Neurooncology of Benign Central and Peripheral Nervous System Tumors

良性中枢和周围神经系统肿瘤的神经肿瘤学

• 批准号: 10265222
• 负责人: Prashant Chittiboina
• 金额: $ 15.07万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10265222
• 关键词: 22q; Affect; Benign; Biological; Biological Markers; Central Nervous System Neoplasms; Clinical assessments; Code; Counseling; Cranial Nerves; Cross-Sectional Studies; Deglutition; Development; Disease Progression; Ependymoma; Excision; Fascicle; Functional disorder; Future; Genes; Germ-Line Mutation; Glioma; Growth; Hearing; Image; Infratentorial Neoplasms; Knowledge; Longterm Follow-up; Magnetic Resonance Imaging; Measurement; Medical; Methods; Monitor; Morbidity - disease rate; Natural History; Nature; Neoplasms; Nerve; Nervous system structure; Neurilemmoma; Neurofibromatosis 2; Neurofibromin 2; Neurologic Deficit; Neuropathy; Numbness; Operative Surgical Procedures; Paralysed; Patients; Pattern; Perilymph; Peripheral Nerve Schwannoma; Peripheral Nerves; Peripheral Nervous System; Peripheral Nervous System Diseases; Peripheral Nervous System Neoplasms; Plant Roots; Population; Proteins; Reporting; Resolution; Risk; Serum; Speech; Spinal nerve structure; Structure; Symptoms; Syndrome; Therapeutic; Time; Treatment outcome; Tumor Biology; Tumor Burden; Tumor Suppressor Genes; Uncertainty; Vestibular Nerve; base; bilateral vestibular Schwannoma; cohort; deafness; hearing impairment; imaging biomarker; meningioma; neoplastic cell; nerve injury; neuro-oncology; prevent hearing loss; prospective; tool; tumor; tumor growth

This ongoing natural history study has resulted in significant improvements in the understanding how NF2 affects patients. We found that central nervous system tumors in NF2 demonstrate a stepwise growth pattern. We also found that these tumors are made of many different populations of tumor cells. These findings emphasize the need for long term follow up of patients with NF2 to evaluate disease progression. Patients with NF2 have symptoms that significantly affect their lives such as hearing loss and speech/swallowing dysfunction. This natural history study has helped us understand how these symptoms arise even when the tumors are very small or quiescent. These findings will help clinicians find better ways to prevent hearing loss and to counsel patients about speech and swallowing problems. We now hope to understand the biologic basis for speech and swallowing dysfunction in patients with NF2. We will study and report the strength of association of MRI findings, clinical assessments cranial nerve deficits and speech/swallowing dysfunction. We hope to identify imaging biomarkers of hearing loss in NF2. We will attempt to discover the mode of peripheral neuropathy in patients with NF2. Lastly, we will attempt to discover previously unknown serum biomarkers associated with high tumor burden in NF2. Using the current cohort of subjects with NF2, we confirmed the presence of increased protein within perilymph by MRI imaging as FLAIR hyperintensity.36 In this cross sectional study, a close correlation between increased protein and hearing loss was demonstrated. This study validated MRI imaging as a method to detect increased protein within perilymph, and as a marker for hearing loss. We now have a convenient, non-invasive tool for monitoring of perilymph protein content. MRI imaging can be performed repeatedly and over long periods to detect changes in perilymph protein with time and with changes in hearing. In another analysis, we found that a large proportion of patients with NF2 report speech and swallow deficits that are not evident on objective measurements. We also found hypoglossal neuropathy unrelated to prior surgical interventions. Our findings suggest that swallowing and speech in problems in NF2 are associated with lower cranial nerve neuropathy, some due to compressive effects of posterior fossa tumors. We found that patients with NF2 present with neuropathy related to peripheral nerve schwannomas as well as unexplained EMG/NCS findings. In instances of distinct schwannoma growth along peripheral nerves, nerve fascicle sparing surgical resection leads to resolution of neuropathic symptoms. EMG/NCS studies and imaging helps guide the management of NF2 patients with high degree of certainty.

这项正在进行的自然历史研究显着提高了人们对 NF2 如何影响患者的理解。我们发现 NF2 中的中枢神经系统肿瘤表现出逐步生长模式。我们还发现这些肿瘤是由许多不同的肿瘤细胞群组成的。 这些发现强调需要对 NF2 患者进行长期随访以评估疾病进展。 NF2 患者的症状会严重影响他们的生活，例如听力丧失和言语/吞咽功能障碍。这项自然史研究帮助我们了解即使肿瘤非常小或处于静止状态，这些症状也是如何出现的。这些发现将帮助临床医生找到更好的方法来预防听力损失，并就言语和吞咽问题向患者提供咨询。 我们现在希望了解 NF2 患者言语和吞咽功能障碍的生物学基础。我们将研究并报告 MRI 结果、临床评估脑神经缺陷和言语/吞咽功能障碍之间的关联强度。我们希望识别 NF2 听力损失的影像生物标志物。我们将尝试发现 NF2 患者周围神经病变的模式。最后，我们将尝试发现与 NF2 高肿瘤负荷相关的先前未知的血清生物标志物。 使用当前 NF2 受试者队列，我们​​通过 MRI 成像证实外淋巴内存在蛋白质增加，称为 FLAIR 高信号。36 在这项横断面研究中，证明了蛋白质增加与听力损失之间的密切相关性。这项研究验证了 MRI 成像作为检测外淋巴内蛋白质增加的方法以及作为听力损失的标志物的方法。我们现在拥有一种方便、非侵入性的工具来监测外淋巴蛋白含量。 MRI 成像可以长期重复进行，以检测外淋巴蛋白随时间和听力变化的变化。 在另一项分析中，我们发现很大一部分 NF2 患者存在言语和吞咽缺陷，而客观测量结果并不明显。我们还发现舌下神经病变与之前的手术干预无关。我们的研究结果表明，NF2 中的吞咽和言语问题与下颅神经神经病变有关，部分原因是后颅窝肿瘤的压迫作用。 我们发现 NF2 患者出现与周围神经鞘瘤相关的神经病变以及无法解释的 EMG/NCS 结果。在神经鞘瘤沿着周围神经生长的情况下，保留神经束的手术切除可以缓解神经病理性症状。 EMG/NCS 研究和影像学有助于高度确定地指导 NF2 患者的治疗。