Adamantinomatous craniopharyngioma: evolution in the management.

BACKGROUND: In spite of the continuous progresses in pediatric neurosurgery, adamantinomatous craniopharyngioma (AC) remains a challenging tumor due to its proximity to optic pathways, pituitary gland, hypothalamus, and Willis' circle, which can result in significant endocrine, cognitive, and neurological morbidity after treatment with subsequent impact on the patient's quality of life (QoL). The relevance that QoL has today explains the changes in the management of AC observed over the time. The goal of the present article is to provide a historical background, to show the milestones in the changes of the AC treatment, and to analyze the current main options to manage such a challenging tumor. MATERIAL AND METHODS: The pertinent literature has been reviewed. Moreover, a comparison between the past and recent personal series is reported. RESULTS: Three main eras have been identified. The first (named Cushing era) was characterized by the need to realize a harmless surgery and to define the best way to approach AC; the second (microscope era) was characterized by a tremendous technical and technological development, with remarkable results in term of safe tumor resection and control but relatively poor QoL outcomes; and the third one (current period) is characterized by an increasing integration between surgery and adjuvant treatments, with relatively minor tumor control but significant improvement of QoL (comparable overall survival). The authors' experience reflects these changes. Two groups of children were compared: 52 cases (mean follow-up: 17.5 years) belong to the historical series (group 1, 1985-2003, aggressive surgical management) and 41 (mean follow-up: 8.5 years) to the current one (Group 2, 2004-2021, integrated management). No significant differences between the two groups were detected about recurrence rate, surgical mortality, and overall survival. However, Group 2 showed significant lower rates of postoperative panhypopituitarism, obesity, and visual deterioration. CONCLUSIONS: Radical surgery allows for a good AC control with a low rate of recurrence but high risk of permanent morbidity. Despite the greater number of recurrences and surgeries, the more conservative policy, based on a combination of treatments, seems to provide the same tumor control with a better QoL. The advances in trans-nasal and trans-ventricular endoscopy, in proton therapy and in the management of the AC cyst are the main factors that allowed such an improvement.

Paths of Evolution of Progressive Anaplastic Meningiomas: A Clinical and Molecular Pathology Study.

Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.

Chiari 1 Malformation and Epilepsy in Children: A Missing Relationship.

Purpose: Once believed a result of pathophysiological correlations, the association between Chiari 1 malformation (CM1) and epilepsy has since been considered as a coincidence, due to missing etiologic or clinical matching points. At present, the problem is being newly debated because of the increasing number of CM1 diagnoses, often among children with seizures. No specific studies on this topic are available yet. The present study aimed at updating the information on this topic by reporting on a series of children specifically enrolled and retrospectively analyzed for this purpose. Methods: All children admitted between January 2015 and June 2020 for epilepsy and CM1 were considered (Group 1). They were compared with children admitted in the same period for symptoms/signs related to CM1 and/or syringomyelia (Group 2). Syndromic patients were excluded, as well as those with tumoral or other overt intracranial lesions. All patients received a complete preoperative work-up, including MRI and EEG. Symptomatic children with CM1/syringomyelia were operated on. The pertinent literature was reviewed. Results: Group 1 was composed of 29 children (mean age: 6.2 years) showing CM1 and epilepsy with several types of seizures. A share of 27% had CM1-related symptoms and syringomyelia. The mean tonsillar ectopia was 7.5 mm. Surgery was performed in 31% of cases. Overall, 62% of children are currently seizure-free (including 5/9 children who were operated on). Tonsillar herniation and syringomyelia regressed in 4/9 cases and 4/8 cases, improved in 4/9 cases and 3/8 cases, and remained stable in 1/9 and 1/8 cases, respectively. CM1 signs/symptoms regressed completely in 6/8 cases and improved or remained stable in one case in each of the two remaining patients. Group 2 consisted of 77 children (mean age: 8.9 years) showing symptoms of CM1 (75%) and/or syringomyelia (39%). The mean tonsillar ectopia was 11.8 mm. Non-specific EEG anomalies were detected in 13 children (17%). Surgery was performed in 76.5% of cases (18 children were not operated on because of oligosymptomatic). Preoperative symptoms regressed in 26%, improved in 50%, remained stable 22%, and worsened in 2%; CM1 radiologically regressed in 39%, improved in 37%, remained unchanged in 22%, and worsened in 2%; and syringomyelia/hydromyelia regressed in 61%, improved in 30%, and was stable in 9%. No statistically significant differences between the two groups were detected regarding the M/F ratio, presence of syringomyelia/hydromyelia, or CM1/syringomyelia outcome; moreover, no correlation occurred between seizure-free condition and PF decompression in Group 1, or between disappearance of EEG anomalies and PF decompression in Group 2. A significant difference between the two groups was noticed regarding the mean age at admission (p = 0.003), amount of tonsillar herniation (p < 0.00001), and PF decompression (p = 0.0001). Conclusions: These findings do not support clinical correlations between CM1 and epilepsy. Their course depends on surgery and antiepileptic drugs, respectively. The analysis of the literature does not provide evidence of a relationship between seizures and cerebellar anomalies such as CM1. Rather than being linked to a syndrome that could explain such an association, the connection between the two now has to be considered to be random.

Neurosurgical Defeats: Critically Ill Patients and the Role of Palliative Care Service.

The onco-functional balance in neuro-oncology requires maximizing tumor removal while rigorously preserving patients' neurological status. When postoperative worsening prevents the implementation of oncologic treatments, palliative care service offers an individualized path for symptom and psychosocial distress relief. Here, we report on a series of 25 patients operated on for malignant brain tumor who did not undergo adjuvant treatments after neurosurgery; they represented 3.9% of the whole institutional surgical series. These patients were significantly older and had a lower preoperative Karnofsky performance status than the whole cohort. Importantly, in 22 out of 25 (88%) cases, a surgical complication occurred, leading to clinical worsening in 21 patients. For the end of life, the majority of patients chose a hospice care facility (72%). While a careful selection of brain tumor patients candidate to neurosurgery is required, palliative care service provided invaluable help in coping with patients' and caregivers' needs.

Craniosynostosis and hydrocephalus: relevance and treatment modalities.

INTRODUCTION: Hydrocephalus is variously associated to syndromic craniosynostosis (CS), while it is randomly encountered in monosutural CS. Pathogenesis is still debated and reliable criteria for the diagnosis of overt hydrocephalus are lacking. Additionally, optimal treatment is controversial since it should balance the need to relieve intracranial hypertension and the risk of recurrence favored by lowering intracranial pressure. METHODS: A thorough review of the literature has been performed. Accordingly, pathogenic theories, diagnostic issues, and treatment options on hydrocephalus presenting in the context of CS are discussed. RESULTS: The association of hydrocephalus to simple CS is considered a fortuitous event. Its treatment is usually driven by the etiology and clinical relevance of hydrocephalus, favoring treatment before surgical correction to reduce CSF-related complications. On the other side, pathogenesis of hydrocephalus in the context of syndromic CS has been mainly related to factors that are secondary to the synostostic process, such as craniocerebral disproportion and venous hypertension. Hydrocephalus complicates 12-15% of syndromic CS, though its incidence is more relevant in FGFR2-related CS and raises up to 88% in Pfeiffer syndrome. Overt hydrocephalus should be properly differentiated by non-tense ventriculomegaly that is more frequent in Apert syndrome. Since intracranial hypertension is constant in syndromic CS even in the absence of active hydrocephalus, radiological monitoring of ventricular size along with intracranial pressure monitoring is essential. Active hydrocephalus occurs more frequently in infants, though stable ventriculomegaly may evolve into overt hydrocephalus after cranial expansion. If hydrocephalus is not clinically prominent, cranial expansion should be favored as first surgical step. Although posterior cranial expansion may address posterior cranial fossa constriction and stabilize ventricular dilation, effectiveness in long-term control of hydrocephalus is not clear. ETV is an effective treatment option, though success rate is affected by the presence of brain malformations and patient age. Extrathecal CSF shunting should be used as last resource due to the increased risk of complications in this context. CONCLUSIONS: The pathogenesis of hydrocephalus complicating syndromic CS should be further investigated. Concomitantly, the definition of reliable diagnostic criteria is advocated in order to promptly and properly identify active hydrocephalus. Finally, treatment algorithm should refine the best timing and treatment options aiming to relieve intracranial hypertension on one side and reduce the risk of restenosis on the other side.