J Med Dent Sci 2013 60 5561

Review
Chronic Subdural Hematoma An Up-to-Date Concept
Yoji Tanaka1) and Kikuo Ohno2)

1) Neurosurgery, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University
(TMDU), Tokyo, Japan
2) Emeritus Professor, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

Chronic subdural hematoma (CSDH) is prevalent

among elderly populations worldwide, and its
mysterious pathogenesis has been discussed in
the literature for decades. The issues remaining to
be solved in regard to CSDH include the initiating
events; the bleeding into the subdural space and
the formation of the outer and inner membranes,
its development; increase and liquefaction of
hematoma, the optimal treatments, and the
natural history. The pathophysiology is becoming
more clear due to recent findings from computed
tomography studies and human models of CSDH.
In this work, we review previous studies on CSDH
and present a new integrated concept about the
development of this common condition after head
injuries.
Key words:subdural fluid collection, chronic subdural
hematoma, inflammation, neomembrane,
head injury, craniotomy, unruptured cerebral
aneurysms
Introduction
Chronic subdural hematoma (CSDH) is defined as
a cystic unclotted hematoma with the outer and inner
membranes in the subdural space. A common disease
in the elderly, CSDH usually develops within one or
two months after a minor head injury. In the computed
tomography (CT) era, many clinicians described the

Corresponding Author: Yoji Tanaka, M.D.

Tokyo Medical and Dental University (TMDU) 1-5-45 Yushima,
Bunkyo-ku, Tokyo 113-8510, Japan
Tel: +81-3-5803-5266Fax: +81-3-5803-0140
E-mail: tanaka.nsrg@tmd.ac.jp
Received January 25Accepted March 8, 2013

clinical process by which CSDH develops after persistent

subdural fluid collection in the weeks following a minor or
moderate head injury.1-6 However, the time gap between
the collection of subdural fluid and the development of
CSDH has not been described in detail, mainly because
there has been no suitable experimental model for
examining it. Today, new knowledge has changed the
thinking about CSDHnamely, it has become clear
that CSDH is occasionally encountered in elderly
patients after a craniotomy for an unruptured cerebral
aneurysm.7-9 We think this finding that CSDH can arise
as a sequela of craniotomy will have a significant impact
on research into the disease. Here, we review previous
studies on CSDH and present a detailed description of
the mechanism of this common disease after head injury.
Historical review of studies on CSDH
before the CT era
CSDH and its causal mechanism, pathophysiological
processes, natural history and treatment methods have
been studied for over 150 years, as this disease is very
common in the elderly around the world. Hundreds of
papers about CSDH have been published. There were
once etiological disputes regarding the pachymeningitis
theory proposed by Virchow10 in 1857 and the trauma
theory proposed by Trotter11 in 1914. A connection
between these two theories was established through
the work of several Japanese researchers, including
Nakamura,12 who examined their clinical patients with
CSDH in 1966, Sakaki et al.,13 who clinicopathologically
studied 31 patients with CSDH in 1972, and Ito et al.,14
who studied autopsy cases of CSDH pathologically in
1974. In those studies, the researchers all assumed
that a thin posttraumatic subdural hematoma played an
important role in the development of an inflammatory
granulation-like neomembrane as the early stage of

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Y. Tanaka et al.

CSDH. It was not until Watanabe et al.15 published their

findings in an animal study in 1972 that the subdural
collection of cerebrospinal fluid (CSF) mixed with blood
became a focus of attention in terms of the development
of CSDH.
Watanabe et al. developed an experimental animal
model of CSDH by mixing blood clots with CSF and
inoculating the resulting solution into the subdural space
of dogs and monkeys, where the clots grew to form an
encapsulated subdural hematoma that was comparable
to human CSDH.16 Although Watanabe et al. were the
first to take note of CSF in the subdural space in the
development of CSDH, and stated that the fibrin that was
formed on the surface of the clot in the presence of CSF
would be essential to induce the capsule formation, they
had no further explanation for the development of the
hemorrhagic membrane.15 In 1974, Appelbaum et al.17
repeated similar experiments in the cat and stated that
CSF was not necessary to produce such special clots,
contrary to the conclusions of Watanabe et al.16 The
issue remains unresolved today.
As described above, the consensus of opinion in the
1970s was that a neomembrane formed by a dural
inflammatory reaction to the presence of subdural blood
or subdural fluid collection is the origin of subdural and
cystic liquefied hematomas. Based on their studies,
Sakaki et al.13 and Ito et al.14 speculated that multiple
bleedings occur inside the neomembrane from abundant
sinusoidal channels, and that the neomembrane splits
into the outer and inner membranes. Thus, we can frame
the hypotheses as follows:
(1) A neomembrane can be formed from CSF mixed with
blood (as Watanabe et al.16 indicated).
(2) Bleeding occurs inside the neomembrane to form
a cystic hematoma (as Sakaki et al.13 and Ito et al.14
suggested).
CT studies of CSDH
In the 1980s, in conjunction with the advent of CT
imaging, numerous papers were published on the
development of CSDH after head injury (Fig.1).1-6
Follow-up CT after head injuries clearly showed that
CSDH developed as a consequence of posttraumatic
subdural fluid collection. Periodical CT scans precisely
captured the developing course of CSDH after head
injury. In 1979 Yamada et al. reported three cases in
which CSDH developed following traumatic subdural
fluid collection.1 In a previous study, we reviewed the
cases of 43 consecutive patients who had traumatic,
bloody subdural fluid collection out of 715 patients who

J Med Dent Sci

Figure 1.Chronic subdural hematoma. Bilateral slight high-density

areas (arrowheads) indicate CSDHs. The hematoma on the right side
is larger with a midline shift to the left side.

underwent CT scans because of a recent head injury.18

Twenty of the 43 patients developed CSDH between 18
and 126 days after the head injury and the mean density
of the subdural fluid collection in these patients upon
admission was 27.1 6.7 Hounsfield units. Our previous
CT study showed that CSDH usually develops as a
consequence of traumatic subdural fluid collection, and
that nearly 50% of patients with asymptomatic subdural
fluid collection might develop CSDH.18
Thus, the knowledge that CSDH requires a precondition
of persistent subdural fluid and that this condition
causes inflammatory change to the inner surface of
the dura mater is most likely due to CT findings.18-20 It is
conceivable that, as a sequel to traumatic head injury, the
brain contusion is accompanied by an outflow of bloody
CSF into the subdural space from the subarachnoid
space in moderately injured victims, and it seems
probable that an arachnoid tear around a bridging vein
causes the subdural collection of slightly bloody CSF in
patients with a minor head injury. A good experimental
model for CSDH would be able to test this hypothesis.
It is thus noteworthy that we have encountered more
than a few patients with a CSDH that developed after
they had undergone a craniotomy as treatment for an
unruptured cerebral aneurysm.
Model of CSDH following craniotomy for
unruptured cerebral aneurysms
CSDH has been confirmed as a complication of
craniotomy in elderly patients with unruptured cerebral

CSDH An Up-to-Date Concept

aneurysms.7-9 Komatsu et al. first reported on three

cases (0.3%) of CSDH among 1,000 craniotomies for
ruptured aneurysms before the CT era, and stated that
such CSDH was extremely rare.7 It is notable that these
three patients underwent direct surgery in the chronic
stage more than two weeks after rupture. Tanaka et al.
also observed postoperative subdural fluid collection in
52% of their 147 patients with intracranial aneurysms
after craniotomy, including 19 patients with unruptured
aneurysms, and reported that the subdural fluid
collection transformed to symptomatic CSDH in three
patients.8 This problem rarely occurs in the treatment
of ruptured aneurysms, probably because the brain is
swollen in the acute stage.
We retrospectively investigated the cases of 76
patients with unruptured cerebral aneurysms who
underwent neck clipping by craniotomy from 1997
to 2010. The study protocol was approved by the
ethical committee of Tokyo Medical and Dental
University Hospital (No.1398, Tokyo, Japan). Eightysix unruptured cerebral aneurysms (80 craniotomies) in
76 consecutive patients ranging from 42 to 85 years
old (average age: 61.57.6) with single or multiple
aneurysms were treated by craniotomy. Four patients
had two craniotomies. Written informed consent for the
use of data was obtained from all patients and their
next of kin before the surgery. CSDH developed in 10
patients (12.5% of 80 craniotomies) ranging from 59
to 72 years old as shown on CT scans. There was a
significant difference (p=0.032) in age between the 66
patients without CSDH (average age: 60.77.7) and
the 10 patients with CSDH (average age: 66.25.2) by

57

Students t-test (by manual calculation). Six of the 10

patients (60%) were male. Five of the 10 patients with
CSDH became symptomatic and were treated with a burr
hole with irrigation. In all 10 of the patients the CSDH
was eventually resolved without neurological deficits.
After the neck clipping in the 76 patients, subdural fluid
composed of CSF usually accumulated postoperatively,
due to sinking of the brain following the removal of
CSF. CT scans were taken in 78 of the 80 craniotomies
postoperatively, mostly on the 1st and around the 7th
postoperative day. Postoperative follow-up CT in 74 of
the patients revealed an enlarged subdural space in 64
craniotomies, compared to the preoperative CT findings.
The enlargement of the subdural space gradually
disappeared with time in most of these patients. No
CSDH was observed in 50 craniotomies without or with
subdural fluid collection of a thickness not more than
4 mm based on CT scans taken on the 4th to 12th day
after surgery. However, CSDH developed in 10 (35.7%)
of 28 craniotomies with subdural fluid collection thicker
than 4 mm in CT scans within the same date range after
surgery (Fig.2 and 3). In particular, 9 (50.0%) of the 18
craniotomies with subdural fluid collection thicker than
5 mm developed CSDH. Thus, this retrospective study
shows that the development of CSDH is associated with
the thickness of the postoperative enlarged subdural
space and is caused by the persistent accumulation of
subdural CSF slightly contaminated with blood cells. Such
a craniotomy for unruptured aneurysms can be a type
of clinical model for CSDH, which is comparable to what
Watanabe et al. intended to produce experimentally.
Another concern is why CSDH did not develop in

Figure 2.Periodical follow-up CT scans after neck clipping of aneurysms. An asymptomatic case with natural resolution of a CSDH
is shown. A: Ten millimeters of subdural fluid collection (7 days after craniotomy); B: The development of CSDH indicated by white
arrowheads (58 days after craniotomy); C: Resolving hematoma (160 days after craniotomy).

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Y. Tanaka et al.

Figure 3.Relationship between the thickness (mm) of the subdural

fluid collection (SDFC) from the 4th to 12th days after 78 craniotomies
and the development of CSDH. A black square indicates a CSDH
transformed from SDFC (white columns) at each thickness of SDFC.

all patients who underwent craniotomy and incision

of the arachnoid membrane. The degree of arachnoid
injury after craniotomy was much larger than that in
cases of minor head injury. However, the incidence
rate of CSDH after craniotomy was not unusually high.
A possible explanation is that re-expansion of the brain
after surgery prevented enlargement of the subdural
space. This could also explain why elderly patients more
frequently suffer from CSDH (brain atrophy) and SAH
patients do not exhibit CSDH (brain swelling).
Integrated consideration of the pathomechanism
of CSDH based on various findings to date
The incisions to the arachnoid membrane during
craniotomy produce conditions similar to those seen
in head injuries. CSF with a small number of blood
cells, including inflammatory cytokines, collects in the
subdural space in cases with postoperative sinking of
the brain. That is, craniotomy for unruptured aneurysms
is a kind of surgical trauma to the brain and may
therefore be identical to minor head injury, as Komatsu
et al. pointed out.7 Such fluid collection mixed with a
blood cell component persists for a certain period,
causing inflammatory changes in the dura mater
(pachymeningitis haemorrhagica interna according
to Virchow10) and could form a neomembrane on the
inner side of the dura mater. In previous studies, the
development of a neomembrane attached to the inner
surface of the dura mater was recognized around CSDH
in autopsy cases of CSDH14 and as pachymeningitis
hemorrhagica interna with chronological changes in
autopsy cases after craniotomy.20 We consider that the
discussion about the causes of neomembrane formation

J Med Dent Sci

(our hypothesis (1)) is resolved, and that the formation

can be attributed both to the presence of a subdural
collection of CSF contaminated with a small number of
blood cells and blood-derived factors20 and to the dural
inflammatory reaction. Our data demonstrating that the
development of CSDH was significantly more frequent
in older than younger patients are also suggestive of a
close relationship between age and the development of
CSDH after minor head injury.
The next question is how the inner membrane is
formed after the development of a neomembrane
above the arachnoid membrane. In other words, does
the hemorrhage go from sinusoids in the neomembrane
into the subdural space directly, or does it go inside the
neomembrane? Sakaki et al.13 and Ito et al.14 proposed a
hypothesis (the same as our hypothesis (2)) that a subdural
primary neomembrane adjacent to the inner side of the
dura mater splits into the inner and outer membranes
by frequent hemorrhages inside the neomembrane and
turns into a cystic hematoma.13,14 We must also consider
the other possibility, that the hemorrhage may occur
directly into the subdural space. However, CSDH is
liquefied without clotting and with the inner membrane
usually localized over the frontal and parietal lobes.13
If the hemorrhage from the neomembrane goes directly
into the subdural space, it should spread widely over
the cerebral hemisphere and it is inexplicable how the
smooth inner membrane is formed so soon. Kawano et
al.19 performed an ultrastructural examination of the
outer and inner membranes of CSDH in 23 patients, and
suggested that CSDH was an intradural hematoma which
is formed within the split dural border cell layer; the
outer membrane consisted of thick granulation tissue;
and a few dural border cells on the underlying arachnoid
membrane formed a thin fibrous inner membrane. Thus,
the formation mechanism of the inner membrane would
favor the hypothesis of Sakaki et al.13 and Ito et al..14
Based on the clinical studies of Takahashi et al.9 and
Tanaka et al.,8 the pathological studies of Ito et al.,14
Schmidt and Neidhardt,20 and Kawano et al.,19 and our
own findings, we induced a chain of developing process
of CSDH as shown in Fig.4. Although there have been
many reports about CSDH following craniotomy and also
about the causal mechanism of CSDH after head injury,
as discussed above, to the best of our knowledge, this
is the first publication that correlates the CSDH after
craniotomy with that after minor head injury.
CSDH is well known to occur in patients with other
conditions, such as renal failure with blood dialysis,21
intracranial hypotension syndrome22,23 including the
patients with CSF shunt, and coagulopathy.24 Some

59

CSDH An Up-to-Date Concept

Figure 4.Differences and common points in the mechanism of development of CSDH between craniotomy for neck
clipping and minor head injury as the preceding etiology. DM: dura mater; AM: arachnoid membrane; SDFC: subdural fluid
collection; NM: neomembrane; OM: outer membrane; IM: inner membrane; CSDH: chronic subdural hematoma.

mild head injury is suspected to contribute to the

development of CSDH in these patients. Formation of
the neomembrane in such cases seems to be due to a
mechanism similar to that after head injury.
Growing and resolving course of
CSDH and treatment
Our research interest has focused on the local
activity of various activated substances in the outer
membrane of CSDH.25-27 This outer membrane is a
source of tissue plasminogen activator and inflammatory
cytokines.28-32 Therefore, CSDH can be studied as a type
of inflammatory phenomenon. In our previous work, we
analyzed the concentrations of inflammatory cytokines
such as interleukin (IL)-6 and IL-8, vascular endothelial
growth factor (VEGF), and prostaglandin E 2 in hematoma
fluid.25 The results showed that there was a linear and
significant relationship between the prostaglandin E 2
concentration in the hematoma fluid and the interval
from the trauma to the initial surgery. We came to the
conclusion that cyclooxygenase-2, which is an enzyme

involved in the synthesis of prostaglandin E 2, might play

a crucial role in the development of CSDH.
What we knew in the CT era about the natural history
of CSDH is that some CSDHs continue to increase in size
to become symptomatic and require aspiration of the
hematoma and others resolve spontaneously. Nagahori
et al. pointed out, based on a comparison of the density
of hematoma on CT and the histological findings of
outer membranes, that exudation from inflammation is
involved in the early stage of hematoma formation, and
that inflammation and hemorrhage are involved in the
subsequent stage of hematoma enlargement.33 Based on
the histological findings reported by Sakaki et al.13 and
Ito et al.,14 there was a natural history from vascular-rich
to regressive periods in the neomembrane, which might
lead to an increase in the size and the spontaneous
resolution of the hematoma. Naganuma et al. reported
four CSDH cases that were followed from head injury to
spontaneous resolution of hematomas on CT scans.34 The
intervals for resolution were 78, 174, 231 and 326 days
after the development of CSDH. In our previous CT study,
7 (35%) of 20 patients who developed CSDH following

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Y. Tanaka et al.

subdural fluid collection resolved spontaneously.18 In

our present study as well, the CSDHs of 5 (50%) of the
10 patients resolved spontaneously and the duration
from the appearance to the disappearance of CSDH on
CT in these 5 patients was 121.877.7 days (Fig.2).
Therefore, we think that the spontaneous cure of a
CSDH is associated with the healing process of the outer
membranenamely, the eradication of the sources of
bleeding.
There have been various treatment methods for CSDH
such as total removal of the outer and inner membranes
with hematoma, trephination, two burr holes with
irrigation, one burr hole with irrigation, solely aspiration
of the hematoma, and nonsurgical drug therapies.35
Total removal of the membranes with a hematoma
occasionally resulted in serious complications and came
to be used very infrequently. At the time of this writing,
one burr hole and saline irrigation is the most common
CSDH treatment in Japan. At our hospital, 210 patients
with CSDH who were treated with one burr hole and
irrigation under local anesthesia between 2006 and
2010 all improved neurologically and were considered
to be cured. Repeat operations were done in six patients
without any complications. One burr hole with irrigation
thus seems to be a safe treatment of choice for CSDH
at present. In addition, this procedure is thought to be
effective to speed the healing process of the vascularrich membrane. The postoperative incidence of seizures
after burr hole treatment is low and similar to that
previously reported for minor head injury. Therefore, the
routine use of antiepileptic prophylaxis is not necessary
in patients with CSDH caused by minor head injuries or
other causes and who are treated by burr hole when
there are no additional lesions present on CT scans.36
It is important to take measures to prevent the
transformation of a subdural fluid collection to CSDH,
though more than 50% of patients with subdural fluid
collection after head injury or craniotomy became
free from the collection spontaneously, according to
the results of our previous CT studies and the study
of unruptured aneurysms (the percentage was even
higher among younger patients). This complication after
craniotomy for unruptured aneurysms provides a model
for further elucidating the causal mechanism of CSDH
and for investigating preventive measures such as drug
prophylaxis to decrease the subdural fluid collection
commonly seen in elderly patients after head injury.

the pathogenesis of CSDH, one of the most common

conditions requiring neurosurgical treatment in the
neurosurgical field. The starting point is a subdural
collection of CSF with blood cells which occurs due to
tears in the arachnoid membrane following contusion of
the brain or slight bleeding from a bridging vein. The next
step is the formation of a primary neomembrane with
a rich vasculature following an inflammatory reaction
by persistent and somewhat bloody subdural fluid
collection. Gradual bleeding with exudation including
various cytokines and activating substances occurs
inside the neomembrane, and the unclotted hematoma
increases in size as an encapsulated hematoma with a
thick outer membrane and thin inner membrane above
the arachnoid membrane, although some hematoma
resolves spontaneously. Natural healing of the hematoma
membrane may occur as part of the regression of the
inflammatory process. A burr hole with irrigation is
thought to be effective to speed this healing process of
the vascular-rich membrane.
Disclosures
The authors have no conflicts of interest to disclose,
and the study was approved by the Conflict of Interest
Committee of Tokyo Medical and Dental University.

1.

2.

3.

4.
5.

6.

Conclusion
We proposed a new integrated concept to describe

7.

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