Like all brain tumors, the clinical presentation of cerebellar astrocytoma reflects the anatomic position of the tumor.

The site of origin of brain tumors in childhood is a considerable factor in prognosis because of differences in biology and surgical accessibility. The symptoms and signs in a child with a brain tumor reflect the neurological dysfunction of the affected site but can also be due to obstruction of normal flow of CSF, localized edema, and associated raised intracranial pressure. These symptoms and signs are varied and are dependent on many factors such as premorbid developmental stage, age, and site of origin. The same symptoms and signs are therefore seen in children regardless of specific tumor histopathology. In infancy, there may be increased head circumference. Brain tumors, especially posterior fossa tumors, should be considered in the differential diagnosis of infantile hydrocephalus. Irritability, anorexia, developmental delay, and regression of intellectual and motor milestones are signs seen in infants and young children. Cranial sutures and fontanelles may remain open due to raised ICP, and fundal examination may therefore show optic pallor rather than papilledema. Separation of cranial sutures leads to resonance on skull percussion (the Macewen or “cracked pot” sign). The well-described “setting sun” sign is seen with downward eye deviation, which is often accompanied by a high-pitched cry. Clinical assessment should always include head circumference, fundal examination, and developmental appraisal.

Symptoms and signs in older children with posterior fossa brain tumors may be more subtle and nonspecific. In school-aged and older children, morning headaches, vomiting, and lethargy make up the typical triad seen with raised intracranial pressure. The headache may have physical suboccipital localization and is rarely continuous. Vomiting is not accompanied by nausea. Raised intracranial pressure can affect other intracranial structures; sixth nerve palsy results in diplopia or blurred vision. This may be a false localizing sign and does not necessarily mean the presence of a posterior fossa lesion, as raised intracranial pressure can be due to other diseases. Deficits of cranial nerves V, VII, and XI should direct investigation to the brainstem. There may be long tract upper motor neuron signs of weakness, hyperreflexia, clonus, and hypertonia, cerebellar signs may result in nystagmus, as well as non-lateralizing gait or truncal ataxia. In any child who presents with visual problems, the optic nerve, chiasm, and visual fields should be carefully evaluated. An afferent pupil defect will be shown by comparing evaluation of both direct and consensual pupillary response to a bright light (Marcus Gunn pupil). It is worth emphasizing that nonlocalizing symptoms of raised intracranial pressure will be the predominant symptoms early in the course of disease.

Pilocytic astrocytomas are slow-growing tumors with a low frequency of malignant transformation and characteristically on imaging have mixed solid and cystic characteristics. These tumors occur most commonly in the cerebellum, optic nerves, or chiasm, with the cerebellum representing the most frequent site [1]. The reported incidence of cerebellar astrocytoma approaches 25 % of all primary pediatric CNS tumors [2]. Cerebellar astrocytoma is most commonly seen in early childhood, with age of peak diagnosis being in the first 14 years of life and a median age of diagnosis at 6 years [3, 4]. This is most likely a reflection of brain maturation and development processes being linked with pathogenesis. The notion that pathways involved in early brain development are involved in the pathogenesis of pediatric cerebellar astrocytomas is supported by distinct differences between pediatric cerebellar astrocytomas and their adult counterparts. While the histology of these tumors, as described in Section 35 is similar between pediatric and adult pilocytic astrocytomas, the genetic profiles are distinct [3, 5], highlighting the need to consider pediatric cerebellar astrocytomas as a separate disease entity to adult tumors when considering therapeutic options. The genetics of pediatric cerebellar astrocytomas are described in Section 32. While these tumors can arise de novo, an increased risk is associated with particular genetic constitutions. In particular, children with neurofibromatosis are at a significantly higher risk of pilocytic astrocytomas, not only in the optic nerves which are the most frequent site of presentation, but also for cerebellar pilocytic astrocytomas [6, 7].

The overall prognosis of children with cerebellar astrocytomas is excellent, with some studies reporting overall 5- and 10-year survival figures of between 80 and 100 % [8–10]. Survival of adult survivors of Pediatric Low-Grade Gliomas is excellent and these tumors do not frequently transform to higher grade tumors [40]. Furthermore, as noted above, the peak incidence of cerebellar astrocytomas is in the preschool and early school years, at a time when postnatal maturation of the brain is occurring. In this group, childhood milestones are developing exponentially, and therapy for cerebellar tumors therefore has potential for significant neurocognitive deficits. The principle of treatment of cerebellar astrocytomas is to attempt maximal tumor control with minimal long-term deficits. It is also clear that the clinical behavior of these tumors is variable, with periods of growth and periods of stability [11]. The therapy modalities available include observation, surgery, chemotherapy, and radiation therapy.

The initial modality of therapy in a child with a cerebellar astrocytoma is surgical, and this has been described in Section 34. Briefly, surgical therapy is directed at controlling complications of the tumor, in particular hydrocephalus, and maximal safe resection of the primary tumor while attempting to minimize long-term surgical morbidity. Gross total resection confers the most favorable prognosis and is considered to be curative in the majority of children [9, 12] with 10-year progression-free survival of up to 95 %. Gross total resection is achievable in 60–80 % of children with cerebellar astrocytoma [12].

Historically, children with subtotal resections were treated with radiation therapy. However, given the morbidity of radiation therapy and the understanding that these tumors have a variable course, are unlikely to undergo malignant transformation, and have periods of extended stability, current therapy strategies aim to defer radiation therapy. Instead they are observed closely and upon clear documentation of disease progression, other therapy is utilized including second-look surgery or chemotherapy [10–13]. Using this approach, children undergo surveillance imaging at three to six monthly intervals. Prospective surveillance studies have reported 5-year progression-free survival rates of between 45 and 65 % in children with residual tumor postprimary resection [14, 15].

In children who have progression after either initial gross total resection or subtotal resection, a multidisciplinary approach to the management is vital. Single institute studies have demonstrated the feasibility of second-look surgery on tumor progression prior to initiation of chemotherapy or radiation therapy. If second-look surgery is able to be performed safely, there is demonstrated reduction in long-term morbidity [11].

Multiple chemotherapy regimen has been utilized to defer radiation. This approach to use chemotherapy was originally for newly diagnosed children but is now also utilized for documented progression. Pilocytic astrocytomas were first shown to be sensitive to carboplatin and vincristine in the 1990s [16]. There is ongoing debate about the utility of vincristine to be effective in crossing the blood-brain barrier, and current treatment incorporates carboplatin, with or without vincristine to stabilize tumors, limit progression or make them potentially amendable to second-look surgery [11]. Other chemotherapy regimens include procarbazine, 6-thioguanine, CCNU, dibromodulcitol with vincristine, and the combination of CCNU with vincristine [17]. Cyclophosphamide in combination with carboplatin and vincristine has not been shown to have any added benefit [18]. However, cyclophosphamide and vincristine has reported to improve progression-free survival [19]. Carboplatin in combination with etopside has also been reported to result in objective responses in progressive astrocytomas [13]. These studies all show that pilocytic astrocytomas are chemoresponsive.

These agents all have their unique side-effect profiles, and the challenge is to use the least morbid regimen without compromising tumor control. The COG study A9952 evaluated event-free survival in children treated with either the carboplatin and vincristine or the TPCV (thioguanine, procarbazine, CCNU, and vincristine) protocol. In this randomized study, there was no statistical difference in outcome; however, there was a trend to improved survival using the TPCV protocol [20]. Carboplatin is very well tolerated, with adverse effects including development of hypersensitivity, thrombocytopenia, myelosuppression, and low incidence of sensorineural hearing. In contrast, alkylating agents such as CCNU carry with them risks of secondary malignancy including myeloid leukemia. Many centers around the world therefore use carboplatin, either with or without vincristine as first-line therapy on documented progression, with the more morbid regimens being reserved for subsequent progression. Children with NF1 carry a higher risk of secondary malignancies, and in these children, alkylating agents, if possible, should be avoided.

While once standard of care postsurgical resection, radiation therapy in children with cerebellar pilocytic astrocytomas is now reserved for those with recurrent episodes of progression that are not stabilized by chemotherapy and in whom further surgery is no longer an option. Section 37 focuses on the role of radiation therapy in cerebellar astrocytomas. Almost all children with PLGGs can be treated without radiation therapy. Given these children are likely to be long-term survivors, attempts are made to spare them the long-term morbidities associated with radiation therapy including second malignancies, vasculopathy and neuro-cogntive deficits. With regard to radiation, caution also needs to be exercised with regard to children with neurofibromatosis type-1 (NF-1) as there is an increased risk of radiation-induced vasculitis (including Moyamoya disease), as well as the aforementioned risk of second malignancy. In what is therefore generally considered a benign tumor, the role of radiation should be reserved for tumors where standard first-line therapy of surgery and/or chemotherapy has failed. With the increasing understanding of the somatic alterations that contribute to tumor formation, targeted therapies are now possible. These include BRAF inhibitors for tumors that harbor the BRAFV600E mutations, MEK inhibitors for those that harbor BRAF duplications, mTOR inhibitors and other targeted therapeutics.

As mentioned above, the long-term prognosis of children with pilocytic astrocytomas is excellent. The majority of children with completely resected tumors are cured and require no further therapy for tumor control. In these children, the focus of therapy is directed toward recognizing potential long-term neurocognitive effects that occur as a result of the tumor, the concurrent hydrocephalus, and subsequent surgical management. Of the children who undergo a subtotal resection, approximately half enjoy 5-year progression-free survival. In these children, the focus is on surveillance for progression, rehabilitation of functional deficits, and surveillance for long-term neurocognitive deficits.