bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal instrumentation in infants, children, and adolescents: a review
Authors: Mendenhall Stephen , Mobasser Dillon , Relyea Katherine , Jea Andrew
Published: February 2019

OBJECTIVE

The evolution of pediatric spinal instrumentation has progressed in the last 70 years since the popularization of the Harrington rod showing the feasibility of placing spinal instrumentation into the pediatric spine. Although lacking in pediatric-specific spinal instrumentation, when possible, adult instrumentation techniques and tools have been adapted for the pediatric spine. A new generation of pediatric neurosurgeons with interest in complex spine disorder has pushed the field forward, while keeping the special nuances of the growing immature spine in mind. The authors sought to review their own experience with various types of spinal instrumentation in the pediatric spine and document the state of the art for pediatric spine surgery.

METHODS

The authors retrospectively reviewed patients in their practice who underwent complex spine surgery. Patient demographics, operative data, and perioperative complications were recorded. At the same time, the authors surveyed the literature for spinal instrumentation techniques that have been utilized in the pediatric spine. The authors chronicle the past and present of pediatric spinal instrumentation, and speculate about its future.

RESULTS

The medical records of the first 361 patients who underwent 384 procedures involving spinal instrumentation from July 1, 2007, to May 31, 2018, were analyzed. The mean age at surgery was 12 years and 6 months (range 3 months to 21 years and 4 months). The types of spinal instrumentation utilized included occipital screws (94 cases); C1 lateral mass screws (115 cases); C2 pars/translaminar screws (143 cases); subaxial cervical lateral mass screws (95 cases); thoracic and lumbar spine traditional-trajectory and cortical-trajectory pedicle screws (234 cases); thoracic and lumbar sublaminar, subtransverse, and subcostal polyester bands (65 cases); S1 pedicle screws (103 cases); and S2 alar-iliac/iliac screws (56 cases). Complications related to spinal instrumentation included hardware-related skin breakdown (1.8%), infection (1.8%), proximal junctional kyphosis (1.0%), pseudarthroses (1.0%), screw malpositioning (0.5%), CSF leak (0.5%), hardware failure (0.5%), graft migration (0.3%), nerve root injury (0.3%), and vertebral artery injury (0.3%).

CONCLUSIONS

Pediatric neurosurgeons with an interest in complex spine disorders in children should develop a comprehensive armamentarium of safe techniques for placing rigid and nonrigid spinal instrumentation even in the smallest of children, with low complication rates. The authors’ review provides some benchmarks and outcomes for comparison, and furnishes a historical perspective of the past and future of pediatric spine surgery.
Premorbid migraine history as a risk factor for vestibular and oculomotor baseline concussion assessment in pediatric athletes
Authors: Moran Ryan N. , Covassin Tracey , Wallace Jessica
Published: February 2019

OBJECTIVE

Migraine history has recently been identified as a risk factor for concussion and recovery. The authors performed a cross-sectional study examining baseline outcome measures on newly developed and implemented concussion assessment tools in pediatrics. The purpose of this study was to examine the effects of premorbid, diagnosed migraine headaches as a risk factor on vestibular and oculomotor baseline assessment in pediatric athletes.

METHODS

Pediatric athletes between the ages of 8 and 14 years with a diagnosed history of migraine headache (n = 28) and matched controls without a history of diagnosed migraine headache (n = 28) were administered a baseline concussion assessment battery, consisting of the Vestibular/Ocular Motor Screening (VOMS), near point of convergence (NPC), and the King-Devick (K-D) tests. Between-groups comparisons were performed for vestibular symptoms and provocation scores on the VOMS (smooth pursuit, saccades, convergence, vestibular/ocular reflex, visual motion sensitivity), NPC (average distance), and K-D (time).

RESULTS

Individuals diagnosed with migraine headaches reported greater VOMS smooth pursuit scores (p = 0.02), convergence scores (p = 0.04), vestibular ocular reflex scores (p value range 0.002–0.04), and visual motion sensitivity scores (p = 0.009). Differences were also observed on K-D oculomotor performance with worse times in those diagnosed with migraine headache (p = 0.02). No differences were reported on NPC distance (p = 0.06) or headache symptom reporting (p = 0.07) prior to the VOMS assessment.

CONCLUSIONS

Pediatric athletes diagnosed with migraine headaches reported higher baseline symptom provocation scores on the VOMS. Athletes with migraine headaches also performed worse on the K-D test, further illustrating the influence of premorbid migraine headaches as a risk factor for elevated concussion assessment outcomes at baseline. Special consideration may be warranted for post-concussion assessment in athletes with migraine headaches.
Impact of surgery timing for craniosynostosis on neurodevelopmental outcomes: a systematic review
Authors: Mandela Rachel , Bellew Maggie , Chumas Paul , Nash Hannah
Published: February 2019

OBJECTIVE

There are currently no guidelines for the optimum age for surgical treatment of craniosynostosis. This systematic review summarizes and assesses evidence on whether there is an optimal age for surgery in terms of neurodevelopmental outcomes.

METHODS

The databases MEDLINE, PsycINFO, CINAHL, Embase + Embase Classic, and Web of Science were searched between October and November 2016 and searches were repeated in July 2017. According to PICO (participants, intervention, comparison, outcome) criteria, studies were included that focused on: children diagnosed with nonsyndromic craniosynostosis, aged ≤ 5 years at time of surgery; corrective surgery for nonsyndromic craniosynostosis; comparison of age-at-surgery groups; and tests of cognitive and neurodevelopmental postoperative outcomes. Studies that did not compare age-at-surgery groups (e.g., those employing a correlational design alone) were excluded. Data were double-extracted by 2 authors using a modified version of the Cochrane data extraction form.

RESULTS

Ten studies met the specified criteria; 5 found a beneficial effect of earlier surgery, and 5 did not. No study found a beneficial effect of later surgery. No study collected data on length of anesthetic exposure and only 1 study collected data on sociodemographic factors.

CONCLUSIONS

It was difficult to draw firm conclusions from the results due to multiple confounding factors. There is some inconclusive evidence that earlier surgery is beneficial for patients with sagittal synostosis. The picture is even more mixed for other subtypes. There is no evidence that later surgery is beneficial. The authors recommend that future research use agreed-upon parameters for: age-at-surgery cut-offs, follow-up times, and outcome measures.
Two-stage surgical treatment for a giant sellar psammomatoid juvenile ossifying fibroma: case report
Authors: Twitchell Spencer , Karsy Michael , Gozal Yair M. , Davidson Christian , Couldwell William T. , Brockmeyer Douglas
Published: February 2019

Psammomatoid juvenile ossifying fibroma (PJOF) is an uncommon, benign fibro-osseous tumor. It is a purely surgical disease, and a review of the literature revealed that adjuvant therapies, including chemotherapy and radiation, play a limited role. The authors report the case of a 16-year-old male refugee who presented with a giant sinonasal PJOF with parasellar invasion, after having been unable to undergo earlier surgical treatment. The delay in presentation resulted in a large lesion with bilateral optic nerve compression, blindness, and frontal lobe compression. The patient was surgically treated with a two-stage combined cranial and endoscopic endonasal surgical approach. The delay in treatment and significant neurological compromise, which necessitated a two-stage approach, are unique from previously reported cases of PJOF.
Impact of sagittal spinopelvic alignment on clinical outcomes and health-related quality of life after decompression surgery without fusion for lumbar spinal stenosis
Authors: Ogura Yoji , Shinozaki Yoshio , Kobayashi Yoshiomi , Kitagawa Takahiro , Yonezawa Yoshiro , Takahashi Yohei , Yoshida Kodai , Yasuda Akimasa , Ogawa Jun
Published: February 2019

OBJECTIVE

Patients with lumbar spinal stenosis (LSS) tend to bend forward to relieve neurological symptoms. They therefore have a positive sagittal vertical axis (SVA). The importance of the SVA value is well known in the field of adult spinal deformity; however, little is known about its impact on LSS. The authors sought to investigate the impact of sagittal spinopelvic alignment on clinical outcome and health-related quality of life (HRQOL) after decompression surgery for LSS.

METHODS

The authors retrospectively reviewed 83 patients who underwent lumbar decompression without fusion between January 2014 and September 2015 with a minimum follow-up of 2 years. Standing whole-spine radiographs were examined preoperatively and at final follow-up. Based on the SVA, patients were allocated to a sagittal balance group (group B; SVA < 50 mm) or a sagittal imbalance group (group I; SVA ≥ 50 mm). The authors compared the groups using Japanese Orthopaedic Association (JOA), Zurich Claudication Questionnaire (ZCQ), Roland-Morris Disability Questionnaire (RMDQ), and the 8-item Short Form Health Survey (SF-8) scores.

RESULTS

Preoperative groups B (group pre-B) and I (group pre-I) included 58 and 25 patients, respectively. Preoperative sagittal malalignment had negative effects on the JOA score recovery rate, postoperative ZCQ physical function domain score, and numeric rating scale (NRS) score of postoperative low-back pain (LBP), but no significant effects were observed for RMDQ and SF-8 domain scores. Postoperatively, groups B (group post-B) and I (group post-I) included 60 and 23 patients, respectively. Group post-I had a significantly worse JOA score recovery rate, postoperative symptom severity domain score in the ZCQ, and NRS score for postoperative LBP. Similarly, the postoperative RMDQ score and the Physical Component Summary score of the SF-8 were significantly worse in group post-I.

CONCLUSIONS

Positive SVA had significantly negative effects on clinical outcome and HRQOL in LSS patients after lumbar decompression surgery.
Reassessing the impact of intraoperative electrocorticography on postoperative outcome of patients undergoing standard temporal lobectomy for MRI-negative temporal lobe epilepsy
Authors: Grewal Sanjeet S. , Alvi Mohammed Ali , Perkins William J. , Cascino Gregory D. , Britton Jeffrey W. , Burkholder David B. , So Elson , Shin Cheolsu , Marsh Richard W. , Meyer Fredric B. , Worrell Gregory A. , Van Gompel Jamie J.
Published: February 2019

OBJECTIVE

Almost 30% of the patients with suspected temporal lobe epilepsy (TLE) have normal results on MRI. Success rates for resection of MRI-negative TLE are less favorable, ranging from 36% to 76%. Herein the authors describe the impact of intraoperative electrocorticography (ECoG) augmented by opioid activation and its effect on postoperative seizure outcome.

METHODS

Adult and pediatric patients with medically resistant MRI-negative TLE who underwent standardized ECoG at the time of their elective anterior temporal lobectomy (ATL) with amygdalohippocampectomy between 1990 and 2016 were included in this study. Seizure recurrence comprised the primary outcome of interest and was assessed using Kaplan-Meier and multivariable Cox regression analysis plots based on distribution of interictal epileptiform discharges (IEDs) recorded on scalp electroencephalography, baseline and opioid-induced IEDs on ECoG, and extent of resection.

RESULTS

Of the 1144 ATLs performed at the authors’ institution between 1990 and 2016, 127 (11.1%) patients (81 females) with MRI-negative TLE were eligible for this study. Patients with complete resection of tissue generating IED recorded on intraoperative ECoG were less likely to have seizure recurrence compared to those with incomplete resection on univariate analysis (p < 0.05). No difference was found in seizure recurrence between patients with bilateral independent IEDs and unilateral IEDs (p = 0.15), presence or absence of opioid-induced epileptiform activation (p = 0.61), or completeness of resection of tissue with opioid-induced IEDs on intraoperative ECoG (p = 0.41).

CONCLUSIONS

The authors found that incomplete resection of IED-generating tissue on intraoperative ECoG was associated with an increased chance of seizure recurrence. However, they found that induction of epileptiform activity with intraoperative opioid activation did not provide useful intraoperative data predictive of improving operative results for temporal lobectomy in MRI-negative epilepsy.
Predicting mortality in traumatic intracranial hemorrhage
Authors: Powers Andrew Y. , Pinto Mauricio B. , Tang Oliver Y. , Chen Jia-Shu , Doberstein Cody , Asaad Wael F.
Published: February 2019

OBJECTIVE

Traumatic intracranial hemorrhage (tICH) is a significant source of morbidity and mortality in trauma patients. While prognostic models for tICH outcomes may assist in alerting clinicians to high-risk patients, previously developed models face limitations, including low accuracy, poor generalizability, and the use of more prognostic variables than is practical. This study aimed to construct a simpler and more accurate method of risk stratification for all tICH patients.

METHODS

The authors retrospectively identified a consecutive series of 4110 patients admitted to their institution’s level 1 trauma center between 2003 and 2013. For each admission, they collected the patient’s sex, age, systolic blood pressure, blood alcohol concentration, antiplatelet/anticoagulant use, Glasgow Coma Scale (GCS) score, Injury Severity Score, presence of epidural hemorrhage, presence of subdural hemorrhage, presence of subarachnoid hemorrhage, and presence of intraparenchymal hemorrhage. The final study population comprised 3564 patients following exclusion of records with missing data. The dependent variable under study was patient death. A k-fold cross-validation was carried out with the best models selected via the Akaike Information Criterion. These models risk stratified the study partitions into grade I (< 1% predicted mortality), grade II (1%–10% predicted mortality), grade III (10%–40% predicted mortality), or grade IV (> 40% predicted mortality) tICH. Predicted mortalities were compared with actual mortalities within grades to assess calibration. Concordance was also evaluated. A final model was constructed using the entire data set. Subgroup analysis was conducted for each hemorrhage type.

RESULTS

Cross-validation demonstrated good calibration (p < 0.001 for all grades) with a mean concordance of 0.881 (95% CI 0.865−0.898). In the authors’ final model, older age, lower blood alcohol concentration, antiplatelet/anticoagulant use, lower GCS score, and higher Injury Severity Score were all associated with greater mortality. Subgroup analysis showed successful stratification for subarachnoid, intraparenchymal, grade II–IV subdural, and grade I epidural hemorrhages.

CONCLUSIONS

The authors developed a risk stratification model for tICH of any GCS score with concordance comparable to prior models and excellent calibration. These findings are applicable to multiple hemorrhage subtypes and can assist in identifying low-risk patients for more efficient resource allocation, facilitate family conversations regarding goals of care, and stratify patients for research purposes. Future work will include testing of more variables, validation of this model across institutions, as well as creation of a simplified model whose outputs can be calculated mentally.
Arterial spin-labeling cerebral perfusion changes after revascularization surgery in pediatric moyamoya disease and syndrome
Authors: Quon Jennifer L. , Kim Lily H. , Lober Robert M. , Maleki Maryam , Steinberg Gary K. , Yeom Kristen W.
Published: February 2019

OBJECTIVE

Moyamoya disease is a dynamic cerebrovascular condition that often requires vascular surveillance. Arterial spin labeling (ASL) is an MR perfusion method that is increasingly used for stroke and other various neurovascular pathologies. Unlike perfusion-weighted MRI, ASL uses endogenous water molecules for signal and therefore obviates gadolinium use; and provides direct, not relative, quantitative cerebral blood flow (CBF) measures. Presently, the potential role of ASL for evaluating postoperative pediatric moyamoya patients is relatively unexplored. This study investigated the role for ASL in evaluating cerebral hemodynamic changes in children who underwent revascularization surgery.

METHODS

This retrospective study examined 15 consecutive pediatric patients with moyamoya disease (n = 7) or moyamoya syndrome (n = 8) presenting between 2010 and 2014 who underwent revascularization and in whom 3T ASL was performed pre- and postoperatively. Postoperative MRI at least 3 months after revascularization procedure was used for analysis. Quantitative CBF in various vascular territories was interrogated: anterior, middle, and posterior cerebral arteries, and basal ganglia supplied by the lenticulostriate collaterals, resulting in evaluation of 20 brain regions.

RESULTS

After revascularization, CBF in the high middle cerebral artery territory significantly increased (p = 0.0059), accompanied by a decrease in CBF to the ipsilateral lenticulostriate-supplied basal ganglia (p = 0.0053). No perfusion changes occurred in the remaining cerebral vascular territories after surgery.

CONCLUSIONS

ASL-based quantitative CBF showed improved cerebral perfusion to the middle cerebral artery territory after revascularization in children with both moyamoya syndrome and disease. Reduced perfusion to the basal ganglia might reflect pruning of the lenticulostriate collaterals, potentially from effects of revascularization. ASL can quantitatively evaluate hemodynamic changes in children with moyamoya after revascularization, and it may be a useful adjunct to routine clinical MRI surveillance.
Leptomeningeal dissemination: a sinister pattern of medulloblastoma growth
Authors: Fults Daniel W. , Taylor Michael D. , Garzia Livia
Published: February 2019

Leptomeningeal dissemination (LMD) is the defining pattern of metastasis for medulloblastoma. Although LMD is responsible for virtually 100% of medulloblastoma deaths, it remains the least well-understood part of medulloblastoma pathogenesis. The fact that medulloblastomas rarely metastasize outside the CNS but rather spread almost exclusively to the spinal and intracranial leptomeninges has fostered the long-held belief that medulloblastoma cells spread directly through the CSF, not the bloodstream. In this paper the authors discuss selected molecules for which experimental evidence explains how the effects of each molecule on cell physiology contribute mechanistically to LMD. A model of medulloblastoma LMD is described, analogous to the invasion–metastasis cascade of hematogenous metastasis of carcinomas. The LMD cascade is based on the molecular themes that 1) transcription factors launch cell programs that mediate cell motility and invasiveness and maintain tumor cells in a stem-like state; 2) disseminating medulloblastoma cells escape multiple death threats by subverting apoptosis; and 3) inflammatory chemokine signaling promotes LMD by creating an oncogenic microenvironment. The authors also review recent experimental evidence that challenges the belief that CSF spread is the sole mechanism of LMD and reveal an alternative scheme in which medulloblastoma cells can enter the bloodstream and subsequently home to the leptomeninges.
The evolution of minimally invasive spine surgery
Authors: Yoon Jang W. , Wang Michael Y.
Published: February 2019

The field of minimally invasive spine surgery (MISS) has rapidly evolved over the past 3 decades. This review follows the evolution of techniques and principles that have led to significant advances in the field. While still representing only a subset of spine surgeries, MISS’s goals of reducing soft-tissue trauma and mitigating the morbidity of surgery are being realized, translating into more rapid recovery, lower infection rates, and higher cost savings. Future advances in technology and techniques can be anticipated.
Postoperative changes in neurological function after 3-column osteotomy: risk factor analysis of 199 patients
Authors: Khashan Morsi , Raad Micheal , El Dafrawy Mostafa H. , Puvanesarajah Varun , Kebaish Khaled M.
Published: February 2019

OBJECTIVE

The authors evaluated the neurological outcomes of adult spinal deformity patients after 3-column osteotomy (3CO), including severity and long-term improvement of neurological complications, as well as risk factors for neurological deficit at 1 year postoperatively. Although 3CO is effective for correcting rigid spinal deformity, it is associated with a high complication rate. Neurological deficits, in particular, cause disability and dissatisfaction.

METHODS

The authors retrospectively queried a prospective database of adult spinal deformity patients who underwent vertebral column resection or pedicle subtraction osteotomy between 2004 and 2014 by one surgeon at a tertiary care center. The authors included 199 adults with at least 1-year follow-up. The primary outcome measure was change in lower-extremity motor scores (LEMSs), which were obtained preoperatively, within 2 weeks postoperatively, and at 6 and 12 months postoperatively. To identify risk factors for persistent neurological deficit, the authors compared patient and surgical characteristics with a declined LEMS at 12-month follow-up (n = 10) versus those with an improved/maintained LEMS at 12-month follow-up (n = 189).

RESULTS

At the first postoperative assessment, the LEMS had improved in 15% and declined in 10% of patients compared with preoperative scores. At the 6-month follow-up, 6% of patients continued to have a decline in LEMS, and 16% had improvement. At 12 months, LEMS had improved in 17% and declined in 5% of patients compared with preoperative scores. The only factor significantly associated with a decline in 12-month LEMS was high-grade spondylolisthesis as an indication for surgery (OR 13, 95% CI 3.2–56).

CONCLUSIONS

Although the LEMS declined in 10% of patients immediately after 3CO, at 12 months postoperatively, only 5% of patients had neurological motor deficits. A surgical indication of high-grade spondylolisthesis was the only factor associated with neurological deficit at 12 months postoperatively.
Rapidly growing, multifocal, benign choroid plexus tumor in an infant: case report
Authors: Misiolek Kalina A. , Osborn Zachary G. , Hauser Natalie , Thomas Diana , Goodman Jessica F. , Fulkerson Daniel H.
Published: February 2019

Choroid plexus papillomas (CPPs) are rare, benign tumors that can arise in young children. Most pediatric patients present with signs of hydrocephalus and require immediate treatment. The natural history of choroid plexus tumors in children without hydrocephalus is poorly defined. In this report, the authors present the very rare case of a child without hydrocephalus but with two intraventricular choroid plexus tumors discovered shortly after birth. Initial imaging had been performed for seizures and showed agenesis of the corpus callosum and enhancing tumors in the third and left lateral ventricles. Sequential imaging demonstrated rapid growth of both tumors. The lateral tumor was removed when the child was 3 months of age. A histological examination of the specimen showed benign features with an elevated mitotic rate. Given the patient’s age of under 3 years, the diagnosis was WHO grade I CPP. The third ventricle tumor grew rapidly. A second surgery was performed and this tumor was resected. Again, the pathological diagnosis was WHO grade I CPP. The authors present this rare case and discuss the current relevant literature.
Pediatric extraosseous sacral chordoma: case report and literature review of embryonic derivation and clinical implications
Authors: Hamilton Kimberly , Rebsamen Susan , Salamat Shahriar , Ahmed Raheel
Published: February 2019

An extraosseous intradural presentation for a sacral chordoma in the pediatric age group has not been reported to date. This is a report on an 11-year-old boy who presented with an extraosseous, intradural sacral chordoma. He underwent gross-total resection and received adjuvant proton beam therapy. Neoplastic transformation of the notochord is reviewed to illustrate the developmental basis for the surgical anatomy and pathogenesis of the classic chordoma variant. Clinical and pathological features are reviewed to differentiate this chordoma presentation from classic osseous chordomas and ecchordosis physaliphora, a related benign developmental notochordal lesion. Finally, the role of developmental signaling in the pathogenesis of chordomas from postembryonic notochordal tissue is discussed.
Epidemiology of pediatric hydrocephalus in Haiti: analysis of a surgical case series
Authors: Ragheb Michael , Shah Ashish H. , Jernigan Sarah , Koru-Sengul Tulay , Ragheb John
Published: February 2019

OBJECTIVE

Hydrocephalus is recognized as a common disabling pediatric disease afflicting infants and children disproportionately in the developing world, where access to neurosurgical care is limited and risk of perinatal infection is high. This surgical case series describes the Project Medishare Hydrocephalus Specialty Surgery (PMHSS) program experience treating hydrocephalus in Haiti between 2008 and 2015.

METHODS

The authors conducted a retrospective review of all cases involving children treated for hydrocephalus within the PMHSS program in Port-au-Prince, Haiti, from 2008 through 2015. All relevant epidemiological information of children treated were prospectively collected including relevant demographics, birth history, hydrocephalus etiology, head circumference, and operative notes. All appropriate associations and statistical tests were performed using univariate and multivariate logistic regression analyses.

RESULTS

Among the 401 children treated within PMHSS, postinfectious hydrocephalus (PIH) accounted for 39.4% (n = 158) of cases based on clinical, radiographic, and endoscopic findings. The majority of children with hydrocephalus in Haiti were male (54.8%, n = 197), born in the rainy season (59.7%, n = 233), and born in a coastal/inland location (43.3%, n = 61). The most common surgical intervention was endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) (45.7%, n = 175). Multivariate logistic regression analysis yielded coastal birth location (OR 3.76, 95% CI 1.16–12.18) as a statistically significant predictor of PIH. Increasing head circumference (adjusted OR 1.06, 95% CI 0.99–1.13) demonstrated a slight trend toward significance with the incidence of PIH.

CONCLUSIONS

This information will provide the foundation for future clinical and public health studies to better understand hydrocephalus in Haiti. The 39.4% prevalence of PIH falls within observed rates in Africa as does the apparently higher prevalence for those born during the rainy season. Although PIH was the most frequent etiology seen in almost all birth locations, the potential relationship with geography noted in this series will be the focus of further research in an effort to understand the link between climate and PIH in Haiti. The ultimate goal will be to develop an appropriate public health strategy to reduce the burden of PIH on the children of Haiti.
MicroRNA-195 protection against focal cerebral ischemia by targeting CX3CR1
Authors: Yang Guang , Liu Zhendong , Wang Lu , Chen Xin , Wang Xiaoxiong , Dong Qi , Zhang Daming , Yang Zhao , Zhou Qi , Sun Jingxian , Xue Linmeng , Wang Xinzhuang , Gao Ming , Li Lili , Yi Ran , Ilgiz Gareev , Ai Jing , Zhao Shiguang
Published: February 2019

OBJECTIVE

It has been reported that microRNA-195 (miR-195) protects against chronic brain injury induced by chronic brain hypoperfusion. However, neither the expression profile of miR-195 nor its potential role during acute ischemic stroke has been investigated. In this study, the authors’ aim was to verify the mechanism of miR-195 in acute ischemic stroke.

METHODS

The plasma levels of miR-195 expression were assessed using real-time PCR in 96 patients with acute ischemic stroke, and the correlation with the National Institutes of Health Stroke Scale score was evaluated. In addition, cerebral infarct volume, neurological score, and levels of miR-195 and CX3CL1/CX3CR1 mRNA and protein expression were assessed in mice subjected to middle cerebral artery occlusion (MCAO) with or without intra-cerebroventricular infusion of lentiviral vector. The inflammatory cytokines tumor necrosis factor–α (TNFα), interleukin (IL)–1β, and IL-6 of mouse brains after MCAO and BV2 cells treated with oxygen-glucose deprivation were measured using enzyme-linked immunosorbent assay, and apoptotic proteins were examined by Western blotting. Direct targeting of CX3CL1/CX3CR1 by miR-195 was determined by immunoblotting and dual luciferase assay.

RESULTS

In ischemic stroke patients, miR-195 was significantly downregulated and expression levels of miR-195 in these patients negatively correlated with the National Institutes of Health Stroke Scale score. In mice after MCAO, miR-195 overexpression decreased infarct volume, alleviated neurological deficits, and most importantly, suppressed an inflammatory response. Meanwhile, miR-195 suppressed the expression of the inflammatory cytokines TNFα, IL-1β, and IL-6 in vitro and in vivo. The authors further discovered that both CX3CL1 and CX3CR1 are direct targets of miR-195, but miR-195 exerts neuroprotective roles mainly through inhibiting CX3CR1-mediated neuroinflammation and subsequent neuronal cell apoptosis.

CONCLUSIONS

Taken together, these findings suggest that miR-195 promotes neuronal cell survival against chronic cerebral ischemic damage by inhibiting CX3CR1-mediated neuroinflammation. This indicates that miR-195 may represent a novel target that regulates neuroinflammation and brain injury, thus offering a new treatment strategy for cerebral ischemic disorders.
Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow–derived mesenchymal stem cells (SB623): a phase 1/2a study
Authors: Steinberg Gary K. , Kondziolka Douglas , Wechsler Lawrence R. , Lunsford L. Dade , Kim Anthony S. , Johnson Jeremiah N. , Bates Damien , Poggio Gene , Case Casey , McGrogan Michael , Yankee Ernest W. , Schwartz Neil E.
Published: February 2019

OBJECTIVE

The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow–derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.

METHODS

This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.

RESULTS

A total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4–10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, −2.1 (95% CI −3.3 to −1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9–29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0–16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1–2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (−0.735, p < 0.01) scores at 24 months.

CONCLUSIONS

In this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.

Clinical trial registration no.: NCT01287936 (clinicaltrials.gov)
ACE-inhibitors: a preventive measure for bone flap resorption after autologous cranioplasty?
Authors: Schütz Alessa , Murek Michael , Stieglitz Lennart Henning , Bernasconi Corrado , Vulcu Sonja , Beck Jürgen , Raabe Andreas , Schucht Philippe
Published: February 2019

OBJECTIVE

Decompressive craniectomy (DC) is an established treatment for refractory intracranial hypertension. It is usually followed by autologous cranioplasty (AC), the reinsertion of a patient’s explanted bone flap. A frequent long-term complication of AC is bone flap resorption (BFR), which results in disfigurement as well as loss of the protective covering of the brain. This study investigates risk factors for BFR after AC, including medical conditions and antihypertensive drug therapies, with a focus on angiotensin-converting enzyme inhibitors (ACEIs), which have been associated with a beneficial effect on bone healing and bone preservation in orthopedic, osteoporosis, and endocrinology research.

METHODS

In this single-center, retrospective study 183 consecutive cases were evaluated for bone flap resorption after AC. Information on patient demographics, medical conditions, antihypertensive therapy, and BFR—defined as an indication for revision surgery established by a neurosurgeon based on clinical or radiographic assessments—was collected. A Kaplan-Meier analysis of time from AC to diagnosis of BFR was performed, and factors associated with BFR were investigated using the log-rank test and Cox regression.

RESULTS

A total of 158 patients were considered eligible for inclusion in the data analysis. The median follow-up time for this group was 2.2 years (95% CI 1.9–2.5 years). BFR occurred in 47 patients (29.7%), with a median time to event of 3.7 years (95% CI 3.3–4.1 years). An ACEI prescription was recorded in 57 cases (36.1%). Univariate Kaplan-Meier analysis and the log-rank test revealed that ACEI therapy (2-year event free probability [EFP] 83.8% ± 6.1% standard error vs 63.9% ± 5.6%, p = 0.02) and ventriculoperitoneal (VP) shunt treatment (2-year EFP 86.9% ± 7.1% vs 66% ± 5.0%, p = 0.024) were associated with a lower probability of BFR. Multiple Cox regression analysis showed ACEI therapy (HR 0.29, p = 0.012), VP shunt treatment (HR 0.278, p = 0.009), and male sex (HR 0.500, p = 0.040) to be associated with a lower risk for BFR, whereas bone fragmentation (HR 1.92, p = 0.031) was associated with a higher risk for BFR.

CONCLUSIONS

Hypertensive patients treated with ACEIs demonstrate a lower rate of BFR than patients treated with other hypertensive medications and nonhypertensive patients. Our results are in line with previous reports on the positive influence of ACEIs on bone healing and preservation. Further analysis of the association between ACEI treatment and BFR development is needed and will be evaluated in a multicenter prospective trial.
Ictal networks of temporal lobe epilepsy: views from high-frequency oscillations in stereoelectroencephalography
Authors: Peng Syu-Jyun , Chou Chien-Chen , Yu Hsiang-Yu , Chen Chien , Yen Der-Jen , Kwan Shang-Yeong , Hsu Sanford P. C. , Lin Chun-Fu , Chen Hsin-Hung , Lee Cheng-Chia
Published: February 2019

OBJECTIVE

In this study, the authors investigated high-frequency oscillation (HFO) networks during seizures in order to determine how HFOs spread from the focal cerebral cortex and become synchronized across various areas of the brain.

METHODS

All data were obtained from stereoelectroencephalography (SEEG) signals in patients with drug-resistant temporal lobe epilepsy (TLE). The authors calculated intercontact cross-coefficients between all pairs of contacts to construct HFO networks in 20 seizures that occurred in 5 patients. They then calculated HFO network topology metrics (i.e., network density and component size) after normalizing seizure duration data by dividing each seizure into 10 intervals of equal length (labeled I1–I10).

RESULTS

From the perspective of the dynamic topologies of cortical and subcortical HFO networks, the authors observed a significant increase in network density during intervals I5–I10. A significant increase was also observed in overall energy during intervals I3–I8. The results of subnetwork analysis revealed that the number of components continuously decreased following the onset of seizures, and those results were statistically significant during intervals I3–I10. Furthermore, the majority of nodes were connected to a single dominant component during the propagation of seizures, and the percentage of nodes within the largest component grew significantly until seizure termination.

CONCLUSIONS

The consistent topological changes that the authors observed suggest that TLE is affected by common epileptogenic patterns. Indeed, the findings help to elucidate the epileptogenic network that characterizes TLE, which may be of interest to researchers and physicians working to improve treatment modalities for epilepsy, including resection, cortical stimulation, and neuromodulation treatments that are responsive to network topologies.
Maffucci syndrome complicated by three different central nervous system tumors sharing an IDH1 R132C mutation: case report
Authors: Nejo Takahide , Tanaka Shota , Ikemura Masako , Nomura Masashi , Takayanagi Shunsaku , Shin Masahiro , Ushiku Tetsuo , Shibahara Junji , Saito Nobuhito , Mukasa Akitake
Published: February 2019

Maffucci syndrome (MS) and Ollier disease (OD) are nonhereditary congenital diseases characterized by multiple enchondromas and/or chondrosarcomas. Recent studies have implicated somatic mosaic mutations of isocitrate dehydrogenase 1 or 2 (IDH1/2) as contributing to the pathogenesis of MS and OD. Occasionally, patients with these disorders may also present with central nervous system (CNS) tumors; however, detailed genetic analyses are limited. In this article, the authors report on a male patient with MS, harboring three CNS tumors that share a common genetic alteration. Over a 9-year period, three separate tumor resections were conducted for sellar, intraparenchymal brainstem, and osseous clival tumors. The histopathological diagnoses were pituitary adenoma, diffuse astrocytoma, and chondrosarcoma, respectively. Sanger sequencing revealed a common IDH1 R132C mutation among all three CNS tumors but not in blood DNA. Administering chemotherapy (nimustine) and subsequent radiation therapy to the brainstem glioma and the residual lesion in the clivus have kept the patient progression free for 18 months. This is the first report demonstrating an IDH1 mutation shared among three different CNS tumors in a single patient with MS. The findings support the hypothesis that in MS and OD, a single common IDH1 mutation triggers tumorigenesis in cells of different origins and locations in a somatic mosaic fashion.
Anatomical assessment of the endoscopic endonasal approach for the treatment of paraclinoid aneurysms
Authors: Tayebi Meybodi Ali , Borba Moreira Leandro , Little Andrew S. , Lawton Michael T. , Preul Mark C.
Published: February 2019

OBJECTIVE

Endoscopic endonasal approaches (EEAs) are increasingly being incorporated into the neurosurgeon’s armamentarium for treatment of various pathologies, including paraclinoid aneurysms. However, few anatomical assessments have been performed on the use of EEA for this purpose. The aim of the present study was to provide a comprehensive anatomical assessment of the EEA for the treatment of paraclinoid aneurysms.

METHODS

Five cadaveric heads underwent an endonasal transplanum-transtuberculum approach to expose the paraclinoid area. The feasibility of obtaining proximal and distal internal carotid artery (ICA) control as well as the topographic location of the origin of the ophthalmic artery (OphA) relative to dural landmarks were assessed. Limitations of the EEA in exposing the supraclinoid ICA were also recorded to identify favorable paraclinoid ICA aneurysm projections for EEA.

RESULTS

The extracavernous paraclival and clinoidal ICAs were favorable segments for establishing proximal control. Clipping the extracavernous ICA risked injury to the trigeminal and abducens nerves, whereas clipping the clinoidal segment put the oculomotor nerve at risk. The OphA origin was found within 4 mm of the medial opticocarotid point on a line connecting the midtubercular recess point to the medial vertex of the lateral opticocarotid recess. An average 7.2-mm length of the supraclinoid ICA could be safely clipped for distal control. Assessments showed that small superiorly or medially projecting aneurysms were favorable candidates for clipping via EEA.

CONCLUSIONS

When used for paraclinoid aneurysms, the EEA carries certain risks to adjacent neurovascular structures during proximal control, dural opening, and distal control. While some authors have promoted this approach as feasible, this work demonstrates that it has significant limitations and may only be appropriate in highly selected cases that are not amenable to coiling or clipping. Further clinical experience with this approach helps to delineate its risks and benefits.
Effective accuracy of stereoelectroencephalography: robotic 3D versus Talairach orthogonal approaches
Authors: Bourdillon Pierre , Châtillon Claude-Edouard , Moles Alexis , Rheims Sylvain , Catenoix Hélène , Montavont Alexandra , Ostrowsky-Coste Karine , Boulogne Sebastien , Isnard Jean , Guénot Marc
Published: February 2019

OBJECTIVE

Stereoelectroencephalography (SEEG) was first developed in the 1950s by Jean Talairach using 2D angiography and a frame-based, orthogonal approach through a metallic grid. Since then, various other frame-based and frameless techniques have been described. In this study the authors sought to compare the traditional orthogonal Talairach 2D angiographic approach with a frame-based 3D robotic procedure that included 3D angiographic interoperative imaging guidance. MRI was used for both procedures during surgery, but MRI preplanning was done only in the robotic 3D technique.

METHODS

All study patients suffered from drug-resistant focal epilepsy and were treated at the same center by the same neurosurgical team. Fifty patients who underwent the 3D robotic procedure were compared to the same number of historical controls who had previously been successfully treated with the Talairach orthogonal procedure. The effectiveness and absolute accuracy, as well as safety, of the two procedures were compared. Moreover, in the 3D robotic group, the reliability of the preoperative MRI to avoid vascular structures was evaluated by studying the rate of trajectory modification following the coregistration of the intraoperative 3D angiographic data onto the preoperative MRI-based trajectory plans.

RESULTS

Effective accuracy (96.5% vs 13.7%) and absolute accuracy (1.15 mm vs 4.00 mm) were significantly higher in the 3D robotic group than in the Talairach orthogonal group. Both procedures showed excellent safety results (no major complications). The rate of electrode modification after 3D angiography was 43.8%, and it was highest for frontal and insular locations.

CONCLUSIONS

The frame-based, 3D angiographic, robotic procedure described here provided better accuracy for SEEG implantations than the traditional Talairach approach. This study also highlights the potential safety advantage of trajectory planning using intraoperative frame-based 3D angiography over preoperative MRI alone.
Intraoperative near-infrared imaging with receptor-specific versus passive delivery of fluorescent agents in pituitary adenomas
Authors: Cho Steve S. , Jeon Jun , Buch Love , Nag Shayoni , Nasrallah MacLean , Low Philip S. , Grady M. Sean , Singhal Sunil , Lee John Y. K.
Published: February 2019

OBJECTIVE

Intraoperative molecular imaging with tumor-targeted fluorescent dyes can enhance resection rates. In contrast to visible-light fluorophores (e.g., 5-aminolevulinic-acid), near-infrared (NIR) fluorophores have increased photon tissue penetration and less contamination from tissue autofluorescence. The second-window ICG (SWIG) technique relies on passive accumulation of indocyanine green (ICG) in neoplastic tissues. OTL38, conversely, targets folate receptor overexpression in nonfunctioning pituitary adenomas. In this study, we compare the properties of these 2 modalities for NIR imaging of pituitary adenomas to better understand the potential for NIR imaging in neurosurgery.

METHODS

A total of 39 patients with pituitary adenomas were enrolled between June 2015 and January 2018 in 2, sequential, IRB-approved studies. Sixteen patients received systemic ICG infusions 24 hours prior to surgery, and another 23 patients received OTL38 infusions 2–3 hours prior to surgery. NIR fluorescence signal-to-background ratio (SBR) was recorded during and after resection. Immunohistochemistry was performed on the 23 adenomas resected from patients who received OTL38 to assess expression of folate receptor–alpha (FRα).

RESULTS

All 16 adenomas operated on after ICG administration demonstrated strong NIR fluorescence (mean SBR 4.1 ± 0.69 [SD]). There was no statistically significant difference between the 9 functioning and 7 nonfunctioning adenomas (p = 0.9). After administration of OTL38, the mean SBR was 1.7 ± 0.47 for functioning adenomas, 2.6 ± 0.91 for all nonfunctioning adenomas, and 3.2 ± 0.53 for the subset of FRα-overexpressing adenomas. Tissue identification with white light alone for all adenomas demonstrated 88% sensitivity and 90% specificity. SWIG demonstrated 100% sensitivity but only 29% specificity for both functioning and nonfunctioning adenomas. OTL38 was 75% sensitive and 100% specific for all nonfunctioning adenomas, but when assessment was limited to the 9 FRα-overexpressing adenomas, the sensitivity and specificity of OTL38 were both 100%.

CONCLUSIONS

Intraoperative imaging with NIR fluorophores demonstrates highly sensitive detection of pituitary adenomas. OTL38, a folate-receptor–targeted fluorophore, is highly specific for nonfunctioning adenomas but has no utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to both functioning and nonfunctioning pituitary adenomas, but it is less specific than targeted fluorophores. Thus, targeted and nontargeted NIR fluorophores play important, yet distinct, roles in intraoperative imaging. Selectively and intelligently using either agent has the potential to greatly improve resection rates and outcomes for patients with intracranial tumors.