SMART syndrome: retrospective review of a rare delayed complication of radiation

Abstract

Background SMART (stroke‐like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients. Methods We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. Results We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43–55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4–28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow‐up of the patients in our cohort was 10 (IQR 6–32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1–52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1–45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age (p = 0.049), temporal lobe involvement (p < 0.001), and diffusion restriction (p = 0.043). Conclusions SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one‐third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.

Prognostic Factors of Stroke-Like Migraine Attacks after Radiation Therapy (SMART) Syndrome

“…18 Prior research in the setting of SMART syndrome has shown that the use of steroids was not significantly associated with worse clinical outcomes. 13,19 One study has proposed that to control seizure activity, a short course of highdose steroids can be considered for treatment. 2 However, whether steroid introduction can result in better clinical outcomes has still not been established.…”

“…The most commonly associated neurologic symptoms include hemiparesis (13/20), migraine-type headache (12/20), seizure (11/20), and speech impairment (9/20), findings consistent with those in prior studies. 2,13,14 Hemiparesis was the most prevalent remaining symptom at follow-up.…”

“…5,12 The neurologic symptoms and characteristic MR imaging features typically resolve, but the symptoms can remain persistent despite long-time observation, with a high rate of recurrence. 1,2,13,14 Still, the relationship between clinical outcomes and imaging features has not been fully investigated. Therefore, our study aimed to assess the factors associated with the outcome of clinical SMART syndrome by reviewing patient demographics, neurologic symptoms, and MR imaging features at diagnosis.…”

Be Smart to Identify the Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome

“…Hypotheses regarding pathophysiology for SMART include radiation-induced endothelial damage leading to impaired cerebrovascular autoregulation [3]. In the literature, the onset of symptoms ranges from one to 35 years after initial radiation [1].…”

A Case of Postoperative SMART Syndrome in a Medulloblastoma Survivor

“…Although the pathophysiology of SMART syndrome remains poorly understood, some authors have speculated that deranged autoregulation caused by endothelial damage may be a causative factor. 6,7 In their review of radiotherapy-induced vasculopathy, Murphy et al specifically identified cerebrovascular accidents, moyamoya syndrome, vascular malformation, and hemorrhage as some of the principal vascular pathologies that take place years following cranial irradiation. 9,10 Given the high incidence of infarcts (not in an arterial distribution) demonstrated by Singh et al as well as the contrast enhancement found in most cases, it is thought that radiotherapy-induced vasculopathy plays a role in the pathogenesis of SMART syndrome.…”