Evolution of epilepsy comorbidities in seizure free patients: Is no seizure a synonym of no epilepsy?

Epilepsy is a prevalent neurological disorder, with most patients achieving seizure freedom through antiseizure medications (ASM). However, being seizure-free does not necessarily equate to being free from epilepsy-related comorbidities. This review explores the persistence of psychiatric, cognitive, and social challenges in seizure-free patients and their impact on quality of life (QoL). Seizure-free patients generally report a better QoL than those with active epilepsy, with scores approaching those of the general population. However, detailed analyses reveal impairments in specific subdomains, such as emotional well-being, energy levels, and employment concerns. The most significant determinants of QoL in seizure-free patients include ASM side effects, psychiatric symptoms, and social functioning. Notably, polytherapy is associated with a poorer QoL. After epilepsy surgery, improvements in QoL are well documented, especially in the first two years postoperatively. However, for some patients, achieving seizure freedom does not necessarily result in significant QoL improvements, often due to persistent psychiatric or cognitive impairments. Psychiatric comorbidities, particularly depression and anxiety, remain a significant determinant of QoL in seizure-free patients, sometimes exerting a greater influence than seizure control itself. Depression is significantly more prevalent in patients treated with ASMs, especially those on polytherapy. After surgery, 15-45% of patients achieve remission from psychiatric disorders, particularly those who become seizure-free. Cognitive deficits could persist in seizure-free patients, particularly in those on ASMs. Studies have reported impairments in verbal fluency, memory, and processing speed, especially in patients with magnetic resonance imaging lesions or early epilepsy onset. ASM withdrawal has been associated with improved verbal fluency, psychomotor speed, and attention in some patients, but not necessarily in overall QoL. After epilepsy surgery, cognitive outcomes vary, with verbal memory decline being the most concerning effect, particularly after left-sided resections. However, some patients experience cognitive improvements, particularly in executive functioning and IQ in children. Importantly, QoL improvements post-surgery are generally independent of cognitive changes, as long as seizure control is achieved. Seizure freedom positively impacts employment, with studies reporting that seizure-free patients are significantly more likely to obtain or retain full-time employment. However, barriers remain, including stigma and employer perceptions of epilepsy. Driving ability is crucial to patient independence, with up to 80% of seizure-free patients regaining their license. While most seizure-free patients achieve financial and residential independence, social adaptation can be challenging. Some patients and families struggle with the "burden of normality," which describes difficulties adjusting to life without epilepsy. This can lead to strained family dynamics and, in some cases, divorce. Achieving seizure freedom is a critical goal, but it is not synonymous with complete recovery from epilepsy-related burdens. A comprehensive approach, including psychiatric, cognitive, and social assessments, is essential to optimize the well-being of seizure-free patients.

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