Full length articleA systematic review of the risks factors associated with the onset and natural progression of hydrocephalus
Introduction
Hydrocephalus is a condition in which excess cerebrospinal fluid (CSF) builds up inside the cavities of the brain (known as ventricles). Under normal conditions, CSF bathes the Central Nervous System (CNS, referring to the brain and spinal cord) and provides protection through cushioning and support; it brings nutrients to the brain, removes waste, and helps regulate intracranial pressure (National Institute of Neurological Disorders and Stroke, 2011, Spina Bifida and Hydrocephalus Association of Ontario, 2013, Spina Bifida and Hydrocephalus Canada, 2007, Princeton Brain and Spine Care, 2012). CSF is continually being produced, cycled through the CNS, and reabsorbed by the bloodstream. Hydrocephalus occurs when the rate of production of CSF is greater than the rate of re-absorption, and/or when drainage pathways are blocked. When this happens, the excess CSF accumulation may cause swelling and/or abnormal widening of the ventricles, which can create potentially harmful pressure on surrounding tissue.
Symptoms of hydrocephalus can vary with age. During infancy there may be vomiting, sleepiness, and the head circumference can increase to accommodate the extra fluid, which can be a visible change (National Institute of Neurological Disorders and Stroke, 2011). Hydrocephalus in older children and adults can have symptoms such as headaches, vomiting, balance problems, urinary incontinence and even memory loss (National Institute of Neurological Disorders and Stroke, 2011). Diagnosis of hydrocephalus may require a neurological exam, a computed tomography (CT) or magnetic resonance imaging (MRI) exam (National Institute of Neurological Disorders and Stroke, 2011).
Hydrocephalus can be congenital (CHC) (developed prior to birth) or acquired (AHC) (developed during or after birth) and can occur at any age. Congenital hydrocephalus typically results from specific genetic abnormalities or developmental disorders (e.g., neural tube defects such as spina bifida), while acquired hydrocephalus is more often attributed to illness, injury, environmental or other factors. A closer examination of both of these subtypes is the purpose of the present review (National Institute of Neurological Disorders and Stroke, 2011, Spina Bifida and Hydrocephalus Association of Ontario, 2013, Spina Bifida and Hydrocephalus Canada, 2007, Princeton Brain and Spine Care, 2012).
Hydrocephalus can also be categorized as communicating or non-communicating (obstructive) according to the presence and/or location of a blockage. In communicating hydrocephalus, CSF is free to flow (i.e., communicate) between the ventricles, as no blockage occurs within the ventricular system. In obstructive hydrocephalus, a blockage occurs within the ventricular system, often within one or more of the narrow pathways that connect the ventricles (Princeton Brain & Spine Care, 2012). There are two additional related conditions, which do not clearly fit into either of these categories: hydrocephalus ex-vacuo and normal pressure hydrocephalus (NPH). Hydrocephalus ex-vacuo is not truly a form of hydrocephalus; it occurs when a stroke or traumatic injury leads to brain tissue loss or shrinkage, and, in turn, results in a compensatory widening of ventricular space (National Institute of Neurological Disorders and Stroke, 2011). This condition is outside the scope of the current review. NPH is characterized by enlarged cerebral ventricles with only intermittently elevated cerebrospinal fluid pressure; this type is often diagnosed based on a common set of symptoms including gait disturbance, loss of control of bladder function, and dementia (Pyykko et al., 2012). Predisposing factors for NPH may include: increasing age, subarachnoid hemorrhage, head trauma, infection, tumor, meningitis, and/or complications of surgery (National Institute of Neurological Disorders and Stroke, 2011). Idiopathic NPH (INPH) is a specific subtype of NPH that characteristically develops in the absence of any such predisposing factors (Pyykko et al., 2012). A common complication with INPH is hyponatraemia (i.e., low plasma sodium concentration).
The most frequent method of treatment for hydrocephalus is the surgical insertion of a shunt system, which allows for improved drainage and CSF re-absorption (National Institute of Neurological Disorders and Stroke, 2011, Spina Bifida and Hydrocephalus Association of Ontario, 2013, Spina Bifida and Hydrocephalus Canada, 2007, Princeton Brain and Spine Care, 2012). One measure of disease progression in hydrocephalus, particularly in infants, is whether the hydrocephalus is acute and resolves without surgical intervention or persists such that a shunt is required.
The incidence and prevalence of hydrocephalus is linked to etiology. Incidence of congenital hydrocephalus is estimated at about 3 per 1000 live births in the US; overall prevalence is estimated at 0.5% (Spina Bifida and Hydrocephalus Canada, 2007). On the other hand, the total incidence of acquired hydrocephalus is much harder to estimate because it is due to many and varied factors, including illness, injury, environmental and other unknown factors. However, it is noteworthy that about 100,000 shunts are implanted each year in developed countries (Spina Bifida and Hydrocephalus Canada, 2007). NPH is estimated to affect more than 1 in 200 adults over age 55 years (Spina Bifida and Hydrocephalus Association of Ontario, 2013).
The epidemiological characteristics of hydrocephalus on the whole are not well understood. Although considerable research exists into various individual risk factors for hydrocephalus onset, given the complexity of the disorder and its many potential etiologies, a combination of genetic and environmental factors may be at play for any or all subtypes (National Institute of Neurological Disorders and Stroke, 2011). Far less is known about the factors that affect progression. In light of these problems, effort is required to elucidate and gain a better understanding of the varied risk factors for both onset and progression of hydrocephalus and to integrate them into a more unified picture. The first step towards this objective was to systematically evaluate the published literature, including systematic reviews, meta-analyses and observational studies on the subject.
Section snippets
Rationale
The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. This systematic review will provide a comprehensive summary of currently available evidence on risk factors for disease onset and progression, including biological, lifestyle, socioeconomic, environmental,
Criteria for considering studies for this review
The following is a brief description of the methodology used for selecting both non-genetic and genetic association studies. A complete description of methods and approach used in this study has been published in a separate paper (Hersi et al., 2017).
Search results
After searching six databases, 1285 unique references were identified (Fig. 1). After level one, title and abstract screening, 274 were reviewed at level two screening. Only two of these references remained after level two, full article screening, and these went on to have quality assessment scoring using the AMSTAR tool.
Two studies (Goh et al., 2006, Stothard et al., 2009) were found that examined the impact of a risk factor on the onset of hydrocephalus. After quality assessment using the
Discussion
This is the first systematic review that has sought to identify all known risk factors linked to the onset and natural progression of hydrocephalus. This systematic review has highlighted several risk factors that could play a role in the onset of hydrocephalus, and limited evidence for two risk factors for disease progression. This study also brings to light critical gaps in the current knowledge base and offers suggestions for future research to fill those gaps.
Conclusions
In conclusion, the potential risk factors for hydrocephalus onset are numerous and vary according to the category of disease. While a growing body of work exists, heterogeneity in study designs and populations to date create a lack of generalizability, and very few factors have been adequately scrutinized through duplication. As well, much more work is needed to determine the possible risk factors for the natural progression of hydrocephalus, both congenital and acquired. The limited evidence
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgements
Support for the project was provided by the Public Health Agency of Canada in association with Neurological Health Charities Canada. We are grateful to Dr. Paige Terrien Church and Dr. Mark Hamilton for their expert advice and feedback upon review of an earlier version of this article. Additional support was provided by Yannick Fortin PhD(c).We would like to also thank Dr. Shalu Darshan for editorial support in finalizing this manuscript.
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