|Year : 2015 | Volume
| Issue : 4 | Page : 335-340
Brain tumors in infants
Seyyed Mohammad Ghodsi1, Zohreh Habibi2, Sara Hanaei2, Ehsan Moradi2, Farideh Nejat2
1 Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
2 Department of Neurosurgery, Children's Hospital Medical Center, Tehran University of Medical Science, Tehran, Iran
|Date of Web Publication||20-Jan-2016|
Department of Neurosurgery, Children's Hospital Medical Center, Tehran University of Medical Science, Tehran
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Brain tumors in infants have different clinical presentations, anatomical distribution, histopathological diagnosis, and clinical prognosis compared with older children. Materials and Methods: A retrospective analysis was done in patients <12 months old who were operated on for primary brain tumor in Children's Hospital Medical Center since 2008 to 2014. Results: Thirty-one infants, 20 males and 11 females, with the mean age of 7.13 months (0.5–12) were enrolled. There were 16 supratentorial and 15 infratentorial tumors. The presenting symptoms included increased head circumference (16); bulge fontanel (15); vomiting (15); developmental regression (11); sunset eye (7); seizure (4); loss of consciousness (4); irritability (3); nystagmus (2); visual loss (2); hemiparesis (2); torticollis (2); VI palsy (3); VII, IX, X nerve palsy (each 2); and ptosis (1). Gross total and subtotal resection were performed in 19 and 11 cases, respectively. Fourteen patients needed external ventricular drainage in the perioperative period, from whom four infants required a ventriculoperitoneal shunt. One patient underwent ventriculoperitoneal shunting without tumor resection. The most common histological diagnoses were primitive neuroectodermal tumor (7), followed by anaplastic ependymoma (6) and grade II ependymoma. The rate of 30-day mortality was 19.3%. Eighteen patients are now well-controlled with or without adjuvant therapy (overall survival; 58%), from whom 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.6%), and 2 cases are still on chemotherapy. Conclusion: Brain tumors in infants should be treated with surgical resection, followed by chemotherapy when necessary.
Keywords: Brain tumor, infants, surgical treatment
|How to cite this article:|
Ghodsi SM, Habibi Z, Hanaei S, Moradi E, Nejat F. Brain tumors in infants. J Pediatr Neurosci 2015;10:335-40
| Introduction|| |
Central nervous system (CNS) tumors are among the most common neoplasms in children., Intracranial tumors with the onset of symptoms before the age of 1 year once were considered to be rare; however, increasing numbers of such tumors have been detected in recent decades thanks to widespread use of modern imaging techniques.,,
Several series of brain neoplasms of infancy have been previously published, most of them date back to the last decade.,,,,,,, Herein, we investigated 31 brain tumors discovered in children <1 year during a period of 6 years. Different characteristics of tumors have been described based on their topographic distribution, either in supratentorial or infratentorial location.
| Materials and Methods|| |
In this retrospective study, we reviewed the filed database of 31 patients <12 months old, selected among 231 patients who were operated on for primary brain tumor in Children's Hospital Medical Center between April 2008 and April 2014. Those with scalp tumors, cavernous malformation, orbital tumors with intracranial extension, metastases, and nonsurgical tumors like radiologically typical optic pathway glioma and diffuse pontine glioma were not included in the study.
Tumors were divided into two groups based on the topographic distribution, namely infratentorial and supratentorial compartments [Figure 1]. Analysis of the filed database, including patient's age and gender, presenting symptoms and signs, surgical interventions, postoperative complications, cerebrospinal fluid (CSF) diversion, histopathological diagnosis, adjuvant therapy, and perioperative mortality was done for each group separately.
|Figure 1: (a) T1-weigted post-gadolinium injection axial magnetic resonance imaging shows a large supratentorial mass in a 15-day-old neonate. Postoperative histopathological diagnosis was mature teratoma (case 27). (b and c) T2-weighted axial and T1-weighted post gadolinium sagittal images show an infratentorial mass in a 2-month girl who presented with vomiting and tense fontanel. Tissue diagnosis was anaplastic ependymoma (case 9)|
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The study was approved by the Institutional Ethics Committee. All surgical procedures and follow-up assessments were performed by the same neurosurgical team.
| Results|| |
Among 231 patients who underwent brain tumor surgeries from April 2008 to April 2014, 31 infants - 20 males and 11 females - with the age ranging between 0.5 and 12 months (mean; 7.13 ± 4.046) were consecutively enrolled [Table 1]. There were 16 supratentorial and 15 infratentorial tumors (supratentorial to infratentorial ratio; 1.06). The presenting symptoms and signs of patients in both groups are tabularized in [Table 2]. The most common presenting sign of supratentorial tumors was an increase in head circumference (11 of 16) and in infratentorial tumors was vomiting (10 of 15). Overall, head enlargement was the most frequent presentation in this series. Four patients were in a bad condition at presentation, with central apnea and loss of consciousness demanding urgent intervention.
|Table 1: Patients with primary brain tumors diagnosed under the age of 1 year|
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|Table 2: The presenting symptoms and signs of infants with brain tumors in supratentorial and infratentorial compartment|
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Surgical resection was performed in 30 infants. One patient in posterior fossa group (case no. 2) underwent ventriculoperitoneal shunting in an emergent setting and was scheduled for further management, but the parents refused tumor surgery. From those who underwent surgery, gross total resection (GTR) was achieved in 19 infants (10 in infratentorial and 9 in the supratentorial group). For the remainder 11 cases, subtotal resection  or biopsy (2 cases of optic pathway glioma) was performed. CSF diversion methods and postoperative complications are summarized in [Table 1].
The histopathological diagnoses of tumors in supratentorial and infratentorial compartments are presented in [Table 3].
|Table 3: Histopoathological diagnosis of patients with brain tumors diagnosed under the age of 1 year|
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From those who survived 30 days after surgery, 17 patients with malignant pathology received adjuvant chemotherapy. Four patients with posterior fossa tumors (2 ependymoma and 2 medulloblastoma) experienced tumor recurrence in spite of chemotherapy, from them one died before any surgical intervention, and three others underwent reoperation plus adjuvant therapy leading to death in one and tumor control in other 2 patients. Four patients received radiation after the age of 3 years [Table 1].
The mean follow-up period was 30.3 ± 19.66 months (6–74 months). Currently, 18 patients are well-controlled with or without adjuvant treatment (overall survival; 58%); from whom 11 patients have survived with chemo/radiation (4 in supratentorial vs. 7 in the infratentorial cohort), and 7 patients with more indolent pathologies are good without adjuvant therapy (all in the supratentorial group). Among all 18 survivors, 13 cases are tumor free (disease free survival; 41.9%), 3 cases have residual masses with fixed or decreased size (progression-free survival; 9.67%), and 2 cases have not completed chemotherapy courses. There were 6 deaths during adjuvant therapy, added to 6 early postoperative deaths yield the overall mortality rate of 38.7% [Table 4].
|Table 4: Follow-up of patients operated on for brain tumors under the age of 1 year|
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| Discussion|| |
Overall, 1.4–8.45% of all brain tumors of children occur under the age of 1 year. The incidence of pediatric CNS tumors has gradually increased in recent decades. Although the underlying cause of this upward rate could lie in improved diagnostic tools, one extensive study proposed that the significant increase in tumor incidence can point to potential environmental influences. Whatever the cause and nature, the prognosis is usually poor, and the outcome is largely related to the size and location of the tumor, the general condition of the infant at the time of diagnosis, and surgical resectability., The younger age of patients, the absence of a well-accepted protocol, and limitations of adjuvant therapy makes the management more challenging to deal with.
According to most published works, the gender ratio of brain tumors in infants is equal or slightly male dominated. The male to female ratio was 1.1 and 1.4 in studies by Chung et al. and Mapstone, respectively. Information collected from 11 series, with a total number of 1289 infants, revealed a slight male predominance of 53%. Correspondingly, there was a male predominance of 64.5% in the current study. However, unlike other studies Haddad et al. found a female predominance in this age group, and Rickert et al. reported no gender preference.
Although pediatric brain tumors tend to be more located in the posterior fossa, the predominant location of infantile brain tumors was supratentorial in most series.,, In a study by Haddad et al., the anatomical distribution followed the adult pattern in that 67% were supratentorial. Likewise, a Korean study revealed supratentorial location predominance with a ratio of 2 (14–7). Pooled data from 11 series showed that 65% of these tumors were in the supratentorial area. The result of the current study showed only slight supratentorial predominance with the ratio of 1.06. A higher proportion of posterior fossa tumors in this series can be attributed to referral bias. Genetics, domestic nutritional behavior, ethnic and cultural factors may have influences on the anatomical distribution of infantile brain tumors. However, the sample size is too small to draw the exact conclusion about the tumor location in Iranian infants.
The location might be correlated with outcome, too. In a study by Mapstone, most infratentorial tumors had malignant pathologies (9 of 11), whereas most supratentorial tumors demonstrated nonmalignant histopathological patterns (8 of 11). Correspondingly in our series, 60% of infratentorial tumors versus 31.2% of supratentorial tumors had pathologies with WHO grade III and IV.
Brain tumors during the 1st year of life are clinically silent because of the lack of symptoms and verbal complaints. The ability of the infant's skull to expand and accommodate the rising intracranial pressure (ICP) and the brain's capacity for functional adaptation can delay the manifestation of clinical signs. The above-mentioned factors allow for considerable tumor growth with scarce nonspecific symptoms, the most common of which are macrocrania and vomiting, often in association with hydrocephalus., In Chung's study, only 4 patients out of 21 had head circumference <90 percentile. Half of infants in Haddad's series exhibited either hydrocephalus or asymptomatic increase in head circumference. Elevated ICP with ventriculomegaly was reported by Mapstone and Warf in 73% of patients. In a composite series of 1289 infant, macrocrania was observed in more than half of the patients. In concordance with the previous studies, enlarged head circumference was the leading presentation in our series (51.6%), followed by vomiting and bulge/tense fontanel (48.3%). More specific neurological signs including cranial nerves involvement or hemiparesis were only detected in 3.2–9.6% of cases due to the mentioned adaptability and late presentation.
Because of delayed presentation, the tumor has ample time to expand and fill most of intracranial space, making surgical resection technically demanding. Indeed, one striking aspect of brain tumors in infancy is their frequent large size, which can be a practical challenge in surgical management.
In the study by Chung et al., gross total and subtotal resection was achieved in 40% and 30%, respectively. Mapstone and Warf had 8 of 22 GTR, 12 of 22 subtotal resections, and 2 cases of biopsy. In Bognár's series, the rate of gross total, subtotal, and partial resection was 43%, 50%, and 7%, respectively. Mohanty et al. published series of 31 infants in 2013, 62% of them underwent a gross total or near-total excision. Accordingly, GTR was possible in 61.2% of our patients. The increased rate of resection can be attributed to improved diagnostic tools and better neuro-anesthesia techniques.
Fourteen patients in current series (46.6%) had postoperative external ventriculostomy, most of them were in the infratentorial category. Even so, with gradual tapering the external drainage system, only 12.9% of patients needed a permanent ventriculoperitoneal shunt. The International Society of Pediatric Neurosurgery (ISPN) survey conducted by Di Rocco et al. revealed 44% CSF diversion requirement. Twenty percentage of infants in Bognár's study needed shunt implantation, as well. Overall, it can be supposed that with appropriate management of external ventriculostomy, the rate of shunt requirement might decrease. However, this discussion is still open.
The outcome of surgery depends on the size of the tumor, histopathological diagnosis, and more importantly the infant's preoperative general condition. Most of the perioperative mortalities in this series occurred in patients with poor general condition, preoperative loss of consciousness, apnea or lower cranial nerves deficit. Operative mortality within the first 30 days of surgery was 19.3% in the current study, compared with 33% in Jooma's series, and 13% in Bognár's series. The extensive sensitivity of infants to blood loss, the concept of massive transfusion, and the importance of hypothermia should be appreciated to prevent operative mortality as much as possible.
The histological distribution of malignant to benign brain tumors is higher in neonates (100%) and infants (53%) compared with older children (43%). According to a worldwide study by Di Rocco, the ten most common types of brain tumors in infancy are, in descending order, astrocytoma, medulloblastoma, ependymoma, choroid plexus papilloma, primitive neuroectodermal tumor (PNET), teratoma, sarcoma, meningioma, ganglioglioma, and neuroblastoma. In a recent study by Mohanty et al., choroid plexus tumors were the most common pathologies, followed by medulloblastoma. Overall, astrocytoma and PNET account for the majority of pathological diagnoses in most other series. The most common tumor in a report by Mapstone and Warf was PNET (41%) followed by astrocytoma (36%). Furthermore, in Rickert's series of 22 infants, PNET was the most frequent pathology. In Haddad's study, however, astrocytoma slightly outnumbered PNET (7 versus 6 out of 22 cases). In a literature review by Larouche, astrocytic tumors represented the largest group (30.5%) followed by medulloblstoma (12.2%). Oi et al. stressed on ethnical differences in the types of brain tumors in a report of five Far-Eastern countries that had a higher incidence of medulloblastoma compared with the reports of western countries. In our series, there were 7 PNETs (22.5%) followed by 6 anaplastic ependymomas (19.3%) and 4 classic ependymomas (12.9%). Even though, summating all ependymomas, pilomyxoid and pilocytic astrocytomas (4), subependymal giant cell astrocytoma (1), and desmoplastic infantile ganglioglioma (1) as “glial tumors”, the total number of this category will be 16 cases (51.6%) and surpass PNET category. Hence, diverse ranges of tumor types in different series could be influenced by the subtypes classifications used by authors. For instance, in some studies, like ISPN survey, medulloblastoma has been defined as a separate category from supratentorial PNET.
Previously, patients with malignant or unresectable tumors underwent radiotherapy, but one should be aware of the serious adverse effects of radiation on growing brain of infants. Clinical observations and experimental data suggest that the immature brain is much more susceptible to irradiation and intellectual or growth retardation, delayed hypopituitarism, and occlusive neurovascular complications have been reported., Accordingly, radiation therapy was not administrated to patients younger than 3 years in the current series, and only 4 cases received radiotherapy for tumor control when they reached the age of 3 years. Anyway, Radcliffe et al. documented a mean intelligence quotient loss of 27 points in children younger than 7 years after whole-brain radiotherapy.
Chemotherapy remains a more accepted and well-tolerated method in this age group and has proven beneficial as an adjuvant therapy once the mass is incompletely resected, or in cases with malignant pathology.,
According to the previous investigations, the survival among patients younger than 1 year of age was less than that of older patients. Poor prognosis and high mortality in this age group have been attributed to the risks of anesthesia, difficulty in postoperative care, lack of voluntary control of water and salt intake, and the biological behavior of tumor itself. Prognosis may also depend on tumor location. In our series, overall survival in patients with posterior fossa tumors (7/11) was worse than that in group with supratentorial tumors (11/16). This finding is in concordance with a previous series of 100 infants demonstrating the shortest average length of survival in patients with posterior fossa tumors. This can be due to either hydrocephalus or impaired vital structures of the brain stem in the vicinity of the tumor.
The overall survival of 58% during a mean follow-up period of 30.3 ± 19.66 months in the current study appears to represent a similar pattern to the reported survival in recent decades while showing an improved rate over that in earlier reports. In published series dates back to 1930s and 1950s, 1-year survival in infants with brain tumor ranged between 27% and 37%., In a study by Jooma et al., in 1980, the rate of survival at 1 year and 5 years was 45% and 21%, respectively. In studies by Mapstone and Warf in 1991 and Mohanty et al. in 2013, overall survival was 58% and 68%, respectively., Improved survival in contemporary reports may reflect earlier disease detection due to advanced imaging technology, enhanced surgical techniques, better postoperative surveillance with early diagnosis of recurrence, and routine use of more effective chemotherapy.
Shortcomings and need for further studies
There are several limitations in the current study. The sample size was relatively small, and longitudinal follow-up was limited. The study design was retrospective that can impose potential inherent limitations in data collection.
The results of this study need to be replicated in a larger sample, preferably by prospective design and longer follow-up.
| Conclusion|| |
The results of this study are in concordance with similar studies conducted in western and Far-Eastern countries. Radical surgery with preserving vital structures is the treatment of choice in these patients, followed by chemotherapy in cases of malignant pathologies or incomplete resection. Despite the fact that our knowledge of brain tumors in the 1st year of life is still limited, progress has been observed in the management and prognosis of these tumors over the time which can be attributed to better knowledge of the clinical and biological behavior of tumors that allow tailoring of treatment according to the tumor characteristics.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]