J Neurosurg (3 Suppl Pediatrics) 104:157–159, 2006 What we don’t (but should) know about hydrocephalus MARVIN BERGSNEIDER, M.D., MICHAEL R. EGNOR, M.D., MILES JOHNSTON, PH.D., DORY KRANZ, M.A., JOSEPH R. MADSEN, M.D., JAMES P. MCALLISTER II, PH.D., CURT STEWART, M.P.A., MARION L. WALKER, M.D., AND MICHAEL A. WILLIAMS, M.D. Department of Neurosurgery, University of California at Los Angeles, California; Department of Neurosurgery, New York Spine and Brain Surgery, State University of New York, Stony Brook, New York; Neuroscience Research Program, Sunnybrook & Women’s Health Sciences Centre, Toronto, Ontario, Canada; Hydrocephalus Association, San Francisco, California; Department of Neurosurgery, Boston Children’s Hospital, Boston, Massachusetts; Department of Neurosurgery, Children’s Hospital of Michigan, Detroit, Michigan; Brain Child Foundation, Carefree, Arizona; Division of Pediatric Neurosurgery, Primary Children’s Hospital, Salt Lake City, Utah; and Department of Neurology, The Johns Hopkins Hospital, Baltimore, Maryland PIn an effort to identify critical gaps in the prevailing knowledge of hydrocephalus, the authors formulated 10 key questions. 1) How do we define hydrocephalus? 2) How is cerebrosinal fluid (CSF) absorbed normally and what are the causes of CSF malabsorption in hydrocephalus? 3) Why do the ventricles dilate in communicating hydrocephalus? 4) What happens to the structure and function of the brain when it is compressed and stretched by the expanding ven- tricles? 5) What is the role of cerebrovenous pressure in hydrocephalus? 6) What causes normal-pressure hydroceph- alus? 7) What causes low-pressure hydrocephalus? 8) What is the pathophysiology of slit ventricle syndrome? 9) What is the pathophysiological basis for neurological impairment in hydrocephalus, and to what extent is it reversible? 10) How is the brain of a child with hydrocephalus different from that of a young or elderly adult? Rigorous answers to these questions should lead to more effective and reliable treatments for this disorder. KEY WORDS • hydrocephalus • critical issues • normal-pressure hydrocephalus • treatment • pediatric neurosurgery The problem isn’t with what we don’t know, the problem is ment of hydrocephalus. More than 30% of new shunts fail with what we do know that isn’t so. within 1 year.7,12 Fewer than one third of new shunts survive —WILL ROGERS 10 years without revision.13,15 In some large pediatric neuro- Hardly any other pathological condition has been accorded surgery services, the ratio of shunt revisions to placement of more determined attention on the part of the medical profession new shunts is 2.5:1.15,16 Authors of a recent randomized con- . than has hydrocephalus. And in hardly a single other condi- trolled multicenter study have shown that a half century of tion have cures been so elusive or so often wrecked on purely research in shunt valve design has produced little if any im- mechanical obstacles. provement in the rate of shunt survival.7 —LEO DAVIDOFF, 19294 Perhaps the obstacles on which our cure for hydroceph- alus has been wrecked are conceptual. Is there more to hy- Barely 25 years after Davidoff decried the lack of a cure drocephalus than our long-held and oversimplified concept for hydrocephalus, effective shunts came into existence. Since then, thousands of children and adults have received of it as a plumbing problem of mismatched CSF production treatment for this disorder, often resulting in significant and resorption treated by the insertion shunts or the surgi- symptomatic recovery and improvement in development cal diversion of CSF flow through ventriculostomies? Do and functional ability. Nonetheless, Davidoff’s phrase “so we really understand how hydrocephalus and its treatment often wrecked on purely mechanical obstacles” was pro- affect the brain? As neuroscientists, we must ask the fol- phetic. Fifty years later, the mechanical obstacle of shunt lowing questions: what do we know about hydrocephalus, failure remains the rule, not the exception, in the manage- and how do we know it? And, perhaps more important, what don’t we know about hydrocephalus that we ought to Abbreviations used in this paper: CSF = cerebrospinal fluid; know? ICP = intracranial pressure; NPH = normal-pressure hydroceph- Working together with support from the Brain Child alus; SVS = slit ventricle syndrome. Foundation, an organization dedicated to conducting inno- J. Neurosurg: Pediatrics / Volume 104 / March, 2006 157 M. Bergsneider, et al. vative research in hydrocephalus, we have formulated 10 all patients when ventricular volume is reduced? Is brain questions that we believe reflect critical gaps in our knowl- reexpansion necessary for all patients to be successfully edge of hydrocephalus. Rigorous answers to these ques- treated? And why do some patients with untreated hydro- tions would produce important gains in our understanding cephalus appear to have no neurological impairment? Al- of this condition that could lead to more effective and reli- though more details of the cellular pathology associated able treatment. with hydrocephalus have been forthcoming,5,6 a true under- standing of injury mechanisms, their multiple interactions, and the role of neural plasticity has escaped us. Thus, the Question 1: How Do We Define Hydrocephalus? reasons for reconstitution of the cortical mantle are still not clear. By gaining a complete understanding of the cellular A rigorous definition of hydrocephalus is surprisingly dif- basis for cortical reexpansion, we will no doubt discover ficult and is becoming more complicated. From a physio- many of the fundamental mechanisms that put the hydro- logical perspective, the finding of enlarged ventricles com- cephalic brain at risk and provide the basis for recovery. bined with high ICP represents only one presentation along a spectrum of disorders ranging from pseudotumor cerebri to low-pressure hydrocephalus. From a clinical perspective, how should we classify patients with hydrocephalus, from Question 5: What Is the Role of Cerebrovenous truly asymptomatic to severely impaired individuals, and Pressure in Hydrocephalus? how do we measure recovery after treatment? From the ana- tomical perspective, given the success of endoscopic third Increased cerebrovenous pressure has been found in vir- ventriculostomy in patients with communicating hydroceph- tually all clinical and experimental studies of hydrocepha- alus and shunt failure, does the concept of obstructive versus lus, and cerebrovenous hypertension also plays a role in “communicating” hydrocephalus need to be reassessed? pseudotumor cerebri. Nevertheless, displacement of venous blood is the main source of rapid compliance in the cranio- spinal axis in response to expanding masses or hydroceph- Question 2: How Is CSF Absorbed Normally and alus. The role and interactions of cerebrovenous pressure What Are the Causes of CSF Malabsorption in and blood volume in ICP pathophysiology and intractable Hydrocephalus? shunt problems deserve further investigation. Most surgeons do not question the dogma that hydro- cephalus is caused by the mechanical obstruction of the ab- sorption of CSF through the arachnoid villi, although there Question 6: What Causes NPH? is considerable evidence that the arachnoid villi are not It is not clear whether idiopathic NPH shares a common the principal sites of CSF absorption at normal CSF pres- pathophysiology with secondary communicating hydroceph- sures.1,8,17 Do lymphatic or vascular pathways mediate CSF alus of known causes. Can the cause or causes of idiopathic absorption? If CSF water can move freely, and bidirection- NPH be discovered, and thus prevented? Are there critical ally across brain capillary membranes, is it time to recon- relationships between NPH, degenerative dementias, and sider the concept of CSF “absorption?”9,10 If we are to make subcortical ischemic vascular disease, and how do they in- progress, we must be willing to expand into an exciting, al- fluence clinical presentation and outcomes? Understanding beit more complex, scientific frontier of CSF physiology the cause of NPH may lead to preventive measures, risk fac- that relies less on bulk flow and more heavily on intimate tor–based screening, and better diagnostic tools and clinical relationships between pulsatile CSF and blood movement outcomes. within the intracranial compartment. Question 3: Why Do the Ventricles Dilate in Question 7: What Causes Low-Pressure Communicating Hydrocephalus? Hydrocephalus? The question asked by Dandy and Blackfan3 in 1914, and Low-pressure hydrocephalus is an enigma. A clear view reiterated many times by others, has still not been answered: of this perplexing condition, in which patients with ventric- how can the ventricles dilate and the subarachnoid spaces ulomegaly show symptoms of hydrocephalus and even signs be compressed when the subarachnoid and the ventricular of brain herniation despite zero or negative ICP, may provide CSF are in free communication? A static pressure gradient a much deeper understanding of hydrocephalus. in communicating hydrocephalus would seem to violate the Pascal law. Fundamentally, do we understand the patho- physiology of communicating hydrocephalus as well as we Question 8: What Is the Pathophysiology of SVS? think we do? Shunt overdrainage continues despite various valve de- signs specifically aimed to prevent it,14 and clinical experi- Question 4: What Happens to the Structure and ence suggests that the symptoms of SVS do not correlate Function