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2-Hydroxyglutarate magnetic resonance spectroscopy in adult brainstem glioma

Hirofumi Iwahashi, Hiroaki Nagashima, Kazuhiro Tanaka, Takiko Uno, Mitsuru Hashiguchi, Masahiro Maeyama, Yuichiro Somiya, Masato Komatsu, Takanori Hirose, Tomoo Itoh, Ryohei Sasaki, and Takashi Sasayama

OBJECTIVE

Adult brainstem gliomas (BSGs) are rare tumors of the CNS that are poorly understood. Upregulation of the oncometabolite 2-hydroxyglutarate (2HG) in the tumor indicates the mutation of isocitrate dehydrogenase (IDH), which can be detected by magnetic resonance spectroscopy (MRS). Although histological examination is required for the definitive diagnosis of BSG, 2HG-optimized MRS (2HG-MRS) may be useful, considering the difficult nature of brainstem lesion biopsy. The aim of this study was to evaluate the utility of 2HG-MRS for diagnosing IDH-mutant adult BSG.

METHODS

Patients with a radiographically confirmed brainstem tumor underwent 3T MRS. A single voxel was set in the lesion with reference to the T2 or fluid-attenuated inversion recovery image and analyzed according to the 2HG-tailored MRS protocol (point-resolved spectroscopic sequence; echo time 35 msec). All patients underwent intraoperative navigation-guided or CT-guided stereotactic biopsy for histopathological diagnosis. The status of IDH and H3K27M mutations was confirmed by immunohistochemistry and direct DNA sequencing. In addition, the authors examined the relationship between patients’ 2HG concentrations and survival time.

RESULTS

Ten patients (7 men, 3 women; median age 33.5 years) underwent 2HG-MRS and biopsy. Four patients had an H3K27M mutation and 4 had an IDH1 mutation (1 R132H canonical IDH mutation, 2 R132S and 1 R132G noncanonical IDH mutations). Two had neither H3K27M nor IDH mutations. The H3K27M and IDH mutations were mutually exclusive. Most tumors were located in the pons. There was no significant radiological difference between mutant H3K27M and IDH on a conventional MRI sequence. A 2HG concentration ≥ 1.8 mM on MRS demonstrated 100% (95% CI 28%–100%) sensitivity and 100% (95% CI 42%–100%) specificity for IDH-mutant BSG (p = 0.0048). The median overall survival was 10 months in IDH–wild-type BSG patients (n = 6) and could not be estimated in IDH-mutant BSG patients (n = 4) due to the small number of deaths (p = 0.008).

CONCLUSIONS

2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.

In Journal of Neurosurgery Publish Before Print

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Association of calcium channel blockers with lower incidence of intracranial aneurysm rupture and growth in hypertensive patients

*Qingyuan Liu, Jiangan Li, Yisen Zhang, Xinyi Leng, Mahmud Mossa-Basha, Michael R. Levitt, Shuo Wang, and Chengcheng Zhu

OBJECTIVE

Calcium channel blockers (CCBs) are antihypertensive agents with potential vascular protection effects. This study investigated whether CCB usage was associated with a lower incidence of unruptured intracranial aneurysm (UIA) instability (growth and rupture) in patients with hypertension.

METHODS

UIA patients were included in two prospective, multicenter cohort studies (IARP-CP and 100-Project cohorts). All patients received conservative treatment and were regularly followed up every 6 months by CT angiography for 2 years. Patients taking CCBs at least 5 days per week were considered CCB users; otherwise, they were considered non-CCB users. The primary endpoint was UIA instability (rupture, growth of > 20% and/or 1 mm in any dimension, or appearance of a new dome irregularity on imaging follow-up).

RESULTS

A total of 392 UIA patients with hypertension (191 male, 201 female; median age 57 years) were included with a mean follow-up duration of 21.7 ± 5.2 months. The primary endpoint was met in 81 patients (20.7%) during follow-up, including 68 patients with aneurysms that grew and 13 with aneurysms that ruptured. CCB users had a lower UIA instability rate than non-CCB users (27/237 [11.4%] vs 54/155 [34.8%], p < 0.001). Multivariable Cox analysis demonstrated that CCB use was associated with a lower risk of UIA instability (HR 0.37, 95% CI 0.22–0.61; p < 0.001). The protective effect of CCB use was consistent in patients taking a single antihypertensive agent (HR 0.22, 95% CI 0.12–0.40; p < 0.001) and patients taking > 1 antihypertensive agent (HR 0.42, 95% CI 0.20–0.87; p = 0.021). For patients with controlled hypertension, CCB use was still associated with a lower risk of UIA instability (HR 0.22, 95% CI 0.09–0.52; p = 0.001).

CONCLUSIONS

In UIA patients with hypertension, CCB use was associated with a lower incidence of aneurysm instability.

In Journal of Neurosurgery Publish Before Print

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Comparison of the Contour Neurovascular System and Woven EndoBridge device for treatment of wide-necked cerebral aneurysms at a bifurcation or sidewall

Constantin Hecker, Erasmia Broussalis, Johannes A. R. Pfaff, Slaven Pikija, Christoph J. Griessenauer, and Monika Killer-Oberpfalzer

OBJECTIVE

The authors compared the Contour Neurovascular System (Contour) with the Woven EndoBridge (WEB) device for the treatment of wide-necked cerebral aneurysms at a bifurcation or sidewall.

METHODS

Prospective clinical and radiological data were collected for all patients treated with either the Contour or WEB at a tertiary university hospital from May 2018 to June 2022.

RESULTS

In patients who had at least 3 months of follow-up data available (median patient age 60.0 [IQR 51.8–67.0] years, male/female ratio 1:1.4), the authors compared 40 aneurysms in 34 patients treated with the Contour and 30 aneurysms in 30 patients treated with the WEB. Overall, 26 middle cerebral artery, 24 anterior communicating artery, 9 basilar artery tip, 4 posterior communicating artery, 4 internal carotid artery, 1 anterior cerebral artery, 1 posterior inferior cerebellar artery, and 1 superior cerebellar artery aneurysm were treated. In the Contour cohort, complete occlusion at last follow-up was achieved for 30 aneurysms (75%) and a small neck remnant was seen in 6 aneurysms (15%), summing up to an adequate occlusion rate of 90%. One aneurysm (2.5%) had to be retreated, and 1 symptomatic thromboembolic event (2.5%) was observed with complete remission at discharge. Three adjunctive stents (10%) had to be used due to branch occlusion. In the WEB cohort, adequate occlusion was also seen in 90% of aneurysms (complete occlusion in 19 [63.3%] and remnant neck in 8 [26.7%], with a retreatment rate of 20%). Four WEBs (13.3%) needed additional stent placement due to device protrusion into a branch, 2 asymptomatic thromboembolic events (6.7%) were noted, and 1 major ischemic event (3.3%) due to M2 occlusion was noted. One patient treated with the WEB died between follow-ups of causes unrelated to the aneurysm, treatment, or device. Time from first measurement to deployment and thus total treatment time was significantly shorter in the Contour group (p = 0.004), regardless of whether a prior angiogram was available for aneurysm measurement and device sizing.

CONCLUSIONS

Results for the Contour were promising, although longer follow-up is necessary to draw more solid conclusions on the utility and risk profile of this new device compared with the already widely used WEB device. Adequate occlusion at last follow-up was the same for both devices, whereas the probability of complete occlusion at last follow-up was significantly higher for the Contour, and the WEB showed a significantly higher retreatment rate. Median deployment times were significantly shorter with the Contour than the WEB.

In Journal of Neurosurgery Publish Before Print

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Editorial. Pitfalls in the practice of neurosurgery: identifying those at greatest risk

William T. Couldwell, Robert E. Harbaugh, and James T. Rutka

In Journal of Neurosurgery Publish Before Print

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Improvement of postural stability and gait velocity after cervical decompression surgery in patients with cervical spondylotic myelopathy

Hamid Hassanzadeh, Jon Raso, Pramod N. Kamalapathy, Evan Dooley, Varun Puvanesarajah, Lawal Labaran, Eric Solomon, Brook A. Mitchell, and Shawn Russell

OBJECTIVE

Cervical spondylotic myelopathy (CSM) is a progressive degenerative condition that can lead to significant neurological deficits, including gait instability. Biomechanical alterations of gait and its various components are poorly understood. The goal of the current study was to determine how spatiotemporal gait parameters, as well as postural and dynamic stability, change after surgery in CSM patients.

METHODS

A total of 47 subjects were included, with 23 test subjects and 24 controls. Baseline measurements were made for both cohorts. In the CSM cohort, repeat measurements were made at 3 and 6 months postoperatively. To record spatiotemporal and dynamic stability parameters, subjects performed walking trials over force plates on a 15-m runway. To assess postural stability, standing balance trials were conducted on a floor-mounted force plate. Three-dimensional motion analysis cameras and gait modeling software were used to quantify and visually represent results. Statistical analysis was completed using repeated-measures ANOVA and paired t-tests. Significance was set at p < 0.05.

RESULTS

CSM patients had significantly increased gait velocity at the 6-month follow-up (mean 0.948 ± 0.248 m/sec/leg length) versus baseline (mean 0.852 ± 0.257 m/sec/leg length) (p = 0.039). The tilted ellipse area was significantly decreased at the 6-month follow-up compared with baseline (mean 979.8 ± 856.7 mm2 vs 598.0 ± 391.1 mm2, p = 0.018). Angular momentum excursion was not significantly different between baseline and the 3- and 6-month follow-ups.

CONCLUSIONS

CSM patients displayed significant improvement in gait velocity and postural stability parameters after decompressive surgery. Dynamic stability parameters did not change significantly during the study period.

In Journal of Neurosurgery: Spine Publish Before Print

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Influence of the living Pareto chart and data transparency on patient outcomes in neurosurgery

Helen H. Shi, Sixia Chen, Laura Propester, Jami Valenzuela, Joanna Gernsback, Virendra R. Desai, Karl Balsara, Kristin Zieles, and Andrew Jea

OBJECTIVE

Quality improvement (QI) tools are increasingly being used to calibrate healthcare quality. Achieving healthcare quality is essential, as there is a movement toward value-based healthcare delivery. Visual management, such as a living Pareto chart, is a strategy for improvement within the QI framework. The authors herein hypothesized that transparency of data through a living Pareto chart is a powerful way to improve patient outcomes and gain clinical efficiency.

METHODS

The authors retrospectively reviewed patient outcomes and complications; cerebrospinal fluid (CSF) leaks; shunt, baclofen, and other surgical site infections; readmission rates; and same- or next-day appointments in a cohort of patients at the Riley Hospital for Children from November 1, 2016, to May 31, 2020. Similarly, they reviewed neurosurgical outcomes and complications at a second institution, the Oklahoma Children’s Hospital, where a living Pareto chart was utilized from February 1, 2021, to March 31, 2022. The discrete frequency and rates per month of outcomes and complications were graphed on scatterplots, Pearson correlation coefficients were calculated to measure the strength of the relationship between event frequency and time, and best-fit lines illustrated the relationship between those points through the least-squares method.

RESULTS

At both the Riley Hospital for Children and Oklahoma Children’s Hospital, the use of a living Pareto chart to display data transparently was associated with decreasing infections, and it was associated with decreasing readmissions at Riley. On the other hand, it encouraged same- or next-day clinic appointments to be offered to patients and families. Interestingly, CSF leaks were not mitigated with data transparency alone.

CONCLUSIONS

Transparency is a driver of change in patient, provider, and institutional behaviors. It is an essential element of QI and patient safety, as well as building a culture of trust. Readmissions, infections, and same- or next-day appointments were influenced by the living Pareto chart; however, CSF leaks remained recalcitrant to data transparency. Other QI strategies may be necessary to positively affect the occurrence of CSF leaks in neurosurgery.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Intraoperative stimulation mapping of thalamocortical tracts in asleep and awake settings: novel electrophysiological, anatomical, and tractographic paradigms

Anna Alexandratou, Rania-Iman Virjee, Aisha Ghare, Viktoria Sefcikova, Caroline Micallef, Laura Mancini, Manni Waraich, D. Ceri Davies, Hannah Keeble, and George Samandouras

OBJECTIVE

Despite the disabling deficits of motor apraxia and sensory ataxia resulting from intraoperative injury of the superior thalamocortical tracts (TCTs), region-specific electrophysiological localization is currently lacking. Herein, the authors describe a novel TCT mapping paradigm.

METHODS

Three patients, 1 asleep and 2 awake, underwent glioma resection affecting primarily the somatosensory cortex and underlying TCT. Stimulation was performed at the median, ulnar, and posterior tibial nerves. Parameters comprised single anodal pulses (duration 200–500 μsec, 2.1–4.7 Hz) with a current ranging from 10 to 25 mA. Recordings were captured with a bipolar stimulation probe, avoiding the classic collision technique. Positive localization sites were used to tractographically reconstruct the TCT in the third case.

RESULTS

Employing one electrophysiological paradigm, the TCT was localized subcortically in all 3 cases by using a bipolar probe, peak range of 19.6–29.2 msec, trough of 23.3–34.8 msec, stimulation range of 10–25 mA. In the last case, tractographic reconstruction of the TCT validated a highly accurate TCT localization within a specific region of the posterior limb of the internal capsule.

CONCLUSIONS

The authors describe the first electrophysiological technique for intraoperative localization and protection of the TCT in both asleep and awake craniotomies with tractographic validation, while avoiding the collision paradigm. None of the above paradigms have been previously reported. More data are required to further validate this technique.

In Journal of Neurosurgery Publish Before Print

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Letter to the Editor. Ruptured AVMs in children

David C. Lauzier, Anja I. Srienc, Samuel J. Cler, and Joshua W. Osbun

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Long-tunneled versus short-tunneled external ventricular drain: a quasi-experimental study in a cohort of pediatric patients

Amparo Saenz, Juan Pablo Mengide, Romina Argañaraz, and Beatriz Mantese

OBJECTIVE

The primary aim of this study was to compare external ventricular drain (EVD)–related infection rates and mechanical complications between long-tunneled EVDs (LTEVDs) with an interposed valve and short-tunneled EVDs (STEVDs) in a cohort of pediatric patients. The second objective was to compare hospital resources used for LTEVDs versus STEVDs in the same cohort of patients and the same study period.

METHODS

The study consisted of a quasi-experimental investigation comparing a prospective group of patients who received LTEVDs with a retrospective (historic) cohort of patients treated with STEVDs. The prospective nonrandomized quasi-experimental protocol of the LTEVD cohort included patients who needed an EVD for more than 3 days. Data were recorded prospectively as the patients were added to the study, until reaching the sample size established by the protocol. The comparison group of the STEVD cohort was retrospectively collected from patients’ records. Patients were included consecutively, from newest to oldest, starting with the last STEVD inserted at the authors’ hospital until reaching the sample size established in the protocol. The inclusion and exclusion criteria for both groups were the same.

RESULTS

One hundred thirty-four patients were included in this quasi-experimental study; there were 67 in each group. LTEVDs reduced the odds of having an EVD-related infection by 92% (OR 0.08, 95% CI 0.01–0.39; p = 0.002). Compared to STEVDs, the LTEVDs reduced by 69% the odds of having a CSF leak (OR 0.31, 95% CI 0.10–0.91; p = 0.03). Neither CSF blockage (OR 0.12, 95% CI 0.01–1.08; p = 0.06) nor displacement (OR 0.73, 95% CI 0.15–3.43; p = 0.69) showed a statistically significant difference between groups. More resources were allocated to STEVDs than to LTEVDs in most areas considered in this study.

CONCLUSIONS

Compared to STEVDs, LTEVDs are a cost-effective and safe method to reduce EVD-related infection rates and other complications in pediatric patients. The authors believe that reducing the infection rate and complications and giving the patient more independence outweighs the additional costs that this new technique may entail.

In Journal of Neurosurgery: Pediatrics Publish Before Print

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Natural history of antiplatelet nonresponders undergoing carotid artery stenting

Sandeep Muram, Kapilan Panchendrabose, Matthew E. Eagles, Mohammed S. Abdul Salam, Muneer Eesa, Ejaife O. Agbani, Michael D. Hill, Jay Riva-Cambrin, and Alim P. Mitha

OBJECTIVE

Routine antiplatelet responsiveness testing for patients undergoing carotid artery stenting procedures is not performed at most endovascular centers and remains a topic of controversy within the neurointerventional community. The objective of this study was to determine if nonresponsiveness to acetylsalicylic acid or clopidogrel was associated with the development of symptomatic thromboembolic events in patients undergoing carotid stenting procedures.

METHODS

A prospective study was conducted at the Foothills Medical Centre in Calgary, Alberta, Canada, from August 2019 to July 2021. Patients undergoing carotid artery stenting procedures and who were receiving dual antiplatelet therapy were enrolled in the study. Responsiveness to the antiplatelet medications was determined through whole blood impedance aggregometry. The primary outcome was development of a symptomatic thromboembolic event within 90 days after the procedure. The treating physicians were blinded to the aggregometry results for the duration of the study.

RESULTS

One hundred two procedures were performed in 100 patients. Eight thromboembolic events (8%) occurred during the study. Age (p = 0.03) and nonresponsiveness to clopidogrel (p = 0.003) were associated with the development of thromboembolic events. The multivariable model showed that clopidogrel nonresponsiveness was independently associated with the development of a thromboembolic event (adjusted OR 6.14, 95% CI 1.25–30.11, p = 0.03).

CONCLUSIONS

This study demonstrated that patients who were identified as clopidogrel nonresponders, using whole blood impedance aggregometry, were at an increased risk of developing thromboembolic events. Larger studies are needed to assess the utility of routine platelet function testing prior to carotid artery stenting procedures.

In Journal of Neurosurgery Publish Before Print