Neurofibromatosis-1, or von Recklinghausen NF, is one of the most common autosomal-dominant CNS disorders with an incidence of about 1 per 2,500–3,000 live births [28, 29]. About half of all cases are inherited; the other half arise de novo. The most common genetic abnormality associated with NF results in the loss of a tumor suppressor gene. NF-1 patients are prone to the development of pilocytic astrocytomas and gliomas involving the optic pathway in children [30]. An estimated 15–20 % of children with NF-1 are afflicted with an optic pathway glioma (OPG), with a majority of symptomatic children diagnosed before the age of 6 [3, 31, 32]. Rodriguez et al. [30] reported that in NF-1 patients with pilocytic astrocytomas and indeterminate subtype low-grade astrocytoma, extent of resection was not significantly associated with recurrence, radiographic progression, or tumor location. However, patients who undergo GTR have a better overall survival (OS) rate than those who undergo STR or biopsy (100 % vs. 52 % and 65 % at 10 years, respectively) [30]. Chemotherapy is considered a first-line therapy in children with NF-1 and afflicted with low-grade gliomas. A Children’s Oncology Group phase III trial of 401 children treated with different chemotherapy regimens revealed 5 year OS rates of 98 % for patients with NF-1 vs. 86 % for non-NF-1 children, suggesting a more favorable prognosis in the context of NF-1 [33]. Radiation therapy in patients with NF-1 is limited due to the increased risk of second malignancies [34] and radiation-related cerebral vasculopathies [35]. Sharif et al. [34] reported a high incidence of second nervous system tumors in NF1 OPG patients, with an increased risk in irradiated patients (4 malignant peripheral-nerve sheath tumors in 12 irradiated NF-1 OPG patients vs. 3/48 NF-1 controls).

Neurofibromatosis-2, or bilateral acoustic NF, is more rare than NF-1 with an incidence of 1 in 25,000 live births [36–38]. Though NF-2 is often associated with adult onset, Evans et al. [39] showed that at least 18 % of NF-2 patients present in childhood and are likely to have a more severely debilitating disease course. Furthermore, 10–18 % of children presenting with a meningioma or schwannoma are likely to have NF-2 with prolonged follow-up [39]. Eighth nerve dysfunction is a much more common symptom in children than in adults. Nunes and MacCollin [40] reported that hearing loss owing to vestibular tumors affected 9/12 children and 11/24 ears by age 18 years. Treatment for NF-2 is primarily surgical; optimal management includes presymptomatic resection for vestibular schwannomas [40]. Vestibular schwannomas in NF-2 patients are more difficult to treat than those with sporadic unilateral VS given the association with the eighth cranial nerve (vestibulocochlear) and as such surgery almost always leads to loss of the cochlear nerve and total deafness [41]. Depending on the location of the tumor, surgical resection via a middle fossa or retrosigmoid approach with partial or complete tumor removal may preserve hearing [42]. SRS is a controversial treatment of vestibular schwannomas in NF-2 and is currently being extensively debated [43]. While radiosurgery may preserve hearing function and arrest tumor growth, the presence of acoustic neuroma is still of threat to the patient [42].

Meningiomas are rare in children, accounting for 0.4–4.6 % of all CNS tumors in the pediatric population [44, 45]. As previously discussed, meningiomas within the pediatric age group are often the first sign of neurofibromatosis 2 [46]. Pediatric meningiomas are most commonly intracranial (90 %), followed by intraspinal (6 %), intraorbital (2 %), and elsewhere (2 %). These tumors are frequently located in the cerebral convexity, followed by intraventricular, falcine, parasagittal, anterior, and middle cranial fossa [47]. Perry et al. [48] noted that meningiomas in the pediatric population have a high frequency of brain invasion and are more phenotypically and genotypically aggressive when compared to adults. Surgical management is difficult in children due to location of tumors, larger size at presentation, relatively less blood volume in children, and risks inherent in long operations such as massive blood transfusions and hypothermia [49]. The goal of treatment is considered gross total resection with resection of the dural origin or attachment recommended to lower the risk of recurrence [45, 50]. In the largest series of 87 pediatric patients by Rushing et al. [50], mortality rate and recurrence rate were reported as 10.6 % and 19.4 %, respectively. There is limited data on the use of SRS in children, reported only in case reports. In one such report, SRS was used to successfully treat a child with recurrent meningioma in association with meningioangiomatosis [51]. Recurrent meningioma has also been successfully treated in three children using Gamma knife radiosurgery [52, 53].

Treatment for high-grade tumors without brain stem involvement in children is generally approached by surgical resection followed by adjuvant therapy. The main goals of surgery for these malignant tumors include obtaining a histological diagnosis and reducing the burden of the tumor by decreasing mass effect. High-grade tumors that have the treatment option of stereotactic radiosurgery following surgical resection include glioblastomas, ependymomas, medulloblastomas, ependymoblastomas, pineoblastomas, and CNS primitive neuroectodermal tumors (PNETs). GTR is achieved less for eloquent brain areas such as the thalamus and the basal ganglia than noneloquent areas such as the superficial cortical locations not associated with essential functions (63 % vs. 91 %, respectively) [54].

The most dangerous congenital vascular malformations are arteriovenous malformations (AVMs). Prevalence in adults is about 18 per 100,000 and AVMs account for between 1 and 2 % of all strokes, 3 % of strokes in young adults, and 9 % of subarachnoid hemorrhages [103]. AVMs usually present between ages 10 and 40 with the most common symptoms being headache, seizures, focal neurologic deficits, and intracranial hemorrhage; however, at least 15 % of people affected by AVMs are asymptomatic [103]. The long-term crude annual case fatality rates are between 1 and 1.5 % [103]. After a hemorrhage, the annual mortality can be as high as 18 % [104]. Ninety percent of AVMs in the brain are located supratentorially, while the rest are located in the posterior fossa. The Spetzler-Martin Intracranial AVM grading scale [105] was devised based upon size, location, and deep venous drainage. The lesion grade (I–V) is derived by summing assigned points in each category. Complete surgical excision of a grade I lesion (small <3 cm, located in a non-eloquent region such as the anterior frontal lobe, and with solely superficial drainage) would have very little risk of any resulting morbidity or mortality. On the other hand, a grade V lesion (larger than 6 cm, located within or adjacent to eloquent brain areas and with some drainage into the deep venous system) would have significant morbidity and mortality [105]. Surgical resection is the treatment of choice for grade I–III AVMs, due to its high cure rate (reported from 89 to 98.4 %) and low morbidity and mortality [106, 107]. In children, AVMs are most frequently located in the basal ganglia, thalamus, corpus callosum, brainstem, or within the motor, speech, or visual cortex [108, 109] and are the most frequent cause of intracranial hemorrhage in children [110–112]. Mortality from AVM hemorrhage in the pediatric population is much greater for cerebellar AVM than for AVM in the cerebral hemisphere (57 % to 4.5 %, respectively, p < 0.0001) [113]. While surgery is the mainstay of treatment for AVMs, endovascular embolization has become a useful additional technique along with radiosurgery as an alternative for high-risk lesions. After primary stereotactic radiosurgery, Pan et al. [114] reported a pediatric AVM obliteration rate of 65 % at 48 months following the procedure. When needed, additional SRS led to a total obliteration rate of 81 % [114]. Kano et al. [110] showed an even higher total obliteration with SRS of 70 % with at least 4 years of follow-up. Similar obliteration rates were obtained with Gamma knife radiosurgery, as Dinca et al. [115] reported 71.3 % for a one time treatment and 82.7 % overall. Thus, GKS is considered to be a valid active management option for pediatric AVM, though limitations include delayed effect with persistence of bleeding risk for 2–4 years posttreatment [115] (Case Study 31.4, Figs. 31.9 and 31.10).