Epilepsy Program, Pablo Tobón Uribe Hospital, Neuroclinica, University of Antioquia, Medellín, Colombia.
Epilepsy Department, Neuromédica, Medellín, Colombia.
Epilepsia. 2019 Aug;60(8):1610-1618. doi: 10.1111/epi.16276. Epub 2019 Jul 1.
Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition.
We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data.
Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery.
Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.
强制正常化（FN）是一种引人关注的现象，其特征为先前未经控制的癫痫患者在癫痫发作得到控制或减少时出现精神障碍。本研究旨在描述这种情况的临床特征。
我们对 MEDLINE、EMBASE、Cochrane 和 Scielo 进行了系统综述，检索时间范围为 1953 年 1 月至 2018 年 1 月。收集了临床、脑电图和影像学数据。我们考虑了所有儿童和成人的结果。由于可用数据有限，我们没有进行荟萃分析。
在 2606 篇摘要中，有 36 篇符合 FN 的诊断标准；评估了 193 次 FN 发作，其中 77 次进行了广泛分析。60%的病例为女性。平均年龄±标准差（SD）为 28.3±14.2 岁。大多数患者为局灶性（80%）症状性（44%）癫痫。大多数患者报告高发作频率（58%）和多药治疗（51%）。患者主要表现为精神病（86.4%）、情绪障碍（25.8%）和分离（4.5%）。在精神病组中，常出现被害妄想（52.6%）和关系妄想（47.3%）。FN 由抗癫痫药物（AED）（48.5%）引起，主要是左乙拉西坦，癫痫手术（31.8%）或迷走神经刺激（13.6%）引起。治疗方法相同，包括抗惊厥药物停药（47%）或减量（25%）；大多数病例开始使用抗精神病药物（73%）。在 35%的患者中，精神症状部分得到控制，65%的患者症状完全缓解。与手术触发的 FN 相比，用 AED 触发并停药的患者中（87%）有 87%的患者症状完全缓解。
FN 是一种其病理生理学仍不确定的实体。与 AED 停药相比，抗精神病药物的使用并不能预测精神症状的完全缓解。尽管药物触发的 FN 患者对治疗有积极反应，但手术触发的 FN 患者的预后仍不清楚。
