Dr. Lauren Beslow

Department of Pediatrics & Department of Neurology

Yale University School of Medicine, USA.

Victoria Murphy:

My guest today is Dr. Lauren Beslow from the Department of Pediatrics & Department of Neurology, Yale University School of Medicine, USA . Dr. Beslow a very warm welcome to you, thank you for joining us.

Dr. Beslow:

Thank you for having me.

Victoria Murphy:

Today we are here to discuss a paper you authored in Frontiers In Neurology in July 2012. The title of your paper was ‘Modified Pediatric ASPECTS Correlates with Infarct Volume in Childhood Arterial Ischemic Stroke’. Dr. Beslow, what were the objectives of your study?

Dr. Beslow:

Larger infarct volume as a percent of supratentorial brain volume (SBV) predicts poor outcome and hemorrhagic transformation in childhood arterial ischemic stroke (AIS). In pediatrics, we express infarct volume as a percent of brain volume rather than in mLs to account for the varying head sizes of children of different ages. However, volumetric measurements require pre-processing of images and manual segmentation techniques that are extremely time consuming and are therefore not practical in the acute setting for either clinical or research purposes. Our group recognized a need for an easily performed, quick and reliable proxy measure for infarct volume. In adult stroke, the Alberta Stroke Program Early CT Score (ASPECTS) semiquantitatively assess infarct volume. Members of our group modified this score for pediatric and demonstrated that in perinatal acute arterial ischemic stroke, higher modASPECTS predicted seizures at follow-up.  However, the relationship of the modified pediatric ASPECTS to actual infarct volume and the interrater reliability of the score were not determined. The objectives were to establish the relationship of modASPECTS to infarct volume in perinatal and childhood AIS and to establish the interrater reliability of the score.

Victoria Murphy:

How is the modified pediatric ASPECTS different from the adult ASPECTS?

Dr. Beslow:

The adult ASPECTS was originally developed to assess semiquantitatively infarct volume on CT scan and was later modified for use on diffusion weighted MRI. The pediatric modification uses diffusion weighted imaging. The adult ASPECTS only scores regions of the middle cerebral artery (7 cortical regions M1-M6 and the insula, the caudate nucleus, the internal capsule, and the lentiform nucleus). Since 25-30{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} of pediatric stroke occurs in territories outside the MCA, in the modified pediatric ASPECTS, 5 additional scoring regions were added. These include a proximal region of the anterior cerebral artery territory (A1), a distal region of the anterior cerebral artery territory (A2), an inferior region of the posterior cerebral artery territory (P1), a superior region of the posterior cerebral artery (P2), and the thalamus. Therefore, in the adult ASPECTS, each MCA has 10 possible points whereas in the pediatric score, each hemisphere has 15 possible points. Finally, in the adult score, and normal hemisphere is scored as 10, and a point is subtracted for each infarcted region. In the pediatric score, a normal hemisphere is scored as 0, and a point is added for each infarcted region.

Victoria Murphy:

How was it designed?

Dr. Beslow:

We performed a cross sectional study of 31 neonates and 40 children identified from a tertiary care center stroke registry with supratentorial AIS and acute MRI with diffusion-weighted imaging (DWI) and T2 axial sequences.

Infarct volume was expressed as a percent of SBV using computer-assisted manual segmentation tracings which were performed in a program called ITK-SNAP. ModASPECTS was performed on DWI by three independent raters including a pediatric stroke neurologist, a pediatric neurologist, and a pediatric neurology fellow. The modASPECTS were compared among raters and to infarct volume as a percent of SBV.

Victoria Murphy:

What types of patients were included?

Dr. Beslow:

Subjects were neonates and children with supratentorial arterial ischemic stroke. Subjects were identified from a single tertiary care center stroke registry. In the current study, perinatal subjects were ≥37 weeks gestational age with acute AIS within the first 28 days of life and presented between January 1, 2004 and October 31, 2009. Childhood subjects were age >28 days to 18 years inclusive presenting with acute AIS between January 2005 and November 2008. All subjects’ infarcts were confirmed by MRI demonstrating restricted diffusion within an arterial vascular territory conforming to the localization of acute neurologic deficit.  For inclusion in the study, an axial diffusion weighted image (DWI) with apparent diffusion coefficient (ADC) map and an axial T2 image were required.

Victoria Murphy:

What were the study endpoints?

Dr. Beslow:

The study endpoint was the correlation of the modASPECTS scores to the volumetric measurements of infarct volume as a percent of brain volume. A secondary endpoint was to determine whether a modASPECTS cutoff exists that differentiates between strokes > and < 5{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} of supratentorial brain volume since that was a volumetric cutoff that was predictive of hemorrhagic transformation and of poorer outcome in our previous study. Finally, we aimed to determine the interrater reliability of the score among 3 raters of varying clinical experience.

Victoria Murphy:

What were the results?

Dr. Beslow:

ModASPECTS correlated well with infarct volume. Spearman rank correlation coefficients (ρ) for the perinatal and childhood groups were 0.76, p<0.001 and 0.69, p<0.001, respectively. Excluding 1 perinatal and 2 childhood subjects with multifocal punctate ischemia without large or medium-sized vessel stroke, ρ for the perinatal and childhood groups were 0.87, p<0.001 and 0.80, p<0.001, respectively.

A modASPECTS of 5 maximized the sensitivity for differentiating large from small infarcts.

Childhood subgroup group: The sensitivity and specificity of a modASPECTS of ≥5 for correctly predicting a large infarct were 80{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} (95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} CI 65.4{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}-90.4{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}) and 87{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} (95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} CI 76.7{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}-93.9{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}), respectively.

Perinatal subgroup: The sensitivity and specificity of a modASPECTS of ≥5 for correctly predicting a large infarct were 85{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} (95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} CI 73.4{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}-92.9{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}) and 80{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} (95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} CI 61.4{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}-92.3{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208}), respectively.

The intraclass correlation coefficients for the three raters for the neonates and children were 0.93 [95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} confidence interval (CI) 0.89-0.97, p<0.001] and 0.94 (95{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} CI 0.91-0.97, p<0.001) respectively.

Victoria Murphy:

Are there any limitations to the study?

Dr. Beslow:

Our study has several limitations. A region was scored as positive even if a small part of a modified pediatric ASPECTS score region was infarcted. Furthermore, each involved region in the modified pediatric ASPECTS is given equal weight (1 point) even though areas like the M1-M6  represent more volume than smaller areas like the internal capsule, insula, or caudate. Both of these factors may cause the modified pediatric ASPECTS to overestimate the infarct volume as a percent of SBV in some patients. An extreme scenario for which the modified pediatric ASPECTS overestimates stroke volume is multifocal punctate ischemia, as demonstrated by the great improvement of the Spearman  rank correlation coefficient when excluding such patients (1 subject in perinatal group, 2 subjects in childhood group). Conversely, a subject with stroke affecting fewer than 5 of the MCA regions could still have a stroke volume >5{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} SBV if the entire regions are affected, thereby causing the modified pediatric ASPECTS to underestimate the true stroke volume as a percent of SBV. About 15{cf2c27d335602139ec9071daca508545599ba8f9ca09b366fd00e5c28736f208} of subjects were classified incorrectly as large versus small infarcts, and misclassifications were evenly distributed in either direction. Therefore, one should consider scenarios in which classification could be incorrect when applying the score. Despite these limitations, both the sensitivity and the specificity of the method were high. However, we do not recommend the use of the modified pediatric ASPECTS for use in children with isolated multifocal punctate ischemia.

Victoria Murphy:

What conclusions can be drawn from these results?

Dr. Beslow

This study demonstrates that the easily and quickly performed modified pediatric ASPECTS estimates arterial ischemic infarct volume as a percent of supratentorial brain volume for perinatal and childhood infarction with excellent interrater reliability and validity.  In the future, we hope that this will be a valuable tool for easily and reliably stratifying subjects according to infarct volume for clinical trials and for outcome prediction.

Victoria Murphy:

Can these results be considered conclusive?

Dr. Beslow:

Prospective studies are required to confirm its use for identifying children at risk for hemorrhagic transformation or poor long term outcome. Also, in order to expand the use of the score, its performance should be evaluated among other rater groups like intensivists and research assistants.

Victoria Murphy:

Dr. Beslow thank you for joining us today, it has been a pleasure.

Dr. Beslow:

Thank you very much, I enjoyed our discussion.