Testimony Congressional Pediatric and Adult Hydrocephalus Caucus Michael A. Williams, MD, FAAN Medical Director, Sandra and Malcolm Berman Brain & Spine Insitute Director, Adult Hydrocephalus Center, Sinai Hospital of Baltimore Mr. Chairman and Members of the Caucus, Thank you for the privilege of speaking before the Congressional Pediatric and Adult Hydrocephalus Caucus. I am Michael A. Williams, a neurologist, and Medical Director of the Sandra and Malcolm Berman Brain & Spine Institute at Sinai Hospital of Baltimore, where I direct the Adult Hydrocephalus Center. I am also the President-elect of the International Society for Hydrocephalus and Cerebro-Spinal Fluid Disorders, the ISHCSF, and I am a member of the American Academy of Neurology, which has over 18,000 U.S. members. I have cared for patients with hydrocephalus for more than 20 years over my entire career, starting as a NeuroICU specialist at Johns Hopkins where I cared for acute, life-threatening forms of hydrocephalus. I then developed an integrated program of care for adults with chronic forms of hydrocephalus, focusing on the use of physiologically-based testing to correctly determine whether a patient would benefit from a shunt. As a result, I ceased my work in the ICU to focus my efforts on hydrocephalus for the last decade. I have also been active as a member of the Medical Advisory Board for the Hydrocephalus Association for more than 15 years, and I have worked closely with them to promote the care of patients with hydrocephalus, and to promote research in hydrocephalus. My aim today is to provide you background on the nature of hydrocephalus, the population it affects, the available treatments, and the state of clinical and basic research. Let me start with basics. The term hydrocephalus translates as water on the brain. More specifically, however, it
Michael A. Williams, MD Page 2/8 means the abnormal accumulation of spinal fluid from its site of secretion inside the ventricles of the brain to its site of resorption into the bloodstream over the top of the brain. The ventricles or spinal fluid cavities of the brain are normal structures that we all have. The term hydrocephalus is often a shorthand term for enlargement or dilation of the ventricles, but it is worth noting that the ventricles can also appear enlarged if there is atrophy or withering of the substance of the brain, as can happen with disorders like Alzheimer dementia. The enlargement of the ventricles in this circumstance is not considered hydrocephalus, but this overlap in the appearance of the brain scans in elderly patients with degenerative dementias and those with hydrocephalus creates the circumstance of frequent misdiagnosis for both groups. If hydrocephalus is caused by impaired circulation or resorption of spinal fluid, then the causes of impaired circulation are key to the disorder. In infants and newborns, a congenital malformation of the brain, such as spina bifida or aqueductal stenosis can cause an overt physical obstruction to flow. Alternately, in infants, children, adolescents, and young, middleaged or elderly adults, any process that causes inflammation and subsequent scarring in the spinal fluid spaces of the brain can cause hydrocephalus. Examples include infections, like meningitis from bacteria, viruses, tuberculosis, or fungi, or bleeding that can occur with ruptured cerebral aneurysms, arterio-venous malformation, or mild, moderate or severe traumatic brain injury. Thus, hydrocephalus can be either a primary or a secondary disorder, and it can affect patients of any age or stage of life, from in utero to infancy to senescence. Regardless of the cause or the site of obstruction to spinal fluid circulation, the result is that spinal fluid begins to collect behind the obstruction, like water behind a dam, causing the ventricles to enlarge. This enlargement in simplest terms causes stretching and distortion of the brain, alterations in blood flow to the brain, and alterations of the composition of the interstitial fluid of the brain, which cause the brain cells (neurons and glia) to malfunction, which results in
Michael A. Williams, MD Page 3/8 symptoms. If left untreated, hydrocephalus can become irreversible with permanent impairment. The symptoms of hydrocephalus depend on the age or stage of life at which it develops. The primary hydrocephalus symptoms in children are different from those in young and middle-aged adults, which differ from those in the elderly. As but one example, hydrocephalus in the elderly produces a syndrome known as normal pressure hydrocephalus, or NPH. Its symptoms are shuffling gait, urinary urgency and incontinence, and cognitive impairment or dementia which also happen to be the three most common problems of the aging population. As a result, patients and their physicians often overlook the possibility of NPH because they attribute the symptoms to old age. But if you diagnose and treat NPH, you can make a dramatic difference in a patient s life, as you will hear in testimony later today. From a population and medical economic perspective, in 2007 in the Journal of Neurosurgery I published research using the Medicare Database and showed that 5-year Medicare expenditures in elderly adults with hydrocephalus who receive shunt surgery are $25,000 less than expenditures for those who do not receive shunt surgery. While only 25% of patients received shunts, the potential cost savings extrapolated to $184 million over 5 years. Thus, identification and treatment of hydrocephalus benefits both individual and population health. Although hydrocephalus has been recognized as a disorder of infants and children since ancient times, no effective treatment existed until the mid-1950s. Therefore, children with hydrocephalus often died of the disorder, or survived with severe developmental delay. Because hydrocephalus began before the bones of the skull had fused, the head often enlarged to immense proportions as the hydrocephalus progressed. The first successful treatment for hydrocephalus, known as a shunt was invented in 1956 by a man named John Holter, whose son Casey was born with spina bifida and hydrocephalus. John Holter filed for a U.S. patent almost exactly 55 years ago on October 2, 1956, and patent #2,969,066 was issued in 1961.
Michael A. Williams, MD Page 4/8 A shunt is a deceptively simple device, consisting of one tube that is inserted into the spinal fluid space (usually the ventricles in the brain), connected to a one-way valve mechanism that helps to regulate the flow of the fluid, connected to a second tube that conveys the spinal fluid to a site where it can be reabsorbed (usually the abdominal cavity or the vena cava, which is the large vein leading directly to the heart). A shunt is essentially a tiny plumbing system, or as one of my patients termed it, a downspout. Shunts revolutionized the care of children with hydrocephalus. Children who would have died now survived. As a matter of fact, I care for several adults from this first generation whose shunts are older than I am. With the success of the shunt, however, arrived the ultimately tragic misconception that hydrocephalus had been cured. Physicians of that era, and even physicians now concluded, it s just a simple problem of CSF circulation that s easily corrected with the shunt. Nothing could be farther from the truth, but the misconception that hydrocephalus was cured led to a virtual stagnation in the basic and clinical research of the disorder for two, if not three generations of patients with hydrocephalus. Once we got past the initial 10-15 years of medical reports on series of patients with hydrocephalus, including the first of many reports on the complications of shunts and shunt surgery, there was little substantial research performed except for that needed by shunt manufacturers to demonstrate that their shunts were equivalent to existing devices so they could obtain FDA approval. What is the consequence of this dearth of research? Imagine, if you would, an automobile from 1956, before we had GPS, or airbags, or seatbelts, or any of the myriad safety devices that we now take for granted. Would you put yourself or your family in a 1956 automobile and drive high speed on the interstate? Of course not. It wouldn t be safe. But now consider that although the
Michael A. Williams, MD Page 5/8 manufacturing methods and the size of the shunts has changed over the years, their fundamental design has not changed since they were invented in 1956. Shunts can make a dramatic difference, but shunts are among the least reliable of all medical devices on the planet. Shunt failure, shunt malfunction, and shunt complications, including infections, occur at a frightening rate, and frequently result in more harm to patients. If pacemakers or artificial hips failed at the rate at which shunts fail, there would be a deafening public outcry. A research paper published in the journal Neurosurgery in 2005 found that the cost of shunt surgery in the United States is over $1 billion per year, and over 40% of hospital admissions were for shunt malfunction. The fact of the matter is that we expect shunt failure to occur in our patients time after time after time. And we live with this because we have no choice. There is no alternative treatment except for a procedure called endoscopic third ventriculostomy, or ETV, which can be used only in a minority of hydrocephalus patients. We have no choice. There is no medication to treat hydrocephalus. We have no choice. We have no choice except to treat our patients as best we can with a malfunction-prone device, the design of which predates Sputnik! We endeavor to take good care of our patients, but we need advances in research to do even better. The reality of hydrocephalus is that it is a far more complex disorder than anybody ever realized, and I can tell you as the President-elect of the ISHCSF that of the approximately 10 million physicians and millions more scientists around the world, no more than ~250 of them truly understands this. The global knowledge deficit in terms of research and clinical practice harms patients. Those of us in the hydrocephalus scientific community have known this for a long time, and we ve worked diligently to make a change. We are a tiny cadre of physicians and scientists struggling to make the discoveries that will lead to significant changes in the quality of our patients lives.
Michael A. Williams, MD Page 6/8 As I said, we aren t standing idly by. I had the pleasure of working hand-in-hand with the Hydrocephalus Association beginning in 2004 to work with the NIH to convene a workshop titled Hydrocephalus: Myths, New Facts, and Clear Directions in Bethesda from September 29 to October 1, 2005. More than 150 neurosurgeons, neurologists, laboratory-based scientists, patient advocates, patients, parents, and program staff from five institutes and one office within the NIH assembled for a day-and-a-half of plenary discussions that summarized the current knowledge, challenged existing dogma and mythology, and identified critical gaps in research and clinical treatment. It was there that I first publically made the point that I will share with you now. Our focus on hydrocephalus as a plumbing problem to be fixed with a shunt was wrong from the very beginning. We were so blinded by the success of the shunt that we utterly failed to see that hydrocephalus is not a CSF disorder. Yes, that s right. I said that hydrocephalus is not a CSF disorder. Hydrocephalus is a brain disorder. The symptoms of hydrocephalus are caused by a reversible injury to the brain, and yet we know very little about the injury and recovery mechanisms. There is no other disorder in neurology or neurosurgery in which symptoms can be present for months or years, as they are in hydrocephalus, and yet reversed in days or weeks with the insertion of a shunt. The cascade of events within brain cells (neurons and glia) that lead to recovery that are unleashed by the insertion of a shunt are poorly understood, and yet, if we can understand how the brain is protected from apparent permanent injury, and how the recovery mechanisms from the injury work, then we could develop the potential for medical or biologic treatments for hydrocephalus that either augment treatment with a shunt, or replace the need for a shunt entirely. And if we can make these mechanisms work for hydrocephalus, then we have the
Michael A. Williams, MD Page 7/8 potential to test their applicability to other disorders of the brain, such as stroke, or ALS, or Parkinsonism, or Alzheimer disease, to name but a few. I want to take just a moment to mention that besides hydrocephalus, there are other significant disorders of CSF circulation that have significant health impact and for which there has been little research. These include arachnoid cysts, Chiari malformations, syringomyelia, and spontaneous intracranial hypotension (low CSF pressure). I d like to draw special attention to a disorder known as pseudotumor cerebri, or intracranial hypertension, which is a disorder of elevated spinal fluid pressure with small ventricles that causes severe headaches, but more importantly causes swelling and injury to the optic nerves and, in extreme circumstances, can cause blindness. I serve on the Scientific Advisory Team of the Intracranial Hypertension Research Foundation. Pseudotumor is also treated with shunts, and other treatment modalities exist, but it is a challenging problem to treat. Pseudotumor, as a disorder of spinal fluid circulation, may be affecting astronauts in long-duration space flights. A recently published paper in the journal Ophthalmology describes abnormal eye findings in 7 astronauts after longduration space flight, and 2 of the 4 astronauts who had a spinal tap after returning to earth had elevation of the spinal fluid pressure. I have been part of a group of scientists speaking to NASA over the last 18-24 months about this problem. The risk in long-duration space flight is that astronauts could develop significant visual impairment en route to Mars or the asteroid belt, and not have a safe and effective way to prevent or manage the disorder. NASA has defined a high research priority for VIIP, Visual Impairment Intracranial Pressure, in a recent announcement for research funding, but the amount of funding is modest. Research to improve our understanding of CSF circulation in microgravity could be key to our ability to conduct long-duration space exploration.
Michael A. Williams, MD Page 8/8 As I finish my testimony, I want to take a moment to mention the hydrocephalus research priorities that came out of the 2005 NIH Hydrocephalus Workshop. The white paper, which was published in the Journal of Neurosurgery in 2007, outlines an extensive list of research issues and questions to be addressed. I won t list them all, but let me highlight the major categories: Basic Research, Clinical Research, Research Infrastructure, Clinical Care. The last of them, Clinical Care, can only improve with advances in clinical and basic research. Clinical and basic research can only be produced if we have a critical mass of talented young physician scientists and basic scientists to conduct the research, and to do this, we need an expanded research infrastructure, which means the creation of research networks that include centers of excellence with research mentors, support for data and specimen sharing, and funding for the research networks and research projects. I want to thank you for your attention and your patience. I hope I ve been able to convey a sense of the importance and impact of hydrocephalus in such a short period of time. I m sure it won t surprise you to hear that I could share much more with you, and if there s time for questions now, or if you or your staff which to be in contact with me later, I would be more than happy to provide additional thoughts and insight. Thank you once again.