9Bilateral vestibular schwannomas: the challenge of neurofibromatosis type 2

Patrick Grover

Expert commentary Robert Bradford

Case history

A 17-year-old female presented to her GP with a 1-year history of left-sided hearing loss, worsening balance, generalized headaches, and numbness affecting the left side of her face and tongue. She had previously been treated for left-sided otitis media and externa, and had undergone ear syringing for wax. Her previous medical history included meningitis as a child, but she had suffered no permanent neurological deficits. She had no family or social history of note.

On examination she had multiple café au lait spots over her abdomen and nodular fleshy polyps on her elbows, knees, and shins. She had bilateral sensorineural hearing deficits worst on the left side. Light touch and pin prick sensations were reduced on the left side of her face in the V2 and V3 dermatomes. Corneal reflex was absent in the left eye. There was uvular deviation to the left and tongue deviation to the left with right-sided wasting, consistent with glossopharyngeal and hypoglossal cranial nerve deficits. There was no facial nerve dysfunction. Cerebellar examination elicited slight left-sided dysmetria.

MRI demonstrated bilateral homogenously enhancing cerebellopontine angle mass lesions expanding the internal acoustic meati (Figure 9.1). The left-sided lesion measured 37 × 27 × 25mm and caused significant compression of the pons and medulla. The right-sided lesion was smaller at 23 × 14 × 11mm. Two further small extra-axial enhancing lesions were present in the right olfactory groove and abutting the right petrous ridge. There was no associated hydrocephalus. Audiometry confirmed bilateral sensorineural hearing loss particularly on the left side.

These findings were consistent with bilateral vestibular schwannoma and additional supratentorial meningiomata, with an underlying diagnosis of NF2. The patient’s symptoms and signs were predominantly localized to the larger left cerebellopontine angle lesion, which was debulked through a left retrosigmoid craniotomy and sub-occipital approach. The patient was started on dexamethasone (4mg qds po/iv). Post-operatively, the patient experienced hearing loss in her left ear, but no additional cranial nerve dysfunction. She subsequently developed hydrocephalus, for which a ventriculo-peritoneal shunt was inserted, and recovered well thereafter.

The gross pathological appearance of the resected fragments was of tan/grey pieces of tissue with a granular appearance. Histology showed multiple interlacing bundles of spindle cells with no atypical features, characteristic of a WHO Grade I schwannoma (Table 9.1).

Learning point Diagnostic criteria for neurofibromatosis type 2

The Manchester criteria are the most widely used criteria for defining neurofibromatosis [1]. They describe neurofibromatosis type 2 (NF2) associated lesions as meningioma, glioma, schwannoma, neurofibroma, or posterior subcapsular lenticular

opacities. Diagnosis requires one of the following:

●Bilateral vestibular schwannomas

●A first-degree relative with NF2 and either a unilateral vestibular schwannoma or two NF2 associated lesions.

●Unilateral acoustic neuroma and two NF2 associated lesions.

●Multiple meningiomas and either a unilateral acoustic neuroma or two NF2 associated lesions.

Right

Discussion

Vestibular schwannomas are benign tumours that are said to originate predominantly from the superior vestibular nerve. Their incidence is estimated to be between two and twenty cases per million worldwide, comprising approximately 5–10% of intracranial tumours [2]. They arise in the cerebellopontine angle accounting for approximately 90% of mass lesions in this location [3]. Speculation that their incidence may be increased by mobile phone exposure has been the subject of several studies, most of which have found no association [4]. However, the recent multi-national INTERPHONE case-control study suggested an increased incidence of ipsilateral tumours after 10 years usage [5]. They compared 678 cases of vestibular schwannoma and 3553 controls, retrospectively, interviewing participants to determine mobile phone usage. There was no overall increase in the risk of developing vestibular schwannoma (OR 0.9, 95% CI 0.7–1.1), but the risk of developing a tumour on the same side of the head as reported phone usage was statistically greater after 10 years (OR 1.8, 95% CI 1.1–3.1).

Vestibular schwannomas arise from the neurolemmal sheath of the vestibular nerve at the junction between oligodendrocytes and Schwann cells known as the Obersteiner–Redlich zone, approximately 8–12mm from the brainstem. They are characterized by spindle cells arranged in tightly compact fascicles within Antoni type A areas, and loosely compacted in Antoni type B areas. Bilateral vestibular schwannomas are pathognomonic of NF2 and are caused by mutations of the neurofibromin 2 gene found on chromosome 22q. This codes for tumour suppressor protein merlin, also known as schwannomin, which has roles in cellular proliferation and cell adherence [6]. Mutations in neurofibromin 2 are also found in a significant proportion of sporadic vestibular schwannomas [7].

Nearly all patients present with unilateral hearing loss with or without tinnitus. Balance disturbance affects around two-thirds of patients and headaches are similarly common. Facial numbness due to trigeminal nerve involvement can be a feature in up to one-third, whereas symptoms relating to the other surrounding cranial nerves are uncommon. On examination, a sensorineural hearing deficit is

Learning point Genetics of neurofibromatosis type 2

NF2 is autosomal dominant with high penetrance in inherited cases leading to clinical manifestations by the age of 60 in almost all affected individuals [8]. However, more than 50% of cases are sporadic and, of these, approximately one-third are mosaic—only a proportion of cells carry the mutation, which

occurs after conception [8]. These patients will have a milder clinical course and a less than 50% chance of passing the mutation to their offspring.

Expert comment The presentation of neurofibromatosis type 2

In adulthood, NF2 most commonly presents with symptoms and

signs of vestibular schwannoma, particularly unilateral hearing loss. A smaller proportion are diagnosed from alternative lesions, such as intracranial meningiomas causing seizures and headaches, ocular tumours leading to visual loss, spinal masses resulting in limb weakness and sensory disturbance, and cutaneous stigmata. More severe cases present in the paediatric population, where symptoms and signs from these alternative lesions are more prevalent [11].

almost universal. Nystagmus, facial hypoaesthesia and an abnormal corneal reflex are each elicited in approximately one-third of patients. Facial weakness and oculomotor nerve palsy may be detected infrequently. Large tumours (>3cm) can present with symptoms and signs of brainstem compression, lower cranial nerve damage, ataxia, or raised intracranial pressure due to obstruction of the fourth ventricle causing non-communicating hydrocephalus [9,10].

Clinical tip Cranial nerve examination in vestibular schwannoma

The differential diagnosis of a patient with unilateral hearing and balance loss remains wide and a thorough cranial nerve examination is crucial. Although intimately associated with the VIIIth cranial nerve (Figure 9.3), the VIIth nerve is much less often clinically affected by compression. Symptoms and signs of trigeminal nerve involvement are slightly more common although still seen in less than 20% of cases [10]. Loss of the corneal reflex is a particularly useful sign as it often precedes facial hypoaesthesia [9].

c

b

a

Expert comment

Indications for intervention in vestibular schwannoma in NF2 used in our practice include tumours that are:

●Greater than 3cm.

●2–3cm if enlarging on serial imaging.

●1–2cm if growing, with poor hearing. In those with good hearing, hearing preservation surgery may be undertaken with cochlear nerve implant if required

Expert comment

Cerebrospinal fluid leakage

CSF leakage is a common and troublesome complication of vestibular schwannoma surgery causing significant morbidity. Rates tend to be highest with the translabyrinthine approach. The incidence can be minimized with meticulous dural closure (not possible with translabyrinthine surgery), intra-operative fat and fascia grafting, use of fibrin glue, and post-operative lumbar CSF drainage.

Figure 9.4 Vestibular schwannoma as seen through a retrosigmoid transmeatal approach. a, retractor; b, cerebellum; c, vestibular schwannoma; d temporal bone.

enables access to almost all tumours with the possibility of hearing preservation (Figure 9.4) [22]. However, cerebellar retraction is required and the facial nerve is encountered late, resulting in higher rates of facial nerve palsy.

The translabyrinthine approach sacrifices vestibular and cochlear function on that side, but has the advantage of being a predominently extracranial approach with early identification of the facial nerve. Preservation rates of greater than 90% for small tumours and 50% for large tumours may be expected with this technique [23]. The middle cranial fossa approach is largely extradural and enables hearing preservation also, but is limited to small intracanalicular tumours, and carries a high risk of damage to the geniculate ganglion and facial nerve palsy [24]. It is important to recognize that these rates are case series from experienced centres representing exceptional outcomes. Rates of serviceable hearing preservation after surgery, for example, are not typically as high as quoted in the literature. Furthermore, all procedures carry a risk of CSF leakage in between 10 and 20% of cases, and a small risk of mortality (<1%).

Stereotactic radiosurgery and fractionated radiotherapy are increasingly used in the management of small vestibular schwannomas. A non-randomized prospective study of eighty-two patients treated at the Mayo clinic, Minnesota, USA, compared gamma knife stereotactic radiosurgery in forty-two patients, with microsurgery carried out on thirty-six patients for tumours of similar size and clinical profile [25]. At a mean of 42 months follow-up, facial nerve function was preserved in 96% of the gamma knife group and 75% of the surgical group, while useful hearing was maintained in 63% of gamma knife patients compared with only 5% of the surgical cohort. Operated patients also had significantly worse physical functioning, and pain at 3- and 12-month follow-up.