Hashmi Syeda Amrah, Sachdeva Seerat, Sindhu Udeept, Tsai Carolyn, Bonda Kalyanchakradhar, Keezer Mark, Zawar Ifrah, Punia Vineet
Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Clinical Observer, Epilepsy Center, Cleveland Clinic, Cleveland, Ohio, USA.
Epilepsia Open. 2024 Dec;9(6):2128-2143. doi: 10.1002/epi4.13046. Epub 2024 Sep 9.
Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management.
由于全球人口结构的变化以及癫痫的自然病史，老年人在癫痫患者（PWE）中占很大比例。与衰老相关的病理生理变化会降低耐受性，并增加我们对应激源的易感性，这表现为虚弱。虚弱与不良健康结局密切相关。本叙述性综述探讨了虚弱与癫痫之间的相互作用，特别是在老年人中，强调了其临床意义，包括其在管理PWE中的作用。从机制上讲，虚弱是通过分子和细胞损伤之间的复杂相互作用发展而来的，包括基因组不稳定、线粒体功能障碍和激素变化。这些因素导致全身肌肉量、骨密度和器官功能下降。虚弱的概念已从主要的身体综合征演变为包括社会、心理和认知维度。关注身体表现的“表型虚弱”模型和量化健康缺陷的“缺陷积累”模型为理解和评估虚弱提供了框架。由于导致虚弱的风险因素患病率较高，PWE可能更容易出现虚弱。这些因素包括但不限于多种药物治疗、更高的合并症、低运动水平、社会隔离、低维生素D和骨质疏松症。我们缺乏用于测量虚弱的商业生物标志物，但可以使用自我或医疗服务提供者管理的虚弱量表进行诊断。最近开发PWE特异性虚弱量表的尝试很有前景。与实际年龄不同，虚弱是可逆的，因此应强烈考虑使用多学科护理团队对其进行管理。虚弱会因其对药代动力学和药效学的影响而影响抗癫痫药物（ASM）的耐受性。虽然虚弱对ASM癫痫控制疗效的影响尚不清楚，但其与包括癫痫手术在内的总体不良结局的明确关联促使我们在治疗老年PWE时考虑其存在和影响。在未来的研究中纳入虚弱测量对于提高我们对虚弱在PWE健康中的作用的理解至关重要。通俗易懂的总结：虚弱是人体机能下降的状态。癫痫患者更容易出现虚弱。在对他们的管理中应考虑到这一点。
