Stevering Carmen, Lequin Maarten, Szczepaniak Kinga, Sadowski Krzysztof, Ishrat Saba, De Luca Alberto, Leemans Alexander, Otte Willem, Kwiatkowski David J, Curatolo Paolo, Weschke Bernhard, Riney Kate, Feucht Martha, Krsek Pavel, Nabbout Rima, Jansen Anna, Wojdan Konrad, Sijko Kamil, Glowacka-Walas Jagoda, Borkowska Julita, Domanska-Pakiela Dorota, Moavero Romina, Hertzberg Christoph, Hulshof Hanna, Scholl Theresa, Petrák Bořivoj, Maminak Miroslav, Aronica Eleonora, De Ridder Jessie, Lagae Lieven, Jozwiak Sergiusz, Kotulska Katarzyna, Braun Kees, Jansen Floor
Department of Pediatric Neurology, University Medical Center Utrecht Brain Center, Utrecht, The Netherlands.
Department of Radiology, University Medical Center, Utrecht, The Netherlands.
Epilepsia. 2025 Feb;66(2):356-368. doi: 10.1111/epi.18190. Epub 2024 Dec 6.
Previous retrospective studies have reported vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), although clinical impact is unknown. We evaluated the association between vigabatrin and predefined brain magnetic resonance imaging (MRI) changes in a large homogenous tuberous sclerosis complex (TSC) cohort and assessed to what extent VABAM-related symptoms were reported in TSC infants.
The Dutch TSC Registry and the EPISTOP cohort provided retrospective and prospective data from 80 TSC patients treated with vigabatrin (VGB) before the age of 2 years and 23 TSC patients without VGB. Twenty-nine age-matched non-TSC epilepsy patients not receiving VGB were included as controls. VABAM, specified as T2/fluid-attenuated inversion recovery hyperintensity or diffusion restriction in predefined brain areas, were examined on brain MRI before, during, and after VGB, and once in the controls (at approximately age 2 years). Additionally, the presence of VABAM accompanying symptoms was evaluated.
Prevalence of VABAM in VGB-treated TSC patients was 35.5%. VABAM-like abnormalities were observed in 13.5% of all patients without VGB. VGB was significantly associated with VABAM (risk ratio [RR] = 3.57, 95% confidence interval [CI] = 1.43-6.39), whereas TSC and refractory epilepsy were not. In all 13 VGB-treated patients with VABAM for whom posttreatment MRIs were available, VABAM entirely resolved after VGB discontinuation. The prevalence of symptoms was 11.7% in patients with VABAM or VABAM-like MRI abnormalities and 4.3% in those without, implicating no significant association (RR = 2.76, 95% CI = .68-8.77).
VABAM are common in VGB-treated TSC infants; however, VABAM-like abnormalities also occurred in children without either VGB or TSC. The cause of these MRI changes is unknown. Possible contributing factors are abnormal myelination, underlying etiology, recurrent seizures, and other antiseizure medication. Furthermore, the presence of VABAM (or VABAM-like abnormalities) did not appear to be associated with clinical symptoms. This study confirms that the well-known antiseizure effects of VGB outweigh the risk of VABAM and related symptoms.
既往回顾性研究报告了 vigabatrin 相关的脑磁共振成像异常（VABAM），但其临床影响尚不清楚。我们在一个大型同质性结节性硬化症（TSC）队列中评估了 vigabatrin 与预定义的脑磁共振成像（MRI）变化之间的关联，并评估了 TSC 婴儿中报告的 VABAM 相关症状的程度。
荷兰 TSC 登记处和 EPISTOP 队列提供了 80 例 2 岁前接受 vigabatrin（VGB）治疗的 TSC 患者以及 23 例未接受 VGB 治疗的 TSC 患者的回顾性和前瞻性数据。纳入 29 例年龄匹配、未接受 VGB 治疗的非 TSC 癫痫患者作为对照。VABAM 定义为预定义脑区的 T2/液体衰减反转恢复高信号或扩散受限，在 VGB 治疗前、治疗期间和治疗后对脑 MRI 进行检查，对照组仅检查一次（约 2 岁时）。此外，评估是否存在 VABAM 伴随症状。
接受 VGB 治疗的 TSC 患者中 VABAM 的患病率为 35.5%。在所有未接受 VGB 治疗的患者中，13.5%观察到类似 VABAM 的异常。VGB 与 VABAM 显著相关（风险比[RR]=3.57，95%置信区间[CI]=1.43 - 6.39），而 TSC 和难治性癫痫与 VABAM 无关。在所有 13 例接受 VGB 治疗且有 VABAM 且有治疗后 MRI 资料的患者中，停用 VGB 后 VABAM 完全消失。有 VABAM 或类似 VABAM 的 MRI 异常的患者中症状患病率为 11.7%，无此类异常的患者中为 4.3%，两者无显著关联（RR = 2.76，95%CI = 0.68 - 8.77）。
VABAM 在接受 VGB 治疗的 TSC 婴儿中很常见；然而，类似 VABAM 的异常也发生在未接受 VGB 治疗或无 TSC 的儿童中。这些 MRI 变化的原因尚不清楚。可能的促成因素包括髓鞘形成异常、潜在病因、癫痫复发和其他抗癫痫药物。此外，VABAM（或类似 VABAM 的异常）的存在似乎与临床症状无关。本研究证实，VGB 众所周知的抗癫痫作用超过了 VABAM 及相关症状的风险。
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