Department of Neurology, Odense University Hospital, Odense, Denmark.
BRIDGE - Brain Research Inter Disciplinary Guided Excellence, Odense University Hospital, Odense, Denmark.
Epilepsia Open. 2024 Jun;9(3):1088-1095. doi: 10.1002/epi4.12944. Epub 2024 Apr 18.
The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital. Clinical characteristics and seasonality of patients fulfilling the diagnostic criteria for NORSE were compared with patients with refractory SE (RSE) due to other reasons and with the seasonal variation of autoantibodies associated with autoimmune encephalitis in the Danish autoimmune encephalitis register. In this cohort, 26 patients met NORSE criteria. As compared to RSE patients not fulfilling NORSE criteria (n = 152), NORSE patients were more likely to have symptoms of systemic inflammation (C-reactive protein concentrations ≥10 mg/L or fever ≥38°C) at admission; nine fulfilled the criteria for febrile infection related epilepsy syndrome (FIRES). In contrast to the even seasonal distribution of patients with RSE not fulfilling the NORSE criteria, admissions due to NORSE peaked during the winter (46.1%, p = 0.04 as compared to non-NORSE RSE); six out of nine FIRES episodes occurred in the winter season. The seasonal variation was not explained by a seasonal variation of the detection rates of autoantibodies associated with autoimmune encephalitis (incl. NMDAR, LGI1, CASPR2, GABAR, GFAP) in a Danish nationwide register (n = 259). In conclusion, we confirm the seasonality of NORSE in a Danish cohort, however, with a peak during winter suggesting a geographical variation not solely explained by autoimmune encephalitis associated with known autoantibodies. PLAIN LANGUAGE SUMMARY: The study investigated the seasonal patterns of new-onset refractory status epilepticus (NORSE), i.e. severe seizures that occur without an obvious cause and require very intensive treatment. In contrast to the previously observed peak frequency in summer, this Danish study found that NORSE cases peak in winter. Furthermore, the seasonal variation in NORSE cases was not found to be associated with autoimmune encephalitis caused by known autoantibodies. Together with the high rate of patients showing symptoms of systemic inflammation compared to other status epilepticus patients, the data suggest a link between misdirected immune system responses and NORSE. The study can therefore help in the further search for the currently unknown causes of NORSE.
新起难治性癫痫持续状态（NORSE）的发病机制通常不明确。最近，一项成人和儿童混合队列的研究表明，NORSE 存在季节性变化，夏季高发。因此，我们在此研究了丹麦癫痫持续状态（SE）队列的季节性变化。这项回顾性队列研究纳入了 2008 年至 2017 年在奥登塞大学医院诊断和治疗的年龄≥18 岁的 SE 患者。我们比较了符合 NORSE 诊断标准的患者与因其他原因导致难治性 SE（RSE）的患者以及丹麦自身免疫性脑炎登记处中与自身免疫性脑炎相关的自身抗体的季节性变化。在该队列中，26 例患者符合 NORSE 标准。与不符合 NORSE 标准的 RSE 患者（n=152）相比，NORSE 患者入院时更有可能出现全身炎症症状（C 反应蛋白浓度≥10mg/L 或发热≥38°C）；9 例符合发热性感染相关癫痫综合征（FIRES）标准。与不符合 NORSE 标准的 RSE 患者均匀的季节性分布相反，NORSE 患者的入院高峰出现在冬季（46.1%，与非 NORSE RSE 相比，p=0.04）；9 例 FIRES 发作中有 6 例发生在冬季。这种季节性变化不能用丹麦全国性登记处（n=259）中与自身免疫性脑炎相关的自身抗体（包括 NMDAR、LGI1、CASPR2、GABAR、GFAP）检测率的季节性变化来解释。总之，我们在丹麦队列中证实了 NORSE 的季节性，但冬季高峰表明存在地域差异，这不仅仅是由与已知自身抗体相关的自身免疫性脑炎引起的。
