Hussain Shaun A, Tsao Jackie, Li Menglu, Schwarz Madeline D, Zhou Raymond, Wu Joyce Y, Salamon Noriko, Sankar Raman
Division of Pediatric Neurology, David Geffen School of Medicine and Mattel Children's Hospital UCLA, Los Angeles, California, U.S.A.
School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia, U.S.A.
Epilepsia. 2017 Apr;58(4):674-682. doi: 10.1111/epi.13712. Epub 2017 Feb 23.
Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible-and largely asymptomatic-signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena.
Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure.
We identified 507 brain MRI studies among 257 patients with infantile spasms. VGB treatment was documented in 143 children, with detailed exposure data available for 104, of whom 45 had at least one MRI study during VGB treatment. Among the limited subset of asymptomatic children who underwent MRI (n = 40), 6 exhibited VABAM. Risk of asymptomatic VABAM was dose-dependent, as peak (but not cumulative) VGB dosage was strongly associated with asymptomatic VABAM (p = 0.0028). In an exploratory analysis, we encountered 4 children with symptomatic VABAM among 104 patients with detailed VGB exposure data. Risk of symptomatic VABAM was seemingly dose-independent, and potentially associated with concomitant hormonal therapy (i.e., prednisolone and adrenocorticotropic hormone [ACTH]) (p = 0.039).
We have demonstrated dose-dependent risk of asymptomatic VABAM and uncovered a possible association between symptomatic VABAM and concomitant hormonal therapy. Caution should be exercised in the use of high VGB dosage (i.e., >175 mg/kg/day), and further study is warranted to confirm the potential impact of hormonal therapy.
尽管氨己烯酸（VGB）与视网膜毒性之间的联系已广为人知，但很少有人关注VGB相关脑异常在磁共振成像（MRI）上的风险（VABAM），即丘脑、基底神经节、脑干被盖和小脑核中可逆且大多无症状的信号变化。我们利用一个大型婴儿痉挛症队列，着手确定这些现象的预测因素。
对婴儿痉挛症患儿进行回顾性识别。在不知道是否接触VGB的情况下，对脑部MRI报告进行系列审查。发现VABAM后，系统审查记录以确定是否存在可归因于VGB的症状。另外，依次审查病程记录以识别和量化VGB暴露情况。
我们在257例婴儿痉挛症患者中识别出507项脑部MRI研究。143名儿童有VGB治疗记录，其中104名有详细的暴露数据，45名在VGB治疗期间至少进行了一次MRI研究。在接受MRI检查的无症状儿童有限子集中（n = 40），6例出现VABAM。无症状VABAM的风险呈剂量依赖性，因为VGB峰值（而非累积）剂量与无症状VABAM密切相关（p = 0.0028）。在一项探索性分析中，在104例有详细VGB暴露数据的患者中，我们遇到4例有症状的VABAM患儿。有症状VABAM的风险似乎与剂量无关，且可能与同时进行的激素治疗（即泼尼松龙和促肾上腺皮质激素[ACTH]）有关（p = 0.039）。
我们已证明无症状VABAM存在剂量依赖性风险，并发现有症状VABAM与同时进行的激素治疗之间可能存在关联。使用高剂量VGB（即>175 mg/kg/天）时应谨慎，有必要进一步研究以确认激素治疗的潜在影响。
