LETTER TO THE EDITORS

History of post-stroke epilepsy in ancient China

Yan Wang • Yun-Cao Fan • Cheng-Long Xie •

Guo-Qing Zheng

Received: 12 November 2010 / Revised: 8 February 2011 / Accepted: 9 February 2011 / Published online: 24 February 2011

� Springer-Verlag 2011

Dear Sirs,

Seizure and epilepsy are harmful and worsen the disability

of stroke patients. In 1881, Hughlings Jackson [1, 2] first

noted that the phenomenon of seizure activity was related

to stroke and he described partial seizure that occurred in

the setting of embolic stroke. However, the phenomenon of

epilepsy has been known for over 3,000 years, the earliest

recorded account being in an Akkadian text called the

Sakikku (written around 1067–1046 BC) [3]. Since then,

several studies have been published that observed the

association between stroke and the ensuing seizure and

post-stroke epilepsy has become a well-recognized entity.

However, it is unclear when this disease was first observed

and reported in ancient time. Traditional Chinese Medicine

(TCM) has a long and rich history, and has existed for

thousands of years. It is still being used today as a form

of healthcare in both China and worldwide. About

2,000 years ago, Jinguiyaolue (Synopsis of Prescriptions of

the Golden Chamber, SPGC) by Zhang Zhongjing (AD

152–219) at the end of the Han Dynasty recorded the

Tanjian (Paralysis and Epilepsy) under the chapter titled

Zhongfeng (Apoplexy) which was treated by Fengyintang

(Feng-yin Decoction, FYD) [4]. Thus, the relation between

seizures and stroke was recognized in the third century in

China. From then on, studies on post-stroke epilepsy and

its therapy have extended over thousands of years in China

until now. There is a wealth of information and studies in

the Chinese literature. However, it is not readily accessible

to western scientists because of language barriers. The aim

of this study is, therefore, to do historical research on post-

stroke epilepsy in Chinese medical treatises, so as to fill a

gap in our knowledge by providing a translated summary

of related articles.

Since ancient times, stroke and epilepsy have been very

common and serious neurological disorders in the world.

Written in the late part of the Warring States Period (BC

476–221), the earliest extant Chinese prescription book,

Wushierbingfang (Prescriptions for Fifty-two Diseases),

described 52 diseases and 52 prescriptions in detail. Pre-

scription for Epilepsy of Infant as a prescription for epi-

lepsy has already been described in this book [5]. The

oldest and greatest extant classic TCM literature in China is

Huangdineijing (Huangdi’s Internal Classic), which is

composed of two books, Suwen (Plain Questions) and

Lingshu (Miraculous Pivot). It is actually a product of

various unknown authors from the Warring States Period

to the Han Dynasty (475 BC–220 AD). There are also

separate descriptions of stroke and epilepsy in this book

[6]. This book describes different stroke-related symptoms

such as hemiplegia (paralysis on one side of the body),

difficulty with speech, face distortion, loss of conscious-

ness, paralysis with speech difficulty, and paralysis with

unconsciousness. Under the section Miraculous Pivot in

this book, one type of stroke is described in the following

manner. ‘‘Fei (one type of stroke) is a kind of disease. The

patients present with sensory disturbance on the body and

soft paralysis of extremities. Patients with mild con-

sciousness disorder and partial expressions are treatable.

Patients with no verbal response are untreatable’’. It was

quite advanced at that time to judge the prognosis of stroke

by the state of consciousness disorder, and to judge the

level of consciousness by the ability to speak. The

descriptions of epilepsy in Huangdi’s Internal Classic, and

in many others published later, were the generalized

Y. Wang � Y.-C. Fan � C.-L. Xie � G.-Q. Zheng (&)

Center of Neurology and Rehabilitation, The Second Affiliated

Hospital of Wenzhou Medical College, 109 Xueyuan West

Road, Wenzhou 325027, People’s Republic of China

e-mail: gq_zheng@sohu.com

123

J Neurol (2011) 258:1555–1558

DOI 10.1007/s00415-011-5959-3

convulsive seizures [7]. It is described in Miraculous Pivot

that the patient with seizure may suddenly scream, with

muscle rigidity all over the body, difficulty in breathing,

palpitation, and painful feeling in the back after the attack.

Chao Yuanfang (610 AD) accurately described the symp-

toms of epilepsy with tonic-clonic seizures in his book

Zhubingyuanhoulun (Treatise on the Pathogenesis and

Manifestations of All Diseases). ‘‘The patients with sei-

zures may suddenly fall down, foam at the mouth, devia-

tion of mouth towards one side, rolling up of the eyes, and

the flexion and extension of limbs. The patients may suffer

from loss of consciousness and regaining consciousness is

slow [8].’’

Doctor Zhang Zhongjing (AD 152–219), known as the

Chinese Hippocrates in the Eastern Han Dynasty (206 BC–

220 AD), was famous for his great book of TCM: Shang-

hanzabinglun (Treatise on Cold Damage and Miscellaneous

Diseases). This book was divided into two different parts:

Shanghanlun (Treatise on Cold Damage Diseases), and

SPGC, which is referred to as the ancestor of prescriptions.

The concept of pattern identification/syndrome differenti-

ation and treatment was first raised in this book, laying a

foundation for the development of clinical medicine. SPGC,

as the first clinical medicine classic in China, attaches much

importance to diagnosing miscellaneous diseases of internal

organs. The fifth chapter is titled ‘‘On pulse, syndrome

complex and treatment of apoplexy and acute arthritis’’,

with possible post-stroke epilepsy and its therapy recorded.

The original texts are as follows: ‘‘Disease brought on by

pathogenetic Wind will cause symptoms such as hemiplegia

or monoplegia, known as apoplexy. It is a case of Bi syn-

drome of TCM which means pathogenetic obstruction with

feeble-speedy pulse…if the evil-wind invades the collater-

als, the patient will have a feeling of numbness on the skin

and muscles; when it invades the channels, there will be a

feeling of serious heaviness of the body; when it invades the

Fu-organs, the patient will suffer from unconsciousness;

and when it invades the Zang-organs, difficulty with speech

and emission of saliva at the mouth can occur…FYD could

eliminate paralysis and epilepsy caused by stirring of wind

due to (liver)-heat [4].’’ The ingredients and dosages of

FYD are shown in Table 1. The author’s own notes are as

follows: ‘‘FYD could treat post-stroke seizure (or convul-

sive wind-epilepsy) in adults, and also frightened epilepsy

and clonic convulsions in infant. There may be frequent

attacks of epilepsy everyday and the curative effects of

other prescriptions are usually not very good. FYD is an

effective prescription because it could clear heat and

extinguish wind [4].’’

In Zhang’s SPGC, stroke is classified as channel and

collaterals being attacked or Zang-fu organs being

attacked, according to the disturbance of consciousness,

and this classification is still in use today. The definitions

of stroke in TCM include: (1) Channel and Collaterals

(Meridian) Stroke: the patients are in a conscious state, but

there may be loss of feeling or motor weakness on one side

of the extremities or hemiplegia, mouth and tongue twisted

to one side, difficulty with speech or loss of ability to

speak; (2) Zang-Fu Stroke: the patients have lost con-

sciousness with one side of the body paralyzed, mouth and

tongue twisted to one side, unclear speech or loss of the

ability to speak.

In his text on ‘‘apoplexy’’, Zhang accurately showed his

observation on the phenomenon of the combination of

paralysis and epilepsy. This should be regarded as the

earliest record for post-stroke epilepsy. Although based on

the theoretical framework of TCM, Zhang explained this

disease as resulting from stirring of wind due to liver-heat.

This record was nearly two thousand years earlier than the

report from Hughlings Jackson.

Table 1 The ingredients of the Fengyin Decoction and their modern pharmacological actions

Ingredient Dosage (liang) Modern pharmacological actions

Rhubarb 3 Relieves fever, diarrhea effect, lowers blood pressure

Bone fossil of big mammals 3 Sedation function, reduces excitability of nerve and muscle

Dried ginger 3 Hypnotic effect, restrains spontaneous movement, relieves fever and pain

Gypsum 6 Relieves fever, sedation function, inhibits excitability of nerve and muscle

Gypsum lamelliforme 6 Relieves fever

Talc 6 Protects digestive tract of stomach

Fluorite 6 Sedation function

Halloysitum rubrum 6 Protects digestive tract of stomach

Halloysitum album 6 Sedation function

Oyster shell 2 Sedation function, anticonvulsion, reduces excitability of nerve cell

Cassia twig 2 Sedation function, anticonvulsion

Liquorice root 2 Sedation function, hypnotic effect

Converting the dosage in the Eastern Han Dynasty into today’s dosage: 1 Liang = 15.625 g

1556 J Neurol (2011) 258:1555–1558

123

The middle period of this research is defined from the

Three Kingdoms Period to the Qing Dynasty (AD

220-1911). Wang Tao recorded in Vol. 15 of Waitaimiyao

(Medical Secrets of an Official; also, Arcane Essentials

from the Imperial Library): ‘‘In 308 AD of Western Jin

Dynasty (AD 265–316), many adults and infants got the

disease of wind-epilepsy. The patients got aphasia, or had a

temperature and half-body convulsion. Many died within a

few days. FYD was used and received very significant

curative effect [9].’’ This record shows that FYD was a

good prescription as an antiepileptic and anticonvulsant.

Sun Simiao (AD 541 or 581–682), during the Tang

Dynasty (AD 618–907), is known as the king of pharma-

cology and prescriptions. His best known work is Bei-

jiqianjinyaofang (Essential Prescriptions Worth a

Thousand Gold for Emergencies). In the fifth chapter titled

‘‘Wind-Epilepsy’’ in Vol. 14, he recorded fluoritum powder

for boiling [10], a synonym of FYD, and used this pre-

scription for epilepsy. These records showed that FYD was

still used in the Tang Dynasty.

Unfortunately, because of frequent warfare between the

Eastern Han Dynasty and the Western Jin Dynasty, the

original book of SPGC disappeared from sight gradually. In

the late Song Dynasty (AD 1023–1063), Zhang Zhongjing’s

relic book SPGC was fortunately found by Wang Zhu of the

imperial academy (Xue-shi-yuan) in the imperial libraries

(known in Chinese as Guan-ge) [11]. In AD 1068–1077,

Lin Yi, a TCM expert in a state institution known as the

Bureau for Re-editing of Medical Books that was set up by

imperial government of the Song Dynasty in 1057 AD,

re-edited SPGC with other experts. From then on, dozens of

annotations on SPGC appeared and SPGC has been handed

down. There are also many annotations and commentaries

on FYD. The records of post-stroke epilepsy and its pre-

scription FYD obtained better transmission.

In 1406 AD of the Ming Dynasty (AD 1368–1644), the

largest ancient Chinese prescription book (61,739 pre-

scriptions included), Pujifang (Prescriptions for Universal

Relief), was published by Zhu Su et al. One synonym of

FYD, anti-epilepsy decoction [12], was included in Vol.

378 on the chapter Infant and Child Epilepsy of this book.

In the Qing Dynasty (AD 1644–1911), Yu Chang identified

the phenomenon of ‘‘post-stroke seizure’’ again in Vol. 3

under the title Stroke of his book Yimenfalu (Principles for

Medical Profession) and also treated this disease with FYD.

The original text is as follows: ‘‘FYD could treat post-

stroke seizure in adult, and also frightened epilepsy and

clonic convulsion in infant. It seems to be very easy for this

decoction to cure these kinds of diseases. The effect is very

significant [13].’’

In 1956, Huang [14] (1911–1970) thought that the words

of SPGC were too profound for the understanding of

beginners and explanations from various experts in the past

dynasties were not perfect enough. He tried to give an

explanation once again with the combination of TCM

theories and personal academic experiences, so that Jin-

guiyaolueshiyi (Exegesis of Synopsis of Prescriptions of the

Golden Chamber) was written. In this book, it is empha-

sized that post-stroke epilepsy could be treated with FYD.

In modern periodicals, the report of treating epilepsy

with FYD was first seen in 1962. Shang [15] treated two

cases of epilepsy with FYD and the treatment was shown to

be effective. From January 1970 to December 1980, Bai

et al. [16] treated 100 cases of epilepsy with FYD, and the

results were as follows: cure (no recurrence in 2 years), 46

cases; excellence (no recurrence in 6 months, treatment

once again could control the attack), 46 cases; effective

(attack frequency decreased), 25 cases; no effect (no

change of pathogenetic condition), 14 cases. This study

took account of the diagnostic methods of western medi-

cine, so that the diagnosis was definite and the study pro-

vided the Level 3 evidence. In 2003, Wang et al. [17]

treated 21 cases of epilepsy after cerebral infarction with

FYD. The results were as follows: excellent (compared

with pre-therapy, the intermissive time lengthened for more

than 1 year), 18 cases; effective (during attack, the symp-

toms were lightened and the intermissive time lengthened

significantly), 2 cases; ineffective (frequent attack or

symptoms worsened or died), 1 case. This is a clinical trial

for FYD in the treatment of post-stroke epilepsy in the real

sense. But up to now, there are no large sample, multi-

centre, double-blind, randomized and controlled clinical

trials. Although there is still a lack of reliable scientific

evidence, TCM treatment for epilepsy is very popular in

China because of the long-term experience with rather

good curative effect. FYD and other herbs are also com-

monly used in post-stroke seizure. Thus, more stringent

data are still required for evaluating post-stroke seizure

treatment with TCM, if TCM therapy is to gain acceptance

with evidence-based medicine.

Wang [18] and Li et al. [19] summarized modern

pharmacological actions of a single ingredient of FYD

(Table 1). For example, bone fossil of big mammals and

gypsum had a sedative function. Cassia twig and oyster

shell had sedative and anticonvulsive effects. Fluorite,

gypsum, bone fossil of big mammals, oyster shell, contain

calcium, which could lower the excitability of nerves and

muscles. Although, until now, there are mainly pharma-

cological and drug efficacy studies on single ingredients of

FYD and lack of pharmacological studies on the whole

prescription, the previous pharmacological studies are

providing preliminary scientific evidence for the clinical

application of FYD. Therefore, FYD has potential prospect

of development and clinical application. It is urgent and

meaningful to do the assessment of the pharmacology,

safety and efficacy of FYD for post-stroke epilepsy.

J Neurol (2011) 258:1555–1558 1557

123

In conclusion, the records of post-stroke epilepsy and its

therapy could date back to the third century in China, and

the earliest recorded account was in SPGC. Studies on

post-stroke epilepsy and its therapy extended over thou-

sands of years in China until now. Some modern pharma-

cologic and clinical researches have been conducted on its

prescription FYD and showed potential effective results.

More evidence from properly controlled studies are needed

to further confirm the therapeutic effects of FYD, and thus

it would contribute more to the treatment of post-stroke

epilepsy worldwide.

Acknowledgments This work is supported by the Key Project of

Wenzhou Municipal Science and Technology Bureau in Zhejiang

province of China (grant number Y20070038).

Conflict of interest The authors declare that they have no conflict

of interest.

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