The role of neurosurgeons in global public health: the case of folic acid fortification of staple foods to prevent spina bifida.

OBJECTIVE: The global neurosurgery movement arose at the crossroads of unmet neurosurgical needs and public health to address the global burden of neurosurgical disease. The case of folic acid fortification (FAF) of staple foods for the prevention of spina bifida and anencephaly (SBA) represents an example of a new neurosurgical paradigm focused on public health intervention in addition to the treatment of individual cases. The Global Alliance for the Prevention of Spina Bifida-F (GAPSBiF), a multidisciplinary coalition of neurosurgeons, pediatricians, geneticists, epidemiologists, food scientists, and fortification policy experts, was formed to advocate for FAF of staple foods worldwide. This paper serves as a review of the work of GAPSBiF thus far in advocating for universal FAF of commonly consumed staple foods to equitably prevent SBA caused by folic acid insufficiency. METHODS: A narrative review was performed using the PubMed and Google Scholar databases. RESULTS: In this review, the authors describe the impact of SBA on patients, caregivers, and health systems, as well as characterize the multifaceted requirements for proper spina bifida care, including multidisciplinary clinics and the transition of care, while highlighting the role of neurosurgeons. Then they discuss prevention policy approaches, including supplementation, fortification, and hybrid efforts with folic acid. Next, they use the example of FAF of staple foods as a model for neurosurgeons' involvement in global public health through clinical practice, research, education and training, and advocacy. Last, they describe mechanisms for involvement in the above initiatives as a potential academic tenure track, including institutional partnerships, organized neurosurgery, neurosurgical expert groups, nongovernmental organizations, national or international governments, and multidisciplinary coalitions. CONCLUSIONS: The role of neurosurgeons in caring for children with spina bifida extends beyond treating patients in clinical practice and includes research, education and training, and advocacy initiatives to promote context-specific, evidence-based initiatives to public health problems. Promoting and championing FAF serves as an example of the far-reaching, impactful role that neurosurgeons worldwide may play at the intersection of neurosurgery and public health.

Anterior Cervical Discectomy with Instrumented Allograft Fusion: Lordosis Restoration and Comparison of Functional Outcomes among Patients of Different Age Groups.

OBJECTIVE: To investigate clinical parameters of anterior cervical discectomy and fusion (ACDF) treatment and outcomes using osseous allografts in different age groups, study the postoperative results of restoration of lordosis, and evaluate the utility of bone allografts for ACDF, including graft subsidence. METHODS: We reviewed data from 154 patients with clinical symptoms and radiologic signs of disc herniation and/or cervical spondylosis. Decompression was achieved through discectomy, osteophyte ablation, endplate drilling, and foraminotomy. Fusion was achieved with allografts, demineralized bone matrix, and cervical plates/screws. The relationships between preoperative and postoperative cervical spine configuration (ie, Benzel's criteria), pain intensity, and neurologic status were analyzed. RESULTS: The mean patient age was 51 years, and the median duration of symptoms was 6 months. The mean age differed significantly between the patients with diabetes and those without diabetes. The mean body mass index (BMI) was 30.36. Fifty-two patients had disc herniation, and 102 had spondylosis. Surgery was performed on a total of 313 levels. The median duration of follow-up was 24 months. Marked improvements in postoperative spine configuration or preservation of lordosis were recorded. Overall, 122 patients were neurologically intact, and 32 patients experienced residual postsurgery neurologic deficits (minor, n = 22; moderate, n = 9; severe, n = 1). Postoperative pain intensity and neurologic status were significantly improved. Outcomes were excellent in 66 patients, good in 61, fair in 24, and poor in 3 (no mortality). No significant differences in patient age, smoking habits, diabetes, or BMI were seen among outcomes, or between patients with soft disc herniation or spondylosis. CONCLUSIONS: Osseous allografting can excellently restore cervical lordosis regardless of age and is an excellent graft choice for ACDF. Patients of advanced age with comorbidities should not be denied surgery.

Surgical and molecular considerations in the treatment of pediatric thalamopeduncular tumors.

OBJECTIVE Thalamopeduncular tumors are a group of pediatric low-grade gliomas that arise at the interface of the thalamus and brainstem peduncle. They typically occur within the first 2 decades of life, presenting with progressive spastic hemiparesis. Treatment strategies, including surgical intervention, have varied significantly. The authors present their experience in the treatment of 13 children, ages 2-15 years, with non-neurofibromatosis-related pilocytic astrocytomas located in the thalamopeduncular region. METHODS Between 2003 and 2016, 13 children presenting with progressive spastic hemiparesis due to a pilocytic astrocytoma at the interface of the thalamus and cerebral peduncles were identified. Medical records were reviewed retrospectively for clinical, radiological, pathological, and surgical data. Formalin-fixed, paraffin-embedded tissue was obtained for 12 cases and tested for KIAA1549-BRAF fusion and BRAF V600E point mutation. RESULTS On preoperative diffusion tensor imaging tractography (performed in 12 patients), the ipsilateral corticospinal tract was displaced laterally in 1 case (8.3%), medially in 1 case (8.3%), anterolaterally in 10 cases (83%), and posteriorly in no cases. Ten patients underwent resection via a transtemporal, transchoroidal approach, which was chosen to avoid further damage to motor function in cases of tumors that caused anterolateral or medial corticospinal tract displacement. With this approach, complications included hemianopia, oculomotor palsy, and tremor at a rate of 50%. Among the 12 patients with obtainable follow-up (mean 50.9 months), none received adjuvant therapy, and only 2 (17%) experienced recurrence or progression. KIAA1549-BRAF fusions were present in 10 cases (83%), while BRAF V600E was absent (0%). The 2 fusion-negative tumors had clinical features atypical for the series, including multi-focality and infiltration. CONCLUSIONS Transcortical, transchoroidal resection of thalamopeduncular tumors through the middle temporal gyrus allows for a high rate of gross-total resection and cure. Diffuse tensor tractography is a critical component of the preoperative planning process to determine the location of white matter tracts in proximity. Molecular status may correlate with clinical features, and the presence of BRAF lesions offers an additional target for future novel therapeutics.

Clinical Characteristics and Long-Term Outcomes of Movement Disorders in Childhood Thalamic Tumors.

BACKGROUND: We studied the outcomes of movement disorders that were associated with childhood thalamic tumors. METHODS: We retrospectively reviewed 83 children with thalamic tumors treated at our institution from 1996 to 2013 to document the incidence and outcome of movement disorders. Magnetic resonance imaging was used to analyze the involvement of thalamic nuclei, and three instruments were used to rate the severity of the disorders. RESULTS: Nine (11%) patients had one or more of the following movement disorders: postural tremor, resting tremor, ballism, dystonia, myoclonus, and athetosis. Median age at tumor diagnosis was seven years (range, 0.25 to 11 years), and the average age at movement disorder onset was eight years (range, 1.5 to 11 years). Movement disorders developed at a median of 1.5 months (range, 0 to 4 months) after surgical resection. The severity of the disorders was either unchanged or slightly improved during follow-up. The red nuclei were the only thalamic structures that showed tumor involvement in all nine patients. CONCLUSIONS: No specific injury of the thalamic nuclei was associated with movement disorders in children with thalamic tumors, and the severity of these disorders did not change over time.

Delayed methotrexate excretion in infants and young children with primary central nervous system tumors and postoperative fluid collections.

PURPOSE: High-dose methotrexate (HD-MTX) has been used to treat children with central nervous system tumors. Accumulation of MTX within pleural, peritoneal, or cardiac effusions has led to delayed excretion and increased risk of systemic toxicity. This retrospective study analyzed the association of intracranial post-resection fluid collections with MTX plasma disposition in infants and young children with brain tumors. METHODS: Brain MRI findings were analyzed for postoperative intracranial fluid collections in 75 pediatric patients treated with HD-MTX and for whom serial MTX plasma concentrations (MTX) were collected. Delayed plasma excretion was defined as (MTX) ≥1 µM at 42 hours (h). Leucovorin was administered at 42 h and then every 6 h until (MTX) <0.1 µM. Population and individual MTX pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling. RESULTS: Fifty-eight patients had intracranial fluid collections present. Population average (inter-individual variation) MTX clearance was 96.0 ml/min/m² (41.1 CV %) and increased with age. Of the patients with intracranial fluid collections, 24 had delayed excretion; only 2 of the 17 without fluid collections (P < 0.04) had delayed excretion. Eleven patients had grade 3 or 4 toxicities attributed to HD-MTX. No significant difference was observed in intracranial fluid collection, total leucovorin dosing, or hydration fluids between those with and without toxicity. CONCLUSIONS: Although an intracranial fluid collection is associated with delayed MTX excretion, HD-MTX can be safely administered with monitoring of infants and young children with intracranial fluid collections. Infants younger than 1 year may need additional monitoring to avoid toxicity.

Surgical management of tumors producing the thalamopeduncular syndrome of childhood.

OBJECT: Thalamopeduncular tumors arise at the junction of the inferior thalamus and cerebral peduncle and present with a common clinical syndrome of progressive spastic hemiparesis. Pathologically, these lesions are usually juvenile pilocytic astrocytomas and are best treated with resection with the intent to cure. The goals of this study are to define a common clinical syndrome produced by thalamopeduncular tumors and to discuss imaging characteristics as well as surgical adjuncts, intraoperative nuances, and postoperative complications relating to the resection of these neoplasms. METHODS: The authors present a retrospective review of their experience with 10 children presenting between 3 and 15 years of age with a thalamopeduncular syndrome. Formal preoperative MR imaging was obtained in all patients, and diffusion tensor (DT) imaging was performed in 9 patients. Postoperative MR imaging was obtained to evaluate the extent of tumor resection. A prospective analysis of clinical outcomes was then conducted by the senior author. RESULTS: Pilocytic astrocytoma was the pathological diagnosis in 9 cases, and the other was fibrillary astrocytoma. Seven of 9 pilocytic astrocytomas were completely resected. Radical surgery was avoided in 1 child after DT imaging revealed that the corticospinal tract (CST) coursed through the center of the tumor, consistent with the infiltrative nature of fibrillary astrocytoma as identified by stereotactic biopsy. In 8 patients, tractography served as an important adjunct for designing a surgical approach that spared the CST. In 6 cases the CSTs were pushed anterolaterally, making a transsylvian approach a poor choice, as was evidenced by the first patient in the series, who underwent operation prior to the advent of tractography, and who awoke with a dense contralateral hemiparesis. Thus, subsequent patients with this deviation pattern underwent a transcortical approach via the middle temporal gyrus. One patient exhibited medial deviation of the tracts and another had lateral deviation, facilitating a transtemporal and a transfrontal approach, respectively. CONCLUSIONS: The thalamopeduncular syndrome of progressive spastic hemiparesis presenting in children with or without symptoms of headache should alert the examiner to the possibility of a tumoral involvement of CSTs. Preoperative tractography is a useful adjunct to surgical planning in tumors that displace motor pathways. Gross-total resection of pilocytic astrocytomas usually results in cure, and therefore should be entertained when developing a treatment strategy for thalamopeduncular tumors of childhood.