Tumors of the auditory nervous system

Presentation: 19 Giten George

Definitions
1. Neoplasm: The word neoplasm literally means a new growth, from the Greek neo-,

2.

3. 4.

5.

6. 7.

new + plasma, that which is formed, or a growth. Neoplasms can be benign or malignant. Malignant: Any malignant growth or tumor is caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream, cancerous. Benign tumor: Tumor that is not cancerous Metastasis: An active process by which tumor cells move from the primary location of a cancer. Malignant tumors have no enclosing capsule, cells escape, become emboli, and are transported by the lymphatic circulation/ the bloodstream to implant in lymph nodes and other organs far from the primary tumor. Secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Multiple tumors may develop. Enchondral - Situated, formed or occurring within cartilage. Extraaxial- Off the axis; applied to intracranial lesions that do not arise from the brain itself. External to the pia. Meninges, nerve sheath etc.

8. Intra-axial Intra axial is a term that denotes lesions that are within the brain

parenchyma, Internal to the pia.

9. Infratentorial region of the brain is the area located below the tentorium cerebelli. The

area of the brain above the tentorium cerebelli is the supratentorial region. The infratentorial region contains the cerebellum, while the supratentorial region contains the cerebrum. Relevant Brain anatomy Two types of neural cells in the nervous system: I. II. Neurons - For processing, transfer, and storage of information Neuroglia For support, regulation & protection of neurons CNS neuroglia PNS neuroglia 1) Astrocytes 2) Oligodendrocytes 3) Microglia 4) Ependymal cells 1) Schwann cells (neurolemmocytes) 2) Satellite cells

Glial cells In the CNS, there are 2 types of glia distinguished by size and embryonic origin.

Macroglia, including astroglia and oligodendroglia, are the larger glial cells which originate from the neural plate. The astrocytes form glial end feet on the blood vessels, the processes of astrocytes insinuate themselves into the spaces between neurons, cell bodies, axons dendrites and synapses. The Oligodendrocytes are smaller than the astrocytes and have fewer and smaller processes. Microglia, smaller and originate from mesoderm. Macrophagic function, they can migrate in the mature CNS, play an important function in the removal of degeneration debris following injury. Phagocytize cellular wastes & pathogens Ependymal cells line the ventricles, one cell thick. The cells contact one another through gap junctions, and their ventricular faces have numerous microvilli and cilia. Arachnoid layer and space: A delicate, spiderweb-like membrane/tissue. Literally from Latin "spider web-like". One of the three meninges. It is interposed between the two other meninges, the more superficial dura mater and the deeper pia mater, and is separated from the pia mater by the subarachnoid space.

Types of glial cells N- Neuron, OOligodendrocyte, A- Astrocyte, BVBlood vessel.

Posterior skull base 1) Cerebellopontine angle 2) Clival 3) Jugular foramen 4) Foramen magnum Cerebellopontine Angle - Space filled with cerebrospinal fluid. It has the brain stem as its medial boundary, the cerebellum as its roof and posterior boundary, and the posterior surface of the temporal bone as its lateral boundary. The floor of the cerebellopontine angle is formed by the lower cranial nerves (IX-XI) and their surrounding arachnoid investments. The flocculus of the cerebellum may lie within the cerebellopontine angle and may be closely associated with cranial nerves VIII and VII as they cross the cerebellopontine angle to enter the internal auditory canal.

Borders Medial Lateral surface of the brainstem Lateral Petrous bone Superior Middle cerebellar peduncle & cerebellum Inferior Arachnoid tissue of lower cranial nerves Posterior Inferior cerebellar peduncle

Tumor types
1. Chloroma - Malignant, green-colored tumor arising from myeloid tissue, associated

with myelogenous leukemia; it can occur anywhere in the body but has an affinity for the central nervous system, bone, and soft tissues of the head and neck.
2. Myeloid- Derived from, or resembling bone marrow or the spinal cord. Tumor -

Myeloma
3. Neurinoma: Tumor (usually benign) of the sheath surrounding a nerve. 'Neuroma':

'nerve tumor (Greek) 4. Lymphoma - a cancer in the lymphatic system; 5. Ependymoma - Glial tumors that arise from ependymal cells within the central nervous system (CNS)
6. Astrocytoma- Neoplasms that develop from astrocytes. 7. Chordoma Malignant tumor arising in the axial skeleton from embryonic remains of

the notochord
8. Chondrosarcoma - Malignant cartilage tumor that originates from enchondral bones.

When it develops in the skull base, it usually arises in the parasellar area, cerebellopontine angle, or paranasal sinuses.
9. Hemangioma- Abnormal buildup of blood vessels in the skin or internal organs. 10. Hemangioblastoma - Tumors of the central nervous system that originate from

the vascular system usually during middle-age.

11. Medulloblastoma - Highly malignant primary brain tumor that originates in

the cerebellum or posterior fossa.

12. Papilloma- Benign epithelial tumor growing exophytically (outwardly projecting) in

finger-like fronds. In this context papilla refers to the projection created by the tumor, not a tumor on an already existing papilla.
13. Lipoma - Tumors containing fat. Clinically, CPA lipomas can cause slowly

progressive neurological symptoms and signs affecting cranial nerves or brain stem. Because these lesions usually are strongly attached to the surrounding structures, any surgical attempts of complete resection can result in neural or vascular damage.

14. Chondrosarcoma- Skull base tumor, rare, slow-growing with a potentially lethal

outcome due to compression of adjacent tissues, such as the carotid artery and cranial nerves.
15. Arachnoid cysts - Cerebrospinal fluid-filled sacs that are located between the brain

and the arachnoid membrane. Primary arachnoid cysts are present at birth and are the result of developmental abnormalities in the brain and spinal cord that arise during the early weeks of gestation. Secondary AC develops as a result of head injury, meningitis, or tumors, or as a complication of brain surgery. The majority of arachnoid cysts form outside the temporal lobe of the brain in an area of the skull known as the middle cranial fossa.
16. Epidermoid cyst - Connsist of epidermal and connective tissue structures usually in

the form of a sac. They have the capacity for independent progressive growth often at the expense of neighbouring bone and have a tendency to reform after removal. The cerebellopontine angle is the most common site of occurrence of intracranial epidermoids. 17. Cholesterol granulomas- Occur in the pneumatized petrous apex of the temporal bone but also may be seen in other pneumatized portions of the temporal bone, including mastoid air cells and middle ear space. It is not a neoplasm but a descriptive term used for a granulomatous reaction to blood breakdown products, primarily cholesterol. They are thought to arise secondarily following disease states where normally ventilated air-containing bony spaces are obstructed, such as in chronic or acute otitis media, cholesteatoma, or mastoiditis

Cerebellopontine Angle Tumors can be grouped into 7 categories. This classification is conductive to differential diagnosis based on location. 1) Extra-axial lesions 2) Intra- axial lesions 3) Extra-dural lesions I. Extra axial lesions can be further divided into the following sub categories a. Vestibular Schwannoma b. Meningioma and simulants - Leptomeningeal metastases - Primary meningeal Lymphoma - Primary meningeal melanoma - Meningeal sarcoidosis - Hypertrophic pachymeningitis

c. Epidermoid and other cysts - Arachnoid cyst - Cysticercal cyst d. Nonvestibular Posterior Fossa schwannomas V, VII, IX, X, XI, XII

II.

Intra- axial lesions a. Brainstem tumor - Astrocytoma - Lymphoma - Hemangioma b. Cerebellar tumor - Astrocytoma - Hemangioblastoma - Metastases - Lymphoma - Hemangioma - Medulloblastoma

c. Forth ventricular tumor - Ependymoma - Choroid plexus - Papilloma III. Extradural Lesions a. Bone lesions - Cysts, e.g., Cholesterol cyst, Epidermoid cyst, Mucocele b. Tumors, e.g., Chordoma, chondroma, giant cell tumor, myeloma, metastases c. Paragangliomas (Glomus Jugulare tumor)

INTRACANALICULAR LESIONS Acoustic & facial schwannoma, Hemangioma, Meningioma, Metastasis, Glioma, Lipoma, Osteoma

Classification based on source of lesion Primary tumors of the CPA Vestibular Schwannoma Meningioma Arachnoid cyst Epidermoid cyst Schwannoma of V, VII, IX, X, XI nerves Primary melanoma Hemangioma Lipoma, dermoid, teratoma Secondary tumors of the CPA Paraganglioma Ceruminoma Chondroma-chondrosarcoma Chordoma Extension of cerebellar and petrous bone tumors Metastases

Neurofibromatosis Von Recklinghausens disease (1882) occurs in three forms (overlap of forms also occurs). I. Central forms, known as neurofibromatosis-II (NF-II) A. Multiple intracranial and intraspinal tumors B. Bilateral acoustic schwannomas II. Peripheral form (NF-I) (today, only NF-I is referred to as von Recklinghausens disease) A. Cafe ole spots III. Visceral form NF-II Microscopically, NF-II schwannomas are histologically identical to sporadic acute unilateral acoustic schwannomas. In some cases they may show an intermediate pattern between meningioma and schwannoma (the cells of schwannomas and meningiomas originate from the neural crest). Bilateral acoustic tumors are a principle clinical feature of neurofibromatosis type II, although other manifestations, including peripheral neurofibroma (tumor on nerve sheath of peripheral nerves), meningioma, glioma are often present as well. Multiple schwannomas involving an individual nerve, or involving numerous nerves, as well as multiple meningiomas. NF-II tumors may be more invasive and may infiltrate the cochlear nerve as compared to the sporadic acoustic neuroma. This infiltration may be responsible for low success rate with tumor removal in hearing preservation. There are three clinical subtypes of NF-II. Gardners subtype (milder form) 1. Onset of symptoms, usually HL from bilateral vestibular schwannomas. 2. Few or other associated brain or spinal cord tumors. 3. Main age of onset is 27 years, only 12% have meningiomas Wisharts subtype (severe form) 1. Multiple intracranial and spinal tumors. 2. Developed at an early age with rapid progression of signs and symptoms. 3. Average age of presentation 17.4 years, 70% with meningiomas.

Third subtype, called the Lee/Abbott subtype 1. Childhood cataracts and early death due to cranial and spinal meningiomas and schwannomas. 2. Average age of presentation 14 years, 70% incidence of meningiomas. von HippelLindau disease (Features related to hearing) VHL disease is a complex multisystem disorder, the autosomal dominantly inherited disorder von HippelLindau disease (VHL) is caused by germline mutations in the VHL tumor suppressor gene (TSG). VHL mutations predispose to the development of a variety of tumors (most commonly retinal and central nervous system haemangioblastomas). CNS haemangioblastomas are a cardinal feature of VHL disease and are the presenting feature in 40% of cases. Overall CNS haemangioblastomas occur in 6080% of VHL patients and most commonly occur in the cerebellum, spinal cord and brain stem with supratentorial lesions being rare. Patients with cerebellar haemangioblastomas typically present with symptoms of increased intracranial pressure and limb or truncal ataxia (depending on the precise location of the tumour) and the clinical presentation of CNS haemangioblastomas reflects their mass effect. Haemangioblastomas with an associated cyst tend to become symptomatic sooner. Endolymphatic sac tumors (ELST) can be detected by MRI or CT imaging in up to 11% of patients. (Heffner, 1996). Bilateral ELSTs are considered pathognomonic for VHL disease. Although often asymptomatic, the most frequent clinical presentation is hearing loss (mean age 22 years), but tinnitus and vertigo also occur in many cases. Differentiating extra axial and intra axial lesions Summery of extra-axial and intra-axial brainstem auditory disorders- Jerger and Jerger. (1975) Pure tone audiogram In intra-axial lesion average threshold levels were 1 -15 dB at all frequencies plus good PB max scores. This data closely approximated observations by other investigators (Liden, 1969; Parker, 1968; Jerger, 1960a). Normal acoustic reflex contractions. Auditory symptoms in both ears or the contralateral ear only. verage s for the extra axial lesion patients were 60 dB for 500, 1000 and 2000 Hz, and 80 dB for 4000 Hz, they also had poor PB max scores. Absent/decaying acoustic reflexes. Auditory symptoms on the ipsi-lateral ear only All audiometric test results showed an overall between the 2 groups, the degree of overlap is relatively small for pure tone sensitivity measures, but more extensive for acoustic reflex, PB max scores and roll over.

In contrast to the flat audiometeric configuration in IA lesions, the EX lesion group showed a steeply sloping audiometric contour. The same have also been reported by Flower in 1965 and Johnson in 1969, 1972. The roll over phenomenon was observed in both the groups, but could not differentiate the groups. If the intra-axial mass produces an exophytic extension into the CPA, the extra-axial symptomatology caused by the exophytic extension may mask the primary intra-axial site.

Correlation of Audiological and histopathological findings Vestibular Schwannoma (Extra axial lesion) 80% of tumors arising in the CPA are vestibular schwannomas(VS). The tumor arises from the Schwann cells, which surround the sheath of the CN VIII, not from the nerve itself. Vestibular schwannoma (also known as acoustic neuroma, acoustic neurilemoma, or acoustic neurinoma) is a slow growing, intracranial extra-axial benign tumor that usually develops from the vestibular nerve or very rarely from the cochlear nerve (less than 5 percent). There are 2 major types of VS. The sporadic type, occurs in 95% of all cases, is unilateral, and usually affects individuals 40 to 60 years old. VS associated with neurofibromatosis type 2 are typically bilateral, autosomal dominant, and usually affects teens and young adults. (Ho, 2002) Because vestibular schwannomas arise from the investing Schwann cell, tumor growth generally compresses vestibular fibers to the surface. Destruction of vestibular fibers is slow and gradual and the reduced vestibular function is compensated for by central cerebral mechanisms. Consequently, many patients experience little or no imbalance. Once the tumor has grown sufficiently large to fill the internal auditory canal, it may continue to grow either by eroding or expanding the bone and/or by extending out into the cerebellopontine angle. Vestibular

schwannomas, like other space occupying lesions, produce symptoms by any of four recognizable mechanisms: (1) blockage of the cerebrospinal fluid spaces, (2) displacement of the brainstem, (3) compression of vessels or (4) compression of nerves. Vestibular schwannomas can continue to grow until they reach 34 cm in intracranial size before symptoms of major mass effect develop. The facial nerve is quite resistant to the stretching imposed by tumor growth without clinically apparent deterioration of function until the tumor has reached a very large size. The cochlear and vestibular nerves, on the other hand, are much more sensitive to this stretching and compression so that even small tumors confined to the internal auditory canal may produce early symptoms in the form of hearing loss or vestibular disturbance. As the tumor approaches 1.5 cm in intracranial diameter, it generally begins to abut the lateral surface of the brainstem. Further growth can occur only by compressing or displacing the brain stem toward the contralateral side. A 2.0 cm tumor usually extends sufficiently far anteriorly and superiorly to compress the trigeminal nerve and sometimes produces facial hypoesthesia (impairment of sensitivity). Growth over 4.0 cm generally results in progressive effacement of the cerebral aqueduct and fourth ventricle with eventual development of hydrocephalus. However, other mechanisms may be responsible for the occasional development of hydrocephalus in tumors as small as 2.0 cm. A known factor of importance is the increase (up to 1015 fold) of cerebrospinal fluid protein content in the presence of a vestibular schwannoma (Rogg, 2005) Etiology Merlin is defined as a tumor suppressor gene because its inactivation or loss of expression was found in all NF2 tumors as well as 60 80 % of sporadic meningiomas and schwannomas. Both unilateral and bilateral vestibular schwannomas may form due to malfunction of a gene on chromosome 22, which produces a protein (merlin) that controls the growth of Schwann cells. In NF2 patients, the faulty gene on chromosome 22 is inherited and is present in all or most somatic cells. However, in individuals with unilateral vestibular schwannoma, for unknown reasons this gene loses its ability to function properly and is present only in the schwannoma cells (Lanser, 1992). Vestibular symptoms Vestibular symptoms are uncommon as the presenting symptom of a VS, despite the fact that the tumor originates on the vestibular nerve. This partly may be due to the slow-growing nature of the tumor so that an episode of vertigo years prior may be forgotten. Sudden vertigo with nausea and vomiting, similar to vestibular neuritis, is reported to occur in 5% to 19% of patients. This presenting symptom mainly occurs in patients with small tumors.

Compensation can be complete with no residual symptoms. Dysequilibrium or unsteadiness is a more common symptom later in the course of VS. Patients may note the symptoms on rapid motion of the head or body only or as a constant state. Constant symptoms are associated with increasing tumor size, with impingement on the cerebellum and brainstem occurring in addition to encroachment on the vestibular nerves. Phases of tumor growth - 1) Intracanalicular 2) Cisternal 3) Compressive 4) Hydrocephalic - Jackler (2000)

Treatment Watchful waiting has been recommended for the elderly and for infirm patients with tumors <1 cm who would be poor candidates for surgery or radiation. (Because the slow growing tumor is not expected to cause a health risk within their expected lifetime) In up to 57% of VS cases, no further tumor growth occurs after diagnosis; in about 8% of these cases, tumor regression is noted (Mohr, 2005). A little more than half of patients will experience further hearing loss. Unfortunately, there are no prediction rules for determining who is at risk for tumor growth and hearing loss. A recent study found that conservative management was a cost-effective approach for tumors <1.5 cm in any age group (Anthony, 2009) provided there was no increase in complications from continued tumor growth. Follow-up MRI can be used as a surveillance tool.

Audiological test results The signs and symptoms present at diagnosis are almost exclusively auditory, and only rarely are other neurologic symptoms found in the absence of auditory symptoms. A number of authors (Chandrasekhar, 1995; Salesnick, 1992; Thomson, 1990) verified that the initial or presenting symptom is hearing loss with or without tinnitus in about 80% of patients. Tinnitus only about 7% of patients, and hearing loss only - 60% to 70%. The percentage of patients with hearing loss or tinnitus (or both) at the time of diagnosis is about 95% or greater in AN patients even in patients with small tumors. Correlation between degree of HL & time since symptoms started A small correlation may exist between the degree of hearing loss and the amount of time symptoms have been present, but such a wide variation exists that generalization is difficult. Correlation between degree of HL & tumor size The symptoms of hearing loss or tinnitus are independent of tumor size, but there is a definite trend toward better hearing in tumors less than 1 cm. (Stipkovits, 1998) Pure Tone Audiometry Progressive, unilateral, sensorineural hearing loss, which typically begins in the high frequencies and progresses to involve the lower frequencies.

 20% of the patients will present with sudden sensorineural hearing loss (Sauvaget et al, 2005). Additionally, 20% will present with recurrent fluctuating hearing loss. Less common are the vestibular complaints. As the tumor enlarges, neurological changes may be evidenced as decreased function of CN VII and V. With continued growth, a patient may develop hydrocephalus from brainstem compression. 10 - 25% of patients have severe to profound hearing losses, with PTA greater than 80 dB at the time of their initial audiogram. Duration Can be either progressive or sudden. Sudden sensorineural hearing loss (SSHL) has been defined as a sensorineural hearing loss of > 30 dB over at least 3 contiguous audiometric frequencies that develop in a period of a few hours to 3 days. (Brackmann, 1981) Characteristics of acoustic neuroms (AN) with sudden HL differed from other AN presentations in several ways: (1) smaller tumor, (2) shorter duration after onset, (3) lower incidence of dizziness or other neurologic symptoms, (4) a trough-type audiogram configuration, and (5) a higher incidence of a normal caloric response on electronystagmography. A higher incidence of the subjective symptom of aural fullness was also noted. Of 14 patients with intracanalicular tumors, 5, or 36%, had a sudden hearing loss. A vascular cause or a cause from nerve compression, due to the high incidence of midfrequency loss and the low incidence of dizziness. (Ogawa, 1991). Configuration of hearing loss Classically, the patient with an VS or other CPA tumor has been described as having a highfrequency sloping SNHL. The U-shaped configuration has the greatest hearing loss at 2000 Hz. Generally, no typical shape is found for any one type of tumor; however, Kanzaki, 1991 and Dornhoffer, 1994 noted that 20% to 22% of small and intracanalicular tumors had a U-shaped audiometric configuration. The peak configuration has the best hearing thresholds at 2000 Hz, with increasing losses at the low and high frequencies (HF) Majority of losses are of the HF nature with abrupt HF losses a major proportion. Cause of the hearing loss 1) Direct VIII nerve compression explains slowly progressive hearing loss. Most vestibular schwannomas arise from one of the vestibular nerves at the junction of the proximal and distal nerves (also the junction of the Olivodendroglia and the Schwann cells). For tumors that originate in the cochlear nerve, they originate more distally. These slowly

growing lesions within the confines of the bony IAM will cause slow compression of the cochlear nerve. The hearing loss will reflect this compression of the cochlear nerve. The rate and amount of hearing loss will vary depending on the rate of growth of the tumor, the plasticity of the verve, the consistency of the tumor, the location within the IAC and the amount of early expansion into the CPA. The pure tone loss may be seen quiet late in the course of the tumor growth, because as Woellner (1955) demonstrated, if the organ of corti is intact, 75% of the auditory nerve fibers need to be destroyed before pure tone hearing is affected. This mechanism also partially explains the middle- and high- frequency losses associated with VIII nerve tumors. 2) Location of high and low frequency fibers to explain high frequency loss. Sando (1964) demonstrated anatomically that the high frequency auditory fibers from the basal turn of the cochleaare located inferiorly and laterally all the way from the spiral ganglion to the cochlear nuclei in the brainstem, whereas the middle and apical fibers twist about the axis from the spiral ganglion to the cochlear nuclei. The apical fibers actually make 1 turns about the long axis before reaching the brainstem. They are also more centrally located in the nerve. These differences in position within the nerve, allow for earlier involvement of the high-frequency basal fibers and a variable involvement of the middle- and low- frequency fibers. 3) Increased pressure in the IAC (Badie and colleagues, 2001) They measured intracanalicular pressure in 15 patients undergoing tumor resection. The pressure directly correlated with the size of the tumor within the IAC. There was a strong trend toward lower IAC pressure in patients with better pre-operative hearing, but the differences were not statistically significant. 4) Vascular compression ( Explains sudden HL) Anterior inferior cerebellar artery loops into the internal auditory meatus a variable distance, and the internal auditory artery arises from the loop of the Anterior inferior cerebellar artery, the blood supply to the cochlea should be at risk with expanding lesions of the IAC. The internal auditory artery further divides into its vestibular branches. So lesions in the internal artery should result in vertigo, or in very rapid deterioration of cochlear function, especially in the low frequency since blood supply to the cochlear apex is more tenuous (Perlman, 1955; Kimura, 1955) But the symptoms are not typically seen in vestibular schwannoma. Also, acute vascular compression should cause electrocochleographic changes identified by a decreased cochlear microphonic, which is also not seen often. The mechanism for sudden hearing loss is thought to be a vascular occlusive event. 5) Myelin and axon compression damage (Lehnhardt, 1990)

Early in the course of compression, the myelin damage might be the only lesion, allowing for tone decay and acoustic reflex decay without recruitment. Auditory brainstem evoked responses would also be delayed. This would be the typical picture of AN. Later on, as myelin and axon compression both become involved, the ABR would be delayed, still without recruitment. If the tumor compression changes, for instance, in cessation of tumor growth or recovery from intratumor hemorrhage, enough axons may remain to allow for adequate nerve conduction and remyelinization may occur. Therefore recruitment may be positive, the ABR may be positive, but tone decay may not occur. 6) Lesions of the olivocochlear system or auditory efferents Has been implicated in early hearing losses with auditory distortion, but little pure tone threshold increase. Deficits of the efferent system will affect the O Cs of the cochlea causing difficulty with speech understanding in noise and the subjective sensation of distortion while having little effect on the pure tone perception. Outer hair cell function as evaluated by OAE should be reduced or absent in ears affected by cochlear hearing losses (Telischi, 2000) Distortion product otoacoustic emissions (DPOAEs) should be normal in VS patients if the hearing thresholds are better than 45 to 50 dB HL and the loss is purely retrocochlear (neural compression), and DPOAEs should be abnormal in losses that have a cochlear (vascular or inner ear biochemical) component. Telischi(2000) reported on 97 patients with VS who underwent DPOAE testing. He found that from 37% to 57% of tumors were classified as having a cochlear loss pattern, and 41% to 59% had a retrocochlear pattern depending on the analysis method used. He concluded that the majority showed evidence of reduced outer hair cell function in at least one frequency. The effects on the OAEs did not reverse after tumor resection even when other behavioral and objective hearing measures improved, implying a nonreversible cochlear or efferent pathway damage. These findings are compatible with previous studies that have demonstrated biochemical and magnetic resonance image (MRI) changes in the ipsilateral cochlea of some VS patients. 7) Biochemical changes within the perilymph of the cochlea ( Explains cochlear HL) As early as 1950, Dix and Hallpike found changes in the characteristics of perilymph in VS patients. Somers and coworkers (2001) reported on MRI studies in AN and meningiomas, and showed increased postoperative hearing preservation in ears with normal intralabyrinthine and lateral IAC fluid characteristics versus ears with hypointense perilymph and fundus cerebrospinal fluid (CSF) images. They theorized that an arterial vascular compromise in the IAC secondary to mechanical obstruction by the tumor leads to reversible and irreversible intracochlear changes. Some MRI changes returned to normal after tumor removal, but many times OAEs do not revert to normal, again suggesting possible reversible biochemical changes but permanent hair cell injury. 8) High Tumor volume

Grabel and colleagues (1991) suggested that the chronic effect of high tumor volume within the infratentorial compartment may also play a role in VS hearing loss when they showed a strong positive correlation between maximum tumor volume and prolonged ABR interpeak latencies for waves III through V following stimulation of the nontumor side. This suggests tumor volume-generated distortion as an additional factor in tumors that extend into the CPA. 9) Traction of the VIIIth CN Sekiya and colleagues (1986) demonstrated in dogs that gentle traction on the eighth nerve in the CPA could lead to hemorrhages within the nerve and secondary auditory deficits. This mechanism may help explain the hearing loss associated with other tumors within the CPA that cause nerve distortion without significant compression. It may also help explain the tinnitus and hearing loss that may accompany neurovascular compression of the eighth nerve in the CPA. The hearing losses associated with neurotologic entities, and especially those of VS, most likely involve multiple mechanisms, any or all of which may be seen in any one lesion. The variety of mechanisms possible for the hearing loss of neurotologic lesions also helps explain the variety of hearing losses that may be seen. The cochlear nucleus is a unique brainstem structure, only its afferent input is ipsilateral, coming from the cochlea by way of the auditory nerve. Consequently, damage to the nucleus can mimic VIIIth nerve dysfunction. (Jerger & Jerger, 1974), because it may only produce ipsilateral pure tone deficits (Dublin, 1976). Tumors situated in the CPA region may affect the cochlear nucleus and produce central auditory deficits. Speech Audiometry The very poor SDS for the tumors in general supports a HL mechanism of neural compression. Thomsen and colleagues discussed the concept that discrimination at high presentation levels is primarily an inner hair cell function, and 95% of the fibers in the auditory nerve originate in the inner hair cells. Therefore, the neural compression would inhibit inner hair cell function with the resultant poor discrimination, especially at increasing presentation levels. (This can also be used to explain rollover phenomenon, which occurs at higher levels) Speech discrimination Speech discrimination scores will be reduced out of proportion to the level of the hearing loss. Reason - An anatomic correlation indicates in humans between the degree of auditory nerve fiber loss and the level of speech discrimination. Woellner (1955) found that up to 75% of the

nerve fiber loss could still leave a patient with nearly normal pure tone hearing, but that complex speech processing suffered. The roll over phenomenon defined as a decrease of greater than 20% in SDS on affected side when the stimulus intensity is progressively increased. Its sensitivity to tumors is only 65%. (McFarland, 1989). In central lesions rollover can be present on the side opposite to the lesion, and VIIIth nerve on affected side. Discrepancy between recognition of words and sentences. Rollover present Decreased ability to understand words as the intensity is increased. The degree of hearing loss and speech discrimination deficits varies widely, but historically patients have had moderate to severe pure tone losses with poor speech discrimination scores (SDS) on presentation. Acoustic Reflexes 95% - Absent stapedial reflexes. In 1952, Metz first noted the absence of acoustic reflex as a marker for RCP. Subsequently, the sensitivity of the acoustic reflex in diagnosis of acoustic neuroma has been reported to be as low as 17% and as high as 90%. (Hardy, 1989; Anderson, 1980) R Horizontal Unibox Diagonal
Intra axial brainstem disorder eccentric to one side (left)

L (Probe ear)
Intra axial and/or extra axial brainstem disorder. Intra axial and/or extra axial brainstem disorder. Right nerve disorder (left side)/severe cochlear loss (in left ear)

Inverted L-shape

Acoustic reflex decay Acoustic reflex decay, defined as decay of 50% of a tone administered at 10 dB over threshold, was originally described by Anderson in 1969 and was found to have a sensitivity of 85% in predicting the presence of an AN (McFarland, 1989). Variability in sensitivity in various reported series has ranged from 36% to 100% (Anderson, 1980; Hardy, 1989). Auditory Brainstem Response (ABR)

The 4 main parameters that can be used are 1) High rate versus low rate of stimulation (Pratt and Sohmer, 1976) 2) IT 5 3) Wave V/I amplitude 4) Inter peak latencies For high rates of stimulation in ABR, due to the presence of tumor, there occurs brainstem distress which leads to increased recovery time as compared to normals. Therefore there is a longer than normal latency difference between the high and the low rates of stimulation. Tumors within the brainstem can result in degraded waveforms, increased latencies, and absent waves generated rostral to the site of lesion (Jerger et al., 1978; Starr and Achor, 1975) Incase of large tumors abnormal recordings from contralateral side have been recorded (Nodar & Kinney, 1980) For wave V/I amplitude ratio, both the waves need to be found for a ear. Wave V is expected to be greater than wave I by a ratio of at least 1 if the ratio falls below 1 v - this is an indication of RCP. Tumors have been observed in patients when the wave V/I amplitude ratio is less than 0.5 (Starr & Hamilton, 1976) A reliable parameter in the diagnosis of CPA tumor is the interaural wave V latency differences (IT5). Using the Selters and Brackmann [1977] 0.2 ms criterion for the IT5 delay (i.e. abnormal IT5 > 0.2 ms), if one ear has normal hearing and the involved ear has hearing better than 50 dB at 4kHz. To correct for the HL at 4kHz, for each 10dB increase above 50 dB, a 0.1 msec should be subtracted from the wave V latency when comparing the results between the 2 ears (Brackmann, 1990) When the hearing threshold is greater than 50 dB at 4 kHz, the ABR is of reduced diagnostic power. There were a few cases where the IT5 measure for the lower intensity click detected a tumor missed by the IT5 measure for the higher intensity click and vice-versa. Thus, it appears that for an individual case, click level may affect the results of the IT5 measure. Smaller tumors tend to manifest IT5 abnormalities, whereas larger tumors lead to a total loss of waveforms (Jackler, 1992). Unfortunately, ABR misses a significant number of tumors, especially those of a nonacoustic origin. (1) High-frequency fibers dominate the standard click-evoked ABR latency measure, (2) Tumors will be missed if these high-frequency fibers are not sufficiently affected by the tumor (3) Small tumors do not always affect the subset of high-frequency fibers sufficiently. Stacked ABR (Don et al., 1997) The derived-band ABR technique consists of recording ABRs first to broad-band clicks presented alone then to a series of simultaneous ipsilateral presentations of the clicks and high-pass filtered pink noise with varying cutoff frequencies.

The cut-off frequency of the high-pass noise is successively lowered from one run to the next in octave steps from 8 kHz to 500 Hz. This process masks progressively lower frequency regions of the cochlea. Subtracting the response for one run from the previous one forms a derived-band response. The theoretical CFs of the five derived-band ABRs are 11.3, 5.7, 2.8, 1.4, and 0.7 kHz. It can be shown that the sum of these derived-band ABRs is essentially the same as the click alone ABR (ABR to clicks presented alone). However, much of the activity in the derived-band ABRs is not seen in the click alone ABR due to phase cancellation of activity. A - ABR responses to clicks and high-pass masking noise B - Derived band ABRs with center frequencies noted C - Aligned derived-band ABRs into above to form the Stacked ABR. D - The Stacked ABR on the tumor side is reduced by over 50% in comparison to the nontumor side.

The stacked ABR is obtained by (1) temporally aligning the derived-band ABR waveforms so that the peak latencies of wave V in each derived band coincide, (2) adding together these aligned derived-band ABR waveforms. The wave V peaks of the derived-band ABRs are aligned to the wave V peak latency for the arbitrarily selected 5.7 kHz CF derived band. By temporally aligning the peak activity initiated from each segment of the cochlea, we synchronize the total activity and remove the phase-cancelling effect that occurs in the standard response. The stacked ABR amplitude is the peak to- trough measure of wave V in the stacked ABR. Thus, compared to standard ABR amplitude measures, the amplitude of the stacked ABR wave V reflects more directly the total amount of activity initiated across the cochlea When activity initiated from any part of the cochlea is blocked or desynchronized by a tumor at the 8th nerve level, then the stacked ABR amplitude will be reduced. As demonstrated by Don et al. (1997), such reduction may not occur for the standard ABR wave V amplitude. Many small tumor cases have clinically normal hearing. One possible explanation for such cases is that the small tumor mainly desynchronizes but does not block the activity of some fibers. This would reduce their synchronous contribution to the stacked ABR but allow simple nonsynchronous activation by audiometric tones presented at normal threshold levels. This leads to the hypothesis that the amount of reduction in the stacked ABR measured from patients having both a small tumor and hearing loss should be greater than expected from the hearing loss alone. The frequency specific responses can also be evoked using tone burst ABR, where frequency specific tone bursts can be presented, and then the responses can be summed similar to stacked ABR. The Advantages of an ABR Test over an MRI Scan for Small Tumor Screening These problems of high cost, unavailability (rural areas), patient discomfort, and risks to patients with metal implants, are circumvented by using ABR tests. Interaural SABR (ISABR) amplitude difference measure To improve the sensitivity and specificity of the SABR amplitude measures ability to detect small unilateral acoustic tumors. The variability between ears of a given individual is small. Immune to variables that affect the absolute SABR amplitudes because it is a relative measure. It is better at assessing tumor patients with very large and non-tumor patients with very small absolute SABR amplitudes. In the study by Don et al. [2005], the mean reduction observed for the 54 small acoustic tumor patients relative to the 78 non tumor normal hearing subjects was

approximately 50%. That is, by the time the patient seeks medical attention for his/her symptoms, synchronous neural activity has been reduced, on average, by 50%. Even with this average amount of reduction, it is conceivable that in individuals with normally very large SABR amplitudes, a tumor may still not reduce the SABR amplitude below the criterion level. For example, if an individual who would normally have a SABR that is twice as large as the mean for NTNH subjects had a small tumor that reduced the SABR by 50%, the SABR amplitude would then be equivalent to the mean of NTNH subjects and fall within the normal criterion limits. Thus the tumor would be missed and the tests sensitivity would be compromised. If the average reduction is 50%, there will obviously be a number of cases where the reduction is less than as well as greater than 50%. Those tumors that reduce the SABR amplitude by less than 50% may be missed as well. This problem of missing tumors in individuals with normally very large SABRs or reductions of less than 50% can be minimized if it can be shown that the SABR is typically very similar between ears such that an interaural comparison can be used, much like the standard IT5 latency measure developed by Selters and Brackmann (1977). Likewise, specificity could be improved for individuals who would normally have low SABR amplitudes or amplitudes that are low due to either hearing loss or age (Don et al., 2005). In these individuals, with the exception of bilateral tumor cases, equal but below criterion SABR amplitudes in both ears would be suggestive of a non-tumor subject. However, when feasible and valid, the interaural measure may be helpful because it uses the individual patient as his/her own control rather than absolute values of the SABR amplitude generated by a specific population. Hearing loss (HL) reduces synchronous neural output and thus, the SABR amplitude. If there is HL in a tumor ear, the sensitivity of the SABR measure improves because both the tumor and the HL reduce the SABR amplitude. But if there is a significantly greater HL in the nontumor ear of a tumor patient, the reduction in the SABR amplitude due to the tumor may be matched by the reduction due to the hearing loss in the non-tumor ear. As a result, not only will the specificity of the SABR measure be adversely affected due to the significantly reduced SABR amplitude in the non-tumor ear, but the interaural amplitude difference will be reduced and the sensitivity of the ISABR measure will be compromised. A method of compensating for the HL would be valuable in these cases. Each dB difference in the interaural clinical PTA reduced the SABR amplitude by an additional 1.35%. It can be used as a general guideline in compensating for the effect of HL in small tumor cases. Clinically, the IT5, SABR, and ISABR measures can be used together to maximize efficient detection of small unilateral acoustic tumors.

Electronystagmography Lesions involving the vestibular end-organs and the vestibular nerve are classified as "peripheral". Lesions beginning at the vestibular nuclei and proceeding centrally through the brain stem and cortex are classified as "central". For example, an internal auditory canal (IAC) acoustic neuroma would be considered "peripheral" for vestibular test purposes, although it would not be considered peripheral for audiologic purposes. Acoustic neuroma primarily affects the vestibular nerve whereas Mnire's disease has its primary effect in the vestibular end-organs. A cerebellopontine angle tumor would be an example of a "central" vestibular lesion if its primary impact and presence involved the vestibular pathways in the brain stem or cerebellum. More commonly, acoustic neuromas tend to create both peripheral (caloric weakness) and central (gaze nystagmus, poor pursuit, or saccadic dysmetria) vestibular test abnormalities depending primarily on the site and size of the lesion. The central vestibular system and its cerebellar connections may be affected by a metastatic tumors - hemangioblastomas (Tognetti,1986), hemangiomas (Eller,1976), and germ cell line tumors,. The same tumors that affect the peripheral vestibular nerve in the cerebellopontine angle may also compress the brainstem, resulting in central vestibular pathology. In addition, primary intra-axial tumors, such as gliomas, ependymomas, and medulloblastomas (Watson,1981) in young patients may produce central vestibular dysfunction. Two relatively pure isolated forms of central nystagmus are downbeat and upbeat nystagmus. In the case of downbeat nystagmus pathology usually interrupts the fibers crossing in the dorsal tegmentum of the medulla. This relatively selective involvement of information coming from the posterior canals leads to a slow phase drift of the eyes up and a secondary correctional movement with a fast phase down. Clinically, downbeat nystagmus is usually seen with cerebellar degeneration or pathology at the cervical medullary junction. Gaze (fixation) test

Rotary gaze nystagmus usually is consistent with a brain stem lesion, often involving the vestibular nuclei (Cogan, 1977). It is observed in such disease processes as large, spaceoccupying lesions that distort the floor of the fourth ventricle wherein the vestibular nuclei are housed. Rotary gaze nystagmus has been reported in cerebellar disease as well (Zee, 1987). It should be noted that in very early stages of an acute, unilateral peripheral vestibular lesion, a rotary component to the predominantly horizontal nystagmus may be present. This should be considered whenever a patient is in an acute stage of vertigo secondary to a unilateral peripheral vestibular lesion where a strong spontaneous nystagmus is present. Direction-fixed, horizontal - Peripheral vestibular (end-organ or nerve); weakened ear usually is away from fastcomponent of nystagmus (that is, right-beating nystagmus suggests left ear weakness; left beating suggests right ear weakness); nystagmus enhanced with eye closure

Direction-changing, horizontal - Brain stem; cerebellar lesions Vertical - Upbeating gaze nystagmus suggests lesion in brain stem or cerebellum; downbeating gaze nystagmus suggests lesion in cerebellum or cervicomedullary junction Rotary - Brain stem (vestibular nuclei); also seen in cerebellar disease Periodic alternating - Cerebellum, brain stem, or cervicomedullary junction Saccade test

Saccadic abnormality is seen as small catch-up eye movements in both directions in order for the eyes to reach the target. This is referred to as hypometric saccadic eye movement and is seen in brain stem/cerebellar disease. Ipsilateral dysmetria - Cerebellopontine angle lesions on same side as dysmetria Bilateral dysmetria - Cerebellum or brain stem lesions Ocular pursuit test (sensitive test for CNS dysfunction within the ENG battery)

When a patient's visual pursuit system is impaired, rapid corrective eye movements replace the smooth pursuit movement so the eye can "catch up" with the moving target. When the cath-up movements form a "stair-step" pattern consisting of small saccadic movements, the defect is referred to as saccadic pursuit. Saccadic pursuit is seen frequently in patients with cerebellar disease. Visual pursuit abnormalities are usually caused by lesions in the brain stem, cerebellum, or cerebral cortex. However, acute peripheral vestibular lesions that cause a spontaneous nystagmus also may affect the smooth pursuit test unilaterally and must be considered. In this situation a unilateral pursuit tracing abnormality may be secondary to a peripheral lesion when there is no actual deficit within the pursuit per se. Optokinetic test

The purpose of the optokinetic test (OKN) system is to maintain visual fixation when the head is in motion. Isolated OKN abnormalities are thought to reflect cerebral cortex disease, and when they appear in conjunction with a direction-changing gaze nystagmus, they are thought to represent brain stem or cerebellar dysfunction (Coats, 1975). When the lesion is in the BS, an abnormal OKN response is more commonly asymmetric not because of dysfunction within the OKN system, but because of the presence of the gaze nystagmus. Static positional test

The purpose of static positional testing is to determine if changes in head position create nystagmus or modify already existing nystagmus. When a spontaneous nystagmus is present, the direction of the fast phase and the intensity of the slow phase should be noted. This allows the clinician to monitor changes over time. Nystagmus that beats toward the undermost ear is called geotropic, and nystagmus that beats toward the uppermost ear is referred to as ageotropic. It has been suggested that ageotropic nystagmus is seen more commonly in central vestibular disease, and geotropic is seen more commonly in peripheral vestibular disease. But, both types are caused by peripheral vestibular disease more often than central disease. Caloric test (most specific test within the ENG battery)

Used to induce endolymph flow in the semicircular canals (primarily the horizontal canal) by creating a temperature gradient from the lateral to the medial part of the canal. Failure of fixation suppression (FFS) - Cerebellum; ensure that patient has sufficient visual acuity to allow fixation on target. Unilateral or bilateral weakness. Almost always peripheral vestibular disease

ENG tests the function of the horizontal SCC, which is innervated by the superior vestibular nerve, a normal test suggests that the tumor if present, may be originating from the inferior vestibular nerve. In 1990, Welling et al found an ENG sensitivity of 70% in their series of patients with AN, and concluded that the ENG was not cost effective. Small acoustic neuromas manifest ipsilateral reduced vestibular responses and spontaneous nystagmus opposite to the side of the tumor. Large tumors frequently manifest additional finding such as failure of fixation suppression, bilateral slowing of optokinetic nystagmus, saccadic pursuit and occational bilateral horizontal gaze nystagmus. It is also frequent for large tumors to not manifest any ENG abnormalities. (Nedzelski, 1983) Otoacoustic emissions The diagnostic value is limited. From a review of several reports Robinette and Durrant (1997) found that only 20% of 316 patients with surgically confirmed CN VIII tumors had mild or greater hearing loss with EOAE present to support the diagnosis of RCP. This lack of diagnostic precision can be attributed to cochlear hearing losses that frequently accompany CN VIII tumors. The cochlear loss is thought to be due to the restriction of blood supply to the cochlea related to the tumor growth. (Levine et al, 1984) + (Point 6 causes of hearing loss) Cochlear Origin of Early Hearing Loss in VS (Victor, Mann (2009))

A group of 19 VS patients with normal/symmetrical hearing and a group of 20 VS patients with mild HL (threshold at any tested frequency better than 45 dB HL) on the tumor ear side. DPOAE amplitude between the tumor & nontumor ear were studied at frequencies of 1, 1.4, 2, 2.8, and 4 kHz. Tumor size did not differ significantly between the two groups. Results: DPOAE amplitudes do not differ strongly between the ears in VS patients with normal/symmetrical hearing but are decreased compared with the nontumor ear at frequencies 1, 1.4, 2, and 2.8 kHz in VS. Conclusion: Amplitudes of DPOAEs begin to decrease even at the early stages of HL in VS patients, which suggest a cochlear origin of early HL in these patients. DPOAEs may be used in a clinical setting to monitor progression of cochlear damage at the early stages of HL in VS patients.

Telischi, 1995 Studied effect of acoustic neuromas ( N) on the amplitudes of evoked OAEs and to compare these findings with tumor-induced hearing levels. Tests of behavioral audiometry, DPOAE & TEOAE were performed on 44 patients with AN. Results - Majority of ears with AN displayed one of two patterns: a cochlear pattern (OAE amplitude decreased or absent O Es) or a noncochlear pattern (where O Es were present) Although behavioral hearing thresholds were higher with larger tumors, OAE levels exhibited no clear relationship to tumor size. The findings support the notion that ANs may cause HL according to two types of influence that act at different levels of the peripheral auditory system. The tumor's cochlear effect on evoked OAE activity is most likely caused by an indirectly mediated compromise of the organ of Corti's vascular supply. It is probable that the direct pressure of the tumor on the eighth cranial nerve is responsible for the observed noncochlear effects. Using DPOAEs and TEOAEs, Telischi et. al. (1995) found that HL involved the cochlea in 71 % and neural elements in 41% of the 44 patients with AN. When DPO Es and PT s were compared in 97 patients with N Telischi (2 ) assigned 55 (57%) to the cochlear damage group, 40 (41%) to the noncochlear damage group, and 2 (2%) to an intermediate group. Colleaux, 1998 (Prognosis)

TEOAEs in ears with AN are found in younger patients with a lower preoperative mean PTA loss and are accompanied by fewer functional complaints.

TEOAEs (when present) indicate a better preservation of inner ear vasculature. TEOAE presence in the pathological ear could provide an additional criterion or predictive factor for the successful outcome of attempted hearing-conservation surgery in ears with ANs. Contralateral suppression of OAE Maurer et al (1995) recorded TEOAE in 6 of 20 patients with unilateral VS. The amplitudes of these emissions were significantly smaller than those in a normal control group. The application of contralateral white noise (40, 50, 60 dB HL) did not suppress the amplitude of the TEOAE in the tumor ears, but in the ear without tumor greater suppression effects were noted than in the control group. Maurer tentatively suggested that the VS had reduced efferent function on the affected side, and that some counterintuitive effect was present contralaterally. This study contained the suggestion that a VS compressing the vestibular divisions of the VIIIth nerve, specifically the inferior, affects the efficacy of the efferent function on that side. It should be noted however that this effect was demonstrable in only a minority of patients. Ryan et al. (1991) did a study in which they found intact OAEs in the affected ear, but no suppression effect, suggesting blockage of efferent conduction on the side of the tumor. Contralateral Suppression of TEOAE in Patients with CPA Tumor (Ferguson et al. (2001)) Aim: Investigate the effect of CPA tumor on the medial efferent nerve pathways to both tumor and non-tumor ears by examining alterations in TEOAE amplitude that result from contralateral acoustic stimulation. Design: Contralateral suppression of TEOAEs using broadband noise was measured preoperatively in 17 patients with unilateral CPA tumor and 17 normally hearing controls, matched for age and gender. Results: Control ears sig. more suppression than the tumor and non-tumor ears in the patient group. There was, however, no significant difference in suppression between the tumor and nontumor ears, and the statistical correlation for suppression between them was high. Effect of age on suppression in both the control and patient groups where suppression reduced as age increased. Four of the 17 patients had TEOAEs, which were clearly present in the tumor ear despite substantial hearing loss, three of which had no measurable hearing.

Conclusions: Neural compression by CPA tumor disrupts the medial efferent nerve control mechanism to the OHCs of tumor ears. Also reduces transmission of afferent nerve impulses from the tumor ear, which cross over to the medial olivo-cochlear complex and reduce the inhibitory control of OHC function in the non-tumor cochlea. These findings show that for a majority of the patients, there is a cochlear involvement, although the tumor occurs on the nerve. Vestibular Evoked Myogenic Potential Click-evoked myogenic potentials can be recorded with surface electrodes over each sternocleidomastoid muscle. Latencies and amplitudes of responses will be measured. VEMPs were absent or decreased in 77% with acoustic neuroma (n=48). Thirty-nine of the 62 patients showed absence of responses on the affected side, 9 showed decreased responses, and 14 showed normal responses. In other words, 48 patients (77%) showed abnormal amplitudes. All patients with AN who showed latency prolongation had large tumors that compressed the brainstem. These results suggest that brainstem lesions, especially those in the vestibulospinal tract, are required for the prolongation of p13. From the practical viewpoint, p13 showed prolongation of the latency more frequently than n23. The SD of n23 was greater than that of p13, resulting in a wider normal range of n23 than p13. Therefore, p13 is a better parameter for evaluation of the latency of VEMP. VEMP testing could still be a useful neurophysiological test for diagnosing acoustic neuroma because VEMP testing and caloric testing could classify ANs according to the involved nerves: the inferior vestibular nerve or the superior vestibular nerve.

Tests used previously

Because up to 20% of the acoustic neuroma patients manifest a cochlear type HL rather than retrocochlear HL (Flood, 1984), the accurate diagnosis of RCP is of limited clinical value. Tone decay test (TDT) Anderson(1980) found a sensitivity of 46% and Hardy (1989) found a sensitivity of 45% to the detection of acoustic neuroma. Suprathreshold Adaptation Test (STAT) Sensitivity is in the range of 45% towards acoustic neuroma (McFarland, 1989). Mechanism through which tumors cause symptoms Tinnitus Mechanism for tinnitus is thought to be the same as that of hearing loss, neural or vascular compression. Because tinnitus, like hearing loss can be considered to be a manifestation of a dysfunctional auditory nerve, the two may occur concurrently. (Edwards, 1951). Unilateral tinnitus in the absence of hearing loss warrants investigation, because few patients with VS present with tinnitus in the absence of hearing loss. Ephaptic Coupling It has been suggested that as a VS grows and takes up space within the internal auditory canal it compresses auditory nerve fibers causing them to cross talk by ephaptic coupling. (Moller, 1984) Sunderland (1991) noted that the formation of such artificial synapses was characteristic of any injury that leads to failure of the insulating properties of the nerve sheath, whether it is nerve section, crushing by ligature, or even moderate compression, introduces an artificial synapse created where denuded axons are in contact. This phenomenon would mean that the random firing of one or more nerve fibers would generate a pattern across many fibers of the auditory nerve, this being perceived as a tinnitus sound. Cochlear Dysfunction The finding that a proportion of patients with VS have an associated cochlear hearing loss may suggest cochlear involvement in tinnitus generation. Moffat et al (1989) noted audiological findings that were indicative of a cochlear or mixed cochlear/retrocochlear lesion in 36 of a series of 49 patients with sporadic unilateral VS (73%). Prasher et al (1995) reported absent transient evoked otoacoustic emissions (TEOAE) in 19 of 26 patients with VS (73%) in all patients in whom TEOAE was absent, a hearing loss of 40 dB HL (hearing loss) or greater was present, and this was assumed to be cochlear in origin. There has been little specific consideration in the literature of the pathophysiological mechanisms of cochlear hearing loss in VS.

Schucknecht (1993) proposed the mechanisms of ischemia causing atrophy of the cochlea and the vestibular labyrinth by compromising blood flow in the internal labyrinthine artery which runs through the internal auditory canal (IAC) and/or biochemical degradation of the cochlea and the vestibular labyrinth. Evidence for ischemic and biochemical vestibular labyrinth injury in VS has been reported by Jahnke and Neuman (1992) who studied specimens taken from nine patients during translabyrinthine surgery. Examination with electronmicroscopy demonstrated significant degenerative changes that were thought to be the result of prolonged protein intoxication of the labyrinth (via increased perilymph protein concentrations) and by compression of labyrinthine blood vessels by the tumor. Similar mechanisms were suggested for cochlear dysfunction in such cases. O'Connor and colleagues (1981) had earlier identified high protein levels in the perilymph of patients with VS, though not in a patient group with meningioma in the IAC, and suggested that this may be a mechanism specific to VS. Efferent System Dysfunction An alternative hypothesis considers the presence of medial and lateral efferent fibers within the inferior division of the vestibular nerve. Sahley (1997) A VS arising from or impinging upon the inferior vestibular nerve might be expected to reduce the effectiveness of efferent influence upon the cochlea, and thus perhaps cause signals in the afferent peripheral auditory pathway to be perceived as more intense than would otherwise be the case. Thus a tinnitus signal might appear more intense as a result of the lesion in the internal auditory meatus. Baguley et al (2002) reviewed the effect upon tinnitus of vestibular nerve section, which involves section of the auditory medial efferent fibers which run in the inferior vestibular nerve. While this procedure is almost exclusively applied to patients with Meniere's disease that has proved refractory to medical treatment, it does represent an opportunity to determine if ablation of the medial efferent system influences tinnitus. Reviewing 18 papers reporting surgical series involving a total of 1318 patients, the authors reported that there was no evidence of a consistent exacerbation of tinnitus following vestibular nerve section, causing them to question the influence of the efferent system upon tinnitus. Cortical Reorganization There is a good evidence of plastic change in the central auditory system following change in peripheral function in both animals and humans. Further, there is a hypothesis that a consequence of such change may be overrepresentation of certain auditory frequencies Moore (2003) and of spontaneous bursting at boundary areas in the primary auditory cortex; there is a growing body of evidence that these may be mechanisms of tinnitus. Given that a VS is associated with a hearing loss in the majority of cases, and that this is due to change in cochlear and/or cochlear nerve function, some cortical plastic change should be expected as a consequence. In this event any associated tinnitus should be similar in generation to tinnitus in general that is associated with hearing loss. It would also follow that

if the peripheral status were to change further, such as with destructive (translabyrinthine) surgery, then the tinnitus would change as a consequence. Vertigo Occurs due to loss of peripheral vestibular input via the vestibular nerve. The distorted, diminished or absent vestibular information from the side of the tumor is gradually compensated for by the central vestibular nuclei. Acute vestibular dysfunction can occur as a result of early intracanalicular compression of functioning vestibular nerve by the tumor, and adequate contralateral compensation strategies have not yet developed. Disequilibrium The cerebellum is responsible for integration of sensory information, including visual, proprioceptive, tactile, and vestibular input. Disequilibrium occurs when insufficient or conflicting orientation information is obtained or when normal peripheral inputs are not well integrated centrally. Large VSs cause cerebellar or Bs compression and adversely affects the ability of the central vestibular system to compensate for vestibular nerve dysfunction and may eventually lead to a decompensation of the previously adapted deficit. Cerebellar dysfunction Incoordination, ataxia - Symptoms The cerebellum is functionally divided into lateral and midline structures. The midline is composed of flocculus and nodulus, both of which receive vestibular nerve input. The flocculus, which is frequently compressed by the VS is thought to play a large role in coordination of the vestibule-ocular reflex. Cerebellar dysfunction is usually caused by gradual lateral compression, so midline structures are rarely involvedwith slow growing VSs. Trigeminal nerve dysfunction Occurs secondary to compression of the nerve high in the CPA between the superior aspect of the tumor and the tentorium. Trigeminal neuralgia may be caused by a vascular loop compressing the Vth nerve at its root entry zone. And this may also occur due to extrinsic tumor compression on the loop and trigeminal nerve. Large tumors are capable of displacing the BS to the contralateral side, which in turn may lead to compression of the opposite trigeminal nerve and subsequent dysfunction. Headaches Cephalgia may be caused due to compression and localized irritation of the neural, vascular or dural contents of the IAC or petrous face. This is a local phenomenon distinct from hydrocephalus, and may be mediated by direct dural innervations by the branches of the trigeminal nerve.

Increased intracranial pressure Raised ICP occurs as a result of obstruction of the forth ventricle by the compressive effects of the tumor transmitted through the cerebellum and the brain stem. Diplopia associated with increased ICP is thought not to occur by the direct compression by the tumor but rather by stretching of the abducens nerve. Facial nerve dysfunction Compression begins within the bony confines of the IAC. When the tumor gets larger the nerve gets thinned and ribbon like as the anterior surface of the cisternal portion of the tumor compresses the nerve against the porus acousticus, thereby stretching it at its root entry zone. The nerve is highly resistant to compression and stretch, as noted by the low frequency of facial nerve clinical dysfunction as compared to the VIII nerve. Findings in the 2 most common lesions Meningiomas and Epidermoids Meningiomas A meningioma is one of the most common primary brain tumors. Arises from cells of the arachnoid membrane. Therefore, these tumors actually arise outside the brain itself, but because of their close proximity to nervous system structures, they are often touching or pushing into parts of the brain or spinal cord Most meningiomas are benign and very slow growing, rarely malignant. Most meningiomas are named for their site of origin. Example - skull base, cerebellopontine, foramen magnum to name a few, all referring to various anatomical locations around the central nervous system. When small, most meningioma are asymptomatic. Depending on their location, as they enlarge, they can start to invade or cause compression of neurological structures. Can be suspected when a patient presents with a large tumor and relatively normal hearing. They do not deform the bony auditory canal. Audiological Findings

Meningioma, in this diagram, extends along the internal auditory canal, causing total destruction of all nerves.

Clinically, an intracranial meningioma may remain silent until it penetrates the temporal bone, most commonly causing progressive hearing loss, vertigo, tinnitus, otalgia etc. Recurrent otitis media with otorrhea and the development of granulation tissue may be seen. The incidence of tinnitus and hearing loss is somewhat lower than in VS patients, with only 60% to 75% of patients showing an auditory symptoms at the time of diagnosis, compared with 95% or more of patients with VS. The patients with meningioma also showed a higher percentage with hearing loss less than 20 dB and discrimination greater than 80% than did VS patients; otherwise, the configuration of the loss and appearance audiometrically is identical with that for patients with AN. Marangos (2001) demonstrated a higher incidence of normal hearing, binaural symmetry, and normal ABR in patients with meningiomas than those with acoustic neuroma. PTA findings Laird (1985) identified 8 of 15 patients with meningioma, or 53%, as having a PTA of 0 to 20 dB. Granick (1995) identified 6, or 26%, of their group with a PTA of 0 to 20 dB. Both these studies considered posterior fossa meningiomas. Hearing loss or tinnitus was found in 60% of meningioma patients by Laird (1985) and in 75% by Granick (1995). Epidermoid cyst Linthicum(1974) reported involvement of the 7th cranial nerve as the most common sign and first lesion to occur followed by an unilateral hearing loss. Unilateral HL has also been reported as the first presenting sign. Mechanism - It tends to "strangle" the 7th nerve and reduce its blood supply, therefore it is the first presenting sign. An acoustic neuroma in contrast may stretch the nerve but impulses can still be conducted.

Trigeminal neuralgia- Cause may be either local irritation from cholesterol seeping through the cyst wall or compression from a vascular loop against the nerve root entry zone. Audiological tests confirm the presence of a retrocochlear lesion and determines the function of the 7th and 8th cranial nerves. Auditory brainstem responses have been found to be useful in differentiating various lesions of the cerebellopontine angle. Secondary tumors Glomus tumors Glasscock et al. clarified the definitions of glomus tympanicum tumors as those in the tympanic cavity and the mastoid, and glomus jugulare tumors as those involving the jugular bulb and the base of the skull. Glomus jugulare tumors originate from the chief cells of the paraganglia, or glomus bodies, located within the wall (adventitia) of the jugular bulb, and can be associated with either the auricular branch of the vagus nerve (Arnold nerve) or the tympanic branch of the glossopharyngeal nerve (Jacobson nerve). Paraganglia are small (< 1.5 mm) masses of tissue composed of clusters of epithelioid (chief) cells within a network of capillary and precapillary caliber vessels. Neural infiltration by paragangliomas following a sequence of the tumor approaching the nerve, contacting the epineurium, invading the perineurium along the perivascular spaces of the neural capillary supply, and penetrating the endoneurium.

The protympanic and hypotympanic of paraganglioma. (From Spector GJ, et al; Glomus jugulare tumors of the temporal bone.

Intracranial extension, according to Spector and colleagues (1979) is most likely to occur within two dangerous triangles: the hypotympanic and the protympanic. These slow-growing tumors that extend along anatomic planes of least resistance (along blood vessels and mastoid air-cell tracts and through cranial nerve foraminae). The hypotympanic triangle is delimited by the inferior petrosal sinus, the sigmoid sinus, and the internal jugular vein. Extension from the hypotympanic triangle may occur intraluminally

in the great veins of the triangle, extraluminally along the carotid sheath into the neck, or along the cranial nerves at the base of the skull. The protympanic triangle is determined by the Eustachian tube opening, the tensor tympani tendon, and the zygomatic root cells. Further growth may then progress along the lumen of the eustachian tube to the nasopharynx, within air cell tracts to the petrous apex, or along the IAC into the middle cranial fossa. In glomus jugulare tumors, the hearing loss can be either sensorineural or conductive. As described by Alford and Guilford (1962) and Brammer (1984) more than 90% of patients with glomus tumors present with hearing loss. In lfords series 2 patients were examined; 13 had infralabyrinthine tumors and 12 had glomus tympanicum tumors. All the patients in this series with SNHL had infralabyrinthine tumors. Only one of the patients with infralabyrinthine tumors had normal hearing, but the ABR was positive in this case. Hearing loss occurs in 90% of patients with glomus tympanicum tumors and in 70% of patients with glomus jugulare tumors, but only rarely in patients with glomus vagale tumors. The hearing loss is more often conductive than sensorineural. Pulsatile tinnitus, an audible bruit, or spontaneous aural bleeding can be seen in 60% to 70% of patients with tympanicumor jugulare tumors and in 30% of those with vagale paragangliomas (Briut is the term for the unusual sound that blood makes when it rushes past an obstruction turbulent flow in an artery). Mechanism - HL and VII CN deficit Paragangliomas can grow laterally, producing otologic symptoms (conductive hearing loss, pulsatile tinnitus, or a retrotympanic mass), and medially, resulting in the jugular foramen (or Vernets syndrome), consisting of glossopharyngeal, vagus, and spinal accessory deficits. Involvement of the facial nerve occurs in approximately 20% of patients with tympanicum or jugulare tumors. The vertical mastoid segment is the usual site of compression, although compression in the soft tissue of the stylomastoid foramen may also be the cause. Metastatic tumors

Metastatic tumors most commonly gain access to the temporal bone by hematogenous spread. (Schuknecht, 1968). Breast, lung, kidney, prostate, and stomach carcinoma, in descending order of frequency, have been reported as metastasizing to the temporal bone. Deposition of tumor cells occurs predominantly in the petrous marrow; the sluggish flow in the sinusoidal capillaries promotes filtering of the tumor cells from the circulation. (Schuknecht, 1968) Involvement of the petrous apex can be found nearly uniformly (Nelson, 1991). Metastatic deposition within the air cell spaces of the temporal bone is also quite common and leads to tympanic cavity and facial nerve involvement. Invasion of the otic capsule is uncommon, reflecting its resistance to neoplastic invasion. (Berlinger, 1980) Lymphomas and leukemias infiltrate the petrous apex almost without exception, subsequently following the submucosal plane of the mastoid air cells, the ossicles, the middle ear muscles and tendons, the eustachian tube, the IAC, and the subcutaneous tissues of the external auditory canal. (Berlinger, 1980) Regional, extracranial neoplasms, most commonly pharyngeal carcinoma, extend directly into the temporal bone by preformed pathways such as the eustachian tube, the carotid canal, the foramen lacerum, the foramen ovale, and the jugular foramen (Nelson, 1991). Similarly, malignant intracranial tumors may secondarily involve the temporal bone by routes described in the discussion of meningiomas, paragangliomas, and vestibular schwannomas. Leptomeningeal extension, in which the malignant tumor cells diffusely proliferate in a lamellar manner along the pia-arachnoid of the brain and spinal cord, may develop both with distant primary neoplasms and primary intracranial tumors, especially medulloblastomas. Bilateral IAC invasion with disruption of the facial and cochleovestibular nerves is characteristic and may lead to transgression of the cribrose areas and membranous labyrinth. (Berlinger, 1980) Example : Leptomeningial metastasis While 30% of the cases with unilateral metastases are asymptomatic, in the remainder the common symptoms were facial nerve paralysis, HL and tinnitus, all of progressive onset, although 32% of the patients experienced a sudden onset of these symptoms accompanied by vertigo and disequilibrium. Suzuki et al. (1997) discussed four patients with gastric carcinoma all of whom presented with sudden bilateral hearing loss. Diffuse leptomeningeal carcinoma was detected in two of the cases and inner ear hemorrhage in the other two. Although the mechanism of sudden hearing loss due to inner ear hemorrhage is not clearly understood, it may be due to biochemical changes in inner ear fluids (Suzuki, 1997). Many of the audiological and vestibular symptoms found with leukemia are probably referable to changes in the biochemistry of these sensitive structures.

This may stem from altered blood vessel permeability secondary to deficient platelets and alterations in the selective ion concentrations between the endolymph and the perilymph (Adams, 1980). Maddox (1976) emphasized the triad of symptoms of otalgia, periauricular swelling, and facial nerve paresis as being highly suspect for malignant involvement of the temporal bone, otorrhea may be absent and the tympanic membrane appears normal. Thus, pain and CN VII paralysis in a chronically draining ear must immediately arouse a suspicion of malignant disease (Adams, 1971). Other tumors Schuknecht and associates (1968) emphasized hearing loss as a common early manifestation of hematogenous or directly extending metastatic tumors of the temporal bone, with conductive hearing loss reflecting eustachian tube dysfunction and secondary serous otitis media; less frequently, ossicular destruction, mucosal invasion, and tympanic membrane infiltration precipitated the conductive hearing loss. SNHL is a manifestation of cochlear nerve compression or destruction, or cochlear invasion along the IAC. Rapidly progressive uni- or bilateral SNHL, especially if associated with uni- or bilateral facial paresis, vertigo, and widespread neurologic signs, is suggestive of leptomeningeal temporal bone involvement. Chloromas are localized, green masses of leukemic cells, associated particularly with acute myeloblastic leukemia. Shanbrom and Finch (1958) have cited data indicating that of those patients with chloromas, approximately half will have temporal bone involvement. Leukemic infiltrations in general may precipitate recurrent otitis and acute symptomatology related to hemorrhage. Chloromas have been associated with compressive effects on the facial and cochleovestibular nerves, tympanomastoiditis, otalgia, hearing loss, and vertigo.

Summary diagram of the effect of an astrocytoma (glioblastoma) of the pons on the facial, cochlear, and vestibular nerves.

Lipomas (Kitamura, 1990) are rare but are also associated with hearing loss in at least two thirds of the cases. Cranial nerve Schwannomas

1) Trigeminal Nerve Schwannomas ( Can be either Ganglionic / Trigeminal root) Trigeminal schwannomas of the ganglionic segment result in facial numbness or pain and corneal hypesthesia in 80% to 90% of patients, which are the initial complaints in about 60% of these patients. Few patients (10% to 20%), however, never develop trigeminal dysfunction. Tumors of the ganglionic segment are more frequently associated with facial pain (52%) than those of the trigeminal root (28%) (Mc Cormick et al., 1988). Diplopia is present in 50% by the time of diagnosis and is usually due to an abducens palsy. Facial weakness and hearing loss are rare symptoms of this lesion. Tumors of the trigeminal root account for 20% to 30% of trigeminal schwannomas and are usually confined to the posterior fossa (Jeffersons type B tumors). The clinical presentation is usually a combination of hearing loss, tinnitus, and facial nerve and cerebellar dysfunction. 6% of patients with trigeminal schwannomas initially complain of hearing loss. 2) Facial Nerve Schwannomas Slowly progressive facial weakness is the typical clinical presentation of a facial nerve schwannoma. Facial spasms may also be observed. Patients with schwannomas of the facial nerve in the CPA are known to present with hearing loss that can be conductive, sensorineural, or mixed (Lee,1989). Hearing loss of a conductive, sensorineural, or mixed nature occurs in approximately 50% of patients. Facial schwannomas located in the middle ear may cause conductive hearing loss, whereas tumors in the labyrinth and internal auditory channel usually result in cochlear or retrocochlear hearing dysfunction, respectively. Tinnitus and vertigo, or dizziness, occur in 13% and 10%, respectively. External manifestations of the tumor such as a mass, pain, or otorrhea occur in 30% or more of patients (Lipkin et al., 1987). These tumors are rare, accounting for only 1.5% of cerebellopontine angle tumors (Baker and Ojemann, 1993). May involve the tympanic or vertical segments in most patients (58% and 48%, respectively) and multiple segments are almost always affected. 3) Jugular Foramen Schwannomas Schwannomas of the caudal cranial nerves are rare. Jugular schwannomas, which include schwannomas from the glossopharyngeal, vagus, and spinal accessory nerves are not distinguishable from one another. They have been classified into 3 types according to their location: (1) Type A tumors grow predominantly intracranially, (2) Type B tumors grow predominantly at the jugular foramen, and (3) Type C tumors grow predominantly extracranially.

Type A tumors tend to cause acoustic or cerebellar symptoms, and type B and C tumors tend to be associated with the jugular foramen syndrome. Labyrinthine Neoplasms Labyrinthine Schwannoma Other tumors Malignant neoplasms like Squamous cell carcinoma, Adenoid cystic carcinoma in adult or rhabdomyosarcoma of the temporal bone in the child may extend to the labyrinth. Metastasis may extend perineurally along the cochlear nerve and penetrate the cochlea. Endolymphatic sac tumors are rare, low-grade malignant neoplasms of the temporal bone, which may be hemorrhagic and invade the vestibule and cochlea. Labyrinthine Schwannoma Most common benign neoplasm of the labyrinth. Histologically identical to those found in the IAC. They can be found either in the cochlea or in the vestibule. In patients with neurofibromatosis they are more frequent in the vestibular system. (Babin & Harker, 1980 ) Isolated intralabyrinthine schwannomas are more common in the cochlea. Branches of these nerves reach the ampullae of the semicircular canals and large schwannomas will eventually grow into the ampullae. Presenting symptoms- SNHL , Vertigo (or both) Can be stable or progressively worsening. [Clinically indistinguishable from Menieres disease] In the past these lesions were diagnosed during destructive labyrinthectomy for intractable Menieres disease. The following are case studies and audiological findings mentioned according to the levels of the auditory nervous system. 1) Cochlear 2) Intracanalicular 3) Vascular 4) Cerebellar 5) Cranial posterior fossa 6) Petrous Apex

1.

2. 3. 4.

References Desouza C. E., Desouza, R., Sperling, N., Tae yoon,H. , Abdelhamid,M. M., Sharma, R. R, Goel, A. (1989) Cerebellopontine angle epidermoid cysts: a report on 30 cases; Journal of Neurology, Neurosurgery, and Psychiatry;52: 986-990 Sataloff and Sataloff; Hearing loss, 4th edition Cadoni,G., Agostino, S., Volante, M., and Scipione M.S.(2006) Acta Otorhinolaryngol Ital.; 26(2): 115117. Amano, T et al. (2009) Cerebellar hemangioblastoma manifesting as hearing disturbance. Neurol Med Chir (Tokyo); 49(9):418-20.

5. Bush, M. (2010) Hemangioblastoma of the Cerebellopontine Angle. Arch Otolaryngol Head Neck Surg. 2010;136(7):734-738 6. Baguley DM, Humphriss RL, Axon PR, Moffat DA (2006) The clinical characteristics of tinnitus in patients with vestibular schwannoma Skull base;16(2):49-58 7. Steward, O., (1989). Principles of Cellular, Molecular, and Developmental Neuroscience. Berlin: Springer-Verlag 8. Joseph JT. (2006) Diagnostic Neuropathology Smears. 9. Valente, M., Hosford-Dunn, H., & Roeser, R. Eds. (2000). Audiology: Treatment. New York: Thieme. 10. Don M, Kwong B, Tanaka C, Brackmann D, Nelson R: The Stacked ABR: A sensitive and specific screening tool for detecting small acoustic tumors. Audiol Neurotol 2005; 10: 274290. 11. Don, M., Kwong, B., Tanaka C., Interaural Stacked Auditory Brainstem Response Measures for Detecting Small Unilateral Acoustic Tumors; Audiol Neurotol;17:5468 12. Brackmann,D., and Moises A. Chapter 188: Differential Diagnosis of Neoplasms of the Posterior Fossa 13. Kim, C.H., Yun Suk An, and Joong Ho Ahn (2009); Petrous Apex Cholesterol Granuloma Presenting as Endolymphatic Hydrops: A Case Report; Clin Exp Otorhinolaryngol; 2(3): 151154. 14. ER Maher et al (2011); von HippelLindau disease: A clinical and scientific review; European Journal of Human Genetics, 17 15. Takami, T, Terakawa, Y. (2011) Medulloblastoma Manifesting as Sudden Sensorineural Hearing Loss; J Korean Neurosurg Soc 50 : 51-53. 16. Karadeli, E., Kayahan, E. (2010), Inner ear lipoma; Diagn Interv Radiol 2010; 16:2426 17. Singh, V. (1992) Osteoma of the internal auditory canal presenting with sudden unilateral hearing loss; The Journal of Laryngology and Otology, Vol. 106, pp. 905-907 18. Symptoms of neurologic disease; In Jackler RK, Brackmann DE (eds): Neurotology. Mosby Publishers, St. Louis, MO 19. Selesnick SH, Jackler RK. Clinical manifestations and Audiologic Diagnosis of Acoustic Neuromas. Otolaryngol Clinics NA, June 1992; 25 (3): 521-551.