Neurooncology of Benign Central and Peripheral Nervous System Tumors

这项正在进行的自然历史研究在理解NF2如何影响患者方面取得了重大进展。我们发现NF2的中枢神经系统肿瘤呈阶梯式生长。我们还发现，这些肿瘤是由许多不同群体的肿瘤细胞组成的。这些发现强调了对NF2患者进行长期随访以评估疾病进展的必要性。NF2患者的症状会严重影响他们的生活，如听力损失和言语/吞咽功能障碍。这项自然历史研究帮助我们了解了即使在肿瘤非常小或静止的情况下，这些症状是如何产生的。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。我们将研究和报告MRI表现、临床评估、脑神经缺陷和言语/吞咽功能障碍之间的相关性。我们希望找出NF2患者听力损失的成像生物标志物。我们将尝试发现NF2患者周围神经病变的模式。最后，我们将尝试发现以前未知的血清生物标记物与NF2的高肿瘤负荷相关。 使用当前的NF2受试者队列，我们通过MRI成像证实外淋巴中存在FLAIR高信号的蛋白质增加。36在这项横断面研究中，蛋白质增加与听力损失密切相关。这项研究验证了MRI成像是一种检测外淋巴液中蛋白质增加的方法，并作为听力损失的标志。我们现在有了一种方便的、非侵入性的工具来监测外淋巴蛋白质含量。核磁共振成像可以在长时间内重复进行，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患者报告了在客观测量中不明显的言语和吞咽障碍。我们还发现舌下神经病与先前的手术干预无关。我们的研究结果表明，NF2患者吞咽和说话问题与下颅神经病变有关，其中一些是由于后颅窝肿瘤的压迫效应。 我们发现NF2患者存在与周围神经神经鞘瘤相关的神经病变，以及原因不明的EMG/NCS表现。在周围神经有明显神经鞘瘤生长的病例中，保留神经束的手术切除可缓解神经病变症状。EMG/NCS研究和成像有助于高度确定地指导NF2患者的治疗。

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.