Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPGco / Estudio multicéntrico colaborativo del manejo neuroquirúrgico del craneofaringioma pediátrico en España: S-PedCPGco

Purpose To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. Methods We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. Results The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7–357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. Conclusions Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity (AU)

Objetivo Presentar un análisis descriptivo de los craneofaringiomas pediátricos tratados en varios hospitales españoles, definiendo los factores relacionados con la recurrencia y realizando un análisis crítico de los resultados. Métodos Estudio retrospectivo multicéntrico de los craneofaringiomas pediátricos tratados entre 2000-2017. Se recogieron variables epidemiológicas, clínicas y radiológicas, el objetivo de la primera cirugía, la tasa de recurrencia y su abordaje, los tratamientos adyuvantes, así como las complicaciones y la morbilidad permanente. Se estudió la relación estadística entre la progresión y el número de progresiones con las variables independientes. Resultados Se incluyeron 69 niños tratados en 8 hospitales españoles. La mayoría de los tumores se extendían por varios compartimentos intracraneales al diagnóstico, con invasión hipotalámica en el 41,3%. Habitualmente, la primera estrategia de tratamiento fue la resección radical (71%), con algunos pacientes tratados con radioterapia o quimioterapia intraquística. La tasa de progresión tras la primera cirugía fue del 53% en un seguimiento medio de 88,2 meses (rango 7-357). En el grupo de resección radical recurrieron un 38,8% de los tumores, un 40% en el de resección subtotal o biopsia y un 93,3% en el de fenestración quística±reservorio Ommaya. La mortalidad fue de un 7,2%. Las variables relacionadas de forma significativa con progresión fueron el tiempo de seguimiento, el tamaño del tumor y el objetivo de la primera cirugía. Conclusiones Los resultados obtenidos fueron aceptables en control de la enfermedad, secuelas hormonales o visuales y mortalidad, aunque hay varias áreas susceptibles de mejora. Nuestros objetivos a corto plazo deberían estar orientados a crear un registro nacional de craneofaringiomas pediátricos, alcanzar un consenso respecto al algoritmo de tratamiento y mejorar el diagnóstico de la disfunción hipotalámica para evitar morbilidad (AU)

Multicentric and collaborative study of Spanish neurosurgical management of pediatric craniopharyngiomas: S-PedCPG.co.

PURPOSE: To present a descriptive analysis of pediatric craniopharyngiomas (PedCPG) treated in various Spanish hospitals, defining factors related to recurrence and performing a critical analysis of the results. METHODS: We undertook a multicenter retrospective review of PedCPG treated between 2000 and 2017. Data collected included epidemiological variables, clinical and radiological characteristics, goal of first surgery, rate of recurrence and its approach, adjuvant treatment, complications and permanent morbidity. Associations were studied between progression and number of progressions and independent variables. RESULTS: The study involved 69 children from 8 Spanish hospitals. Most of the tumors invaded several intracranial compartments at diagnosis, with the hypothalamus involved in 41.3% of cases. The first treatment strategy was usually gross total resection (GTR) (71%), with some patients treated with radiotherapy or intracystic chemotherapy. The progression rate after first surgery was 53% in a mean follow-up of 88.2 months (range 7-357). In the GTR group 38.8% of tumors recurred, 40% in the group of subtotal resection or biopsy and 93.3% in the cyst fenestration±Ommaya reservoir group. Mortality was 7.2%. Follow-up period, size of the tumor and goal of first surgery were significantly related with progression. CONCLUSIONS: Our results in terms of disease control, hormonal or visual impairment and mortality were acceptable, but there are several areas for improvement. Our short-term goals should be to create a national register of PedCPG, reach a consensus about a treatment algorithm, and improve diagnosis of hypothalamic dysfunction to avoid preventable morbidity.

Development of Machine Learning-Based Predictor Algorithm for Conversion of an Ommaya Reservoir to a Permanent Cerebrospinal Fluid Shunt in Preterm Posthemorrhagic Hydrocephalus.

BACKGROUND: An Ommaya reservoir can be used to treat posthemorrhagic hydrocephalus secondary to intraventricular hemorrhage of prematurity until an acceptable weight can be obtained to place a permanent shunt. Identifying newborns at higher risk of developing shunt conversion may improve the management of these patients. This study aimed to develop a predictive algorithm for conversion of an Ommaya reservoir to a permanent shunt using artificial intelligence techniques and classical statistics. METHODS: A database of 43 preterm patients weighing ≤1500 g with posthemorrhagic hydrocephalus (Papile grades III and IV with Levene ventricular index >4 mm above the 97th percentile) managed with an Ommaya reservoir at our institution between 2002 and 2017 was used to train a k-nearest neighbor algorithm. Validation of results was done with cross-validation technique. Three scenarios were calculated: 1) considering all features regardless whether or not they are correlated with the output variable; 2) considering the features as predictors if they have a correlation >30% with the output variable; 3) considering the output of the previous analysis. RESULTS: When considering the outputs of a previous multivariate analysis, the algorithm reached 86% of cross-validation accuracy. CONCLUSIONS: The use of machine learning-based algorithms can help in early identification of patients with permanent need of a shunt. We present a predictive algorithm for a permanent shunt with an accuracy of 86%; accuracy of the algorithm can be improved with larger volume of data and previous analysis.

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours.

Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogeneous antigen expression, limited infiltration of T cells into the tumour, the selective trafficking provided by the blood-brain barrier, and the immunosuppressive tumour microenvironment have emerged as the main hurdles that need to be overcome for the success of CAR T cell therapy. In this review, we will focus mainly on the characteristics of the deadliest high-grade CNS paediatric tumours (medulloblastoma, ependymoma, and high-grade gliomas) and the potential of CAR T cell therapy to increase survival and patients' quality of life.

Spinal adrenal cortical adenoma associated with Beckwith-Wiedemann syndrome: case report and review of the literature.

PURPOSE: Ectopic adrenal cortical adenoma in the spinal region is extremely rare. The majority of cases of ectopic adrenocortical tissue are found along the path of embryonic migration within the urogenital tract. Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to tumor development, including adrenal lesions. To date, only eight spinal cases have been reported. This is the third reported case in pediatric population, the first one associated with genetic syndrome and the first benign to recur. We review the current literature on this topic. CASE DESCRIPTION: We present a 2-year-old boy affected by Beckwith-Wiedemann syndrome who developed a tumor at L4-L5 level. He underwent a gross total resection with MRI post-surgery demonstrating non-residual tumor. Histology disclosed an ectopic adrenal cortical adenoma with oncocytic features. Immunohistochemically was positive for inhibin-alpha, synaptophysin, and melan-A. It was negative for chromogranin A, GFAP, S-100, and other markers. One year later, he developed a recurrence at the same level being necessary a second surgery leaving a small sheet of residual tumor. CONCLUSION: Spinal adrenocortical adenomas are exceptional, and its behavior could be related to other conditions such as BWS. Gross total resection can be curative but a tight follow-up is needed. Immunohistochemical studies that include inhibin-alpha, synaptophysin, and melan-A can be useful in differential diagnosis as ultrastructural study. The decision on how to treat these patients is difficult given the low number of cases.

Deep brain stimulation for obsessive-compulsive disorder: is the side relevant?

BACKGROUND: Deep brain stimulation for obsessive-compulsive disorder (OCD) has targeted several subcortical nuclei, including the subthalamic nucleus (STN) and the nucleus accumbens. While the most appropriate target is still being looked for, little attention has been given to the side of the stimulated hemisphere in relationship to outcome. METHODS: We report 2 patients diagnosed with OCD, one having symmetry obsessions and the other one with sexual-religious obsessive thoughts. They were implanted bilaterally with deep electrodes located at both STN and nuclei accumbens. The effectiveness of the stimulation was tested for every possible paired combination of electrodes guided by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction. RESULTS: In both cases, the combination of electrodes which best relieved the OCD symptoms was both the left STN and left accumbens. In case 1, the preoperative Y-BOCS score was 33, and 1 month after stimulation it was 16. In case 2, the Y-BOCS scores were 33 and 3, respectively, with the patient being free of obsessions. CONCLUSION: Some reports suggest that lesion stimulation or stimulation of only the right side relieves OCD symptoms. However, anatomical and functional studies are not conclusive as to which side is most affected in OCD. Possibly, each OCD patient has an individualized optimal side to stimulate.

Effect of recombinant human growth hormone on peripheral nerve regeneration: experimental work on the ulnar nerve of the rat.

Neurotrophic factors may be used to improve the growth and repair of injured peripheral nerves. In this study we determined the effectiveness of recombinant human growth hormone on peripheral nerve injury in the Wistar rat. The ulnar nerve of the rat was sectioned and its proximal and distal ends were sutured to either end of a silastic tube, with the aim of encouraging regeneration through the tube. 32 ulnar nerve specimens were randomized into two groups: 18 nerves regenerating under the influence of recombinant growth hormone, and 14 nerves regenerating in its absence. The study was performed over a period of 8 weeks and progression of regeneration was assessed with regular surface electroneurography every 1-2 weeks after surgery. In the group receiving recombinant growth hormone, it comprised a significant improvement in the recovery of conduction velocity, and a more gradual increase in the amplitude of motor potential from the fifth week onwards was observed. Histological analysis of study specimens in the recombinant hormone group revealed an improved architecture of the regenerating nerve, a greater density of nerve fibers, and increased myelination with a lesser degree of endoneural fibrosis. Our work demonstrates the positive effect of the administration of recombinant human growth hormone in obtaining significantly improved conduction velocities, and a greater improvement in nerve regeneration from the fifth week of monitoring when compared to the control group. Histological analysis in the group receiving hormone showed acceptable degree of myelination with little granulation tissue and fibrosis.