Epidemiology and Management Trends of Neuro-Oncology in Nigeria: A Systematic Review and Pooled Analysis.

OBJECTIVE: Access to neuro-oncologic care in Nigeria has grown exponentially since the first reported cases in the mid-1960s. In this systematic review and pooled analysis, we characterize the growth of neurosurgical oncology in Nigeria and build a reference paper to direct efforts to expand this field. METHODS: We performed an initial literature search of several article databases and gray literature sources. We included and subsequently screened articles published between 1962 and 2021. Several variables were extracted from each study, including the affiliated hospital, the number of patients treated, patient sex, tumor pathology, the types of imaging modalities used for diagnosis, and the interventions used for each individual. Change in these variables was assessed using Chi-squared independence tests and univariate linear regression when appropriate. RESULTS: A total of 147 studies were identified, corresponding to 5,760 patients. Over 4000 cases were reported in the past 2 decades from 21 different Nigerian institutions. The types of tumors reported have increased over time, with increasingly more patients being evaluated via computed tomography (CT) and magnetic resonance imaging (MRI). There is also a prevalent use of radiotherapy, though chemotherapy remains an underreported treatment modality. CONCLUSIONS: This study highlights key trends regarding the prevalence and management of neuro-oncologic pathologies within Nigeria. Further studies are needed to continue to learn and guide the future growth of this field in Nigeria.

Management and outcomes of pediatric traumatic brain injury in Africa: a systematic review.

OBJECTIVE: Traumatic brain injury (TBI) carries a major global burden of disease; however, it is well established that patients in low- and middle-income countries, such as those in Africa, have higher mortality rates. Pediatric TBI, specifically, is a documented cause for concern as injuries to the developing brain have been shown to lead to cognitive, psychosocial, and motor problems in adulthood. The purpose of this study was to investigate the reported demographics, causes, management, and outcomes of pediatric TBI in Africa. METHODS: A literature search was conducted using PubMed, Global Index Medicus, Embase, Scopus, Google Scholar, African Journals Online, and Web of Science. Various combinations of "traumatic brain injury," "head injury," "p(a)ediatric," "Africa," and country names were used. Relevant primary data published in the English language were included and subjected to a risk of bias analysis. Variables included age, sex, TBI severity, TBI cause, imaging findings, treatment, complications, and outcome. RESULTS: After screening, 45 articles comprising 11,635 patients were included. The mean patient age was 6.48 ± 2.13 years, and 66.3% of patients were male. Of patients with reported data, mild, moderate, and severe TBIs were reported in 57.6%, 14.5%, and 27.9% of patients, respectively. Road traffic accidents were the most reported cause of pediatric TBI (50.53%) followed by falls (25.18%). Skull fractures and intracerebral contusions were the most reported imaging findings (28.32% and 16.77%, respectively). The most reported symptoms included loss of consciousness (24.4%) and motor deficits (17.1%). Surgical management was reported in 28.66% of patients, with craniotomy being the most commonly reported procedure (15.04%). Good recovery (Glasgow Outcome Scale score 5, Glasgow Outcome Scale-Extended score 7-8) was reported in 47.17% of patients. Examination of the period post-2015 demonstrated increased spread in the literature regarding pediatric TBI in Africa. CONCLUSIONS: This study provides a comprehensive overview of the literature regarding pediatric TBI in Africa and how it has evolved alongside global neurosurgical efforts. Although there has been increased involvement from various African countries in the neurosurgical literature, there remains a relative paucity of data on this subject. Standardized reporting protocols for patient care may aid in future studies seeking to synthesize data. Finally, further studies should seek to correlate the trends seen in this study, with primary epidemiological data to gain deeper insight into the disease burden of pediatric TBI in Africa.

The scope, trends, and challenges of neurosurgical research in Nigeria: A bibliometric review.

OBJECTIVE: This study investigates the scope, trends, and challenges of neurosurgical research in Nigeria since inception of the specialty in 1962. METHODS: A bibliometric review of the neurosurgical literature from Nigeria was done. Variables extracted included year and journal of publication, article topic, article type, research type, study design, article focus area, and limitations. Descriptive and quantitative analyses were performed for all variables. Trends of research publications were described in three periods - pioneering (1962-1981), recession (1982-2001), and resurgent (2002-2021). RESULTS: Of the 1023 included articles, 10.0% were published in the pioneering period, 9.2% in the recession period, and 80.8% in the resurgent period. Papers were predominantly published in World Neurosurgery (4.5%) and Nigerian Journal of Clinical Practice ( 4.0%). 79.9% of the 4618 authors were from Nigerian institutions. 86.3% of the articles covered clinical research and were mainly focused on service delivery and epidemiology (89.9%). The most prominent topics were traumatic brain injury (25.8%) and CNS malignancy (21.4%). Only 4.4% of the publications received funding, mostly from agencies in the US (31.7%). Barriers to neurosurgical research included lack of clinical databases (18.0%), increasing burden of disease (12.5%), and diagnostic challenges (12.4%). CONCLUSION: Neurosurgical research in Nigeria continues to grow due to increased training, workforce, and infrastructural improvements. Addressing the major challenges through establishment of research databases, development of evidence-based management guidelines, and increasing research training, funding and opportunities can increase research capacity in Nigeria.

Scoping review on the state of racial disparities literature in the treatment of neurosurgical disease: a call for action.

OBJECTIVE: Racial disparities are ubiquitous across medicine in the US. This study aims to assess the evidence of racial disparities within neurosurgery and across its subspecialties, with a specific goal of quantifying the distribution of articles devoted to either identifying, understanding, or reducing disparities. METHODS: The authors searched the MEDLINE, EMBASE, and Scopus databases by using keywords to represent the concepts of neurosurgery, patients, racial disparities, and specific study types. Two independent reviewers screened the article titles and abstracts for relevance. A third reviewer resolved conflicts. Data were then extracted from the included articles and each article was categorized into one of three phases: identifying, understanding, or reducing disparities. This review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. RESULTS: Three hundred seventy-one studies published between 1985 and 2023 were included. The distribution of racial disparities literature was not equally spread among specialties, with spine representing approximately 48.3% of the literature, followed by tumor (22.1%) and general neurosurgery (12.9%). Most studies were dedicated to identifying racial disparities (83.6%). The proportion of literature devoted to understanding and reducing disparities was much lower (15.1% and 1.3%, respectively). Black patients were the most negatively impacted racial/ethnic group in the review (63.3%). The Hispanic or Latino ethnic group was the second most negatively impacted (25.1%). The following categories-other outcomes (28.0%), the offering of treatment (21.6%), complications (18.6%), and survival (16.7%)-represented the most frequently measured outcomes. CONCLUSIONS: Although strides have been taken to identify racial disparities within neurosurgery, fewer studies have focused on understanding and reducing these disparities. The tremendous rise of literature within this domain but the relative paucity of solutions necessitates the study of targeted interventions to provide equitable care for all patients undergoing neurosurgical treatment.

Association of moyamoya vasculopathy with autoimmune disease: a systematic review and pooled analysis.

Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.

Machine Learning to Predict Successful Opioid Dose Reduction or Stabilization After Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation (SCS) effectively reduces opioid usage in some patients, but preoperatively, there is no objective measure to predict who will most benefit. OBJECTIVE: To predict successful reduction or stabilization of opioid usage after SCS using machine learning models we developed and to assess if deep learning provides a significant benefit over logistic regression (LR). METHODS: We used the IBM MarketScan national databases to identify patients undergoing SCS from 2010 to 2015. Our models predict surgical success as defined by opioid dose stability or reduction 1 year after SCS. We incorporated 30 predictors, primarily regarding medication patterns and comorbidities. Two machine learning algorithms were applied: LR with recursive feature elimination and deep neural networks (DNNs). To compare model performances, we used nested 5-fold cross-validation to calculate area under the receiver operating characteristic curve (AUROC). RESULTS: The final cohort included 7022 patients, of whom 66.9% had successful surgery. Our 5-variable LR performed comparably with the full 30-variable version (AUROC difference <0.01). The DNN and 5-variable LR models demonstrated similar AUROCs of 0.740 (95% CI, 0.727-0.753) and 0.737 (95% CI, 0.728-0.746) ( P = .25), respectively. The simplified model can be accessed at SurgicalML.com . CONCLUSION: We present the first machine learning-based models for predicting reduction or stabilization of opioid usage after SCS. The DNN and 5-variable LR models demonstrated comparable performances, with the latter revealing significant associations with patients' pre-SCS pharmacologic patterns. This simplified, interpretable LR model may augment patient and surgeon decision making regarding SCS.

Evolution of Intracranial-Intracranial Bypass Surgery: A Bibliometric Analysis.

OBJECTIVE: Modern cerebrovascular bypass surgery uses either extracranial-intracranial (EC-IC) or intracranial-intracranial (IC-IC) approaches. Compared with EC-IC bypasses, IC-IC bypasses allow neurosurgeons to safely address tumors, aneurysms, and other lesions using shorter grafts that are well matched to the size of recipient vessels. Fewer than 100 articles have been published on IC-IC bypasses compared with more than 1000 on EC-IC bypasses. This study examined the increase of interest and innovation in IC-IC bypass. METHODS: PubMed and Web of Science were searched using keywords specific to IC-IC bypass, yielding 717 articles supplemented with 36 reports from other databases and gray literature. The articles were reviewed, and 98 articles were selected for further evaluation. Final articles were categorized as innovations or retrospective studies. Publication metrics were passed through an analytic program to assess statistical measures of growth. RESULTS: The number of publications describing innovations (n = 52) and retrospective studies (n = 46) in IC-IC surgical techniques increased exponentially (R2 = 0.983 and R2 = 0.993, respectively), with both interest and research in the field increasing. The rate of publications in each group also increased. In recent years, increasing numbers of global institutions have researched and published on IC-IC bypasses. CONCLUSIONS: As more work is undertaken on IC-IC bypasses, it is critical for knowledge to be shared through research, collaboration, publication, and early teaching within residency training programs. This field has increased exponentially in the past 2 decades and has yet to reach an inflection point, indicating possible additional interest and growth over time.

Stent Design Affects Femoropopliteal Artery Deformation.

BACKGROUND: Poor durability of femoropopliteal artery (FPA) stenting is multifactorial, and severe FPA deformations occurring with limb flexion are likely involved. Different stent designs result in dissimilar stent-artery interactions, but the degree of these effects in the FPA is insufficiently understood. OBJECTIVES: To determine how different stent designs affect limb flexion-induced FPA deformations. METHODS: Retrievable markers were deployed into n = 28 FPAs of lightly embalmed human cadavers. Bodies were perfused and CT images were acquired with limbs in the standing, walking, sitting, and gardening postures. Image analysis allowed measurement of baseline FPA foreshortening, bending, and twisting associated with each posture. Markers were retrieved and 7 different stents were deployed across the adductor hiatus in the same limbs. Markers were then redeployed in the stented FPAs, and limbs were reimaged. Baseline and stented FPA deformations were compared to determine the influence of each stent design. RESULTS: Proximal to the stent, Innova, Supera, and SmartFlex exacerbated foreshortening, SmartFlex exacerbated twisting, and SmartControl restricted bending of the FPA. Within the stent, all devices except Viabahn restricted foreshortening; Supera, SmartControl, and AbsolutePro restricted twisting; SmartFlex and Innova exacerbated twisting; and Supera and Viabahn restricted bending. Distal to the stents, all devices except AbsolutePro and Innova exacerbated foreshortening, and Viabahn, Supera, Zilver, and SmartControl exacerbated twisting. All stents except Supera were pinched in flexed limb postures. CONCLUSIONS: Peripheral self-expanding stents significantly affect limb flexion-induced FPA deformations, but in different ways. Although certain designs seem to accommodate some deformation modes, no device was able to match all FPA deformations.

Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients.

BACKGROUND: Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM). OBJECTIVE: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort. METHODS: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines. RESULTS: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (<70 yr, P = .02) and tumor volume (<11 cc, P = .03) were favorable prognostic factors for OS. CONCLUSION: The maximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patients with nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA.

A temporal examination of calcium signaling in cancer- from tumorigenesis, to immune evasion, and metastasis.

BACKGROUND: Although the study of calcium (Ca2+) is classically associated with excitable cells such as myocytes or neurons, the ubiquity of this essential element in all cellular processes has led to interest in other cell types. The importance of Ca2+ to apoptosis, cell signaling, and immune activation is of special import in cancer. MAIN: Here we review the current understanding of Ca2+ in each of these processes vital to the initiation, spread, and drug resistance of malignancies. We describe the involvement of Ca2+, and Ca2+ related proteins in cell cycle checkpoints and Ca2+ dependent apoptosis and discuss their roles in cellular immortalization. The role of Ca2+ in inter-cellular communication is also discussed in relevance to tumor-stromal communication, angiogenesis, and tumor microinvasion. The role that Ca2+ plays in immune surveillance and evasion is also addressed. Finally, we discuss the possibility of targeting Ca2+ singling to address the most pressing topics of cancer treatment: metastatic disease and drug resistance. CONCLUSION: This review discusses the current understanding of Ca2+ in cancer. By addressing Ca2+ facilitated angiogenesis, immune evasion, metastasis, and drug resistance, we anticipate future avenues for development of Ca2+ as a nexus of therapy.

Limb flexion-induced axial compression and bending in human femoropopliteal artery segments.

BACKGROUND: High failure rates of femoropopliteal artery (FPA) interventions are often attributed in part to severe mechanical deformations that occur with limb movement. Axial compression and bending of the FPA likely play significant roles in FPA disease development and reconstruction failure, but these deformations are poorly characterized. The goal of this study was to quantify axial compression and bending of human FPAs that are placed in positions commonly assumed during the normal course of daily activities. METHODS: Retrievable nitinol markers were deployed using a custom-made catheter system into 28 in situ FPAs of 14 human cadavers. Contrast-enhanced, thin-section computed tomography images were acquired with each limb in the standing (180 degrees), walking (110 degrees), sitting (90 degrees), and gardening (60 degrees) postures. Image segmentation and analysis allowed relative comparison of spatial locations of each intra-arterial marker to determine axial compression and bending using the arterial centerlines. RESULTS: Axial compression in the popliteal artery (PA) was greater than in the proximal superficial femoral artery (SFA) or the adductor hiatus (AH) segments in all postures (P = .02). Average compression in the SFA, AH, and PA ranged from 9% to 15%, 11% to 19%, and 13% to 25%, respectively. The FPA experienced significantly more acute bending in the AH and PA segments compared with the proximal SFA (P < .05) in all postures. In the walking, sitting, and gardening postures, average sphere radii in the SFA, AH, and PA ranged from 21 to 27 mm, 10 to 18 mm, and 8 to 19 mm, whereas bending angles ranged from 150 to 157 degrees, 136 to 147 degrees, and 137 to 148 degrees, respectively. CONCLUSIONS: The FPA experiences significant axial compression and bending during limb flexion that occur at even modest limb angles. Moreover, different segments of the FPA appear to undergo significantly different degrees of deformation. Understanding the effects of limb flexion on axial compression and bending might assist with reconstructive device selection for patients requiring peripheral arterial disease intervention and may also help guide the development of devices with improved characteristics that can better adapt to the dynamic environment of the lower extremity vasculature.

Morphometric roadmaps to improve accurate device delivery for fluoroscopy-free resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Uncontrolled hemorrhage from vessel injuries within the torso remains a significant source of prehospital trauma mortality. Resuscitative endovascular balloon occlusion of the aorta can effectively control noncompressible hemorrhage, but this minimally invasive technique relies heavily on imaging not available in the field. Our goal was to develop morphometric roadmaps to enhance the safety and accuracy of fluoroscopy-free endovascular navigation of hemorrhage control devices. METHODS: Three-dimensional reconstructions of computed tomographic angiography scans from 122 trauma patients (mean [SD] age, 47 [24] years; range 5-93 years; 64 males; 58 females) were used to measure centerline distances from femoral artery access sites to the major aortic branch artery origins. Morphometric roadmap equations were created using multiple linear regression analysis to predict distances to the origins of the major arteries in the chest, abdomen, and pelvis using torso length, demographics, and risk factors as independent variables. A 40-mm-long occlusion balloon was then virtually deployed targeting Zones 1 and 3 of the aorta using these equations. Balloon placement accuracy was determined by comparing predicted versus actual measured distances to the target zone locations within the aortas from the database. RESULTS: Torso length and age were the strongest predictors of centerline distances from femoral artery access sites to the major artery origins. Male sex contributed to longer distances, while diabetes and smoking were associated with shorter distances. Hypertension, dyslipidemia, and coronary artery disease had no effect. With the use of morphometric roadmaps, virtual occlusion balloon placement accuracy was 100% for Zone 3 of the aorta, compared with 87% accuracy when using torso length alone. CONCLUSION: Morphometric roadmaps demonstrate a potential for improving the safety and accuracy of fluoroscopy-free aortic occlusion balloon delivery. Continued development of minimally invasive hemorrhage control techniques holds promise to improve prehospital mortality for patients with noncompressible exsanguinating torso injuries. LEVEL OF EVIDENCE: Therapeutic study, level IV; diagnostic study, level III.

In situ longitudinal pre-stretch in the human femoropopliteal artery.

In situ longitudinal (axial) pre-stretch (LPS) plays a fundamental role in the mechanics of the femoropopliteal artery (FPA). It conserves energy during pulsation and prevents buckling of the artery during limb movement. We investigated how LPS is affected by demographics and risk factors, and how these patient characteristics associate with the structural and physiologic features of the FPA. LPS was measured in n=148 fresh human FPAs (14-80 years old). Mechanical properties were characterized with biaxial extension and histopathological characteristics were quantified with Verhoeff-Van Gieson Staining. Constitutive modeling was used to calculate physiological stresses and stretches which were then analyzed in the context of demographics, risk factors and structural characteristics. Age had the strongest negative effect (r=-0.812, p<0.01) on LPS and could alone explain 66% of LPS variability. Male gender, higher body mass index, hypertension, diabetes, coronary artery disease, dyslipidemia and tobacco use had negative effects on LPS, but only the effect of tobacco was not associated with aging. FPAs with less pre-stretch had thicker medial layers, but thinner intramural elastic fibers with less dense and more fragmented external elastic laminae. Elastin degradation was associated with decreased physiological tethering force and longitudinal stress, while circumferential stress remained constant. FPA wall pathology was negatively associated with LPS (r=-0.553, p<0.01), but the effect was due primarily to aging. LPS in the FPA may serve as an energy reserve for adaptive remodeling. Reduction of LPS due to degradation and fragmentation of intramural longitudinal elastin during aging can be accelerated in tobacco users. STATEMENT OF SIGNIFICANCE: This work studies in situ longitudinal pre-stretch (LPS) in the human femoropopliteal artery. LPS has a fundamental role in arterial mechanics, but is rather poorly studied due to lack of direct in vivo measurement method. We have investigated LPS in the n=148 human femoropopliteal arteries in the context of subject demographics and risk factors, and structural and physiologic characteristics of the artery. Our results demonstrate that LPS reduces with age due to degradation and fragmentation of intramural elastin. LPS may serve as an energy reserve for adaptive remodeling, and reduction of LPS can be accelerated in tobacco users.