Acoustic neuroma overview

# Overview
vestibular schwannoma is the most common tumor of the cerebellopontine angle in adults. It is approximately 8-9% of all intracranial tumors. The term vestibular schwannoma is preferred over acoustic neuroma which is a misnomer. Acoustic neuroma is a noncancerous tumor.  In 1777, Eduard Sandifort first described Acoustic neuroma. In 1822, Wishart described Bilateral acoustic neuroma for the first time. It grows slowly from an overproduction of Schwann cells and is additionally called a vestibular schwannoma. The tumor then presses on the hearing and balance nerves within the internal ear. Schwann cells normally encircle and support nerve fibers. An outsized tumor can compress the facial nerve, which controls facial muscles and sensation or it can compress brain structures.  Acoustic neuroma may be classified according to the findings on magnetic resonance imaging (MRI), microscopic histopathology, association with neurofibromatosis type 2 or not. On microscopic histopathological analysis, an acoustic neuroma may display two types of growth patterns: Antoni type A and Antoni type B. Screening for acoustic neuroma is not recommended at any age. Approximately 50% of all acoustic neuromas grow slowly 1 - 2 mm in one year. The growth rate is more rapid (greater than 2 mm/year) in about 20% of the patients. The tumor does not metastasize to other parts of the body. Widespread access to sensitive neuro-diagnostic imaging has led to a remarkable rise in the detection of vestibular schwannomas.  Gadolinium-enhanced MRI scan is the definitive diagnostic test for acoustic neuroma and can identify tumors as small as 1-2 millimeters in diameter. Acoustic neuroma characterized by hypointense lesion on T1-weighted MRI, and hyperintense lesion on T2-weighted MRI of brain. Treatment strategies are often divided into an observational wait-and-scan approach, irradiation, microsurgery, and a mixture of these methods. Each strategy features a set of benefits and limitations. Complication include long-term facial-nerve paralysis, bilateral hearing loss, or chronic dizziness or imbalance and these may require rehabilitative intervention.

# Historical Perspective
- In 1777, Eduard Sandifort first described Acoustic neuroma.
- In 1822, Wishart described Bilateral acoustic neuroma for the first time. The patient under study became progressively deaf, blind, had uncontrollable vomiting, headaches, and facial jerking and died at 21 years of age. Wishart found numerous tumors in the skull at autopsy. He described the following: The seventh cranial nerve pair was diseased in the same manner; a tumor of the size of a small nut, and very hard, being attached to each of them, just where they enter the meatus auditorius internus."
- In 1833, Charles Bell provided the first known report of a case of the neuroma, demonstrating the relationship of the tumor to the cerebellopontine angle.
- In 1894, Charles Ballance successfully removed an acoustic neuroma surgically. Since then, tremendous efforts of many surgeons have been continuing to provide surgical approaches to improve outcomes of treatments and decrease side effects of interventions.
- Early in 1925, Dandy reported, operative mortality in acoustic neuroma was ranging from 67% to 84%. Harvey Cushing, through increased experience and partial, intracapsular removal of the tumor, was able to reduce the mortality rate to 11%.
- Because of the concern of tumor regrowth, Walter Dandy suggested total removal of the tumor by intracapsular enucleation followed by deliberate, painstaking dissection of the capsule from the brainstem through a suboccipital approach, which became the standard technique for removing acoustic neuromas for the next many years. Although there were improvements in diagnosis and treatment, mortality rate was still high.
- Dr William House had developed the middle cranial fossa approach for decompensation of the internal auditory canal in 1960. He performed a series of cadaver sections to find a method to expose the cerebellopontine angle through mastoid to preserve the facial nerve, the tympanic membrane, and posterior canal wall which leads to development of translabyrinthine approach.
- In 1965, when the first international symposium on acoustic neuroma was organized, leading neurosurgeons, otologists, neurologists, and audiologists attended the meeting and covered an expanded range of subjects.
- Over the years, the recognized approaches include: retrosigmoid, middle fossa, and translabyrithine. The approach had to be selected depending on the size and location of the tumor as well as patients general condition and preoperative hearing condition

# Classification
Acoustic neuroma may be classified according to the findings on
- magnetic resonance imaging (MRI)
- microscopic histopathology; Based on microscopic histopathology, acoustic neuroma may be classified into four subtypes:
- Associated with neurofibromatosis type 2 or not.
- Koos grading scale provides four grades based on extra meatal extension and compression of the brain stem , a reliable method for tumor classification which is used in practice now a days.
- In addition, several disease variants, including macrocytic and hemorrhagic vestibular schwannomas, may have a more aggressive course.

# Pathophysiology
- Acoustic neuroma arises from Schwann cells  of the vestibulocochlear (eighth cranial) nerve, which are the cells involved in the conduction of nervous impulses along axons, nerve development, and regeneration. On microscopic histopathological analysis, an acoustic neuroma may display two types of growth patterns: Antoni type A and Antoni type B.
- Antoni type A growth pattern is composed of elongated cells with cytoplasmic processes arranged in fascicles, little stromal matrix, and verocay bodies. Antoni type B growth pattern is composed of a loose meshwork of cells, less dense cellular matrix, microcysts, and myxoid change.
- Depending on size, tumors may be fully confined to the internal auditory canal or may extend to varying degrees into the cerebellopontine angle. As a tumor grows, it expands within the confines of the internal auditory canal and exerts pressure on adjacent nerves before growing medially into the cerebellopontine angle.
- Larger tumors that extend into the cerebellopontine angle may compress the trigeminal nerve located cranially, the lower cranial nerves located caudally, and the brain stem and cerebellum medially.
- Progressive medial effacement of the pons may result in obstruction of the fourth ventricle and subsequent obstructive hydrocephalus leading to severe heading and vomiting.
- Neurofibromatosis type 2 is a rare autosomal dominant disorder caused by pathogenic variants within the NF2 gene; nearly half of affected people have a positive family history, and the remaining cases result from new variants.
- As acoustic neuromas are benign tumors in nature, there is no well established criteria for the staging of acoustic neuromas.

# Causes
- Numerous studies show the correlation between Neurofibromatosis type 2 (NF2) and acoustic neuroma. Other causes can include Constant or continuous exposure to loud noise (such as music or work-related noise) Neck or face radiation can lead to acoustic neuroma many years later and cellular telephone use. Bilateral acoustic neuromas affect both ears and are inherited (genetic mutations in neurofibromatosis-2/NF-2 genes).

# Differential Diagnosis
- Vestibular schwannoma must be differentiated from Schwannomas originating from other nerves (e.g., facial-nerve schwannoma), meningiomas (In contrast to vestibular schwannomas, posterior fossa meningiomas involve the internal auditory canal less frequently and typically grow eccentrically to the medial canal opening), metastases from primary tumors at other sites, or malignant peripheral nerve sheath tumors that develop new or secondarily within preexisting schwannomas, either spontaneously or after radiation treatment.  Acoustic neuroma must also be differentiated from the intracranial epidermoid cyst ( Epidermoid are the third most common tumor of the cerebellopontine angle and are isointense to surrounding cerebrospinal fluid on T1 and T2 weighted imaging), facial nerve schwannoma, trigeminal schwannoma, ependymoma, leiomyoma, intranodal palisaded myo-fibro-blastoma, malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor, neurofibroma, Meniere's disease, and Bell's palsy.

# Epidemiology and Demographics
- Enhanced diagnostics leading to increase detection has lead to rising in the incidence of vestibular schwannoma.  It is approximately 8-9% of all intracranial tumors.
- From the 1900s the incidence of vestibular schwannomas remained static since patients presented with large tumors causing symptoms that had grown over a period of years without being detected.
- The incidence of acoustic neuroma ranges from 0.3 to 1 per 100, 000 individuals in 1970, current incidence rates range from 3 to 5 cases per 100,000 person-years.
- 20 cases per 100,000 person-years in patients aged 70 years.
- A lifetime prevalence is exceeding 1 case among 500 persons.
- Sporadic unilateral vestibular schwannomas, which account for more than 95% of cases. Women are more commonly affected by acoustic neuroma than men. Most cases of acoustic neuroma develop in individuals between 30 and 60 years of age.
- Denmarks national registry showed the average age at diagnosis increased from 49 to 60 years, the mean tumor size decreased from 2.8 cm to 0.7 cm.
- Developed countries with widespread access to MRI, population-based data suggest that up to 25% of all new cases are diagnosed incidentally during imaging that was obtained for unrelated indications like severe headache or imbalance problem.

# Risk Factors
Common risk factors in the development of acoustic neuroma are
- neurofibromatosis type 2
- radiation exposure
- Less common risk factors include sporadic defects in tumor suppressor genes
- Exposure to loud noise
- History of parathyroid adenoma
- The use of cellular phones
- Several groups have suggested that environmental exposures, such as cell phone use or long-term noise exposure may increase the risk of tumorigenesis but this relation is still under study.

# Screening
- According to the U.S. Preventive Services Task Force (USPTF), screening for acoustic neuroma is not recommended. Evaluation for NF-2 should be done in individuals with an apparently sporadic vestibular schwannoma occurring before the age of 30, or a spinal tumor or meningioma occurring at less than 20 years of age.
- Indications for screening MRI study include sudden or asymmetric sensorineural hearing loss detected through pure-tone and speech audiometry.
- Patients with an isolated, unilateral vestibular schwannoma who do not have other signs of neurofibromatosis type 2 and have no affected relatives generally do not need to undergo genetic testing, nor do their family members.
- The average age at diagnosis increased from 49 to 60 years, the mean tumor size decreased from 2.8 cm to 0.7 cm because of early detection of the tumor via advanced technology.

# Natural History, Complications and Prognosis
- Approximately 50% of all acoustic neuromas grow slowly (1 - 2 mm/year). The growth rate is more rapid (greater than 2 mm/year) in about 20% of the patients. The tumor does not metastasize to other parts of the body. Hearing loss, when occurs, is irreversible. If left untreated, an acoustic neuroma can block the flow of cerebrospinal fluid and cause hydrocephalus, which may lead to severe vision problems and difficulty breathing and swallowing.
- Complications of acoustic neuroma include hearing loss, Hydrocephalus, and recurrence of the tumor. Small, slow-growing tumors may not need treatment. Patients experience a similar quality of life whether treatment is observation, radiation, or surgery.
- Large tumors associated with symptomatic brain-stem compression, hydrocephalus, trigeminal neuralgia or neuropathy, or a combination of these complications.
- Although many of the stigmata of facial-nerve injury can be electively managed, incomplete eye closure must be aggressively treated to reduce the risk of exposure keratopathy, commonly manifested as blurred vision, ocular pain, and redness.
- An important ramification of increased disease detection is a potential for overtreatment, which could result in unnecessary complications and health care expenditures. Many patients, who just decades ago would have lived out their lives without having their tumors detected, are now receiving treatment.
- Population-based data showed that 334 of 636 patients had a useful hearing at diagnosis, with a speech discrimination score of more than 70% (indicating that 70% percent of words were repeated back correctly by the patient), but after 10 years of observation, only 31% retained hearing above this threshold. Notably, 88% of patients who started with a speech discrimination score of 100% still had a score of more than 70% at 10 years, suggesting that excellent speech comprehension at diagnosis portends favorable long-term hearing outcomes.
- Unfortunately, since symptom progression is not strongly correlated with tumor growth and since the growth rate is highly variable, patients who are lost to follow-up are at increased risk for the development of a large tumor, with an associated increase in the risk of a poor outcome with eventual treatment.
- The risk of secondary cancer from radiosurgery approaches 0.02%.

# Diagnostic Study of Choice
Widespread access to sensitive neuro-diagnostic imaging has led to a remarkable rise in the detection of vestibular schwannomas.  Gadolinium-enhanced MRI scan is the definitive diagnostic test for acoustic neuroma and can identify tumors as small as 1-2 millimeters in diameter. On brain MRI, acoustic neuroma is characterized by a hypo-intense lesion on T1-weighted MRI, and hyperintense lesion on T2-weighted MRI.

# History and Symptoms
Chronic gradual unilateral hearing impairment is that the commonest complaint resent in 95% of the patients. Common symptoms include chronic gradual unilateral hearing loss, ringing within the ear, Disequilibrium, facial numbness, facial pain, and Headache. Less common symptoms include facial muscle weakness, taste disturbances, dryness of the eyes, sudden lacrimation, speech problem, difficulty swallowing, aspiration, hoarseness, and ear pain, ipsilateral sensorineural hearing loss in more than 90% of patients.
Hearing loss is usually subtle initially and should first become apparent when the patient is employing a telephone or lying in bed with the contralateral ear covered.
Symptoms of dizziness or imbalance in up to 61% of patients, and complaint of asymmetric tinnitus in 55%. Tinnitus is assumed to result from cochlear deafferentation and cortical maladaptation  a mechanism akin to deafferentation pain, as seen in the phantom limb syndrome, tinnitus may persist even after surgery.
There is an increasing difficulty with sound localization and speech comprehension in the presence of background noise, which results from the loss of binaural hearing. Similarly, symptoms of vertigo and continuous dizziness occur in only about 8% and 3% of cases, respectively.
Patients with large tumors that compress the brain stem and cerebellum may have hypoesthesia during a trigeminal distribution, secondary tic douloureux, cerebellar dysmetria, and ataxia, or slowly progressive hydrocephalus without alteration of consciousness.
Symptom progression isn't strongly correlated with tumor growth. The sensorineural deafness and vestibular hypofunction aren't reversed even with tumor treatment.

# Physical Examination
Patients with acoustic neuroma usually appear normal. Physical examination of patients with acoustic neuroma is usually remarkable for Sensorineural hearing loss in the affected ear, positive Rinne test, abnormal Weber test, Papilledema, Nystagmus, Diplopia on lateral gaze, decreased or absent ipsilateral corneal reflex, facial twitching or hypesthesia, Drooling, drooping on one side of the face, loss of taste, and ataxia.

# Laboratory Findings
There are no diagnostic laboratory findings associated with acoustic neuroma.

# Electrocardiogram
There are no electrocardiogram findings associated with acoustic neuroma.

# X Ray
There are no x-ray findings associated with acoustic neuroma.

# Echocardiography/Ultrasound
There are no echocardiography or ultrasound findings associated with acoustic neuroma.

# CT
CT scan of the head may be diagnostic of acoustic neuroma. Findings on CT scan diagnostic of acoustic neuroma include erosion and widening of the internal acoustic canal.

# MRI
25% of all new cases are diagnosed incidentally during imaging that was obtained for unrelated indications (e.g., headache). Gadolinium-enhanced MRI scan is the definitive diagnostic test for acoustic neuroma and can identify tumors as small as 1-2 millimeter in diameter highly sensitive and specific accurate radiologic diagnosis in most cases, without the need for a confirmatory biopsy. On brain MRI, acoustic neuroma characterized by hypo intense mass on T1-weighted MRI, and hyperintense mass on T2-weighted MRI.

# Other Imaging Findings
There are no other imaging findings associated with acoustic neuroma.

# Other Diagnostic Studies
Audiometry as the best initial screening test for the diagnosis of acoustic neuroma. It can detect asymmetric sensorineural hearing impairment in about 95% of the patients. Brain stem-evoked response audiometry (ABR, BAER, or BSER) may be done in some cases with unexplained asymmetries in standard audiometric testing as a further screening measure and an abnormal auditory brain stem response test should be followed by an MRI.

# Medical Therapy
Treatment strategies are often divided into an observational wait-and-scan approach, irradiation, microsurgery, and a mixture of those methods. each strategy features a set of benefits and limitations. As such, patient preference plays a serious role in shared decision-making. Tumor size chiefly drives treatment recommendations; however, deciding is additionally guided by the subtle patient- and provider-related factors. Several new drug therapies that aim to halt tumor growth, including aspirin and monoclonal antibodies, have recently been explored but remain investigational. The foremost consistent predictor of future growth during an observational strategy is larger tumor size at diagnosis.

### Wait-and-Scan Approach
Typically, tumors that have a maximal diameter of but 1.5 cm within the cerebellopontine angle are considered for a wait-and-scan approach. The wait-and-scan approach has gained popularity for a minimum of two reasons: many tumors are now discovered as small masses in older people with mild symptoms; furthermore, reports over the past 15 years have documented radiographically that only 22 to 48% of tumors have shown growth (most commonly defined as an increase of 2 mm in diameter). The mainstay of therapy for acoustic neuroma is surgery and radiotherapy. Since acoustic neuroma tends to be slow-growing and should be a benign tumor, careful observation with follow-up MRI scans every 6 to 12 months could even be appropriate for elderly patients, patients with small tumors, patients with significant medical conditions, and patients who refuse treatment.

# Surgery
Surgery is that the mainstay of treatment for acoustic neuroma. If growth is definitively confirmed, most patients receive a recommendation to undergo radiosurgery or microsurgery. Patients with age under 65 years, medium to large-grade tumors, significant deafness , or higher headache severity scores will have more satisfying outcomes from surgery as compared with observation. There are three main surgical approaches for the removal of an acoustic neuroma: translabyrinthine, retro sigmoid or sub-occipital, and middle fossa approach. The choice of a specific approach is predicated on several factors including the dimensions and site of the tumor and whether or not the preservation of hearing may be a goal. Active monitoring of the tumor with serial imaging, signifying a transition in clinical care from up-front microsurgical resection, which epitomized treatment in earlier eras, to management of the chronic disease.

## Radiosurgery
It is performed in an outpatient setting, with no activity restrictions for the patient after radiosurgery. It prevents tumor growth but doesn't cure. The diameter of but 3.0 cm within the cerebellopontine angle is typically considered to be candidates for radiosurgery. the utilization of highly conformal radiation, defined as radiation delivered in 1 to five fractions to an image-defined target, with maximal sparing of the encompassing tissue. Gamma-knife radiosurgery is one sort of conformal radiation. Gamma knife treatment consists of 192 cobalt-60 sources arranged concentrically to deliver an ovoid isocenter of radiation performed under local anesthesia the dose prescribed is typically 12 to 14 Gy at the five hundred isodose lines, delivered during a single fraction. Treatment typically incorporates a stereotactic head frame and thin-slice, noncontrast-enhanced computerized tomography, and contrast-enhanced axial MRI to stereotactically target the tumor in three-dimensional space. Linear acceleratorbased platforms also are employed by many centers. Most of those systems involve one, collimated radiation beam with a gantry that rotates around the patient, creating a focused arc of radiation that stereotactically targets the lesion of interest. Transient tumor enlargement within the primary 3 years after radiosurgery is common, although variable tumor shrinkage eventually occurs in additional than half treated cases. tumor control is reported in additional than 90% of cases of vestibular schwannoma at 10 years of follow-up. Radiosurgical treatment failure is usually defined by tumor growth that persists for quite 3 years, the event of signs or symptoms related to progressive mass effect, and rapid tumor enlargement. Salvage microsurgery is usually recommended after failure.

### Cyber-knife radiotherapy
Cyber knife involves frameless, LINAC-based radiation delivered by means of a highly maneuverable robotic arm with 6 df for movement, with real-time image guidance. This treatment plan prescribes hypo fractionated radiation, at a dose of 25 Gy delivered in 5 fractions to the 80% isodose line.

### Delivery of high-energy photon radiation using LINAC systems.
The linear accelerator (LINAC)based systems use one , collimated radiation beam with a mobile gantry to make a focused arc of radiation, with frameless stereotaxis; the patient is usually immobilized with the utilization of a customized, soft, plastic mask . The treatment plan prescribes a dose of 12.5 Gy delivered to the 80% isodose line during a single fraction.
It causes radiation-induced brainstem edema, trigeminal neuropathy or neuralgia, and hydrocephalus, also as diminished long-term tumor control. the danger of secondary cancer from radiosurgery approaches 0.02%

## Microsurgery
Microsurgery is usually preferred for the treatment of tumors that are larger than 3 cm in diameter. the treatment of choice for giant tumors related to symptomatic brain-stem compression, hydrocephalus, tic douloureux or neuropathy, or a mixture of those complications and enormous tumor size. All procedures are performed while the patient is under general anaesthesia and need the utilization of an binocular microscope with intraoperative neural monitoring. There are three primary microsurgical approaches wont to remove vestibular schwannomas are the center fossa, translabyrinthine, and retro sigmoid approaches.
The goal is maximal tumor extraction with the protection of neurologic function. Intraoperative facial-nerve monitoring with electromyography is routinely used. Cochlear-nerve monitoring is usually used when hearing conservation is attempted, and monitoring of other regional cranial nerves could also be included for giant tumors. The patient is hospitalized for two to 4 days after the procedure and is ambulatory at the time of discharge. The danger of tumor recurrence after gross total resection is 0 to twenty. 
Fortunately, the prospect of other major neurovascular complications, like permanent injury to other regional cranial nerves or perioperative stroke, is rare, even with large tumors. The prevalence of postoperative spinal fluid leak is 9 to 13%, aseptic meningitis 2 to 4%, and culture-positive bacterial meningitis 1%.
There's a risk of eye dryness due to damage to the facial and incomplete eye closure must be aggressively treated to scale back the danger of exposure keratopathy, commonly manifested as blurred vision, ocular pain, and redness.

# Primary Prevention
There are no established measures for the primary prevention of acoustic neuroma.

# Secondary Prevention
Secondary prevention strategies following acoustic neuroma treatment include follow-up MRI scans. Imaging and audiological evaluation are commonly performed 6 months after the diagnostic MRI so as to spot a fast-growing tumor or a more aggressive process mimicking a vestibular schwannoma. If there's no growth at 6 months, imaging and hearing assessments are performed annually thereafter until year 5, when many specialists advocate every other year assessments. lifelong follow-up is suggested, to attenuate the value of ongoing tumor surveillance and therefore the risk of adverse events associated with contrast medium, several groups have transitioned to the utilization of thin-slice, heavily T2-weighted resonance cisternography without contrast medium, which features a high degree of accuracy and interrater reliability. Research showed that excellent speech comprehension at diagnosis portends favorable long-term hearing outcomes. After radiosurgery, patients undergo audiometric evaluation and MRI studies annually for the primary 3 years, then every other year until 10 years, then every 5 years indefinitely.

# Rehabilitation
Those with long-term facial-nerve paralysis, bilateral hearing loss, or chronic dizziness or imbalance may require rehabilitative intervention.
For patients in whom serviceable hearing is maintained within the ipsilateral ear, observation (i.e., no additional hearing rehabilitation) or use of a standard hearing aid is usually adequate. surgical means (i.e., bone-conduction implants) or nonsurgical means (e.g., contralateral routing of signals  hearing aids. Research showed that excellent speech comprehension at diagnosis portends favorable long-term hearing outcomes.
Facial-nerve paralysis is rare overall, but the danger approaches 50% among patients with large tumors. nervous disorder and eye dryness are primary concerns within the early postoperative period. Eye lubricants and moisture chambers generally provide adequate protection. Usually, referral to an ophthalmologist for upper eyelid weight placement, punctal plugs, or tarsorrhaphy should be considered if longer-term paralysis is anticipated or ophthalmologic complications appear. Improvement is usually greatest within 6 months after the onset of paralysis, but continued recovery is often seen for up to 18 months.
People who report substantial dizziness or imbalance should undergo a comprehensive balance assessment to accurately identify any coexisting disorders and to assess and mitigate the danger of falling. Common conditions which will exacerbate dizziness include peripheral neuropathy, age-related loss of contralateral vestibular function, vision loss, and vestibular migraine. The mammalian peripheral vestibular apparatus has limited regenerative capacity. Thus, balance therapy is that the therapeutic mainstay for people that have troublesome symptoms associated with chronic vestibular hypofunction.