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Silviu Sabou, Apostolos Lagaras, Rajat Verma, Irfan Siddique and Saeed Mohammad

OBJECTIVE

Sagittal imbalance and loss of lumbar lordosis are the main drivers of functional disability in adult degenerative scoliosis. The main limitations of the classic posterior lumbar interbody fusion technique are increased risk of neurological injury and suboptimal correction of the segmental lordosis. Here, the authors describe the radiological results of a modified posterior lumbar interbody fusion and compare the results with a historical cohort of patients.

METHODS

Eighty-two consecutive patients underwent surgical treatment for degenerative scoliosis/kyphosis in a single tertiary referral center for complex spinal surgery. Fifty-five patients were treated using the classic multilevel posterior lumbar interbody fusion (MPLIF) technique and 27 were treated using the modified MPLIF technique to include a release of the anterior longitudinal ligament (ALL) and the annulus. A radiographic review of both series of patients was performed by two independent observers. Functional outcomes were obtained, and patients were registered in the European Spine Tango registry.

RESULTS

The mean L4–5 disc angle increased by 3.14° in the classic MPLIF group and by 12.83° in MPLIF plus ALL and annulus release group. The mean lumbar lordosis increased by 15.23° in the first group and by 25.17° in the second group. The L4–S1 lordosis increased on average by 4.92° in the classic MPLIF group and increased by a mean of 23.7° in the MPLIF plus ALL release group when both L4–5 and L5–S1 segments were addressed. There were significant improvements in the Core Outcome Measures Index and EQ-5D score in both groups (p < 0.001). There were no vascular or neurological injuries observed in either group.

CONCLUSIONS

The authors’ preliminary results suggest that more correction can be achieved at the disc level using posterior-based ALL and annulus release in conjunction with posterior lumbar interbody fusion. They demonstrate that ALL and annulus release can be performed safely using a posterior-only approach with minimal risk of vascular injury. However, the authors recommend that this approach should only be used by surgeons with considerable experience in anterior and posterior spinal surgery.

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Günther Deuschl, Kenneth A. Follett, Ping Luo, Joern Rau, Frances M. Weaver, Steffen Paschen, Frank Steigerwald, Lisa Tonder, Valerie Stoker and Domenic J. Reda

OBJECTIVE

Several randomized studies have compared the effect of deep brain stimulation (DBS) of the subthalamic nucleus with the best medical treatment in large groups of patients. Important outcome measures differ between studies. Two such major studies, the life-quality study of the German Competence Network for Parkinson’s disease (LQ study) and the US Veterans Affairs/National Institute of Neurological Disorders and Stroke trial (VA/NINDS trial), were compared here in order to understand their differences in outcomes.

METHODS

Unless otherwise noted, analyses were based on those subjects in each study who received a DBS implant (LQ study 76 patients, VA/NINDS trial 140 patients) and who had data for the measurement under consideration (i.e., no imputations for missing data), referred to hereafter as the “as-treated completers” (LQ 69 patients, VA/NINDS 125 patients). Data were prepared and analyzed by biostatisticians at the US Department of Veterans Affairs Cooperative Studies Program Coordinating Center, the Coordinating Center for Clinical Trials Marburg, and Medtronic, under the direction of two authors (G.D. and K.A.F.). Data were extracted from the respective databases into SAS data sets and analyzed using SAS software. Analyses were based on the 6-month follow-up data from both studies because this was the endpoint for the LQ study.

RESULTS

Pre-DBS baseline demographics differed significantly between the studies, including greater levodopa responsiveness (LDR) in the LQ study population than in the VA/NINDS group. After DBS, LQ subjects demonstrated greater improvement in motor function (Unified Parkinson’s Disease Rating Scale, Motor Examination [UPDRS-III]), activities of daily living (ADLs), and complications of therapy. Medication reduction and improvements in life quality other than ADLs were not significantly different between LQ and VA/NINDS subjects. When the two populations were compared according to pre-DBS LDR, the “full responders” to levodopa (≥ 50% improvement on UPDRS-III with medication) in the two studies showed no significant difference in motor improvement with DBS (LQ 18.5 ± 12.0–point improvement on UPDRS-III vs VA/NINDS 17.7 ± 15.6–point improvement, p = 0.755). Among levodopa full responders, ADLs improved slightly more in the LQ group, but scores on other UPDRS subscales and the Parkinson’s Disease Questionnaire-39 were not significantly different between the two studies.

CONCLUSIONS

This comparison suggests that patient selection criteria, especially preoperative LDR, are the most important source of differences in motor outcomes and quality of life between the two studies.

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Anja I. Srienc, Pei-Pei Chiang, Abby J. Schmitt and Eric A. Newman

OBJECTIVE

Cortical spreading depolarization (CSD) has been linked to poor clinical outcomes in the setting of traumatic brain injury, malignant stroke, and subarachnoid hemorrhage. There is evidence that electrocautery during neurosurgical procedures can also evoke CSD waves in the brain. It is unknown whether blood contacting the cortical surface during surgical bleeding affects the frequency of spontaneous or surgery-induced CSDs. Using a mouse neurosurgical model, the authors tested the hypothesis that electrocautery can induce CSD waves and that surgical field blood (SFB) is associated with more CSDs. The authors also investigated whether CSD can be reliably observed by monitoring the fluorescence of GCaMP6f expressed in neurons.

METHODS

CSD waves were monitored by using confocal microscopy to detect fluorescence increases at the cortical surface in mice expressing GCaMP6f in CamKII-positive neurons. The cortical surface was electrocauterized through an adjacent burr hole. SFB was simulated by applying a drop of tail vein blood to the brain through the same burr hole.

RESULTS

CSD waves were readily detected in GCaMP6f-expressing mice. Monitoring GCaMP6f fluorescence provided far better sensitivity and spatial resolution than detecting CSD events by observing changes in the intrinsic optical signal (IOS). Forty-nine percent of the CSD waves identified by GCaMP6f had no corresponding IOS signal. Electrocautery evoked CSD waves. On average, 0.67 ± 0.08 CSD events were generated per electrocautery episode, and multiple CSD waves could be induced in the same mouse by repeated cauterization (average, 7.9 ± 1.3 events; maximum number in 1 animal, 13 events). In the presence of SFB, significantly more spontaneous CSDs were generated (1.35 ± 0.37 vs 0.13 ± 0.16 events per hour, p = 0.002). Ketamine effectively decreased the frequency of spontaneous CSD waves (1.35 ± 0.37 to 0.36 ± 0.15 CSD waves per hour, p = 0.016) and electrocautery-stimulated CSD waves (0.80 ± 0.05 to 0.18 ± 0.08 CSD waves per electrocautery, p = 0.00002).

CONCLUSIONS

CSD waves are detected with far greater sensitivity and fidelity by monitoring GCaMP6f signals in neurons than by monitoring IOSs. Electrocautery reliably evokes CSD waves, and the frequency of spontaneous CSD waves is increased when blood is applied to the cortical surface. These experimental conditions recapitulate common scenarios in the neurosurgical operating room. Ketamine, a clinically available pharmaceutical agent, can block stimulated and spontaneous CSDs. More research is required to understand the clinical importance of intraoperative CSD.

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Victoria L. Morgan, Baxter P. Rogers, Adam W. Anderson, Bennett A. Landman and Dario J. Englot

OBJECTIVE

The objectives of this study were to identify functional and structural network properties that are associated with early versus long-term seizure outcomes after mesial temporal lobe epilepsy (mTLE) surgery and to determine how these compare to current clinically used methods for seizure outcome prediction.

METHODS

In this case-control study, 26 presurgical mTLE patients and 44 healthy controls were enrolled to undergo 3-T MRI for functional and structural connectivity mapping across an 8-region network of mTLE seizure propagation, including the hippocampus (left and right), insula (left and right), thalamus (left and right), one midline precuneus, and one midline mid-cingulate. Seizure outcome was assessed annually for up to 3 years. Network properties and current outcome prediction methods related to early and long-term seizure outcome were investigated.

RESULTS

A network model was previously identified across 8 patients with seizure-free mTLE. Results confirmed that whole-network propagation connectivity patterns inconsistent with the mTLE model predict early surgical failure. In those patients with networks consistent with the mTLE network, specific bilateral within-network hippocampal to precuneus impairment (rather than unilateral impairment ipsilateral to the seizure focus) was associated with mild seizure recurrence. No currently used clinical variables offered the same ability to predict long-term outcome.

CONCLUSIONS

It is known that there are important clinical differences between early surgical failure that lead to frequent disabling seizures and late recurrence of less frequent mild seizures. This study demonstrated that divergent network connectivity variability, whole-network versus within-network properties, were uniquely associated with these disparate outcomes.

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Qinghua Zhao, Benlong Shi, Xu Sun, Zhen Liu, Hao Su, Yang Li, Zezhang Zhu and Yong Qiu

OBJECTIVE

Intraspinal anomalies associated with congenital scoliosis (CS) complicate the decision-making process for spinal correction surgery in CS patients. Recently, deformity correction surgery without prior prophylactic neurological intervention has been recognized to be safe in CS patients with intact or stable neurological status. However, no case-control study has identified the surgical outcomes and risks of spinal correction surgery in this patient population. The authors sought to investigate the safety and efficacy of spinal correction surgery for CS associated with untreated intraspinal anomalies (split cord malformation [SCM], tethered cord, and/or syringomyelia) with intact or stable neurological status.

METHODS

A group of CS patients with intraspinal anomalies (CS+IA) and another group of CS patients without intraspinal anomalies (CS-IA) undergoing 1-stage posterior correction surgery were retrospectively reviewed. The radiographic and clinical outcomes and postoperative complications were compared between the 2 groups.

RESULTS

There were 57 patients in the CS+IA group and 184 patients in the CS-IA group. No significant difference was observed in age, sex, spinal curve pattern, main Cobb angle, and flexibility of the main curve between the 2 groups (p > 0.05 for all). The postoperative correction rates of the major curve were comparable between the 2 groups (53.5% vs 55.7% for the CS+IA and CS-IA groups, respectively, p > 0.05). No significant difference was observed in the incidence of either implant-related or neurological complications between 2 groups. No patients in the CS+IA group developed neurological complications, whereas 1 patient in the CS-IA group experienced transient weakness of the left lower extremity after surgery.

CONCLUSIONS

Coexisting intraspinal anomalies (SCM, tethered cord, and/or syringomyelia) in CS patients with normal or stable neurological status do not significantly increase the risk of neurological complications of correction surgery. Prophylactic neurosurgical intervention for intraspinal anomalies before correction surgery might be unnecessary for these patients.

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Eun Young Han, He Wang, Dershan Luo, Jing Li and Xin Wang

OBJECTIVE

For patients with multiple large brain metastases with at least 1 target volume larger than 10 cm3, multifractionated stereotactic radiosurgery (MF-SRS) has commonly been delivered with a linear accelerator (LINAC). Recent advances of Gamma Knife (GK) units with kilovolt cone-beam CT and CyberKnife (CK) units with multileaf collimators also make them attractive choices. The purpose of this study was to compare the dosimetry of MF-SRS plans deliverable on GK, CK, and LINAC and to discuss related clinical issues.

METHODS

Ten patients with 2 or more large brain metastases who had been treated with MF-SRS on LINAC were identified. The median planning target volume was 18.31 cm3 (mean 21.31 cm3, range 3.42–49.97 cm3), and the median prescribed dose was 27.0 Gy (mean 26.7 Gy, range 21–30 Gy), administered in 3 to 5 fractions. Clinical LINAC treatment plans were generated using inverse planning with intensity modulation on a Pinnacle treatment planning system (version 9.10) for the Varian TrueBeam STx system. GK and CK planning were retrospectively performed using Leksell GammaPlan version 10.1 and Accuray Precision version 1.1.0.0 for the CK M6 system. Tumor coverage, Paddick conformity index (CI), gradient index (GI), and normal brain tissue receiving 4, 12, and 20 Gy were used to compare plan quality. Net beam-on time and approximate planning time were also collected for all cases.

RESULTS

Plans from all 3 modalities satisfied clinical requirements in target coverage and normal tissue sparing. The mean CI was comparable (0.79, 0.78, and 0.76) for the GK, CK, and LINAC plans. The mean GI was 3.1 for both the GK and the CK plans, whereas the mean GI of the LINAC plans was 4.1. The lower GI of the GK and CK plans would have resulted in significantly lower normal brain volumes receiving a medium or high dose. On average, GK and CK plans spared the normal brain volume receiving at least 12 Gy and 20 Gy by approximately 20% in comparison with the LINAC plans. However, the mean beam-on time of GK (∼ 64 minutes assuming a dose rate of 2.5 Gy/minute) plans was significantly longer than that of CK (∼ 31 minutes) or LINAC (∼ 4 minutes) plans.

CONCLUSIONS

All 3 modalities are capable of treating multiple large brain lesions with MF-SRS. GK has the most flexible workflow and excellent dosimetry, but could be limited by the treatment time. CK has dosimetry comparable to that of GK with a consistent treatment time of approximately 30 minutes. LINAC has a much shorter treatment time, but residual rotational error could be a concern.

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Sahin Hanalioglu, Balkan Sahin, Omer Selcuk Sahin, Abdulbaki Kozan, Melih Ucer, Ulas Cikla, Steven L. Goodman and Mustafa K. Baskaya

OBJECTIVE

In daily practice, neurosurgeons face increasing numbers of patients using aspirin (acetylsalicylic acid, ASA). While many of these patients discontinue ASA 7–10 days prior to elective intracranial surgery, there are limited data to support whether or not perioperative ASA use heightens the risk of hemorrhagic complications. In this study the authors retrospectively evaluated the safety of perioperative ASA use in patients undergoing craniotomy for brain tumors in the largest elective cranial surgery cohort reported to date.

METHODS

The authors retrospectively analyzed the medical records of 1291 patients who underwent elective intracranial tumor surgery by a single surgeon from 2007 to 2017. The patients were divided into three groups based on their perioperative ASA status: 1) group 1, no ASA; 2) group 2, stopped ASA (low cardiovascular risk); and 3) group 3, continued ASA (high cardiovascular risk). Data collected included demographic information, perioperative ASA status, tumor characteristics, extent of resection (EOR), operative blood loss, any hemorrhagic and thromboembolic complications, and any other complications.

RESULTS

A total of 1291 patients underwent 1346 operations. The no-ASA group included 1068 patients (1112 operations), the stopped-ASA group had 104 patients (108 operations), and the continued-ASA group had 119 patients (126 operations). The no-ASA patients were significantly younger (mean age 53.3 years) than those in the stopped- and continued-ASA groups (mean 64.8 and 64.0 years, respectively; p < 0.001). Sex distribution was similar across all groups (p = 0.272). Tumor locations and pathologies were also similar across the groups, except for deep tumors and schwannomas that were relatively less frequent in the continued-ASA group. There were no differences in the EOR between groups. Operative blood loss was not significantly different between the stopped- (186 ml) and continued- (220 ml) ASA groups (p = 0.183). Most importantly, neither hemorrhagic (0.6%, 0.9%, and 0.8%, respectively; p = 0.921) nor thromboembolic (1.3%, 1.9%, and 0.8%; p = 0.779) complication rates were significantly different between the groups, respectively. In addition, the multivariate model revealed no statistically significant predictor of hemorrhagic complications, whereas male sex (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.7–20.5, p = 0.005) and deep-extraaxial-benign (“skull base”) tumors (OR 3.6, 95% CI 1.3–9.7, p = 0.011) were found to be independent predictors of thromboembolic complications.

CONCLUSIONS

In this cohort, perioperative ASA use was not associated with the increased rate of hemorrhagic complications following intracranial tumor surgery. In patients at high cardiovascular risk, ASA can safely be continued during elective brain tumor surgery to prevent potential life-threatening thromboembolic complications. Randomized clinical trials with larger sample sizes are warranted to achieve a greater statistical power.

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William P. Nobis, Karina A. González Otárula, Jessica W. Templer, Elizabeth E. Gerard, Stephen VanHaerents, Gregory Lane, Guangyu Zhou, Joshua M. Rosenow, Christina Zelano and Stephan Schuele

OBJECTIVE

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death for patients with refractory epilepsy, and there is increasing evidence for a centrally mediated respiratory depression as a pathophysiological mechanism. The brain regions responsible for a seizure’s inducing respiratory depression are unclear—the respiratory nuclei in the brainstem are thought to be involved, but involvement of forebrain structures is not yet understood. The aim of this study was to analyze intracranial EEGs in combination with the results of respiratory monitoring to investigate the relationship between seizure spread to specific mesial temporal brain regions and the onset of respiratory dysfunction and apnea.

METHODS

The authors reviewed all invasive electroencephalographic studies performed at Northwestern Memorial Hospital (Chicago) since 2010 to identify those cases in which 1) multiple mesial temporal electrodes (amygdala and hippocampal) were placed, 2) seizures were captured, and 3) patients’ respiration was monitored. They identified 8 investigations meeting these criteria in patients with temporal lobe epilepsy, and these investigations yielded data on a total of 22 seizures for analysis.

RESULTS

The onset of ictal apnea associated with each seizure was highly correlated with seizure spread to the amygdala. Onset of apnea occurred 2.7 ± 0.4 (mean ± SEM) seconds after the spread of the seizure to the amygdala, which was significantly earlier than after spread to the hippocampus (10.2 ± 0.7 seconds; p < 0.01).

CONCLUSIONS

The findings suggest that activation of amygdalar networks is correlated with central apnea during seizures. This study builds on the authors’ prior work that demonstrates a role for the amygdala in voluntary respiratory control and suggests a further role in dysfunctional breathing states seen during seizures, with implications for SUDEP pathophysiology.

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Matthew D. Hall, Yazmin Odia, Joshua E. Allen, Rohinton Tarapore, Ziad Khatib, Toba N. Niazi, Doured Daghistani, Lee Schalop, Andrew S. Chi, Wolfgang Oster and Minesh P. Mehta

Diffuse intrinsic pontine gliomas (DIPGs) frequently harbor the histone H3 K27M mutation. Gliomas with this mutation commonly overexpress dopamine receptor (DR) D2 and suppress DRD5, leading to enhanced sensitivity to DRD2 antagonism. This study reports the first clinical experience with the DRD2/3 antagonist ONC201 as a potential targeted therapy for H3 K27M–mutant DIPG. One pediatric patient (a 10-year-old girl) with H3 K27M–mutant DIPG was enrolled in an investigator-initiated, IRB-approved compassionate-use study and began single-agent ONC201 treatment 1 month after completing radiotherapy. The study endpoints were clinical and radiographic response (primary) and toxicities (secondary).

The patient presented with House-Brackmann grade IV facial palsy and unilateral hearing loss. MRI demonstrated a 2.3 × 2.1 × 2.8–cm pontomedullary tumor. Stereotactic biopsy confirmed H3 K27M–mutated DIPG. The tumor was treated with radiotherapy, but 1 month after completion of that treatment, the tumor and neurological symptoms showed only minimal change, and ONC201 treatment was initiated as described above. The tumor volume sequentially decreased by 26%, 40%, and 44% over the next 6 months, and remained stable at 18 months. Ipsilateral hearing normalized and the facial palsy improved to House-Brackmann grade I by 4 months. After 1 year of ONC201 treatment, 2 new lesions were identified outside of the prior high-dose radiotherapy volume. The patient was treated with dexamethasone, bevacizumab, and additional focal radiotherapy to these new tumors. These tumors remained stable in size over the subsequent 6 months on MRI. To date, no adverse events have been observed or reported due to ONC201. The patient remains clinically improved as of the latest follow-up visit, 19 months after starting ONC201 and 22 months from diagnosis. This case supports further investigation of this novel agent targeting H3 K27M–mutated DIPG.