Neurol Med Chir (Tokyo) 47, 448452, 2007

Nationwide Survey of the Etiology and Associated

Conditions of Prenatally and Postnatally Diagnosed
Congenital Hydrocephalus in Japan
Kouzo MORITAKE, Hidemasa NAGAI, Takeshi MIYAZAKI, Noriko NAGASAKO,
Mami YAMASAKI*, and Akiko TAMAKOSHI**
Department of Neurosurgery, Shimane University School of Medicine, Izumo, Shimane;
*Department of Neurosurgery and Clinical Institute, Osaka National Hospital, National Hospital
Organization, Osaka; **Medical Department of Preventive Medicine/Biostatistics and Medical
Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Aichi

Abstract
A nationwide survey in 2000 investigated the causative and associated central nervous system (CNS) lesions of congenital hydrocephalus in Japan. The etiology and associated diseases in 393 patients with
congenital hydrocephalus were analyzed and compared between 193 patients with prenatally diagnosed
(fetal) hydrocephalus and 181 with postnatally diagnosed (infantile) hydrocephalus. Of 393 patients of
congenital hydrocephalus, 355 (90.3%) had primary hydrocephalus and 28 (7.1%) had secondary
hydrocephalus. Of 355 patients with primary hydrocephalus, 85 (23.9%) had simple hydrocephalus associated with no other CNS anomaly and 270 (76.1%) had complicated hydrocephalus associated with
other CNS anomalies. Destructive cystic lesions, holoprosencephaly, and agenesis of the corpus callosum were significantly predominant in fetal hydrocephalus. Arachnoid cyst was somewhat
predominant in infantile hydrocephalus. The majority of cases of congenital hydrocephalus were primary hydrocephalus and two thirds were complicated hydrocephalus. Several complications showed
marked predominance in fetal hydrocephalus.
Key words:

congenital hydrocephalus,

fetal hydrocephalus,

Introduction

February 19, 2007;

Accepted

nationwide survey,

Japan

acquired causes of hydrocephalus are reported to be

spina bifida, aqueductal stenosis, and premature
birth with low weight in infancy with ventricular
hemorrhage.1,3,5,6,8,9,11)
The present study investigated the etiology and associated diseases of congenital hydrocephalus in
Japan in cases diagnosed prenatally (fetal hydrocephalus) and postnatally (infantile hydrocephalus).

Hydrocephalus involves an abnormal increase in the

volume of cerebrospinal fluid manifesting primarily
as enlargement of the ventricles, and may be associated with cerebral atrophy and mental retardation.310,13) Computed tomography, ultrasonography,
magnetic resonance (MR) imaging, and other supplementary techniques now allow observation of the
evolution and progression of hydrocephalus from
the earliest to the final stages.3) Consequently, the
concept and classification of hydrocephalus have
changed.8,9)
The prevalence of hydrocephalus is reported to be
0.82 per 1000 live births, 0.49 for children with infantile hydrocephalus and 0.33 for children with
meningomyelocele.11) The etiology was prenatal in
55% and perinatal in 44% of children with infantile
hydrocephalus.11) The most common congenital and
Received
2007

etiology,

Materials and Methods

A nationwide survey of congenital hydrocephalus in
Japan was carried out in 2000 under the sponsorship
of the Ministry of Health, Labor and Welfare of
Japan. An initial postcard questionnaire was sent in
January 2000 to 2440 departments of pediatrics, neurosurgery, or obstetrics and gynecology in Japan.
Congenital hydrocephalus was defined as increased
retention of cerebrospinal fluid in the ventricles associated with ventricular dilation diagnosed up to 12
months after birth.9) This asked about the number of
patients with hydrocephalus who had visited the

August 22,

448

Congenital Hydrocephalus in Japan

outpatient clinics or had been hospitalized between
January 1 and December 31, 1999. Individual questionnaires, asking for epidemiological and clinical
details, were sent to the 1861 departments (76.3%)
that had replied to the first survey.
The prevalence of congenital hydrocephalus varies substantially depending on the inclusion criteria of the study.14) In this study, hydrocephalus was
classified by etiology into two groups, primary
hydrocephalus caused by developmental disorders
and secondary hydrocephalus caused by nondevelopmental insults, such as hemorrhage, tumor,
or infection.3) Primary hydrocephalus was further
classified into simple hydrocephalus (isolated
hydrocephalus14)) with no other concomitant central
nervous system (CNS) anomaly except for aqueduct
stenosis, and complicated hydrocephalus with other
complicating CNS anomalies.
A total of 393 patients with congenital
hydrocephalus were identified, 193 with fetal
hydrocephalus, 181 with infantile hydrocephalus,
and 19 with unspecified hydrocephalus diagnosed at
an unknown time. The etiology of hydrocephalus
and other pathologic conditions was analyzed in
each of the patients with congenital hydrocephalus,
and were compared between the fetal hydrocephalus and infantile hydrocephalus groups. All personal
data items were subjected to privacy protection.
Statistical analysis used the chi-squared (x2) test
and Kruskal-Wallis H test, and were conducted with
Excel 2004 (version 11.2.3; Microsoft, Redmond,
Wash., U.S.A.) and SPSS (version 8.0 for Windows;
SPSS, Chicago, Ill., U.S.A.) with significance accepted at the 5% level.

I. Etiologies of congenital hydrocephalus

Tables 1 and 2 show the results of etiological classification of the 355 (90.3%) patients with primary
hydrocephalus and the 28 (7.1%) patients with secondary hydrocephalus, respectively. The remaining
10 patients (2.5%) had unknown etiology.
Table 3 shows the causative and associated CNS
lesions in the 270 patients with complicated

Table 1

hydrocephalus. Fetal and infantile hydrocephalus

showed significant differences in the associated
complications (Kruskal-Wallis H test, p 0.0063).
Several types of complicated hydrocephalus showed
marked predominance for fetal hydrocephalus compared to infantile hydrocephalus, with ratios of
holoprosencephaly 8:0, congenital destructive cystic
lesions
(porencephaly,
schizencephaly,
and
hydranencephaly) 8:1, and agenesis of the corpus
callosum 3:1. In contrast, arachnoid cyst, the most
representative intracranial cystic lesion, was somewhat predominant in the infantile hydrocephalus
group, with a ratio of 1:3.
Secondary hydrocephalus occurred almost equally in patients with fetal hydrocephalus and infantile
hydrocephalus (Table 2). About two thirds (19 of 28)
of cases were associated with intracranial hemorrhage. Tumors were predominant in the fetal
hydrocephalus group and infection in the infantile
hydrocephalus group, but not significantly (p
0.31).

II.

Associated hereditary and/or familial diseases

Ten (2.8%) of the 355 patients with primary
hydrocephalus had siblings with hydrocephalus,
seven males, two females, and one unspecified, of
whom three patients had simple hydrocephalus and
seven had complicated hydrocephalus (3 agenesis of
the corpus callosum, 2 myelomeningocele, 1 encephalocele, and 1 Dandy-Walker malformation).
Fifteen (4.2%) of the 355 patients with primary
hydrocephalus (10 males and 5 females) had synTable 2

Results

449

Patients with
hydrocephalus

secondary

congenital

Cause of secondary
congenital
hydrocephalus

Fetal
hydrocephalus

Infantile
hydrocephalus

Total

Hemorrhage
Tumor
Infection

10
4
1

9
1
3

19
5
4

Total

15

13

28

Patients with primary congenital hydrocephalus

Type of primary congenital hydrocephalus

Fetal
hydrocephalus

Infantile
hydrocephalus

Unspecified
hydrocephalus

Total

Simple hydrocephalus
Complicated hydrocephalus

36
139

43
121

6
10

85
270

Total

175

164

16

355

Neurol Med Chir (Tokyo) 47, October, 2007

K. Moritake et al.

450
Table 3

Cases of complicated primary hydrocephalus according to causative and associated central nervous system (CNS) lesions

Causative and associated CNS lesions

Fetal
hydrocephalus

Infantile
hydrocephalus

Unspecified
hydrocephalus

Total

Myelomeningocele
Chiari 2
Chiari 1
Agenesis of corpus callosum
Dandy-Walker malformation
Encephalocele
Arachnoid cyst
Poren-, schizen-, hydranencephaly
Holoprosencephaly
Cerebral dysgenesis
Syringomyelia
Occult spinal dysraphism
Craniosynostosis
Choroid plexus hyperplasia
Achondroplasia
Others

44
29
5
23
14
11
3
8
8
3
3
1
1
0
0
16

44
21
6
7
15
9
8
1
0
1
2
1
2
1
3
11

3
2
1
1
1
0
0
1
1
0
0
0
0
0
0
0

91
52
12
31
30
20
11
10
9
4
5
2
3
1
3
27

dromic congenital anomalies, including three with

achondroplasia, and all had infantile hydrocephalus. Fifty-nine (16.6%) of the 355 patients with primary hydrocephalus had associated congenital anomalies outside the CNS, such as cardiac anomalies
and cleft lip. Such anomalies appeared in six of 10
patients whose siblings had hydrocephalus, in six of
10 who showed chromosome aberrations, and in 12
of 15 who had syndromic congenital anomalies.

Discussion
Hydrocephalus is commonly associated with other
CNS pathologies, which may adversely affect the
prognosis.1,3,10) In our nationwide survey of congenital hydrocephalus, around 90% of cases were classified as primary hydrocephalus and only about 10%
as secondary hydrocephalus. The ratio of secondary
hydrocephalus in our study is clearly lower than
those in other reports,5,6,9) where the etiology of
hydrocephalus was intracranial hemorrhage in
1030% of the cases with congenital hydrocephalus
and intracranial infection in 520%. This might be
related with the low reply rate in patients with intracranial hemorrhage or infection because of the
poor prognosis and difficulties in treatment which
were suspected in our questionnaire survey. Of the
patients with primary hydrocephalus, about 80%
had other accompanying CNS anomalies (complicated hydrocephalus). Therefore, the majority of cases
of congenital hydrocephalus are complicated
hydrocephalus, which present with various
problems related to management. Marked

predominance of complicated hydrocephalus was

observed in both fetal hydrocephalus and infantile
hydrocephalus.
The time of diagnosis of hydrocephalus differed
significantly between the types of complicated
hydrocephalus. The predominance of these complications would be related to the difference in the time
of diagnosis of hydrocephalus in each patient, which
in turn would be related to etiology. Marked
predominance of holoprosencephaly, congenital
destructive cystic lesions, and agenesis of the corpus
callosum was noted in the fetal hydrocephalus
group, possibly because cystic lesions and distinct
dysgenetic lesions of the brain are identified more
easily by prenatal ultrasonography. However,
arachnoid cyst, the most representative intracranial
cystic lesion, was predominant in the infantile
hydrocephalus group. Myelomeningocele, present
in about 30% of the patients in this group, tends to
be overlooked by ultrasonography unless the lesion
is sufficiently large to visualize, but over half of the
cases were identified prenatally, probably because
of the association with hydrocephalus.
The fact that arachnoid cyst was exceptionally
predominant in the infantile hydrocephalus group
suggests a different natural history from other CNS
cystic lesions and mainly postnatal development.
Analysis of 54 fetuses with prenatally diagnosed intracranial cysts found that 45% of the cysts were detected after the 30th week of gestation, in contrast to
normal ultrasonography findings at 22 weeks.12) Sylvian cysts, which are overwhelmingly dominant in
childhood, and hydrocephalus, which is frequently

Neurol Med Chir (Tokyo) 47, October, 2007

Congenital Hydrocephalus in Japan

associated with intracranial cysts in children, were
both rare. These findings demonstrate that both intracranial cysts and accompanying hydrocephalus
develop late in pregnancy or postnatally. This observation might explain the exceptional predominance
of arachnoid cyst in the infantile hydrocephalus
group.
Among the causes of secondary hydrocephalus,
tumor was predominant in the fetal hydrocephalus
group and infection was predominant in the infantile hydrocephalus group. This tendency seems to
reflect the fact that tumors are easily detectable by
intrauterine ultrasonography and/or MR imaging
because of the distinctive features and secondary
changes, such as shift or deformity of the ventricles
and other surrounding structures. On the other
hand, detection of hydrocephalus caused by infectious disease is considered difficult because of the
few distinguishing morphological features in prenatal imaging studies.
The role of ultrasonography in recognizing the
cause of fetal hydrocephalus was reported by many
authors.1,14) However, prenatal diagnosis based on
an early ultrasound scan is not always reliable as
ventriculomegaly usually starts after 20 weeks of
gestation, the importance of additional clinical investigations is stressed.15) There are also many
reports which described the importance of MR imaging for correct diagnosis and reliable prognosis,
even though incomplete myelination and gyration
may lead to difficulty in analysis.10,12) As MR imaging can give some idea of the prognosis by evaluating the myelination pattern, which is not possible
with ultrasonography, it provide significant additional information that can affect parent counseling,
prenatal intervention, and postnatal management.10)
Statistical evaluation of the relationship between
age at diagnosis or initial surgery for hydrocephalus
and neurodevelopmental outcome suggested that
etiology was a major determinant of outcome in children who underwent early postnatal surgical treatment of fetal hydrocephalus.2) The relationship between the etiology and clinical outcome in the
patients identified by the current survey will be
reported in a subsequent paper.
About 3.0% of patients with primary hydrocephalus had siblings with hydrocephalus, and many of
these patients had various chromosomal aberrations
or syndromic congenital anomalies. Almost all cases
were infantile hydrocephalus. Anomalies outside
the CNS, such as cardiac anomalies and cleft lip,
were common in patients whose siblings had
hydrocephalus and in patients who had syndromic
congenital anomalies. A study on the etiology and
presumed recurrent risk of siblings in a series of 35

Neurol Med Chir (Tokyo) 47, October, 2007

451

patients with congenital hydrocephalus in combination with aqueduct stenosis identified a genetic etiology in 13 patients (37.1%) with an increased recurrence risk for siblings.4) Fifteen of 155 cases of
prenatally detected mild ventriculomegaly had associated chromosomal anomalies, all of which occurred in the presence of other major anomalies.14)
Although chromosomal abnormalities are rarely associated with hydrocephalus in general, a karyotype
study will be necessary to investigate hereditary or
familial factors that might predispose individuals to
hydrocephalus.15,16)
Despite the significant limitations of this
retrospective study, the findings provide a guide for
preoperative counseling of patients and their families to help them maintain realistic expectations
about outcome. The results regarding the etiological
distribution of congenital hydrocephalus may provide the basis for the future development of better
management and for defining standards.

Acknowledgment
This work supported by Health Sciences Research
Grants
for
Specific
Diseases
``Intractable
Hydrocephalus'' from the Ministry of Health,
Labour and Welfare, Japan, No. 1999-SD-17, Mami
Yamasaki.

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Address reprint requests to: Kouzo Moritake, M.D., Department of Neurosurgery, Shimane University School of
Medicine, 891 Enyacho, Izumo, Shimane
6938501, Japan.

Commentary
The authors have analyzed a nationwide survey on
the etiology and associated conditions of prenatally
and postnatally diagnosed congenital hydrocephalus.
They received information on 393 patients. The vast
majority of patients had primary hydrocephalus. In
this group, the majority had associated CNS anomalies including holoprosencephaly, agenesis of the
corpus callosum, and cystic lesions. While the results
are somewhat typical of previous analyses of the
etiology of hydrocephalus, the authors should receive
credit for conducting this survey and acquiring the
data. As with any survey, it would be nice to know the
response rate, the co-operativity of the pediatricians
and obstetricians, and the time of the diagnosis in
utero or after delivery. Regional rate reporting and

sample size errors may be some of the additional limitations to this study. Still, the authors have amassed a
sizeable dataset on congenital hydrocephalus in
Japan, and this information should be of value when
professionals, including neurosurgeons, are asked to
counsel families whose fetus or baby is diagnosed
with congenital, primary hydrocephalus.
James T. RUTKA, M.D., F.R.C.S.C., F.A.C.S., F.A.A.P.
Dan Family Chair in Neurosurgery
Division of Neurosurgery
The University of Toronto
Toronto, Ontario, Canada
This is a very interesting paper. The authors reported
393 patients with congenital hydrocephalus. 193
patients suffered from fetal hydrocephalus and 181
patients had infantile hydrocephalus. The majority of
cases of congenital hydrocephalus were primary
hydrocephalus. Destructive cystic lesion, holoprosencephaly, and agenesis of the corpus callosum were
predominant in fetal hydrocephalus. Arachnoid cyst
was common seen in infantile hydrocephalus.
Hydrocephalus unassociated with neural tube
defect is a clinical entity of diverse etiology. There is
an excess of males affected with hydrocephalus,
resulting from the existence of a well-defined X-linked
recessive form of the condition. It was suggested that
in some cases of congenital hydrocephalus the etiology was the same as that of neural tube defects. Consideration should therefore be given to possible primary prevention and to the need for appropriate
antenatal investigation to detect and deal with congenital hydrocephalus.
Evaluation of fetal central nervous system (CNS) by
ultrasonography is frequently limited, particularly in
the early stage of gestation and ultrasonography findings are occasionally inconclusive or are insufficient
for prenatal diagnosis or for guiding treatment
choices. Fetuses with questionable abnormal
ultrasonography findings should be sent for further
evaluation with MRI. The later is helpful to detect
fetal CNS abnormalities, and it is a supplement to
ultrasonography in complicated pregnancies.
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2)

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281284, 1984
Strain L, Gosden CM, Brock DJ, Bonthron DT: Genetic
heterogeneity in X-linked hydrocephalus: linkage to
markers within Xq27.3. Am J Hum Genet 54: 236243,
1994

Shuyuan YANG, M.D.

Department of Neurosurgery
Tianjin Medical University Hospital
Tianjin, P.R.C.

Neurol Med Chir (Tokyo) 47, October, 2007