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Barry Ting Sheen Kweh, Jin W. Tee, F. Cumhur Oner, Klaus J. Schnake, Emiliano N. Vialle, Frank Kanziora, Shanmuganathan Rajasekaran, Marcel Dvorak, Jens R. Chapman, Lorin M. Benneker, Gregory Schroeder, and Alexander R. Vaccaro

OBJECTIVE

The purpose of this study was to describe the genesis of the AO Spine Sacral and Pelvic Classification System in the context of historical sacral and pelvic grading systems.

METHODS

A systematic search of MEDLINE, EMBASE, Google Scholar, and Cochrane databases was performed consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all existing sacral and pelvic fracture classification systems.

RESULTS

A total of 49 articles were included in this review, comprising 23 pelvic classification systems and 17 sacral grading schemes. The AO Spine Sacral and Pelvic Classification System represents both the evolutionary product of these historical systems and a reinvention of classic concepts in 5 ways. First, the classification introduces fracture types in a graduated order of biomechanical stability while also taking into consideration the neurological status of patients. Second, the traditional belief that Denis central zone III fractures have the highest rate of neurological deficit is not supported because this subgroup often includes a broad spectrum of injuries ranging from a benign sagittally oriented undisplaced fracture to an unstable “U-type” fracture. Third, the 1990 Isler lumbosacral system is adopted in its original format to divide injuries based on their likelihood of affecting posterior pelvic or spinopelvic stability. Fourth, new discrete fracture subtypes are introduced and the importance of bilateral injuries is acknowledged. Last, this is the first integrated sacral and pelvic classification to date.

CONCLUSIONS

The AO Spine Sacral and Pelvic Classification is a universally applicable system that redefines and reorders historical fracture morphologies into a rational hierarchy. This is the first classification to simultaneously address the biomechanical stability of the posterior pelvic complex and spinopelvic stability, while also taking into consideration neurological status. Further high-quality controlled trials are required prior to the inclusion of this novel classification within a validated scoring system to guide the management of sacral and pelvic injuries.

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Enrique Osorio Fonseca, Luis C. Cadavid, Jorge Cespedes, John Vargas, Matthew Grady, L. Fernando Gonzalez, Miguel Enrique Berbeo, Edgar G. Ordóñez-Mora, Edgar G. Ordóñez-Rubiano, and Jorge E. Alvernia

The history of Colombian neurosurgery is a collective legacy of neurosurgeon-scientists, scholars, teachers, innovators, and researchers. Anchored in the country’s foundational values of self-determination and adaptability, these pioneers emerged from the Spanish colonial medical tradition and forged surgical alliances abroad. From the time of Colombian independence until the end of World War I, exchanges with the French medical tradition produced an emphasis on anatomical and systematic approaches to the emerging field of neurosurgery. The onset of American neurosurgical expertise in the 1930s led to a new period of exchange, wherein technological innovations were added to the Colombian neurosurgical repertoire. This diversity of influences culminated in the 1950s with the establishment of Colombia’s first in-country neurosurgery residency program. A select group of avant-garde neurosurgeons from this period expanded the domestic opportunities for patients and practitioners alike. Today, the system counts 10 recognized neurosurgery residency programs and over 500 neurosurgeons within Colombia. Although the successes of specific individuals and innovations were considered, the primary purpose of this historical survey was to glean relevant lessons from the past that can inform present challenges, inspire new opportunities, and identify professional and societal goals for the future of neurosurgical practice and specialization.

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Sarah Gao, Lan Jin, Jennifer Moliterno, Zachary A. Corbin, Ranjit S. Bindra, Joseph N. Contessa, James B. Yu, and Henry S. Park

OBJECTIVE

Because of the aggressive nature of glioblastoma, patients with unresected disease are encouraged to begin radiotherapy within approximately 1 month after craniotomy. The aim of this study was to investigate the potential association between time interval from biopsy to radiotherapy with overall survival in patients with unresected glioblastoma.

METHODS

Patients with unresected glioblastoma diagnosed between 2010 and 2014 who received adjuvant radiotherapy and concurrent chemotherapy were identified in the National Cancer Database. Demographic and clinical data were compared using chi-square and Wilcoxon rank-sum tests. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression modeling.

RESULTS

Among 3456 patients with unresected glioblastoma, initiation of radiotherapy within 3 weeks of biopsy was associated with a higher hazard of death compared with later initiation of radiotherapy. After excluding patients who received radiotherapy within 3 weeks of biopsy to minimize the effects of confounders associated with short time intervals from biopsy to radiotherapy, the median interval from biopsy to radiotherapy was 32 days (IQR 27–39 days). Overall, 1782 (66.82%) patients started radiotherapy within 5 weeks of biopsy, and 885 (33.18%) patients started radiotherapy beyond 5 weeks of biopsy. On multivariable analysis, there was no significant difference in overall survival between these two groups (HR 0.96, 95% CI 0.88–1.50; p = 0.374).

CONCLUSIONS

In patients with unresected glioblastoma, a longer time interval from biopsy to radiotherapy does not appear to be associated with worse overall survival. However, external validation of these findings is necessary given that selection bias is a significant limitation of this study.

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Takashi Mamiya, Fumiaki Kanamori, Kinya Yokoyama, Akinobu Ota, Sivasundaram Karnan, Kenji Uda, Yoshio Araki, Satoshi Maesawa, Kazuhiro Yoshikawa, and Ryuta Saito

OBJECTIVE

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions.

METHODS

The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions.

RESULTS

The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis.

CONCLUSIONS

The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.

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Kazuya Kanemaru, Hideyuki Yoshioka, Koji Hashimoto, Takuma Wakai, Nobuo Senbokuya, Toru Tateoka, Norito Fukuda, Takako Umeda, Hiroshi Onishi, and Hiroyuki Kinouchi

OBJECTIVE

Retrograde leptomeningeal venous drainage (RLVD) of a dural arteriovenous fistula (dAVF) is associated with neurological morbidity and unfavorable outcomes. However, the direct damage to cortical neurons by dAVF with RLVD has not been elucidated. 123I-iomazenil (123I-IMZ) SPECT can reveal cerebral blood flow and cortical neuronal damage in early and late images, respectively. This study aimed to assess the cerebral venous congestive encephalopathy caused by dAVF using 123I-IMZ SPECT.

METHODS

Based on the pre- and posttreatment MRI findings, patients were divided into three groups: a normal group, an edema group, and an infarction group. Radioactive counts in the early and late images of 123I-IMZ SPECT were investigated using the affected-to-contralateral side asymmetry ratio (ACR).

RESULTS

None of the patients in the normal group showed any symptoms related to venous congestion. In contrast, all the patients in the edema and infarction groups developed neurological symptoms. The ACR in early images in the edema group was significantly lower than that in the normal group and significantly higher than that in the infarction group. The ACR in the late images of the infarction group was significantly lower than those of the normal and edema groups. After treatment, the neurological signs disappeared in the edema group, but only partial improvement was observed in the infarction group. The ACR in early images significantly improved after treatment in the edema group, but the ACR in late images did not change in any groups.

CONCLUSIONS

123I-IMZ SPECT is useful for evaluating hemodynamic disturbances and neuronal damage in dAVFs. The reduction in early images was correlated with the severity of venous congestive encephalopathy, and the significant reduction in late images is a reliable indicator of irreversible venous infarction caused by RLVD.

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Serge Marbacher, Basil Erwin Grüter, Stefan Wanderer, Lukas Andereggen, Marco Cattaneo, Patricia Trost, Philipp Gruber, Michael Diepers, Luca Remonda, and Hans-Jakob Steiger

OBJECTIVE

Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA–based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping.

METHODS

Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models.

RESULTS

The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence.

CONCLUSIONS

The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

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Dhanushan Dhayalan, Avital Perry, Christopher S. Graffeo, Øystein Vesterli Tveiten, Amanda Muñoz Casabella, Bruce E. Pollock, Colin L. W. Driscoll, Matthew L. Carlson, Michael J. Link, and Morten Lund-Johansen

OBJECTIVE

The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function.

METHODS

VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines.

RESULTS

A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration.

CONCLUSIONS

Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.

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Saud Alzahrani, Harley Brito da Silva, Tak-Ho Chu, Zain Tariq, Daniel Umansky, David A. Elliott, and Rajiv Midha

OBJECTIVE

The objective of this study was to test whether regenerating motor axons from a donor nerve can travel in a retrograde fashion using sensory branches to successfully reinnervate a motor nerve end organ.

METHODS

This study has two parts. In part I, rats (n = 30) were assigned to one of five groups for obturator nerve (ON)–to–femoral nerve transfer: group 1, ON-to–saphenous nerve (SN) distal stump; group 2, ON-to-SN proximal stump without femoral nerve proper (FNP) injury; group 3, ON-to-SN proximal stump with FNP crush injury; group 4, ON-to-SN proximal stump with FNP transection injury; and group 5, gold standard transfer, ON-to–motor femoral nerve (MFN) branch. At 8 weeks, retrograde labeling was done from the distal MFN, and the spinal cords were examined to assess the degree of obturator motor axon regeneration across the five groups. In part II, only group 4 was examined (n = 8). Through use of immunostaining and optical tissue clearing methods, the nerve transfer networks were cleared and imaged using light-sheet fluorescence microscopy to visualize the regeneration pathways in 2D and 3D models at 2- and 8-week time points.

RESULTS

Proximal FNP transection (group 4) enabled a significantly higher number of retrogradely regenerated motor axons compared with control groups 1–3. Moreover, group 4 had modest, but nonsignificant, superiority of motor neuron counts compared with the positive control group, group 5. Optical tissue clearing demonstrated that the axons traveled in a retrograde fashion from the recipient sensory branch to the FNP mixed stump, then through complex turns, down to distal branches. Immunostaining confirmed the tissue clearing findings and suggested perineurium disruption as a means by which axons could traverse across fascicular boundaries.

CONCLUSIONS

Sensory branches can transmit regenerating axons from donor nerves back to main mixed recipient nerves, then distally toward target organs. The extent of retrograde regeneration is markedly influenced by the type and severity of injury sustained by the recipient nerve. Using a sensory branch as a bridge for retrogradely regenerating axons can open new potential horizons in nerve repair surgery for severely injured mixed nerves.

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Alan R. Tang, Philip J. Davis, Kristen L. Williams, Alan Z. Grusky, Katherine S. Hajdu, Brian Q. Hou, Aaron M. Yengo-Kahn, Scott L. Zuckerman, and Douglas P. Terry

OBJECTIVE

Adolescents sustaining sport-related concussion often experience difficulties with the return-to-learn (RTL) process. Whereas the initial symptom burden has predicted prolonged RTL, no studies have established a relationship between acute cognitive symptoms and RTL duration. The authors sought to evaluate the relationship between initial cognitive symptoms and RTL duration.

METHODS

A retrospective single-institution cohort study of adolescent athletes aged 12–23 years who were evaluated within 5 days of a diagnosed sport-related concussion between November 2017 and October 2020 was conducted. Athletes missing cognitive symptom ratings and RTL data were excluded. The primary exposure variable was the Cognitive Symptom Ratio (CSR), defined as total cognitive symptom cluster score divided by total Post-Concussion Symptom Scale (PCSS) score from the initial clinic visit. Primary and secondary outcomes were time to RTL and total length of care, respectively. Multivariable Cox proportional hazards modeling was used to assess the effect of CSR on RTL duration.

RESULTS

Of 653 athletes evaluated within 5 days of injury, 346 patients were included in the final cohort. Athletes reported a median initial PCSS score of 21 (interquartile range [IQR] 6–37) and a median cognitive symptom score of 4 (IQR 0–9). Most patients endorsed some degree of difficulty concentrating (n = 212, 61.3%). The median CSR was 0.18 (IQR 0.00–0.27). On multivariable regression analysis, a higher CSR was associated with prolonged RTL duration (HR 0.30, 95% CI 0.13–0.69, p = 0.004). When initial PCSS score was added to the model, the previously significant association between CSR and RTL was no longer significant (HR 0.67, 95% CI 0.29–1.59, p = 0.367). When dichotomized based on frequency distribution, a higher proportion of patients with low CSR achieved RTL by 7 days postinjury (82.2% vs 69.9%, p = 0.007), a difference not seen at 14 days (92.2% vs 87.3%, p = 0.133).

CONCLUSIONS

An acute ratio of cognitive symptoms may predict patients at increased risk for prolonged RTL and those with normal PCSS scores who may experience difficulties once resuming school activities.