Stroke-like Migraine Attacks After Radiation Therapy Syndrome Research Articles

Early clinical, radiological and EEG improvement following L-arginine infusion in SMART syndrome

ObjectivesTo report the clinical, radiological (MRI) and neurophysiological (EEG) changes in a case of SMART (stroke-like migraine attacks after radiation therapy) syndrome following treatment with intravenous L-arginine. MethodsA 60-year-old woman had, ten years prior, been diagnosed with primary CNS diffuse large B cell lymphoma, and was successfully treated with curative chemotherapy and whole brain radiotherapy. She presented acutely with left-sided headache, teichopsia and dysphasia following a chest infection. MRI of the brain showed striking left parieto-occipital gyral swelling, diffusion restriction, leptomeningeal enhancement, and increased cerebral blood volume. Her EEG showed an excess of slow activity diffusely, particularly over the left temporal lobe. A diagnosis of SMART syndrome was made. Intravenous L-arginine (0.5 g/kg) was administered. ResultsA few hours post infusion, her migrainous headache subsided and her mentation improved. Her MRI brain performed six days post infusion showed reduced cortical swelling and hyperperfusion, and her EEG showed less temporal slowing. She continued to improve cognitively. DiscussionThis is the first report of SMART syndrome with a response to L-arginine, reflected clinically by a measurable improvement in cognition, brain perfusion and EEG parameters, encouraging further clinical studies.

Comprehensive Update and Review of Clinical and Imaging Features of SMART Syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a delayed complication of cranial irradiation, with subacute onset of stroke-like symptoms including seizures, visual disturbance, speech impairment, unilateral hemianopsia, facial droop, and aphasia, often associated with migraine-type headache. The diagnostic criteria were initially proposed in 2006. However, the diagnosis of SMART syndrome is challenging because clinical symptoms and imaging features of SMART syndrome are indeterminate and overlap with tumor recurrence and other neurologic diseases, which may result in inappropriate clinical management and unnecessary invasive diagnostic procedures. Recently, various imaging features and treatment recommendations for SMART syndrome have been reported. Radiologists and clinicians should be familiar with updates on clinical and imaging features of this delayed radiation complication because recognition of this entity can facilitate proper clinical work-up and management. This review provides current updates and a comprehensive overview of the clinical and imaging features of SMART syndrome.

Uncommon Presentation of an Uncommon Disease: Stroke-like Migraine Attacks after Radiation Therapy in a Patient with Sudden Onset Expressive Aphasia and Cryptogenic Fevers (P3-5.029)

<h3>Objective:</h3> To present a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome accompanied by fever. <h3>Background:</h3> SMART syndrome is an uncommon condition that presents as migraines with focal neurologic deficits in patients who have undergone brain radiation. This syndrome can present decades after completion of radiation therapy and therefore represents a unique diagnostic challenge. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 26-year-old man with a history of myxopapillary ependymoma status post whole brain radiation therapy 15 years prior presented with 3 days of headaches, sudden onset aphasia, and fevers. Initial exam was significant for severe expressive aphasia with only 1–2 words of speech production. Head CT was unremarkable. CT angiography demonstrated slightly decreased arborization of the distal MCA territory vessels in the left cerebral hemisphere but was otherwise unremarkable. Patient was empirically treated for CNS infection with antimicrobial therapy. CSF analysis was unremarkable, as was the remainder of his infectious workup. Long term EEG monitoring showed focal slowing in the left hemisphere but did not show any epileptiform activity. MRI was completed with arterial spin labeling (ASL) sequence, which showed increased perfusion in the left cerebral hemisphere, consistent with SMART syndrome. Patient’s exam gradually improved over the following week. He followed up in clinic 6 weeks later and his symptoms had significantly improved. He was almost back to baseline. Fevers and headaches had completed resolved. <h3>Conclusions:</h3> This case of SMART syndrome has the typical findings of sudden onset migraines and focal neurologic deficits in a patient who previously underwent brain radiation therapy. Our case was unique in that the patient had fevers of unknown origin; a phenomenon that has only been reported in one prior case. The use of MRI perfusion or ASL can aid in the diagnosis; in this case showing increased perfusion over the affected cerebral hemisphere. <b>Disclosure:</b> Dr. Gill has nothing to disclose. Dr. Gill has nothing to disclose. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Akcea Therapeutics. Gino Mongelluzzo has nothing to disclose.

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

Prognostic factors of stroke-like migraine attacks after radiation therapy (SMART) syndrome have not been fully explored. This study aimed to assess clinical and imaging features to predict the clinical outcome of SMART syndrome. We retrospectively reviewed the clinical manifestations and imaging findings of 20 patients with SMART syndrome (median age, 48 years; 5 women) from January 2016 to January 2020 at 4 medical centers. Patient demographics and MR imaging features at the time of diagnosis were reviewed. This cohort was divided into 2 groups based on the degree of clinical improvement (completely versus incompletely recovered). The numeric and categoric variables were compared as appropriate. There were statistically significant differences between the completely recovered group (n = 11; median age, 44 years; 2 women) and the incompletely recovered group (n = 9; median age, 55 years; 3 women) in age, months of follow-up, and the presence of steroid treatment at diagnosis (P = .028, .002, and .01, respectively). Regarding MR imaging features, there were statistically significant differences in the presence of linear subcortical WM susceptibility abnormality, restricted diffusion, and subcortical WM edematous changes in the acute SMART region (3/11 versus 8/9, P = .01; 0/11 versus 4/9, P = .026; and 2/11 versus 7/9, P = .022, respectively). Follow-up MRIs showed persistent susceptibility abnormality (11/11) and subcortical WM edematous changes (9/9), with resolution of restricted diffusion (4/4). Age, use of steroid treatment at the diagnosis of SMART syndrome, and MR imaging findings of abnormal susceptibility signal, restricted diffusion, and subcortical WM change in the acute SMART region can be prognostic factors in SMART syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome presenting as a migraine copycat: A case report

Background: Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a possible long term consequence of cranial beam radiation therapy and may present as a perfect mimic of migraine with or without aura. Methods and Results: We present a 57-year-old man suffering from diffuse astrocytoma and presenting with SMART syndrome perfectly mimicking his antecedent migraine with visual aura. He was treated with intravenous steroid therapy inducing rapid response. Conclusion: SMART syndrome is a rare complex delayed complication of brain radiation therapy, which may present as an isolated migraine with or without aura even decades after cranial radiation. Thus, a sudden intensification or relapse of a previous migraine in a patient with remote cranial radiotherapy constitutes a red flag even decades after cranial irradiation and cured or stable tumor disease on a recent brain MRI. Moreover, SMART syndrome adds to the list of secondary headaches not yet listed in the current International Classification of Headache Disorders, 3rd edition (ICHD3).

MR-PET Findings in SMART (Stroke-Like Migraine Attacks after Radiation Therapy) Syndrome.

MR-PET Findings in SMART (Stroke-Like Migraine Attacks after Radiation Therapy) Syndrome.

Clinical Presentation and Management of SMART Syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome represents a rare but serious condition manifesting years after cranial radiation therapy (RT).1 Characterized by migraine-type headaches, stroke-like deficits, seizures, and MRI abnormalities, including cortical gyriform enhancement in irradiated brain regions, SMART is diagnostically and therapeutically challenging.2-6 Distinction from tumor progression is difficult and treatment options are limited.2 Although frequently reversible,5 SMART episodes can recur6 and effectuate persistent neurologic or imaging sequelae.3

Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome: A Comprehensive Review.

SMART syndrome is a delayed complication of cranial irradiation that can be misconstrued as tumor recurrence or some other intracranial neurological disease. Recognition of this clinical syndrome is imperative as it can obviate the need for invasive diagnostic testing and can provide reassurance to both the patient and their loved ones. SMART syndrome is generally considered a reversible clinical syndrome; however, neurological deficits may become permanent. Pathophysiology of SMART syndrome may involve cerebrovascular autoregulation impairment, neuronal dysfunction leading to trigeminovascular system impairment and/or cortical spreading depression, and seizures. In addition to MRI brain with gadolinium, other imaging modalities, such as CT perfusion, MR perfusion, MR spectroscopy, and FDG PET/CT, aid in arriving to the diagnosis sooner. Patients should also undergo electroencephalogram in order to promptly identify and treat seizures. There are currently no clear guidelines on how to effectively treat SMART syndrome, but treatment may involve anti-seizure medication, anti-hypertensives, anti-platelet, and steroid therapy. This review provides a comprehensive understanding of the clinical characteristics of SMART syndrome from presentation to diagnostic evaluation. We also discuss radiographic features and treatment strategies for this rare disease. With increased radiotherapy utilization, prompt clinical recognition of SMART syndrome and further development of a comprehensive diagnostic approach to SMART syndrome utilizing newer radiographic modalities as well as treatment algorithms to effectively treat this clinical condition will be imperative.

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

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. We conducted a retrospective cohort study of all consecutive adult patients (≥18years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. 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 (>10weeks) correlated with an older age (p=0.049), temporal lobe involvement (p<0.001), and diffusion restriction (p=0.043). SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10weeks occurred in one-third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome-a case series and review.

Cranial irradiation is used both prophylactically and for the treatment of brain tumors. There are various complications associated with it. The rare complication of stroke-like migraine attacks after radiation therapy (SMART) syndrome usually occurs several years after radiation therapy but is a reversible phenomenon. It usually presents with headaches, seizures, or other focal neurological deficits concerning stroke or recurrence of the underlying disease. We aim to present two cases of SMART syndrome highlighting the typical presentation, imaging findings, and differential diagnosis. We also conducted the literature review since the early recognition of this rare delayed onset complication is crucial, given its self-limited course and to avoid misinterpretations of the cases. Our extensive review favors MRI, CT, and prolonged EEG monitoring to rule out other differentials and showed that initiation of corticosteroid therapy and antiepileptic treatment were helpful in the resolution of symptoms and prevent recurrences. Therefore, future studies should be focused on early identification and management guidelines for SMART syndrome.

Protracted Recovery From Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome: A Case Report

The purpose of this case report is to document a protracted course of recovery and the deficits exhibited by a person with SMART syndrome.

Unusual case of recurrent SMART (stroke-like migraine attacks after radiation therapy) syndrome (P2.6-019)

Unusual case of recurrent SMART (stroke-like migraine attacks after radiation therapy) syndrome (P2.6-019)

SMART (stroke-like migraine attacks after radiation therapy) syndrome responded to steroid pulse therapy: Report of a case and review of the literature

This report presents a case of stroke-like migraine attacks after radiation therapy (SMART) syndrome in a 31-year-old man in whom symptoms and radiological findings resolved with steroid pulsed therapy and reviews the literatures with special emphasis on the use of steroids against SMART syndrome. The patient had a past history of left temporal anaplastic astrocytoma and was treated with surgery followed by local 72 Gy radiation therapy and chemotherapy using Nimustine Hydrochloride. Four years after the surgery, he was suffering from subacute progressing symptoms of headache, right hemianopia, right hemiparesis and aphasia from 2 to 4 days before admission to our hospital. At first he was diagnosed as symptomatic epilepsy but after extensive examination, the final diagnosis was SMART syndrome. His symptoms soon improved with steroid pulse therapy. In the literature, steroid pulse therapy is not necessarily a standard of care for SMART syndrome, but it seemed to decrease the need of biopsy. As the lesions of SMART syndrome require differential diagnosis from recurrences, biopsy was performed in some cases. However, lack of benefit and possible detriment is reported with biopsy of SMART lesions. Through this experience we suggest that steroid pulse therapy may provide speedy recovery from symptoms, and it should be considered before other invasive investigations or treatments.

F20. Focal status epilepticus in a patient with stroke like migraine attacks after radiation therapy (SMART) syndrome

Stroke like migraine attacks after radiation therapy (SMART) syndrome is a rare and under-recognized delayed complication of brain irradiation. It is characterized by cortical thickening with associated cortical gadolinium enhancement on magnetic resonance imaging (MRI) and with migraine headaches, typically reversible stroke like symptoms and focal seizures. Focal status epilepticus (SE) is a rare phenomenon associated with SMART syndrome. We present a case of SMART syndrome with focal seizures and SE. We also reviewed the literature on SMART and SE. A 46 year old male with history of human immunodeficiency virus, hypertension, diabetes mellitus II, brain lymphoma (treated with brain irradiation) presented with a two week history of right parietal headache with involuntary left leg movement and left hemi-neglect on exam. MRI showed evidence of cortical and subcortical T2/FLAIR hyperintensity with cortical and leptomeningeal enhancement involving the right parietal region. Serum paraneoplastic and infectious workup was negative. Cerebrospinal fluid (CSF) analysis was remarkable for albuminocytologic dissociation. CSF cytology was negative for malignancy. Electroencephalogram (EEG) sowed slowing over the right parasagittal area without evidence of epileptiform activity. Symptom resolution was achieved with intravenous valproic acid 500 mg twice daily (BID). He remained asymptomatic until readmission 9 months later for a 2 week history of right parietal headache along with altered sensory perception of the left arm and leg in space and left sensory extinction. CSF analysis and brain MRI findings were unchanged. Brain biopsy was negative for malignancy. EEG showed multiple electrographic seizures in the right posterior region. The SE was treated with brivaracetam 100 mg BID, valproic acid 500 mg BID and vigabatrin 1500 mg BID and later with topamax 200 mg BID, levetiracetam 1500 mg BID and lacosamide 100 mg BID. Seizure freedom was achieved at 3 weeks. Patient was discharged home on levetiracetam 500 mg BID and lacosamide 100 mg BID. Patient was readmitted a week later for agitation prompting discontinuation of both medications with initiation of eslicarbazepine 1200 mg daily was initiated with no recurrence of symptoms or side effects. At a 4 week follow up he remained asymptomatic. We reviewed the literature and identified five previously reported cases of SE associated with SMART syndrome. Seizures are not uncommon in patients with SMART syndrome likely secondary to underlying cortical irritability. Focal SE is rare and can be seen with SMART syndrome. Our report emphasizes the need to recognize SMART syndrome in a patient with headache and focal SE with a history of brain irradiation.

Stroke-like Migraine Attacks after Radiation Therapy (SMART) Syndrome Followed by Cerebral Infarction

A 36-year-old man with a history of irradiation for acute lymphoblastic leukemia developed headache with cortical dysfunction lasting for 4 weeks. The clinical features were consistent with stroke-like migraine attacks after radiation therapy (SMART) syndrome. Six months later, he developed cerebral infarction due to occlusions of the left anterior and middle cerebral arteries. This is the first case report describing SMART syndrome followed by severe cerebral infarction. Although an association between the two episodes was not assumed, this case indicates that protective therapies against infarction might need to be considered for patients with SMART syndrome.

Stroke-like migraine attacks after radiation therapy: A misnomer?

To understand the frequency of electrographic and clinical seizures in patients with stroke-like migraine attacks after radiation therapy (SMART), and determine whether SMART warrants comprehensive electroencephalographic (EEG) monitoring and aggressive seizure management. We searched our magnetic resonance brain imaging report database for all patients between January 2013 and December 2015 for suspected SMART syndrome. Clinical inclusion criteria were further applied as follows: inpatient adults (>18 years of age) with history of cranial radiation presenting with acute neurologic deficits as primary admission reason who lacked evidence of recurrent or new brain malignancy, stroke, or infectious agents in cerebrospinal fluid. Six patients were identified. All 6 patients underwent prolonged video EEG monitoring as part of our standard protocol. All patients but 1 were found to have multiple or prolonged electrographic seizures consistent with status epilepticus during video EEG monitoring. Their neurological deficit and/or mental status change improved in parallel with resolution of the seizure activity. SMART is likely a misnomer that underestimates the significance of seizures and status epilepticus in the pathophysiology and clinical presentation of the syndrome. Systematic continuous EEG monitoring and appropriate seizure management is warranted to reduce symptom duration and optimize clinical outcome.

Reversible hemispheric hypoperfusion in two cases of SMART syndrome

Stroke-like migraine attacks after radiation therapy (SMART) syndrome manifests as prolonged episodes of cortical dysfunction, years after cranial irradiation. We present two cases demonstrating reversible hemispheric hypoperfusion. Case 1 presented with left hemispheric symptoms following previous similar episodes. CT perfusion (CTP) demonstrated reversible hemispheric hypoperfusion; subsequent investigations were consistent with SMART syndrome. Case 2 presented following the third episode of a hemispheric syndrome with near-identical CTP abnormalities. L-arginine was administered with rapid reversal of clinical and CTP abnormalities. We conclude that SMART syndrome may demonstrate significant hypoperfusion on hyperacute CTP without subsequent infarction. Impaired cerebrovascular autoregulation probably contributes to cortical dysfunction in SMART syndrome. L-arginine warrants investigation as a potential treatment.

The syndrome of stroke-like migraine attacks after radiation therapy associated with prolonged unresponsiveness in an adult patient.

The syndrome of stroke-like migraine attacks after radiation therapy (SMART) is an extremely rare complication of cerebral irradiation. It is characterized by reversible episodic neurological dysfunction, commonly associated with headaches and occasionally with seizures, occurring years after cranial radiotherapy. Approximately a dozen cases have been reported in adult patients to date. In 1997, a 48-year-old man underwent resection of a right cerebellar metastasis from renal cell carcinoma, followed by whole-brain irradiation. Two years later he began experiencing recurrent episodes of headache associated with reversible left hemiparesis, dysphasia, visual field defects, and confusion. Over subsequent years these episodes increased in frequency, and in 2009 and 2010 the patient experienced 2 episodes associated with seizures and characterized by severe depression in level of consciousness (GCS 5); the latter of these was particularly prolonged, with neurological recovery requiring almost 6 months. Cortical and leptomeningeal gadolinium enhancement was demonstrated on magnetic resonance imaging during the second episode. Repeated electroencephalography studies did not demonstrate any epileptiform activity, and extensive workup including brain biopsy failed to identify any neoplastic, vascular, or infective pathology. The diagnosis of SMART syndrome was therefore made. Reduced level of consciousness of such severity and duration as observed here has not previously been described in SMART syndrome. This report, however, suggests that an excellent prognosis can be expected even in cases of prolonged unresponsiveness. The pathogenic mechanisms of SMART syndrome remain unclear, but may involve pathways common to both migraine and epilepsy.

Headaches in Brain Tumor Patients: Primary or Secondary?

Headaches occur commonly in all patients, including those who have brain tumors. It has been argued that there is a classic "brain tumor headache type" - defined by the International Headache Society as one that is localized, progressive, worse in the morning, aggravated by coughing or bending forward, develops in temporal and often spatial relation to the neoplasm, and resolves within 7 days of surgical removal or treatment with corticosteroids. Using the search terms "headache and brain tumors," "intracranial neoplasms and headache," and "facial pain and brain tumors," we reviewed the literature from the past 20 years on brain tumor-associated headache and reflected upon the International Classification of Headache Disorders-3 (ICHD-3). In a separate, complementary paper, the proposed mechanisms of brain tumor headache are reviewed. We discuss multiple clinical presentations of brain tumor headaches, present the ICHD-3 diagnostic criteria for each type of headache, and then apply our findings to the ICHD-3. Our primary and major finding was that brain tumor headaches can present similarly to primary headaches in those with a predisposition to headaches, suggesting that following ICHD-3 criteria could cause a clinician to overlook a headache caused by a brain tumor. We further find that some types of headaches are not explicitly discussed in the ICHD-3 and also propose that the International Headache Society formally define SMART (Stroke-like Migraine Attacks after Radiation Therapy) syndrome given the increasing amount of literature on this disorder. Our literature review revealed that brain tumor headache uncommonly presents with classic brain tumor headache characteristics and often satisfies criteria for a primary headache category such as migraine or tension-type. Thus, clinicians may miss headaches due to brain tumors in following ICHD-3 criteria, and the distinction between primary and secondary headache disorders may not be so clear-cut.

SMART syndrome: a late reversible complication of radiotherapy

A 43-year-ol d female had a cerebellar pilocytic astrocy-toma operated 27 years ago. Reoperation and radiation ther-apy were employed in a recurrence 13 years ago. One week before admission, progressive drowsiness, disorientation in time and space, slurred speech and worsening of a residual right hemiparesis begun. Cerebrospinal ˜ uid (CSF) analysis and electroencephalography (EEG) were unremarkable. She improved without speci˚ c therapy.Recently recognized stroke-like migraine attacks after radiation therapy (SMART) is a syndrome which consists of prolonged, unilateral neurological symptoms that are spon-taneously reversible