School of Medicine

Charge to the Group
Katrina Gwinn-Hardy, NINDS, Program Director

Introduction of Chairs:
Michael A. Williams, Marion L. (Jack) Walker, J.P. (Pat) McAllister

Brief Outline of the Day
Katrina Gwinn-Hardy NINDS

Breakout Sessions

The six plenary talks will introduce the most current knowledge, challenge the existing dogma and mythology surrounding hydrocephalus, and identify critical gaps in research and clinical treatment. As smaller, more focused groups, the Breakout Sessions will help develop strategies for improving our knowledge level and identifying new collaborative opportunities.

Each of the Breakout Groups will be charged with answering several fundamental questions:

1. What is the critical information that has been missing and has impeded progress toward better understanding of the pathophysiology of hydrocephalus, its clinical manifestations, its treatment, and its outcomes?
2. What is the best way to obtain this information?
3. How can research in related disorders be utilized to improve our understanding of hydrocephalus, and vice versa?
4. How can clinicians, clinical researchers, and basic scientists collaborate more effectively?
5. What are the critical differences between Pediatric Hydrocephalus and Adult Hydrocephalus?

Each 3-hour Breakout Session will be led by 3 co-moderators who will facilitate a discussion among the breakout session invited participants to address the specific questions for each session. Participants will be asked to choose one session to attend, and each session will include about 30 participants.

Following the Breakout Sessions, all participants will reconvene and the moderators from each group will present a summary of the key ideas proposed and lead an open discussion with all attendees. The consensus from the Breakout Sessions and the open discussion will constitute a major portion of the White Paper that will be produced from this symposium.

Breakout Session 1:
Injury Mechanisms, Neuroprotection, and
Cellular Recovery in Hydrocephalus

Moderators: Michael Williams, Pat McAllister, Marcy Speer

Laboratory and clinically based scientists will discuss the assumptions and myths which have slowed progress in hydrocephalus. While hydrocephalus is often considered a disorder of CSF circulation, and much attention has been focused on CSF physiology, the clinical manifestations of hydrocephalus are the result of altered brain function. Discussions will address the effects of hydrocephalus on the brain, including injury and recovery mechanisms affecting neurons and glia, the potential for recovery of neuronal and clinical function, and exploration of how laboratory models of hydrocephalus may lead to a better understanding of hydrocephalus, development of adjunctive therapies, or development of important clinical translational research.

Major questions:

1. 1. What areas of research in the neurobiology of brain injury and recovery, plasticity, motor control, or dementia that haven’t been applied to hydrocephalus do you see as having immediate and meaningful potential to our understanding of hydrocephalus?
2. What aspects of hydrocephalus could be studied and give rise to immediate and meaningful understanding of brain function, brain injury and recovery, or plasticity? (The inverse of question #1) What additional molecular and laboratory based studies do we need to understand hydrocephalus?
3. What are the most useful in vivo models available now? How could they be improved, and most importantly, what models do we need to develop to further research on the cellular pathophysiology of hydrocephalus?
4. Are there other models of brain injury and recovery that would allow better understanding of the apparent changes in the pathophysiology and treatment of hydrocephalus, especially as humans age?
5. How can the existing animal models be useful to study and develop adjunctive therapies as well as treatment with CSF diversion?
6. What methods or areas of experimental and clinical research ought to be advanced for better understanding of human brain function in hydrocephalus? For example: PET; fMRI; EEG; analysis of CSF for inflammatory markers, demyelination, alteration of neurotransmitters or metabolites, pharmacological supplements to shunt-treatment, gene therapy, behavioral rehabilitation, and stem-cell applications.
   

Breakout Session 2:
New insights into the Pathophysiology of CSF Circulation - Implications for Shunt Design and/or Other Treatments for Hydrocephalus

Moderators: Michael Egnor, Marion L. Walker, Marvin Sussman

This session will focus on CSF pathophysiology, pulsatility, and diagnostic imaging in order to address all aspects of shunt treatments and complications. The traditional model of impaired CSF resorption at the arachnoid villi leading to ventriculomegaly in so-called “communicating hydrocephalus” is being called into question. What are the critical factors in CSF circulation, cerebral blood flow, intracranial compliance or CSF pulsatility that lead to ventricular enlargement, altered brain function? Are these factors amenable to treatments other than shunts or CSF diversion? What laboratory and clinical research questions should be pursued to answer these questions?

Major questions:

1. 1. In what ways are shunts effective, and in what ways are they ineffective or harmful?
2. What assumptions about the pathophysiology of hydrocephalus, including CSF secretion, flow and resorption, cerebral blood flow, and intracranial compliance are the basis for traditional shunt designs? What research needs exist in terms of creation and re-absorption of CSF?
3. What aspects of the pathophysiology of hydrocephalus should be studied to improve our understanding? Are there aspects of other areas of physiology that could be applied to hydrocephalus?
4. What are the most useful in vivo models available now? How could they be improved, and most importantly, what models do we need to develop to further research the pathophysiology of CSF physiology?
5. How might this new knowledge change the way we design or surgically implant shunts, or suggest other approaches to the treatment of hydrocephalus with medical devices or treatments to alter intracranial compliance, CSF flow and CSF pulsatility, including the management of complications, such as slit ventricle syndrome and recurrent shunt obstruction?
6. Does this new knowledge suggest new approaches to the pharmacological treatment of hydrocephalus?
7. What methods or areas of experimental and clinical research ought to be advanced for better understanding of human physiology in hydrocephalus? For example, MRI, ultrasound, or radionuclide techniques.
   

Breakout Session 3:
Clinical Tools, Clinical Trials, and Clinical Outcomes

Moderators: Tony Marmarou, John Kestle, Dory Kranz

There are significant concerns regarding how to diagnose hydrocephalus, particularly in regard to the distinction between compensated and uncompensated hydrocephalus and the need for treatment of children or adults. Even if diagnosis were reliable, there remains a demand for clinical and epidemiological studies. What is the essential information needed to characterize hydrocephalus clinical outcomes in a meaningful way for further research and treatment development?

As we embark on setting a national research agenda with the objective of improving outcomes for those living with hydrocephalus, it is essential that we are clear about which outcomes we intend to improve and how we will measure that improvement. Currently there is little research measuring neuropsychological, cognitive, sensorimotor, or quality of life outcomes such as employability and autonomy for people living with hydrocephalus. Since hydrocephalus in adults may be one of the only examples of a reversible neural injury, there should be opportunities to learn from people living with this disorder so treatment can be improved in this and other conditions.

Major Questions:

1. 1. Are the standards of care for diagnosis and treatment of hydrocephalus, including selection of shunts and surgical approaches, adequately supported by research data?
2. What important clinical research questions regarding the diagnosis and treatment are most in need of study? Are there particular challenges in clinical trial design in hydrocephalus that should be addressed? Is there a role for longitudinal studies in hydrocephalus?
3. Is there adequate expertise and infrastructure within the health care system to provide care to patients with hydrocephalus throughout their lives? Are there barriers to care that should be addressed? Is there research that could help identify or address such barriers?
4. What is known about therapeutic outcomes of hydrocephalus, including not only cognitive, gait and urinary symptoms, but also nausea, vomiting and headache, motor and cognitive development for children, and ADL and quality of life?
5. What physiological, clinical, cognitive, functional, psychosocial or economic outcomes are being measured in other chronic neurological conditions that could be applied to hydrocephalus?
6. Are existing quality of life outcome scales adequate for hydrocephalus, especially considering the different manifestations of the disorder at different stages of life?