黑料网

Immune-checkpoint inhibitors (ICIs), such as anti-PD-1 [1] anti-PD-L1, and anti-CTLA-4 agents, have transformed the landscape of cancer treatment by enhancing the body's immune response against tumors. While these therapies have shown remarkable efficacy across a range of cancers, their use has been linked to a variety of immune-related adverse events (irAEs). Neurological toxicities represent a particularly challenging subset of these irAEs, as they can significantly impact patient quality of life and complicate treatment regimens.  adverse events associated with ICI therapy encompass a wide range of conditions, including but not limited to encephalitis [2], meningitis, peripheral neuropathy, myasthenia gravis, and other central and peripheral nervous system disorders. The pathophysiology underlying these toxicities is complex and often involves immune-mediated mechanisms that can lead to both direct and indirect neuronal damage. The recognition and management of neurological toxicities present unique challenges. Symptoms may be subtle or overlap with other conditions, making early diagnosis difficult. Furthermore, the management of these adverse events requires a multidisciplinary approach, incorporating neurology, oncology, and immunology expertise [3].

This review aims to provide a comprehensive overview of the characterization and management of neurological toxicities in patients undergoing ICI therapy. By exploring the latest research, clinical experiences, and management strategies, we aim to enhance understanding and improve outcomes for patients experiencing these challenging adverse effects [4].

Characterization of neurological toxicities

Understanding the diverse range of neurological toxicities associated with ICIs is critical for effective management. Encephalitis, often presenting with symptoms such as confusion, seizures, and cognitive dysfunction, can be particularly challenging due to its acute onset and potential for severe outcomes. Peripheral neuropathy, characterized by sensory and motor dysfunction, can lead to considerable morbidity and may require modifications to the treatment regimen. Myasthenia gravis and other neuromuscular disorders, while less common, can also arise and require specialized management [5].

Pathophysiological mechanisms

The pathophysiological mechanisms underlying these toxicities are complex and not fully understood. Proposed mechanisms include immune-mediated damage to neural tissues, disruption of the blood-brain barrier, and systemic inflammation. Continued research is needed to elucidate these mechanisms and identify biomarkers that may predict susceptibility to neurological adverse events [6].

Management strategies

Management of neurological toxicities involves early recognition and prompt intervention. A multidisciplinary approach is essential, involving oncologists, neurologists, and other specialists as needed. Initial management often includes corticosteroids and other immunosuppressive agents, but treatment should be tailored to the specific type and severity of the toxicity. In some cases, temporary discontinuation of ICI therapy may be necessary, followed by careful re-evaluation before resuming treatment. Supportive care and rehabilitation also play a crucial role in managing the long-term effects of neurological toxicities. Collaboration with rehabilitation specialists can help address functional impairments and improve patient outcomes.

Neurological adverse events (NAEs)

These are a notable concern in the context of immune-checkpoint inhibitor (ICI) therapy. These events encompass a range of symptoms and conditions affecting the central and peripheral nervous systems. Here’s an overview of common neurological adverse events, their clinical presentation, and management strategies:

Discussion

The emergence of neurological toxicities during immune-checkpoint inhibitor (ICI) therapy underscores the need for heightened awareness and a multidisciplinary approach to patient management. Neurological adverse events, including encephalitis, peripheral neuropathy, and myasthenia gravis, can significantly impact patient quality of life and complicate the overall treatment strategy.

Conclusion

Neurological toxicities associated with immune-checkpoint inhibitors represent a significant challenge in oncology practice. Their diverse presentations and complex pathophysiological mechanisms necessitate a comprehensive understanding and a coordinated approach to management. Early recognition, prompt intervention, and a multidisciplinary care model are essential for optimizing patient outcomes. Future research should focus on better defining the risk factors for neurological toxicities, improving diagnostic tools, and developing targeted therapies to mitigate these adverse effects. Advances in understanding the mechanisms underlying these toxicities will be crucial in enhancing the safety and efficacy of ICI therapies, ultimately benefiting patients and improving their overall quality of life.

1. Fredriksen-Goldsen KI, Kim H-J, Bryan AE, Shiu C, Emlet CA (2017).Gerontologist 57:72-83.

, , Crossref

2. Jessen F, Amariglio RE, Van Boxtel M, Breteler M, Ceccaldi M, et al. (2014) .Alzheimers Dement10: 844-852.

, , Crossref

3. McCracken M, DeHaan G, Obedin-Maliver J (2022) .Curr Opin Obstet34: 62-68.

, , Crossref

4. Institute of Medicine, Board on the Health of Select Populations, Committee on Lesbian, Gay, Bisexual, and Transgender Health Issues and Research Gaps and Opportunities (2011) .聽 National Academies Press (US), Washington (DC), USA.

, , Crossref

5. Dragon CN, Guerino P, Ewald E, Laffan AM (2017) .LGBT Health4: 404-411.

, , Crossref

6. .