Role of sodium fluorescein in pediatric low-grade glioma surgery: an update.

PURPOSE: Complete surgical resection is still the mainstay in the treatment of central nervous system low-grade tumors, eventually resulting curative. The complete surgical removal of these lesions, however, may be difficult in some cases because of their infiltrative nature. Intraoperative adjuncts may be a game changer. Sodium fluorescein (SF) is among the ideal candidates as intraoperative tools to favor the actual recognition of the tumor extension, since it accumulates in areas of altered blood-brain barrier, a typical characteristic of pediatric gliomas, and has a low rate of adverse events. This work proposes an update of previous works about the evaluation of the feasibility and usefulness of a systematic use of SF in a low-grade lesion group of pediatric patients. METHODS: Pediatric patients operated on for a resection or a biopsy of a low-grade glial or glioneuronal lesion (WHO grade I and II) at our Institution between September 2021 and December 2023, with the intraoperative use of sodium fluorescein (SF), were enrolled in the study. We collected pre-operative and postoperative clinical and radiological data, intraoperative findings, and post-operative pathological diagnoses. RESULTS: No adverse events were registered related to the intraoperative use of SF. SF appeared useful for the localization of boundaries of tumors, especially when characterized by a high degree of infiltration or by a deep-seated location, and for the checking of possible tumor remnants at the end of surgery. A good tumor-to-healthy tissue contrast was registered when tumor visualization was in a range between 1 to 2 h and 30 min after SF injection. Possible "false positives" due to intraoperative vascular wall injury and clearance of SF from both tumor and healthy tissue were observed in some cases and still remain open issues. CONCLUSIONS: SF is a feasible and safe intraoperative adjunct tool in the surgical removal of pediatric low-grade tumors. SF may show its usefulness especially in selected cases, such as deep-seated lesions and infiltrating tumors. Its safety profile, user-friendly management, and potential utility in both tumor resections and neuronavigated biopsies favor its wider use in the surgical treatment of pediatric low-grade tumors.

Preoperative 11 C-Methionine PET-MRI in Pediatric Infratentorial Tumors.

PURPOSE: MRI is the main imaging modality for pediatric brain tumors, but amino acid PET can provide additional information. Simultaneous PET-MRI acquisition allows to fully assess the tumor and lower the radiation exposure. Although symptomatic posterior fossa tumors are typically resected, the patient management is evolving and will benefit from an improved preoperative tumor characterization. We aimed to explore, in children with newly diagnosed posterior fossa tumor, the complementarity of the information provided by amino acid PET and MRI parameters and the correlation to histopathological results. PATIENTS AND METHODS: Children with a newly diagnosed posterior fossa tumor prospectively underwent a preoperative 11 C-methionine (MET) PET-MRI. Images were assessed visually and semiquantitatively. Using correlation, minimum apparent diffusion coefficient (ADC min ) and contrast enhancement were compared with MET SUV max . The diameter of the enhancing lesions was compared with metabolic tumoral volume. Lesions were classified according to the 2021 World Health Organization (WHO) classification. RESULTS: Ten children were included 4 pilocytic astrocytomas, 2 medulloblastomas, 1 ganglioglioma, 1 central nervous system embryonal tumor, and 1 schwannoma. All lesions showed visually increased MET uptake. A negative moderate correlation was found between ADC min and SUV max values ( r = -0.39). Mean SUV max was 3.8 (range, 3.3-4.2) in WHO grade 4 versus 2.5 (range, 1.7-3.0) in WHO grade 1 lesions. A positive moderate correlation was found between metabolic tumoral volume and diameter values ( r = 0.34). There was no correlation between SUV max and contrast enhancement intensity ( r = -0.15). CONCLUSIONS: Preoperative 11 C-MET PET and MRI could provide complementary information to characterize pediatric infratentorial tumors.

Unruptured cerebral arteriovenous malformation in children: Outcome in treated and untreated patients.

BACKGROUND: The management of unruptured cerebral arteriovenous malformation (URCAVM) is highly controversial; however, data regarding URCAVM in children are scarce. MATERIAL AND METHODS: We retrospectively reviewed consecutive children followed for URCAVM in our department between 2001 and 2021. RESULTS: Out of 36 patients, 12 were initially managed by observation, and 24 underwent first-line treatment: 8 by microsurgery, 10 by radiosurgery, 2 by embolization, and 4 by combined treatment. Mean follow-up of the whole group was 63months. Complete cure of the malformation was obtained in 14 patients (58%) in the treatment group: 8/8 in the microsurgery group, 5/10 in the radiosurgery group, 1/4 in the combined treatment group, and none in the embolization group. Two of the initially non-treated patients presented cerebral hemorrhage, with significant neurological consequences. In the treatment group, 5 patients presented new neurological deficits, only 1 of which, however, was functionally significant. Headache improved in 11 cases, mostly in the treatment group. Overall, 6 patients in the treatment group became asymptomatic, versus none in the observation group. CONCLUSIONS: The treatment of URCAVM is a reasonable option in many pediatric cases, considering the cumulative risk of cerebral hemorrhage during the child's lifetime, as well as the symptoms specific to URCAVM. Microsurgery, when feasible, offers the best functional results and control of the AVM; however, the risk-benefit ratio should be weighed on a case-by-case basis. More studies will be needed to inform treatment decisions in pediatric URCAVM.

Clinical interest of molecular study in cases of isolated midline craniosynostosis.

In some cases of infants with apparently isolated single-suture synostosis, an underlying variant can be found. We aimed to determine the molecular substratum in isolated sagittal and metopic craniosynostosis. To this end, we included all infants who presented isolated midline synostosis (sagittal or metopic) and had undergone surgery at the craniosynostosis national reference center of Lyon University Hospital. All infants were examined by a multidisciplinary team including neurosurgeons, clinical geneticists and neuropsychologist. Among 101 infants tested, 13 carried a total of 13 variants; that is, 12.9% of the infants carried a variant in genes known to be involved in craniosynostosis. Seven infants carried SMAD6 variants, 2 in FGFR2, 1 in TWIST1, one in FREM1, one in ALX4 and one in TCF12. All variants were detected at the heterozygous level in genes associated with autosomal dominant craniosynostosis. Also, neurodevelopmental testing showed especially delayed acquisition of language in children with than without variants in SMAD6. In conclusion, a high percentage of young children with isolated midline craniosynostosis, especially in isolated trigonocephaly, carried SMAD6 variants. The interpretation of the pathogenicity of the genes must take into account incomplete penetrance, usually observed in craniosynostosis. Our results highlight the interest of molecular analysis in the context of isolated sagittal and/or metopic craniosynostosis to enhance an understanding of the pathophysiology of midline craniosynostosis.

Sodium fluorescein in pediatric oncological neurosurgery: a pilot study on 50 children.

BACKGROUND: Sodium fluorescein (SF) is currently considered a valid intraoperative adjunct in the resection of high-grade brain lesions in adults. Experiences in pediatric groups and in low-grade gliomas and other low-grade lesions are still limited in literature, and subjective evaluation of fluorescence is still a limitation. MATERIAL AND METHODS: This study retrospectively reviewed all patients with brain or spine lesions operated on from September 2021 to July 2022 in the Pediatric Neurosurgery Unit of Hôpital Femme Mère Enfant, Lyon, who had received 5 mg/kg of 10%. Surgery was performed using a YELLOW560 filter at crucial times. At the end of surgery, the first operator completed a questionnaire, including his opinion on whether SF had been useful in tumor resection, recorded as a binary variable. Post hoc, surgical images were reviewed using ImageJ, an open-source Java image processing platform. In order to compare independent discrete variables, we applied the Student's t test, and we applied the Chi-square or Fisher exact test for binary variables. A threshold of p < 0.05 was set for statistical significance. RESULTS: We included 50 pediatric patients (0.2-17.6 years old). Forty/50 lesions showed SF uptake (80%). The differentiation between healthy and affected tissue, thanks to SF, subjectively evaluated by the surgeon, had as objective counterpart the statistically significant higher brightness of green in lesions, registered by the software (p < 0.001). SF overall allowed a good differentiation in 33/50 lesions, and overall utility of SF has been noted in 67% of them. When specifically considering gliomas, overall utility reached 75%. CONCLUSION: SF is a feasible, safe, and useful intraoperative adjunct in pediatric neurosurgery. In particular, it seems to have a promising role in some low-grade infiltrating glial tumors. The subjective evaluation of fluorescence seems to be reliable with respect to image analyses software.

Sodium fluorescein in pediatric neurosurgery: a systematic review with technical considerations and future perspectives.

BACKGROUND: Sodium fluorescein (SF) is routinely used in several centers as a valid intraoperative adjunct in adult oncological neurosurgery. Its use in pediatric neurosurgery is increasing, although its role is not yet well-defined in children. We reviewed the current literature in order to evaluate the use of SF in children with CNS and PNS lesions. METHODS: For this systematic review, we searched PubMed, Scopus, and Embase databases, and forward and backward citations for studies published between database inception and July 31st, 2022. We included any article type or congress abstract adding at least a new case, without restrictions of language or publication status, concerning the use of SF in neurosurgical procedures in patients under 18 years of age. We excluded studies concerning purely vascular cases and cerebrospinal fluid leaks. RESULTS: Of 4094 records identified, 19 articles were eligible and included for further analysis. As per July 31st, 2022, at least 119 patients aged from 11 months to 17.9 years underwent surgery with SF. No serious adverse events were reported. A large variety of tumor types was operated, in most cases resected under the specific YELLOW 560 nm filter after a low-dose SF injection (2-5 mg/kg) at the end of anesthesia induction. SF was reported particularly useful in gangliogliomas and pilocytic astrocytomas. DISCUSSION/CONCLUSION: Given its easy-to-use profile, low cost, and safety, SF seems to be a feasible and valid adjunct in the pediatric population when aiming at individuating a biopsy target or maximizing extent of resection, particularly in some tumor types. Further studies are required to strengthen the evidence on its impact on outcomes.

Auricles Anomalies in Patients With a TCF12 Gene Mutation.

Craniostenosis is a morphological anomaly affecting about 0.5 of 1000 births and one third of the cases are of genetic origin. Among the syndromes responsible for craniostenosis, there is the Saethre-Chotzen syndrome due to a mutation of the TWIST 1 gene located on chromosome 7. This polymalformative syndrome classically includes a particular morphology of the auricles. The penetrance is variable and results in a phenotypic variability at the origin of "Saethre-Chotzen like" clinical pictures for which the TWIST 1 gene mutation is sometimes not found. Recently, the TCF 12 gene has been implicated in some of these cases. Among the multiple facial malformations, we have carefully examined the particular morphology of the auricle of these patients. The authors found several abnormalities in patients with a TCF 12 gene mutation, namely a thickened and hammered upper pole of the helix, a narrow concha without crux cymbae and a thickened lobe. These morphological features may guide the diagnosis and allow an earlier search for a TCF 12 gene mutation.

Spinal lesions caused by abusive trauma in young children.

BACKGROUND AND PURPOSE: Spinal lesions are increasingly recognized as an integral part of the child abuse spectrum; however, the description of lesions, their biomechanics, true incidence, clinical impact, and medicolegal implications are poorly understood. MATERIAL AND METHODS: We report from the literature and our personal experience on abusive spinal lesions (ASL) in children under 3 years, compared with cases of abusive head injuries (AHI) without spinal lesions on the one hand and with accidental spinal lesions on the other. RESULTS: Between 2002 and 2021, we collected 12 observations of ASL, 4 male and 8 female. These were compared with 338 cases of infants having AHI without ASL and 18 cases of accidental spinal trauma in the same age group. Fractures were found in 10 cases of ASL: wedge fracture in 9, and complete disruption with paraplegia in one, which required emergency reduction and stabilization with a good motor recovery. Two patients had intraspinal hemorrhagic lesions without fracture, associated in one case with tetraplegia which contributed to the fatal outcome. ASL affected girls more often and had a more severe clinical presentation; more than half of ASL involved the lumbar levels, which were unaffected in accidental traumas. CONCLUSIONS: ASL are not exceptional, and their presence corroborates cranial lesions indicating child abuse. Two etiologies emerge from this study: wedge fractures and cervical spinal cord lesions caused by shaking and the rare thoraco-lumbar dislocation indicating a particularly violent assault. Systematic MRI study of the spine is warranted in cases of child abuse.

Pediatric Low-Grade Glioma Surgery with Sodium Fluorescein: Efficient Localization for Removal and Association with Intraoperative Pathological Sampling.

Low-grade gliomas are among the most common CNS lesions in pediatrics and surgery is often the first-line treatment. Intraoperative tools have been developed to maximize the results of surgery, and in particular dyes such as sodium fluorescein (SF) have been investigated in high-grade adult lesions. The use of SF in pediatric low-grade gliomas is still unclear. We retrospectively reviewed 22 pediatric CNS low-grade gliomas operated on with SF from September 2021 to October 2022. A total of 86% of lesions showed SF uptake, which was helpful intraoperatively (confirmation of initial localization of the tumor, or identification of tumor remnants) in 74% of them. The intraoperative fluorescence seems associated with gadolinium enhancement at the preoperative MRI. Interestingly, the extemporaneous pathological sampling (EPS) was informative in every case showing SF uptake, whereas in cases without SF uptake, the EPS was non-informative, although the tissue was later confirmed as pathological. These findings highlight the interest of SF for perioperative diagnosis of tumor tissue and may suggest in which cases the differentiation of tumor-healthy tissue could be especially blurred, posing difficulties for the pathologist.

Non-accidental head injury of infants: legal implications for the pediatric neurosurgeon.

BACKGROUND: Though the neurosurgeon's role in non-accidental head injury (NAHT) is the prompt recognition and care of the inflicted injuries, he/she should be aware of the possible legal implications related to this particular neurosurgical condition. MATERIAL AND METHODS: Based on published data and their own clinical and medico-legal practice, the authors review the role of the neurosurgeon in NHAT. RESULTS: Besides the contribution that can be given by the neurosurgeon to a correct differential diagnosis, he/she is likely to be involved in the interpretations of the pathological findings in the case where the judge may request for a medical opinion concerning etiology, circumstances, severity, and consequences. As a member of a multidisciplinary team, usually the neurosurgeon is only requested for information regarding the lesions he was called to recognize and treat. Nevertheless, such information may have a pivotal part in the evaluation process. Consequently, the neurosurgeon should be able to reach a correct differential diagnosis of NAHT among all the events that may share similar clinical and anatomo-pathological characteristics and be aware of the ongoing scientific controversies related to the diagnosis and pathophysiology. CONCLUSIONS: In practical terms, the pediatric neurosurgeon is called to individuate and record all the precise details of the condition to be eventually offered to the judge in case of controversy. Whereas the diagnosis of NAHT should be evoked at the initial phase in order not to leave the child unprotected, all possible alternative hypotheses should be ruled out "beyond reasonable doubt" for the court. The medical file should be maintained in the record carefully and be accessible even after a long time.

Decompressive surgery in abusive head injury: Experience from a Singapore children's hospital and a review of literature.

PURPOSE: Abusive head trauma (AHT) is a major cause of morbidity and mortality in children. Studies on pediatric head injury observe that AHT patients often have a higher incidence of malignant cerebral oedema and, overall, worse prognosis. There are limited studies with a focus on the outcome of decompressive surgery in children with AHT. This is a study undertaken to review our institutional experience on the role of decompressive surgery in AHT patients and objectively assess its outcomes, in corroboration with current literature. METHODS: This is an ethics-approved, retrospective study. Inclusion criteria consist of all children with a diagnosis of AHT managed by the Neurosurgical Service, KK Women's and Children's Hospital. Demographical and clinical variables are incorporated in the statistical analyses. RESULTS: From 2011 to 2021, a total of 7 patients required decompressive surgery for AHT. Mean age of the cohort was 17.1 months (with the majority of patients being male (n = 5, 71.4%). During the follow-up period, there was 1 mortality (14.3%), 3 patients developed cerebral palsy (42.9%), and 3 patients had post-traumatic epilepsy (42.9%). With regards to functional outcome, 4 patients (57.1%) had a favorable KOSCHI score at 6 months follow-up. CONCLUSION: Decompressive surgery in children with AHT presents with its own unique challenges. We therein present our neurosurgical experience in decompressive surgery for this extremely vulnerable group of patients. Given the potential role of decompressive surgery in AHT, the development of an objective marker to select such patients who may benefit most from intervention should be the way forward.

The role of the pediatric neurosurgeon in abusive head injuries: a survey of members of the International Society for Pediatric Neurosurgery.

BACKGROUND AND PURPOSE: Pediatric neurosurgeons are at the forefront of the clinical management of abusive head injuries (AHI) all over the world. However, the discrepancies regarding medical practice and legal requirements in different centers have not been assessed before. MATERIAL AND METHODS: We decided to perform an online survey among members of the International Society for Pediatric Neurosurgery (ISPN) regarding their activity, their usual clinical practice regarding the medical and legal management of AHI, and their involvement in judiciary proceedings, research, and prevention campaigns. RESULTS: Ninety members of the ISPN participated in the survey, representing 26% of the registered members. Most responders were senior pediatric neurosurgeons practicing in a university hospital. Their responses show great homogeneity regarding surgical, intensive care, and legal management. We also noted the widespread use of invasive intracranial pressure monitoring and decompressive craniotomy. By contrast, the responses show great disparity regarding the circuit of patients. This disparity may be an obstacle to the collection of data and clinical research, as well as for the involvement of neurosurgeons in multidisciplinary evaluation. A minority of neurosurgeons were engaged in research and actions of prevention. CONCLUSION: Pediatric neurosurgeons play a pivotal role in the diagnosis and medical management of AHI. Because of their proficiency in head trauma and cerebrospinal fluid disorders, it is desirable that they become more implicated in multidisciplinary meetings, medical expertise, and scientific research, as well as actions of prevention.

Abusive head injuries in infants: from founders to denialism and beyond.

INTRODUCTION: Abusive head injuries is a major cause of severe morbidity and the main cause of mortality by head trauma in infants. MATERIAL AND METHODS: Based on published data and their own clinical and medicolegal practice, the authors review briefly the historical roots and emergence of the concept of abusive head injuries (AHI), until the present scientific understanding of shaken baby syndrome (SBS) and Silverman syndrome. They then discuss the present epidemic of denialism and how this challenge to science should be seen as a stimulus to increase research and improve the accuracy of diagnosis and medical practice. RESULTS: The denial of SBS is especially damaging because it undermines the possibilities of prevention and reparation for victims. The authors expand on AHI being part of a wider context of domestic violence and the prevention of child abuse being part of a broad and long-term endeavor to defend civilization values. CONCLUSIONS: Prevention of AHI is a major challenge for the future. In the fields of science and prevention of child abuse, the input of pediatric neurosurgeons should not be underestimated.

Answer to Lynøe: Interesting data about confessions and abusive head trauma, but suboptimal analysis.

The authors of the cited paper respond to the critics formulated by a Swedish leading expert regarding methodology shortcomings of our study "Confessed versus denied inflicted head injuries in infants: similarities and differences." They admit some methodological limitations but maintain their conclusions that the diagnosis was correct in the confession and denial groups and that the denial was more difficult in the more severe cases.

Crouzon Syndrome Anatomy, Usefulness of Vestibular Orientation.

ABSTRACT: Spatial resolution of computerized tomographic scanner has reached a level to which accurate anatomic measurements could be done in. Three-dimensional accurate measurements require a reliable referential system. In craniology landmarks are usually selected in the skull base. For craniofacial malformation the classical landmarks are of no help so the authors have used the vestibular orientation to study a series of 50 Crouzon syndrome computerized tomographic scan and compare the results (shape, position, linear mensuration, volumes…) with 122 controls in unaffected patients. The authors have confirmed Crouzon description of a high level of polymorphism in phenotypes, the authors propose an organigram to understand the abnormal growth patterns in crouzon syndrome, which lead to such consequences. This polymorphism implies that the planning of surgical treatment should be tailored for each case.

Cerebellar mutism syndrome in pediatric head trauma with cerebellar injury.

PURPOSE: Cerebellar mutism syndrome (CMS) after cerebellar injury in pediatric head trauma is a poorly recognized condition that is not properly diagnosed or treated in our daily practice. We aimed to clinically identify this syndrome after isolated posttraumatic cerebellar injury and to propose pathophysiological explanation. METHODS: We retrospectively analyzed 8 consecutive children presenting with isolated cerebellar injury over 16 years. Clinical presentation, radiological type and localization of injury, clinical initial CMS symptoms, and long-term neurocognitive outcome were reviewed. RESULTS: Out of 8 patients presenting with isolated traumatic cerebellar injury, we diagnosed 2 cases with initial clinical symptoms of CMS. Both patients had an injury damaging median structures of the posterior fossa, especially the fourth ventricle and dentate nuclei. Initial symptoms lasted more than 1 month for one patient, who still presented concentration difficulties almost 1 year after the head injury. CONCLUSION: CMS after traumatic cerebellar injury does exist, even if it seems to be a very rare entity. It has to be better detected and studied in order to enrich pathophysiological knowledge about CMS of all etiologies and to bring our concerned patients the suitable follow-up and rehabilitative care that they could benefit from.