Patient case: 45-year-old female with Meningioma. Genetic variant: NF2 (K322), AKT1(E17K). Other conditions: None.

Clinical trial: Natural History Study of Patients With Neurofibromatosis Type 2

Summary: This study will examine over the long-term the progress of patients with neurofibromatosis Type 2 (NF2), a condition associated with tumors of the nerves, brain and spinal cord. It will study patients tumors to learn how fast they can grow and if certain factors might affect their growth. It will also examine the effects of the tumors on patients abilities to carry out activities of daily living.
  People between 8 and 75 years of age with NF2 may be eligible for this study. Participants undergo the following procedures:
  Initial evaluation, including hearing, eye and balance testing, gait (walk) testing, magnetic resonance imaging (MRI) scans of the brain and spine, blood tests, and physical and neurological examinations.
  MRI scans of the brain and spine every 6 months to follow the size and number of tumors.
  Physical and neurological examinations and blood tests every 6 months.
  Auditory tests every 12 months. These tests evaluate middle and inner ear function and the patient s ability to hear tones at different frequencies and to hear words at different volumes. The subject responds to tones and words that are delivered through earphones.
  Eye examination every 1 to 2 years.
  Gait testing every 12 months if a spinal cord tumor causes problems with sensation or muscle control in the arms and legs Subjects joints are measured while they walk across a room several times as scientific cameras record their movements.
  Vestibular testing if the patient experiences changes in balance or undergoes treatment for vestibular schwannoma (a tumor that develops on the hearing and balance nerves). These tests check the function of various components of the balance system (eyes, inner ear, or leg and body sensation and muscles). They include:
  -  Videoelectronystagmogram Tracks subjects eye movements while they follow moving red lights with their eyes.
  -  Vestibular evoked myogenic potential Assesses subjects neck muscle movements in response to noise.
  -  Posturography Determines which parts of the balance system the subject relies on most. Subjects stand on a platform and try to maintain their balance while changes are made to the platform and the environment.
  -  Rotary chair test Subjects eye movements are monitored as they follow red spots and strips of light with their eyes while seated in a rotary chair that turns side to side at several speeds.

Detailed description: Objective
  The objective of this prospective natural history study on neurofibromatosis type 2 (NF2) is to gain clinical and molecular insight into the effects of this tumor suppressor syndrome on tumor development and progression and to identify factors linked to symptom evolution.
  Study Population
  Two hundred fifty patients, ages 8-75, with a clinical or genetic diagnosis of NF2 will participate in this study.
  Design
  Study participants will be evaluated with a thorough physical and neurologic examination upon enrollment. This initial outpatient evaluation will include ophthalmologic examination, magnetic resonance imaging with contrast of the craniospinal axis, NF2 research blood procurement and serum biomarker testing. Patients with measurable hearing will have audiology assessment performed during the initial visit. Patients with untreated vestibular schwannomas will have vestibular assessment performed during the initial visit. Whole genome/whole exome sequencing may be performed on blood or tissue obtained from subjects enrolled in this study who have surgery under a related study.
  Patients with tumors that affect speech and swallowing production will be seen by a speech language pathologist at the following visit, where a standard clinical assessment of speech and swallowing function will be done. In patients with tumors that affect independent functioning associated with activities of daily living, a physical therapy and occupational therapy assessment will be performed at the following visit.
  Subjects will be followed as outpatients for five years, during which clinical, radiologic and serum biomarker evaluation will be performed annually. Auditory testing will be performed annually for patients with measurable hearing. Patients with initially untreated vestibular schwannomas will be followed annually with vestibular testing. Ophthalmologic evaluation will performed every one to three years, depending on the severity of ocular lesions. Peri-operative speech and swallowing reassessments will be performed as medically indicated, when tumors that may affect these abilities are treated. Functional status testing will be repeated peri-operatively and annually thereafter when tumors that may affect independent functioning are treated.
  If clinical symptoms attributable to any NF2-associated lesion are progressive in nature or warrant treatment intervention, testing may be repeated more frequently.
  Outcome measures
  Based on data derived from this study, we hope to identify factors that predict tumor development, forecast tumor growth and that underlie symptom formation. These findings should permit the safer treatment of the subset of tumors that will cause symptoms and avoid the unnecessary treatment of lesions that will remain stable (not requiring treatment) in these patients. Moreover, this prospective natural history study should be useful in identifying the stochastic factors that underlie the biology of these tumors.

Eligibility: -  INCLUSION CRITERIA:
  -  All patients will have the clinical diagnosis of NF2 by established clinical criteria or genetic testing.
  -  Males and females between the ages of 8 and 75.
  -  Capacity to undergo serial MRI scanning of the CNS.
  EXCLUSION CRITERIA:
  -  Clinically unstable condition that precludes serial clinical and imaging evaluation (i.e. Class 3 congestive heart failure, severe chronic renal insufficiency, severe chronic obstructive pulmonary disease).
  -  Allergy or relative contraindications to MRI contrast agents.
  -  Contraindication to MRI scanning such as surgery that involves metal clips or wires, which might be expected to cause tissue damage or produce image artifacts.
  -  Patients with severe chronic renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73 m2), hepatorenal syndrome or post-liver transplantation.
  -  Patients who are pregnant at time of intake visit.

Relevance to patient case: possibly relevant