Department of Neurology, Tongji Hospital Affiliated To Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Blvd, Wuhan, 430030, People's Republic of China.
Department of Radiology, Tongji Hospital Affiliated To Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Psychopharmacology (Berl). 2022 Jan;239(1):173-184. doi: 10.1007/s00213-021-06004-5. Epub 2021 Oct 30.
Investigation of associated risk factors of valproic acid (VPA)-induced tremor helped in increasing tolerance and optimizing treatment scheme individually.
To determine the risk factors of VPA-induced tremor, with particular attention on identifying tremor-susceptible gene mutations.
Epileptic patients taking VPA were divided into a tremor and a non-tremor groups. A mutation of rs9652490 in the leucine-rich repeat and immunoglobulin domain-containing Nogo-receptor-interacting protein 1 (LINGO-1) gene was determined by Sanger sequencing. Cerebellar atrophy was assessed, and various cerebellar dimensions were measured on magnetic resonance imaging (MRI) scans.
One hundred and eighty-one of 200 subjects were included. Multivariate regression analysis indicated several VPA-induced tremor-related factors: females (OR = 2.718, p = 0.014), family history of tremor (OR = 7.595, p = 0.003), treatment duration (> 24 months; OR = 3.294, p = 0.002), and daily dosage (> 1,000 mg/d; OR = 19.801, p = 0.008) of VPA. Chi-square tests revealed that treatment with VPA magnesium-ER (p = 0.030) and carbamazepine combination (p = 0.040) reduced the incidence of tremor. One hundred and seventy-six gene sequencing and 86 MRI results excluded any significant difference between the two groups in the mutation of rs9652490 within LINGO-1, the ratio of cerebellar atrophy or the cerebellar-dimension values (p > 0.05). However, mutation of rs9652490 within LINGO-1 was correlated with increased cerebellar atrophy (p = 0.001), reduced cerebellar hemisphere thickness (p = 0.025), and right cerebellar hemisphere longitudinal diameter (p = 0.047).
Our cohort indicated risk (female, positive family history of tremor, daily dosage > 1000 mg and treatment duration > 24 months of VPA) and protective factors (VPA magnesium-ER and combination with CBZ) of VPA-induced tremor. Mutation of rs9652490 within LINGO-1 correlated with cerebellar atrophy, neither was correlated with VPA-induced tremor.
研究丙戊酸（VPA）诱导震颤的相关风险因素有助于提高耐受性和优化个体化治疗方案。
确定 VPA 诱导震颤的风险因素，特别关注识别震颤易感基因突变。
将服用 VPA 的癫痫患者分为震颤组和非震颤组。通过 Sanger 测序确定富含亮氨酸重复和免疫球蛋白域的 Nogo 受体相互作用蛋白 1（LINGO-1）基因中 rs9652490 突变。评估小脑萎缩，并在磁共振成像（MRI）扫描上测量各种小脑尺寸。
200 名受试者中有 181 名被纳入。多变量回归分析表明了一些与 VPA 诱导震颤相关的因素：女性（OR=2.718，p=0.014）、震颤家族史（OR=7.595，p=0.003）、治疗时间（>24 个月；OR=3.294，p=0.002）和 VPA 日剂量（>1000mg/d；OR=19.801，p=0.008）。卡方检验显示 VPA 镁 ER（p=0.030）和卡马西平联合治疗（p=0.040）降低了震颤的发生率。176 名基因测序和 86 名 MRI 结果排除了 LINGO-1 内 rs9652490 突变、小脑萎缩比例或小脑尺寸值在两组之间的任何显著差异（p>0.05）。然而，LINGO-1 内 rs9652490 突变与小脑萎缩增加（p=0.001）、小脑半球厚度减少（p=0.025）和右侧小脑半球纵向直径减少（p=0.047）相关。
我们的队列表明了 VPA 诱导震颤的风险因素（女性、震颤家族史阳性、VPA 日剂量>1000mg 和治疗时间>24 个月）和保护因素（VPA 镁 ER 和与 CBZ 联合治疗）。LINGO-1 内 rs9652490 突变与小脑萎缩相关，与 VPA 诱导震颤无关。
