Benign brainstem tumors in children: a retrospective series of 42 patients treated in Lyon

Benign brainstem tumors in children: a retrospective series of 42 patients treated in Lyon | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Benign brainstem tumors in children: a retrospective series of 42 patients treated in Lyon pierre-aurélien beuriat, Rel Gerald Boukaka, alexandru szathmari, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6565692/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Child's Nervous System → Version 1 posted 10 You are reading this latest preprint version Abstract Introduction: Brainstem tumors represent 15% of brain tumors in children. 80% of these tumors are diffuse pontine tumors with a global bad prognosis also with the tailored chemotherapies and radiotherapy. 20% of these tumors are benign and present a good prognosis with only a surgical treatment. Material: All patients admitted with the diagnosis of brainstem tumor in the Pediatric Neurosurgical Department between January 1997 and December 2021 have been considered for this study. We excluded patients with a diagnosis of DIPG or any other malignant histopathology. Results Out of 112 patients with a brainstem tumor, 42 patients had a proved benign histological diagnosis and were included in this study. The average age, at diagnosis, was 8 years old with a median age of 4,7 years. All patients were operated. Forty-eight surgical procedures were realized for the 42 patients: 8 biopsies and 40 direct approaches. Seventeen patients had a surgical treatment for hydrocephalus. Regarding surgical outcome, 8 patients presented motor deficits, six improved while in other two the deficit was unchanged but non impeding the walk. The major clinical complication after surgery was cranial nerve palsy present in 18 patients. Two patients deceased in the early post-operative period and 2 patients for a recurrence after seven and eight years after the diagnosis. 38 patients are alive. Conclusion Benign brainstem tumors can be associated with a favorable evolution, a low growing rate and, when symptomatic, curable with surgery. The surgical resection has to be safe and reasonable to avoid catastrophic complications. The results of surgery are particularly conditioned by the skills and experience of the surgeon. brainstem tumors pediatric surgery chemotherapy radiotherapy DIPG low-grade Figures Figure 1 Figure 2 Introduction Surgery of brainstem lesions represent an arduous challenge for neurosurgeons. “Brainstem” is a complex structure with several nuclei crucial for somato-motor and somato-visceral functions, and major white matter tracts connecting the brain with the medulla therefore with a high surgical risk.[ 1 ] [ 2 ] Brainstem tumors represent 15% of children brain tumors and 80% these tumors are diffuse intrinsic pontine gliomas (DIPG) that have a dismal prognosis. This also means that, 20% have a more favourable prognosis.[ 3 ] [ 4 ] [ 5 ] Paediatric low-grade brainstem tumors are more likely to be well-circumscribed associated with better prognosis. Brainstem low-grade gliomas can be classified by location, as tectal midbrain, tegmental midbrain, focal pontine, pontomedullary, medullary, and cervico-medullary. [ 2 ][ 6 ][ 7 ]. Several articles have been published on brainstem anatomy reporting safe entry zones to facilitate their removal. Most of these studies are related to cavernoma surgery and few are related to brainstem tumor surgery in children. [ 8 ][ 9 ][ 10 ][ 11 ] We have already reported our experience with brainstem tumors [ 3 ] but we want to focus particularly the treatment of benign lesions treated in the Pediatric Neurosurgical Department of Lyon (France). Materiel and methods All patients admitted with the diagnosis of brainstem tumor in the Pediatric Neurosurgical Department at the “Hôpital Femme Mère Enfant” (Hospices Civils of Lyon, Lyon, France) between January 1997 and December 2021 have been considered for this study. We excluded patients with a diagnosis of DIPG or any other malignant histopathology. We also excluded patients without a clinical history, radiological images and without a documented post-surgical follow-up. The surgical removal was judged by the neurosurgeon who performed the surgery and by the post-operative MRI realized in the first 48 hours after the procedure[ 12 ] : complete removal was considered when no tumor was visible on the post-operative MRI, near total removal when few mms. of tumor were visible and the resection was more than 90% of the initial volume; sub-total when less than 75% of the initial volume was removed, partial when < 50% of the initial volume and biopsy when lessen than 25% of the initial volume was removed.[ 12 ] The study protocol was approved by the local ethics committee. Of 112 patients treated for a brainstem tumor, only 42 patients had a proved benign histological diagnosis and were included in this study. Results The average age of patient, at diagnosis, was 8-year-old with a median age of 4,7 years, and a range between 9 months and 18 years. A slight prevalence of girls with a sex ratio of 0,82 (M/F: 19/23). The clinical symptomatology was characterized by signs of intracranial hypertension in 10 patients (23,8%) and cranial nerve palsy in 11 patients (26,1%), balance disorders in 5 patients (12,12%). Motor and sensitive deficits were also present in 8 patients (19%), concentration troubles associated with weight loss in 4 patients (9,5%), anorexia in 3 patients (7,1%) and in a patient the discovery was done after a cranial trauma. Regarding the cranial nerve’s deficit, the distribution of the deficit was as follow: 3rd nerve (n = 1), 5th nerve (n = 1), 6th nerve (n = 2), 7th nerve (n = 2), 8th nerve (n = 1), 9th and 10th nerve (n = 2) and 11th nerve (n = 2). All patients were studied with a cranio-spinal MRI before the surgical procedure without and with gadolinium. The localization of tumors is described in Fig. 1 Five patients presented an extension of the tumor in the cerebellar hemisphere and 4 patients in the cerebello-pontine angle. An extension inside the fourth ventricle was observed in 28 patients. All patients were operated. Forty-eight surgical procedures were realized for the 42 patients: 8 biopsies and 40 direct approaches. A patient treated with an ETV without biopsy and followed with radiological and clinical control every year is not included in this series. Regarding surgical outcome, the removal was considered total in 16 patients, subtotal in 13 and partial in 7. In two patients the resection was total after a second-look surgery. Four patients were operated again after a partial removal and after a complementary chemotherapy. Concerning biopsies, they were realized with an open approach in two patients, while in other two cases it was realized with the neuronavigational assistance after the rapid evolution shoved by the MRI of control after a first subtotal surgery. In the others four cases we used a stereotactic approach with the ZD system. Concerning patients treated for a hydrocephalus, a VP shunt was realized in 11 patients and an ETV in six patients. In eight patients the shunt was realized before the biopsy or before the surgical approach of the lesion while in the others three cases after the surgical resection for a post-operative acute hydrocephalus. We never used an external temporary ventricular drainage. Peri-surgical complications A patient presented a perioperative cerebellar diffuse edema after the closure of the dura mater that led to a partial cerebellar resection of a contusion area on the right cerebellar hemisphere, a dural graft and the suppression of the bone flap to prevent the post-operative intracranial hypertension and pharmacological induced coma for 48 hours. The patient progressively woke-up with a cerebellar ataxia that improved progressively in the following six months when she was operated again for closing the posterior fossa with its autologous bone flap A patient presented a cerebral ischemia after a perioperative air embolism without clinical evident consequences. Post-operative clinical complications The major clinical complication was represented by cranial nerve palsy present in 18 patients. One or several nerves deficits could be present. A facial nerve palsy was present in four patients, in six patients the palsy concerned the abducens nerve, in three patient the oculomotor nerve, in eight patients the palsy concerned the mixes nerves with two patients needed a temporary tracheotomy. Eight patients presented a motor deficit with six improved while in other two the deficit was unchanged but non impeding the walk. Histopathology The histological diagnosis was a grade I ganglioglioma in 11 patients; a gangliocytoma in 2 patients, a pilocytic astrocytoma in 17 patients, an astrocytic low-grade glioma in 10 cases, a glioneuronal tumor in two cases. A biomolecular and genetic study was realized in 32 patients. In six patients, with a ganglioglioma, was found a positivity for the mutation V600 E in the ganglioglioma group. In four patients, with a pilocytic astrocytoma, the transcript KIAA1549 was present. The GFAP was positive in 66% of the tumors, the Olig 2 in 37%, the ATRX in 3,7%, The P53 was low in 18,5% and between 3 and 15%; the Ki67was between 2 and 10% in 44,4%. The mutation of Histone H3K27m was always absent. Progression Seven patients presented a tumoral progression. Four patients were reoperated: the location was latero-bulbar in two cases, bulbar in one case and at level of the tectal plate in one case. The first surgery was judged total in three cases, and was subtotal in one case. The histological diagnosis was a pilocytic astrocytoma in three cases and ganglioglioma in a case. The second surgery was again complete in three cases and a simple large biopsy in one case. In all cases a chemotherapy was realized with a reduction or a stabilization of the tumoral growth. Mortality We observed two post-operative death after five and eight months for respiratory complications in both cases. Two patients for a tumoral progression were treated with chemotherapy and radiotherapy: a new biopsy shoved a histological malignant transformation, seven and eight years after the initial diagnosis and dead for the progression of the disease in the same year. Consequently, the survival rate was of 90,4% (Fig. 2 ). Tectal plate tumors results Fourteen patients with tectal tumors were WHO grade I tumors with 85% pilocytic astrocytomas and 15% ganglioglioma. All tumors were exophytic and consequently all of them benefited of an aggressive resection. The presence of astrocytomas with well delimited tumoral plane make surgery easier to attain a complete removal instead that the different behavior of ganglioglioma that does not present a clear cleavage plane with an increased risk to leave pieces of tumors in place and an increased risk of sequels[ 14 ]. Discussion Brainstem low-grade gliomas are rare childhood brain tumors and, despite their benign histopathology, have the potential to cause significant neurologic morbidity.[ 12 ] [ 15 ] [ 16 ] Whenever feasible, surgical gross total resection or safe maximal resection has been proposed as the treatment.[ 17 ] Several studies reported sustained disease control after complete tumor resection supporting this statement, as our results showing no recurrences among the patients with a t total resection. [ 17 ] Favorable results have been reported for low-grade brainstem gliomas when an extended resection is realized versus a simple biopsy [ 18 ] Low-grade brainstem tumors are slow-growing tumors with in many times indolent course and favorable prognosis. Consequently, policy of watching and see can be justified because the potential growth is estimated to only 4 mm. in tumor diameter for year.[ 12 ] A retrospective review of 96 patients treated at Hospital for Sick Children in Toronto, reported a favorable outcome after upfront observation as a first-line management in some patients with brainstem low-grade gliomas and significant residual tumor after resection.[ 4 ] [ 19 ] A very good progression-free survival of 70% was similarly noted for cervicomedullary low-grade gliomas following surgical resection alone, by Robertson et al [ 4 ]. Lundar et al demonstrated a favorable 47% progression-free survival in 15 patients with low-grade midbrain tumors that were surgically resected upfront [ 14 ]. No further adjuvant therapy or repeat resection was required in these patients, the majority of whom had not undergone a total resection.[ 4 ] [ 20 ] Thus, expectant surveillance is a safe approach for many brainstems low-grade gliomas with residual tumor after diagnosis. However, a significant fraction of these tumors can progress and require additional treatment, for which both chemotherapy and radiotherapy have been effective therapies also if, sometimes, a safe surgical resection can be evaluated and realized. [ 9 ][ 21 ] Surgery Surgery has been indicated as the treatment of choice whenever possible because the potential surgical sequels have to be balanced with the potential risk of their evolution in function of the location. When surgery is possible, it demands experience and a great ability to avoid mortality and to reduce the rate of sequels. The brainstem has been divided in different area that can be approached by several entry zones points as reported by different authors in literature.[ 8 ] [ 2 ] [ 10 ] [ 9 ] At different levels of the brainstem to know the precise location of the safety entry zone is of capital importance but in reality, what is important, to approach these tumors from the smallest distance from the normal structures and where tumors present their exophytic portion. The exophytic portion of brainstem tumor can be removed without entering in the functional brainstem area in the majority of cases. [ 2 ] [ 13 ] It is important to avoid the nuclei of the cranial nerves at different levels as, the long motor and sensitive fibers to avoid motor and sensitive aggravation deficits, or whenever already present, to reduce the risk of their aggravation. For surgery of focal tectal plate tumors the resection of one colliculi can be possible at the condition of preserving the other, and in more giant lesions, the extended resection is possible without crossing the plane of aqueduct. [ 13 ] [ 20 ] Surgery of tectal plate tumors was reported in years ninenty by professor Lapras. [ 20 ] [ 22 ] Sometimes after an extended resection in the tectal plate a “beauty sleeping syndrome” can be observed that recover progressively as reported already in Lyon. [ 20 ] [ 23 ] [ 13 ] For the surgical removal, it is important to dispose of a good ultrasonic aspirator with hand piece of different length and to dispose of a good bipolar forceps to obtain a rapid control of hemorrhage. The neuronavigation is useful to give an idea of the progression of the resection helping to avoid the functioning structures. The choice of the approach depends by the precise location of the tumors and its development inside or outside of the brainstem. At level of the midbrain the approaches can be anterior or posterior or postero-lateral in function of the origin of the tumor and its axis of development. In cases of anterior or antero-lateral mesencephalic peduncular location we used a pterional transylvian approach. If tumors are low located the orbito-zygomatic approach can help to have a deeper exposition also if the space remains narrow for the presence mainly of the vascular structures and of the third cranial nerve. For lesion of the posterior midbrain, we prefer the suboccipital trantentorial approach that give a large vision of the tectal plate, and of the pineal region with all the venous arch represented by both the basilar veins and the Galen vein.[ 24 ] In our experience, as already established by C.Lapras, it is important to know the limits of the resection if all the tectal plate is involved in the tumors and avoid to exceed the plane of the aqueduct and inferiorly the plane passing through the encroachment of fourth nerves. [ 20 ] [ 24 ] We reported already a series of 27 pediatric patients operated with good results. [ 13 ] At this period the genetic studies helped to individualize favorable prognostic factors and the possibility of chemotherapy to control the disease. In two patients that presented a recurrence, a second surgery shoved a more aggressive tumor that were treated with a protocol of chemotherapy. Also, for these tumors, it is important to perform molecular studies to enhance the diagnostic precision of biopsies or of surgery supporting the histological diagnosis. The follow-up with MRI gives the possibility to discover a malignant progression, with a modification of a contrast enhancement or a growth progression that with a new biopsy. The surgical removal in this region is easier than the resection of gangliogliomas because the cleavage plane is better delimitated. For pontine lesions with lateral extension in the cerebello-pontine angle we have used mainly a lateral approach through the cerebello-pontine angle while for posterior located or focal lesion, we have preferred the posterior median trans ventricular approach. For lateral pontine location, the subtemporal approach can give a large vision and control or the tumoral resection. The problems are related with the compression of the temporal lobe and the possible venous ischemia, and the lesion of the fourth cranial nerve related to the opening of the tentorium posterior to the fourth nerve. [ 25 ] [ 26 ] For bulbo-medullary approach the median approach trans the posterior sulcus was the approach more used specially with an exophytic extension in the fourth ventricle. The entity of the resection has to be modulated in function of the vascularization of the tumor, the extension of the exophytic portion and the presence of a cleavage plane around the tumors. In case of extension inside the cerebellar hemisphere the resection can be pushed in the cerebellar area until the brainstem is joined. After the resection frequently benign brain stem tumors can remain silent for long time and sometimes also if a strategy with chemotherapy can be useful and effective to reduce the rate of neurological sequels, a simple wait and see observance can be judicious because the low-grade tumors are frequently indolent and with a low growth rate. [ 17 ] A total removal in our series was reported in16 patients (40%), a subtotal resection in 12 patients (27,6%) and it was partial in 7 patients (23,4%) according the standards of literature[ 17 ] The neurophysiology is important as important the use of neuronavigation and of tractography, also if for us, the main important think is to avoid inadvertent coagulation of arterial or venous vessels responsible of heavy consequences with severe sequels. Despite the multiple entry zone described in literature, the more important think, to resect tumors in these difficult regions, is to remain inside the tumors and to respect the vascular supplies, because through small incision it is always difficult to recognized nuclei or nervous functional fibers to reduce the incidence of deficits and for this the control of the electrophysiological parameters by a neurophysiologist in the operative room is of paramount importance. The rate of sequels, in our series, was of 38% and concerned mainly cranial nerves as observed in 16 patients in the early post operative period. The most affected nerves were the mixed nerves that were responsible of a temporary tracheotomy in two patients that was possible to remove in the following six months. A palsy of the facial nerve was observed in four patients, regressive in two patients and was definitive in the others two. The sixth nerve palsy was diagnosed in six patients and definitive in two that needed a surgical correction to improve the strabismus. At the end the cranial nerve deficits were present in only eight patients (20%). Motor and cerebellar deficits were present and stabilized in 15% of patients non impeding the walk and also the normal activity in daily occupations. In our series the early post-operative mortality was, after six and eight months from surgery, of 4,7% and definitively of 9,5% after a follow up of 8 years because two patients deceased for an evolving disease at level of the ponto-bulbar junction despite a complementary treatment with chemotherapy. In the series of Cavalheiro the rate of sequels was of 21% while the rate of mortality was of only 1,9% but related only to an early post-operative period. [ 2 ] Concerning the treatment of hydrocephalus, in our long-lasting review, eleven patients needed a shunt and only six patients definitively were treated with an ETV. The ETV permits a biopsy of some extrinsic tumors with an anterior development in the interpeduncular cistern [ 27 ] but this option was employed only in one of our cases, and for tumors bulging in the third ventricle, two cases in our series. For tectal plate tumors, on the contrary of pineal tumors, we don’t think that the endoscopic biopsy through the third ventricle can be indicated, because tectal tumors does not develop inside of the third ventricle but normally push the normal posterior wall inside the ventricle and, consequently, to have a specimen of the tumor, the biopsy forceps have to cross the normal structures with the risk to increase deficits and the possibility to obtain normal tissue without pathological material. For brainstem biopsy, we prefer actually, to use the assistance of the neuronavigation with the system Medtronic that, in our experience, is sure, effective and can also be adopted for biopsy in very young patients with the possibility to obtain samples in the different axis of the cardinal points turning of 90° the needle for biopsy. [ 3 ] The biopsy of brainstem tumors remains a challenging procedure [ 28 ] also if associated with a low risk as reported in literature [ 18 ] [ 29 ]. The rate of morbidity was evaluated a < 2% and the efficacy at a rate of 94% of cases [ 27 ]. Recently the robot-assisted stereotactic biopsy technic has been used with favorable results and a low rate of complications [ 30 ] Chemotherapy and Radiotherapy Chemotherapy is effective as adjuvant therapy against relapse/progression of brainstem low-grade gliomas, and as salvage therapy for recurrent or progressive tumors.[ 12 ] [ 17 ] In these settings, chemotherapy may obviate high-risk surgical tumor resection or repeat resection, and may permit deferral of radiotherapy in a young child until an older age when better tolerated. Chemotherapy seems particularly advantageous for treatment of tumors in young children with a high-risk lesion for surgical resection, in presence of neurologic deficits that may worsen with any further tumor growth.[ 31 ] Nevertheless, in view of the overall favorable prognosis of these tumors, sometimes even after minimal surgical intervention and with no adjuvant therapy, the potential for treatment- related long-term morbidity should be kept prominently in mind when making therapeutic decisions. Going forward, molecular characterization of these tumors will be important to individualize targeted therapies with the hope of reducing adverse effects of complementary therapy. In our series 12 patients were treated with chemotherapy in eight case adjuvant treatment and in four cases when a progression of the disease was recordered by the MRI of control. The association with vincristine and carboplatin was used in eight patients, BCNU with Cisplatinum in a patient, Oncovin and Carboplatin in a case, and a protocol with only vinblastine was realized in two cases. All the treatments were decided by the oncologists of our team in the neuro-oncological meeting of concertation and in accord with the protocols of the French Society of Pediatric Oncology. In a patient the treatment was stopped for hematological toxicity. Seven patients after chemotherapy were treated with radiotherapy and, in another patient, the irradiation was realized after a new look surgery followed by another cycle of chemotherapy. The profiling and genomic studies of gliomas as in others tumors, give the possibility to improve the prognostic factors that conditionate the good evolution of patients. The choice of drugs for targeted treatment can improve the evolution and the survival of patients. [ 31 ] In benign gliomas genetic modifications are present in different percentage. In our series the mutation V600-BRAF and the KIAA1549 was confirmed in gangliogliomas and in pilocytic astrocytomas. The role of radiotherapy is well reported in literature as well the sequels in pediatric patients also if attenuated by the fact that the irradiation is directed mainly in the posterior fossa with mild adverse effects.[ 32 ] [ 33 ]In the last time the proton therapy has been proposed because associated with a low rate of toxicity. [ 34 ] [ 35 ] [ 34 ] For Indelicato the rate of toxicity for brainstem irradiation is higher than photon therapy varying between zero and 10%. [ 36 ] The possibility of toxicity for treatment of brainstem tumors, either with chemotherapy and either with radiotherapy, have to push to consider, that sometimes tumors can have after surgery, also after a sub-total removal, an indolent and slow evolution that can postpone the decision for complementary treatments. Survival and quality of life The rate of survival in our series of benign brainstem tumors was of 90% with a rate of mortality of 10% (4 cases, two cases after surgery and 2 patients after six and eight years for the evolution of the disease). 72% of patients had a survival superior to ten years and 94% a survival superior to five years. The survival reported in literature for benign brainstem tumors was of 90% at five years and 75% at ten years, with better prognosis for grade I tumors than for grade II [ 16 ]. The quality of life was evaluated mainly with the evolution of the scholar program and the capacity to work. Twenty-five patients were in scholar program: four with the level of the high school certificate, four patients in elementary school, six patients in middle class, three with the certificate level, three patients with the level of senior technician certificate. Four patients followed a normal scholar program but with a school help. Four patients presented a clinical brainstem syndrome characterized by explosive behavior with irascibility, troubles of the memory and problems of concentration and pathological smile and cry. This pathology improved during the treatment[ 17 ] but did not disappear completely [ 37 ] Recently Jia reported impairment of the behavioral emotional cognition in children in a larger series of patients studied with the children behavioral check list (CBCL) [ 37 ] It is evident that all these patients should be studied to understand better the mechanism responsible, at different level of the brainstem, of the clinical neuropsychological problems. Our approach in some patients, with the cerebellar stimulation, put in evidence some interesting things as the sovrapposition of the mouths and the hand, the mouth and the tongue the segmentary representation of the arm on the foot, or the possibility to release movements of the jaw and of the lips etc. [ 38 ] [ 39 ] How these data can explain neuropsychological problems is not yet clear but sufficiently intricating for us to continue our explorations. The brainstem is regulated by the mediators as the norepinephrine, dopamine, and serotonin that coordinate the pathways of the behavior, cognition and emotion projecting in the cerebellar area, the cortical cerebral region through the the fronto-pontine loop, the cortico-ponto-cerebellar circuit, the cerebello—thalamic-cortical pathways. We have not to forget the amigdalo-hypothalamus-periaqueductal-ventro medial hypothalamus. The fact that we have considered, for our study, only patients with WHO classification of grade I and II is certainly is limiting, but confirms the fact that the evolution of benign brainstem tumors can be good and also with a long survival as confirmed by our series that concerned in 67% of cases the diagnosis of pilocytic astrocytoma and ganglioglioma of grade I. Despite the good evolution, it is necessary also a very long follow-up because two cases of our series presented a disease evolution after eight and nine years with a histological transformation and without responding to a chemotherapic treatment. The long-term transformation and aggressivity was reported by Maertens in tectal plate tumors in adult patients [ 40 ] while in the series of Upadhyaya 8 patients (32%) of the 25 reported presented a progressive disease at five months of the diagnosis with a range, 3 months to 16 years. Conclusion Benign brainstem tumors have been individualized as lesions that can be associated with a favorable evolution, a low growing rate and, when symptomatic, curable with surgery, on the contrary, of what happen with high grade lesions with, still actually, an unfavorable prognosis. Surgery in exophytic form or in focal localized tumors can attain a surgical total resection in 68% of cases with a potential cure and an acceptable rate of sequels evaluated, in the more recent series, at 20% of cases.[ 2 ] [ 12 ] [ 17 ] The surgical resection has to be safe and reasonable to avoid catastrophic evolution but surgery is particularly related to the ability of surgeons that have to use all the instruments that can help the surgical maneuvers. The discussion in oncological pediatric concertation staff, is always difficult to choose between the risks related to the surgery and the risks related to the natural history of tumors and the risks of complementary treatments and their collateral effects, either for chemotherapy or radiotherapy.[ 41 ] [ 35 ] [ 34 ] In some case the removal of tumors can be done with the dissection in a surgical plan as in cases of tectal plate tumors or remaining in the tumoral bed with the help of the Cusa cavitron that permits the progressive removal through a very small entrance door. It is also impossible to predict coagulation of intratumoral vessels responsible of ischemic lesions. Until the discovery of targeted chemotherapy of benign brainstem tumor, a reasonable surgical resection has to be the treatment of election for tumors that present exophytic development or evolutive growth. Surgery can be also useful in cases of recurrences as in four cases of our series followed in two cases by a treatment with chemotherapy. Consequently for us, the decisional tree for benign brainstem tumors could be the following: for asymptomatic tumors a simple follow-up with yearly MRI; for tumors with hydrocephalus, ETV or a shunt +/- biopsy; for focal tumors resection surgery with a reasonable safe resection; for tumors with a subtotal resection wait and see or second look surgery with chemotherapy followed, in patients older than 7 years, by radiotherapy. Declarations Author Contribution PAB, RGB, CM performed researchPAB and CM wrote the manuscriptPAB, AS, FDR, CM performed surgeryAV performed histological analysisCM supervised the studyall authors reviewed the manuscript References Serra C, Türe H, Fırat Z et al (2024) Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series. 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Acta Neurochir (Wien) 126:76–83. https://doi.org/10.1007/BF01476414 Lapras C, Patet JD, Mottolese C, Lapras C (1987) Direct surgery for pineal tumors: occipital-transtentorial approach. Prog Exp Tumor Res 30:268–280 Bognar L, Fischer C, Turjman F et al (1994) Tectal plate gliomas. Part III: Apparent lack of auditory consequences of unilateral inferior collicular lesion due to localized glioma surgery. Acta Neurochir (Wien) 127:161–165. https://doi.org/10.1007/BF01808760 Mottolese C, Szathmari A, Beuriat PA et al (2015) Tectal plate tumours. Our experience with a paediatric surgical series. Neurochirurgie 61:193–200. https://doi.org/10.1016/j.neuchi.2013.12.007 Sen CN, Sekhar LN (1990) The subtemporal and preauricular infratemporal approach to intradural structures ventral to the brain stem. J Neurosurg 73:345–354. https://doi.org/10.3171/jns.1990.73.3.0345 McLaughlin N, Ma Q, Emerson J et al (2013) The extended subtemporal transtentorial approach: the impact of trochlear nerve dissection and tentorial incision. J Clin Neurosci Off J Neurosurg Soc Australas 20:1139–1143. https://doi.org/10.1016/j.jocn.2012.11.006 Sheikh SR, Patel NJ, Recinos VMR (2024) Safety and Technical Efficacy of Pediatric Brainstem Biopsies: An Updated Meta-Analysis of 1000 + Children. World Neurosurg 189:428–438e2. https://doi.org/10.1016/j.wneu.2024.06.163 Jallo GI, Biser-Rohrbaugh A, Freed D (2004) Brainstem gliomas. Childs Nerv Syst ChNS. Off J Int Soc Pediatr Neurosurg 20:143–153. https://doi.org/10.1007/s00381-003-0870-6 Walker DA, Liu J, Kieran M et al (2013) A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method. Neuro-Oncol 15:462–468. https://doi.org/10.1093/neuonc/nos330 Dawes W, Marcus HJ, Tisdall M, Aquilina K (2019) Robot-assisted stereotactic brainstem biopsy in children: prospective cohort study. J Robot Surg 13:575–579. https://doi.org/10.1007/s11701-018-0899-x Chen LH, Pan C, Diplas BH et al (2020) The integrated genomic and epigenomic landscape of brainstem glioma. Nat Commun 11:3077. https://doi.org/10.1038/s41467-020-16682-y Freeman CR, Bourgouin PM, Sanford RA et al (1996) Long term survivors of childhood brain stem gliomas treated with hyperfractionated radiotherapy. Clinical characteristics and treatment related toxicities. Pediatr Oncol Group Cancer 77:555–562. https://doi.org/10.1002/(SICI)1097-0142(19960201)77:33.0.CO;2-3 Edwards MS, Wara WM, Ciricillo SF, Barkovich AJ (1994) Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. J Neurosurg 80:20–25. https://doi.org/10.3171/jns.1994.80.1.0020 Haas-Kogan D, Indelicato D, Paganetti H et al (2018) National Cancer Institute Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury. Int J Radiat Oncol 101:152–168. https://doi.org/10.1016/j.ijrobp.2018.01.013 Correia D, Indelicato DJ, Paulino AC et al (2024) Evolution of Proton Radiation Therapy Brainstem Constraints on the Pediatric Proton/Photon Consortium Registry. Pract Radiat Oncol 14:e507–e514. https://doi.org/10.1016/j.prro.2024.05.013 Indelicato DJ, Flampouri S, Rotondo RL et al (2014) Incidence and dosimetric parameters of pediatric brainstem toxicity following proton therapy. Acta Oncol Stockh Swed 53:1298–1304. https://doi.org/10.3109/0284186X.2014.957414 Jia H, Zhang P, Gu G et al (2022) Brainstem tumors may increase the impairment of behavioral emotional cognition in children. J Neurooncol 160:423–432. https://doi.org/10.1007/s11060-022-04161-x Mottolese C, Szathmari A, Beuriat P-A et al (2015) Sensorimotor mapping of the human cerebellum during pineal region surgery. Neurochirurgie 61:101–105. https://doi.org/10.1016/j.neuchi.2013.05.004 Mottolese C, Richard N, Harquel S et al (2013) Mapping motor representations in the human cerebellum. Brain J Neurol 136:330–342. https://doi.org/10.1093/brain/aws186 Mohme M, Fritzsche FS, Mende KC et al (2018) Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm. Neurosurg Focus 44:E15. https://doi.org/10.3171/2018.3.FOCUS1850 Fjæra LF, Indelicato DJ, Handeland AH et al (2022) A case-control study of linear energy transfer and relative biological effectiveness related to symptomatic brainstem toxicity following pediatric proton therapy. Radiother Oncol J Eur Soc Ther Radiol Oncol 175:47–55. https://doi.org/10.1016/j.radonc.2022.07.022 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 30 Jul, 2025 Read the published version in Child's Nervous System → Version 1 posted Editorial decision: Revision requested 29 Jun, 2025 Reviews received at journal 24 Jun, 2025 Reviews received at journal 23 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers agreed at journal 15 Jun, 2025 Reviewers invited by journal 15 Jun, 2025 Editor assigned by journal 01 May, 2025 Submission checks completed at journal 01 May, 2025 First submitted to journal 30 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6565692","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":472155384,"identity":"94fd7278-7b67-4874-a3e4-7c34c4b5b6b2","order_by":0,"name":"pierre-aurélien beuriat","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"pierre-aurélien","middleName":"","lastName":"beuriat","suffix":""},{"id":472155385,"identity":"bd4aceda-5358-4901-8fb9-f98889103fb4","order_by":1,"name":"Rel Gerald Boukaka","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Rel","middleName":"Gerald","lastName":"Boukaka","suffix":""},{"id":472155386,"identity":"990d8b7a-421f-4b7e-9453-33283e5a8e5b","order_by":2,"name":"alexandru szathmari","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"alexandru","middleName":"","lastName":"szathmari","suffix":""},{"id":472155387,"identity":"d1b1f549-9fd5-495b-ad3f-45b82761be51","order_by":3,"name":"alexandre vasiljevic","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"alexandre","middleName":"","lastName":"vasiljevic","suffix":""},{"id":472155388,"identity":"e4fb3fb0-eff1-4e62-8f55-675b4922635b","order_by":4,"name":"federico di rocco","email":"","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"federico","middleName":"di","lastName":"rocco","suffix":""},{"id":472155389,"identity":"f85d2b2a-9e81-4caa-b80f-b8bf7c10d2d6","order_by":5,"name":"carmine mottolese","email":"data:image/png;base64,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","orcid":"","institution":"Hospices Civils de Lyon","correspondingAuthor":true,"prefix":"","firstName":"carmine","middleName":"","lastName":"mottolese","suffix":""}],"badges":[],"createdAt":"2025-04-30 14:08:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6565692/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6565692/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00381-025-06908-z","type":"published","date":"2025-07-30T16:13:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84872815,"identity":"a2325d3f-0744-4b29-86f6-4cd2d49ee91a","added_by":"auto","created_at":"2025-06-18 09:17:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54694,"visible":true,"origin":"","legend":"\u003cp\u003ePie chart depicting the anatomical localization of the tumors\u003c/p\u003e","description":"","filename":"fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6565692/v1/a064a6288d13561777231baa.png"},{"id":84872817,"identity":"d583c9ff-5309-4013-b3dd-049f29d61bae","added_by":"auto","created_at":"2025-06-18 09:17:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":43951,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival Curve of the Lyon Series\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6565692/v1/73f2ce48b8c0244a2622cf26.png"},{"id":88268211,"identity":"38fadda7-e3ad-4bc2-b79f-8d042f3d3675","added_by":"auto","created_at":"2025-08-04 16:50:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":596045,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6565692/v1/7fe6e1fe-b6cb-4b1d-918f-cb95c9b3d555.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Benign brainstem tumors in children: a retrospective series of 42 patients treated in Lyon","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgery of brainstem lesions represent an arduous challenge for neurosurgeons. \u0026ldquo;Brainstem\u0026rdquo; is a complex structure with several nuclei crucial for somato-motor and somato-visceral functions, and major white matter tracts connecting the brain with the medulla therefore with a high surgical risk.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBrainstem tumors represent 15% of children brain tumors and 80% these tumors are diffuse intrinsic pontine gliomas (DIPG) that have a dismal prognosis. This also means that, 20% have a more favourable prognosis.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003ePaediatric low-grade brainstem tumors are more likely to be well-circumscribed associated with better prognosis. Brainstem low-grade gliomas can be classified by location, as tectal midbrain, tegmental midbrain, focal pontine, pontomedullary, medullary, and cervico-medullary. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e][\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e][\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Several articles have been published on brainstem anatomy reporting safe entry zones to facilitate their removal. Most of these studies are related to cavernoma surgery and few are related to brainstem tumor surgery in children. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e][\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWe have already reported our experience with brainstem tumors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] but we want to focus particularly the treatment of benign lesions treated in the Pediatric Neurosurgical Department of Lyon (France).\u003c/p\u003e"},{"header":"Materiel and methods","content":"\u003cp\u003eAll patients admitted with the diagnosis of brainstem tumor in the Pediatric Neurosurgical Department at the \u0026ldquo;H\u0026ocirc;pital Femme M\u0026egrave;re Enfant\u0026rdquo; (Hospices Civils of Lyon, Lyon, France) between January 1997 and December 2021 have been considered for this study. We excluded patients with a diagnosis of DIPG or any other malignant histopathology. We also excluded patients without a clinical history, radiological images and without a documented post-surgical follow-up.\u003c/p\u003e \u003cp\u003eThe surgical removal was judged by the neurosurgeon who performed the surgery and by the post-operative MRI realized in the first 48 hours after the procedure[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] : complete removal was considered when no tumor was visible on the post-operative MRI, near total removal when few mms. of tumor were visible and the resection was more than 90% of the initial volume; sub-total when less than 75% of the initial volume was removed, partial when \u0026lt;\u0026thinsp;50% of the initial volume and biopsy when lessen than 25% of the initial volume was removed.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e The study protocol was approved by the local ethics committee. Of 112 patients treated for a brainstem tumor, only 42 patients had a proved benign histological diagnosis and were included in this study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe average age of patient, at diagnosis, was 8-year-old with a median age of 4,7 years, and a range between 9 months and 18 years. A slight prevalence of girls with a sex ratio of 0,82 (M/F: 19/23).\u003c/p\u003e \u003cp\u003eThe clinical symptomatology was characterized by signs of intracranial hypertension in 10 patients (23,8%) and cranial nerve palsy in 11 patients (26,1%), balance disorders in 5 patients (12,12%). Motor and sensitive deficits were also present in 8 patients (19%), concentration troubles associated with weight loss in 4 patients (9,5%), anorexia in 3 patients (7,1%) and in a patient the discovery was done after a cranial trauma.\u003c/p\u003e \u003cp\u003eRegarding the cranial nerve\u0026rsquo;s deficit, the distribution of the deficit was as follow: 3rd nerve (n\u0026thinsp;=\u0026thinsp;1), 5th nerve (n\u0026thinsp;=\u0026thinsp;1), 6th nerve (n\u0026thinsp;=\u0026thinsp;2), 7th nerve (n\u0026thinsp;=\u0026thinsp;2), 8th nerve (n\u0026thinsp;=\u0026thinsp;1), 9th and 10th nerve (n\u0026thinsp;=\u0026thinsp;2) and 11th nerve (n\u0026thinsp;=\u0026thinsp;2).\u003c/p\u003e \u003cp\u003eAll patients were studied with a cranio-spinal MRI before the surgical procedure without and with gadolinium. The localization of tumors is described in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFive patients presented an extension of the tumor in the cerebellar hemisphere and 4 patients in the cerebello-pontine angle. An extension inside the fourth ventricle was observed in 28 patients.\u003c/p\u003e \u003cp\u003eAll patients were operated. Forty-eight surgical procedures were realized for the 42 patients: 8 biopsies and 40 direct approaches. A patient treated with an ETV without biopsy and followed with radiological and clinical control every year is not included in this series.\u003c/p\u003e \u003cp\u003eRegarding surgical outcome, the removal was considered total in 16 patients, subtotal in 13 and partial in 7. In two patients the resection was total after a second-look surgery. Four patients were operated again after a partial removal and after a complementary chemotherapy.\u003c/p\u003e \u003cp\u003eConcerning biopsies, they were realized with an open approach in two patients, while in other two cases it was realized with the neuronavigational assistance after the rapid evolution shoved by the MRI of control after a first subtotal surgery. In the others four cases we used a stereotactic approach with the ZD system.\u003c/p\u003e \u003cp\u003eConcerning patients treated for a hydrocephalus, a VP shunt was realized in 11 patients and an ETV in six patients. In eight patients the shunt was realized before the biopsy or before the surgical approach of the lesion while in the others three cases after the surgical resection for a post-operative acute hydrocephalus. We never used an external temporary ventricular drainage.\u003c/p\u003e\n\u003ch3\u003ePeri-surgical complications\u003c/h3\u003e\n\u003cp\u003eA patient presented a perioperative cerebellar diffuse edema after the closure of the dura mater that led to a partial cerebellar resection of a contusion area on the right cerebellar hemisphere, a dural graft and the suppression of the bone flap to prevent the post-operative intracranial hypertension and pharmacological induced coma for 48 hours. The patient progressively woke-up with a cerebellar ataxia that improved progressively in the following six months when she was operated again for closing the posterior fossa with its autologous bone flap\u003c/p\u003e \u003cp\u003eA patient presented a cerebral ischemia after a perioperative air embolism without clinical evident consequences.\u003c/p\u003e\n\u003ch3\u003ePost-operative clinical complications\u003c/h3\u003e\n\u003cp\u003eThe major clinical complication was represented by cranial nerve palsy present in 18 patients. One or several nerves deficits could be present. A facial nerve palsy was present in four patients, in six patients the palsy concerned the abducens nerve, in three patient the oculomotor nerve, in eight patients the palsy concerned the mixes nerves with two patients needed a temporary tracheotomy. Eight patients presented a motor deficit with six improved while in other two the deficit was unchanged but non impeding the walk.\u003c/p\u003e\n\u003ch3\u003eHistopathology\u003c/h3\u003e\n\u003cp\u003eThe histological diagnosis was a grade I ganglioglioma in 11 patients; a gangliocytoma in 2 patients, a pilocytic astrocytoma in 17 patients, an astrocytic low-grade glioma in 10 cases, a glioneuronal tumor in two cases.\u003c/p\u003e \u003cp\u003eA biomolecular and genetic study was realized in 32 patients. In six patients, with a ganglioglioma, was found a positivity for the mutation V600 E in the ganglioglioma group. In four patients, with a pilocytic astrocytoma, the transcript KIAA1549 was present.\u003c/p\u003e \u003cp\u003eThe GFAP was positive in 66% of the tumors, the Olig 2 in 37%, the ATRX in 3,7%, The P53 was low in 18,5% and between 3 and 15%; the Ki67was between 2 and 10% in 44,4%. The mutation of Histone H3K27m was always absent.\u003c/p\u003e\n\u003ch3\u003eProgression\u003c/h3\u003e\n\u003cp\u003eSeven patients presented a tumoral progression.\u003c/p\u003e \u003cp\u003eFour patients were reoperated: the location was latero-bulbar in two cases, bulbar in one case and at level of the tectal plate in one case. The first surgery was judged total in three cases, and was subtotal in one case. The histological diagnosis was a pilocytic astrocytoma in three cases and ganglioglioma in a case. The second surgery was again complete in three cases and a simple large biopsy in one case.\u003c/p\u003e \u003cp\u003eIn all cases a chemotherapy was realized with a reduction or a stabilization of the tumoral growth.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMortality\u003c/h2\u003e \u003cp\u003eWe observed two post-operative death after five and eight months for respiratory complications in both cases.\u003c/p\u003e \u003cp\u003eTwo patients for a tumoral progression were treated with chemotherapy and radiotherapy: a new biopsy shoved a histological malignant transformation, seven and eight years after the initial diagnosis and dead for the progression of the disease in the same year.\u003c/p\u003e \u003cp\u003eConsequently, the survival rate was of 90,4% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTectal plate tumors results\u003c/h3\u003e\n\u003cp\u003eFourteen patients with tectal tumors were WHO grade I tumors with 85% pilocytic astrocytomas and 15% ganglioglioma. All tumors were exophytic and consequently all of them benefited of an aggressive resection.\u003c/p\u003e \u003cp\u003eThe presence of astrocytomas with well delimited tumoral plane make surgery easier to attain a complete removal instead that the different behavior of ganglioglioma that does not present a clear cleavage plane with an increased risk to leave pieces of tumors in place and an increased risk of sequels[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBrainstem low-grade gliomas are rare childhood brain tumors and, despite their benign histopathology, have the potential to cause significant neurologic morbidity.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWhenever feasible, surgical gross total resection or safe maximal resection has been proposed as the treatment.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Several studies reported sustained disease control after complete tumor resection supporting this statement, as our results showing no recurrences among the patients with a t total resection. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFavorable results have been reported for low-grade brainstem gliomas when an extended resection is realized versus a simple biopsy [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eLow-grade brainstem tumors are slow-growing tumors with in many times indolent course and favorable prognosis. Consequently, policy of watching and see can be justified because the potential growth is estimated to only 4 mm. in tumor diameter for year.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e A retrospective review of 96 patients treated at Hospital for Sick Children in Toronto, reported a favorable outcome after upfront observation as a first-line management in some patients with brainstem low-grade gliomas and significant residual tumor after resection.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eA very good progression-free survival of 70% was similarly noted for cervicomedullary low-grade gliomas following surgical resection alone, by Robertson et al [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Lundar et al demonstrated a favorable 47% progression-free survival in 15 patients with low-grade midbrain tumors that were surgically resected upfront [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNo further adjuvant therapy or repeat resection was required in these patients, the majority of whom\u003c/p\u003e \u003cp\u003ehad not undergone a total resection.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThus, expectant surveillance is a safe approach for many brainstems low-grade gliomas with residual tumor after diagnosis. However, a significant fraction of these tumors can progress and require additional treatment, for which both chemotherapy and radiotherapy have been effective therapies also if, sometimes, a safe surgical resection can be evaluated and realized. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e][\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSurgery\u003c/h2\u003e \u003cp\u003eSurgery has been indicated as the treatment of choice whenever possible because the potential surgical sequels have to be balanced with the potential risk of their evolution in function of the location.\u003c/p\u003e \u003cp\u003eWhen surgery is possible, it demands experience and a great ability to avoid mortality and to reduce the rate of sequels.\u003c/p\u003e \u003cp\u003eThe brainstem has been divided in different area that can be approached by several entry zones points as reported by different authors in literature.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAt different levels of the brainstem to know the precise location of the safety entry zone is of capital importance but in reality, what is important, to approach these tumors from the smallest distance from the normal structures and where tumors present their exophytic portion. The exophytic portion of brainstem tumor can be removed without entering in the functional brainstem area in the majority of cases. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIt is important to avoid the nuclei of the cranial nerves at different levels as, the long motor and sensitive fibers to avoid motor and sensitive aggravation deficits, or whenever already present, to reduce the risk of their aggravation.\u003c/p\u003e \u003cp\u003eFor surgery of focal tectal plate tumors the resection of one colliculi can be possible at the condition of preserving the other, and in more giant lesions, the extended resection is possible without crossing the plane of aqueduct. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Surgery of tectal plate tumors was reported in years ninenty by professor Lapras. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSometimes after an extended resection in the tectal plate a \u0026ldquo;beauty sleeping syndrome\u0026rdquo; can be observed that recover progressively as reported already in Lyon. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFor the surgical removal, it is important to dispose of a good ultrasonic aspirator with hand piece of different length and to dispose of a good bipolar forceps to obtain a rapid control of hemorrhage. The neuronavigation is useful to give an idea of the progression of the resection helping to avoid the functioning structures.\u003c/p\u003e \u003cp\u003eThe choice of the approach depends by the precise location of the tumors and its development inside or outside of the brainstem.\u003c/p\u003e \u003cp\u003eAt level of the midbrain the approaches can be anterior or posterior or postero-lateral in function of the origin of the tumor and its axis of development.\u003c/p\u003e \u003cp\u003eIn cases of anterior or antero-lateral mesencephalic peduncular location we used a pterional transylvian approach. If tumors are low located the orbito-zygomatic approach can help to have a deeper exposition also if the space remains narrow for the presence mainly of the vascular structures and of the third cranial nerve.\u003c/p\u003e \u003cp\u003eFor lesion of the posterior midbrain, we prefer the suboccipital trantentorial approach that give a large vision of the tectal plate, and of the pineal region with all the venous arch represented by both the basilar veins and the Galen vein.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn our experience, as already established by C.Lapras, it is important to know the limits of the resection if all the tectal plate is involved in the tumors and avoid to exceed the plane of the aqueduct and inferiorly the plane passing through the encroachment of fourth nerves. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eWe reported already a series of 27 pediatric patients operated with good results. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAt this period the genetic studies helped to individualize favorable prognostic factors and the possibility of chemotherapy to control the disease. In two patients that presented a recurrence, a second surgery shoved a more aggressive tumor that were treated with a protocol of chemotherapy.\u003c/p\u003e \u003cp\u003eAlso, for these tumors, it is important to perform molecular studies to enhance the diagnostic precision of biopsies or of surgery supporting the histological diagnosis. The follow-up with MRI gives the possibility to discover a malignant progression, with a modification of a contrast enhancement or a growth progression that with a new biopsy. The surgical removal in this region is easier than the resection of gangliogliomas because the cleavage plane is better delimitated.\u003c/p\u003e \u003cp\u003eFor pontine lesions with lateral extension in the cerebello-pontine angle we have used mainly a lateral approach through the cerebello-pontine angle while for posterior located or focal lesion, we have preferred the posterior median trans ventricular approach. For lateral pontine location, the subtemporal approach can give a large vision and control or the tumoral resection. The problems are related with the compression of the temporal lobe and the possible venous ischemia, and the lesion of the fourth cranial nerve related to the opening of the tentorium posterior to the fourth nerve. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFor bulbo-medullary approach the median approach trans the posterior sulcus was the approach more used specially with an exophytic extension in the fourth ventricle.\u003c/p\u003e \u003cp\u003eThe entity of the resection has to be modulated in function of the vascularization of the tumor, the extension of the exophytic portion and the presence of a cleavage plane around the tumors.\u003c/p\u003e \u003cp\u003eIn case of extension inside the cerebellar hemisphere the resection can be pushed in the cerebellar area until the brainstem is joined.\u003c/p\u003e \u003cp\u003eAfter the resection frequently benign brain stem tumors can remain silent for long time and sometimes also if a strategy with chemotherapy can be useful and effective to reduce the rate of neurological sequels, a simple wait and see observance can be judicious because the low-grade tumors are frequently indolent and with a low growth rate. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eA total removal in our series was reported in16 patients (40%), a subtotal resection in 12 patients (27,6%) and it was partial in 7 patients (23,4%) according the standards of literature[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe neurophysiology is important as important the use of neuronavigation and of tractography, also if for us, the main important think is to avoid inadvertent coagulation of arterial or venous vessels responsible of heavy consequences with severe sequels.\u003c/p\u003e \u003cp\u003eDespite the multiple entry zone described in literature, the more important think, to resect tumors in these difficult regions, is to remain inside the tumors and to respect the vascular supplies, because through small incision it is always difficult to recognized nuclei or nervous functional fibers to reduce the incidence of deficits and for this the control of the electrophysiological parameters by a neurophysiologist in the operative room is of paramount importance.\u003c/p\u003e \u003cp\u003eThe rate of sequels, in our series, was of 38% and concerned mainly cranial nerves as observed in 16 patients in the early post operative period.\u003c/p\u003e \u003cp\u003eThe most affected nerves were the mixed nerves that were responsible of a temporary tracheotomy in two patients that was possible to remove in the following six months.\u003c/p\u003e \u003cp\u003eA palsy of the facial nerve was observed in four patients, regressive in two patients and was definitive in the others two.\u003c/p\u003e \u003cp\u003eThe sixth nerve palsy was diagnosed in six patients and definitive in two that needed a surgical correction to improve the strabismus.\u003c/p\u003e \u003cp\u003eAt the end the cranial nerve deficits were present in only eight patients (20%).\u003c/p\u003e \u003cp\u003eMotor and cerebellar deficits were present and stabilized in 15% of patients non impeding the walk and also the normal activity in daily occupations.\u003c/p\u003e \u003cp\u003eIn our series the early post-operative mortality was, after six and eight months from surgery, of 4,7% and definitively of 9,5% after a follow up of 8 years because two patients deceased for an evolving disease at level of the ponto-bulbar junction despite a complementary treatment with chemotherapy.\u003c/p\u003e \u003cp\u003eIn the series of Cavalheiro the rate of sequels was of 21% while the rate of mortality was of only 1,9% but related only to an early post-operative period. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eConcerning the treatment of hydrocephalus, in our long-lasting review, eleven patients needed a shunt and only six patients definitively were treated with an ETV.\u003c/p\u003e \u003cp\u003eThe ETV permits a biopsy of some extrinsic tumors with an anterior development in the interpeduncular cistern [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] but this option was employed only in one of our cases, and for tumors bulging in the third ventricle, two cases in our series.\u003c/p\u003e \u003cp\u003eFor tectal plate tumors, on the contrary of pineal tumors, we don\u0026rsquo;t think that the endoscopic biopsy through the third ventricle can be indicated, because tectal tumors does not develop inside of the third ventricle but normally push the normal posterior wall inside the ventricle and, consequently, to have a specimen of the tumor, the biopsy forceps have to cross the normal structures with the risk to increase deficits and the possibility to obtain normal tissue without pathological material.\u003c/p\u003e \u003cp\u003eFor brainstem biopsy, we prefer actually, to use the assistance of the neuronavigation with the system Medtronic that, in our experience, is sure, effective and can also be adopted for biopsy in very young patients with the possibility to obtain samples in the different axis of the cardinal points turning of 90\u0026deg; the needle for biopsy. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe biopsy of brainstem tumors remains a challenging procedure [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] also if associated with a low risk as reported in literature [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The rate of morbidity was evaluated a\u0026thinsp;\u0026lt;\u0026thinsp;2% and the efficacy at a rate of 94% of cases [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently the robot-assisted stereotactic biopsy technic has been used with favorable results and a low rate of complications [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eChemotherapy and Radiotherapy\u003c/h2\u003e \u003cp\u003eChemotherapy is effective as adjuvant therapy against relapse/progression of brainstem low-grade gliomas, and as salvage therapy for recurrent or progressive tumors.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] In these settings, chemotherapy may obviate high-risk surgical tumor resection or repeat resection, and may permit deferral of radiotherapy in a young child until an older age when better tolerated. Chemotherapy seems particularly advantageous for treatment of tumors in young children with a high-risk lesion for surgical resection, in presence of neurologic deficits that may worsen with any further tumor growth.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eNevertheless, in view of the overall favorable prognosis of these tumors, sometimes even after minimal surgical intervention and with no adjuvant therapy, the potential for treatment- related long-term morbidity should be kept prominently in mind when making therapeutic decisions. Going forward, molecular characterization of these tumors will be important to individualize targeted therapies with the hope of reducing adverse effects of complementary therapy.\u003c/p\u003e \u003cp\u003eIn our series 12 patients were treated with chemotherapy in eight case adjuvant treatment and in four cases when a progression of the disease was recordered by the MRI of control.\u003c/p\u003e \u003cp\u003eThe association with vincristine and carboplatin was used in eight patients, BCNU with Cisplatinum in a patient, Oncovin and Carboplatin in a case, and a protocol with only vinblastine was realized in two cases. All the treatments were decided by the oncologists of our team in the neuro-oncological meeting of concertation and in accord with the protocols of the French Society of Pediatric Oncology.\u003c/p\u003e \u003cp\u003eIn a patient the treatment was stopped for hematological toxicity.\u003c/p\u003e \u003cp\u003eSeven patients after chemotherapy were treated with radiotherapy and, in another patient, the irradiation was realized after a new look surgery followed by another cycle of chemotherapy.\u003c/p\u003e \u003cp\u003eThe profiling and genomic studies of gliomas as in others tumors, give the possibility to improve the prognostic factors that conditionate the good evolution of patients. The choice of drugs for targeted treatment can improve the evolution and the survival of patients. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn benign gliomas genetic modifications are present in different percentage. In our series the mutation V600-BRAF and the KIAA1549 was confirmed in gangliogliomas and in pilocytic astrocytomas.\u003c/p\u003e \u003cp\u003eThe role of radiotherapy is well reported in literature as well the sequels in pediatric patients also if attenuated by the fact that the irradiation is directed mainly in the posterior fossa with mild adverse effects.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]In the last time the proton therapy has been proposed because associated with a low rate of toxicity. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFor Indelicato the rate of toxicity for brainstem irradiation is higher than photon therapy varying between zero and 10%. [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe possibility of toxicity for treatment of brainstem tumors, either with chemotherapy and either with radiotherapy, have to push to consider, that sometimes tumors can have after surgery, also after a sub-total removal, an indolent and slow evolution that can postpone the decision for complementary treatments.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSurvival and quality of life\u003c/h2\u003e \u003cp\u003eThe rate of survival in our series of benign brainstem tumors was of 90% with a rate of mortality of 10% (4 cases, two cases after surgery and 2 patients after six and eight years for the evolution of the disease).\u003c/p\u003e \u003cp\u003e72% of patients had a survival superior to ten years and 94% a survival superior to five years.\u003c/p\u003e \u003cp\u003eThe survival reported in literature for benign brainstem tumors was of 90% at five years and 75% at ten years, with better prognosis for grade I tumors than for grade II [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe quality of life was evaluated mainly with the evolution of the scholar program and the capacity to work.\u003c/p\u003e \u003cp\u003eTwenty-five patients were in scholar program: four with the level of the high school certificate, four patients in elementary school, six patients in middle class, three with the certificate level, three patients with the level of senior technician certificate.\u003c/p\u003e \u003cp\u003eFour patients followed a normal scholar program but with a school help.\u003c/p\u003e \u003cp\u003eFour patients presented a clinical brainstem syndrome characterized by explosive behavior with irascibility, troubles of the memory and problems of concentration and pathological smile and cry.\u003c/p\u003e \u003cp\u003eThis pathology improved during the treatment[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] but did not disappear completely [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eRecently Jia reported impairment of the behavioral emotional cognition in children in a larger series of patients studied with the children behavioral check list (CBCL) [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIt is evident that all these patients should be studied to understand better the mechanism responsible, at different level of the brainstem, of the clinical neuropsychological problems.\u003c/p\u003e \u003cp\u003eOur approach in some patients, with the cerebellar stimulation, put in evidence some interesting things as the sovrapposition of the mouths and the hand, the mouth and the tongue the segmentary representation of the arm on the foot, or the possibility to release movements of the jaw and of the lips etc. [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] How these data can explain neuropsychological problems is not yet clear but sufficiently intricating for us to continue our explorations.\u003c/p\u003e \u003cp\u003eThe brainstem is regulated by the mediators as the norepinephrine, dopamine, and serotonin that coordinate the pathways of the behavior, cognition and emotion projecting in the cerebellar area, the cortical cerebral region through the the fronto-pontine loop, the cortico-ponto-cerebellar circuit, the cerebello\u0026mdash;thalamic-cortical pathways. We have not to forget the amigdalo-hypothalamus-periaqueductal-ventro medial hypothalamus.\u003c/p\u003e \u003cp\u003eThe fact that we have considered, for our study, only patients with WHO classification of grade I and II is certainly is limiting, but confirms the fact that the evolution of benign brainstem tumors can be good and also with a long survival as confirmed by our series that concerned in 67% of cases the diagnosis of pilocytic astrocytoma and ganglioglioma of grade I.\u003c/p\u003e \u003cp\u003eDespite the good evolution, it is necessary also a very long follow-up because two cases of our series presented a disease evolution after eight and nine years with a histological transformation and without responding to a chemotherapic treatment.\u003c/p\u003e \u003cp\u003eThe long-term transformation and aggressivity was reported by Maertens in tectal plate tumors in adult patients [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e] while in the series of Upadhyaya 8 patients (32%) of the 25 reported presented a progressive disease at five months of the diagnosis with a range, 3 months to 16 years.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBenign brainstem tumors have been individualized as lesions that can be associated with a favorable evolution, a low growing rate and, when symptomatic, curable with surgery, on the contrary, of what happen with high grade lesions with, still actually, an unfavorable prognosis.\u003c/p\u003e \u003cp\u003eSurgery in exophytic form or in focal localized tumors can attain a surgical total resection in 68% of cases with a potential cure and an acceptable rate of sequels evaluated, in the more recent series, at 20% of cases.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe surgical resection has to be safe and reasonable to avoid catastrophic evolution but surgery is particularly related to the ability of surgeons that have to use all the instruments that can help the surgical maneuvers. The discussion in oncological pediatric concertation staff, is always difficult to choose between the risks related to the surgery and the risks related to the natural history of tumors and the risks of complementary treatments and their collateral effects, either for chemotherapy or radiotherapy.[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn some case the removal of tumors can be done with the dissection in a surgical plan as in cases of tectal plate tumors or remaining in the tumoral bed with the help of the Cusa cavitron that permits the progressive removal through a very small entrance door.\u003c/p\u003e \u003cp\u003eIt is also impossible to predict coagulation of intratumoral vessels responsible of ischemic lesions.\u003c/p\u003e \u003cp\u003eUntil the discovery of targeted chemotherapy of benign brainstem tumor, a reasonable surgical resection has to be the treatment of election for tumors that present exophytic development or evolutive growth.\u003c/p\u003e \u003cp\u003eSurgery can be also useful in cases of recurrences as in four cases of our series followed in two cases by a treatment with chemotherapy.\u003c/p\u003e \u003cp\u003eConsequently for us, the decisional tree for benign brainstem tumors could be the following:\u003c/p\u003e \u003cp\u003efor asymptomatic tumors a simple follow-up with yearly MRI;\u003c/p\u003e \u003cp\u003efor tumors with hydrocephalus, ETV or a shunt +/- biopsy;\u003c/p\u003e \u003cp\u003efor focal tumors resection surgery with a reasonable safe resection;\u003c/p\u003e \u003cp\u003efor tumors with a subtotal resection wait and see or second look surgery with chemotherapy followed, in patients older than 7 years, by radiotherapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003ePAB, RGB, CM performed researchPAB and CM wrote the manuscriptPAB, AS, FDR, CM performed surgeryAV performed histological analysisCM supervised the studyall authors reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSerra C, T\u0026uuml;re H, Fırat Z et al (2024) Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series. 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Radiother Oncol J Eur Soc Ther Radiol Oncol 175:47\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.radonc.2022.07.022\u003c/span\u003e\u003cspan address=\"10.1016/j.radonc.2022.07.022\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"brainstem tumors, pediatric, surgery, chemotherapy, radiotherapy, DIPG, low-grade","lastPublishedDoi":"10.21203/rs.3.rs-6565692/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6565692/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eBrainstem tumors represent 15% of brain tumors in children. 80% of these tumors are diffuse pontine tumors with a global bad prognosis also with the tailored chemotherapies and radiotherapy. 20% of these tumors are benign and present a good prognosis with only a surgical treatment.\u003c/p\u003e\u003ch2\u003eMaterial:\u003c/h2\u003e \u003cp\u003eAll patients admitted with the diagnosis of brainstem tumor in the Pediatric Neurosurgical Department between January 1997 and December 2021 have been considered for this study. We excluded patients with a diagnosis of DIPG or any other malignant histopathology.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of 112 patients with a brainstem tumor, 42 patients had a proved benign histological diagnosis and were included in this study. The average age, at diagnosis, was 8 years old with a median age of 4,7 years. All patients were operated. Forty-eight surgical procedures were realized for the 42 patients: 8 biopsies and 40 direct approaches. Seventeen patients had a surgical treatment for hydrocephalus. Regarding surgical outcome, 8 patients presented motor deficits, six improved while in other two the deficit was unchanged but non impeding the walk. The major clinical complication after surgery was cranial nerve palsy present in 18 patients. Two patients deceased in the early post-operative period and 2 patients for a recurrence after seven and eight years after the diagnosis. 38 patients are alive.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBenign brainstem tumors can be associated with a favorable evolution, a low growing rate and, when symptomatic, curable with surgery. The surgical resection has to be safe and reasonable to avoid catastrophic complications. The results of surgery are particularly conditioned by the skills and experience of the surgeon.\u003c/p\u003e","manuscriptTitle":"Benign brainstem tumors in children: a retrospective series of 42 patients treated in Lyon","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-18 09:17:17","doi":"10.21203/rs.3.rs-6565692/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-29T17:22:07+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-25T00:01:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-23T19:53:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"231052858221832472481892277809111766590","date":"2025-06-16T18:29:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229405985626653109525462556094277412427","date":"2025-06-16T10:45:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150296746907686218141678546330317318948","date":"2025-06-15T22:06:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-15T21:14:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-01T06:01:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-01T06:00:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Child's Nervous System","date":"2025-04-30T13:58:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d6952152-61a4-4572-bdee-ada1a49b8a45","owner":[],"postedDate":"June 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:42:19+00:00","versionOfRecord":{"articleIdentity":"rs-6565692","link":"https://doi.org/10.1007/s00381-025-06908-z","journal":{"identity":"childs-nervous-system","isVorOnly":false,"title":"Child's Nervous System"},"publishedOn":"2025-07-30 16:13:15","publishedOnDateReadable":"July 30th, 2025"},"versionCreatedAt":"2025-06-18 09:17:17","video":"","vorDoi":"10.1007/s00381-025-06908-z","vorDoiUrl":"https://doi.org/10.1007/s00381-025-06908-z","workflowStages":[]},"version":"v1","identity":"rs-6565692","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6565692","identity":"rs-6565692","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}