Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Epilepsia. 2023 Sep;64(9):2385-2398. doi: 10.1111/epi.17695. Epub 2023 Jul 4.
Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures.
Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated.
Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures.
Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.
癫痫发作是副肿瘤性神经综合征的常见表现。本研究的目的是描述具有高风险副肿瘤自身抗体（>70%癌症相关性）的患者的癫痫发作特征和结局，并确定与持续癫痫发作相关的因素。
回顾性分析 2000 年至 2020 年期间有癫痫发作和高风险副肿瘤自身抗体的患者。评估最后一次随访时与持续癫痫发作相关的因素。
共确定 60 例患者（男性 34 例，发病时中位年龄 52 岁）。最常见的潜在抗体为 ANNA1-IgG（Hu；n=24，39%）、Ma2-IgG（n=14，23%）和 CRMP5-IgG（CV2；n=11，18%）。26 例（43%）患者以癫痫发作为首发症状，38 例（63%）存在恶性肿瘤。83%的患者癫痫发作持续>1 个月，60%的患者仍有持续癫痫发作，几乎所有患者（55/60，92%）在最后一次随访时仍在服用抗癫痫药物，中位时间为癫痫发作后 25 个月。与其他抗体相比，最后一次随访时持续癫痫发作与 Ma2-IgG 或 ANNA1-IgG 相关（p=0.04），最高癫痫发作频率至少为每日（p=0.0002）、脑电图（EEG）上有癫痫发作（p=0.03）和有边缘性脑炎（LE）的影像学证据（p=0.03）。在整个随访过程中，48%的患者死亡，LE 患者的死亡率高于无 LE 患者（p=0.04）。最后一次随访时存活的 31 例患者中，55%的患者仍间歇性发作。
具有高风险副肿瘤自身抗体的癫痫发作常对抗治疗有抵抗。持续癫痫发作与 ANNA1-IgG 和 Ma2-IgG、高癫痫发作频率以及 EEG 和影像学异常相关。尽管有一部分患者可能对抗免疫治疗有反应并实现癫痫无发作，但预后不良的情况经常发生。LE 患者的死亡率更高。
