Volume 5, Number 1 | Spring 2010

Kampo Medicine - Current Research
Effect of Goreisan on Chronic Subdural Hematoma－From the Goreisan Symposium 2010”－
Mitsusuke Miyagami
Department of Neurosurgery and Rehabilitation,
Takenozuka Nohsinkei Rehabilitation Hospital
Sonoda Daiichi Hospital

Introduction
Chronic subdural hematoma (hereafter CSDH)
is a gradual accumulation of blood below the duramater over more than three weeks, generally after
a minor head injury. The hematoma is
encapsulated, in which old liquefied blood is found.
In recent years, increases in the number of theelderly and image analyzing examinations such as
CT/MR images have contributed to an improved
detection of CSDHs, for which surgery is arecognized and established method of treatment.
However, even if CSDH shows up on CT images,some patients do not exhibit the signs andsymptoms indicative of CSDH or merely show
very mild symptoms. There are also patients who
do not desire an operation. Moreover, therecurrence of CSDH after surgery occurs in 10 to20%12,19,23 of patients. Patients who are prone tobleeding or have complications are hesitant toundergo surgery. On the other hand, it must be
kept in mind that CSDHs may heal
spontaneously,3,16 which is said to occur in 2.8 to
21% of patients with mild mass effect who do notshow signs and symptoms or have very mild
symptoms.4,15,17 For this reason, non-operative
treatment may be selected depending on thepatient. In terms of non-operative procedures for
CSDHs, hyperosmolar therapy8,22 with mannitoland steroid hormone therapy1,2,18 have beenreported. Recently, practitioners in the field of
neurosurgery have had another look at Kampo
treatment and treatment of CSDH with Kampo
medicines 9,10,14,21,15 for CSDHs has occasionallybeen seen. However, only a few case reports havebeen published and Kampo treatment has not

6been established for CSDH.
Since January 2006, we have used goreisan forsome patients with CSDH and studied its
efficacy.11 This study reports the efficacy of the
medicine for CSDH obtained through conducting
CTs with long-term follow-up.
Subjects and Methods
As stated above, surgery is an accepted
treatment for CSDH. However, we used goreisan
for CSDH in the following types of patients (withtheir consent and that of their family members):(1) those who did not desire surgery, (2) those who
did not exhibit signs or symptoms, or very mild
symptoms, and (3) those who were prone tobleeding or presented with systemically badhealth conditions. The subjects enrolled in thetrial were 22 patients with CSDH (the number ofhematomas was 27). Their ages ranged from 50 to98, with 18 subjects 70 years old or above. Nine
subjects had right-sided hematomas, 8 had
left-sided, and 5 had bilateral. Fourteen subjects
had experienced trauma. Two subjects developed
recurrent CSDH after surgery as the firsttreatment. At the start of treatment after CSDH
developed, 8 patients presented without any
symptoms, 7 had headaches or dizziness, and 5
had mild motility disorder. In terms ofcomplications, 5 patients had dementia. Eachsubject had one of the following complications:diabetes mellitus, dialysis, cerebral infarction,
cerebral hematoma, terminal colon cancer, or
jaundice.
The CT findings were examined for the
maximum width of the hematomas and their CT
density. Twenty hematomas, the largest number,
had a maximum width of 10 to 19 mm just before
treatment, 4 hematomas had 20 to 25 mm, and 3
had 9 mm or less. The CT density at the start oftreatment with goreisan was evaluated as iso,high, or mixed in 14 hematomas and low in 13
hematomas. The period of follow-up by CT was
4–29 weeks (Table 1).

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 5, Number 1 | Spring 2010

Table 1. Summary of cases with chronic subdural hematomas treated with goreisan..

TSUMURA Goreisan Extract Granules (Extract of goreisan, 7.5 g divided into 3 doses in three times
a day, basically before meals) was orally administered to all patients with CSDH regardless of thepatients’ pathological conditions from the Kampo perspective. The patients who were able to take themedicine for four weeks or more were assigned to the study. With the disposition of the primary doctor,
hemostatic agents (tranexamic acid and carbazochrome sodium sulfonate) were used in combination for
7 non-selected subjects. The effectiveness of goreisan was assessed based on whether the hematoma
had resolved or decreased in size as determined by a CT. Results (Figure 1, 2)

Figure 1. Change in maximum thickness of hematomas
with iso/high ( ) or mixed ( ) density on a CT afteradministration of goreisan.

Figure 2. Change in maximum thickness ofhematomas with low density on a CT afteradministration of goreisan. ● effective cases〇ineffective cases

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Volume 5, Number 1 | Spring 2010

Results
The treatment with goreisan resulted in a highlevel of improvement in 23 (85%) of 27 CSDHs,
including hematomas that had disappeared or
shrunk, whereas treatment was ineffective for 4
CSDHs (15%) since they remained unchanged
after administration of the medicine. In the 23
CSDHs responsive to goreisan, 12 hematomas
disappeared and 11 shrank (Table 1). In 17
CSDHs (74%) out of the 23 CSDHs that showed
improvement, the hematomas began to shrink
within four weeks after administration and thenthey gradually shrank further or disappeared. Of
the 12 CSDHs that disappeared, 10 took less than
14 weeks to disappear. None of the hematomas
grew after administration of goreisan for fourweeks or more, so there were also no CSDH casesthat needed surgery. In the meantime, there wereno adverse effects associated with the medicationin any of the cases.
We studied the time-dependent changes in thedensity level of hematomas after administrationof goreisan. The medicine was effective in all 14
CSDHs with density levels of mixed or high/iso on
a CT before treatment. That is, 14 CSDHs all
improved with 8 resolved hematomas and theother 6 shrank (Figure 1). Of the 13 CSDHs withlower density on a CT, 9 showed an improvementwith the hematoma disappearing or shrinking,while 4 CSDHs remained unchanged andnon-responsive to the administration of goreisan(Figure 2). The results of the study show that
CSDHs with hematoma density levels of iso/highor mixed were more responsive to goreisan. We
consider that further research with many morepatients will be needed.
A representative caseCase: K. H. (Figure 3)
79 years old, female: Bilateral chronic subdural
hematoma (CSDH) (L>R).
On November 19, X year, the patient fell down
and banged her head. On January 10 of thefollowing year, she visited our facility,

8

complaining of a mild gait disorder. CT
examination revealed a bilateral CSDH (right: 8mm, left: 5 mm) with iso density and theadministrationofhemostatic
agents(carbazochrome sodium sulfonate 3 tablets andtranexamic acid 3 tablets a day) was commenced.
A CT scan during a follow-up visit on February 7
indicated enlarged hematomas, having amaximum width of 10 mm on the right and 20 mmon the left, with mixed density on both sides. For
this reason, goreisan 7.5 g (divided into 3 doses)
was commenced with the hemostatic agents. The
hematomas began to decrease in size after sevenweeks: the right hematoma disappeared and theleft one remained unchanged with a maximum
width of 20 mm. However, the extent of thehematoma tended to decrease. On April 20, thedensity decreased to low and shrinkage was
obvious. In the 14th week, the CSDH dissolved
completely (Figure 3). The gait disorder also
disappeared and she recovered her normal gait.

Figure 3. CT scan of case 2 (K.H.) before and afteradministration of goreisan. 06,2,7; before
administration, 06,3,30;, 06,4,20;, and 06,5,25; 7,
10 and 14 weeks after administration of goreisan.
Discussion
A widely-accepted theory13 of the etiology andgrowth mechanism of CSDH is that hematoma
enlargement occurs through blood leakage andconstantorintermittent
bleedingfromneovascular vessels in a false membrane into the

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 5, Number 1 | Spring 2010

capsule and the cavity of a hematoma in order toenhance local fibrinolytic activity inside thehematoma and its outer membrane. On the other
hand, the old theory of osmosis pressure is stillprevalent, but the cause is not known in detail. As
nonsurgical management of CSDHs, the use ofdiuretics or steroids has been claimed to beeffective. More specifically, effectiveness has beenreported for mannitol 20% osmotherapy by Suzuki,
et al.22 and Kinjyo, et al.;8 the combination
therapy with steroid hormone and 50% glucose by
Ambrosetto, et al.; １ and the steroid-alone
hormone therapy by Glover, et al.２ and Rudiger,
et al.18
In recent years, CSDH has occasionally beentreated using the aquaretic Kampo medicines of“goreisan” and “saireito.” Seki, et al.21 usedgoreisan in 8 cases of CSDH and obtained
improvement in 4 cases. Onuki10 and Ueno, et al.25
reported that hematomas had resolved in all caseswith the combination treatment of goreisan andprednisolone. Muramatsu, et al.14 reported theeffectiveness of goreisan; they used the Kampo
medicine alone in 11 cases and in 10 of the cases,
the hematomas disappeared or shrank. Kitahara9
had favorable results using saireito, which ismade up of two formulae: “goreisan” and“shosaikoto”. Kitahara reported that improvement
could be obtained even if administration of
antithrombogenic agents continued.
Since 2008, a number of reports on thetreatment of initial and recurrent CSDHs withgoreisan have been published and all of thesereports suggest its usefulness.
We treated 22 cases of CSDHs (27 hematomas):goreisan alone was administered in 15 cases, andgoreisanandhemostatic
agentswere
administered in combination in 7 cases, resulting
in effectiveness in 23 hematomas — 12
hematomas were resolved and the other 11 shrank.
We believe this improvement was due to theeffectiveness of goreisan rather than spontaneous

healing. This is based on the following: (1) casesthat had a tendency for the hematomas to growbefore the administration of goreisan, and manycases that did not have a tendency for thehematomas to shrink were included; (2) there
were cases that showed a tendency for thehematomas to shrink from an early stage after theadministration of goreisan; and (3) higher rates ofeffectiveness of the treatment were shown
compared to the frequency of spontaneous
resolution of CSDHs in the past. In general, thehematomas started to shrink three to four weeks
after the start of administration of goreisan, andthey disappeared within 14 weeks afteradministration in most cases. There were only a
few cases in which shrinkage started within 2
weeks. To assess the effect of CSDH treatment
with this Kampo medicine, a continued
administration for at least three to four weeks ormore is required.

Goreisan, which consists of the five crude drugsofarismarhizoma,tuckahoe,
polyporussclerotium, atractylodes lancea rhizoma, andcassia twig, is a typical diuretic Kampo medicine.
This diuretic medicine clinically has anti-edema
action6,20 and is generally prescribed forpathological conditions such as headache, cerebral
edema, ascites, gastroenteritis, ophthalmic
disorders, hangover, and pain. Although themechanism of the effect of the medicine on CSDHs
is unclear, the diuretic actions may be the main
contributing factor as the usefulness of mannitol
osmotic diuretic agents has been reported.8,22
Unlike the diuretic agents used in Western
medicine such as mannitol, this Kampo diuretic
medicine is characterized by the role ofantidiuretic actions in a hydrated state and therole of regulating the actions of water metabolism
in a hyperhydrated state.24 It is said that thediuretic mechanism is involved in the inhibition ofwater channel aquaporins (AQPs), which increasewater permeability in cell membranes, whereas
goreisan inhibits the action of the aquaporins.5,20
According to Isohama,5 the constituent crude

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drugs of goreisan, especially atractylodes lancea
rhizoma, polyporus sclerotium, and tuckahoe(poria sclerotium), inhibit cell membrane water
permeability. In particular, AQP4, which is mostabundant in the brain but also distributed in large
numbers in astroglia cells adhered to capillary
endothelial cells, is said to be involved in water
permeability.6 Atractylodes lancea rhizoma, thecrude drug of the atractylodes family contained ingoreisan used for CSDH treatment, has been usedin many medicines as well as the ones used in our
experiment. Ueno, et al.25 have also reported thatgoreisan containing atractylodes ovatae rhizoma
was effective for CSDHs.
Our experiment suggests that goreisan is more
effective if the hematoma density on a CT is iso,high, or mixed, compared to low density. The
reasons, however, are not known in detail.
Meanwhile, in the cases of relatively new
hematomas with iso density or high density,
hematoma capsules often show the sinusoidal
channel layer, which is filled with capillaries. On
the other hand, in the hematomas with low
density, old bleeding to a certain extent canpossibly be found with relatively fewer vessels.
This means that CSDHs with low density have acomparatively long course and the vessels in thehematoma capsule may be relatively scarce. So, it
is possible that AQP4 surrounding the vessels arealso relatively reduced, causing the reduced
inhibition of water permeability.
goreisan is orally administered for treatment,
unlike mannitol or steroid drugs, and it did notcause any adverse effects in the cases in ourstudy11 and in other reported cases.10,14,21,24,25 We
consider goreisan to be an easy-to-use medicine
and useful for the future nonsurgical managementof CSDHs.
Conclusion
1. Goreisan was administered in 22 cases of CSDH
with 27 hematomas for four weeks or more andthe results showed it was effective in 23
hematomas (85%) with the hematomas
disappearing or shrinking.
10

2. Goreisan did not cause any obvious adverse
effects in the cases in our own study and inreported cases to date. It is a safe and useful
drug for nonsurgical therapy of chronic
subdural hematomas.
References
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Post-traumatic
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continued to take antithrombogenic agents. 19th
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Gakujutsushukai Shorokushu (19 themes)
November 13, 2010
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