Madjidov Abraham, Abbott Mary-Alice, Mullen Katherine M, Hicks Richard, Schlaug Gottfried
Department of Neurology, Baystate Medical Center, University of Massachusetts Chan Medical School - Baystate, Springfield, MA, United States.
Department of Pediatrics, Baystate Medical Center, University of Massachusetts Chan Medical School - Baystate, Springfield, MA, United States.
Front Hum Neurosci. 2025 May 14;19:1568937. doi: 10.3389/fnhum.2025.1568937. eCollection 2025.
We present a 50-year-old female who has a longstanding history of migraine with aura. She experienced one episode of partial visual field loss associated with a small acute/subacute lesion involving the cortex and subcortical white matter (showing contrast enhancement), alongside extensive white matter hyperintensities. Given these findings, CADASIL was suspected. Genetic testing identified a rare heterozygous variant (c.6102dup, p.Gly2035Argfs*60), currently classified as a variant of uncertain significance. Concurrent cerebrospinal fluid analysis revealed elevated myelin basic protein, an elevated IgG index, and 4 oligoclonal bands, indicating an inflammatory process. Her visual evoked potentials showed no evidence of optic nerve or tract impairment. Approximately 9 months later, the occipital lesion evolved into encephalomalacia and gliosis without enhancement, while the extensive white matter hyperintensities remained stable. A repeat lumbar puncture 1 year later showed persistently elevated myelin basic protein and IgG index, now with 7 oligoclonal bands (some shared with serum). Currently, her neurological examination is normal. She is managed on dual antiplatelet therapy, and her migraines are effectively controlled with calcium-channel blocker prophylaxis. Notably, her mother, diagnosed with multiple sclerosis for several decades despite imaging findings suggestive of CADASIL, shares the same variant. One of her two children tested negative for the variant and had normal imaging, while the other minor child has a significant history of migraines with aura. Our patient's clinical presentation and comprehensive findings raise the possibility of an inflammatory phenotype potentially associated with the rare c.6102dup variant, though causation remains unclear. Coexistence with another demyelinating central nervous system disease is possible, and further research is needed to clarify this relationship. If inflammatory variants of CADASIL exist, alternative treatments targeting inflammation may need consideration.
我们报告了一位50岁女性，她有长期的伴先兆偏头痛病史。她经历了一次部分视野缺损发作，与一个累及皮质和皮质下白质的小急性/亚急性病变（显示对比增强）相关，同时伴有广泛的白质高信号。鉴于这些发现，怀疑为伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）。基因检测发现了一种罕见的杂合变异（c.6102dup，p.Gly2035Argfs*60），目前被归类为意义未明的变异。同时进行的脑脊液分析显示髓鞘碱性蛋白升高、IgG指数升高以及4条寡克隆带，提示存在炎症过程。她的视觉诱发电位未显示视神经或视束受损的证据。大约9个月后，枕部病变演变为软化灶和胶质增生，无强化，而广泛的白质高信号保持稳定。1年后重复腰椎穿刺显示髓鞘碱性蛋白和IgG指数持续升高，现在有7条寡克隆带（部分与血清共有）。目前，她的神经系统检查正常。她接受双重抗血小板治疗，偏头痛通过钙通道阻滞剂预防得到有效控制。值得注意的是，她的母亲尽管影像学表现提示CADASIL，但已被诊断为多发性硬化症数十年，与她有相同的变异。她的两个孩子中，一个检测该变异为阴性且影像学正常，另一个年幼的孩子有明显的伴先兆偏头痛病史。我们患者的临床表现和综合检查结果提示可能存在一种与罕见的c.6102dup变异相关的炎症表型，尽管因果关系尚不清楚。可能与另一种脱髓鞘性中枢神经系统疾病共存，需要进一步研究来阐明这种关系。如果存在CADASIL的炎症变异，可能需要考虑针对炎症的替代治疗方法。
