Refractory Seizures During Sodium Valproate Therapy: A Case Report on Recognition of the Drug-Related Pitfall in MELAS

doi:10.3969/j.issn.1673-5765.2026.04.014

Chinese Journal of Stroke ›› 2026, Vol. 21 ›› Issue (4): 508-516.DOI: 10.3969/j.issn.1673-5765.2026.04.014

Refractory Seizures During Sodium Valproate Therapy: A Case Report on Recognition of the Drug-Related Pitfall in MELAS

TAN Qingjing¹, HUANG Meihua², LIU Yanfang³, ZHOU Heng³, CHEN Weiqi³, WANG Yilong^{3,4,5,6,7,8,9}

1Department of Neurology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China
2The First Clinical Faculty of Guangxi University of Chinese Medicine, Nanning 530001, China
3Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
4Chinese Institute for Brain Research, Beijing 102206, China
5National Center for Neurological Disorders, Beijing 100070, China
6Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100070, China
7China National Clinical Research Center for Neurological Diseases, Beijing 100070, China
8Beijing Laboratory of Oral Health, Beijing 100069, China
9Tiantan Clinical & Translational Center for Rare Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2026-01-15 Revised:2026-04-09 Accepted:2026-04-16 Online:2026-04-20 Published:2026-04-20
Contact: WANG Yilong, E-mail: yilong528@ailiyun.com

丙戊酸钠治疗无效的癫痫发作：MELAS药物陷阱识别1例报道

谭庆晶¹，黄美华²，刘艳芳³，周衡³，陈玮琪³，王伊龙^{3，4，5，6，7，8，9}

1南宁 530023 广西中医药大学第一附属医院神经内科
2南宁 530001 广西中医药大学第一临床医学院
3北京 100070 首都医科大学附属北京天坛医院神经病学中心
4北京 102206 北京脑科学与类脑研究所
5北京 100070 国家神经疾病医学中心
6北京 100070 首都医科大学人脑保护高精尖创新中心
7北京 100070 神经系统疾病国家临床医学研究中心
8北京 100069 口腔健康北京实验室
9北京 100070 首都医科大学附属北京天坛医院天坛罕见神经疾病临床与转化中心

通讯作者: 王伊龙 yilong528@ailiyun.com
基金资助:
国家自然科学基金杰出青年基金（延续资助）（82425101）
广西自然科学基金面上项目（2023GXNSFAA026200）
北京市科技新星计划资助（20230484245）

Abstract

Abstract: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) is a maternally inherited oxidative phosphorylation disorder caused by mitochondrial DNA mutations. In its early stage, MELAS often presents with seizures, headache, or stroke-like episodes, and is therefore prone to be misdiagnosed as seizure and inappropriate exposure to drugs with mitochondrial toxicity. This paper reports a 15-year-old male patient who initially presented with recurrent headache accompanied by convulsions. The patient had been treated at an external hospital with long-term oral sodium valproate for presumed migraine and epilepsy, but with poor clinical response. Subsequently, the patient developed symptoms of stroke-like episodes, including aphasia and hemianopia. Brain MRI revealed cortical migratory lesions extending beyond vascular territories, together with a characteristic “lace-like” sign. Combined with developmental retardation, elevated blood lactate, and the presence of the mitochondrial DNA m.3243A>G mutation, a definitive diagnosis of MELAS was established. Sodium valproate was discontinued, and mitochondrial-targeted supportive therapy centered on L-arginine was initiated, after which the patient showed short-term clinical improvement. Combined with literature review, this case highlights that MELAS and its potential drug-related pitfalls should be strongly suspected in adolescents with epilepsy who fail to respond to sodium valproate and show stroke-like imaging changes. Early genetic testing and timely adjustment of treatment strategies are essential.

Key words: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode; Sodium valproate; Drug-related pitfall; Lace-like sign

摘要： 线粒体脑肌病伴高乳酸血症和卒中样发作（mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode，MELAS）是由线粒体DNA突变导致的母系遗传性氧化磷酸化障碍疾病，早期常以癫痫、头痛或卒中样发作起病，易被误诊为癫痫而误用具有线粒体毒性的抗癫痫药物。本文报道1例15岁男性患者，以反复头痛伴抽搐起病，外院按偏头痛、癫痫给予长期口服丙戊酸钠治疗，但疗效欠佳。患者后续出现失语、偏盲等卒中样发作症状。头颅MRI检查示跨血管分布的皮质“游走性”病灶及“花边征”，结合患者发育迟缓、血乳酸水平升高及线粒体DNA m.3243A>G突变，最终确诊为MELAS。在停用丙戊酸钠并启动以L-精氨酸为核心的线粒体支持治疗后，患者临床症状短期内有所改善。本例报道结合文献复习提示，对于青少年丙戊酸钠治疗无效且伴卒中样影像学改变的癫痫发作，应高度警惕MELAS及其潜在药物陷阱，应尽早开展遗传学筛查并及时调整治疗策略。

关键词: 线粒体脑肌病伴高乳酸血症和卒中样发作; 丙戊酸钠; 药物陷阱; 花边征

CLC Number:

TAN Qingjing, HUANG Meihua, LIU Yanfang, ZHOU Heng, CHEN Weiqi, WANG Yilong. Refractory Seizures During Sodium Valproate Therapy: A Case Report on Recognition of the Drug-Related Pitfall in MELAS[J]. Chinese Journal of Stroke, 2026, 21(4): 508-516.

谭庆晶, 黄美华, 刘艳芳, 周衡, 陈玮琪, 王伊龙. 丙戊酸钠治疗无效的癫痫发作：MELAS药物陷阱识别1例报道[J]. 中国卒中杂志, 2026, 21(4): 508-516.

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https://www.chinastroke.org.cn/EN/Y2026/V21/I4/508

References

[1] FLOREZ I，PIRRONE I，CASIQUE L，et al. Independent origin for m.3243A>G mitochondrial mutation in three Venezuelan cases of MELAS syndrome[J/OL]. Clin Biochem，2022，109-110：98-101[2026-04-08]. https://doi.org/10.1016/j.clinbiochem.2022.09.007.
[2] NA J H，LEE Y M. Diagnosis and management of mitochondrial encephalopathy，lactic acidosis，and stroke-like episodes syndrome[J/OL]. Biomolecules，2024，14（12）：1524[2026-04-08]. https://doi.org/10.3390/biom14121524.
[3] HO P H，LI R，CHU C Y，et al. Adult-onset mitochondrial encephalopathy，lactic acidosis，and stroke-like episodes（MELAS）：a case report and review of its conventional and diffusion-weighted MRI features[J]. Neurology Asia，2024，29（2）：465-470.
[4] KHASMINSKY V，AURIEL E，LUCKMAN J，et al. Clinicoradiologic criteria for the diagnosis of stroke-like episodes in MELAS[J/OL]. Neurol Genet，2023，9（4）：e200082[2026-04-08]. https://doi.org/10.1212/NXG.0000000000200082.
[5] YANG X B，XU Y M，ZHANG S M，et al. Multiparametric MRI detection of cerebral metabolism：a tool for early differentiation between MELAS and ischemic cerebral infarction[J]. Quant Imaging Med Surg，2025，15（10）：9466-9478.
[6] ESPINOSA‐JOVEL C，VALENCIA N. The current role of valproic acid in the treatment of epilepsy：a glimpse into the present of an old ally[J]. Curr Treat Options Neurol，2024，26（8）：393-410.
[7] MANCUSO M，PAPADOPOULOU M T，NG Y S，et al. Management of seizures in patients with primary mitochondrial diseases：consensus statement from the InterERNs Mitochondrial Working Group[J/OL]. Eur J Neurol，2024，31（7）：e16275[2026-04-08]. https://doi.org/10.1111/ene.16275.
[8] FINSTERER J. A review of the advances in the medical management of epilepsy associated with myoclonic epilepsy with ragged-red fibers（MERRF）syndrome[J/OL]. Cureus，2025，17（4）：e82875[2026-04-08]. https://doi.org/10.7759/cureus.82875.
[9] NA J H，LEE Y M. Therapeutic approach to epilepsy in patients with mitochondrial diseases[J]. Yonsei Med J，2025，66（3）：131-140.
[10] BARROS C D S，COUTINHO A，TENGAN C H. Arginine supplementation in MELAS syndrome：what do we know about the mechanisms？[J/OL]. Int J Mol Sci，2024，25（7）：3629[2026-04-08]. https://doi.org/10.3390/ijms25073629.
[11] HUANG L J，LI H，ZHONG J M，et al. Efficacy and safety of the ketogenic diet for mitochondrial disease with epilepsy：a prospective，open-labeled，controlled study[J/OL]. Front Neurol，2022，13：880944[2026-04-08]. https://doi.org/10.3389/fneur.2022.880944.
[12] FINSTERER J，MEHRI S. Apply the Hirano or Japanese criteria when diagnosing MELAS[J/OL]. Ann Med Surg（Lond），2022，84：104965[2026-04-08]. https://doi.org/10.1016/j.amsu.2022.104965.
[13] XU S，JIANG J L，CHANG L L，et al. Multisystem clinicopathologic and genetic analysis of MELAS[J/OL].
Orphanet J Rare Dis，2024，19（1）：487[2026-04-08]. https://doi.org/10.1186/s13023-024-03511-4.
[14] KITAMURA T，SHIJO M，YOKOI M，et al. Stroke-like lesions confined to the cerebellum in MELAS and a possible association with neuronal hyperexcitability[J]. J Neurol，2023，270（1）：565-568.
[15] TETSUKA S，OGAWA T，HASHIMOTO R，et al. Clinical features，pathogenesis，and management of stroke-like episodes due to MELAS[J]. Metab Brain Dis，2021，36（8）：2181-2193.
[16] PAI V，SITOH Y Y，PUROHIT B. Gyriform restricted diffusion in adults：looking beyond thrombo-occlusions[J/OL]. Insights Imaging，2020，11（1）：20[2026-04-08]. https://doi.org/10.1186/s13244-019-0829-0.
[17] FINSTERER J，ALIYEV R. Metabolic stroke or stroke-like lesion：peculiarities of a phenomenon[J/OL].
J Neurol Sci，2020，412：116726[2026-04-08]. https://doi.org/10.1016/j.jns.2020.116726.
[18] RATNAIKE T E，ELKHATEEB N，LOCHMÜLLER A，et al. Evidence for sodium valproate toxicity in mitochondrial diseases：a systematic analysis[J/OL]. BMJ Neurol Open，2024，6（1）：e000650[2026-04-08]. https://doi.org/10.1136/bmjno-2024-000650.
[19] TIKHONOVA L，MAEVSKY E，MONTOLIU C，et al. Valproate damaging effect on erythrocyte metabolism as a decisive factor in the development of encephalopathy[J/OL]. Biomolecules，2025，15（4）：588[2026-04-08]. https://doi.org/10.3390/biom15040588.
[20] Będkowska N，ZONTEK A，PAPROCKA J. Stroke-like episodes in inherited neurometabolic disorders[J/OL]. Metabolites，2022，12（10）：929[2026-04-08]. https://doi.org/10.3390/metabo12100929.
[21] MULLIN N K，ANFINSON K R，RIKER M J，et al. Sensitive quantification of m.3243A>G mutational proportion in non-retinal tissues and its relationship with visual symptoms[J]. Hum Mol Genet，2022，31（5）：775-782.
[22] LU Y Y，DENG J W，ZHAO Y Y，et al. Patients with MELAS with negative myopathology for characteristic ragged-red fibers[J/OL]. J Neurol Sci，2020，408：116499[2026-04-08]. https://doi.org/10.1016/j.jns.2019.116499.
[23] CAI H，LI L M，ZHANG M，et al. Case report：late-onset MELAS syndrome with mtDNA 5783G>A mutation diagnosed by urinary sediment genetic testing[J/OL]. Front Genet，2024，15：1367716[2026-04-08]. https://doi.org/10.3389/fgene.2024.1367716.
[24] SANCHEZ-CONTRERAS M，SWEETWYNE M T，TSANTILAS K A，et al. The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging[J/OL]. Elife，2023，12：e83395[2026-04-08]. https://doi.org/10.7554/eLife.83395.

Refractory Seizures During Sodium Valproate Therapy: A Case Report on Recognition of the Drug-Related Pitfall in MELAS

丙戊酸钠治疗无效的癫痫发作：MELAS药物陷阱识别1例报道

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