Risk factors and long-term outcomes in smart syndrome: a multicenter study

SMART (Stroke-like migraine attacks after radiotherapy) is a rare, late-onset complication of cranial radiotherapy (RT) consisting in episodes of neurological dysfunction associated with migraine-type headaches. We aimed to identify factors associated with the severity of first SMART episode, recurrence and overall survival.

We retrospectively reviewed patients diagnosed with modified SMART criteria (2010-2023) from nine Spanish hospitals. Demographic, clinical, neuroimaging, treatment and outcome data were analyzed.

Thirty-one patients (48% females) were included. Median age at SMART diagnosis was 49 (16-80) years. Median latency after RT was 13 (1-36) years. Most patients had primary brain tumors (84%). Nearly half received focal RT (45%), 32 % whole-brain RT and 23% received both. Severe episodes occurred in 61% (n = 19): 13 met a single severity criterion (intensive care unit admission, n = 1; status epilepticus (SE), n = 1; long-lasting episode, n = 11), and six met multiple criteria. Male sex (OR = 6.5, p = 0.024) and longer latency between RT and SMART onset (OR = 1.15, p = 0.016) were independently associated with severe presentation. Recurrent episodes occurred in 45%. The presence of ictal cortical FLAIR hyperintensity (OR = 0.08, p < 0.032) and longer episode duration (OR = 0.92, p < 0.035) were linked to lower recurrence. SE and known tumor prognostic factors predicted poorer survival.

This study highlights the heterogeneous long-term outcome of SMART syndrome. Severe initial episodes are common, especially in males and those with longer RT latency. Cortical FLAIR hyperintensity and prolonged first episodes are associated with reduced recurrence risk, while SE has a negative impact on survival.