Diagnostic Overshadowing in Lennox-Gastaut Syndrome: Immerslund-Gräsbeck Syndrome Unmasked by Radiosurgical Stress

In complex neurodevelopmental disorders such as Lennox-Gastaut syndrome (LGS), treatable metabolic comorbidities may be masked by the severity of the primary phenotype. We report an 8-year-old boy with LGS and bilateral polymicrogyria whose underlying Imerslund-Gräsbeck syndrome was unmasked following a palliative Gamma Knife corpus callosotomy. Although the patient underwent Gamma Knife corpus callosotomy, his seizures remained uncontrolled. Consequently, vagus nerve stimulator implantation was planned; however, severe anemia (hemoglobin: 3.3 g/dL) was detected on admission for the procedure. Initially, the hematologic abnormalities were attributed to polypharmacy, prompting a dose reduction in antiepileptic medications. A concurrent anemia workup revealed vitamin B 12 deficiency, and intramuscular B 12 replacement therapy was initiated. However, because the macrocytic anemia was unexpectedly severe and other hematopoietic lineages remained unaffected, advanced investigations were performed. Genetic analysis revealed compound heterozygous missense variants in the CUBN gene. Following parenteral vitamin B 12 replacement, the patient achieved not only hematologic recovery but also a remarkable reduction in seizure frequency over the subsequent 9 months. This case illustrates diagnostic overshadowing and underscores the necessity of considering comprehensive genetic and metabolic testing in refractory epilepsy, as addressing a metabolic second hit can significantly optimize neurologic outcomes.