Head Ultrasound lesions and developmental progress: Predicting Long-Term Outcomes part 2

Two recent articles that give much more information about the predictive capacity of head ultrasounds.

Many articles about head ultrasounds and outcomes use the Papile classification. This classification was developed for simple classification of periventricular hemorrhage types as seen on CT scan into broad categories. The fourth of of those broad categories is extremely broad.

There are 2 major problems with the current use of the Papile classification. The first being that a modestly sized intraventricular hemorrhage, which subsequently develops ventricular dilatation, may be referred to as a grade 3 hemorrhage. A large intraventricular hemorrhage which acutely dilates the ventricles is also referred to as a grade 3 hemorrhage. These 2 occurrences do not necessarily have the same consequences, and should be differentiated, but in many publications it is not clear whether such a discrimination has been made.

More importantly I think, a grade 4 hemorrhage can refer to a multitude of different injuries. A small localized intracerebral hemorrhage, and huge bilateral hemorrhagic destruction of the hemispheres are both referred to as grade 4 hemorrhage, and subsequently grouped together in outcome studies. It is self-evident that they must have different consequences for brain function, but finding the relative significance of these 2 variations is next to impossible in the literature.

It also seems very likely that frontal, parietal, temporal, and occipital hemorrhages may have different effects, but again there has been little published information to use to inform parents. Furthermore, an echodense lesion may appear to be a hemorrhage to one person, but may be thought to be infaction or oedema to another.

This huge problem has been addressed by the ELGAN study (a multi-center prospective cohort study of Extremely Low Gestational Age Newborns); that is, inter-rater variability in interpretation of head ultrasounds, both in how the findings are perceived, and how they are reported. By variations in how they are perceived I mean that even when sonologists are asked to just determine whether there is a parenchymal lesion, (which they can then note as being an echodensity or echolucency), they are often unable to agree. In one report from the study (Kuban K, Adler I, Allred E, Batton D, Bezinque S, Betz B, Cavenagh E, Durfee S, Ecklund K, Feinstein K et al: Observer variability assessing US scans of the preterm brain: the ELGAN study. Pediatr Radiol 2007, 37(12):1201-1208. http://www.springerlink.com/content/k2637421vj4vvq74/?MUD=MP) they noted that when one sonologist reported an echodense lesion, about 50% of the time the lesion was not reported by another sonologist. Similarly, about 40% of echolucent lesions were not reported by a second sonologist. We often make critical decisions based on these findings, so these discrepancies are very concerning.

Similarly variable are the terms used by sonologists to report the same lesions. The same lesion may be referred to as early PVL, late PVL, or periventricular hemorrhagic infarction, by different sonologists. (Westra S, Adler I, Batton D, Betz B, Bezinque S, Durfee S, Ecklund K, Feinstein K, Fordham L, Junewick J et al: Reader variability in the use of diagnostic terms to describe white matter lesions seen on cranial scans of severely premature infants: The ELGAN study. Journal of Clinical Ultrasound 2010, 38(8):409-419. http://onlinelibrary.wiley.com/doi/10.1002/jcu.20708/abstract)

For this reason, the ELGAN study decided to describe simply whether or not there was an echolucent or echodense lesion; but as noted above this did not eliminate the differences in interpretation.

To get back to the two recent publications referred to at the start of this post:

Michael O’Shea and the ELGAN study investigators (O’Shea TM, Kuban KC, Allred EN, Paneth N, Pagano M, Dammann O, Bostic L, Brooklier K, Butler S, Goldstein DJ et al: Neonatal cranial ultrasound lesions and developmental delays at 2 years of age among extremely low gestational age children. Pediatrics 2008, 122(3):e662-669. http://pediatrics.aappublications.org/content/122/3/e662.long) have compared the location of echodense and echolucent lesions and the neurodevelopmental outcomes at 2 years of age, according to neurologic exam and Bayley 2 MDI and PDI.

They have shown that lesions in different areas of the brain have different impacts on the likelihood of low Bayley MDI and PDI scores. One example is the figure shown below showing the effects of an echolucent lesion in different locations on the scores on a 2 year Bayley exam (the proportions with an MDI <70 are on the left, PDI <70 on the right:

Percentage of children whose scan had an echolucency in a particular location and who had an MDI of <70 (black numbers on the left side of the brain) or a PDI of <70 (black numbers on the right side of the brain) on the BSID-II

The other article from Stephanie Merhar and others (Merhar SL, Tabangin ME, Meinzen-Derr J, Schibler KR: Grade and laterality of intraventricular haemorrhage to predict 18-22 month neurodevelopmental outcomes in extremely low birthweight infants. Acta Paediatr 2012, 101(4):414-418. http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.2011.02584.x/abstract ) has examined the association between whether periventricular hemorrhages were unilateral or bilateral and Bayley Scores. They found several interesting things. Most importantly infants with grade 4 hemorrhage (referred to as PVHI in the ELGAN studies) did NOT have worse Bayley scores at 2 years, unless the lesion was bilateral. Infants with unilateral grade 4 hemorrhages had a range of Bayley MDI scores which was very similar to those with unilateral subependymal hemorrhage.

Secondly, even among those with bilateral PHVI if they did not develop either sepsis or receive postnatal steroids, then only 25% had an MDI less than 70. In contrast, those who had Bilateral PVHI and had either sepsis or steroids or both had an increasing proportion of children with low Bayley scores.

To me this means that the preterm brain has a huge potential for repair and recovery. When a serious injury occurs, even if a large part of the brain is affected,  there is a chance of recovery and good outcome, but if that repair is interrupted by sepsis or dexamethasone, then the outcomes are much worse. These results should make us pause and reflect: bilateral parenchymal hemorrhages do not necessarily lead to an MDI less than 70, even those with an MDI less than 70 will often have IQ in the “normal” range in later life. Very few will be profoundly multiply disabled. The addition of multiple other insults during hospitalisation progressively worsens outcome.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , . Bookmark the permalink.

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