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Localized anaplastic lymphoma kinase–positive histiocytosis in a cerebellar hemisphere with long-term treatment: illustrative case

Eita Kumagai, Mio Tanaka, Fuminori Iwasaki, Masakatsu Yanagimachi, Daisuke Hirokawa, Hiroaki Goto, and Yukichi Tanaka

BACKGROUND

Anaplastic lymphoma kinase (ALK)–positive histiocytosis (ALK-H) is an emerging entity in the category of histiocytic neoplasms that was first reported as a multisystemic disease in three infants in 2008. The clinicopathological spectrum of ALK-H has been expanded to include localized disorders in specific organs, but the features of this subtype are not well known. The authors report a case of ALK-H localized in the central nervous system that was difficult to treat and review the relevant literature.

OBSERVATIONS

The authors reviewed archival histiocytic tumors at their institute and found a pediatric case of ALK-H localized in a cerebellar hemisphere that had previously been reported as histiocytic sarcoma. Chemotherapy (approximately 1 year), additional surgery, and conventional chemotherapy (approximately 2.5 years) led to clinical remission, and maintenance chemotherapy was continued (approximately 1.5 years). Three years after completing treatment, a high-grade glioma was found in a cerebral hemisphere, and the patient died of the glioma 2 years later.

LESSONS

Although the prognosis of ALK-H is generally good according to prior cases, the authors’ case required long-term conventional chemotherapy, suggesting the tumor displayed aggressive characteristics. Early administration of ALK inhibitors may be necessary.

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An anatomo-functional study of the interactivity between the paracentral lobule and the primary motor cortex

Yusuke Kimura, Shoto Yamada, Katsuya Komatsu, Rei Enatsu, Ryota Sato, Chie Kamada, Ayaka Sasagawa, Tsukasa Hirano, Masayasu Arihara, and Nobuhiro Mikuni

OBJECTIVE

The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain.

METHODS

This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)—the convexity and the interhemispheric fissure—that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed.

RESULTS

Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients.

CONCLUSIONS

This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

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Assessing pediatric neurosurgery capacity in La Paz, Bolivia: an illustrative institutional experience of a lower-middle-income country in South America

Victor M. Lu, Jorge Daniel Brun, Toba N. Niazi, and Jorge David Brun

OBJECTIVE

The current pediatric neurosurgery capacity in lower-middle-income countries (LMICs) in South America is poorly understood. Correspondingly, the authors sought to interrogate the neurosurgical inpatient experience of the sole publicly funded pediatric hospital in one of the largest regional departments of Bolivia to better understand this capacity.

METHODS

A retrospective review of all neurosurgical procedures performed at the Children’s Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria") between 2019 and 2023 was conducted after institutional approval using a recently implemented national electronic medical record system.

RESULTS

A total of 475 neurosurgical admissions satisfied inclusion for analysis over the 5-year span. The majority of admissions were from within the La Paz Department (87%) via the emergency department (77%), without private insurance (83%). The most common indications for neurosurgical intervention were trauma (35%), followed by hydrocephalus (28%), congenital disease (12%), infection (5%), and craniosynostosis (3%). Overall, the median age at time of surgery was 2.0 years, and the median operating time was 1.5 hours with a minority of intraoperative complications (2%). The most common inpatient complication was unplanned return to the operating room (19%), most commonly seen in congenital indications. At final discharge, the median postoperative length of stay was 10 days. Twenty-seven (6%) of the 475 patients died during hospitalization, most commonly seen in tumor indications. Of the 448 patients who were discharged, 299 (67%) returned for at least one follow-up appointment.

CONCLUSIONS

There is restricted breadth in neurosurgical indications and outcomes achievable at the Children’s Hospital of La Paz, Bolivia. As such, the capacity of pediatric neurosurgery at institutions in LMICs in South America such as this one is very limited. Identifying and prioritizing actionable interventions to improve this capacity is institution- and LMIC-dependent, and as such, future efforts will need to be tailored appropriately.

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Contemporary cohort of cerebral cavernous malformations: natural history and utility of follow-up MRI

Kelly D. Flemming, Robert D. Brown Jr., and Giuseppe Lanzino

OBJECTIVE

This study reports the natural history of cerebral cavernous malformations (CCMs) in a contemporary cohort with prospectively collected data from multiple sources, access to follow-up imaging, integrated electronic medical records, and detailed imaging review by study investigators. The authors aimed to define the first prospective symptomatic hemorrhage (SH) and severe SH rates, determine the risk of a second prospective SH, and identify risk factors for SH.

METHODS

From a prospectively maintained database of adult patients with radiologically defined CCM, those with radiation-induced CCM, those who underwent surgery within 3 months postdiagnosis, and those with < 1 year of follow-up were excluded. The patients’ medical history and radiological features of the CCM were recorded at the time of diagnosis. Follow-up annual written surveys were completed for 5 years after the initial diagnosis and then semiannually thereafter in addition to medical record and follow-up imaging review. Outcomes of interest included SH and severe SH.

RESULTS

Of 315 patients, 58.7% were female and 19.7% had familial CCMs. At diagnosis, 37.1% of patients had ruptured CCMs and 28.9% of the CCMs were located in the brainstem. The 5-year cumulative rates of prospective SH and severe SH in those with ruptured CCMs at diagnosis were 41.2% and 12.8%, respectively, compared with 6.1% and 2.5% in patients with unruptured CCMs at diagnosis (p < 0.0001). Risk factors for prospective SH included a ruptured CCM at diagnosis and persistent or new hyperintensity on T1-weighted MRI performed > 3 months after baseline MRI. For those with a ruptured CCM at diagnosis, the risk of developing a second prospective SH was similar to that of developing a first SH.

CONCLUSIONS

In a contemporary cohort of adult patients with CCM, the authors report 5-year SH and severe SH rates, rates of second prospective hemorrhage, and predictors of SH. Persistent or new hyperintensity on T1-weighted MRI may be a useful marker of disease activity.

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Design and radiological confirmation of 3-column cortical bone trajectory in the lumbar spine

Jia-Qi Wang, Ren-Jie Zhang, Lu-Ping Zhou, Chong-Yu Jia, Bo Zhang, Rui Sheng, Shu Fang, and Cai-Liang Shen

OBJECTIVE

The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis.

METHODS

Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed.

RESULTS

Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width.

CONCLUSIONS

Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.

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Do expandable cage size and number of cages matter in transforaminal lumbar interbody fusion at L5–S1? A comparative biomechanical analysis using finite element modeling

Mohamad Bakhaidar, Balaji Harinathan, Karthik Banurekha Devaraj, Narayan Yoganandan, and Saman Shabani

OBJECTIVE

Expandable transforaminal lumbar interbody fusion (TLIF) cages were designed to address the limitations of static cages. Bilateral cage insertion can potentially enhance stability, fusion rates, and segmental lordosis. However, the benefits of unilateral versus bilateral expandable cages with varying sizes in TLIF remain unclear. This study used a validated finite element spine model to compare the biomechanical properties of L5–S1 TLIF by using differently sized expandable cages inserted unilaterally or bilaterally.

METHODS

A finite element model of X-PAC expandable lumbar cages was created and used at the L5–S1 level. This model had cage dimensions of 9 mm in height, 15° in lordosis, and varying widths and lengths. Various placements (unilateral vs bilateral) and sizes were examined under pure moment loading to evaluate range of motion, adjacent-segment motion, and endplate stress.

RESULTS

Stability at the L5–S1 level decreased when smaller cages were used in both the unilateral and bilateral cage models. In the unilateral model, cage 1 (the smallest cage) resulted in 47.9% more motion at the L5–S1 level compared to cage 5 (the largest cage) in flexion, as well as 64.8% more motion in extension. Similarly, in the bilateral TLIF model, bilateral cage 1 led to 49.4% more motion at the L5–S1 level in flexion and 73.4% more motion in extension compared to bilateral cage 5. Unilateral insertion of cage 5 provided superior stability in flexion and surpassed cages 1–3 in extension when compared to cages inserted either unilaterally or bilaterally. Reduced motion at L5–S1 correlated with increased adjacent-segment motion at L4–5. Bilateral TLIF resulted in greater adjacent-segment motion compared to unilateral TLIF with the same-size cages. Inferior endplates experienced higher stress during flexion and extension than superior endplates, with this difference being more pronounced in the bilateral model. In bilateral cage placement, stress differences ranged from 46.3% to 60.0%, while they ranged from 1.1% to 9.6% in unilateral cages. Qualitative analysis revealed increased focal stress in unilateral cages versus bilateral cages.

CONCLUSIONS

The authors’ study shows that using a large unilateral TLIF cage may offer better stability than the bilateral insertion of smaller cages. While large bilateral cages increase adjacent-segment motion, they also provide a uniform stress distribution on the endplates. These findings deepen our understanding of the biomechanics of the available expandable TLIF cages.

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Examining barriers to care: a retrospective cohort analysis investigating the relationship between hospital volume and outcomes in pediatric patients with cerebral arteriovenous malformations

Michael G. Brandel, Hernan Gonzalez, David D. Gonda, Michael L. Levy, Edward R. Smith, Sandi K. Lam, William T. Couldwell, Jeffrey Steinberg, and Vijay M. Ravindra

OBJECTIVE

Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors’ aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers.

METHODS

Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids’ Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed.

RESULTS

Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06–0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02–0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals.

CONCLUSIONS

In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

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Federal and foundational research funding trends for cerebrovascular neurosurgeons: the decline of the cerebrovascular surgeon-scientist?

Sangami Pugazenthi, Anja I. Srienc, Luke Cantu, Anna L. Huguenard, Emad Eskandar, William J. Mack, Sepideh Amin-Hanjani, Ananth K. Vellimana, Joshua W. Osbun, and Gregory J. Zipfel

OBJECTIVE

The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time.

METHODS

Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009 and 2021 was surveyed using NIH RePORTER and Blue Ridge Institute for Medical Research data. The K12 Neurosurgeon Research Career Development Program and NREF grant data were queried for CV-focused grants. Pearson R correlation, chi-square analysis, and the Mann-Whitney U-test were used for statistical analysis.

RESULTS

From 2009 to 2021, NIH funding increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). During this time period, there has been an increase in the total number of CV surgeons (p < 0.0001), the number of NIH-funded CV surgeons (p = 0.0034), and the percentage of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0398) and the number of NIH grants per CV surgeon (p = 0.4257) have increased. Nevertheless, CV surgeons have been awarded a decreasing proportion of the overall pool of neurosurgeon-awarded NIH grants during this time period (p = 0.3095). In addition, there has been a significant decrease in the number of K08, K12, and K23 career development awards granted to CV surgeons during this time period (p = 0.0024). There was also a significant decline in the proportion of K12 (p = 0.0044) and downtrend in early-career NREF (p = 0.8978) grant applications and grants awarded during this time period. Finally, NIH-funded CV surgeons were more likely to have completed residency less recently (p = 0.001) and less likely to have completed an endovascular fellowship (p = 0.044) as compared with non–NIH-funded CV surgeons.

CONCLUSIONS

The number of CV surgeons is increasing over time. While there has been a concomitant increase in the number of NIH-funded CV surgeons and the number of NIH grants awarded per CV surgeon in the past 12 years, there has also been a significant decrease in CV surgeons with K08, K12, and K23 career development awards and a downtrend in CV-focused K12 and early-career NREF applications and awarded grants. The latter findings suggest that the pipeline for future NIH-funded CV surgeons may be in decline.

Open access

Fractured vertebra antedisplacement reconstruction technique: a feasible treatment choice for posttraumatic thoracolumbar kyphosis

Tao Xu, Shanxi Wang, Huang Fang, Hua Wu, and Feng Li

OBJECTIVE

The goal of this study was to evaluate the feasibility of the fractured vertebra antedisplacement reconstruction technique for the treatment of posttraumatic thoracolumbar kyphosis (PTK).

METHODS

A total of 22 patients with PTK who were treated with the fractured vertebra antedisplacement reconstruction technique were retrospectively analyzed. The radiological evaluation included global kyphosis, thoracolumbar angle, and sagittal vertical axis. The clinical evaluation included visual analog scale pain score, Oswestry Disability Index score, SF-12 Health Survey score, and American Spinal Injury Association grade. The complications were recorded.

RESULTS

The mean global kyphosis was 55.0° ± 12.6° preoperatively, 8.5° ± 5.0° postoperatively, and 10.3° ± 4.8° at the latest follow-up (p < 0.001). The average total kyphosis correction achieved was 44.7° ± 14.2°, with a range of 23.4°–79.4°, indicating a mean final correction of 80.1%. The mean thoracolumbar angle was 46.2° ± 13.2° preoperatively, 6.6° ± 4.5° postoperatively, and 7.6° ± 4.2° at the latest follow-up (p < 0.001). The mean sagittal vertical axis was improved significantly, from 51.1 ± 24.2 mm preoperatively to 28.5 ± 17.4 mm at the latest follow-up (p = 0.001). One patient (4.5%) experienced single intervertebral fusion nonunion, and 1 patient (4.5%) experienced distal screw loosening. No patients experienced any neurological deterioration. The visual analog scale pain score, Oswestry Disability Index score, SF-12 Health Survey score, and American Spinal Injury Association grade achieved significant improvement at the latest follow-up.

CONCLUSIONS

Fractured vertebra antedisplacement reconstruction technique can effectively correct kyphosis, reconstruct spinal stability, and improve the patient’s symptoms and neurological function. This technique is safer, minimally traumatic, and less technically demanding to avoid osteotomy-related complications. It is a feasible treatment choice for PTK.

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Interictal discharge traveling waves recorded from stereoelectroencephalography electrodes

Alexander G. Yearley, Elliot H. Smith, Tyler S. Davis, Daria Anderson, Amir M. Arain, and John D. Rolston

OBJECTIVE

Interictal epileptiform discharges (IEDs) are intermittent high-amplitude electrical signals that occur between seizures. They have been shown to propagate through the brain as traveling waves when recorded with epicortical grid–type electrodes and small penetrating microelectrode arrays. However, little work has been done to translate experimental IED analyses to more clinically relevant platforms such as stereoelectroencephalography (SEEG). In this pilot study, the authors aimed to define a computational method to identify and characterize IEDs recorded from clinical SEEG electrodes and leverage the directionality of IED traveling waves to localize the seizure onset zone (SOZ).

METHODS

Continuous SEEG recordings from 15 patients with medically refractory epilepsy were collected, and IEDs were detected by identifying overlapping peaks of a minimum prominence. IED pathways of propagation were defined and compared to the SOZ location determined by a clinical neurologist based on the ictal recordings. For further analysis of the IED pathways of propagation, IED detections were divided into triplets, defined as a set of 3 consecutive contacts within the same IED detection. Univariate and multivariate linear regression models were employed to associate IED characteristics with colocalization to the SOZ.

RESULTS

A median (range) of 22.6 (4.4–183.9) IEDs were detected per hour from 15 patients over a mean of 23.2 hours of recording. Depending on the definition of the SOZ, a median (range) of 20.8% (0.0%–54.5%) to 62.1% (19.2%–99.4%) of IEDs per patient traversed the SOZ. IEDs passing through the SOZ followed discrete pathways that had little overlap with those of the IEDs passing outside the SOZ. Contact triplets that occurred more than once were significantly more likely to be detected in an IED passing through the SOZ (p < 0.001). Per our multivariate model, patients with a greater proportion of IED traveling waves had a significantly greater proportion of IEDs that localized to the SOZ (β = 0.64, 95% CI 0.01–1.27, p = 0.045).

CONCLUSIONS

By using computational methods, IEDs can be meaningfully detected from clinical-grade SEEG recordings of patients with epilepsy. In some patients, a high proportion of IEDs are traveling waves according to multiple metrics that colocalize to the SOZ, offering hope that IED detection, with further refinement, could serve as an alternative method for SOZ localization.