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Risk assessment of motor function using nTMS-based tractography

J Neurosurg 128:800–810, 2018

Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking (DTI FT) based on nTMS data are increasingly used for preoperative planning and resection guidance in patients suffering from motor-eloquent brain tumors. The present study explores whether nTMS-based DTI FT can also be used for individual preoperative risk assessment regarding surgery-related motor impairment.

METHODS Data derived from preoperative nTMS motor mapping and subsequent nTMS-based tractography in 86 patients were analyzed. All patients suffered from high-grade glioma (HGG), low-grade glioma (LGG), or intracranial metastasis (MET). In this context, nTMS-based DTI FT of the corticospinal tract (CST) was performed at a range of fractional anisotropy (FA) levels based on an individualized FA threshold ([FAT]; tracking with 50%, 75%, and 100% FAT), which was defined as the highest FA value allowing for visualization of fibers (100% FAT). Minimum lesion-to-CST distances were measured, and fiber numbers of the reconstructed CST were assessed. These data were then correlated with the preoperative, postoperative, and follow-up status of motor function and the resting motor threshold (rMT).

RESULTS At certain FA levels, a statistically significant difference in lesion-to-CST distances was observed between patients with HGG who had no impairment and those who developed surgery-related transient or permanent motor deficits (75% FAT: p = 0.0149; 100% FAT: p = 0.0233). In this context, no patient with a lesion-to-CST distance ≥ 12 mm suffered from any new surgery-related permanent paresis (50% FAT and 75% FAT). Furthermore, comparatively strong negative correlations were observed between the rMT and lesion-to-CST distances of patients with surgery-related transient paresis (Spearman correlation coefficient [rs]; 50% FAT: rs = –0.8660; 75% FAT: rs = –0.8660) or surgery-related permanent paresis (50% FAT: rs = –0.7656; 75% FAT: rs = –0.6763).

CONCLUSIONS This is one of the first studies to show a direct correlation between imaging, clinical status, and neurophysiological markers for the integrity of the motor system in patients with brain tumors. The findings suggest that nTMSbased DTI FT might be suitable for individual risk assessment in patients with HGG, in addition to being a surgery-planning tool. Importantly, necessary data for risk assessment were obtained without significant additional efforts, making this approach potentially valuable for direct clinical use.

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Management of spinal infection: a review of the literature

Acta Neurochirurgica (2018) 160:487–496

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2–7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient’s general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.

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Massive Brain Swelling and Death After Cranioplasty: A Systematic Review

World Neurosurg. (2018) 111:99-108.

Although cranioplasty is a common procedure, it may cause a variety of complications. Massive brain swelling after cranioplasty (MBSC) is an unusual complication that has been reported more frequently in recent years. Most of the existing information about this condition is speculative and the cause remains unclear.

METHODS: A PubMed and Scopus search adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed to include studies reporting patients with MBSC. Different information was analyzed in these cases to describe the characteristics and identify risk factors for MBSC.

RESULTS: The search yielded 19 articles with a total of 26 patients. All studies were case reports and small case series. In most patients, preoperative intracranial hypotension and a considerable degree of sinking of skin flap were identified; this was the only constant finding observed in these cases. In addition, we propose a grading system to estimate the degree of preoperative sinking of skin flap and an algorithm with recommendations to decrease the incidence of MBSC.

CONCLUSIONS: MBSC is an unusual, highly lethal, and probably underreported condition. The information gathered in this review indicates that MBSC occurs secondary to a cascade of pathologic events triggered by the bone flap implantation. This evidence suggests that the primary pathologic change is a sudden increase in the intracranial pressure acting on a brain chronically exposed to intracranial hypotension.

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Frontal Keyhole Craniotomy for Resection of Low- and High-Grade Gliomas

Neurosurgery 82:388–396, 2018

Minimally invasive techniques are increasingly being used to access intraaxial brain lesions.

OBJECTIVE: To describe a method of resecting frontal gliomas through a keyhole craniotomy and share the results with these techniques.

METHODS: We performed a retrospective review of data obtained on all patients undergoing resection of frontal gliomas by the senior author between 2012 and 2015.We describe our technique for resecting dominant and nondominant gliomas utilizing both awake and asleep keyhole craniotomy techniques.

RESULTS: After excluding 1 patient who received a biopsy only, 48 patients were included in the study. Twenty-nine patients (60%) had not received prior surgery. Twenty-six patients (54%) were diagnosed with WHO grade II/III tumors, and 22 patients (46%) were diagnosedwith glioblastoma. Twenty-five cases (52%)were performed awake.At least 90% of the tumor was resected in 35 cases (73%). Three of 43 patients with clinical follow-up experienced permanent deficits.

CONCLUSION: We provide our experience in using keyhole craniotomies for resecting frontal gliomas. Our data demonstrate the feasibility of using minimally invasive techniques to safely and aggressively treat these tumors.

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Fully endoscopic combined transsphenoidal and supraorbital keyhole approach for parasellar lesions

J Neurosurg 128:685–694, 2018

Parasellar tumors that extend far laterally beyond the internal carotid artery or that are fibrous and adhere firmly to critical structures are difficult to remove totally via the endoscopic transsphenoidal approach alone. In such cases, a combined transsphenoidal-transcranial approach is effective to achieve maximal resection in a single stage. In this paper, a new minimally invasive surgical technique for complicated parasellar lesions, a fully endoscopic combined transsphenoidal–supraorbital keyhole approach, is presented.

METHODS A retrospective review of patients who had been treated via a fully endoscopic combined transsphenoidal– supraorbital keyhole approach for complicated parasellar lesions was performed. The data for resection rate, perioperative mortality and morbidity, and postoperative outcomes were analyzed.

RESULTS A total of 12 fully endoscopic combined transsphenoidal–supraorbital keyhole approaches were performed from March 2013 to February 2016; 10 were for pituitary adenomas and 2 were for craniopharyngiomas. Gross-total resection or near-total resection was achieved in 7 of 12 cases. Among the 11 patients who had presented with preoperative visual disturbances, 7 had visual improvement. However, 1 patient showed deterioration in visual function. No patient experienced postoperative hemorrhage, needed additional surgical treatment, or had postoperative CSF leakage.

CONCLUSIONS In the combined transsphenoidal and transcranial approach, safe and effective cooperative manipulation with 2 surgical corridors can be performed for complicated parasellar lesions. The goal of this procedure is not to achieve gross-total resection, but to achieve safe resection. Moreover, this new surgical approach offers neurosurgeons a simpler operative field with less invasiveness than the conventional microscopic combined approach. The fully endoscopic combined endonasal–supraorbital keyhole approach is an efficacious procedure for complicated parasellar lesions with acceptable results.

 

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Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Banana-Shaped and Straight Cages: Radiological and Clinical Results from a Prospective Randomized Clinical Trial

Neurosurgery 82:289–298, 2018

In minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF), cage type and position play important roles in fusion achievement and sagittal alignment correction. However, no prospective randomized comparison of the results using different types of cage has been reported to date.

OBJECTIVE: To compare the radiological and clinical outcomes of unilateral MIS-TLIF using 2 types of cage.

METHODS: All candidates for single-level MIS-TLIF were randomized into banana-shaped cage and straight-cage groups. Plain radiographs and computed tomography scans were used for assessment of cage positions, fusion status, disc height, segmental lordotic angle, cage subsidence, and pelvic parameters. Clinical outcome was assessed using visual analog scale and Oswestry Disability Index scores.

RESULTS: Forty-four and 40 consecutive patients were operated on using banana-shaped and straight cages, respectively. Cage position was more anterior and lateral in the straightcage group and more medial and posterior in the banana-shaped cage group. Solid fusion was achieved in 95.2% and 96.6% of the 2 groups, respectively, at 12 mo. The change in disc height and segmental lordotic angle postoperatively was significantly greater in the banana-shaped cage group. The incidence of subsidence during follow-up was significantly higher in the banana-shaped cage group (P<.04). Clinically, the visual analog scale and Oswestry Disability Index scores decreased significantly after surgery in both groups, with no significant difference between the groups.

CONCLUSION: Our preliminary outcomes suggest that the subsidence rate may be higher using banana-shaped cages in MIS-TLIF, possibly due to their more medial final position.

 

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Stereotactic radiosurgery in the treatment of parasellar meningiomas: long-term volumetric evaluation

J Neurosurg 128:362–372, 2018

Parasellar meningiomas tend to invade the suprasellar, cavernous sinus, and petroclival regions, encroaching on adjacent neurovascular structures. As such, they prove difficult to safely and completely resect. Stereotactic radiosurgery (SRS) has played a central role in the treatment of parasellar meningiomas. Evaluation of tumor control rates at this location using simplified single-dimension measurements may prove misleading. The authors report the influence of SRS treatment parameters and the timing and volumetric changes of benign WHO Grade I parasellar meningiomas after SRS on long-term outcome.

METHODS Patients with WHO Grade I parasellar meningiomas treated with single-session SRS and a minimum of 6 months of follow-up were selected. A total of 189 patients (22.2% males, n = 42) form the cohort. The median patient age was 54 years (range 19–88 years). SRS was performed as a primary upfront treatment for 44.4% (n = 84) of patients. Most (41.8%, n = 79) patients had undergone 1 resection prior to SRS. The median tumor volume at the time of SRS was 5.6 cm3 (0.2–54.8 cm3). The median margin dose was 14 Gy (range 5–35 Gy). The volumes of the parasellar meningioma were determined on follow-up scans, computed by segmenting the meningioma on a slice-by-slice basis with numerical integration using the trapezoidal rule.

RESULTS The median follow-up was 71 months (range 6–298 months). Tumor volume control was achieved in 91.5% (n = 173). Tumor progression was documented in 8.5% (n = 16), equally divided among infield recurrences (4.2%, n = 8) and out-of-field recurrences (4.2%, n = 8). Post-SRS, new or worsening CN deficits were observed in 54 instances, of which 19 involved trigeminal nerve dysfunction and were 18 related to optic nerve dysfunction. Of these, 90.7% (n = 49) were due to tumor progression and only 9.3% (n = 5) were attributable to SRS. Overall, this translates to a 2.64% (n = 5/189) incidence of direct SRS-related complications. These patients were treated with repeat SRS (6.3%, n = 12), repeat resection (2.1%, n = 4), or both (3.2%, n = 6). For patients treated with a margin dose ≥ 16 Gy, the 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progression-free survival rates are 100%, 100%, 95.7%, 95.7%, 95.7%, 95.7%, and 95.7%, respectively. Patients treated with a margin dose < 16 Gy, had 2-, 4-, 6-, 8-, 10-, 12-, and 15-year actuarial progressionfree survival rates of 99.4%, 97.7%, 95.1%, 88.1%, 82.1%, 79.4%, and 79.4%, respectively. This difference was deemed statistically significant (p = 0.043). Reviewing the volumetric patient-specific measurements, the early follow-up volumetric measurements (at the 3-year follow-up) reliably predicted long-term volume changes and tumor volume control (at the 10-year follow-up) (p = 0.029).

CONCLUSIONS SRS is a durable and minimally invasive treatment modality for benign parasellar meningiomas. SRS offers high rates of growth control with a low incidence of neurological deficits compared with other treatment modalities for meningiomas in this region. Volumetric regression or stability during short-term follow-up of 3 years after SRS was shown to be predictive of long-term tumor control.

 

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Fronto-orbitozygomatic approach: functional and cosmetic outcomes in a series of 169 patients

J Neurosurg 128:466–474, 2018

Advantages of the fronto-orbitozygomatic (FOZ) approach have been reported extensively in the literature; nevertheless, restoration of normal anatomy and the esthetic impact of surgery are increasingly important issues for patients and neurosurgeons. The aim of this study was to analyze functional and cosmetic outcomes in a series of 169 patients with different pathologies who underwent surgery in which the FOZ approach was used.

METHODS Between January 2000 and December 2014, 250 consecutive patients underwent surgery with an FOZ approach as the primary surgical treatment. Follow-up data were available for only 169 patients; 103 (60.9%) of these patients were female and 66 (39.1%) were male, and their ages ranged from 6 to 77 years (mean 46.9 years; SD 15.6 years). Mean follow-up time was 66 months (range 6–179 months; SD 49.5 months). Evaluation of clinical outcomes was performed with a focus on 4 main issues: surgical complications, functional outcome, cosmetic outcome, and patient satisfaction. The additional time needed to perform orbitotomy and orbital reconstruction was also evaluated.

RESULTS The permanent postoperative complications included forehead hypesthesia (41.4%) and dysesthesia (15.3%), frontal muscle weakness (10.3%), exophthalmos (1.4%), enophthalmos (4.1%), diplopia (6.6%; 2% were related to surgical approach), and persistent periorbital and eyelid swelling (3%). Approximately 90% of the patients reported subjectively that surgery did not affect their quality of life or complained of only minor problems that did not influence their quality of life significantly. The mean time needed for orbitotomy and orbital reconstruction was approximately half an hour.

CONCLUSIONS Comprehensive knowledge of the potential complications and overall clinical outcomes of the FOZ approach can be of great utility to neurosurgeons in balancing the well-known benefits of the approach with potential additional morbidities.

 

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Endonasal endoscopic pituitary surgery in the elderly

J Neurosurg 128:429–436, 2018

Pituitary adenomas are benign, slow-growing tumors that cause symptoms either through mass effect or hormone overproduction. The decision to operate on a healthy young person is relatively straightforward. In the elderly population, however, the risks of complications may increase, rendering the decision more complex. Few studies have documented the risks of surgery using the endonasal endoscopic approach in a large number of elderly patients. The purpose of this study was to audit a single center’s data regarding outcomes of purely endoscopic endonasal transsphenoidal resection of pituitary adenomas in elderly patients and to compare them to the current literature.

METHODS A retrospective review of a prospectively acquired database of all endonasal endoscopic surgeries done by the senior authors was queried for patients aged 60–69 years and for those aged 70 years or older. Demographic and radiographic preoperative data were reviewed. Outcomes with respect to extent of resection and complications were examined and compared with appropriate statistical tests.

RESULTS A total of 135 patents were identified (81 aged 60–69 years and 54 aged 70 years or older [70+]). The average tumor diameter was slightly larger for the patients in the 70+ age group (mean [SD] 25.7 ± 9.2 mm) than for patients aged 60–69 years (23.1 ± 9.8 mm, p = 0.056). There was no significant difference in intraoperative blood loss (p > 0.99), length of stay (p = 0.22), or duration of follow-up (p = 0.21) between the 2 groups. There was a 7.4% complication rate in patients aged 60–69 years (3 nasal and 3 medical complications) and an 18.5% complication rate in patients older than 70 years (4 cranial, 3 nasal, 1 visual, and 2 medical complications; p = 0.05 overall and 0.013 for cranial complications). Cranial complications in the 70+ age category included 2 postoperative hematomas, 1 pseudoaneurysm formation, and 1 case of symptomatic subdural hygromas.

CONCLUSIONS Endonasal endoscopic surgery in elderly patients is safe, but there is a graded increase in complication rates with increasing age. The decision to operate on an asymptomatic or mildly symptomatic patient in these age groups should take this increasing complication rate into account. The use of a lumbar drain or lumbar punctures should be weighed against the risk of subdural hematoma in patients with preexisting atrophy.

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Clival chordomas: considerations after 16 years of endoscopic endonasal surgery

J Neurosurg 128:329–338, 2018

In the past decade, the role of the endoscopic endonasal approach (EEA) has relevantly evolved for skull base tumors. In this study, the authors review their surgical experience with using an EEA in the treatment of clival chordomas, which are deep and infiltrative skull base lesions, and they highlight the advantages and limitations of this ventral approach.

METHODS All consecutive cases of chordoma treated with an EEA between 1998 and 2015 at a single institution are included in this study. Preoperative assessment consisted of neuroimaging (MRI and CT with angiography sequences) and endocrinological, neurological, and ophthalmological evaluations, which were repeated 3 months after surgery and annually thereafter. Postoperative adjuvant therapies were considered.

RESULTS Sixty-five patients (male/female ratio 1:0.9) were included in this study. The median age was 48 years (range 9–80 years). Gross-total resection (GTR) was achieved in 47 cases (58.7%). On univariate analysis, primary procedures (p = 0.001), location in the superior or middle third of the clivus (p = 0.043), extradural location (p = 0.035), and histology of conventional chordomas (p = 0.013) were associated with a higher rate of GTR. The complication rate was 15.1%, and there were no perioperative deaths. Most complications did not result in permanent sequelae and included 2 CSF leaks (2.5%), 5 transient cranial nerve VI palsies (6.2%), and 2 internal carotid artery injuries (2.5%), which were treated with coil occlusion of the internal carotid artery without neurological deficits. Three patients (3.8%) presented with complications resulting in permanent neurological deficits due to a postoperative hematoma (1.2%) causing a hemiparesis, and 2 permanent ophthalmoplegias (2.5%). Seventeen patients (26.2%) have died of tumor progression over the course of follow-up (median 52 months, range 7–159 months). Based on Kaplan-Meier analysis, the survival rate was 77% at 5 years and 57% at 10 years. On multivariate analysis, the extent of tumor removal (p = 0.001) and the absence of previous treatments (p = 0.001) proved to be correlated with a longer survival rate.

CONCLUSIONS The EEA was associated with a high rate of tumor removal and symptom control, with low morbidity and preservation of a good quality of life. These results allow for a satisfactory overall survival rate, particularly after GTR and for primary surgery. Considering these results, the authors believe that an EEA can be a helpful tool in chordoma surgery, achieving a good balance between as much tumor removal as possible and the preservation of an acceptable patient quality of life.

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Navigated 3D–ultrasound versus conventional neuronavigation during awake resections of eloquent low-grade gliomas

Acta Neurochir (2018) 160:331–342

The data showing usefulness of navigated 3D– ultrasound (3DUS) during awake resections of eloquent gliomas are sparse. Results of surgeries performed using 3DUS were never compared to procedures guided by standard neuronavigation. The aim of this work is to assess the effectiveness of 3DUS during awake resections of eloquent low-grade gliomas (LGGs) by comparing surgical results of two series of patients operated on using conventional neuronavigation and using 3DUS. To our knowledge, a similar study is lacking in the literature.

Methods During a 4-year period (September 2006 to August 2010) 21 awake resections of LGGs guided by neuronavigation (series 1, S1) were consecutively performed in Department of Neurosurgery in Bratislava. During another 4-year period (August 2010 to July 2014) 28 awake resections of LGGs guided by 3DUS (series 2, S2) were consecutively conducted. In both patients series, the eloquent cortical and subcortical structures were intraoperatively detected by direct electrical stimulation. Extent of tumor resection (EOR) and functional outcome in both series were compared.

Results EOR was significantly greater (p = 0.022) in S2 (median = 93.25%; mean = 86.79%), as compared to S1 (median 87.1%; mean = 75.85%). One permanent minor deficit in S1 and 2 minor deficits in S2 occurred, the difference was not significant (p = 0.999).

Conclusions Our work represents the first study comparing results of surgeries guided by 3DUS versus conventional navigation. The extent of awake resections of eloquent LGG guided by 3DUS was greater comparing to awake resections guided by standard neuronavigation; use of 3DUS had no impact on the number of new permanent deficits.

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The surgical treatment of tumors of the fourth ventricle

J Neurosurg 128:339–351, 2018

Fourth ventricle tumors are rare, and surgical series are typically small, comprising a single pathology, or focused exclusively on pediatric populations. This study investigated surgical outcome and complications following fourth ventricle tumor resection in a diverse patient population. This is the largest cohort of fourth ventricle tumors described in the literature to date.

METHODS This is an 18-year (1993–2010) retrospective review of 55 cases involving patients undergoing surgery for tumors of the fourth ventricle. Data included patient demographic characteristics, pathological and radiographic tumor characteristics, and surgical factors (approach, surgical adjuncts, extent of resection, etc.). The neurological and medical complications following resection were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were reviewed to determine patient recovery. Patient, tumor, and surgical factors were analyzed to determine factors associated with the frequently encountered postoperative neurological complications.

RESULTS There were no postoperative deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of patients experienced at least 1 major neurological complication, while 31% had minor complications only. New or worsening gait/focal motor disturbance (56%), speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most common neurological deficits in the immediate postoperative period. Of these, cranial nerve deficits were the least likely to resolve at follow-up. Multivariate analysis showed that patients undergoing a transvermian approach had a higher incidence of postoperative cranial nerve deficits, gait disturbance, and speech/swallowing deficits than those treated with a telovelar approach. The use of surgical adjuncts (intraoperative navigation, neurophysiological monitoring) did not significantly affect neurological outcome. Twenty-two percent of patients required postoperative CSF diversion following tumor resection. Patients who required intraoperative ventriculostomy, those undergoing a transvermian approach, and pediatric patients (< 18 years old) were all more likely to require postoperative CSF diversion. Twenty percent of patients suffered at least 1 medical complication following tumor resection. Most complications were respiratory, with the most common being postoperative respiratory failure (14%), followed by pneumonia (13%).

CONCLUSIONS The occurrence of complications after fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae were frequent, but a substantial number of patients had neurological improvement at long-term followup. Of the neurological complications analyzed, postoperative cranial nerve deficits were the least likely to completely resolve at follow-up. Of all the patient, tumor, and surgical variables included in the analysis, surgical approach had the most significant impact on neurological morbidity, with the telovelar approach being associated with less morbidity.

 

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Transcondylar approach for resection of lateral medullary cavernous malformation

Acta Neurochir (2018) 160:291–294

Resection of a medullary cavernous malformation requires aggressive exposure, but there is controversy on how much occipital condyle can be safely removed during the transcondylar approach.

Method We describe and demonstrate the use of the transcondylar approach to a medullary cavernous malformation, with emphasis on adequate surgical exposure while preserving the atlanto-occipital joint.

Conclusions Despite conservative handling of the occipital condyle, craniocervical stability may vary in patients after transcondylar surgery. A “dynamic” computer tomography, with views of the atlanto-occipital joint at each end-rotational extreme, may be the best postoperative assessment tool to evaluate the stability of the craniocervical junction.

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Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma

J Clin Oncol 36. © 2018

https://doi.org/10.1200/JCO.2017.75.8219

DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients.

Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens.

Results In group A (n = 25), 20% of patients survived > 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in >3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8+ and T-bet+ cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration.

Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent highgrade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.

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Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy

Acta Neurochirurgica (2018) 160:317–324

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions.

Methods This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis.

Results Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%.

Conclusions Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

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Brainstem Cavernous Malformations: Surgical Indications Based on Natural History and Surgical Outcomes

World Neurosurg. (2018) 110:55-63

Cavernous malformations (CMs) are uncommon lesions occurring in the central nervous system, with an incidence of approximately 0.5% in the general population and constituting 5%e10% of all intracranial vascular malformations. Among CMs, prevalence within the brainstem as reported in the literature has ranged from 4% to 35%. With their precarious location and potentially devastating clinical events, brainstem CMs have attracted attention from neurosurgeons, and with these surgeons’ unrelenting efforts, the microsurgical techniques to treat these lesions in the brainstem have greatly improved in recent decades. Although surgical outcomes reported in the literature have been satisfying, surgical intervention has become increasingly contraindicated because of the tendency for a benign clinical course in brainstem CMs, after weighing this fact against the high risk of surgical morbidity. Thus, it is advisable to operate on patients with symptomatic lesions abutting the pial or ependymal surface of the brainstem or where lesions are accessible to safe entry zones, which have caused more than 1 significantly symptomatic hemorrhage and can be defined as aggressive. However, treatment remains controversial for deep-seated lesions away from the surface of the brainstem or lesions that are inaccessible to safe entry zones. Other treatments, such as radiosurgery and medication, are still debatable, which might be as an alternative for lesions amenable to but at high risk with surgery.

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Design and Testing of 2 Novel Scores That Predict Global Sagittal Alignment Utilizing Cervical or Lumbar Plain Radiographs

Neurosurgery 82:163–171, 2018

Global sagittal deformity is an established cause of disability. However, measurements of sagittal alignment are often ignored when patients present with symptoms localizing to the cervical or lumbar spine.

OBJECTIVE: To develop scoring scales to predict the risk of sagittal malalignment in patients with only cervical or lumbar spine radiographs.

METHODS: A retrospective review of a prospectively maintained multicenter adult spinal deformity database was performed. Primary outcome (sagittal malalignment) was defined as a C7 plumbline ≥ 50 mm. Two multivariate logistic regressions were performed using patient characteristics and measurements derived from cervical or lumbar radiographs as covariates. Point scores were assigned to age, body mass index (BMI), and lumbar lordosis or T1 slope by rounding their ß coefficients to the nearest integer.

RESULTS: Nine hundred seventy-nine patients were included, with 652 randomly assigned to the derivation cohort (used to build the score) and 327 comprising the validation set. Final cervical score for the primary outcome included BMI ≥ 25 (1 point), age ≥ 55 yr (2 points), and T1 slope ≥ 27º (2 points). Final lumbar score for the primary outcome included BMI≥25 (1 point), age≥55 yr (1 point), and lumbar lordosis ≥45º (–1 points). High scores for both the cervical and lumbar spine presented with high specificity and positive likelihood ratios of sagittal malalignment.

CONCLUSION: We developed scoring scales to predict global sagittal malalignment utilizing clinical covariates and cervical or lumbar radiographs. Patients with high scores may prompt imaging with long-cassette plain films to evaluate for global sagittal imbalance.

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Surgical approach to posterior inferior cerebellar artery aneurysms

Acta Neurochir (2018) 160:295–299

The far-lateral is a standardised approach to clip aneurysms of the posterior inferior cerebellar artery (PICA). Different variants can be adopted to manage aneurysms that differ in morphology, topography, ruptured status, cerebellar swelling and surgeon preference.

Method We distinguished five paradigmatic approaches aimed to manage aneurysms that are: proximal unruptured; proximal ruptured requiring posterior fossa decompression (PFD); proximal ruptured not requiring PFD; distal unruptured; distal ruptured.

Conclusions Preoperative planning in the setting of PICA aneurysm surgery is of paramount importance to perform an effective and safe procedure, to ensure an adequate PFD and optimal proximal control before aneurysm manipulation.

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Medina® Embolization Device for the Treatment of Intracranial Aneurysms

Neurosurgery 82:155–162, 2018

The Medina Embolization Device (MED) is a new concept device that combines the design of a detachable coil and the one of an intrasaccular flow disruption device.

OBJECTIVE: To evaluate the feasibility, safety, and 6- to 9-mo effectiveness of this new device for the treatment of intracranial wide-necked aneurysms.

METHODS:Twelve patients (10 females,meanage=56 yr)with 13 wide-necked intracranial aneurysms (3 ruptured; 10 unruptured) were treated by means of the MED from January 2015 to October 2015. In 15% of the cases, MEDs were used in a standalone fashion; in 85% of the cases, additional regular coils were used. Adjunctive compliant balloon was used in 4 of 13 cases (31%). Procedure-related complications were systematically recorded; discharge and 6- to 9-mo follow-up modified Rankin Scale was assessed. Angiographic follow-up was performed with a mean delay of 5.5 ± 1.7 mo. Occlusion rate was evaluated in postprocedure and at midterm follow-up using the Roy–Raymond scale.

RESULTS: The deployment of the MED was feasible in all cases. No perforation was recorded. One case of thromboembolic complication was observed in a ruptured anterior communicating artery aneurysm, without any clinical consequence at follow-up. Grade A occlusion rate was 61.5% in postprocedure and 83% at 6-mo follow-up. Two cases (17%) of recanalization were documented angiographically.

CONCLUSION: The MED is a new generation device combining the design of a detachable coil and an intrasaccular flow disruption device. According to our early experience, this device is safe and provides a satisfactory occlusion rate at angiographic follow-up of 6mo.

 

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Dual-labeling with 5–aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas

J Neurosurg 128:399–405, 2018

Fluorescence guidance with 5–aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue.

METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System).

RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green braintissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection.

CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

 

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