Katherine Sear

Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke Results of the Vascular Effects of Infection in Pediatric Stroke Study

Background and Purpose Although arteriopathies are the most common cause of childhood arterial ischemic stroke (AIS), and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with AIS.Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (&kgr;=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy.

PURPOSE To assess, in a retrospective cohort study, rates and predictors of first and recurrent stroke in patients treated with cranial irradiation (CRT) and/or cervical irradiation at ≤18 years of age. METHODS AND MATERIALS We performed chart abstraction (n=383) and phone interviews (n=104) to measure first and recurrent stroke in 383 patients who received CRT and/or cervical radiation at a single institution between 1980 and 2009. Stroke was defined as a physician diagnosis and symptoms consistent with stroke. Incidence of first stroke was number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine cumulative incidence of first and recurrent stroke. RESULTS Among 325 subjects with sufficient follow-up data, we identified 19 first strokes (13 ischemic, 4 hemorrhagic, 2 unknown subtype) occurring at a median age of 24 years (interquartile range 17-33 years) in patients treated with CRT. Imaging was reviewed when available (n=13), and the stroke was confirmed in 12. Overall rate of first stroke was 625 (95% confidence interval [CI] 378-977) per 100,000 person-years. The cumulative incidence of first stroke was 2% (95% CI 0.01%-5.3%) at 5 years and 4% (95% CI 2.0%-8.4%) at 10 years after irradiation. With each 100-cGy increase in the radiation dose, the stroke hazard increased by 5% (hazard ratio 1.05; 95% CI 1.01-1.09; P=.02). We identified 6 recurrent strokes; 5 had available imaging that confirmed the stroke. Median time to recurrence was 15 months (interquartile range 6 months-3.2 years) after first stroke. The cumulative incidence of recurrent stroke was 38% (95% CI 17%-69%) at 5 years and 59% (95% CI 27%-92%) at 10 years after first stroke. CONCLUSION Cranial irradiation puts childhood cancer survivors at high risk of both first and recurrent stroke. Stroke prevention strategies for these survivors are needed.

Rates and characteristics of radiographically detected intracerebral cavernous malformations after cranial radiation therapy in pediatric cancer patients

Rates and characteristics of intracerebral cavernous malformations after cranial radiation therapy remain poorly understood. Herein we report on intracerebral cavernous malformations detected on follow-up imaging in pediatric cancer patients who received cranial radiation therapy at age ≤18 years from 1980 to 2009. Through chart reviews (n = 362) and phone interviews (n = 104) of a retrospective cohort, we identified 10 patients with intracerebral cavernous malformations. The median latency time for detection of intracerebral cavernous malformations after cranial radiation therapy was 12 years (range 1-24 years) at a median age of 21.4 years (interquartile range = 15-28). The cumulative incidence was 3% (95% confidence interval 1%-8%) at 10 years post cranial radiation therapy and 14% (95% confidence interval 7%-26%) at 15 years. Three patients underwent surgical resection. Two surgical specimens were pathologically similar to sporadically occurring intracerebral cavernous malformations; one was consistent with capillary telangiectasia. Intracerebral cavernous malformations are common after cranial radiation therapy and can show a spectrum of histologic features.

Survival after chemotherapy and stem cell transplant followed by delayed craniospinal irradiation is comparable to upfront craniospinal irradiation in pediatric embryonal brain tumor patients

Pediatric embryonal brain tumor patients treated with craniospinal irradiation (CSI) are at risk for adverse effects, with greater severity in younger patients. Here we compare outcomes of CSI vs. high-dose chemotherapy (HD), stem cell transplant (SCT) and delayed CSI in newly diagnosed patients. Two hundred one consecutive patients treated for medulloblastoma (72 %), supratentorial primitive neuroectodermal tumor (sPNET; 18 %) or pineoblastoma (10 %) at two institutions between 1988 and 2014 were retrospectively identified. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared by log-rank tests. Adjuvant CSI regimens were used for 56 % of patients (upfront-CSI), and HD/SCT regimens were used in 32 % of patients. HD/SCT patients were significantly younger than those receiving upfront-CSI (2.9 vs. 7.8 years; P < 0.0001). There were no differences in metastases, extent of resection, or CSI dose between upfront-CSI and HD/SCT patients, but median follow-up was shorter in the HD/SCT group (6.2 vs. 3.9 years; P = 0.007). There were no significant outcome differences between upfront-CSI and HD/SCT patients who received CSI as a prophylaxis or following relapse (OS 66 % vs. 61 %, P = 0.13; PFS 67 % vs. 62 %, P = 0.12). Outcomes were equivalent when restricting analyses to HD/SCT patients who received prophylactic CSI prior to relapse (OS 66 % vs. 65 %, P = 0.5; PFS 67 % vs. 74 %, P = 0.8). At last follow-up, 48 % of HD/SCT patients had received neither definitive nor salvage radiotherapy. In this retrospective cohort, outcomes with adjuvant HD/SCT followed by delayed CSI are comparable to upfront-CSI for carefully surveyed pediatric embryonal brain tumor patients. Future prospective studies are required to validate this finding, and also to assess the impact of delayed CSI on neurocognitive outcomes.

Large Vessel Arteriopathy After Cranial Radiation Therapy in Pediatric Brain Tumor Survivors

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA. We identified 10 patients with cerebral arteriopathy. The cumulative incidence of arteriopathy 5 years post–cranial radiation therapy was 5.4% (CI 0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial ischemic stroke 2.4 years post–cranial radiation therapy in the distribution of a radiation-induced stenotic artery. We conclude that large vessel arteriopathies can occur within a few years of cranial radiation therapy and can become apparent on MRA in under a year.

Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke

Background and Purpose Although arteriopathies are the most common cause of childhood arterial ischemic stroke (AIS), and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with AIS.Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (&kgr;=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke Results of the VIPS Study

Background and Purpose Although arteriopathies are the most common cause of childhood arterial ischemic stroke (AIS), and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with AIS.Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (&kgr;=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.