Vestibular Schwannomas in Children

Otology & Neurotology 22:903 907 2001, Otology & Neurotology, Inc. Vestibular Schwannomas in Children Vijay B. Pothula, Tristram Lesser, Conor Mallucci, Paul May, and P. Foy Departments of Otolaryngology and Neurosurgery, University Hospital Aintree, Liverpool, England, U.K. Objective: This article highlights the clinical presentation and management issues of unilateral vestibular schwannomas in children. We demonstrate how the presentation differs from neurofibromatosis type 2 (NF2) and from adult unilateral vestibular schwannomas. Study Design: This article is composed of a series of three cases and a literature review. Setting: The study was performed at a university hospital (tertiary referral center). Patients: Three children, aged 9, 11, and 13 years, with histologically confirmed vestibular schwannomas were studied. All children under 16 years of age in the world literature with unilateral vestibular schwannomas were reviewed. Intervention: Analysis of presentation and surgical management of these three children and those children reported in the literature. Main Outcome Measure: Pattern of presentation relative to children with NF2 and people with adult unilateral vestibular schwannomas. Results: Two patients had multiple cranial nerve weakness and recurrence, and one patient had successful removal of the tumor with preservation of all functions of the cranial nerves, including the facial nerve. Conclusion: Vestibular schwannomas in children are very uncommon. It is likely that it is the first manifestation of NF2, but it may also be a variant of sporadic vestibular schwannomas. A presentation of three cases and a review of 36 other cases in the literature demonstrates how the presentation is different from adult sporadic vestibular schwannomas and NF2 because it lacks primary audiological symptoms. The study also provides evidence of non-nf2 vestibular schwannomas presenting in children and suggests that it is likely that these are a variant of unilateral sporadic vestibular schwannomas. The search for the features of NF2 in these cases remains mandatory. Key Words: Sporadic Vestibular schwannoma Children. Otol Neurotol 22:903 907, 2001. Vestibular schwannomas in the absence of any indication of neurofibromatosis type 2 (NF2) are very rare in children. We report the cases of three children, aged 9, 11, and 13 years, with vestibular schwannomas, bringing the total in the world literature to 39 children. None of the three children in our series presented with otologic symptoms. In the literature, only 59% of the children had deafness or tinnitus as presenting symptoms. These tumors are more common in boys, and they tend to present late, with raised intracranial pressure, cerebellar symptoms, or multiple cranial nerve palsies. The tumors can be vascular, difficult to remove, and are associated with significant postoperative neurologic impairments. Vestibular schwannomas may be the first manifestation of NF2. The patients and their first-degree relatives should be screened with gadolinium-enhanced magnetic resonance imaging (MRI) scans of the brain and spinal cord, have their skin examined for café-au-lait spots, and undergo slit-lamp examination for cataracts and Lisch nodules. Address correspondence and reprint requests to Dr. Vijay B. Pothula, Consultant ENT Surgeon, Royal Albert Edward Infirmary, Wigan Lane, Wigan WN1 2NN, England, U.K. CASE REPORTS Case 1 A 9-year-old boy presented who was noted to have megalocephaly shortly after birth but had developed fairly typically during the first few months of life. Ventriculomegaly was diagnosed at 1 year of age by a computed tomographic scan. There was bilateral dilation of the lateral ventricles. Subsequent scans showed no increase in the size of the ventricles, however, so the condition was not treated. At 20 months of age, he developed strabismus and diminished visual acuity of 6/18 in both eyes. At 4 years of age, his visual acuity was 6/9 in each eye, with moderate convergent squint of approximately 15 degrees. He remained well until he presented to the pediatrician with headaches and vomiting at age 9 years. On examination, he was noted to have papilledema with altered level of consciousness. MRI scanning of the brain revealed a large 5-cm tumor in the left cerebellopontine angle (Fig. 1). All cranial nerves were intact, but no attempt was made to get an audiogram performed, because vestibular schwannoma was not suspected at that stage, and hence no neurotologist was involved. He underwent a left retrosigmoid craniotomy and subtotal 903

904 V. B. POTHULA ET AL. hearing loss but did not bring this fact to the doctors attention, because they did not think it was significant. He passed the normal developmental checkup at 8 months by distraction tests and later passed a preschool screening audiogram. He underwent total excision of the tumor by means of a retrosigmoid suboccipital approach. Postoperatively, he had palsy in cranial nerves V, VI, VII, and VIII. Histology was reported as a vestibular schwannoma. Immediate postoperative MRI scans showed no residual tumor, but scans 18 months after the operation showed recurrence of the tumor in the cerebellopontine angle extending into the internal auditory meatus. He has been referred to the neurotologist, and a second operation to remove the residual tumor is planned. FIG. 1. T1-weighted postgadolinium MRI scan showing >5-cm tumor in the left cerebellopontine angle. The center of the tumor shows necrosis. Note the tumor pushing the brainstem to the other side and compressing the fourth ventricle. removal of the tumor. Peroperatively, this tumor was noted to be very vascular and needed an exchange transfusion; consequently, only subtotal removal of the tumor was achieved. During the operation, the blood loss exceeded 2 L. The patient had a transfusion of7uofblood and 2 U of fresh frozen plasma. Postoperatively, he had weakness in cranial nerves V, VI, VII, and X. He also developed profound sensorineural hearing loss on the side on which he had the operation, whereas he had normal thresholds on the other side. Histology revealed a vestibular schwannoma. Retrospective inquiry of his hearing status indicated that his hearing had been normal at routine developmental checkups at both 9 months and 5 years of age. He underwent a second operation 20 months after the first, during which complete removal of the tumor was achieved by means of a translabyrinthine approach by a combined neurosurgical and neurotologic team. A hypoglossofacial nerve anastomosis was performed because no nerve stump could be identified at the brainstem. One year after the second operation, followup scanning of his brain and spinal cord showed no evidence of recurrence or a second tumor elsewhere. Case 2 An 11-year-old boy presented to the pediatric neurosurgeons because of ataxia and repeated falls during the previous 6 months. On examination, he was ataxic with left cerebellar signs, left lateral rectus palsy, and mild facial weakness. MRI scanning showed a solid 5-cm tumor in the left cerebellopontine angle that was associated with brainstem compression and obstructive hydrocephalus. Other cranial nerves were normal on examination. No audiogram or balance tests were performed, because vestibular schwannoma was not suspected. V.B.P. s inquiry about the boy s preoperative hearing status revealed that the parents had noticed that the boy had mild Case 3 This 13-year-old boy had a history of recurrent intermittent headaches and vomiting. Migraine was diagnosed, and he was treated with propranolol, metoclopramide, and paracetamol. He failed to improve, however, and an MRI scan showed a large 6-cm tumor in the right cerebellopontine angle (Fig. 2). A neurologic examination revealed papilledema and right-sided cerebellar incoordination, but all the other cranial nerves were intact. Pure-tone audiometry showed that he had a 60- to 70-dB sensorineural hearing loss on the right side and normal hearing on the left side, but he did not undergo any vestibular investigations. He underwent a suboccipital transmeatal combined neurosurgical and neurotologic approach with complete tumor removal. Histology confirmed a vestibular schwannoma. There was normal facial function after surgery, and postoperative MRI scanning showed no evidence of a tumor. A follow-up scan obtained 2 years postoperatively did not show any evidence of recurrence. This case is the only one among the three reported here that was diagnosed as vestibular schwannoma preoperatively and in which a FIG. 2. Large 6-cm tumor of the right cerebellopontine angle shown on T2-weighted MRI scan.

VESTIBULAR SCHWANNOMAS IN CHILDREN 905 neurotologist s intervention was sought at the time of primary surgery. DISCUSSION TABLE 1. Total number of cases reported so far of children fewer than 16 years old with unilateral vestibular schwannomas Ref. No. Number of cases Boys Girls Age (yr) 1 1 2 1 1 14 3 1 1 8 4 2 1 1 11, 14 5 1 1 10 6 1 1 13 7 1 1 14 8 1 1 7 9 1 1 13 10 1 1 10 11 1 1 1 12 3 1 2 14, 14, 14 13 1 1 9 14 1 1 10 15 1 1 9 16 1 1 13 17 1 1 1 18 1 1 13 19 1 1 Unknown 20 1 10 21 1 1 9 22 1 1 14 23 3 2 1 16, 11, 14 24 1 1 6 25 1 1 15 26 3 2 1 13, 13, 16 27 3 2 1 12, 13, 14 (Current study) 3 3 9, 11, 13 Total 39 27 11 Vestibular schwannomas are very rare in children, especially schwannomas that are not associated with NF2. Including our 3 cases, only 39 cases have been reported in children younger than 16 years of age (1 27) (Table 1). Our review disclosed a predisposition of boys to develop these tumors, which is in accordance with the findings of Ishikawa et al. (26). Schulman et al. (17) and Chen et al. (24), however, found no greater predisposition to development of these tumors in either sex. The incidence of these tumors in adults is estimated to be 1 per 100,000 annually (28), whereas their true incidence in children is difficult to ascertain because of their rarity. Pirsig et al. (29) described the temporal bone findings in two early Bronze Age children excavated from the prehistoric burial site at Franzhausen, Austria. These skulls date from approximately 2000 to 2300 BC and thus are approximately 4,000 years old. Both children exhibited marked widening of one internal auditory meatus, and one child seems to have had expansion of the internal auditory meatus into the vestibule and cochlea. The changes are particularly, elegantly, and hauntingly shown on computed tomographic images of the cadaveric temporal bones. The authors suggested that these two children had had NF2 (30). Until relatively recently, little was known about the factors that might render an individual prone to develop a vestibular schwannoma. However, advances in molecular biology have made it clear that a defect of chromosome 22q is responsible for the development of both sporadic unilateral vestibular schwannomas and the bilateral lesions of NF2 (30). Wu et al. (31) suggested that molecular analysis of tumor material of the patient for germline mutations on the NF2 gene may distinguish sporadic from familial cases. Among adults with vestibular schwannoma, 90% of patients present with unilateral hearing loss and tinnitus (30). Even though children also have deafness and tinnitus, this goes unnoticed for months or years until they develop cerebellar symptoms, facial and other cranial nerve palsies, or symptoms of raised intracranial pressure. Among our three cases, two presented with symptoms of headache and vomiting suggestive of raised intracranial pressure. The third presented with unsteadiness of gait that indicated a cerebellar lesion. None of the three children presented to an otolaryngologist or a neurologist primarily. No audiologic or vestibular investigations were assessed preoperatively in the first two cases, and only a pure-tone audiogram could be performed in the third case before surgery. The presenting symptoms of 39 published patients (including our 3 cases) are shown in Table 2. The growth rate of vestibular schwannomas among adults is known to vary from virtual dormancy to rapid growth of 1 cm/yr (32). Kasantikul et al. (33) suggest that growth rates may follow different time courses on the basis of the patient s age, with the growth rate during the first and second decades of life being accelerated. Furthermore, Wiet et al. (34) speculate that pregnancy and puberty may cause rapid enlargement of the schwannoma. Beatty et al. (35), however, performed immunohistochemical stains for estrogen, progesterone, and proliferating cell antigen in six female patients; one patient was pregnant, and the other five women were 2 to 10 months postpartum. They compared these patients with a control group of 6 men and 12 nonpregnant women, all with schwannomas of similar size, and concluded that pregnancy does not significantly stimulate the cellular growth of acoustic schwannomas. Curley et al. (36), in their analysis of tissue samples from 14 acous- TABLE 2. Review of clinical presentation of vestibular schwannomas in children Clinical presentation No. of patients % Deafness and tinnitus 23 58.9 Cerebellar symptoms 7 17.9 Facial palsy 10 25.6 Symptoms of raised ICP 14 35.8 ICP, intracranial pressure.

906 V. B. POTHULA ET AL. tic neuromas, failed to demonstrate the presence of estrogen or progesterone receptors. The majority of the tumors in our review presented as a large cerebellopontine angle mass; however, the description of the size of the tumor varies from precise measurement to the size of a small orange, an egg, or an apricot. Some of these tumors are extremely vascular, as in our first case, which needed exchange transfusion. The hemorrhage experienced during surgery results in prolonged operations, difficulty in identifying structures, and, ultimately, abandonment of procedures when only partial resections have been completed (23). It has been recommended that children with large vestibular schwannomas should undergo angiography before surgical excision so that the feasibility of preoperative tumor embolization can be determined and performed where indicated (15,23). It has been proposed that pediatric patients with a history of unilateral vestibular schwannoma and their first-degree relatives should undergo screening for manifestations of NF2. The screening consists of an MRI scan with gadolinium enhancement of the brain and spine, skin examination for café-au-lait spots, eye examination for posterior capsular cataracts and Lisch nodules, and genetic studies for germline mutations (37). All 3 patients reported in this series had no family history of NF2, have undergone thorough clinical examination and radiologic examination for evidence of NF2, and have shown no features suggestive of NF2. The blood and tumor specimens of the patients have been sent to look for germline mutations in NF2 genes. If both NF2 mutations are identified in the tumor, or one NF2 mutation with heterozygosity is identified, and if these are not present in the blood sample, then the patient can be reassured that the chance of being affected by NF2 is very small. 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