Enhancing Facial Nerve Neuroprotection and Regeneration Through Omega-3 Supplementation Following Vestibular Schwannoma Resection
Enhancing Facial Nerve Neuroprotection and Regeneration Through Omega-3 Supplementation Following Vestibular Schwannoma Resection
The purpose of this research is to develop a therapeutic agent to help improve facial nerve outcomes and ultimately improve long-term quality-of-life following surgical resection of vestibular schwannomas. It is possible the therapeutic agent may impact tumor control rates as well, and this will also be studied. Using rigorous scientific methods, we will assess whether these factors are impacted by the treatment agent (Omega-3) versus placebo control (cellulose).
Vestibular schwannomas (VS) are common, often-benign intracranial neoplasms, however surgical resection carries high risk of causing neurologic impairments that may severely impact patient quality-of-life. The most morbid common postoperative deficit is facial weakness due to the close anatomic proximity of VS with the facial nerve, which is frequently stretched and attenuated by the tumor itself, and subject to additional mechanical stress during surgery. In addition to disfiguring cosmesis, facial weakness carries the secondary effects of abnormal speech, ocular morbidity from inadequate eye closure and corneal lubrication, and dysfunctional swallowing mechanics. Some patients may eventually recover partial facial nerve function; however, this is an unreliable process that proceeds slowly over months to years, if at all. At present, no pharmacologic avenue exists for promoting facial nerve neuroprotection or regeneration. Correspondingly, the development of a therapeutic agent to stimulate improved facial nerve outcomes would markedly enhance patient outcomes and quality-of-life.
In the anterior skull base, loss of olfaction is a common sequela of following endoscopic surgical resection due to direct nerve manipulation, impacting approximately 25% of patients who undergo endoscopic endonasal tumor resection. In a recent randomized clinical trial, postoperative supplementation with omega-3 yielded a significant, sustained 1-2-point improvements on the University of Pennsylvania Smell Identification Test as assessed at six weeks, three months, and six months post-operatively. Although mechanistic understanding of the relationship between omega-3 supplementation and olfactory function preservation is incompletely understood, preliminary data support the hypothesis of direct neural regeneration and/or neuro-protective effects through anti-demyelination effects. More specifically, polyunsaturated fatty acids have been shown to modulate neural plasticity and provide a protective role in maintaining functional neuronal cell membranes thought to be critical for maintaining nerve connectivity and function. It is also possible that omega-3, a known anti-inflammatory agent through reducing local IL-6, TNF, NFkB, impacts the innate immune system to mitigate demyelination and other destructive post-treatment inflammatory injuries to cranial nerves and surrounding support cells. Given the highly interrelated mechanisms-of-injury resulting in olfactory deficit after anterior skull base surgery and facial weakness after VS resection, application of omega-3 fatty acids may provide similar benefits with respect to facial nerve protection and/or rehabilitation. As a fascinating aside, new pre-clinic animal model evidence also suggests that omega-3 fatty acid supplementation may result in delayed progression in a neuroblastoma xenograft model. These effects are attributed to anti-inflammatory and anti-angiogenic effects via anti-VEGF and other anti-proliferative growth factors; factors also implicated in VS pathophysiology, suggesting that omega-3 may also impact early tumor control as well. We hypothesize that post-operative omega-3 supplementation will improve facial nerve function following resection of vestibular schwannomas and enhance early tumor control rates.
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