord afflictions.

Nonsurgical treatment of chronic subdural hematoma with tranexamic acid


J Neurosurg 119:332–337, 2013

Chronic subdural hematoma (CSDH) is a common condition after head trauma. It can often be successfully treated surgically by inserting a bur hole and draining the liquefied hematoma. However, to the best of the authors’ knowledge, for nonemergency cases not requiring surgery, no reports have indicated the best approach for preventing hematoma enlargement or resolving it completely. The authors hypothesized that hyperfibrinolysis plays a major role in liquefaction of the hematoma. Therefore, they evaluated the ability of an antifibrinolytic drug, tranexamic acid, to completely resolve CSDH compared with bur hole surgery alone.

From 2007 to 2011, a total of 21 patients with CSDH seen consecutively at Kuki General Hospital, Japan, were given 750 mg of tranexamic acid orally every day. Patients were identified by a retrospective records review, which collected data on the volume of the hematoma (based on radiographic measurements) and any complications. Follow-up for each patient consisted of CT or MRI every 21 days from diagnosis to resolution of the CSDH.

Of the 21 patients, 3 with early stages of CSDH were treated by bur hole surgery before receiving medical therapy. The median duration of clinical and radiographic follow-up was 58 days (range 28–137 days). Before tranexamic acid therapy was initiated, the median hematoma volume for the 21 patients was 58.5 ml (range 7.5–223.2 ml); for the 18 patients who had not undergone surgery, the median hematoma volume was 55.6 ml (range 7.5–140.5 ml). After therapy, the median volume for all 21 patients was 3.7 ml (range 0–22.1 ml). No hematomas recurred or progressed.

Chronic subdural hematoma can be treated with tranexamic acid without concomitant surgery. Tranexamic acid might simultaneously inhibit the fibrinolytic and inflammatory (kinin-kallikrein) systems, which might consequently resolve CSDH. This medical therapy could prevent the early stages of CSDH that can occur after head trauma and the recurrence of CSDH after surgery.

X-Stop Versus Decompressive Surgery for Lumbar Neurogenic Intermittent Claudication


Spine 2013 ;38:1436–1442

Objective. To compare the outcome of indirect decompression by means of the X-Stop (Medtronics Inc., Minneapolis, MN) implant with conventional decompression in patients with neurogenic intermittent claudication due to lumbar spinal stenosis.

Summary of Background Data. Decompression is currently the “gold standard” for lumbar spinal stenosis but is affl icted with complications and a certain number of dissatisfi ed patients. Interspinous implants have been on the market for more than 10 years, but no prospective study comparing its outcome with decompression has been performed.

Methods. After power calculation, 100 patients were included: 50 in the X-Stop group and 50 in the decompression group. Patients with symptomatic 1- or 2-level lumbar spinal stenosis and neurogenic claudication relieved on fl exion were included. X-Stop operations were performed under local anesthesia. The mean patient age was 69 (49–89) years, and the male/female distribution was 56/44. Minimal dural sac area was in all cases except two 80 mm 2 or less. The noninferiority hypothesis included 6, 12, and 24 months of follow-up, and included. intention-to-treat as well as as-treated analyses. The primary outcome meansure was the Zürich Claudication Questionnaire, and the secondary outcome measures was the visual analogue scale pain, Short-Form 36 (SF-36), complications, and reoperations.

Results. The primary and secondary outcome measures of patients in both groups improved signifi cantly. The results were similar at 6, 12, and 24 months and at no time point could any statistical difference between the 2 types of surgery be identifi ed. Three patients (6%) in the decompression group underwent further surgery, compared with 13 patients (26%) in the X-Stop group ( P = 0.04). Results were identical in intention-to-treat and astreated analyses.

Conclusion. For spinal stenosis with neurogenic claudication, decompressive surgery as well as X-Stop are appropriate procedures. Similar results were achieved in both groups, however, with a higher number of reoperations in the X-Stop group. Patients having X-Stop removal and decompression experienced results similar to those randomized to primary decompression.

Level of Evidence: 1

Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma



J Neurosurg 118:1202–1219, 2013

Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose–escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM).

Methods. Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, sidefiring laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation.

Results. Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals–Case Medical Center). Their average age was 55 years (range 34–69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70–90). The mean tumor volume was 6.8 ± 5 cm3 (range 2.6–19 cm3), the percentage of tumor treated was 78% ± 12% (range 57%–90%), and the conformality index was 1.21 ± 0.33 (range 1.00–2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62–767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose.

Conclusions. NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. Clinical trial registration no.: NCT00747253 (ClinicalTrials. gov).

A Simple Protocol to Prevent External Ventricular Drain Infections


Neurosurgery 72:993–999, 201

External ventricular drains (EVDs) are associated with high rates of infection, and EVD infections cause substantial morbidity and mortality.

OBJECTIVE: To determine whether the introduction of an evidence-based EVD infection control protocol could reduce the rate of EVD infections.

METHODS: This was a retrospective analysis of an EVD infection control protocol introduced in a tertiary care neurointensive care unit. We compared rates of cerebrospinal fluid culture positivity and ventriculitis for the 3 years before and 3 years after the introduction of an evidence-based EVD infection control protocol. A total of 262 EVD placements were analyzed, with a total of 2499 catheter-days.

RESULTS: The rate of cerebrospinal fluid culture positivity decreased from 9.8% (14 of 143; 11.43 per 1000 catheter-days) at baseline to 0.8% (1 of 119; 0.79 per 1000 catheterdays) in the EVD infection control protocol period (P = .001). The rate of ventriculitis decreased from 6.3% (9 of 143; 7.35 per 1000 catheter-days) to 0.8% (1 of 119; 0.79 per 1000 catheter-days; P = .02).

CONCLUSION: The introduction of a simple, evidence-based infection control protocol was associated with a dramatic reduction in the risk of EVD infection.

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma

Acta Neurochir (2013) 155:33–40

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-weekcycles); patients whose tumor expressed EGFRvIII (4/ 10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n=4) and bevacizumab (n=6), respectively. In the whole cohort (n= 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.

Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma

Acta Neurochir (2012) 154:1371–1378

Combining Gliadel wafers and radiochemotherapy with TMZ may carry the risk of increased adverse events (AE). We analyzed the efficacy and safety in patients with glioblastoma who underwent multimodal treatment with implantation of Gliadel wafers.

Methods One hundred sixty-five consecutive patients with newly diagnosed (77 patients) or recurrent (88 patients) glioblastoma were studied. Forty-seven patients underwent surgery + Gliadel. The impact of age (≥65 vs. <65), resection extent (gross total vs. partial), use of Gliadel and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on overall survival (OS, for patients with newly diagnosed glioblastoma) and on recurrence-survival (for patients with recurrent glioblastoma) was analyzed with Cox regression. The impact of age, history (newly diagnosed vs. recurrent glioblastoma), number of Gliadel wafers implanted (0 vs. <8 vs. 8), resection extent (gross-total vs. partial) and adjuvant treatment (TMZ vs. other schemes/no adjuvant therapy) on the occurrence of AE and on the occurrence of implantation site-related AE (ISAE) was analyzed with the logistic regression model. Significance was set at p<0.05.

Results Multivariate analysis showed the only factor associated with longer survival, both for newly diagnosed and for recurrent GBM, was resection extent. Both patients with a higher number of wafers implanted and patients with recurrent tumors were significantly at risk for AE and ISAE. Patients with eight Gliadel wafers implanted had a 3-fold increased risk of AE and a 5.6-fold increased risk of ISAE, and patients with recurrent tumor had a 2.8-fold increased risk of AE and a 9.3-fold increased risk of ISAE.

Conclusions Adding Gliadel to standard treatment did not significantly improve the outcome. The toxicity after Gliadel use was significantly higher, both for patients with newly diagnosed and patients with recurrent glioblastoma.

Comparison of Infection Rate With the Use of Antibiotic-Impregnated vs Standard Extraventricular Drainage Devices: A Prospective, Randomized Controlled Trial

Neurosurgery 71:6–13, 2012 DOI: 10.1227/NEU.0b013e3182544e31

External ventricular drainage (EVD) catheters provide reliable and accurate means of monitoring intracranial pressure and alleviating elevated pressures via drainage of cerebrospinal fluid (CSF). CSF infections occur in approximately 9% of patients. Antibiotic-impregnated (AI) EVD catheters were developed with the goal of reducing the occurrence of EVD catheter-related CSF infections and their associated complications.

OBJECTIVE: To present an international, prospective, randomized, open-label trial to evaluate infection incidence of AI vs standard EVD catheters.

METHODS: Infection was defined as (1) proven infection, positive CSF culture and positive Gram stain or (2) suspected infection: (A) positive CSF culture with no organisms identified on initial Gram stain; (B) negative CSF culture with a gram-positive or -negative stain; (C) CSF leukocytosis with a white blood cell/red blood cell count .0.02.

RESULTS: Four hundred thirty-four patients underwent implantation of an EVD catheter. One hundred seventy-six patients in the AI-EVD cohort and 181 in the standard EVD catheter cohort were eligible for evaluation of infection. The 2 groups were similar in all clinical characteristics. Proven infection was documented in 9 (2.5%) patients (AI: 4 [2.3%] vs standard: 5 [2.8%], P = 1.0). Suspected infection was documented in 31 (17.6%) patients receiving AI and 37 (20.4%) patients receiving standard EVD catheters, P = .504. Duration of time to suspected infection was prolonged in the AI cohort (8.8 6 6.1 days) compared with the standard EVD cohort (4.6 6 4.2 days), P = .002.

CONCLUSION: AI-EVD catheters were associated with an extremely low rate of catheter-related infections. AI catheters were not associated with risk reduction in EVD infection compared to standard catheters. Use of AI-EVD catheters is a safe option for a wide variety of patients requiring CSF drainage and monitoring, but the efficacy of AI-EVD catheters was not supported in this trial.

Failure of Percutaneous Remodeling of the Ligamentum Flavum and Lamina for Neurogenic Claudication

Neurosurgery 71:86–92, 2012 DOI: 10.1227/NEU.0b013e31825356f5

Percutaneous remodeling of the ligamentum flavum and lamina (PRLL), commercially known as minimally invasive lumbar decompression (mild technique), relies on fluoroscopy and epidural contrast to direct surgical instruments via a 6-mm cannula.

OBJECTIVE: To evaluate the safety and efficacy of PRLL and present, to our knowledge, the first reported imaging findings after PRLL.

METHODS: We performed a prospective study of PRLL for neurogenic claudication. Primary outcomes were Oswestry Disability Index, Short-Form 12 version 2.0 health survey, and visual analog scale for pain at 26 weeks. Analgesic use was also assessed. Postoperative magnetic resonance imaging was performed at 12 weeks. Long-term failure, defined as the poststudy need for secondary surgery, was assessed up to 18 months.

RESULTS: Ten subjects with an average age of 64 years (range, 41-81 years) were treated between September 2008 and January 2009. There were no major adverse events. Mean postoperative visual analog scale score remained significantly reduced throughout 26 weeks (P =.015, analysis of variance). Mean postoperative Oswestry Disability Index was also improved by 1 week and remained significant throughout 26 weeks (P = .024; analysis of variance). However, there was a trend toward increased reliance on narcotic type medications postoperatively. Imaging studies did not show significant decompression of the spinal canal in any patient. In the poststudy period, recurrent claudication requiring laminectomy developed in 6 patients (60%).

CONCLUSION: Throughout 26 weeks, pain and disability scores were decreased; however, PRLL did not improve the degree of stenosis on imaging studies. Although PRLL appears to be safe in this small cohort of patients, poststudy outcomes indicate that the failure rate is unacceptably high.


Transplantation of mesenchymal stem cells after spinal cord injury

Neurosurgery 70:1238–1247, 2012

DOI: 10.1227/NEU.0b013e31824387f9

Although the transplantation of mesenchymal stem cells (MSCs) after spinal cord injury (SCI) has shown promising results in animals, less is known about the effects of autologous MSCs in human SCI.

OBJECTIVE: To describe the long-term results of 10 patients who underwent intramedullary direct MSCs transplantation into injured spinal cords.

METHODS: Autologous MSCs were harvested from the iliac bone of each patient and expanded by culturing for 4 weeks. MSCs (8 · 106) were directly injected into the spinal cord, and 4 x 10(7) cells were injected into the intradural space of 10 patients with American Spinal Injury Association class A or B injury caused by traumatic cervical SCI. After 4 and 8 weeks, an additional 5 x 10(7) MSCs were injected into each patient through lumbar tapping. Outcome assessments included changes in the motor power grade of the extremities, magnetic resonance imaging, and electrophysiological recordings.

RESULTS: Although 6 of the 10 patients showed motor power improvement of the upper extremities at 6-month follow-up, 3 showed gradual improvement in activities of daily living, and changes on magnetic resonance imaging such as decreases in cavity size and the appearance of fiber-like low signal intensity streaks. They also showed electrophysiological improvement. All 10 patients did not experience any permanent complication associated with MSC transplantation.

CONCLUSION: Three of the 10 patients with SCI who were directly injected with autologous MSCs showed improvement in the motor power of the upper extremities and in activities of daily living, as well as significant magnetic resonance imaging and electrophysiological changes during long-term follow-up.

Minimally invasive treatment for intracerebral hemorrhage

Neurosurg Focus 32 (4):E3, 2012.

Spontaneous intracerebral hemorrhage is a serious public health problem and is fatal in 30%–50% of all occurrences. The role of open surgical management of supratentorial intracerebral hemorrhage is still unresolved. A recent consensus conference sponsored by the National Institutes of Health suggests that minimally invasive techniques to evacuate clots appear to be a promising area and warrant further investigation. In this paper the authors review past, current, and potential future methods of treating intraparenchymal hemorrhages with minimally invasive techniques and review new data regarding the role of stereotactically placed catheters and thrombolytics.

A minimally invasive approach to evacuate ICH has been well documented to be a safe practice. Thus far, the CLEAR and MISTIE studies have supported this assertion. An increased rate of clot lysis could potentially be achieved with a combination of mechanical and pharmaceutical approaches. However, more extensive studies need to be conducted to determine whether the additional mechanical effects via ultrasound further yield beneficial long-term outcome versus pharmacological lysis alone. Currently, catheters are being redesigned for this purpose and will be evaluated in additional future clinical trials.

Analysis of three IDE cervical arthroplasty trials

J Neurosurg Spine 16:216–228, 2012. DOI: 10.3171/2011.6.SPINE10623

There are now 3 randomized, multicenter, US FDA investigational device exemption, industry-sponsored studies comparing arthroplasty with anterior cervical discectomy and fusion (ACDF) for single-level cervical disease with 2 years of follow-up. These 3 studies evaluated the Prestige ST, Bryan, and ProDisc-C artificial discs. The authors analyzed the combined results of these trials.

Methods. A total of 1213 patients with symptomatic, single-level cervical disc disease were randomized into 2 treatment arms in the 3 randomized trials. Six hundred twenty-one patients received an artificial cervical disc, and 592 patients were treated with ACDF. In the three trials, 94% of the arthroplasty group and 87% of the ACDF group have completed 2 years of follow-up. The authors analyzed the 2-year data from these 3 trials including previously unpublished source data. Statistical analysis was performed with fixed and random effects models.

Results. The authors’ analysis revealed that segmental sagittal motion was preserved with arthroplasty (preoperatively 7.26° and postoperatively 8.14°) at the 2-year time point. The fusion rate for ACDF at 2 years was 95%. The Neck Disability Index, 36-Item Short Form Health Survey Mental, and Physical Component Summaries, neck pain, and arm pain scores were not statistically different between the groups at the 24-month follow-up. The arthroplasty group demonstrated superior results at 24 months in neurological success (RR 0.595, I2 = 0%, p = 0.006). The arthroplasty group had a lower rate of secondary surgeries at the 2-year time point (RR 0.44, I2 = 0%, p = 0.004). At the 2-year time point, the reoperation rate for adjacent-level disease was lower for the arthroplasty group when the authors analyzed the combined data set using a fixed effects model (RR 0.460, I2 = 2.9%, p = 0.030), but this finding was not significant using a random effects model. Adverse event reporting was too heterogeneous between the 3 trials to combine for analysis.

Conclusions. Both anterior cervical discectomy and fusion as well as arthroplasty demonstrate excellent 2-year surgical results for the treatment of 1-level cervical disc disease with radiculopathy. Arthroplasty is associated with a lower rate of secondary surgery and a higher rate of neurological success at 2 years. Arthroplasty may be associated with a lower rate of adjacent-level disease at 2 years, but further follow-up and analysis are needed to confirm this finding.

Dural sinus stents for idiopathic intracranial hypertension

J Neurosurg 116:538–548, 2012. DOI: 10.3171/2011.10.JNS101410

The use of unilateral dural sinus stent placement in patients with idiopathic intracranial hypertension (IIH) has been described by multiple investigators. To date there is a paucity of information on the angiographic and hemodynamic outcome of these procedures. The object of this study was to define the clinical, angiographic, and hemodynamic outcome of placement of unilateral dural sinus stents to treat intracranial venous hypertension in a subgroup of patients meeting the diagnostic criteria for IIH.

Methods. Eighteen consecutive patients with a clinical diagnosis of IIH were treated with unilateral stent placement in the transverse-sigmoid junction region. All patients had papilledema. All 12 female patients had headaches; 1 of 6 males had headaches previously that disappeared after weight loss. Seventeen patients had elevated opening pressures at lumbar puncture. Twelve patients had opening pressures of 33–55 cm H2O. All patients underwent diagnostic cerebral arteriography that showed venous outflow compromise by filling defects in the transverse-sigmoid junction region. All patients underwent intracranial selective venous pressure measurements across the filling defects. Follow-up arteriography was performed in 16 patients and follow-up venography/venous pressure measurements were performed in 15 patients.

Results. Initial pressure gradients across the filling defects ranged from 10.5 to 39 mm Hg. Nineteen stent procedures were performed in 18 patients. One patient underwent repeat stent placement for hemodynamic failure. Pressure gradients were reduced in every instance and ranged from 0 to 7 mm Hg after stenting. Fifteen of 16 patients in whom ophthalmological follow-up was performed experienced disappearance of papilledema. Follow-up arteriography in 16 patients at 5–99 months (mean 25.3 months, median 18.5 months) showed patency of all stents without in-stent restenosis. Two patients had filling defects immediately above the stent. Four other patients developed transverse sinus narrowing above the stent without filling defects. One of these patients underwent repeat stent placement because of hemodynamic deterioration. Two of the other 3 patients had hemodynamic deterioration with recurrent pressure gradients of 10.5 and 18 mm Hg.

Conclusions. All stents remained patent without restenosis. Stent placement is durable and successfully eliminates papilledema in appropriately selected patients. Continuing hemodynamic success in this series was 80%, and was 87% with repeat stent placement in 1 patient.

Brain stimulation for the treatment of epilepsy

Neurosurg Focus 32 (3):E13, 2012

The treatment of patients with refractory epilepsy has always been challenging. Despite the availability of multiple antiepileptic medications and surgical procedures with which to resect seizure foci, there is a subset of epilepsy patients for whom little can be done. Currently available treatment options for these unfortunate patients include vagus nerve stimulation, the ketogenic diet, and electric stimulation, both direct and indirect, of brain nuclei thought to be involved in epileptogenesis.

Studies of electrical stimulation of the brain in epilepsy treatment date back to the early 20th century, beginning with research on cerebellar stimulation. The number of potential targets has increased over the years to include the hippocampus, subthalamic nucleus, caudate nucleus, centromedian nucleus, and anterior nucleus of the thalamus (ANT).

Recently the results of a large randomized controlled trial, the electrical Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial, were published, demonstrating a significant reduction in mean seizure frequency with ANT stimulation. Soon after, in 2011, the results of a second randomized, controlled trial—the NeuroPace RNS trial—were published. The RNS trial examined closed-loop, responsive cortical stimulation of seizure foci in patients with refractory partial epilepsy, again finding significant reduction in seizure frequency.

In the present review, the authors examine the modern history of electrical stimulation of the brain for the treatment of epilepsy and discuss the results of 2 important, recently published trials, the SANTE and RNS trials.

Percutaneous biopsy of lesions in the cavernous sinus region through the foramen ovale: diagnostic accuracy and limits in 50 patients

J Neurosurg 116:390–398, 2012.DOI: 10.3171/2011.10.JNS11783

The cavernous sinus and surrounding regions—specifically the Meckel cave, posterior sector of the cavernous sinus itself, and the upper part of the petroclival region—are the location of a large variety of lesions that require individual consideration regarding treatment strategy. These regions may be reached for biopsy by a percutaneous needle inserted through the foramen ovale. The aim of this retrospective study was to evaluate the diagnostic accuracy of percutaneous biopsy in a consecutive series of 50 patients referred for surgery between 1991 and 2010.

Methods. Seven biopsies (14%) were unproductive and 43 (86%) were productive, among which 28 lesions subsequently underwent histopathological examination during a second (open) surgery. To evaluate the diagnostic accuracy of the procedure, results from surgery were compared with those from the biopsy.

Results. Sensitivity of the percutaneous biopsy was 0.83 (95% CI 0.52–0.98), specificity was 1 (95% CI 0.79–1), and k coefficient was 0.81.

Conclusions. Because of its valuable diagnostic accuracy, percutaneous biopsy of the cavernous sinus and surrounding regions should be performed in patients with parasellar masses when neuroimaging does not provide sufficient information of a histopathological nature. This procedure would enable patients to obtain the most appropriate therapy, such as resective surgery, corticosteroids, chemotherapy, radiotherapy, or radiosurgery.

Neurosurgery Department. “La Fe” University Hospital. Valencia, Spain


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