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Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas

J Neurosurg 115:740–748, 2011. DOI: 10.3171/2011.6.JNS11252

Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5- ALA)–induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection.

Methods. Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence.

Results. Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses.

Conclusions. Intraoperative confocal microscopy can visualize cellular 5-ALA–induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors’ institution.

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Intraoperative magnetic resonance imaging findings during deep brain stimulation surgery

J Neurosurg 115:852–857, 2011.DOI: 10.3171/2011.5.JNS101457

Deep brain stimulation (DBS) is an established neurosurgical technique used to treat a variety of neurological disorders, including Parkinson disease, essential tremor, dystonia, epilepsy, depression, and obsessive-compulsive disorder. This study reports on the use of intraoperative MR imaging during DBS surgery to evaluate acute hemorrhage, intracranial air, brain shift, and accuracy of lead placement.

Methods. During a 46-month period, 143 patients underwent 152 DBS surgeries including 289 lead placements utilizing intraoperative 1.5-T MR imaging. Imaging was supervised by an MR imaging physicist to maintain the specific absorption rate below the required level of 0.1 W/kg and always included T1 magnetization-prepared rapid gradient echo and T2* gradient echo sequences with selected use of T2 fluid attenuated inversion recovery (FLAIR) and T2 fast spin echo (FSE). Retrospective review of the intraoperative MR imaging examinations was performed to quantify the amount of hemorrhage and the amount of air introduced during the DBS surgery.

Results. Intraoperative MR imaging revealed 5 subdural hematomas, 3 subarachnoid hemorrhages, and 1 intraparenchymal hemorrhage in 9 of the 143 patients. Only 1 patient experiencing a subarachnoid hemorrhage developed clinically apparent symptoms, which included transient severe headache and mild confusion. Brain shift due to intracranial air was identified in 144 separate instances.

Conclusions. Intraoperative MR imaging can be safely performed and may assist in demonstrating acute changes involving intracranial hemorrhage and air during DBS surgery. These findings are rarely clinically significant and typically resolve prior to follow-up imaging. Selective use of T2 FLAIR and T2 FSE imaging can confirm the presence of hemorrhage or air and preclude the need for CT examinations

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Occipital WHO grade II gliomas: oncological, surgical and functional considerations

Acta Neurochir (2011) 153:1907–1917. DOI 10.1007/s00701-011-1125-z

Diffuse WHO grade II glioma (GIIG) involving the occipital lobe is a rare entity. Its surgical resection remains controversial as it implies inducing a permanent visual deficit. For the first time to our knowledge, we report a consecutive surgical series of patients who underwent an occipital lobectomy for an LGG invading visual structures.

Method Six right-handed patients harboring a GIIG revealed by seizures (normal examination except a quadrantanopsia in one case) and located within the occipital lobe (4 left and 2 right tumors) were submitted to surgery. Before making this decision, the benefit-to-risk ratio of the resection was extensively discussed with the patient and his/her family, especially concerning the price to pay to remove the tumor, that is, to voluntarily generate a permanent hemianopsia. All the procedures were performed under awake condition using intraoperative electrostimulation, in order to pursue the resection until sensory-motor and/or language structures were encountered.

Findings An extensive occipital lobectomy was achieved in the six patients, with identification and preservation of sensory-motor pathways in the two cases with a right tumor and detection of language pathways in the four cases with a left tumor. The mean extent of resection was 93% (range: 91–100%). All patients experienced an expected postoperative deficit of the visual field (homonymous hemianopsia). Nonetheless, the six patients resumed a normal social and professional life (KPS at 90 in the 6 cases) with a mean follow-up of 58 months (range: 3–147 months)—with adjuvant treatment in three cases (in addition to a reoperation in two of them).

Conclusions Our findings suggest that, despite a definitive hemianopsia, an extensive surgical resection can be considered in the rare cases of occipital GIIG involving the primary visual structures, with patients able to maintain a normal life—except regarding the medico-legal problem of driving.

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Effectiveness of interspinous implant surgery in patients with intermittent neurogenic claudication: a systematic review and meta-analysis

Eur Spine J (2011) 20:1596–1606.DOI 10.1007/s00586-011-1873-8
Despite an increasing implantation rate of interspinous process distraction (IPD) devices in the treatment of intermittent neurogenic claudication (INC), definitive evidence on the clinical effectiveness of implants is lacking. The main objective of this review was to perform a meta-analysis of all systematic reviews, randomized clinical trials and prospective cohort series to quantify the effectiveness of IPDs and to evaluate the potential sideeffects.
Methods  Data from all studies prospectively describing clinical results based on validated outcome scales and reporting complications of treatment of patients with INC with IPD placement. We searched MEDLINE, EMBASE, Web of Science, Cochrane (CENTRAL), CINAHL, Academic Search Premier, Science Direct up to July 2010. Studies describing patients with INC caused by lumbar stenosis, reporting complication rate and reporting based on validated outcome scores, were eligible. Studies with only instrumented IPD results were excluded.
Results  Eleven studies eligible studies were identified. Two independently RCTs and eight prospective cohorts were available. In total 563 patients were treated with IPDs. All studies showed improvement in validated outcome scores after 6 weeks and 1 year. Pooled data based on the Zurich Claudication Questionnaire of the RCTs were more in favor of IPD treatment compared with conservative treatment (pooled estimate 23.2, SD 18.5–27.8). Statistical heterogeneity after pooled data was low (I-squared 0.0, p =  0.930). Overall complication rate was 7%.
Conclusion  As the evidence is relatively low and the costs are high, more thorough (cost-) effectiveness studies should be performed before worldwide implementation is introduced.

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Dentatorubrothalamic tract in human brain: diffusion tensor tractography study

Neuroradiology(2011)53:787–791.DOI 10.1007/s00234-011-0878-7
The dentatorubrothalamic tract (DRTT) originates  from the dentate nucleus in the cerebellum and terminates in the contralateral ventrolateral nucleus (VL) of the thalamus after decussating to the contralateral red nucleus. Identification of the DRTT is difficult due to the fact that it is a long, multisynaptic, neural tract crossing to the opposite hemisphere.
In the current study, we attempted to identify the DRTT in the human brain using a probabilistic tractography technique of diffusion tensor imaging.
Methods Diffusion tensor imaging was performed at 1.5-T using a synergy-L sensitivity encoding head coil. DRTTs were obtained by selection of fibers passing through three regions of interest (the dentate nucleus, the superior cerebellar peduncle, and the contralateral red nucleus) from 41 healthy volunteers. Probabilistic mapping was obtained from the highest probabilistic location at 2.3 mm above the anterior commissure–posterior commissure level.
Results DRTTs of all subjects, which originated from the dentate nucleus, ascended through the junction of the superior cerebellar peduncle and the contralateral red nucleus and then terminated at the VL nucleus of the thalamus. The highest probabilistic location for the DRTT at the thalamus was compatible with the location of the VL nucleus.
Conclusions We identified the DRTT in the human brain using probabilistic tractography. Our results could be useful in research on movement control.

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Tubular Diskectomy vs Conventional Microdiskectomy for the Treatment of Lumbar Disk-Related Sciatica: Cost Utility Analysis Alongside a Double-Blind Randomized Controlled Trial

Neurosurgery 69:829–836, 2011 DOI: 10.1227/NEU.0b013e31822578f6

Conventional microdiskectomy is the most frequently performed surgery for patients with sciatica caused by lumbar disk herniation. Transmuscular tubular diskectomy has been introduced to increase the rate of recovery, although evidence of its efficacy is lacking.

OBJECTIVE: To determine whether a favorable cost-effectiveness for tubular diskectomy compared with conventional microdiskectomy is attained.

METHODS: Cost utility analysis was performed alongside a double-blind randomized controlled trial conducted among 325 patients with lumbar disk related sciatica lasting .6 to 8 weeks at 7 Dutch hospitals comparing tubular diskectomy with conventional microdiskectomy. Main outcome measures were quality-adjusted life-years at 1 year and societal costs, estimated from patient reported utilities (US and Netherlands EuroQol, Short Form Health Survey-6D, and Visual Analog Scale) and diaries on costs (health care, patient costs, and productivity).

RESULTS: Quality-adjusted life-years during all 4 quarters and according to all utility measures were not statistically different between tubular diskectomy and conventional microdiskectomy (difference for US EuroQol, 20.012; 95% confidence interval, 20.046 to 0.021). From the healthcare perspective, tubular diskectomy resulted in nonsignificantly higher costs (difference US $460; 95% confidence interval, 2243 to 1163). From the societal perspective, a nonsignificant difference of US $1491 (95% confidence interval, 21335 to 4318) in favor of conventional microdiskectomy was found. The nonsignificant differences in costs and quality-adjusted life-years in favor of conventional microdiskectomy result in a low probability that tubular diskectomy is more cost-effective than conventional microdiskectomy.

CONCLUSION: Tubular diskectomy is unlikely to be cost-effective compared with conventional microdiskectomy.

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Neurosurgery and shaving: what’s the evidence?. A review

Journal of Neurosurgery Oct 2011 / Vol. 115 / No. 4 / Pages 670-678. DOI: 10.3171/2011.5.JNS102003.

Many neurosurgeons remove their patients’ hair before surgery. They claim that this practice reduces the chance of postoperative surgical site infections, and facilitates planning, attachment of the drapes, and closure. However, most patients dread this procedure.

The authors performed the first systematic review on shaving before neurosurgical procedures to investigate whether this commonly performed procedure is based on evidence. They systematically reviewed the literature on wound infections following different shaving strategies. Data on the type of surgery, surgery-related infections, preoperative shaving policy, decontamination protocols, and perioperative antibiotics protocols were collected.

The search detected 165 articles, of which 21 studies—involving 11,071 patients—were suitable for inclusion. Two of these studies were randomized controlled trials. The authors reviewed 13 studies that reported on the role of preoperative hair removal in craniotomies, 14 on implantation surgery, 5 on bur hole procedures, and 3 on spine surgery. Nine studies described shaving policies in pediatric patients.

None of these papers provided evidence that preoperative shaving decreases the occurrence of postoperative wound infections. The authors conclude that there is no evidence to support the routine performance of preoperative hair removal in neurosurgery. Therefore, properly designed studies are needed to provide evidence for preoperative shaving recommendations.

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Prospective, randomized, multicenter study of cervical arthroplasty: 269 patients from the Kineflex|C artificial disc investigational device exemption study with a minimum 2-year follow-up

Journal of Neurosurgery: Spine Oct 2011 / Vol. 15 / No. 4 / Pages 348-358. DOI: 10.3171/2011.5.SPINE10769.

Cervical total disc replacement (CTDR) represents a relatively novel procedure intended to address some of the shortcomings associated with anterior cervical discectomy and fusion (ACDF) by preserving motion at the treated level. This prospective, randomized, multicenter study evaluates the safety and efficacy of a new metal-on-metal CTDR implant (Kineflex|C) by comparing it with ACDF in the treatment of single-level spondylosis with radiculopathy.

METHODS

The study was a prospective, randomized US FDA Investigational Device Exemption (IDE) pivotal trial conducted at 21 centers across the US. The primary clinical outcome measures included the Neck Disability Index (NDI), visual analog scale (VAS) scores, and a composite measure of clinical success. Patients were randomized to CTDR using the Kineflex|C (SpinalMotion, Inc.) cervical artificial disc or ACDF using structural allograft and an anterior plate.

RESULTS

A total of 269 patients were enrolled and randomly assigned to either CTDR (136 patients) or to ACDF (133 patients). There were no significant differences between the CTDR and ACDF groups when comparing operative time, blood loss, length of hospital stay, or the reoperation rate at the index level. The overall success rate was significantly greater in the CTDR group (85%) compared with the ACDF group (71%) (p = 0.05). In both groups, the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 24-month follow-up (p < 0.0001). Similarly, the VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 24-month follow-up (p < 0.0001). The range of motion (ROM) in the CTDR group decreased at 3 months but was significantly greater than the preoperative mean at 12- and 24-month follow-up. The ROM in the ACDF group was significantly reduced by 3 months and remained so throughout the follow-up. Adjacent-level degeneration was also evaluated in both groups from preoperatively to 2-year follow-up and was classified as none, mild, moderate, or severe. Preoperatively, there were no significant differences between groups when evaluating the different levels of adjacent-level degeneration. At the 2-year follow-up, there were significantly more patients in the ACDF group with severe adjacent-level radiographic changes (p < 0.0001). However, there were no significant differences between groups in adjacent-level reoperation rate (7.6% for the Kineflex|C group and 6.1% for the ACDF group).

CONCLUSIONS

Cervical total disc replacement allows for neural decompression and clinical results comparable to ACDF. Kineflex|C was associated with a significantly greater overall success rate than fusion while maintaining motion at the index level. Furthermore, there were significantly fewer Kineflex|C patients showing severe adjacent-level radiographic changes at the 2-year follow-up. These results from a prospective, randomized study support that Kineflex|C CTDR is a viable alternative to ACDF in select patients with cervical radiculopathy

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Management of Adult Hydrocephalus With Ventriculoperitoneal Shunts: Long-term Single- Institution Experience

Neurosurgery 69:774–781, 2011 DOI: 10.1227/NEU.0b013e31821ffa9e

Ventriculoperitoneal shunting is the most widely used neurosurgical procedure for the management of hydrocephalus.

OBJECTIVE: To evaluate our long-term single-institution experience in the management of adult hydrocephalus patients with ventriculoperitoneal shunts.

METHODS: Adult patients who underwent ventriculoperitoneal shunt placement for hydrocephalus from October 1990 to October 2009 were included. Medical charts, operative reports, imaging studies, and clinical follow-up evaluations were reviewed and analyzed retrospectively for clinical outcome in adult hydrocephalus patients.

RESULTS: A total of 683 adult patients were included in the study. The most common etiologies of hydrocephalus include idiopathic (29%), tumors and cysts (20%), postcraniotomy (13%), and subarachnoid hemorrhage (13%). The overall shunt failure rate was 32%, and the majority (74%) of shunt revisions occurred within the first 6 months. The median time to first shunt revision was 9.31 months. Etiology of hydrocephalus showed a significant impact on the incidence of shunt revision/failure and on the median time to shunt revision. Similarly, the type of hydrocephalus had a significant effect on the incidence of shunt failure and the median time to shunt revision.

CONCLUSION: A large proportion of patients (32%) experience shunt failure after shunt placement for hydrocephalus. Although the overall incidence of shunt revision was comparable to previously reported studies, the fact that a large proportion of adult populations with shunt placement experience shunt failure is a concern.

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A Proposed Grading System of Brain and Spinal Cavernomas

Neurosurgery 69:807–814, 2011 DOI: 10.1227/NEU.0b013e31821ffbb5
Most cavernomas in the central nervous system are characterized by a benign natural course. Progressive symptoms warrant surgical removal. In the literature, the factors affecting long-term postoperative outcome are not statistically well confirmed.
OBJECTIVE: To perform a multifactorial analysis of risk factors on a large patient series and to use the results to propose a simple grading scale to predict outcome.
METHODS: We studied 303 consecutive patients with cavernomas treated surgically at our department from 1980 to 2009. Follow-up assessment was performed on average 5.7 years postoperatively (range, 0.2-36 years). The main outcome measure was the patients’ condition at the last follow-up on Glasgow Outcome Scale. For statistical analysis, the outcome measure was dichotomized to favorable (Glasgow Outcome Scale 5) and unfavorable (Glasgow Outcome Scale 1-4). Binary logistic regression analysis was used to estimate the effect of age, sex, seizures, preexisting neurological deficits, hemorrhage, and size and location of cavernoma on long-term outcome.
RESULTS: Infratentorial, basal ganglia, or spinal location and preexisting neurological deficit were the only independent risk factors for unfavorable outcome, with relative risks of 2.7 (P = .008) and 3.2 (P = .002), respectively. We formulated a grading system based on a score of 1 to 3. When applied to our series, the proposed grading system strongly correlated with outcome (P < .001, Pearson x2 test). The risk for long-term unfavorable outcome was 13%, 22%, and 55% for grades 1 through 3, respectively.
CONCLUSION: The proposed grading system showed a convincing correlation with postoperative outcome in surgically treated cavernoma patients.
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Efficacy of endoport-guided endoscopic resection for deep-seated brain lesions

Neurosurg Rev (2011) 34:457–463.DOI 10.1007/s10143-011-0319-4

Surgery for deep-seated brain lesions without causing significant trauma to the overlying cortex is difficult because brain retraction is required to approach these lesions.

The aim of this study was to determine the efficacy of endoport-guided endoscopic or microscopic removal for deep-seated lesions using the neuronavigation system.

Between October 2008 and December 2009, 21 patients (17 men and 4 women; average age, 40.8 years) underwent endoport-guided endoscopic tumor removal. We adapted the transparent tubular conduit, so-called “endoport,” to target the lesions under the guidance of neuronavigation. We then determined the efficacy and limitations of this technique with fully endoscopic removal, compared with standard approaches using a spatula retractor. Gross total resection of the lesions was achieved in 14 of 21 patients (66%), and partial removal occurred in four (19%) patients. However, there was failure to remove the lesion through the endoport in three patients (14.3%), requiring the use of blade spatula retractors. In reviewing the seven cases with either failure or partial removal, it was found that a large tumor size (≥3 cm) and calcified lesions were the major factors limiting the application of this technique.

Endoport-guided endoscopic surgery facilitated an accurate and minimally invasive technique for removal of these deep-seated brain lesions. This procedure required a protracted learning curve although, when successful, this approach can minimize brain retraction and provide satisfactory visualization.

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Extension CT scan: its suitability for assessing fusion after posterior lumbar interbody fusion

Eur Spine J (2011) 20:1496–1502. DOI 10.1007/s00586-011-1739-0

Posterior lumbar interbody fusion (PLIF) is a popular procedure for treating lumbar canal stenosis with spinal instability, and several reports concerning fusion assessment methods exist. However, there are currently no definitive criteria for diagnosing a successful interbody fusion in the lumbar spine. We suggested evaluating fusion status using computed tomography (CT) in extension position to detect pseudoarthrosis more precisely.

The purpose of this study was to evaluate its usefulness for determining bone union quality after PLIF.

Eighty-one patients who underwent PLIF at 97 levels were retrospectively enrolled. The study population included 48 men and 33 women (mean age 58.9 years, range 21–85 years). Patients were followed up for more than 12 months after surgery. The mean follow-up period was 27.6 months (range 14–49 months). Fusion status was evaluated using three ways: flexion– extension radiographs, CT images in flexion and extension position. In the flexion–extension radiographs, mobility of more than 3 , a remaining clear zone, or an uncertain bone connection constituted an incomplete union. For CT images, a remaining clear zone, a gas pattern, or an uncertain bone connection constituted an incomplete union.

Flexion– extension radiographs demonstrated a solid fusion in 90.7% of the 97 levels at 10.7 months postoperatively. When fusion was demonstrated on flexion–extension radiographs, the rate of fusion affirmed by flexion CT and extension CT was 87.6 and 69.1% of the levels assessed, respectively. The rate of pseudoarthrosis detected on extension CT images was significantly higher than that on flexion–extension radiographs (P< 0.001) and flexion CT (P< 0.01). The rate of fusion achieved on extension CT was 85.6% at 15.1 months postoperatively.

Extension CT could detect pseudoarthrosis more clearly than flexion–extension radiography and flexion CT. The CT images are influenced by body position and dilating anterior disc space in extension CT contributes to detect pseudoarthrodesis. Thus, extension CT was a useful method for assessing fusion status after PLIF.

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A Detailed Analysis of Functional Magnetic Resonance Imaging in the Frontal Language Area: A Comparative Study With Extraoperative Electrocortical Stimulation

Neurosurgery 69:590–597, 2011 DOI: 10.1227/NEU.0b013e3182181be1

Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined.

OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS).

METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/ concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity.

RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity.

CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.

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Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients

Neurosurg Rev DOI 10.1007/s10143-011-0334-5

Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations.

Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median followup was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P=0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P=0.008 and P<0.001, respectively). The CCJ location was also related to a lower OS (P=0.043) and it was more common in young patients (P=0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease.

Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.

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Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial

J Neurosurg Spine 15:216–227, 2011. DOI: 10.3171/2011.4.SPINE10404

The study aimed to verify the safety and feasibility of applying acidic fibroblast growth factor (aFGF) with fibrin glue in combination with surgical neurolysis for nonacute spinal cord injury.

Methods. This open-label, prospective, uncontrolled human clinical trial recruited 60 patients with spinal cord injuries (30 cervical and 30 thoracolumbar). The mean patient age was 36.5 ± 15.33 (mean ± SD) years, and the male/ female ratio was 3:1. The mean time from injury to treatment was 25.7 ± 26.58 months, and the cause of injury included motor vehicle accident (26 patients [43.3%]), fall from a height (17 patients [28.3%]), sports (4 patients [6.7%]), and other (13 patients [21.7%]). Application of aFGF with fibrin glue and duraplasty was performed via laminectomy, and an adjuvant booster of combined aFGF and fibrin glue (2 ml) was given at 3 and 6 months postsurgery via lumbar puncture. Outcome measurements included the American Spinal Injury Association (ASIA) motor scores, sensory scores, impairment scales, and neurological levels. Examination of functional independence measures, visual analog scale, MR imaging, electrophysiological and urodynamic studies, hematology and biochemistry tests, tumor markers, and serum inflammatory cytokines were all conducted. All adverse events were monitored and reported. Exclusions were based on refusal, unrelated adverse events, or failure to participate in the planned rehabilitation.

Results. Forty-nine patients (26 with cervical and 23 with thoracolumbar injuries) completed the 24-month trial. Compared with preoperative conditions, the 24-month postoperative ASIA motor scores improved significantly in the cervical group (from 27.6 ± 15.55 to 37.0 ± 19.93, p < 0.001) and thoracolumbar group (from 56.8 ± 9.21 to 60.7 ± 10.10, p < 0.001). The ASIA sensory scores also demonstrated significant improvement in light touch and pinprick in both groups: from 55.8 ± 24.89 to 59.8 ± 26.47 (p = 0.049) and 56.3 ± 23.36 to 62.3 ± 24.87 (p = 0.003), respectively, in the cervical group and from 75.7 ± 15.65 to 79.2 ± 15.81 (p < 0.001) and 78.2 ± 14.72 to 82.7 ± 16.60 (p < 0.001), respectively, in the thoracolumbar group. At 24-month follow-up, the ASIA impairment scale improved significantly in both groups (30% cervical [p = 0.011] and 30% thoracolumbar [p = 0.003]). There was also significant improvement in neurological level in the cervical (from 5.17 ± 1.60 to 6.27 ± 3.27, p = 0.022) and thoracolumbar (from 18.03 ± 4.19 to 18.67 ± 3.96, p = 0.001) groups. The average sum of motor items in functional independence measure also had significant improvement in both groups (p < 0.05). The walking/wheelchair locomotion subscale showed increased percentages of patients who were ambulatory (from 3.4% to 13.8% and from 17.9% to 35.7% in the cervical and thoracolumbar groups, respectively). There were no related adverse events.

Conclusions. The use of aFGF for spinal cord injury was safe and feasible in the present trial. There were significant improvements in ASIA motor and sensory scale scores, ASIA impairment scales, neurological levels, and functional independence measure at 24 months after treatment. Further large-scale, randomized, and controlled investigations are warranted to evaluate the efficacy and long-term results.

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Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

Neuro-Oncology DOI:10.1093/neuonc/nor169

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma.

The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers.

With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver- operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.

In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.

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Meta-analysis of instrumented posterior interbody fusion versus instrumented posterolateral fusion in the lumbar spine

J Neurosurg Spine 15:295–310, 2011.DOI: 10.3171/2011.4.SPINE10330

The authors compared the effectiveness of instrumented posterior lumbar interbody fusion (iPLIF) and instrumented posterolateral fusion (iPLF) for the treatment of low-back pain (LBP) due to degenerative lumbar disease.

Methods. Relevant randomized controlled trials (RCTs) and comparative observational studies through December 2009 were identified using a retrieval strategy of sensitive and specific searches. The study design, participant characteristics, interventions, follow-up rate and period, and outcomes were abstracted after the assessment of methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group.
Results. Nine studies were identified—3 RCTs and 6 comparative observational studies. No significant difference was found between the 2 fusion procedures in the global assessment of clinical outcome (OR 1.51, 95% CI 0.71–3.22, p = 0.29) and complication rate (OR 0.55, 95% CI 0.16–1.86, p = 0.34). Both techniques were effective in reducing pain and improving functional disability, as well as restoring intervertebral disc height. Instrumented PLIF was more effective in achieving solid fusion (OR 2.60, 95% CI 1.35–5.00, p = 0.004), a lower reoperation rate (OR 0.20, 95% CI 0.03–1.29, p = 0.09), and better restoration of segmental angle and lumbar lordotic angle than iPLF. There were no significant differences between the fusion methods regarding blood loss (weighted mean difference –179.63, 95% CI –516.42 to 157.15, p = 0.30), and operating time (weighted mean difference 8.03, 95% CI –45.46 to 61.53, p = 0.77).

Conclusions. The authors’ analysis provided moderate-quality evidence that iPLIF has the advantages of higher fusion rate and better restoration of spinal alignment over iPLF. No significant differences were identified between iPLIF and iPLF concerning clinical outcome, complication rate, operating time, and blood loss.

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The Virchow-Robin spaces: delineation by magnetic resonance imaging with considerations on anatomofunctional implications

Childs Nerv Syst. DOI 10.1007/s00381-011-1574-y

The Virchow-Robin spaces (V-R spaces) are well-known, but not systematically understood fluid-filled perivascular spaces that allow the convexity and basal perforating vessels to penetrate deep into the cerebral parenchyma.

Objective This study aims to delineate anatomical characteristics of the normal V-R spaces by MR imaging with considerations on clinical and anatomofunctional implications of the V-R spaces.

Methods In this prospective study with 3T magnetic resonance (MR) imaging, the whole extent of the intracranial V-R spaces was classified into basal, cortical, subcortical, paraventricular, and brainstem segments, on the basis of the topological difference in 105 control subjects. Morphological characteristics in each segment of the V-R spaces are described. For comparison with the neuroimaging appearance, V-R spaces were histologically examined in cadaveric human brains. The physiological functions of the V-R spaces and pathognomonic implications of unusually dilated, but asymptomatic, V-R spaces encountered in five subjects are discussed.

Results The V-R spaces were found to form a complicated, while anatomically highly consistent, intraparenchymal canal network distributed over the whole cerebral hemispheres and connect the cerebral convexity, basal cistern, and ventricular system.

Conclusion The V-R spaces may be essential for drainage routes of cerebral metabolites, additional buoyancy for the brain, and maintenance of homogenous intracranial pressure. MR imaging may be more advantageous in depicting the V-R spaces than histological examination.

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Surgical Management of Craniopharyngiomas in Children: Meta-analysis and Comparison of Transcranial and Transsphenoidal Approaches

Neurosurgery 69:630–643, 2011 DOI: 10.1227/NEU.0b013e31821a872d

Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas.

OBJECTIVE: We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid.

METHODS: Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria.

RESULTS: Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages.

CONCLUSION: Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification.

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Safety and Efficacy of Microporous Polysaccharide Hemospheres in Neurosurgery

Neurosurgery 69[ONS Suppl 1]:ons49–ons63, 2011 DOI: 10.1227/NEU.0b013e3182155a52

Effective hemostasis is mandatory for brain tumor surgery. Microporous polysaccharide hemosphere (MPH) powder, a white powder compounded from potato starch, was recently introduced for surgical and emergency application.

OBJECTIVE: To evaluate the safety and efficacy of MPHs in brain tumor surgery.

METHODS: Thirty-three patients (mean age, 58 years; range, 22-84 years) underwent microsurgical brain tumor resection. Final hemostasis was performed by topical application of MPHs, video recorded, and subsequently analyzed. Blood samples were taken before surgery, before application of hemospheres, and postoperatively. Volume measurements of the tumor, resection cavity, and postoperative hematoma were done on magnetic resonance imaging and computed tomography scans. Clinical examinations focused on neurological outcome, complications, and allergic reactions.

RESULTS: Effective hemostasis was achieved by exclusive use of MPHs in 32 patients. In 1 patient, a single arterial bleeding underwent additional bipolar electrocauterization. Mean operative time was 156.8 minutes (range, 60-235 minutes). Hemostasis with MPHs required 57 seconds (mean; range, 8-202 seconds). Subjective neurosurgeons’ ranking of the hemostasis effect indicated excellent satisfaction. For the first 3 months, there was no hemospheres-related postoperative neurological worsening, no signs of allergic reaction, and no embolic complications. Early postoperative and 3-month follow-up magnetic resonance imaging and computed tomography scans excluded any expansive bleeding complication. As early as postoperative day 1, MPHs were no longer detected. There was no tumor mimicking contrast enhancement.

CONCLUSION: In neurosurgery, MPHs allow fast and effective minimally invasive hemostasis. In this small case series, no adverse reactions were found.

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