Newest Results from ELVIS: Early vs. Late Ventricular Intervention

Newest Results from the Early vs. Late Ventricular Intervention Study (ELVIS) in Preterm Infants with Posthemorrhagic Ventricular Dilation

By: Rebecca A. Dorner, MD MHS
Neonatology Fellow
Johns Hopkins Hospital

The randomized controlled ELVIS trial seeks to answer the question whether earlier or later neurosurgical interventions for preterm infants with posthemorrhagic ventricular dilation are better. In this study, intervention was defined as cerebral spinal fluid tapping by lumbar puncture (maximum of 3), followed by taps from a ventricular reservoir, all before a ventriculoperitoneal (VP) shunt. Early intervention was defined as intervention at a smaller ventricle size cutoff (ventricular index (VI) >97% and anterior horn width (AHW) >6 mm), in comparison to a larger ventricular size (VI>97% + 4 mm and AHW >10 mm).

The first paper1 from the study group analyzed results from 126 infants <34 weeks with grade III/IV intraventricular hemorrhage who participated in the trial from 2006-2016. Randomization to the study groups was at day 9 of life (median). The first intervention took place on day 10 (median) in the early intervention group versus day 15 in the late intervention group. They found that there was no significant difference in rates of the combined outcome of VP shunt or death in infants treated at a low versus high threshold. Shunt incidence was 19% (median) in the early intervention group versus 23% (median) in the late intervention group. Not surprisingly, infants with intervention in the low threshold group had more interventions as their first procedure was earlier.

The newest paper,2 recently published in the Journal of Pediatrics, is an additional analysis of the magnetic resonance imaging (MRI) results from this study. Babies’ MRI results at term age were given a brain injury score (Kidokoro Global Brain Abnormality Score) and ventricle sizes were measured too. This analysis found that infants in the earlier intervention/smaller ventricle size cutoff group had less brain abnormalities overall, and specifically less myelination delay, less thinning of the corpus callosum, less lateral ventricle dilation, and improved white and gray matter subscores. On these term age MRIs ventricle sizes were also lower in the smaller ventricle size cutoff groups.

The authors suggest that although the study failed to demonstrate a further reduction in the need for a VP shunt at the lower threshold, the need for VP shunt placement for both study groups is the lowest reported so far.  Smaller ventricle volumes and lower brain abnormality scores in the MRI studies might indicate the possible beneficial effects of earlier intervention in preterm infants with posthemorrhagic ventricular dilation. However, we still do not know if these improvements in MRI scores will translate to the most important results, lower rates of neurodevelopmental impairments in the future. It is important to wait for these results, as pointed out by Dr. Raye-Ann deRegnier in “The Editors’ Perspectives,” as the interventions (lumbar puncture, reservoir, VP shunt) themselves also have important complications.


  1. de Vries LS, Groenendaal F, Liem KD,  Heep A, Brouwer AJ,  van ‘t Verlaat E, et al. Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed, 104: F70-F75, 2019.
  2. Cizmeci MN, Khalili N, Claessens NHP, Groenendaal F, Liem KD, Heep A, et al. Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial. J Pediatr 208:191-197.e192, 2019

Keystone Symposia Announcement: February 16-19, 2020


Cerebral Fluid Flow and Function: Lymphatics, Glymphatics and the Choroid Plexus

Scientific Organizers: Edwin S. Monuki, Maria Lehtinen, and Maiken Nedergaard

Eldorado Hotel & Spa,Sante Fe, New Mexico on 16-19 February 2020.


  • Scholarship Deadline: Oct 15, 2019
  • Discounted Abstract Deadline: Oct 15, 2019
  • Abstract Deadline: Nov 19, 2019
  • Discounted Registration Deadline: Dec 17, 2019

Summary: The cerebrospinal fluid (CSF) has long been a “missing link” in our understanding of brain form, function, and disease. However, recent work has begun to illuminate how the CSF regulates the brain in ways that extend far beyond its passive historical roles and provides unique opportunities for studying, diagnosing, and potentially treating brain disorders. This Keystone conference brings together an interdisciplinary group of new and established scientists to capture this newfound excitement about the CSF. By exchanging discoveries – about its sources (choroid plexus), routes (glymphatics), drainage (lymphatics), and clinical utilities – and by fostering new ideas, collaborations, and training opportunities, this conference aims to coalesce an international community that can propel the CSF field forward. (Optional/TBD: This meeting is being held jointly with the “medicinal chemistry to cross the blood-brain barrier/BBB” meeting to stimulate thinking about CSF-based medicinal therapies, given the advantages of CSF over blood in being “behind” the BBB and in equilibrating with the interstitial fluid surrounding brain cells.)

For more information click HERE.

Hydrocephalus Society – Call for Abstracts


Call for Abstracts!

The final date for the Abstract Submission for the Eleventh Meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, which will be held in Vancouver, Canada from 13 to 16 September 2019, is approaching!

The Organizing and Scientific Committees welcome the submission of original contributions on the progress and controversies in hydrocephalus. Accepted papers will be presented as oral or e-poster presentations.

Consult the Thematic Sessions and the Submission Guidelines and submit your abstract until 3 May 2019!


Discovery Hydrocephalus 2019!

For more information you can visit their website or send them an e-mail at

Physician Scientist Fellowship: Doris Duke Charitable Foundation Announcement

The Doris Duke Charitable Foundation Announces a

New Award for Subspecialty Fellows


2019 Physician Scientist Fellowships

The Doris Duke Charitable Foundation (DDCF) today announced the creation of the Doris Duke Physician Scientist Fellowship. An open request for proposals will be launched in April 2019 to clinical investigators currently engaged in subspecialty fellowship training. Through the Physician Scientist Fellowship, DDCF aims to encourage emerging physician scientists to establish careers in clinical research.
Click here to find out more.


In keeping with the wishes expressed in Doris Duke’s will, experiments that use animals or primary tissues derived from animals will not be supported by this program.


Join the SRHSB in Spain! Abstracts due February 15th

The 63rd Annual Meeting of the SRHSB

La Laguna, Canarias on 26-29 June 2019.

Abstract Deadline: February 15th

Learn More:

The abstract submission deadline for the 63rd Annual Meeting of the SRHSB is soon approaching. The program will focus mainly on research in hydrocephalus, neural tube defects, and spina bifida, with the days and times designated for each topic contingent upon the abstracts submitted. They are also planning special sessions on brain development and transitional care for patients with hydrocephalus and spina bifida

The SRHSB is a unique meeting that mixes research with fun activities to allow meaningful interactions between colleagues.

Historically, the Canary Islands have been a meeting point between Europe, Africa, and America and is the perfect location to bring together international knowledge about hydrocephalus and spina bifida.

Hosts at La Laguna University:
Agustin Castaneyra-Perdomo, MD, PhD
Dean of the Faculty of Health Sciences, University of La Laguna

Leandro Castaneyra-Ruiz, PhD
Postdoctoral Research Associate at Washington University in St. Louis, USA, and member of the board of the SRSHB

Grant Opportunity! 2019 DoD CDMRP PRMRP Announcement

Hydrocephalus research eligible for CDMRP PRMRP Funding

Congress appropriated $350 million for the FY19 program to solicit proposals in 49 topic areas.

This week the Congressionally Directed Medical Research Program (CDMRP) released the Program Announcement for the Peer Reviewed Medical Research Program (PRMRP). The PRMRP, established in fiscal year 1999 (FY99), has supported research across the full range of science and medicine, with an underlying goal of enhancing the health, care, and well-being of military Service members, Veterans, retirees, and their family members. Program oversight is provided by a programmatic panel with joint military service and interagency representation. Congressional appropriations for the PRMRP totaled $2.0 billion through FY18 and have supported over 1170 awards in 139 different topic areas.

Most pre-applications are due March 14, 2019

The PRMRP has five award mechanisms:
Clinical Trial Award
Discovery Award
Focused Program Award
Investigator-Initiated Research Award
Technology/Therapeutic Development Award

Learn more about the Award Mechanisms and Deadlines.

2018 Discovery Science Award Grantees for PHH Announced


The 2018 Discovery Science Award Recipients for Posthemorrhagic Hydrocephalus!

A big thank you to all of the applicants and reviewers of the 2018 Discovery Science Award (DSA) for Posthemorrhagic Hydrocephalus! We had a great response and are happy to announce that HA was able to award three grants, totaling $900,000 over three years. Funding for the 2018 DSA for PHH came from the generous support of the PHH Campaign and Team Hydro.

Meet the grantees:

Maria Lehtinen, PhD | Boston Children's Hospital
The response of the choroid plexus to preterm hemorrhage
David Limbrick, MD, PhD | Washington University in St. Louis
Pharmacological prevention of posthemorrhagic hydrocephalus of prematurity
Yun Yung, PhD | Scintillon Institute
Drug delivery for posthemorrhagic hydrocephalus

To read about the projects go here:


The Kids First Data Resource Portal is now LIVE!

With more than 28,000 files of genomic and other data, researchers, clinicians, and patients will work together to accelerate research and promote new discoveries.

CHOP is looking to expand this open access database to include children with chronic medical conditions such as hydrocephalus. Greg Heuer (, CHOP, HANDS member) is involved with this effort.

See the press release:

You can start exploring this new resource TODAY! Visit and click on “JOIN NOW” to create your account.

To stay up to date on the latest foundation spotlights and news from the Kids First DRC, sign up for the email newsletter here:

2015-2017 HA Research Report

Download the 2015-2017 HA Research Report Today!

Learn more about HA’s Research Program and grantees. The 2015-2017 Research Report provides a snapshot of HA’s research activities over the past three years. We are excited about our accomplishments and cannot wait to see what is coming next.

Some highlights from the report:

  • $7.8M Spent on Research Programs since 2009
  • $3.9M Spent in the last three years
  • 150 New HANDS members since 2015
  • 18 Grants awarded since 2015
  • 3 Networks supported
  • 2 Workshops hosted

Download the Report Today
2015-2017 HA Research Report

Interested in the 2012-2014 Report?
2012-2014 HA Research Report


Posthemorrhagic hydrocephalus white paper published!

Outcomes from the 2016 PHH Workshop

A new white paper identifies important areas for research and intervention to help reduce the occurrence and effects of posthemorrhagic hydrocephalus (PHH), the most prevalent form of pediatric hydrocephalus in the United States. The paper, “Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop” was published in Fluids and Barriers of the CNS.

The paper summarizes recommendations from the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop, held July 25-26, 2016, at the National Institutes of Health, Neuroscience Center. The workshop brought together a wide range of researchers, including pediatric neurosurgeons, neurologists, neuropsychologists, and other key scientists. Members of the hydrocephalus community, such as family members of people affected by the condition, also participated in the workshop.

“The goals of the workshop were to identify areas of opportunity in posthemorrhagic hydrocephalus research and encourage scientific collaboration across a diverse set of fields. The white paper details the current knowledge base around PHH and offers key research targets for this complex condition,” explained Dr. Jenna Koschnitzky, the Hydrocephalus Association’s National Director of Research Programs.

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) within the cavities of the brain called ventricles. As the CSF builds up, it causes the ventricles to enlarge and the pressure inside the head to increase. PHH develops after a brain bleed and most often occurs in premature infants. It is a common and particularly insidious form of hydrocephalus, accounting for 25 percent of all pediatric hydrocephalus cases. To prevent PHH and the improve long-term outcomes, workshop participants recommended the following areas for future research:

Early Identification: It remains unclear why some children develop PHH after a brain bleed and others do not. Early identification of high risk infants could be an essential component in the development and testing of new therapies. Biomarkers that predict the development of PHH could lead to earlier intervention and improved outcomes.

Preventing Brain Bleeds: The blood vessels in the brain of premature infants are not yet fully developed, making them particularly susceptible to rupture. By protecting or strengthening these blood vessels, scientists could prevent brain bleeds in this vulnerable population.

Stopping Brain Damage: As a result of a brain bleed, blood damages the brain through a variety of mechanisms. Discovering and stopping these blood-derived factors could stop the damage and prevent the development of PHH.

Reestablish CSF Flow: After a brain bleed, it is believed that clots of blood and scar tissue block the flow of cerebrospinal fluid (CSF) through the brain. As the fluid builds up, pressure in the brain increases and causes hydrocephalus. Finding new ways to reestablish CSF flow could prevent PHH and reduce injury due to high brain pressure.

Repairing Brain Damage: PHH can damage the brain and also alter brain development. For example, infants with PHH are likely to suffer from intellectual disabilities and the co-occurrence of epilepsy and cerebral palsy. Finding strategies to repair the brain will improve long-term outcomes for those affected by the condition.

Workshop participants also discussed the importance of identifying the best care practices and treatment approaches for infants with PHH as well as the importance of conducting well designed clinical trials. Optimizing current clinical care across all hospitals will ensure that every infant has the best possible outcome while conducting high quality clinical trials will ensure that new scientific advances quickly become standard clinical practice.

The workshop was developed through the Hydrocephalus Association’s Pipeline to a Cure Initiative, a three-year initiative to increase research efforts focused on PHH.

About the Hydrocephalus Association
Founded in 1983 by parents of children with hydrocephalus, the Hydrocephalus Association has grown to be the nation’s largest and most widely respected organization dedicated to hydrocephalus. The Hydrocephalus Association began funding research in 2009. Since then, HA has committed over $7 million to research, making it the largest nonprofit, non-governmental funder of hydrocephalus research in the U.S. For more information, visit the Hydrocephalus Association website at or call (888) 598-3789.