Case Report: longitudinal imaging in a patient with SMART syndrome after cranial radiotherapy.

Background: Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare, delayed complication of cranial irradiation, characterized by migraine-like headache, seizures, and focal neurological deficits with transient unilateral gyriform cortical enhancement on MRI. It has usually been regarded as a single, isolated post-radiation event. Evidence on recurrence, prodromal manifestations, and any relationship with other radiation-induced vascular lesions remains limited. We hypothesize that SMART syndrome may represent a dynamic spectrum of radiation-induced cortical vulnerability rather than an isolated event. Case description: We present a 48-year-old woman treated for a right parietal anaplastic astrocytoma with surgical resection and cranial radiotherapy in 2001 at an outside institution abroad; the original radiotherapy parameters, including cumulative dose and fractionation, were not retrievable. Twenty-four years later she presented with focal seizure clustering, severe unilateral headache, and transient left-sided hemiparesis. MRI showed extensive unilateral gyriform cortical enhancement confined to the previously irradiated hemisphere. Lumbar puncture, performed after initial stabilization, after corticosteroid initiation, and several weeks after symptom onset, showed a non-inflammatory CSF profile that reduced the likelihood of major inflammatory mimics but did not by itself exclude infectious, autoimmune, or paraneoplastic disease. Short-interval follow-up MRI showed near-complete resolution of the enhancement. Retrospective review identified a similar but milder cortical enhancement episode nine years earlier, in 2016, which may represent an earlier SMART-like manifestation; a peri-ictal imaging change and a concurrent febrile illness at that time preclude a definite retrospective diagnosis. The patient also harbored multiple suspected radiation-associated cavernous malformations, predominantly within the previously irradiated right hemisphere. Conclusion: This longitudinal case supports the hypothesis that SMART syndrome may represent a spectrum of radiation-induced cortical vulnerability, with possible recurrence and earlier, milder manifestations. Its coexistence with these cavernous malformations is compatible with a shared substrate of chronic radiation-induced microvascular injury. We propose a multimodal diagnostic framework that combines clinical assessment, serial MRI, EEG, and exclusionary CSF analysis with short-interval follow-up imaging, to support conservative management and prevent unnecessary invasive interventions in neuro-oncology survivors, while recognizing that clinical deterioration should prompt re-evaluation regardless of initial findings.