China

Shichuo Li

Liwen Wu

Guoming Luan

Weiping Liao

Wenzhi Wang

Jianzhong Wu

Liyun He

Introduction

The People’s Republic of China (hereinafter referred to as China) is located in East Asia and on the West Coast of the Pacific Ocean. China has 9.6 million km² of area and 1.3 billion of population with 56 ethnic groups. Urban population accounts for 42% of the total. The administrative division of the mainland China is 22 provinces, five autonomous regions, and four municipalities directly under the central government.

The following are some public health indicators in China: National health expenditure (2003) of $63.3 (U.S.) per capita and total of $818.7 hundred million (U.S.), which accounted for 5.6% of the gross domestic product (GDP) and 11% of the central government’s expenditure allocated to health; life expectancy at birth (2000), 71, 69, and 73 years for total, male, and female, respectively; birth rate (2003), 12.29 per 1,000; death rate (2003), 6.42 per 1,000; infant mortality rate (2004), 25.5 per 1,000; maternal mortality rate (2004), 50.2 per 100,000; and mortality rate under 5 years of age (2004), 30 per 1,000 live births.

Statistics for public health resources are as follows: doctors per 1,000 inhabitants, 1.7; hospital beds per 1,000 inhabitants, 2.4; total number of health institutes in 2004, 296,492, and among them, 18,396 hospitals; and total number of health personnel in 2004, 5,353,628, and among them, 1,904,771 doctors and assistant doctors.

Since the establishment of the People’s Republic of China in 1949, remarkable advances have been made in the public health system and in employment. These include the following: (a) There has been an extraordinary improvement in measures of people’s health. The life expectancy at birth in 1949 was 35 years, but in 2004 it was 71.8 years. The infant mortality rate in 1949 was 200 per 1,000 live births, but in 2004 it was 25.5. The maternal mortality rate in 1949 was 1,500 per 100,000, but in 2004 it was 50.2. (b) A medical service system has been established that covers the whole nation. The three-tier healthcare system, in rural (county–township–village) and urban areas (city–district–neighborhood) has made great contributions to the improvement of people’s health. (c) A medical insurance system is in development. In urban areas, there are four types of medical insurance systems: (i) “free-of-charge system,” which covers about 50 million public servants, university students, etc.; (ii) basic medical insurance and (iii) supplementary medical insurance, both of which cover about 130 million workers; and (iv) commercialized insurance, which covers part of private enterprises employees. In rural areas, a new “cooperative medical service system” has just been implemented in a pilot stage, and this presently covers about 156 million farmers. (d) There has been great improvement in the prevention and control of communicable diseases. For example, deaths caused by communicable/parasitic diseases fell from first (in the 1950s) to the ninth (in 2004) place as a cause of death; smallpox, poliomyelitis, etc., have been eradicated; there has been effective control of severe acute respiratory syndrome (SARS) and avian influenza; and effective measures and networks have been put in place to control HIV/AIDS, tuberculosis, hepatitis B and schistosomiasis. (e) Remarkable improvements have been made in maternal and child healthcare. The prenatal examination rate has now reached 90%; the hospitalized delivery rate has reached 83%; and the mortality rate of children under 5 years of age has reached 29.9 per 1,000, whereas in 1949, it was 250 to 300 per 1,000.

Beginning in the late 1970s, China implemented an “open-door and reform” policy. Since then, public health work has further improved and in a number of diseases controlled. The medical service system is now under reform and the medical/health services are expanding coverage. The Chinese government has made great efforts toward the strategic goal of “health for all.”

Epilepsy was recognized and described 2,200 years ago in the oldest Chinese medical monograph Medical Classic of the Yellow Emperor (Huang Di Nei Jing). In China, epilepsy has long been treated by traditional Chinese medicine (TCM, meaning herbal medicine, acupuncture/moxibustion, and other folk therapies), and a long experience with epilepsy treatment has accumulated. However, the most effective control of epilepsy has resulted from modern medical practices, including surgical treatment. From the 1950s, clinical diagnosis and treatment of epilepsy in China has improved steadily, but very little research on its public health aspects occured until the 1970s.

What is described in this chapter—that is, the epidemiology, clinical neurologic diagnosis and treatment, epilepsy surgery, basic research, sociopsychological problems, rural community control programs, and TCM recognition of epilepsy in China—covers about the last three decades.

Epidemiology

Epidemiology is the study of the distribution and determinants of disease in human populations. Recently, psychosocial and economic indicators, such as quality of life and standards of care, have been incorporated into epidemiologic research, as their relationship to morbidity became evident.

There are several key difficulties in conducting epidemiologic research on epilepsy and in interpreting the epidemiologic literature.³²^,⁴⁷ These include:

Variations in the definitions and classification of seizures and of epilepsies
Poor case ascertainment due to ignorance or concealment by patients or their families, or due to the fact that some patients are not aware of having seizures
Diagnostic imprecision, even when potential patients are identified
Differences between studies in the age distribution of study populations, or in the place or mode of recruitment of subjects

Table 1 Prevalence Ratio and Incidence Rate of Epilepsy in China

Year	Study	Reporter	Sample population	Prevalence (per 1,000)	Incidence (per 100,000)
1981	Sichuan		426,789	4.8	35
1983	6 cities	Li	63,195	4.4	35
1985	22 provinces	Li	246,812	3.6	26
1992	Jiangsu	Shan	(0–14 yr)	5.9	200
2003	6 rural areas	Wang	55,616	7.0	(active 4.6)

These and other factors all limit the precision and validity of data and comparability among studies. Despite these difficulties, sufficient data are available from a number of studies
to give a useful profile of the epidemiologic characteristics of epilepsy in China.

Prevalence Ratio

Researchers use lifetime prevalence to express the magnitude and scope of the burden of a defined disorder in the population. Point prevalence is the proportion of a defined population with a disease at a given point in time (usually the first or last day of a year). The point lifetime prevalence ratio results for epilepsy in China from some studies are shown in Table 1. We may see that the prevalence for epilepsy in China is about 4 to 6 per 1,000, which is similar to the average figure in industrialized countries. In Wang’s study, patients with epilepsy who had seizures in the past year were categorized as “active epilepsy”; for those cases, the prevalence ratio was found to be 4.6 per 1,000.⁴¹

Incidence Rate

Incidence rate is the rate of occurrence of new cases of epilepsy in a defined population in a specified time period (usually 1 year). Table 1 also shows the incidence rates for epilepsy in China as 26 to 35 per 100,000 individuals per year.

Mortality Rate

Unfortunately in most countries epilepsy is not listed in “cause of death” statistics as an independent disease. Deaths of persons with epilepsy (PWE) are always registered as caused by the underlying disease or some other reason, such as “accident.” Reports from China showed 7.9 per 100,000 per year in urban areas and 6.9 per 100,000 per year in rural areas. The figure from China is higher than that from other countries, and this difference is not explained.⁴⁷

In recent years, the standardized mortality rate (SMR) has been used in the epidemiologic literature to analyze deaths in epilepsy. These analyses show that the SMR for epilepsy patients is more than twice that for the general population. Causes of mortality include (a) underlying brain diseases, such as tumor or infection; (b) seizure-related deaths (status epilepticus; drowning, burns, or other trauma; severe aspiration or airway obstruction by food, etc.; deaths caused by habitual seizures when coexisting with cardiorespiratory disease); (c) suicide; (d) death as a consequence of medical or surgical treatment of epilepsy; and (e) sudden unexplained death in epilepsy (SUDEP), whose causes remain ill-understood.²⁹^,⁴⁷

Research and data on SUDEP are very rare in China. From 1994 to 2004, only three papers on this topic were published, and two of them were literature reviews. Wang et al.⁴⁴ analyzed the clinical and pathologic information of seven cases of SUDEP. They found that all seven cases had edema of the brain and lungs. Some of the patients had reduction of neurons and increase of glial cells. There were no tumors or injuries. All seven died when they had a general tonic–clonic seizure. Two occurred in sleep and four had agitation or fright before death.

One hundred and twenty PWE from four provinces in China who had been part of a project, “community control of epilepsy,” in the late 1980s were followed up 5 years later. Thirteen had died. The mortality rate of this group was 2.2% per year and around 3.4 times higher than the rate in the general population. Among the 13 deceased, two (15.4%) might be categorized as SUDEP. This may be the only epidemiologic information for SUDEP in China.⁴⁰

Distribution by Sex and Age

As reported from most of other countries, in China, the prevalence and incidence of epilepsy is more frequent in men than in women. The prevalence in men and women in urban areas is 1.3:1 and the incidence is 1.7:1; in rural areas, it is 1.1:1 and 1.4:1, respectively. These differences are probably related to the more social and physical activities of men than of women and thus more frequently risk factors and causes for epilepsy are encountered by men. For age-specific prevalence, data from China showed that it is rising with age in childhood and adolescence, then plateauing in middle age, and decreasing in old age. As for age-specific incidence, there are two peaks: in childhood and the elderly. A study from Sichuan province indicated that 80% of epilepsy occurred before 15 years of age. Cerebrovascular disease, brain tumors, and other identifiable causes are responsible for the second peak of incidence in the older age group.²³

Table 2 Relative Frequency of Subtypes of Seizure

Subtype	China 1	China 2	Singapore	Turkey	Tanzania	United States
GS	89.6	77.3	65.2	78.9	58	40
GTCS	81	71.8	56.3	65.4	54.1	23
Absence	4.8	3.9	2.2	4.9	1	6
Other	3.8	1.6	6.7	8.6	2.9	11
PS^a	7.6	18.6	34.8	19.7	31.9	57
SPS	4.8	4.4	2.2	7.4	0.5	21
CPS	2.8	5.9	4.5	12.3	9.2	36
PS > GS	—	8.3	28.1	—	22.2	—
Other	2.8	4.1	—	1.2	10.1	3
CPS, complex partial seizure; GS, generalized seizure; GTCS, generalized tonic–clonic seizure; PS, partial seizure; PS > GS, partial seizure with secondary generalization; SPS, simple partial seizure.

Table 3 Risk Factors for Idiopathic Epilepsy (Case-Control Studies in Six Cities and Rural Areas of 22 Provinces of People’s Republic of China)

Expected risk factor	6 cities		22 rural areas
Expected risk factor	RR^a	p <	RR	p <
Parents’ intermarriage	—	(>0.05)	9	0.001
Epileptics in family	2.5	0.01	15.4	0.001
Previous febrile seizures	7.5	0.01	32.2	0.001
Premature or difficult labor	3.2	0.025	13	0.001
Born when mother >30 yr of age	1.5	0.05	1.4	0.025
^aRR (relative risk) = B/C; B, case (+), control (-); C, case (-), control (+).

Subtypes of Seizures

Table 2 shows the relative frequency of subtypes of seizures reported from China and some other countries.²³ Much of the variation among countries is probably related to differences in methods of data collection, sample size, classification scheme, and certainty of clinical diagnosis. Therefore, it is difficult to compare them or draw inferences. For example, the apparent high proportions of generalized seizures in the two studies from China reflect the fact that those studies focused on convulsive seizures rather than nonconvulsive seizures.

Risk Factors

In epidemiologic studies, scientists usually use retrospective methods (typically case-control studies) to identify risk factors
for epilepsy. For a number of practical reasons, prospective (cohort) methods, although theoretically preferable, are rarely used.

Table 3 shows the results of two case-control studies that were conducted in six cities of China in 1983 and in rural areas of 22 provinces in 1985.²³ The findings generally match those of a number of studies in other countries.⁴⁷ Many epidemiologic studies implicate genetic factors, perinatal factors, and a history of febrile seizures as risk factors for various major kinds of epilepsy, although some controversy persists.

The discovery of epilepsy genes has benefitted from the success of the Human Genome Project, a multinational endeavor that has produced detailed maps of the human chromosomes. The genes responsible for particular genetic epilepsies can now be identified and localized to specific chromosomal regions, ultimately allowing researchers to determine the structure of the encoded molecules. This requires the study of families in which several members are affected with well-characterized epilepsies. The genetic “lesions” responsible for idiopathic epilepsies give rise to various familial epilepsy syndromes.³ A genetic etiology is indicated by, for example, familial incidence and frequent clinical concordance in twin studies.

In most studies, populations with poor perinatal health care, high incidence of premature births and head trauma during delivery, and high infant mortality are at high risk for epilepsy. The major perinatal factors include short gestation, low birth weight, prolonged labor, neonatal asphyxia, and assisted de-livery.

Febrile illness of any kind can trigger seizures in young children. About 3% of children who have febrile convulsions go on to develop epilepsy in later life.

Some investigations suggest that rural populations with poor health services and disadvantaged urban populations should be included in the epilepsy high-risk group: The relevant factors here are almost certainly poverty and low socio-economic status, which are themselves associated with high rates of epilepsy, as they are with so many other diseases.

Causes of Symptomatic Epilepsy

When epilepsy appears to be caused by an identifiable brain disease, it is categorized as symptomatic epilepsy. These causes include head injury; intracranial infection (e.g., neurocysticercosis, malaria); cerebrovascular disease; brain tumor; drugs and alcohol; carbon monoxide poisoning; and effects of ionizing radiation.

Table 4 Putative Causes of Symptomatic Epilepsy Cases in Six Chinese Cities

Putative cause	No. of cases	%
Head injury	29	47.5
Intracranial infection	15	24.6
Cerebrovascular disease	10	16.4
Intracranial tumor	2	3.3
Other	5	8.2
Total	61	100.0

Table 4 shows the results of a retrospective study in six cities of China in 1983.³

Prognosis and Remission

There are very few research reports on the natural history of epilepsy in China. In a survey conducted in the rural areas of 22 provinces in the 1980s, there were 904 cases of epilepsy, 417 of
them were treated, 448 were not, and 39 were unclear. Among the untreated 448 cases, spontaneous remission rate (SRR) at 2 years was 40.4% and at 5 years was 27.4%. Studies showed that SRRs ranged from 20% to 39%. These figures are similar to what Zielinski reported (5-year remission rates of 28.6% to 30.6%).

Factors relative to the prognosis or remission rate (RR) include: (a) Age of onset. The highest RR was reported if onset was between 7 and 9 years old. The RR for those whose onset was before 14 years was 71%, and before 20 years, 42%. For those whose onset was before 1 year and after 40 years, the RR is low because of one increase in number of organic disorders that cause epilepsy in those age groups. (b) Seizure types: Generalized tonic–clonic seizures (GTCSs) had a higher RR (38% to 62%). (c) Frequency of seizures: Low frequency of seizures had a higher RR. More than one seizure per day had an RR of 20% to 27%, fewer than ten seizures per year had an RR of 50% to 57%, and fewer than one seizure per year had an RR of 67%. This indicates that seizure frequency before treatment is an important factor that affects prognosis, but it is an exception for absence seizures. (d) Idiopathic or symptomatic epilepsy: The former (RR of 47% to 63%) has a higher RR than the latter (RR of 24% to 27%). (e) Course of the disorder: Shorter course had a higher RR: <1 year, RR 53%; >5 years, RR 17%. (f) Neuropsychological defects: There were higher RRs if the patients were without these defects.¹⁰^,²³

The impacts of antiepileptic drug (AED) treatment on prognosis are evident. Regular treatment with AEDs may control 70% to 80% of epileptic seizures, whereas with AEDs taken irregularly the RR is similar to untreated. Good compliance with AED treatment leads to good prognosis. One study showed a 92% control rate in a compliant treatment group of children patients, but 56% in the noncompliant group. Recurrence after stopping AED treatment is a major concern of epileptologists. A report from China showed a 24% recurrence rate for 8 years after stopping AEDs, and 55% of the recurrence occurred in the first 1 years.¹⁰

Clinical Diagnosis and Treatment

The diagnosis and treatment of epilepsy in China has improved greatly in the past 50 years, which may be attributed to the practical efforts of neurologists/epileptologists, the development of the electroencephalography (EEG) and other diagnostic equipment and technology, and the broad international academic exchanges.⁴⁹

Diagnosis of Epilepsy

Adequately Using the International Seizure and Epilepsy Classification to Diagnose Epilepsy

The accurate categorization and recognition of seizures and epilepsies are the foundation of correct diagnosis and further in-depth research and communication, and are also reflected in the progressive knowledge about epilepsy. The international classifications in the 1980s have been wildly used, including the Seizure Classification in 1981, the Epilepsy and Epilepsy Syndrome Classification in 1985, and its revision in 1989 proposed by the International League Against Epilepsy (ILAE). These have received common acceptance by most epileptologists. The introduction of the 1981 ILAE seizure classification into China occurred at the first National Epilepsy Conference in 1985, and it was revised somewhat to make it suitable to the practical situation in China.³⁷ The Chinese Classification of Epilepsy and Epilepsy Syndromes, referring to ILAE’s proposal, was recommended in the seventh National Pediatric Neurology Conference in 1995.⁸ The aforementioned classifications of the 1980s are now wildly used in the clinical and research work in China, as well as in research about mesial temporal lobe epilepsy and absence epilepsy, the study of the relationship between mesial temporal epilepsy and hippocampal sclerosis, and clinical observation on uncommon epilepsy syndromes, such as the acquired epileptic aphasia and West syndrome. Since the 1990s, more attention has been given to the clinical research and EEG analysis of frontal lobe epilepsy, which has complex clinical manifestations, and the recognition and diagnosis level to it has been thus much improved.

For the past few decades, much progress has been made in understanding epilepsy symptomatology, etiology, pathology, diagnosis, and treatment. The same progress can be observed in China. In 2001, the ILAE Task Force, led by Prof. Engel, proposed a new classification of epilepsy that reflected the new knowledge in epileptology and influenced the clinical practice greatly. It introduced some new concepts as “axis” in diagnosis, which was helpful to standardize the clinical diagnosis. The proposal was introduced in China soon after its publication and is now used widely.¹ There have been great changes in the classification of epileptic seizures, which rely mostly on the symptoms reflecting the relationship between the symptom and anatomic location that gives clues about the epilepsy syndrome. In addition, classification now emphasizes the psychosocial impacts on the quality of life of epileptic patients in diagnostic procedures. We found that the new proposal was not easy to use with in clinical practice because of lack of detailed explanation in some parts. Epileptic seizures and their semiology, are the core of epilepsy classification. In some degree the new classification ignores changes in high-level cortical function, for example, by excluding classification criteria based on changes in consciousness and neglecting mental manifestations, which are important features of some epileptic seizures. Furthermore, it is difficult to classify occasional seizures observed in clinical work.

The Development of the Electrophysiological Techniques

There are two key features in epilepsy: Clinical seizure and EEG manifestations. EEG is one of the most important auxiliary examinations in epilepsy diagnosis. With no doubt, the emergence of EEG is a milestone that divided the history of epilepsy diagnosis into two stages.

The first EEG machine in China was imported into the Nanjing Brain Disease Hospital in 1949 in China and used in
clinical examinations in 1951. Then a series of training courses about epilepsy and EEG were held by Feng Yingkun from the Peking Union Medical College (PUMC) Hospital. Now EEG testing is used in most hospitals in China. The international system of 10- to 20-electrode placement is used and includes both referential and bipolar recordings. Activating procedures, such as open/close eyes, hyperventilation, intermittent photic stimulation, and sedated sleep are routinely applied in most hospitals. The recording and interpretation of EEG requires expertise, but there are not yet standardized training and qualification systems for EEG technicians in China.

Mesial temporal lobe epilepsy is the most common epilepsy type. Feng Yingkun found that acupuncture pins could be used as substitutes for sphenoidal electrodes with good effect and easy acceptance.¹¹ There have now been more than 30,000 patients who had acupuncture pins used as sphenoidal electrodes in the PUMC Hospital.

Since the 1990s, video-EEG has been performed in many EEG labs in China. The electrocorticogram and deep electrode EEG have been used in some hospitals, which can give more information in locating the epileptogenic foci.

Other Examination Methods

In addition to electrophysiology, some new diagnostic techniques have been introduced in recent years. Imaging the hippocampus is now performed in China. Hippocampus volumetric quantitative measurement techniques are also very helpful in diagnosing and treating mesial temporal epilepsy.

The Establishment of Epilepsy Centers and Epilepsy Clinics

Since the 1990s, specialized epilepsy clinics and centers have been established in the bigger hospitals. These kinds of centers usually include neurologists, pediatric neurologists, neurosurgeons, psychiatrists and social workers. Sophisticated equipment for diagnosis is available and an operating theater equipped. Multidiscipline cooperation is the most important characteristic of such centers/clinics. They serve not only as clinical work sites, but also as sites for research, training, and public education. These centers are important developments in the prevention and control of epilepsy in China.

Drugs for Epilepsy

Medication is still the most important treatment option for patients with epilepsy. Selection of AEDs depends on the type of seizure and syndrome classification. The common AEDs used in China are valproate, carbamazepine, phenytoin, and phenobarbital. Approximately 60% to 70% of epilepsy patients can achieve remission using monotherapy. Polytherapy is chosen when patients’ seizures cannot be controlled by monotherapy. We have found that side effects of rash and neutropenia occur in about 5% to 10% of patients on carbamazepine. Valproate needs careful consideration when it is used in women of child bearing age because of weight-gain and polycystic ovary syndrome effects. Phenytoin and phenobarbital have similar efficacy to carbamazepine but are no longer the first choice because of their adverse effects. However, they are still used as first-line AEDs in rural and poor regions in China. Valproate is drug of first choice in treating generalized seizure, and carbamazepine for focal seizures. Since the 1990s blood levels of AEDs have been available in big hospitals and epilepsy centers.

Since the 1990s, there have become available more than ten new AEDs on the international market, and most of them are useful in cases of intractable epilepsy. With relatively wide spectra, fewer adverse effects, fewer interactions, and better tolerance, the new AEDs offer, more choices for refractory patients. Presently, lamotrigine, topiramate, vigabatrin, gabapentin, and oxcarbazepine are available in China, and zonisamide and levetiracetam are going to be on the market soon. Most new AEDs serve as add-on drugs. The combination of lamotrigine and valproate is better for some refractory epilepsies, but skin rash has occurred.

Epilepsy Surgery: A Review

Although the trephenation opening found on a skull unearthed in Shandong province indicates that the history of surgical treatment of brain disease in China is more than 5,000 years old, modern epilepsy surgery has been available only in recent years. There is no record of epilepsy surgery in the literature or in hospitals’ records before the People’s Republic of China was established in 1949. The earliest record of epilepsy surgery in China may date to the 1950s to 1960s, for example, “traumatic epilepsy” written by Guosheng Duan, “hemispherectomy for West Syndrome” by Yuquan Shi, and “epilepsy surgery” by Yadu Zhao. In the following two decades, some political and social factors resulted in temporary delay in further development of epilepsy surgery.

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