Medical Hypotheses (2008) 70, 1147–1149

http://intl.elsevierhealth.com/journals/mehy

Traumatic subdural effusion evolves into chronic

subdural hematoma: Two stages of the same
inflammatory reaction?
Jun-feng Feng, Ji-yao Jiang *, Ying-hui Bao, Yu-min Liang, Yao-hua Pan

Department of Neurosurgery, RenJi hospital, Shanghai Jiaotong University/School of Medicine, No. 1630,
Dongfang Road, Pudong New District, Shanghai 200127, People’s Republic of China

Received 31 October 2007; accepted 3 November 2007

Summary Traumatic subdural effusion (TSE) is one of the main associated complications of brain trauma. About half
of the asymptomatic TSEs ultimately evolve into chronic subdural hematomas (CSDHs), most of which will be inevitably
treated by surgical evacuation. With the emergence of subdural hydroma (SDH), rupture of bridge-veins, bleeding of
the hydroma wall, hyperfunction of fibrinolysis and increasing protein content in the hydroma are some of the
traditionally cited explanations of the pathogenesis of TSE evolving into CSHD. Despite intensive research and
subsequent advances in surgical techniques of CSDH, a single treatment with measurable clinical impact on the
evolution interruption has yet to be investigated. Compared with peripheral venous blood, inflammatory cytokines
were elevated in TSE and CSDH demonstrated by a number of investigators. Neoformation of capillaries, vascular
hyper-permeability, serum protein exudation and other characteristics of aseptic inflammatory reaction were
observed. Meanwhile, steroid was applied to treat CSDH in several groups, which was generally used as an effective
anti-inflammatory agent. Based on systemic thinking, we hypothesize that TSE and CSDH are different stages, with
different appearances, of the same inflammatory reaction. The evolution from TSE into CSDH and propagation of CSDH
seem to be the results of local aseptic inflammation. Our hypothesis holds potential as a target for therapeutic
intervention.
c 2007 Elsevier Ltd. All rights reserved.

Introduction reported 6–21.6% of all closed head injury [1–3].

Traumatic subdural effusion (TSE), also called as
subdural fluid collection or subdural hydroma
(SDH), is described in the literature as a common
complication of blunt head trauma occurring in a
* Corresponding author. Tel.: +86 21 68383707; fax: +86 21
68383747.
E-mail address: fengjfmail@163.com (J.-y. Jiang).
Most TSE resolves when the brain is well expanded.
However, a few TSEs become chronic subdural
hematomas (CSDHs), which are encapsulated col-
lections of old blood, mostly or totally liquefied
and located between the dura matter and arach-
noid. 16.7–32.8% of all TSEs developed into CSDHs,
especially in the aged [3–5]. And nearly 50% of pa-
tients with asymptomatic or minimally symptom-
atic subdural fluid collection may develop a CSDH


0306-9877/$ - see front matter c 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2007.11.014
1148
[6]. The main clinical manifestations of CSDH in-
clude headache, dizziness, nausea, hemiplegia,
and abnormal mentality. With the disease progress
becoming life-threatening, most CSDHs will be
inevitably treated by surgical evacuation. Burr hole
craniotomy and twist drill craniotomy with a closed
system drainage are generally applied as effective
surgical alternatives [7]. As the genesis and devel-
opment of a CSDH is concerned, neoformation of a
subdural membrane, abnormal vascular permeabil-
ity, defective local hemostasis (hyperfibrinolysis)
and chronic rebleeding are traditional explanations
[8]. In recent years the involvement of inflamma-
tion has been investigated by researchers [9–14].
Despite intensive research and subsequent ad-
vances in surgical techniques of CSDH, a single
treatment with measurable clinical impact on the
evolution interruption has yet to be investigated.
There is an interval between TSE and evolution of
CSDH, 101.5 days in average [5] or 22–100 days
after head injury [4]. What can we choose to inter-
rupt the evolution, but not just observing the
development? On the other hand, some CSDH pa-
tients with co-morbidity or surgical contraindica-
tion have to choose conservative treatments.
Therefore, the pathophysiology of the evolution
from TSE to CSDH and propagation of CSDH have
to be deeply analyzed.
The role of inflammation in the evolu-
tion from TSE into CSDH
There is a rich history of research in the area of TSE
and CSDH with a number of inflammatory cytokines
and indications of local inflammation identified in
their pathogenesis. Interleukin (IL)-6 and IL-8 in
both CSDH and TSE groups were much higher than
those in the blood of both groups, and the levels
in CSDH patients were significantly higher (10
times) than in TSE patients. But the blood levels
of tumor necrosis factor (TNF)-a, IL-1b, IL-6 and
IL-8 in both groups were almost normal [9]. The
concentration of IL-6 and IL-8 was much higher in
the lesion than that in serum, and was significantly
correlated with recurrence of CSDH [11]. The level
of IL-10, an anti-inflammatory cytokine, was signif-
icantly increased with the level of IL-6 and IL-8
increasing in subdural fluid during the formation
of CSDH [12]. Proliferation of fibroblasts and imma-
ture capillaries accompanied by hyperfibrinolytic
activity and increased permeability are ubiquitous
phenomenon during angiogenesis in inflammation,
which were generally observed in the evolution
and propagation of CSDH [10,13–18]. Vascular
Feng et al.
endothelial growth factor (VEGF) was also corre-
lated with the pathogenesis [19]. The pathological
process of TSE and TSDH indicates that local
inflammation is playing a leading role in the patho-
genesis of evolution and propagation of CSDH.
The hypothesis
We therefore hypothesize that TSE and CSDH are
two stages of the same inflammatory reaction.
The evolution from TSE into CSDH and propagation
of CSDH seem to be the results of local inflamma-
tion. Besides the similar inflammatory reaction in
TSE and CSDH, both of them have similar clinical
manifestations and prognoses, displaying as liquid,
space occupying lesions which cause pressure in
the underlying brain [20], ultimately resolved or
progressed to be treated by surgical intervention.
The fundamental distinctions between TSE and
CSDH are appearance of their contents and the dif-
ferent CT values, but not pathogenesis. Solutions
over 10(5)/mm3 red cells or 0.5 g/dl hemoglobin
are represented as being sanguineous, and corre-
spond to 15 Hounsfield’s units measured by the
CT scan, which are the lower limit for a subdural
hematoma [21]. Otherwise, a subdural collection
will be called an effusion or hydroma. The hemo-
globin in hematoma is much more important than
protein, iron or calcium ions in determining the
attenuation values in the CT scan [21]. And it is
the local inflammatory reactions, such as prolifera-
tion of immature capillaries, cytokines, local
hyperfibrinolytic activities and resultant bleeding,
which ultimately increase the hemoglobin in sub-
dural collection [13,17,18,22]. We therefore pro-
pose that TSE and CSDH are different stages, with
different appearances, of the same inflammatory
reaction pathologically. The evolution from TSE
into CSDH and the propagation or recurrence of
CSDH were always considered to be inevitable.
But with our opinion, more therapeutic alterna-
tives can be chose to treat TSE and CSDH, actively
and effectively.
Implication of hypothesis
Aside from careful observation or surgical evacua-
tion, TSE and CSDH can be treated by
anti-inflammatory agents. Administration of meth-
ylprednisolone acetate into the subdural cavity in
an infant with subdural fluid collection was
observed [23]. Steroids can be an alternative
treatment of CSDH, particularly in patients with
Traumatic subdural effusion evolves into chronic subdural hematoma
co-morbidity [24,25] and in elderly or alcoholic pa-
tients [26], with no significant complication from
steroid therapy. Effect of platelet-activating factor
receptor antagonist, etizolam [27], and blocking
the physiological effects of VEGF [19] were both
investigated as conservative therapy. We hypothe-
size that TSE and CSDH are two stages of the same
inflammatory process, which is triggered by brain
trauma. The targeting of anti-inflammatory agents
may therefore represent a promising focus for fu-
ture treatment of interrupting the evolution from
TSE into CSDH and the propagation or recurrence
of CSDH, and pave the way for further discoveries
in these frequent and considerable disorders.
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