Microsurgery for Sporadic<unk>  The Guidelines on the Treatment of Adults with<unk>  issued in 2018 by the Congress of Neurological Surgeons in the U.S. looked at the long-term evolution of treatments for<unk> . The Introduction to the Guidelines stated: "The evolution in treatment over the last century has ultimately led to an environment where functional outcome has taken precedence over disease eradication. With multiple noninvasive management options available, the tolerance of cranial neuropathy in patients with small and medium-sized tumors is low. Today, hearing preservation, facial nerve function, and tumor control remain the primary benchmarks used to evaluate treatment effectiveness and compare outcomes." In other words, tumor management was able to give greater attention to preserving quality of life. The three main surgical approaches to the tumor were the translabyrinthine (incision behind the ear to reach the bony labyrinth), the retrosigmoid (incision behind the ear to reach cerebellopontine angle) and the middle cranial fossa (incision in front of the ear to access the IAC from above). Tumor size was a major factor in determining approach selection. Adjunctive use of the endoscope for enhanced visualization during surgery for IAC tumors gained attention as an emerging technique with advancing technology. For large tumors, a 'facial nerve sparing surgery' evolved offering partial removals, to be followed (as needed) by stereotactic radiosurgery or radiotherapy for 'residuals'. The rate of 'tumor control' appeared to be similar to that for gross total removal surgeries. For small to medium size tumors, the appropriateness of so-called 'hearing preservation surgery' via either the Middle Fossa or Retrosigmoid approach remained controversial. Data from Denmark indicated that primary observation offered the best chance to preserve good hearing the longest. But preserving good hearing in the affected ear remained an elusive goal. Even during observation, although tumors showed no significant growth, hearing deterioration occurred. Stangerup et al reported (2010) that most patients with 100% speech discrimination at diagnosis had the best chance of maintaining good hearing after ten years of observation. Structured surgical training of neurosurgeons and official accreditation replaced the ages-old informal apprenticeship model. Advances in microsurgical instrumentation, the refinement of operative techniques including the introduction of intraoperative facial and cochlear nerve monitoring, and the development of multidisciplinary team-based patient care reduced the incidence of complications related to treatment. There was a trend toward the emergence of high-patient-volume centers for<unk>  surgery where good outcomes and routine patient discharges could become commonplace. The mortality rate for<unk>  surgery fell to less than 1%. In 1991 the NIH Consensus Statement for Acoustic Neuroma observed: "The best published surgical outcomes in the treatment of<unk>  are from medical centers that have highly organized and dedicated teams with a specific interest in these tumors and sufficient continuing experience to develop, refine and maintain proficiency."ref> Radiosurgery and radiotherapy The 1991 NIH Consensus Statement recognized radiation therapy as "a treatment option limited in current practice primarily to patients unable or unwilling to undergo otherwise indicated surgery." The beneficiaries of radiation therapy soon greatly exceeded this limited clientele. The 'Patient Survey' in the U.S. in 2014 by the national Acoustic Neuroma Association showed that 29% of<unk>  patients reported radiosurgery (17%) or radiotherapy (12%) as their treatment of choice. Radiosurgery is the delivery to the<unk>  of a concentrated high radiation dose in a one-day session, whereas radiotherapy involves multiple treatment sessions where the total radiation dose is spread out in fractions over a few days or 3–4 weeks. The main objective in either case is 'tumor control' by damaging tumor cell DNA and stopping blood vessel proliferation (angiogenesis) needed for tumor growth. Tumors may swell following radiation, but this increase in size is transient and does not signal a failed procedure. A failed radiosurgery is uncommon. Radiation doses are calculated in terms of Gray/Gy—the measure of energy deposited by ionizing radiation per kilogram of matter -- "named after the British physicist Louis Harold Gray (1905–1965), a pioneer in the measurement of X-ray and radium radiation and their effects on living tissue." Since<unk> s are noninvasive and well-demarcated from surrounding tissues, as is apparent on MRI scans, radiosurgeons are able to target the tumor volume closely and minimize normal tissue damage. Multisession radiotherapy recommends the advantage of giving time between sessions for biological repair of any damage to normal tissues that may occur, and allows for radiation of the tumor at different times in the cell growth cycle. The CyberKnife radiation system introduced in 1994 recommends a protocol of three sessions known as hypofractionation. Radiation dosages overall were reduced over the years as experience showed that excellent tumor control rates could be maintained even as dosages were lowered to benefit hearing preservation and facial nerve function. Generally, single-session Gamma Knife radiosurgery is limited in use to<unk> s less than 3 cm in diameter to avoid possible complications with facial nerves, brainstem and the cochlea apparatus. The risk of radiation-induced secondary tumors is very small, in the range of 0.01-0.02%. The risk for NF2 patients appears to be slightly higher. Medical and gene therapies The 1991 NIH Consensus Statement recommended attention to "the development of pharmaceutical and other alternative medical treatments, such as tumor suppressing agents." Ideally, a drug could be found to permanently shrink or eradicate<unk> s, with minimal side effects. A key step forward in 1993 was the identification of the NF2 gene and its protein product Merlin, which modulates the complex molecular signaling pathways that control cell proliferation. These pathways that drive<unk>  formation (tumorigenesis) and growth are currently under investigation. A second important field of study in molecular biology investigates ways to stop the formation (angiogenesis) of the new blood vessels that are needed to support tumor growth by supplying nutrients and oxygen. In 1998, the glycoprotein named VEGF (vascular endothelial growth factor) that initiates proliferation was discovered. An anti-VEGF drug named bevacizumab (Avastin) was developed and showed promise in stopping this vascular proliferation. Unfortunately, when tested for NF2 tumors, the therapy required prolonged treatment resulting in hypertension and impaired wound healing. Clinical trials are in progress for other drugs such as everolimus, lapatinib and mifepristone. Common aspirin has been studied as a low-risk therapeutic option. To date, there is no fully efficacious medical therapy for<unk> . The complexity of the molecular biology research involved is truly challenging. The development of a new generation of drugs may become a secondary therapy in view of advances in genome editing during the 1990s that led to the invention of CRISPR in 2009. CRISPR has become the preferred genome editing tool whereby diseases may be treated by correcting causative mutations directly in a patient's genome. Observation of Small<unk>  The 1991 NIH Consensus Statement observed: "There is evidence that some patients with unilateral<unk>  and a subgroup of patients with NF2 may have tumors that fail to progress rapidly, resulting in stable neurologic function for a long time. The use of MRI with contrast enhancement has resulted in the identification of patients with very small, relatively asymptomatic<unk> s for whom the natural history is unknown. Conservative management may be appropriate for these patients." At the time, conservative management (i.e., observation, 'wait-and-watch'/'wait-and-scan') was reserved mainly for elderly or infirm patients. Data on tumor sizes at diagnosis and tumor growth behavior was sparse or contradictory and mainly short-term. The Central Brain Tumor Registry of the U.S., established in 1992, only began to keep records for benign tumors like<unk>  in 2004. In 2006, a landmark study from Denmark, entitled "The Natural History of<unk> ," initiated a significant trend toward observation for managing small<unk> . Researchers in Copenhagen had the advantage that data for all Danish patients diagnosed with<unk>  since 1976 was entered into a national database. The 2006 study by Stangerup et al looked at the data for 1,818 patients (1976–2004) comparing intrameatal<unk>  (in the auditory canal) and extrameatal<unk>  (into the cerebellopontine angle). Remarkably, for the 729 patients having observation management via interval MRI scans, tumor growth was observed in only 17% of intrameatal tumors and 29% of extrameatal tumors. The mean observation time was 3.6 years (range 1–15 years). The researchers concluded: "VS growth occurs within the first 5 years after diagnosis in a limited number of tumors, primarily in tumors with an extrameatal extension. These findings justify primary observation of small tumors." The medical community and<unk>  patients responded positively to these findings. 'Patient Surveys' in the U.S. by the national Acoustic Neuroma Association showed an increase in "Wait-and-Watch" from 4% of respondents in 1998 to 20% in 2012. An important study in 2015 entitled "The Changing Landscape of<unk>  Management in the United States – A Shift Toward Conservatism," predicted that half of all cases of<unk>  would be managed initially with observation by 2026. Stangerup et al have urged caution (2019): "Most studies show that if tumor growth occurs, it is usually detected within the first few years of diagnosis. However, long-term observational studies are desperately needed to guide the development of evidence-based surveillance algorithms
Vestibular schwannoma
Optic nerve sheath meningioma
Intraocular schwannoma
Choroid plexus papilloma
Craniopharyngioma
Optic nerve glioma
Mantleoma
Pinealoma