SNI/SNI Digital-Baghdad neurosurgery educational series.

Background: Access to high-quality neurosurgery online learning is limited in low- and middle-income countries, and Iraq is part of this category. The need for collaboration and connection of people worldwide to exchange ideas and experiences in neurosurgery is a challenge. Surgical Neurology International® (SNI)/SNI Digital stimulated the establishment of the joint effort to bring the discussion about the best experiences in neurosurgery from the United States and Iraq together in an internet meeting format. Methods: An online survey was formulated and distributed to the attendees of the SNI-Baghdad neurosurgery meetings. The survey investigates the last 14 consecutive meetings for the period May/2021-April/2022. The online survey was designed utilizing Google Forms. The survey outline includes demographics, general aspects of the meetings, research aspects, surgical anatomy, neuroradiology, and capacity-building aspects. All these sections of the survey used a 5-point Likert scale. Results: The total number of participants was 84 out of 115 sent, with a response rate of 73.1%. The participants were diverse as they ranged from medical students to attending neurosurgeons. The male-to-female ratio was 1:1. Most attendees were from Baghdad (n = 66 [77.6%]) and the highest number of the responders was from the University of Baghdad (n = 46 [54.1%]). Conclusion: The targeted online collaborative meetings, SNI-Baghdad neurosurgery meeting as an example, give an insight into the effectiveness of such methods in providing a mutually beneficial educational experience between people of different parts of the world, as assessed by a survey initiated and performed by the attendees.

"The most inspiring and mind-blowing meetings ever:" Highlights of the 15th SNI Baghdad Neurosurgery Online Meeting, from Participants' Perspectives.

Background: Education by lectures has been standard for 100 years or more. Given the 21st century technology, people can connect with others around the world instantly, electronically. With the pandemic, teaching changed to one-way information transfer with the loss of interpersonal learning experience. SNI® and now SNI Digital™ have been experimenting with different forms of communication to transfer information. Methods: Using an interactive education model, a meeting for neurosurgeons in Baghdad was held for students, residents, and neurosurgeons, the first in Iraq for a number of years because of the disruption from the war there. A national and international faculty participated. Results: This 15th meeting of the series was described by 42 out of 60 participants as "The best conference I have ever attended." That significant response highlights the importance of such meetings and how they can be at the highest level possible and be a recipe for success. Conclusion: The 15th meeting provides a focused analysis of the underlying characteristics leading to its success so that it can be duplicated.

Cost-effectiveness of short-term neurosurgical missions relative to other surgical specialties.

BACKGROUND: Short-term surgical relief efforts have helped close some gaps in the provision of surgical care in remote settings. We reviewed the published literature on short-term surgical missions to compare their cost-effectiveness across subspecialties. METHODS: PubMed was searched using the algorithm ["cost-effectiveness" AND "surgery" AND ("mission" OR "volunteer")]. Articles detailing the cost-effectiveness of short-term surgical missions in low and middle-income countries (LMIC) were included. Only direct mission costs were considered, and all costs were converted into 2014 USD. RESULTS: Eight articles, representing 27 missions in 9 LMIC countries during 2006-2014, met our inclusion criteria. Latin America was the most frequently visited region. Per capita costs ranged from $259 for cleft lip/cleft palate (CL/CP) missions to $2900 for a neurosurgery mission. Mission effectiveness ranged from 3 disability adjusted life years (DALYs) averted per patient for orthopedic surgery missions to 8.12 DALYs averted per patient for a neurosurgery mission. CL/CP and general surgery missions were the most cost-effective, averaging $80/DALY and $87/DALY, respectively. The neurosurgical, orthopedic, and hand surgery missions averaged the highest costs/DALY averted, with the cost-effectiveness being $357/DALY, $435/DALY, and $445/DALY, respectively. All analyzed missions were very cost effective. CONCLUSION: To date, this is the first study to assess the cost-effectiveness of short-term surgical missions across surgical specialties. Neurosurgical missions avert the largest number of healthy life years compared to other specialties, and thus, could yield a greater long-term benefit to resource-poor communities. We recommend that further studies be carried out to assess the impact of surgical missions in low-resource settings.

Time dependent pattern of cellular characteristics causing ventriculoperitoneal shunt failure in children.

BACKGROUND: Ventriculoperitoneal shunt obstruction remains a major problem in pediatric neurosurgery. We analyzed the tissue reaction to ventriculoperitoneal shunts and compared the histology versus time elapsed to shunt failure. METHODS: 85 ventricular catheter tissues samples obtained from 71 patients were reviewed along with time elapsed to shunt revision. Pathology reports of all tissue samples were divided into three categories: inflammatory based on the presence of lymphocytes, macrophages, and microglial cells; reactive based on the presence of fibro-connective tissue, reactive astrocytes, and Rosenthal fibers; and normal brain tissue based on presence of choroid plexus. These categories were then grouped according to time elapsed to shunt revision. Group I had those shunts revised <6 months, group II included shunts revised between 6 months and 3 years, while group III had shunts revised after more than 3 years. RESULTS: The incidence of inflammatory type of histology was 44% (16/36) in group I, 22% (6/27) in group II, and 18% (4/22) in group III. The reactive histology was 42% (15/36) in group I, 67% (18/27) in group II, and 77% (17/22) in group III. There was a clear noted difference of incidence between inflammatory versus reactive histology between early shunt failure compared to late shunt failure. Incidence of normal brain tissue remained high in group I with 8%, 11% in group II, and none in group III. CONCLUSION: Early shunt obstruction arises from pathologies different from those causing late shunt obstructions.

Correction of Chiari malformation due to closure of a concomitant thoracic meningocele.

INTRODUCTION: Chiari malformations are characterized by hindbrain herniation. Historically, some types have been linked to neural tube defects, but the causal relationship between the two conditions is still unclear. CASE REPORT: We report on a full-term male neonate with a prenatally diagnosed posterior thoracic meningocele, whose MRI demonstrated Chiari malformation. The meningocele was closed in the second week of life. The Chiari-related symptoms rapidly improved following surgery. Postoperative MRI at 7 months of age showed ascent of the cerebellar tonsils to a normal position. DISCUSSION: This case suggests that the traction on the cerebellum by a fixed spinal cord may play a role in the pathogenesis of the multifaceted Chiari malformations.

Suboccipital craniotomy for Chiari I results in evoked potential conduction changes.

BACKGROUND: Management of Chiari I is controversial, in part because there is no widely used quantitative measurement of decompression. It has been demonstrated that brainstem auditory evoked responses (BAER) and somatosensory evoked potentials (SSEP) have decreased conduction latencies after wide craniectomy. We analyzed these parameters in a suboccipital craniectomy/craniotomy procedure. METHODS: Thirteen consecutive patients underwent suboccipital decompression for treatment of symptomatic Chiari I. Craniectomy was restricted to the inferior aspect of the nuchal line, and in most cases the bone flap was replaced. Neuronal conduction was monitored continuously with median nerve somatosensory evoked potentials (M-SEP), posterior tibial nerve somatosensory evoked potentials (T-SEP), BAER, or a combination. The M-SEP N20, T-SEP P37, and BAER V latencies were recorded at four milestones - preoperatively, following craniotomy, following durotomy, and following closure. RESULTS: Five males and eight females, with average age of 9 years, were studied. Clinical improvement was noted in all 13 patients. M-SEP N20 latency decreased from a mean of 18.55 at baseline to 17.75 ms after craniotomy (P = 0.01); to 17.06 ms after durotomy (P = 0.01); and to 16.68 ms after closing (P = 0.02). T-SEP P37 latency did not change significantly. BAER V latency decreased from a mean of 6.25 ms at baseline to 6.14 ms after craniotomy (P = 0.04); to 5.98 ms after durotomy (P = 0.01); and to 5.95 ms after closing (P = 0.45). CONCLUSION: Significant improvements in conduction followed both craniectomy and durotomy. Bone replacement did not affect these results.

The International Tethered Cord Partnership: Beginnings, process, and status.

BACKGROUND: Spina bifida presents a significant cause of childhood morbidity in lower- and middle-income nations. Unfortunately, there is a paucity of literature examining outcomes among children with spina bifida in these countries. The goal of the International Tethered Cord Parternship is twofold: (1) to establish an international surveillance database to examine the correlation between time of repair and clinical outcomes in children with spina bifida and tethered cord; and (2) to foster collaboration among international institutions around pediatric neurosurgical concerns. METHODS: Twelve institutions in 7 countries committed to participating in the International Tethered Cord Partnership. A neurosurgeon at each institution will evaluate all children presenting with spina bifida and/or tethered cord using the survey instrument after appropriate consent is obtained. The instrument was developed collaboratively and based on previous measures of motor and sensory function, ambulation, and continence. All institutions who have begun collecting data received appropriate Institutional Review Board approval. All data will be entered into a Health Insurance Portability and Accountability Act (HIPAA) compliant database. In addition, a participant restricted internet forum was created to foster communication and includes non-project-specific communications, such as case and journal article discussion. RESULTS: From October 2010 to December 2010, 82 patients were entered from the various study sites. CONCLUSION: To our knowledge this is the first international pediatric neurosurgical database focused on clinical outcomes and predictors of disease progression. The collaborative nature of the project will not only increase knowledge of spina bifida and tethered cord, but also foster discussion and further collaboration between neurosurgeons internationally.

Correction of large facial encephalocele with bilateral rare craniofacial clefts.

Treatment of Tessier number 3, 11 craniofacial clefts represent a surgical challenge with complex bone and soft tissue deficits of the lip, cheek, medial orbit, and forehead. The severity of the presenting defect will ultimately determine the number of reconstructive stages required as well as the timing of each stage. Initial surgery in infancy is aimed at functional correction. We present the case of a patient with an expanding fronto-orbital encephalocele, a right number 3, 11 cleft and a left number 3, 10 cleft. The initial procedure repaired the encephalocele and reconstructed the supraorbital and forehead regions. Subsequent surgeries corrected the bilateral facial clefts with cleft lip repair, rotation of the forehead and nasal unit, cheek advancement, and a lower eyelid transposition flap.

Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation.

BACKGROUND: Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown. METHODS: Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients. Potential associations between neurosphere formation and clinical outcome were analyzed retrospectively. RESULTS: Thirty-seven percent of all samples formed renewable neurospheres. Analysis of available clinical outcome data from 51 patients demonstrated significantly increased hazard ratios (HR) for both disease progression (HR = 9.9, P < 0.001) and death (HR = 16.6, P < 0.01) in the neurosphere forming group. Furthermore, neurosphere formation correlated with adverse progression free survival (PFS) in glial and embryonal tumors, but not in mixed glioneuronal tumors. Overall survival (OS) was significantly worse for neurosphere-forming patients with embryonal tumors, as a group and amongst the subgroup with medulloblastoma, but not in the glial group. Multivariate analysis showed that neurosphere formation was associated with diminished PFS and OS independent of age, gender, or treatment. Neurosphere formation was an independent predictor of diminished PFS of glial tumors after adjusting for grade. Multivariate analysis, adjusting for both Ki67 staining and neurosphere formation, demonstrated that neurosphere formation remained predictive of progression whereas Ki67 did not. CONCLUSIONS: Neurosphere formation is more predictive of pediatric brain tumor progression than semi-quantitative Ki67 staining. Pediatric brain tumor derived neurospheres may provide a predictive model for preclinical explorations.

A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens.

The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g., immunohistochemistry) or require large sample sizes (e.g., flow cytometry). Here, we report a microfluidic platform-microfluidic image cytometry (MIC)-capable of quantitative, single-cell proteomic analysis of multiple signaling molecules using only 1,000 to 2,800 cells. Using cultured cell lines, we show simultaneous measurement of four critical signaling proteins (EGFR, PTEN, phospho-Akt, and phospho-S6) within the oncogenic phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. To show the clinical application of the MIC platform to solid tumors, we analyzed a panel of 19 human brain tumor biopsies, including glioblastomas. Our MIC measurements were validated by clinical immunohistochemistry and confirmed the striking intertumoral and intratumoral heterogeneity characteristic of glioblastoma. To interpret the multiparameter, single-cell MIC measurements, we adapted bioinformatic methods including self-organizing maps that stratify patients into clusters that predict tumor progression and patient survival. Together with bioinformatic analysis, the MIC platform represents a robust, enabling in vitro molecular diagnostic technology for systems pathology analysis and personalized medicine.

Suboccipital craniotomy in the surgical treatment of Chiari I malformation.

OBJECT: The object of this study was to present craniotomy for Chiari type I patients. MATERIALS AND METHODS: Six patients with Chiari type I underwent suboccipital craniotomy. All patients showed clinical improvement, and none had any complications. Two patients had syringomyelia; it disappeared in entirety. We describe the procedure for posterior fossa decompression. RESULTS: Three-dimensional volumetric analysis using Vitrea workstation for postoperative posterior fossa volumes was calculated and was seen to have been increased on an average, from pre-operative (168 cc) to postoperative volume (192 cc). CONCLUSION: We thus conclude that suboccipital craniotomy results in resolution of the Chiari symptoms yet achieves effective expansion of posterior fossa.

A case report of intraventricular gliofibroma.

Gliofibroma is a rare tumor with biphasic morphology. We report a case of a 3-month-old girl presenting with increasing head circumference. CT and MRI showed the presence of a large heterogeneous, nonenhancing tumor filling the atria and bodies of the lateral ventricles with caudal extension into the third ventricle. Hydrocephalus was noted. A biopsy was performed and pathology showed the presence of glial and collagenous tissue consistent with the diagnosis of gliofibroma. However, no mitosis or necrosis was seen. Immunohistochemistry was positive for glial fibrillary acid protein, Masson trichrome and reticulin. The patient was followed up for a period of 10 years. Recent MRI showed stable appearance of the tumor and clinically the patient is neurologically intact with normal cognitive development. Our case report has the longest follow-up so far reported in the literature, of 10 years. As evident from our case report, we recommend a conservative treatment approach for gliofibroma with benign histology.

Neurosphere formation is an independent predictor of clinical outcome in malignant glioma.

Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship among neurosphere formation in cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples were cultured in neurosphere conditions from 32 patients with glioma, including a subpopulation of 15 patients with primary glioblastoma. A subsample of renewable neurosphere cultures was xenografted into mouse brain to determine if they were tumorigenic. Our study shows that both renewable neurosphere formation and tumorigenic capacity are significantly associated with clinical outcome measures. Renewable neurosphere formation in cultured human glioma significantly predicted an increased hazard of patient death and more rapid tumor progression. These results pertained to both the full population of glioma and the subpopulation of primary glioblastoma. Similarly, there was a significant hazard of progression for patients whose glioma had tumorigenic capacity. Multivariate analysis demonstrated that neurosphere formation remained a significant predictor of clinical outcome independent of Ki67 proliferation index. In addition, multivariate analysis of neurosphere formation, tumor grade and patient age, demonstrated that neurosphere formation was a robust, independent predictor of glioma tumor progression. Although the lengthy duration of this assay may preclude direct clinical application, these results exemplify how neurosphere culture serves as a clinically relevant model for the study of malignant glioma. Furthermore, this study suggests that the ability to propagate brain tumor stem cells in vitro is associated with clinical outcome.

Brain stem candidiasis mimicking cerebellopontine angle tumor.

BACKGROUND: Infectious process can mimic cerebral tumors. We present the first report of a fugal infection in brainstem mimicking cerebral tumors in the literature. CASE DESCRIPTION: A 17-month-old boy presented with abnormal movements of his left arm and difficulty walking for 2 weeks. The MRI of the patient showed an enhancing partially cystic and partially solid mass in the right CP angle cistern, interpreting as CP tumor. On MRS, there was a decreased N-acetylaspartate/Creatine ratio and an elevated choline/Cr ratio. The patient underwent right retrosigmoid craniotomy and excisional biopsy. On the specimen, there were numerous fungal organisms consistent with Candida species. Our patient recovered completely after and 377-day voriconazole treatment. He was still quite well without neurologic sequelae at follow-up for 2 years. CONCLUSIONS: Brainstem candidiasis in immunocompetent host can masquerade the CP angle tumor. The MRI and MRS are not always diagnostic. Neurosurgical intervention is mandatory to relieve the mass effect in brainstem with high risk and achieve the pathologic diagnosis. Followed by voriconazole treatment, the patient could be treated successfully.

Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.

Emerging evidence suggests that neural stem cells and brain tumors regulate their proliferation via similar pathways. In a previous study, we demonstrated that maternal embryonic leucine zipper kinase (Melk) is highly expressed in murine neural stem cells and regulates their proliferation. Here we describe how MELK expression is correlated with pathologic grade of brain tumors, and its expression levels are significantly correlated with shorter survival, particularly in younger glioblastoma patients. In normal human astrocytes, MELK is only faintly expressed, and MELK knockdown does not significantly influence their growth, whereas Ras and Akt overexpressing astrocytes have up-regulated MELK expression, and the effect of MELK knockdown is more prominent in these transformed astrocytes. In primary cultures from human glioblastoma and medulloblastoma, MELK knockdown by siRNA results in inhibition of the proliferation and survival of these tumors. Furthermore, we show that MELK siRNA dramatically inhibits proliferation and, to some extent, survival of stem cells isolated from glioblastoma in vitro. These results demonstrate a critical role for MELK in the proliferation of brain tumors, including their stem cells, and suggest that MELK may be a compelling molecular target for treatment of high-grade brain tumors.

Choroid plexus hyperplasia: surgical treatment and immunohistochemical results. Case report.

Diffuse villous hyperplasia of the choroid plexus is a rare but potential source of nonobstructive hydrocephalus. In addition to discussing the authors' staged surgical approach and medical management decisions in a patient with this rare and challenging condition, immunohistochemical studies of the choroid plexus epithelium are presented to examine the pathophysiological factors involved in abnormal cerebrospinal fluid (CSF) production in this disease. The patient, a 15-month-old girl born at 36 weeks' gestation, underwent a bilateral craniotomy with resection of the choroid plexus to treat her villous hyperplasia. Immunohistochemical studies of the resected choroid plexus were conducted for the purpose of examining the carbonic anhydrase II (CAII) enzyme and the aquaporin 1 (AQP1) membrane protein. Results were compared with immunohistochemical studies conducted in a small series of autopsy specimens of normal human choroid plexuses. There was no change in the immunoreactivity of CAII in the patient with villous hyperplasia compared with normal controls, whereas AQP1 immunoreactivity was significantly weaker in the patient compared with normal controls. Postoperatively, the patient's CSF overproduction resolved and her neurological symptoms improved over time. Shunting techniques and presently available pharmaceutical treatments alone do not provide adequate treatment of high-output CSF conditions. Surgical removal of the affected choroid plexus is a feasible and effective treatment. Results of the immunohistochemical studies reported here support the suggestion that the CAII enzyme is retained in villous hyperplasia of the choroid plexus. However, there appears to be decreased expression and perhaps downregulation of AQP1 in villous hyperplasia compared with normal choroid plexus. Future studies may elucidate the significance of these observations.

Chiari I anatomy after ventriculoperitoneal shunting: posterior fossa volumetric evaluation with MRI.

INTRODUCTION: Cephalocranial disproportion was said to be responsible for Chiari I malformation after ventriculoperitoneal shunt. We aimed to evaluate if the volumetric characteristics of Chiari I after a ventriculoperitoneal shunt was due to a general volumetric reduction and if it is restricted to the posterior fossa. RESULTS: Our results show that the posterior fossa volume, cisternal, clival length, and posterior cranial fossa volume ratio were reduced in the shunted group compared to the controls (p<0.05). Cerebellar and supratentorial volumes were similar between both groups. Craniocaudal extent, inferior, and superior tonsillar herniations were greater in the shunted group than control (p<0.05). The frontal occipital horn ratio in both groups was within normal range. DISCUSSION: Chiari I anatomy after a ventriculoperitoneal shunt could develop in children and we propose a "posterior cranial fossa disproportion" rather than a "cephalocranial disproportion."

Transcranial Doppler in infantile cerebrospinal fluid disorders: clinical validity.

The present study was designed to investigate a possible relationship between transcranial Doppler sonography (TCD) parameters with infantile hydrocephalus and other types of cerebrospinal fluid (CSF) abnonnalities, i.e. arrested hydrocephalus and essential ventriculomegaly. TCD parameters in the major arteries of the circle of Willis were studied in hydrocephalic children (n = 12) before and after insertion of a ventricular shunt device. It was correlated with TCD parameters of children with CSF disorders (n = 13), in whom no surgery was performed. Also, TCD parameters were assessed in control cases (n = 10). Mean values for medial cerebral artery (MCA) flow velocities were higher in the essential ventriculomegaly (75.38 +/- 4.1) and in the control group (73.93 +/- 3.4) compared with hydrocephalic children (64.13 +/- 5.3). All hydrocephalic children had a higher mean MCA pulsatility index (RI) (1.08 +/- 0.13) and resistance index (RI) (0.64 +/- 0.17) values than the essential ventriculomegaly group (PI: 1.03 +/- 0.48; RI: 0.63 +/- 0.13) and the control group (PI: 0.84 +/- 0.32; RI: 0.57 +/- 0.23). Analysis of all TCD parameters disclosed its usefulness only after a particular and thorough evaluation of the TCD results with special emphasis in the clinical correlation of every case.

Cancerous stem cells can arise from pediatric brain tumors.

Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2, musashi-1, bmi-1, maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.

A mathematical model for self-limiting brain tumors.

It is puzzling that certain brain tumors exhibit arrested exponential growth. We have observed in pediatric low-grade astrocytomas (LGA) at a certain volume approximately 100-150 cm(3) that the tumor ceases to grow. This observation led us to develop a macroscopic mathematical model for LGA growth kinetics that assumes the flow through the surface of the astrocytoma of a triggering agent or "promoter" that is uniformly distributed throughout the tumor, thereby providing relatively homogeneous growth. The model relates the transport of the promoter by the electrochemical potential associated with the tumor and diffusion effects through the surface of the growth and its consumption throughout the tumor volume via a pair of ordinary differential equations. The model assumes a constant growth rate, if the promoter density is above some threshold, and is zero otherwise. We also develop equations for an electrochemical (Nernst) transport mechanism for the promoter, and describes the microscopic basis for the macroscopic evolution to the equilibrium state at a well-defined and universal size. The latter description is unstable to asymmetric perturbations and provides a "star-like" shape for emergent tumors and a spheroidal shape for fully developed ones. The underlying assumption in our hypothesis would also result in tumor growth remission beginning from the periphery and proceeding inwards, a feature that has now been validated clinically.