Outcomes and surgical approaches for pineal region tumors in children: 30 years' experience.

OBJECTIVE: Pineal region tumors account for 2.7%-11% of all CNS tumors in children. In this series, the authors present their surgical results and long-term outcomes from a pediatric pineal region tumor cohort. METHODS: A total of 151 children aged 0-18 years were treated from 1991 to 2020. Tumor markers were collected in all patients; if positive, chemotherapy was performed, and if negative, biopsy was performed, preferably endoscopically. Resection was performed when there was a residual germ cell tumor (GCT) lesion after chemotherapy. RESULTS: The distribution based on histological type, as verified by markers, biopsy, or surgery, was germinoma (33.1%), nongerminomatous GCT (NGGCT) (27.2%), pineoblastoma (22.5%), glioma (12.6%), and embryonal tumor (atypical teratoid rhabdoid tumor) (3.3%). A total of 97 patients underwent resection, and gross-total resection (GTR) was achieved in 64%; the highest GTR rate (76.6%) was found in patients with GCTs, and the lowest (30.8%) was found in those with gliomas. The supracerebellar infratentorial approach (SCITA) was the most common, performed in 53.6% of patients, followed by the occipital transtentorial approach (OTA), performed in 24.7% of patients. Lesions were biopsied in 70 patients, and the diagnostic accuracy was 91.4. The overall survival (OS) rates at 12, 24, and 60 months as stratified by histological type were 93.7%, 93.7%, and 88% for patients with germinomas; 84.5%, 63.5%, and 40.7% for patients with pineoblastomas; 89.4%, 80.8%, and 67.2% for patients with NGGCTs; 89.4%, 78.2%, and 72.6% for patients with gliomas; and 40%, 20%, and 0% for patients with embryonal tumors, respectively (p < 0001). The OS at 60 months was significantly higher in the group with GTR (69.7%) than in the group with subtotal resection (40.8%) (p = 0.04). The 5-year progression-free survival was 77% for patients with germinomas, 72.6% for patients with gliomas, 50.8% for patients with NGGCTs, and 38.9% for patients with pineoblastomas. CONCLUSIONS: The efficacy of resection varies by histological type, and complete resection is associated with higher OS rates. Endoscopic biopsy is the method of choice for patients presenting with negative tumor markers and hydrocephalus. For tumors restricted to the midline and with extension to the third ventricle, a SCITA is preferred, whereas for lesions with extension toward the fourth ventricle, an OTA is preferred.

Awake Microsurgical Resection for Optochiasmatic Cavernous Malformation.

Cavernous malformations (CM) affect approximately 0.5% of the population, with only a limited portion being located in the optic nerve and chiasma. The clinical presentation is determined by their locations. In the optochiasmatic CM, the acute visual disturbance is the most common presentation. Chronically, many show a progressive visual loss, chronic headache, and pituitary disturbances. The differential diagnosis includes optic glioma, arteriovenous malformations, aneurysm, craniopharyngioma, pituitary apoplexy, and inflammatory conditions. In Video 1, we present the case of a 39-year-old woman with a history of a hemorrhagic optochiasmatic cavernoma in 2016, who started using propranolol to reduce the lesion and symptoms of visual loss. Moreover, the first microsurgical resection of the cavernoma and evacuation of the hematoma were performed in the same year. Owing to evolvement from a partial to a total vision loss in the left eye and presentation of new symptoms in the right eye, the patient underwent microsurgical resection. The surgery was performed sequentially. An awake craniotomy was performed to monitor the chiasma and right optic nerve. The postoperative magnetic resonance imaging showed complete resection of the CM, and the patient fully recovered. The patient signed the institutional consent form, stating that he or she accepts the procedure and allows the use of his or her images and videos for any type of medical publications in conferences and/or scientific articles.

Three-Dimensional Quantitative Analysis of the Brainstem Safe Entry Zones Based on Internal Structures.

OBJECTIVE: Brainstem safe entry zones (EZs) are gates to access the intrinsic pathology of the brainstem. We performed a quantitative analysis of the intrinsic surgical corridor limits of the most commonly used EZs and illustrated these through an inside perspective using 2-dimensional photographs, 3-dimensional photographs, and interactive 3-dimensional model reconstructions. METHODS: A total of 26 human brainstems (52 sides) with the cerebellum attached were prepared using the Klingler method and dissected. The safe working areas and distances for each EZ were defined according to the eloquent fiber tracts and nuclei. RESULTS: The largest safe distance corresponded to the depth for the lateral mesencephalic sulcus (4.8 mm), supratrigeminal (10 mm), epitrigeminal (13.2 mm), peritrigeminal (13.3 mm), lateral transpeduncular (22.3 mm), and infracollicular (4.6 mm); the rostrocaudal axis for the perioculomotor (11.7 mm), suprafacial (12.6 mm), and transolivary (12.8 mm); and the mediolateral axis for the supracollicular (9.1 mm) and infracollicular (7 mm) EZs. The safe working areas were 46.7 mm2 for the perioculomotor, 21.3 mm2 for the supracollicular, 14.8 mm2 for the infracollicular, 33.1 mm2 for the supratrigeminal, 34.3 mm2 for the suprafacial, 21.9 mm2 for the infrafacial, and 51.7 mm2 for the transolivary EZs. CONCLUSIONS: The largest safe distance in most EZs corresponded to the depth, followed by the rostrocaudal axis and, finally, the mediolateral axis. The transolivary had the largest safe working area of all EZs. The supracollicular EZ had the largest safe area to access the midbrain tectum and the suprafacial EZ for the floor of the fourth ventricle.

Endoscope-Controlled Microsurgery of a Ruptured Middle Fossa Arachnoid Cyst.

Arachnoid cysts are responsible for 1% of expansive lesions in the central nervous system. Usually, they do not cause neurologic symptoms unless they have expansion or hemorrhage. Intracystic bleeding is caused by trauma or may be spontaneous. There are few cases in the literature of spontaneous hemorrhage of arachnoid cysts. This 2-dimensional video (Video 1) demonstrates the case of a 6-year-old boy who presented with headache and diplopia. At the physical examination, he exhibited right sixth nerve palsy. The complementary examinations revealed a left middle fossa arachnoid cyst classified as Galassi 2. An urgent procedure was planned to fenestrate the cyst. Informed written consent was obtained from the patient's family. Due to the team experience, endoscope-controlled microsurgery was performed. The patient experienced remission of the headache and the diplopia. A CT scan was performed on the first postoperative day and revealed a lamina of acute blood at the subdural space. It was an asymptomatic thin lamina of blood; we opted to watch and follow. One month later, a control MRI revealed a left frontoparietal subdural hematoma. Despite being asymptomatic, the hematoma was determined to have significant mass effect; thus, it was evacuated by a parietal burr-hole. After 1 month, another MRI showed resolution of the frontoparietal hematoma and significant reduction in the arachnoid cyst. There are few cases described of spontaneous rupture of arachnoid cyst; beyond that, we would like to illustrate a step-by-step procedure that is not widely available as a video article.

Combined treatment for a hemispheric cerebellar AVM.

Posterior fossa arteriovenous malformations (AVMs) can be a challenging disease, especially those large in size. AVMs can be treated with a combination of endovascular treatment and microsurgery. Here, the authors present the case of a 16-year-old female patient with progressive dizziness and episodic syncope. The workup of the patient showed a hemispheric cerebellar AVM, Spetzler-Martin grade IV. She underwent combined treatment (endovascular and microsurgery) with no complications and cure of the malformation. The video can be found here: https://youtu.be/rNw_Kyd76Mg.

High-grade gliomas in children and adolescents: is there a role for reoperation?

OBJECTIVE: Tumors of the CNS are the main causes of childhood cancer and have an incidence that exceeds that of leukemia. In addition, they are the leading causes of cancer-related death in childhood. High-grade gliomas account for 11% of such neoplasms and are characterized by aggressive clinical behavior and high morbidity and mortality. There is a lack of studies focusing on the factors that can prolong survival in these patients or guide therapeutic interventions. The authors aimed to investigate the factors related to longer survival durations, with a focus on reoperation for gross-total resection (GTR). METHODS: In this retrospective cohort study, the authors analyzed 78 patients diagnosed with high-grade gliomas occurring across all CNS locations except diffuse intrinsic pontine gliomas. Patients 0 to < 19 years of age were followed up at the Pediatric Oncology Institute. Overall survival (OS) and progression-free survival (PFS) were analyzed in the context of various prognostic factors, such as age, sex, histology, extent of tumor resection, reoperation for GTR, adjuvant treatment, and treatment initiation from 2010 onward. RESULTS: With a mean age at diagnosis of 8.7 years, 50% of the patients were female and approximately 39% underwent GTR at some point, which was already achieved in approximately 46% of them in the first surgery. The median OS was 17 months, and PFS was 10 months. In terms of median OS, the authors found no significant difference between those with reoperation for GTR and patients without GTR during treatment. Significant differences were observed in the OS in terms of the extent of resection in the first surgery, age, sex, Ki-67 expression, adjuvant treatment, and treatment initiation from 2010 onward. Furthermore, the PFS values significantly differed between those with GTR in the first surgery and Ki-67 expression ≥ 50%. CONCLUSIONS: This study demonstrates the importance of GTR for these neoplasms, highlights the role of surgeons in its achievement in the first attempt, and questions the role of reoperation for this purpose. Finally, this study further supports the use of combined adjuvant treatment for the improvement of OS and PFS.

Fetal surgery for occipital encephalocele.

OBJECTIVE: In this study, the authors retrospectively reviewed two cohorts of patients with occipital encephalocele (OE) and demonstrate the technical aspects of an innovative and unprecedented method for fetal OE correction. METHODS: This was a cross-sectional retrospective study of 22 patients who underwent surgery from July 2012 to July 2018. The inclusion criteria for participants were a gestational age between 19 weeks and 27 weeks, a maternal age ≥ 18 years, a normal fetal karyotype, the presence of microcephaly, and a cystic hernial sac with the cystic component accounting for more than 80% of the total volume, which was larger than 10 ml. The fetuses with OE and microcephaly underwent intrauterine repair. The exclusion criteria were the presence of a fetal anomaly not associated with OE, chromosomopathy, presence of the brainstem inside the hernial sac or venous sinuses inside the herniated content, the risk of premature birth, placenta previa, and maternal conditions that would constitute an additional risk for fetal and maternal health, as well as refusal for fetal surgery. The authors reviewed the potential for microcephaly reversal and the long-term neurocognitive development. RESULTS: The authors report the cases of 9 fetuses with OE and microcephaly who underwent intrauterine OE repair at gestational ages of less than 27 weeks (fetal group). One case selected for fetal surgery also presented with placental abruption. All patients who underwent the fetal operation had microcephaly reversal, and 3 patients required ventriculoperitoneal shunting in the 1st year of life. The authors reviewed the cases of 12 patients who underwent postnatal repair. In 10 cases, fetal surgery was refused (postnatal group), and in 2 cases, the inclusion criteria for fetal surgery were not met. The authors evaluated the neurocognitive development of the patients with the Bayley Scales of Infant Development II. The median score for the fetal group was 98.7, and that for the postnatal group was 27.8. CONCLUSIONS: The intrauterine repair of OE may stop the progression of encephalocele sac herniation and result in microcephaly reversal. The fetal group had a better cognitive outcome than the postnatal group. The technique required to correct this defect is feasible for those with previous experience in the correction of fetal myelomeningocele. However, more studies are needed to ensure the efficacy of this procedure.

Glioependymal cyst on the third cranial nerve: case report.

Glioependymal cysts are a rare, congenital, and benign condition. The authors report a case of a 2-year-old female patient who presented with a large exophytic glioependymal cyst located in the left cerebral peduncle, which began with a history of deteriorating function of the left third cranial nerve (CN III). A left 3-piece fronto-orbitozygomatic approach and a microsurgical complete excision of the cyst were performed without complications by accessing the midbrain through the perioculomotor entry zone. The patient's CN III function completely recovered after 3 months. Because there are currently no widely approved and used classification systems for these cysts, their reporting, naming, and classification are quite confusing in the literature. Thus, their origin, classification, and most common locations warrant further investigation. In addition to reporting this case, the authors present their review of the literature.

Cognitive performance in patients with cerebral arteriovenous malformation.

OBJECTIVE: A cerebral arteriovenous malformation (cAVM) can change over time and cause symptoms, but clinical studies tend to define only the patients with ruptured cAVMs as symptomatic and do not consider neurocognitive aspects prior to neurosurgical intervention. The objective of this study was to describe the neurocognitive function of patients with ruptured and unruptured cAVMs according to the Spetzler-Martin (SM) grade, flow status, and anatomical topography. METHODS: In this blinded cross-sectional study, 70 patients of both sexes and ages 18-60 years were evaluated using the Brazilian Brief Neuropsychological Assessment Battery Neupsilin. RESULTS: Of the 70 patients with cAVMs, 50 (71.4%) demonstrated deficits in at least one of the eight neurocognitive domains surveyed, although they did not exhibit neurological deficits. cAVMs in the temporal lobe were associated with memory deficits compared with the general population. The SM grade was not significantly associated with the results of patients with unruptured cAVMs. However, among patients with ruptured cAVMs, there were deficits in working memory in those with high-grade (SM grade) cAVMs and deficits in executive function (verbal fluency) in those with low-grade cAVMs (p < 0.001). CONCLUSIONS: This study indicates that patients with untreated cAVMs, either ruptured or unruptured, already exhibit neurocognitive deficits, even the patients without other neurological symptoms. However, the scales used to evaluate disability in the main clinical studies, such as A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), do not assess neurocognitive alterations and therefore disregard any deficits that may affect quality of life. The authors' finding raises an important question about the effects of interventional treatment because it reinforces the hypothesis that cognitive alterations may be preexisting and not determined by interventions.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X.

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs.

Angular and metric analysis of the neural structures in the cerebellopontine angle.

INTRODUCTION: The cerebellopontine angle (CPA) is a subarachnoid space in the lateral aspect of the posterior fossa. In this study, we propose a complementary analysis of the CPA from the cerebellopontine fissure. METHODS: We studied 50 hemi-cerebelli in the laboratory of neuroanatomy and included a description of the CPA anatomy from the cerebellopontine fissure and its relationship with the flocculus and the 5th, 6th, 7th, and 8th cranial nerves (CN) origins. RESULTS: The average distance from the 5th CN to the mid-line (ML) was 19.2 mm, 6th CN to ML was 4.4 mm, 7-8 complex to ML was 15.8 mm, flocculus to ML was 20.5 mm, and flocculus to 5th CN was 11.5 mm, additionally, and the diameter of the flocculus was 9.0 mm. The angle between the vertex in the flocculus and the V CN and the medullary-pontine line was 64.8 degrees. DISCUSSION: The most common access to the CPA is through the retrosigmoid-suboccipital region and this approach can be done with the help of an endoscope. The anatomy of origins of neural structures tends to be preserved in cases of CPA lesions. CONCLUSION: Knowledge of the average distances between the neural structures in the cerebellar-pontine fissure and the angular relationships between these structures facilitates the use of surgical approaches such as microsurgery and endoscopy.

Clinical Application of an Open-Source 3D Volume Rendering Software to Neurosurgical Approaches.

BACKGROUND: Preoperative recognition of the anatomic individualities of each patient can help to achieve more precise and less invasive approaches. It also may help to anticipate potential complications and intraoperative difficulties. Here we describe the use, accuracy, and precision of a free tool for planning microsurgical approaches using 3-dimensional (3D) reconstructions from magnetic resonance imaging (MRI). METHODS: We used the 3D volume rendering tool of a free open-source software program for 3D reconstruction of images of surgical sites obtained by MRI volumetric acquisition. We recorded anatomic reference points, such as the sulcus and gyrus, and vascularization patterns for intraoperative localization of lesions. Lesion locations were confirmed during surgery by intraoperative ultrasound and/or electrocorticography and later by postoperative MRI. RESULTS: Between August 2015 and September 2016, a total of 23 surgeries were performed using this technique for 9 low-grade gliomas, 7 high-grade gliomas, 4 cortical dysplasias, and 3 arteriovenous malformations. The technique helped delineate lesions with an overall accuracy of 2.6 ± 1.0 mm. 3D reconstructions were successfully performed in all patients, and images showed sulcus, gyrus, and venous patterns corresponding to the intraoperative images. All lesion areas were confirmed both intraoperatively and at the postoperative evaluation. CONCLUSIONS: With the technique described herein, it was possible to successfully perform 3D reconstruction of the cortical surface. This reconstruction tool may serve as an adjunct to neuronavigation systems or may be used alone when such a system is unavailable.

A case of giant fetal intracranial capillary hemangioma cured with propranolol.

Fetal brain tumors are rare. This report describes a giant posterior fossa capillary hemangioma treated with 3 mg/kg/day of propranolol for 6 months. Total regression was confirmed at 1 year, and no additional tumors were observed during the subsequent 2 years. No side effects relating to the use of this drug were detected; thus, the authors believe that propranolol may be useful for treating all intracranial capillary hemangiomas.