Hydrocephalus occurs when cerebrospinal fluid (CSF), which is constantly produced in large quantities, cannot be absorbed or removed from the brain. Hydrocephalus can be caused by a wide variety of developmental abnormalities or injuries; the primary culprits are birth defects, infection, bleeding in or around the brain, trauma, and tumors. In children, this condition is especially damaging because the increasing CSF pressure causes the flexible skull to expand, which both compresses and stretches the overlying brain tissue. The only treatment available consists of draining excess CSF from the chambers (ventricles) within the brain to another site of absorption in the body. Usually CSF is “shunted” to the abdominal or chest cavities, but it can also be directed into the bloodstream. Neurosurgical procedures have recently been developed to open a channel in the floor of a ventricle that allows CSF flow to the spaces surrounding the brain and spinal cord. However, this form of shunt treatment is only palliative. No cure exists for hydrocephalus.


Prevalence and Incidence – The Epidemiological Burden of Hydrocephalus

Hydrocephalus is common. It afflicts people of all ages, and is especially common in children. The incidence of infantile hydrocephalus is approximately one in every 500 live births, making it one of the most common birth defects, more common than Down syndrome or deafness. In the U.S., that would indicate an incidence of 20,000 new shunts per year, which supports a 1988 United States National Health Interview Survey that estimated that 18,000 new shunts were placed annually. According to the NIH website, there are an estimated 700,000 children and adults living with hydrocephalus. In the United States, the healthcare costs for hydrocephalus has exceeded $1 billion per year, but is still much less funded than research on other diseases including juvenile diabetes. It is likely that more people have hydrocephalus, especially the elderly with normal pressure hydrocephalus (NPH), and many have not had a diagnosis established or are so frail that the potential complications of shunt surgery are prohibitive.

It is important to remember that one frequently overlooked aspect of hydrocephalus is that it presents the patient and the family with a life-long struggle for survival and relatively normal function. One of the most performed treatments for hydrocephalus, the cerebral shunt, has not changed since it was developed in the 1950’s. The shunt must be implanted through neurosurgery into the patient’s brain, a procedure which itself may cause brain damage. An estimated 50% of all shunts fail within two years, requiring further surgery to replace the shunts. In addition to the seemingly never-ending trips to the hospital for multiple shunt revisions, families drain their personal and financial resources by the constant care required by their disabled child. Problems may remain consistent throughout the patient’s life. The first patients treated with shunts are approaching 50 years of age. Reports of dyslexia, memory deficits, psychosocial impairments, and job loss are becoming more prevalent.


Current Management is Not Optimal

The management of hydrocephalus is fraught with complications. Approximately 40% of shunts fail and require further surgery within a year, and 60% fail by two years. Infection rates at most centers vary between 5-15% per procedure. Other complications are fairly common including slit-ventricle syndrome and subdural hematomas. The need for hospitalizations and surgery for these patients is substantial. Of all medical devices that are implanted in the body, shunts for hydrocephalus arguably have the highest failure rate.

Hydrocephalus is a disease that appears to be intrinsically preventable or reversible in most patients. The potential for improved treatment is enormous because, unlike many other neurological disorders, the brain of most patients is normal before the onset of hydrocephalus. For those whose hydrocephalus develops during gestation, imaging modalities make it possible to detect the changes early in the fetal period at a time when interventions could be most helpful.


Why Has Progress in Improving Treatments for Hydrocephalus been So Slow?

Hydrocephalus is truly a multi-factorial disorder, with many overlapping causes and injury mechanisms. Furthermore, the proportional impact of these factors and the relationships between each factor are completely unknown. It is extremely difficult to isolate and to focus on just one injury mechanism. This, in turn, causes problems with experimental designs and obstacles to funding “clean” research studies.

Medical instrumentation companies do not view hydrocephalus as a large enough market to warrant significant further research and development. Now that NPH is being recognized as a more prevalent subset of hydrocephalus, some companies are beginning to development better shunt valves and systems; however, they are reluctant to invest in innovative research.

Finally, little is known about the causes of hydrocephalus, and how injury mechanisms contribute to brain damage. The advent of CSF shunts over 50 years ago marked a dramatic improvement in the management of hydrocephalus. However, this milestone seems to have created a mindset that focused on the technological development of CSF drainage systems with little regard for the cellular and biochemical alterations that accompany hydrocephalus. While gains have been made in understanding how different valve configurations perform under various hydrostatic conditions, the cellular bases for neurological impairments have been neglected. To date, only one study using Nimodipine has attempted to protect the hydrocephalic brain, but these interventions produced only limited short-term success. No attempts have been made to reduce any of the other injury mechanisms known to occur in the hydrocephalic brain. Therefore, promoting supplemental pharmacological treatments for hydrocephalus has been minimal.

The situation is most unfortunate. There is much to be gained by what could be an incremental improvement in our understanding and management of hydrocephalus.


Reversibility

Hydrocephalus is one of the few, almost completely reversible, causes of acute coma in the young, and dementia and gait disturbance in the elderly. A hydrocephalic patient can be admitted to the hospital in deep coma, minutes from death, and following treatment of the hydrocephalus, be discharged the next day in a neurologically normal condition.

Hydrocephalus is perhaps the best paradigm of a reversible brain disease in the elderly. An understanding of why it is reversible could lead to a better understanding of neurological recovery benefiting people with other neurological disorders such as stroke, Parkinson's disease, and Alzheimer's disease, in which reversibility is thus far much more limited. The apparent effectiveness of shunting patients with Alzheimer's disease to stabilize the progression of dementia is tantalizing. Rescuing vulnerable neurons and promoting recovery of function has become a common theme in neurobiology, but potentially beneficial approaches, such as stem cell replacement and gene therapy have not been considered in hydrocephalus.

Understanding the reversibility of hydrocephalus could give us deeper insight into strategies for reversing the manifestations of other more intractable neurological disorders.


Prevention

Attempts to prevent brain damage in hydrocephalus, other than refinements in shunt design and timing, have been rare, yet neuroprotection has been the focus of many experimental and clinical studies in stroke and traumatic brain injury. The entire field of neurobiology is replete with examples of neuroprotection, including applications of trophic inhibitors, biochemical interactions, pre-conditioning, and hypothermia, but only the ventricular infusion of nimodipine, a calcium channel blocker, has been tested for preventive therapy. Although many reports have described the gliosis that develops and persists in the hydrocephalic brain, no attempts have been made to reduce reactive astrocytosis or microgliosis, even though glial inhibitors such as minocycline are known to be effective in cerebral ischemia and Parkinson’s disease. By building on successes in other brain injury models, prevention should play a prominent role in the development of supplemental treatments for hydrocephalus.


Basic Science

Neurosurgeons and engineers alike have made impressive gains in the development of better drainage systems for hydrocephalic patients. Nevertheless, their expertise is severely limited by the lack of data on brain damage created by hydrocephalus. There are major gaps in our understanding of the way hydrocephalus damages the brain. The basic physiology of CSF circulation and the pathophysiology of hydrocephalus as well as abnormalities in pulsatile dynamics are poorly understood. The formation of scars and change in cellular structure within brain tissue and the influence in brain function is not well known.

There is much to be learned about the basic biology of CSF circulation, the relationship between CSF dynamics and cerebral blood flow, and the pathophysiology of hydrocephalus. This understanding may lead to more effective treatments for hydrocephalus as well as deeper insight into the pathophysiology of many brain disorders.