History of post-stroke epilepsy in ancient China

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    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 10671046 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

    152219) 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

    476221), 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 (Huangdis 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 BC220 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 Huangdis 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, Peoples Republic of China

    e-mail: gq_zheng@sohu.com


    J Neurol (2011) 258:15551558

    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 152219), 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 pulseif 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 occurFYD couldeliminate 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 authors 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 Zhangs 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 todays dosage: 1 Liang = 15.625 g

    1556 J Neurol (2011) 258:15551558


  • 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 265316), 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 581682), during the Tang

    Dynasty (AD 618907), 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 10231063), Zhang Zhongjings

    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 10681077,

    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 13681644), 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 16441911), 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] (19111970) 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) 258:15551558 1557


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

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



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