Introduction
Hydrocephalus is a relatively common neuropediatric condition, with an incidence of about 0.9 per 1,000 births [
106,
170]. It is defined as the abnormal accumulation of cerebrospinal fluid (CSF) within the ventricles and/or subarachnoid spaces, leading to an increase in intracranial pressure (ICP) [
77]. Raimondi defined it as an increase in CSF volume [
140].
The subtype “external hydrocephalus” is usually defined as a rapid increase in head circumference, combined with enlarged subarachnoid spaces as seen on neuroimaging—especially overlying the frontal lobes—and normal or only moderately enlarged ventricles [
4,
91,
105,
118,
140,
143]. It occurs mainly during infancy, and the subarachnoid space enlargement gradually decreases and disappears over the next years [
91,
110,
118].
Many other terms have been used for the same or similar conditions, for instance, “subdural hygroma” [
30], “subdural effusion” [
92], “benign subdural collections” [
142], “extraventricular obstructive hydrocephalus” [
132], “idiopathic/benign hydrocephalus” [
4,
118], “primitive megalencephaly” [
95], “enlargement of the subarachnoid spaces” [
115], or even “chronic subdural hematoma” [
93]. As some of these names clearly are used for totally different conditions, they will not be a part of this review.
The many terms probably reflect the different views on etiology and outcome (see the following text discussions) and the often difficult neuroimaging differentiation between these conditions. Even more, the anatomical substrate, whether this is subdural fluid or CSF in the subarachnoid space, has been subject to disagreement [
3,
21].
The word “benign” is often used together with “external hydrocephalus,” reflecting the common view that this is a self-limiting condition occurring during infancy, resolving spontaneously during childhood [
6,
20,
77,
125,
129,
163]. Hence, most patients are probably not treated.
The aim of this study is to provide a complete review of the literature, focusing on all aspects of external hydrocephalus: etiology, neuroimaging, symptoms, treatment, and outcome.
Materials and methods
As mentioned above, many different terms have been used concerning benign external hydrocephalus or similar conditions. In order to obtain all relevant information, we therefore included these terms in our search. However, when reviewing the literature, we used this definition of benign external hydrocephalus: an idiopathic condition in infants characterized by a large or rapidly increasing head circumference and radiologically confirmed enlarged frontal subarachnoid spaces.
In the beginning of the era of computed tomography (CT), the differentiation between subdural and subarachnoid fluid collections was difficult, not to say impossible. This fact may of course confound our review, which is why some of the earliest articles have been excluded where there is doubt about the origin of the radiologically detected fluid.
Review of the literature
The following review is based on a systematic search in the PubMed and Web of Science databases. The terms used in the search were “hydrocephalus” combined with any of the following words: external, benign, extraventricular, extracerebral, or idiopathic. Other search terms were: “idiopathic/familial megalencephaly,” “idiopathic/familial macrocephaly,” “subdural effusion,” “benign subdural collections,” “subdural hygroma,” “extraventricular obstructive hydrocephalus,” “subdural/extracerebral/extraaxial/subarachnoid/pericerebral fluid collections,” and “benign communicating hydrocephalus.”
The review includes all original articles written in English or in other languages with an informative English abstract that report cases or larger groups of children with benign external hydrocephalus as defined above. Cases with a known cause of hydrocephalus or with accompanying conditions possibly affecting a long-term neurodevelopmental outcome, such as prematurity, are excluded.
Discussion
What is benign external hydrocephalus?
External hydrocephalus is defined as a rapid increase in head circumference in an infant combined with enlarged frontal subarachnoid spaces as seen on CT, MRI, or cranial ultrasound and with normal or slightly enlarged ventricles.
The underlying mechanism for the formation of external hydrocephalus is poorly understood, although several theories exist. The familial macrocephaly associated with some of the cases indicates that heredity may play a role. CSF flow studies have shown reduced flow over the cerebral convexities; an impairment of CSF absorption through the arachnoid villi therefore seems intuitive. In normal children, it has been shown that the arachnoid villi are not fully mature at birth but that they gradually become so during infancy. This lack of maturation in combination with the pronounced increase in CSF production during the first year of life [
169] may be the underlying mechanism and may also explain why the head starts to grow at around 6 months of age in most cases. This may not be a problem in most children, as their draining capacity through the villi or other draining pathways is balanced against the CSF production. In children with external hydrocephalus, on the other hand, there may be a misbalance because of either delayed maturation or excessive CSF production.
The pronounced increase in CSF production during the first year of life may also explain why external hydrocephalus rarely is described in newborns. The finding that CSF production in boys is greater than in girls may also partly explain the unequal gender distribution.
The delayed maturation theory does not contradict the belief that external hydrocephalus may be an arrested form of internal communicating hydrocephalus. The finding by Maytal et al. about the order in which the CSF-containing compartments dilate supports this view [
110]. Mechanisms believed to cause ordinary hydrocephalus may therefore play a role in the formation of external hydrocephalus, e.g., altered venous sinus pressures [
15] or restriction of arterial pulsation [
71].
In sum, the etiology of external hydrocephalus is most likely multifactorial and, if so, the condition may develop in several ways.
Clinical presentation
By our definition, increased head circumference is found in all patients with external hydrocephalus. In most cases, the head circumference increases disproportionally only during the first year of life, an observation that may support the delayed maturation theory as discussed above. However, as the cranial sutures close between 1 and 2 years of age, it is difficult to exclude a persistently increased ICP. Many children end up with large heads, i.e., they to not normalize, signifying a continued growth stimulus beyond infant age.
Many patients are found to have a delay in gross motor development, although only a few surveys have tested the children using valid neuropsychological test batteries. Reports of children with hypotonia, seizures, vomiting, etc. also indicate that the brain may be under marked strain during one phase of the condition.
The natural history of untreated external hydrocephalus
It seems evident that external hydrocephalus in some cases is associated with delayed psychomotor development. The important questions are whether this delayed development is caused by an increased ICP and whether this increased pressure can interfere with the individual's acquisition of motor, cognitive, emotional, and social skills in the critical phases of the brain's development, thus hampering the future motor and mental functions of the affected child.
The transient delay of development seen up to 4 years of age supports the idea that the lack of increase in head circumference seen in the older children merely is caused by the closing of sutures rather than the actual reduction of a slightly increased ICP.
The majority of patients are described as physically, neurologically, and developmentally normal on follow-up. However, this may only be because the outcome has been evaluated by the relatively coarse methods used in the majority of the studies. Most studies did not use valid developmental tests; subtle psychomotor impairments may therefore have passed as normal. This assumption is supported by the fact that a considerable amount of patients show some forms of developmental delay, including the two studies where children were followed up to school age [
95,
118]. Unfortunately, no studies were designed to show if the patients who ended up with a developmental delay could have been revealed at an earlier stage.
The studies show remarkably varying results for long-term outcome. This makes it hard to conclude and may reflect the heterogeneity that probably exists. Taking the presenting symptoms and additional findings into consideration, together with the motor delay seen in some patients for some time, the statement that this is a benign condition seems questionable.
As discussed above: could the temporary and mild “insult” at a critical age lead to a permanent damage? Animal studies have shown that the development of the young brain occurs step-wise, i.e., specific functions develop within a limited time span, a “critical period” when the brain is ready to learn that developmental task [
10,
18,
81]. Deprivation of stimuli during this critical time may cause deficits, although the process is not entirely irreversible [
72]. It is reasonable to assume, however, that the learning after the closure of this “time window” is much more difficult than when the neural network of the developing brain is still susceptible to new impulses.
Theoretically, the pressure exerted on the brain tissue by the excess CSF in the subarachnoid space during infancy may be high enough to provide imperfect conditions during a critical time of development, thereby giving rise to permanent, irreversible learning difficulties and other problems. The strict sequence of regional perfusion as discussed under “
Neuroimaging” could perhaps be seen as the vascular basis for these critical periods.
Hanlo et al. showed in a study of hydrocephalic infants that raised ICP is related to developmental outcome through the process of myelination as seen on MRI [
76]. Moreover, most children with severely delayed preoperative myelination showed at least a partial recovery following CSF diversion. The importance of myelination is supported by an animal study finding that white matter blood flow seems vulnerable in hydrocephalic kittens [
43].
Neuroimaging
It is difficult to define the limit between a normal and an enlarged subarachnoid space as the definitions used vary as does the subarachnoid space with age. However, a craniocortical width above 10 mm appears to be an absolute sign of pathology. The degree of ventricular dilatation is usually described as “minimal” or “moderate” without more specific measures: this probably explains the variation in incidence of patients with this finding.
Neuroimaging differentiation between external hydrocephalus and subdural hygroma/effusion certainly became easier after the introduction of MRI, and the tools presented are useful. With the addition of CT cisternography, and ultrasound in the youngest, a correct diagnosis should be achieved in most patients. Subdural effusion could be defined as a collection of protein-rich fluid of greater density than the CSF [
79], hence making the differentiation easier both radiologically and biochemically.
Cortical hypoperfusion is seen in some infants and should be further investigated. Studies of adult normal pressure hydrocephalus (NPH) patients have found the hypoperfusion to be more dominant in the frontal areas and that it seems to improve after shunt surgery [
109,
150]. A survey in normal children showed that the distribution of regional cortical blood flow followed a strict sequence in time, matching the behavioral evolution occurring during infancy [
146]. Frontal activity, for instance, remained scarcely recognizable until the second month, after which it rose to present an adult-like pattern at the beginning of the second year. Furthermore, observations using positron emission tomography scan indicate that metabolic deterioration occurs in the cortex surrounding the lateral ventricles in infants with hydrocephalus [
155]. Such features and techniques may dominate the future neuroimaging analysis of this and related conditions.
Surgical treatment and clinical outcome
Since external hydrocephalus can be anatomically considered a communicating hydrocephalus, insertion of a ventriculoperitoneal shunt should be the appropriate surgical method [
16]. Shunting in itself carries some risk [
19,
38,
104], and whether this will equalize the possible benefits of treating external hydrocephalus remains uncertain.
To our knowledge, no systematic studies that compare the effect of surgical treatment and conservative management in external hydrocephalus have been performed. Furthermore, only a few report on the effect of surgical treatment with information about the long-term effects. It seems as if the cases described in the literature were treated because of the presence of obvious signs of increased ICP, not because of fear of the potentially long-term negative effects on psychomotor development. The prevailing view emerging from the existing literature seems to be that external hydrocephalus in its most common form is a benign, self-limiting condition that should be handled conservatively [
4,
6,
91,
122]. By “most common” we mean macrocephalic children without other symptoms and with the typical neuroimaging features. Given the results discussed under “
The natural history of untreated external hydrocephalus”, we question this belief.
In cases where external hydrocephalus is combined with subdural fluid collection, treatment alternatives such as subduroperitoneal shunting, needle aspiration, or burr hole evacuation should be considered.
Only a few studies have reported the outcome after the surgical treatment of external hydrocephalus. As presented under “
Results”, they mainly reported good outcomes of shunting. However, the value is limited as the studies are not easy to compare and the cases are highly selected. Some studies report medical therapy as an effective treatment, but only short-term improvement on symptoms of increased ICP is published.
A detailed analysis of ICP pressure waves seems to yield useful additional information regarding which patients should be treated or not [
52].
Associated conditions
The risk of developing subdural hematoma after minimal or no head injury is reportedly increased in children with external hydrocephalus. The proposed cause is stretching of the bridging veins traversing the enlarged subarachnoid space [
5,
83,
141].
A relatively new, most interesting theory is whether there might be a connection between external hydrocephalus in childhood and the development of idiopathic NPH in the elderly. Bradley et al. found that patients with NPH have significantly larger intracranial volumes than control subjects as studied on MRI [
26]. The authors suggested that these patients may have had external hydrocephalus as children and that they had remained asymptomatic until their later years, when a proposed deep white matter ischemia would occur and yield symptoms [
25]. Wilson and Williams had the same finding as Bradley et al. and reported that about 20% of NPH patients had head circumferences above the 90th percentile, suggesting that external hydrocephalus may be responsible for some, but not all, patients with NPH [
168]. A link between external hydrocephalus and NPH may be the recently described syndrome of hydrocephalus in young and middle-aged adults that appear asymptomatic or with a series of only slight and subtle symptoms which improve after shunt surgery [
41].
Such a possible connection between external hydrocephalus and NPH gives new perspectives to the question of early surgical treatment in these children.
Benign external hydrocephalus—what to do?
Considering the few studies that have dealt with the effect of treatment of external hydrocephalus, it is obvious that more knowledge is needed. For now, the apparent diversity in results and opinions probably reflects a similar variety in clinical courses and patients, this again reflecting the different etiologies and partial inheritance often seen as well as the differences in what is regarded as “normal.” We think that a good way to answer some of these questions is to carry out a larger population-based (retrospective) study, comparing treated (shunted) and untreated children with external hydrocephalus and focusing on developmental outcome on long-term follow-up, including the use of standardized neuropsychological tests. By doing this, it may be possible to reveal subtypes/subgroups of patients with different outcome prognoses, hence in need of different initial managements. Surgical indication could, for instance, be determined by the initial radiological presentation (width of subarachnoid space, diffusion-weighted MRI), by a thorough neuropsychological investigation, or maybe by a combination of all signs and tests available (ICP, CSF flow, etc.).
Hartmut Collmann, Würzburg, Germany
This is a diligently compiled review on a fairly common yet still obscure condition of infancy known under a variety of terms such as “benign macrocephaly,” “benign subarachnoid enlargement,” or “external hydrocephalus”. It is characterized by transient acceleration of head growth, some signs of mild intracranial hypertension, and, morphologically, distinct enlargement of the subarachnoid space, often combined with mild ventricular dilation. In their comprehensive review of the available literature, the authors address all major aspects of this condition, i.e., considerations concerning etiology, pathogenesis, clinical and radiological diagnosis, and prognosis. As to the pathogenic factors, a disproportion between a rapidly increasing CSF secretion rate and delayed maturation of the arachnoid villi is the most commonly held theory. Little attention has been paid as yet to the venous system, and one is wondering if there is any relationship to the pseudotumor cerebri. While the authors underline the transient nature of the abnormal head growth and CSF accumulation, they challenge its completely benign character as a substantial proportion of patients appear to exhibit persistently retarded psychomotor skills. Consequently, they suggest a larger population-based study comparing the outcome of treated and untreated children.
Dieter Hellwig, Hannover, Germany
Benign or “idiopathic” external hydrocephalus is a rare entity in childhood and mostly resolves in the first 2 years after birth. It is characterized by an increased head circumference and neuroimaging shows a subarachnoidal fluid collection over the frontal hemispheres. In most cases, this pathology is asymptomatic and resolves without treatment; however, it is not clear if in some cases it can cause delay in mental, motor, and speech development.
In their review, Zahl et al. included a total of 147 studies. They described several theories about the etiology of benign external hydrocephalus, which seems to be still unclear. They emphasize that the main clinical sign is the rapid increase of head circumference and a tense anterior fontanelle. The final diagnosis is established by CCT or MRI.
The crucial question is if there is a need for treatment either with drugs like acetazolamide or by surgery using shunting procedures.
In accordance with the authors, who stress that there are no controlled studies about the long-term outcome of children with benign external hydrocephalus, I would like to recommend treating this form of communicating hydrocephalus by the insertion of a CSF shunt to prevent psycho-motor defects. In conclusion, there is still a lack in understanding the pathophysiology of this kind of hydrocephalus and controlled trials to evaluate the short- and long-term outcomes are urgently needed.