DOCSLIB.ORG

(Acoustic Neuroma) After Stereotactic Radiosurgery

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(Acoustic Neuroma) After Stereotactic Radiosurgery Otology & Neurotology 24:650–660 © 2003, Otology & Neurotology, Inc. Clinical and Histopathologic Features of Recurrent Vestibular Schwannoma (Acoustic Neuroma) after Stereotactic Radiosurgery *Daniel J. Lee, *†William H. Westra, ‡Hinrich Staecker, §Donlin Long, and *John K. Niparko Departments of *Otolaryngology-Head and Neck Surgery, †Pathology, and §Neurologic Surgery, The Johns Hopkins School of Medicine; and ‡Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Maryland Medicine, Baltimore, Maryland, U.S.A. Objective: Stereotactic radiosurgery for vestibular schwan- the cerebellopontine angle and internal auditory canal. Fibrosis noma entails uncertain long-term risk of tumor recurrence and outside and within the tumor bed varied markedly, complicat- delayed cranial neuropathies. In addition, the underlying histo- ing microsurgical dissection. Light microscopy confirmed the pathologic changes to the tumor bed are not fully characterized. presence of viable tumor in all cases. Histopathologic features We seek to understand the clinical and histologic features of were typical of vestibular schwannoma, and there was no sig- recurrent vestibular schwannoma after stereotactic radiation nificant scarring that could be attributed to radiation effect. therapy. Conclusions: The variable fibrosis in the cerebellopontine Study Design: Retrospective review. angle and lack of radiation changes seen histopathologically in Setting: Tertiary referral center. irradiated vestibular schwannoma suggest that a uniform treat- Patients: Four patients who underwent microsurgical resection ment effect was not achieved in these cases. Although all four of vestibular schwannoma after primary stereotactic radiation patients with preoperative cranial neuropathies were found in- therapy. traoperatively to have fibrosis in the cerebellopontine angle, Intervention: Patients were treated primarily with gamma excellent preservation of facial nerve anatomy and function knife radiosurgery or fractionated stereotactic radiotherapy fol- was possible with salvage microsurgical resection. Additional lowed by salvage microsurgery. Retrosigmoid craniotomy was analyses are needed to clarify the histopathologic and molecu- used in all cases. lar characteristics associated with vestibular schwannoma Main Outcome Measures: Histopathologic review. Preopera- growth after stereotactic radiation. Key Words: Microsur- tive and postoperative facial nerve function was assessed with gical resection—Stereotactic radiation therapy—Vestibular the House-Brackmann scale. schwannoma. Results: We observed highly inconsistent radiation changes in Otol Neurotol 24:650–660, 2003. The mainstay of vestibular schwannoma (VS) man- resulting in minimal morbidity and mortality (1,4,12) agement has traditionally been microsurgical resection and favorable long-term recurrence rates ranging from by an experienced neurotologic and neurosurgical team. 0.5 to 1.5% (3,13). Refinements in neuroanesthesia and Excellent outcomes have been reported from surgery for postoperative critical care have also contributed to the VS regarding anatomic preservation of the facial nerve safety of craniotomy and microsurgical resection for VS. (1–4), facial nerve function (1–5), and serviceable hear- Stereotactic radiosurgery (“gamma knife”) and frac- ing preservation (6–11). Complete tumor removal can be tionated stereotactic radiotherapy (FSR) have become in- achieved through meticulous microsurgical dissection, creasingly popular alternatives to microsurgical resection for the primary treatment of VS. Stereotactic radiosur- gery, developed by Lars Leksell in 1951 (14) and used on Address correspondence and reprint requests to Dr. John Niparko, VS patients for the first time in 1969 (15), involves the Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins School of Medicine, Johns Hopkins Outpatient Center, 601 biologic inactivation of a three-dimensional target by a North Caroline Street, Baltimore, MD 21287, U.S.A.; Email: single dose of ionizing radiation (16). In contrast, FSR [email protected] involves multiple treatment sessions to deliver a thera- 650 ACOUSTIC NEUROMA AFTER STEREOTACTIC RADIOSURGERY 651 peutic radiation dose to the tumor. Regardless of tech- ries of five patients with recurrent VS after stereotactic nique, treatment-related morbidity is comparable, if not radiation. Three of five patients had complete facial improved, in patients who receive radiation therapy com- palsy preoperatively, and significant scarring to the facial pared with microsurgical resection (17–20). Because a nerve and brainstem was encountered intraoperatively. craniotomy and general anesthesia are avoided, radiation This represented a substantially poorer outcome com- therapy is also a reasonable alternative to surgery for the pared with comparably sized tumors treated primarily elderly or patients with symptomatic or growing tumors, with microsurgical resection (1,3,4,12). The purpose of who are poor surgical candidates (21). our retrospective study is to more fully clarify the clini- Approximately 10 in 1 million persons in the United cal presentations, intraoperative findings, histopathol- States are diagnosed with VS (22). Using an estimated ogy, and postoperative follow-up of four patients with 2001 U.S. population of 285 million persons, approxi- recurrent VS after primary stereotactic radiation. mately 3,000 new cases of VS will be diagnosed in 2002. Proponents of radiation therapy predict that in 10 years, PATIENTS AND MATERIALS an equal number of these patients will receive either Subjects used for this study received either primary gamma stereotactic radiation or microsurgery as the primary mo- knife radiosurgery or FSR for VS diagnosed by gadolinium- dality for VS (23). However, the decision to choose mi- enhanced MRI. Informed consent was obtained from all pa- crosurgical resection or radiosurgery is still controver- tients used in this study. In all four subjects, microsurgical sial. The obvious disadvantage with “radiosurgery” or salvage resection was prompted by recurrent tumor growth and radiotherapy is that tumor volume is not directly reduced associated delayed cranial neuropathies. Tumor resection was or removed; treatment success with radiation is measured performed using a retrosigmoid craniotomy approach by a neu- rotologic surgeon and neurosurgeon. Intraoperative cranial in terms of tumor growth suppression as demonstrated by nerve monitoring was used in all cases. A retrospective review serial magnetic resonance imaging (MRI). In addition, of the medical records of two tertiary care medical centers was although radiation therapy for VS has shown low tumor performed. Axial and coronal, gadolinium-enhanced MRI regrowth rates ranging from 2 to 9% (24–26) with mean scans were analyzed and correlated with intraoperative findings follow-up periods of 2 to 5 years (17,20,27–32), long- and histopathology. Hematoxylin and eosin–stained pathologic term studies after consistent radiotherapeutic approaches slides were retrieved from the files of the respective depart- are still needed. ments of surgical pathology. When an irradiated VS becomes symptomatic and dis- plays continued growth, microsurgical salvage is often CASE REPORTS indicated. Unfortunately, the surgery can be complicated Case 1 by scarring and increased perioperative morbidity A healthy 72-year-old woman presented to an outside (11,33–35). Slattery and Brackmann (33) reviewed a se- institution with progressive tinnitus and sensorineural FIG. 1. T1-weighted, post–gadolinium-enhanced MRI scans of the cerebellopontine angle from Case 1. Axial images (A–C) and coronal sections (D–F). (A and D) Pre–gamma knife MRI scans demonstrating a right-sided 1.0-cm VS, with scans at 6 months (B and E) and 20 months (C and F) after radiation. Slight tumor involution seen in B was followed by rapid regrowth to 1.5 cm at 1 year after radiosurgery (MRI scan not shown). Otology & Neurotology, Vol. 24, No. 4, 2003 652 D. J. LEE ET AL. hearing loss. She denied dizziness, headaches, facial countered, with no evidence of radiation-induced nerve twitching, or weakness. A right-sided, 1.0 × 0.7- changes of the posterior and medial surfaces. Complete cm intracanalicular VS was diagnosed (Fig. 1), and she resection of VS was achieved, with anatomic preserva- underwent gamma knife radiosurgery. The radiation dose tion of the facial nerve. delivered was 13 Gy. She initially did well, with 50% tumor involution at 6 months after radiation therapy. Postoperative course However, she began to experience episodic right-sided She recovered uneventfully, with normal facial nerve facial nerve spasms at 12 months after radiosurgery. function (Fig. 2, A–C). Her hospital stay was 5 days. These symptoms were partially relieved with botulinum Now, 15 months after surgery, she has no recurrent facial toxin injections. Serial MRI (Fig. 1) demonstrated in- nerve spasms. Final pathologic findings were consistent creased tumor growth to 1.5 × 1.0 cm after radiosurgery. with vestibular schwannoma. She was referred for surgical management. Case 2 Intraoperative findings A 54-year-old healthy woman presented with unilat- A right suboccipital craniotomy approach was used. eral sensorineural hearing loss and dizziness, and was Significant scarring and fibrosis of the inferior and an- diagnosed with a 2.6-cm left-sided acoustic neuroma. terior portions of this intracanalicular tumor were en- She underwent FSR to 25 Gy. A 6-month follow-up MRI
Load more

Recommended publications
  • Neurofibromatosis Type 2 (NF2)
    International Journal of Molecular Sciences Review Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis Suha Bachir 1,† , Sanjit Shah 2,† , Scott Shapiro 3,†, Abigail Koehler 4, Abdelkader Mahammedi 5 , Ravi N. Samy 3, Mario Zuccarello 2, Elizabeth Schorry 1 and Soma Sengupta 4,* 1 Department of Genetics, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA; [email protected] (S.B.); [email protected] (E.S.) 2 Department of Neurosurgery, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (M.Z.) 3 Department of Otolaryngology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (R.N.S.) 4 Department of Neurology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] 5 Department of Radiology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] * Correspondence: [email protected] † These authors contributed equally. Abstract: Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression.
    [Show full text]
  • Detection of Calcifications in Retinoblastoma Using Gradient
    ORIGINAL RESEARCH HEAD & NECK Detection of Calcifications in Retinoblastoma Using Gradient- Echo MR Imaging Sequences: Comparative Study between In Vivo MR Imaging and Ex Vivo High-Resolution CT F. Rodjan, P. de Graaf, P. van der Valk, T. Hadjistilianou, A. Cerase, P. Toti, M.C. de Jong, A.C. Moll, J.A. Castelijns, and P. Galluzzi, on behalf of the European Retinoblastoma Imaging Collaboration ABSTRACT BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is con- sidered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1–71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor.
    [Show full text]
  • Tinnitus: Ringing in the SYMPTOMS Ears
    Tinnitus: Ringing in the SYMPTOMS Ears By Vestibular Disorders Association TINNITUS WHAT IS TINNITUS? An abnormal noise perceived in one or both Tinnitus is abnormal noise perceived in one or both ears or in the head. ears or in the head. It Tinnitus (pronounced either “TIN-uh-tus” or “tin-NY-tus”) may be can be experienced as a intermittent, or it might appear as a constant or continuous sound. It can ringing, hissing, whistling, be experienced as a ringing, hissing, whistling, buzzing, or clicking sound buzzing, or clicking sound and can vary in pitch from a low roar to a high squeal. and can vary in pitch. Tinnitus is very common. Most studies indicate the prevalence in adults as falling within the range of 10% to 15%, with a greater prevalence at higher ages, through the sixth or seventh decade of life. 1 Gender distinctions ARTICLE are not consistently reported across studies, but tinnitus prevalence is significantly higher in pregnant than non-pregnant women. 2 The most common form of tinnitus is subjective tinnitus, which is noise that other people cannot hear. Objective tinnitus can be heard by an examiner positioned close to the ear. This is a rare form of tinnitus, 068 occurring in less than 1% of cases. 3 Chronic tinnitus can be annoying, intrusive, and in some cases devastating to a person’s life. Up to 25% of those with chronic tinnitus find it severe DID THIS ARTICLE enough to seek treatment. 4 It can interfere with a person’s ability to hear, HELP YOU? work, and perform daily activities.
    [Show full text]
  • Sporadic Schwannomas and Neurofibromas by Herbert B Newton MD (Dr
    Sporadic schwannomas and neurofibromas By Herbert B Newton MD (Dr. Newton, Director of the Neuro-Oncology Center at the Florida Hospital Cancer Institute has no relevant financial relationships to disclose.) Originally released October 15, 1996; last updated March 1, 2017; expires March 1, 2020 Introduction This article includes discussion of sporadic schwannomas and neurofibromas, chitoneuroma, neurilemmoma, perineural fibroblastoma, abducens schwannoma, facial schwannoma, hypoglossal schwannoma, jugular foramen schwannoma, malignant schwannoma, neurofibroma, neurofibrosarcoma, peripheral nerve schwannoma, schwannoma, spinal schwannoma, sporadic neurofibromas, sporadic schwannomas, and trigeminal schwannoma. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations. Overview In this article, the author provides an in-depth review of the pathology, biology, clinical presentation, and treatment options for sporadic schwannomas and neurofibromas. These tumors arise from the nerve sheaths of cranial nerves, nerve roots, spinal nerves, and peripheral nerves. The most common location for schwannomas is the eighth cranial nerve, whereas neurofibromas more commonly arise along the spinal nerve roots. Maximal surgical resection is the treatment of choice for most tumors. Radiotherapy is only used in selected cases. Chemotherapy is still under investigation for therapeutic potential. In this update, the author reviews advances in the molecular biology and therapeutic approaches to these tumors. Key points • Schwannomas are slow-growing extra-axial tumors that can arise from any cranial nerve or spinal nerve root. They most commonly arise from the eighth cranial nerve. • Surgical resection is the treatment option of choice for most tumors. Complete resection can result in a surgical cure. • In selected cases, radiosurgery may be as effective as surgery at local control of tumor growth.
    [Show full text]
  • Acoustic Neuroma
    Acoustic Neuroma DISORDERS This document is adapted from materials available from the National Institutes of Health WHAT IS AN ACOUSTIC NEUROMA? VESTIBULAR An acoustic neuroma (also known as vestibular schwannoma or acoustic SCHWANNOMA neurinoma) is a benign (nonmalignant), usually slow-growing tumor that develops from the balance and hearing nerves supplying the inner ear. A benign slow-growing The tumor comes from an overproduction of Schwann cells—the cells that tumor on the normally wrap around nerve fibers to help support and insulate nerves. balance/hearing nerve. HOW DOES IT DEVELOP? As the acoustic neuroma grows, it compresses the hearing and balance nerves, usually causing unilateral (one-sided) hearing loss, tinnitus ARTICLE (ringing in the ear), and dizziness or loss of balance. As it grows, it can also interfere with the facial sensation nerve (the trigeminal nerve), causing facial numbness. It can also exert pressure on nerves controlling the muscles of the face, causing facial weakness or paralysis on the side of the tumor. Vital life-sustaining functions can be threatened when large 03 tumors cause severe pressure on the brainstem and cerebellum. Unilateral acoustic neuromas account for approximately eight percent of all tumors inside the skull; one out of every 100,000 individuals per year develops an acoustic neuroma. Symptoms may develop in individuals DID THIS ARTICLE at any age, but usually occur between the ages of 30 and 60 years. HELP YOU? Unilateral acoustic neuromas are not hereditary. SUPPORT VEDA @ HOW IS IT DIAGNOSED? VESTIBULAR.ORG Early detection of an acoustic neuroma is sometimes difficult because the symptoms related to its early stages may be subtle, if present at all.
    [Show full text]
  • Incidental Vestibular Schwannomas: a Review of Prevalence, Growth Rate, and Management Challenges
    Neurosurg Focus 33 (3):E4, 2012 Incidental vestibular schwannomas: a review of prevalence, growth rate, and management challenges RICHARD F. SCHMIDT, B.A.,1 ZAIN BOGHANI, B.S.,1 OSAMAH J. CHOUDHRY, M.D.,1 JEAN ANDErsON ELOY, M.D.,1–3 ROBERT W. JYUNG, M.D.,2,3 AND JAMES K. LIU, M.D.1–3 Departments of 1Neurological Surgery and 2Otolaryngology–Head and Neck Surgery; and 3Center for Skull Base and Pituitary Surgery, Neurological Institute of New Jersey, University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, New Jersey With the relatively recent increase in the use of MRI techniques, there has been a concurrent rise in the number of vestibular schwannomas (VSs) detected as incidental findings. These incidental VSs may be prevalent in up to 0.02%–0.07% of individuals undergoing MRI and represent a significant portion of all diagnosed VSs. The manage- ment of these lesions poses a significant challenge for practitioners. Most incidental VSs tend to be small and as- sociated with minimal symptoms, permitting them to be managed conservatively at the time of diagnosis. However, relatively few indicators consistently predict tumor growth and patient outcomes. Furthermore, growth rates have been shown to vary significantly over time with a large variety of long-term growth patterns. Thus, early MRI screen- ing for continued tumor growth followed by repeated MRI studies and clinical assessments throughout the patient’s life is an essential component in a conservative management strategy. Note that tumor growth is typically associated with a worsening of symptoms in patients who undergo conservative management, and many of these symptoms have been shown to significantly impact the patient’s quality of life.
    [Show full text]
  • Hemorrhagic Vestibular Schwannoma: an Unusual Clinical Entity Case Report
    Neurosurg Focus 5 (3):Article 9, 1998 Hemorrhagic vestibular schwannoma: an unusual clinical entity Case report Dean Chou, M.D., Prakash Sampath, M.D., and Henry Brem, M.D. Departments of Neurological Surgery and Neuro-Oncology, The Johns Hopkins Hospital, Baltimore, Maryland Hemorrhagic vestibular schwannomas are rare entities, with only a few case reports in the literature during the last 25 years. The authors review the literature on vestibular schwannoma hemorrhage and the presenting symptoms of this entity, which include headache, nausea, vomiting, sudden cranial nerve dysfunction, and ataxia. A very unusual case is presented of a 36-year-old man, who unlike most of the patients reported in the literature, had clinically silent vestibular schwannoma hemorrhage. The authors also discuss the management issues involved in more than 1000 vestibular schwannomas treated at their institution during a 25-year period. Key Words * acoustic tumor * schwannoma * neuroma * hemorrhage * hemorrhagic vestibular tumor Vestibular schwannomas are the most common tumors found in the cerebellopontine angle (CPA), comprising approximately 80% of all tumors arising in this region. They are usually slow-growing, benign tumors that manifest clinically by directly compressing the neural elements traversing the CPA, including the pons, cerebellum, and the lower cranial nerves. Hemorrhage into a vestibular schwannoma is rare and has been shown to present with acute neurological changes and deterioration. We review the literature on the presenting symptoms of hemorrhagic vestibular schwannomas and describe the case of a man with a large hemorrhagic vestibular schwannoma who presented with signs and symptoms of a slow-growing, insidious compressive lesion. In doing so, we hope to shed light on this unusual clinical entity and discuss management issues.
    [Show full text]
  • Acoustic Neuroma (AKA Vestibular Schwannoma)
    Acoustic Neuroma (AKA Vestibular Schwannoma) What is a vestibular schwannoma? A vestibular schwannoma, also known as an acoustic neuroma, is a benign tumor of a balance nerve between your ear and brain. It originates from Schwann cells which cover this nerve. If you think of the nerve like a copper wire with rubber covering, Schwann cells are the equivalent of the rubber covering. Where exactly is this tumor? Depending on the size, it is in the internal auditory canal +/- the cerebellopontine angle. If you start in your ear canal and go straight toward the center of your head, on the other side of the inner ear you would be in the internal auditory canal. It houses four important nerves – the facial nerve (controls muscles on that side of your face), the cochlear nerve (hearing), and two vestibular nerves (balance). The cerebellopontine angle is a space between the internal auditory canal and your brain (specifically the pons, cerebellum, and temporal lobe). There are several other important nerves which go through this space. Is this cancer? No, and it cannot become cancer. Is this life threatening? Usually it is not, however if it grows to be large enough it can be. What symptoms does it cause? The symptoms are caused by compression of nerves the tumor pushes against. • Hearing loss in one ear – sudden or gradual • Tinnitus (ringing) • Imbalance or dizziness • Facial numbness • Facial weakness How can you know that it is a vestibular schwannoma without a biopsy? It is true that there is no way to know definitively without a biopsy, however we can often tell based on the MRI you had.
    [Show full text]
  • 2017 ESMO Essentials for Clinicians Neuro Oncology
    Epidemiology, pathogenesis and risk factors 1 of brain tumours Introduction; definition “Brain tumours” is the common term to define central nervous system (CNS) neoplasms, or CNS tumours. Brain tumours are not one entity, but diverse The global incidence of all CNS tumours is unknown but histological entities with higher than 45/100 000 patients a year. different causes, prognosis and treatments. The 2016 World Health Organization classification of CNS tumours is based on histopathological and molecular Brain criteria and includes malignant, benign and borderline Tumours tumours. They are categorised as primary or secondary. Glioma (frontal Glioma (cervico- glioblastoma) dorsal astrocytoma) Primary CNS tumours include all primary tumours located in the CNS, the envelopes of the CNS and the beginning of the nerves localised in the skull and spine. In the USA, the incidence rate of all primary malignant and non-malignant CNS tumours is 21.42/100 000 (7.25/100 000 for malignant and 14.17/100 000 for non-malignant tumours). In the USA, among the various histological groups of primary CNS tumours, meningiomas account for 36%, gliomas for 28%, nerve sheath tumours for 8% and lymphomas for 2%. Fronto-basal Vestibular schwannoma meningioma (neurinoma) Secondary CNS tumours are CNS metastases; they are all malignant. CNS metastases are single or multiple. Metastatic tumours are the most frequent type of CNS tumour in adults. The reported incidence of metastatic CNS tumours is increasing but the exact incidence is unknown. In general, the sources of brain metastases (in descending order) are: cancers of the lung, breast, skin (melanoma), kidney and gastrointestinal tract.
    [Show full text]
  • Current Understanding of Neurofibromatosis Type 1, 2, And
    International Journal of Molecular Sciences Review Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis Ryota Tamura Department of Neurosurgery, Kawasaki Municipal Hospital, Shinkawadori, Kanagawa, Kawasaki-ku 210-0013, Japan; [email protected] Abstract: Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for NF1, NF2, and SWN and reviews recent clinical trials which involve NF patients. Keywords: neurofibromatosis type 1; neurofibromatosis type 2; schwannomatosis; molecular tar- geted therapy; clinical trial Citation: Tamura, R. Current Understanding of Neurofibromatosis Int. Type 1, 2, and Schwannomatosis. 1. Introduction J. Mol. Sci. 2021, 22, 5850. https:// doi.org/10.3390/ijms22115850 Neurofibromatosis (NF) is a genetic disorder that causes multiple tumors on nerve tissues, including brain, spinal cord, and peripheral nerves [1–3].
    [Show full text]
  • Clinical Findings of Patients with Vestibular Schwannoma and Unilateral Tinnitus: a Case Study
    Global Journal of Otolaryngology ISSN 2474-7556 Case Report Glob J Otolaryngol Volume 2 Issue 5 - December 2016 Copyright © All rights are reserved by Shreemanti Chakrabarty DOI: 10.19080/GJO.2016.02.555600 Clinical Findings of Patients with Vestibular Schwannoma and Unilateral Tinnitus: A Case Study Shreemanti Chakrabarty* Doctor of Audiology, Southside Regional Medical Center, United States of America Submission: December 16, 2016; Published: December 30, 2016 *Corresponding author: Shreemanti Chakrabarty, Doctor of Audiology, Southside Regional Medical Center, Petersburg VA 23805, USA Abstract The symptoms, signs and clinical findings of a patient diagnosed with Vestibular Schwannoma with unilateral tinnitus are reviewed. The presence of the tumor was confirmed with Magnetic Resonance Imaging (MRI) to determine the size of the tumor. Correlation was found between the presence of hearing loss and subjective perception of tinnitus. Comprehensive diagnostic and vestibular testing was conducted to identify type and severity of hearing loss and vestibular weakness if any. Introduction and also to create information for a possible hearing aid fitting in the future. MRI revealed a tumor of size 0.66 mm in the right Vestibular schwannomais found to occur in 10 per internal auditory canal [4,5]. Videonystagmography revealed a million of the population per year [1]. The tumor is generally sporadic and unilateral, 4% of vestibular schwannoma cases hearing loss mostly unilateral, unilateral tinnitus, imbalance, unilateral caloric weakness of 25% in the right ear. Considering are bilateral with neurofibromatosis. The symptoms include all the clinical findings the patient was diagnosed with right surgical removal of tumor after monitoring the tumor for the There is not much information about the vertigo accompanying sided vestibular schawannoma.
    [Show full text]
  • Empirical Development of Improved Diagnostic Criteria for Neurofibromatosis 2 Michael E
    ARTICLE Empirical development of improved diagnostic criteria for neurofibromatosis 2 Michael E. Baser, PhD†1, Jan M. Friedman, MD, PhD2, Harry Joe, PhD3, Andrew Shenton, BSc†4, Andrew J. Wallace, PhD4, Richard T. Ramsden, FRCS5, and D. Gareth R. Evans, MD4 Purpose: Four sets of clinical diagnostic criteria have been proposed for patients with NF2 do not have bilateral VS at the time of initial 4 neurofibromatosis 2, but all have low sensitivity at the time of initial clinical evaluation. clinical assessment for the disease among patients with a negative Many patients with NF2 become symptomatic when tumors family history who do not present with bilateral vestibular schwanno- are relatively small, and early diagnosis can enhance clinical mas. We have empirically developed and tested an improved set of care in several ways: periodic magnetic resonance imaging diagnostic criteria that uses current understanding of the natural history (MRI) can be used to monitor tumor growth, and genetic coun- and genetic characteristics of neurofibromatosis 2 to increase sensitivity seling can be provided during the reproductive years. In some while maintaining very high specificity. Methods: We used data from cases, surgical excision of a vestibular tumor can be undertaken the UK Neurofibromatosis 2 Registry and Kaplan-Meier curves to before irreversible loss of hearing occurs, or decompression can estimate frequencies of clinical features at various ages among patients be performed to allow tumor growth without damaging adjacent with or without unequivocal neurofibromatosis 2. On the basis of this normal anatomy. analysis, we developed the Baser criteria, a new diagnostic system that Four sets of clinical diagnostic criteria have been proposed incorporates genetic testing and gives more weight to the most charac- for NF2 (Table 1), each based on expert opinion: criteria from teristic features and to those that occur before 30 years of age.
    [Show full text]