Li Zizhong

[Abstract] Objective This paper reports on the satisfactory results obtained in the treatment of 12 138 patients with a diversity of refractory diseases that affect the functioning of the brain including mental retardation, cerebral palsy, epilepsy, senile dementia, sequelae of brain trauma, sequelae of encephalitis, sequelae of cerebrovascular diseases, and hereditary ataxia with Li's Prescription No.5 developed by the author and approaches its mechanism of action. Method The study subjects all met the diagnostic criteria for encephalopathy in DSM Ⅳ-R and CCMD-2-R. Part of the subjects were subjected to Wechsler's psychometry, examination of EEG and chromosome, and skull CT scanning before and after treatment for comparison of therapeutic effectiveness. All the patients were treated with Li's Prescription No.5 only, without any other remedies, oral administration for 6 successive months being a course of treatment. Results Statistics of short-term therapeutic effectiveness six months after treatment showed that the effective rate was 85.6% and the notable effective rate was 66%. Conclusions The present study showed that Li's Prescription No.5 has the effects of improving intelligence, promoting cerebral energy metabolism, promoting somatic and cerebral development, regulating motor function, improving cerebral microcirculation, regulating neurontransmitter, facilitating functional restoration of damaged nerve cells, and resisting free radicals. The author advances the hypothesis of starting "adjusting point" of central nervous system that there might exist an "adjusting point" in the central nervous system which could be started by changing the potential gradient inside and outside the membrane of nerve cells to promote regeneration of nerve cells of the brain.
[Key Words] Li's Prescription No.5 Encephalopathy Adjusting point

About 3% of children over the world are mentally retarded. In China, the incidence is 2%-3% in rural areas and 1% in cities and towns. According to a preliminary investigation, of the 1 200 million Chinese people, 24 million people are mentally retarded. The prophylaxis and treatment of hypophrenia is one of the key measures of improving population quality. The actual causes of hypophrenia are, for the most part, the serial serious

Author's unit: Guangdong Gaoming Medical and Medicinal Institute of Encephalopathy, 2 Heping Lane, Cangjiang Road, Hecheng District, Gaoming, Guangdong 528500, P.R. China, Tel: (0757) 8689692. Fax: (0757) 8689317.
Received April 2, 1999; revision received May 27, 1999; accepted June 10,1999.
consequences caused by long-persistent or more serious perinatal suffocation, and about 20%-25% of the survivors will develop mental retardation (MR), cerebral palsy or secondary epilepsy. (1-4)
Subjects and Methods
Subjects
A total of 12 138 patients with various encephalic diseases were treated, they were aged 3-74 years, mean 15.6 years. Of these, 6 597 had MR; and of the 6 597 cases, 175 had concomitant chromosome abnormalities, 2 076 had concomitant cerebral palsy, 989 had accompanying aphasis, 696 had strabismus, 158 had blindness, 78 had dysacusis, 1 857 had epilepsy, and the remaining were of simple MR. 1 308 had sequelae of cerebrovascular disease, 986 had traumatic cerebral sequelae, 329 had Parkinson's disease, 89 had hereditary ataxia, 1 187 had postencephalitis, 1 210 had senile dementia, 132 had phenylketonuria, and the remaining 300 cases were of other diseases that affect the functioning of the brain.
Methods
1. The 12 138 cases in this series all satisfied the diagnostic criteria in DSM-Ⅳ-R and CCMD-2-R. (5-6)
2. Method of Psychometry (7) The Concise Chinese-revised Wechsler Intelligence Scale Manual was used to test intelligence quotient (IQ). Grading of IQ: marginal state (69-79 points), mild hypophrenia (50-70 points), moderate hypophrenia (35-49 points), severe hypophrenia (20-34 points), and extremely severe hypophrenia (less than 20 points).
3. Accessary Examinations
Electroencephalography (EEG): Of the 8 590 patients in this series who received EEG examination, 5 426 showed moderate-to-severe abnormality, with asymmetrical bilateral waves. Spike and ware waves were found in patients with concomitant epilepsy.
Skull CT Scanning One thousand six
hundred and sixty-nine patients were subjected to pretreatment CT scanning. Eight hundred and fifty-five of them were found to have had different degrees of pathological changes, including focal low density of the brain, widened cerebral sulci, narrowed cerebral gyri, enlarged ventricles, and cystic degeneration. Patients with concomitant monoparesis and cerebral hemiplegia all showed abnormal CT findings.
Chromosome Examination Those
suspected of having a history of genetic diseases were subjected to chromosome examination.
General Laboratory Examinations They were blood urea nitrogen (BUN), glutamic pyruvic transaminase (GPT), white blood cell count (WBC) and haemoglolim (Hb) determinations.
4. Patients in this series were treated with Li's Prescription No.5 only, without any other medicines. Oral administration of Li's Prescription No.5 Capsule (Naolizhibao Capsule) for 6 successive months constitutes one course of treatment. Follow-up studies were made six months after treatment. Part of the patients were subjected to EEG, CT and general laboratory examinations.
5. Criteria for interpreting therapeutic effectiveness.
Six months after treatment the therapeutic effectiveness was interpreted according to the following three criteria:
(1) Notable effect: Noticeable improvement in nervous dysfunction was found. Affected children who had made marked progress in learning and school records and marked improvement in IQ re-test and had shown corresponding strengthened social adaptability based on the feedback from teachers and parents fell into this category.
(2) Effect: Those who had improvement in their behaviour and learning capacity without resulting in a huge hike in their school work belonged to this category.
(3) Failure: Affected children showed little change in their behaviour and learning capacity after treatment.
Results
Short-term Therapeutic Statistics
An effective rate of 85.6% including a notable effective rate of 66% was registered in this series of 12 138 cases half a year after treatment. Treatment of the 12 138 cases with Li's Prescription No.5 was found to have the following characteristics: (1) The medicine takes effect regardless of age and has a better curative effect on congenital encephalopathy; (2) it has a significantly higher curative effect in treating MR caused by chromosome abnormalities than in treating other types of encephalopathy; (3) it promotes growth and development of the organism, such as gain in body height, enlargement of head circumference, correction of strabismus and improvement in looks and in auditory and visual functions; (4) it recovers limb functions of patients with cerebral palsy; (5) it controls the accompanying epilepsy (EEG reexamination showed diminution or disappearance of spike and ware wave after treatment); and (6) part of the patients who had abnormal morphosis of the brain also showed improvement in varying degrees in CT reexamination.
Short-term Therapeutic Statistics of Different Disease Entities
Of the 12 138 cases in this series, the effective rate was 90.8% for MR, 88.7% for sequelae of cerebrovascular disease, 87.0% for traumatic cerebral sequelae, 80.3% for Parkinson's disease, 78.5% for hereditary ataxia, 91.3% for postencephalitis, 85.9% for senile dementia, and 82.3% for phenyketonuria. In none of the cases did adverse reaction occur. The total effective rate was 85.6%.
Typical Cases
Case 1 Zhang, a 7-year-old boy, born 6 weeks premature, weighed only 1.4 kg at birth, had contracted neonatal jaundice complicated with neonatal pneumonia on day 7 after birth. Ten months after birth he still had no tooth eruption. At the age of 3 he could neither raise his head nor walk. At the age of 4.5 he could only utter such monosyllabic sounds as Pa and Ma. He could not respond to the call of nature and could not tell when he was hungry or full. Physical examination showed a dull-witted appearance, a head circumference of 38 cm and a tower-shaped skull, depressed occiput, obliquely upward ocular hypertelorism, relatively broader nose ala, and smaller, disarranged teeth. His tongue often hung outside his mouth. His four limbs had involuntary movement. His upper limbs were intorted, wrists were flexed, both thumbs were adducted. He showed scissors gait with intorted feet. He had hypermyotonia of extremities, hyperreflexia of knee jerk, and positive bilateral Babinski's sign. EEG showed mild abnormality. Skull CT scanning showed broadened cerebral sulci. Chromosome examination confirmed that the patient had 21-trisomy syndrome. He was diagnosed as having (1) severe MR; (2) cerebral palsy. After one year's treatment with Li's Prescription No.5, the affected child had marked improvement in his intelligence, had some cognitive and comprehensive ability and could do one-digit addition and subtraction. At ordinary times he liked watching TV programs for children and could retell the central content of the story he had seen. He became enunciative and fluent. His head circumference increased to 48 cm, the morphological development of his head and facial organs became as normal as that of general children. Involuntary movement of the extremities disappeared, and gait and posture basically returned to normal. He moved his hands freely, walked almost steadily. Skull CT reexamination showed cerebral sulci shrunk. EEG reexamination was basically normal.
Case 2 Mo, a 10-year-old girl, her father was Mo××, a native of the 2nd production team of Lianmin Village, Huadumian Township, Guangdong Province. The affected child usually was in good health, in February 1998 she developed tremor of both hands, which gradually worsened. In April, she had headache and dizziness without nausea, vomiting or fever. On 27 April, she was taken to a hospital in Guangzhou and was found to have had hydrocephalus in skull CT scanning. On 2nd May, she was given ventriculo-abdominal shunt and had her headache abated following the operation. On 31 May, the symptom worsened with transient disturbance of consciousness because of obstruction of drainage-tube. The second operation was performed on 4th June, but, again, followed by obstruction, and two additional operations were performed in July and August, respectively, with internal and external drainage. Following the 4th operation, the affected child developed coma and quadriplegia with fecal and urine incontinence and was given nasal feeding. No abnormal conditions were found in her past and family history. She was born normally, physically well developed and usually got excellent school record. Skull CT scanning showed severe obstructive hydrocephalus and intraparenchymatous low-density shadow of the brain. She was diagnosed as vegetative state due to shunt for obstructive hydrocephalus. She was given Li's Prescription No.5 Capsule for oral administration, 4 capsules each time, 3 times a day in addition to anti-inflammation and expectant treatment. She had head rotation two weeks after taking the medicine, then she opened her eyes and became conscious. At the fourth
week nasal feeding was removed, at this time she could recognize her family members and call their names. Her extremities were movable but spoke slowly. When she came to the hospital 5 months later, she walked freely, spoke more clearly and sang songs. Her memory and counting ability were also considerably regained.
Case 3 Mr. Chen, male, 64 years old. Address: 1 Huyuan Crosscut, Shatai St. Sun Wen Midway, Zhongshan City, Guangdong Province. Date of first visit: 18th July, 1998. The patient had had tremor of right upper limb from 1984 on, followed by involvement of right lower limb, he enunciated unclearly. In 1998, he had tremor in his extremities and head, especially in static state, he changed his posture slowly and walked hard. In 1990, a skull CT scanning made in a hospital in Guangzhou showed no abnormality, he was diagnosed as having Parkinson's disease and was given madopar and artane (trihexyphenidyl hydrochloride). His symptoms got improved but again worsened with the withdrawal of the medicines. He was conscious and gave negative results of medical examination. Neurological examination showed a stony expression, unclear enunciation, hypermyotonia of extremities, and involuntary tremor, especially in static state. He had difficulty in moving steps, and when walking he had no associated movement of the extremities. Skull CT scanning showed the presence of encephalatrophy. He was given Li's Prescription No.5 Capsule for oral administration, 5 capsules each time, three times a day, tremor abated three months later and was basically controlled six months later. He began to walk at a brisk pace with smiling expression. He became quick in thinking and clearer in enunciation.
Case 4 He, male, aged 23 years, a native of Caizhou Village, Shangyuan Country, Nanzhuang Township, Nanhai City. Date of first visit: 3 rd February, 1999. The patient had had tremor of hands, inaccurate holding, unsteady walking, and liability to fall, especially in turning a corner since 1996. He enunciated unclearly and ate slowly. His symptoms gradually worsened. He could not work and could not take care of himself in daily life. The patient had previously been treated at several hospitals without any notable effect. Skull CT scanning showed cerebellar atrophy. Investigation of family history of the patient revealed that his father, He××, aged 50 years, also had tremor of hands, unsteady walking and unclear enunciation in recent years and that his grandfather began to walk unsteadily at the age of 46 years, sometimes fell on the ground, could only do simple labor and died of disease several years later. The patient was conscious, he entered the consulting room under the support of two other persons. Medical examination gave negative results. Neurological examination showed no abnormalities of cranial nerves but horizontal nystagmus. He had drunken gait, unsteady action in finger-nose test, and was clumsy in diadochokinesia. Romberg's test showed unsteady action in opening eyes and even more unsteady action in closing eyes. He spoke plosively with unclear enunciation. Skull CT scanning showed cerebellar atrophy. He was diagnosed as having hereditary cerebellar ataxia and was given Li's Prescription No.5 Capsule for oral administration, 5 capsules each time, three times a day. After taking the medicine for 1 month and over, he walked more steadily and enunciated more clearly. He now served as a platform-scale man.
Case 5 Luo, female, aged 70 years, a native of Lantang Village, Daping Township, Xingning City, Guangdong Province. Date of first visit: 14th September, 1998. Since June 1997 the patient had gradually become timid, stubborn, uncommunicative and repeated in doing simple housework. Her memory was failing with the result that she could not tell the relationship between herself and her family members, could not find the way to home and quickly forgot what her family members urged her again and again. But she still could tell the persons or things she knew tens years ago. She gave negative results in medical examination, and no focal signs were found in neurological examination. Skull CT scanning showed encephalatrophy, IQ=61 points. She was diagnosed as having senile dementia and was given Li's Prescription No.5 Capsule for oral administration. Six months later, her memory got improved and she thought clearly in talking. She could recall and find the
thing she put, and communicate with her family members on her own initiative, being less timid and stubborn. IQ=88 points.
Pharmacological and Toxicological Study and Conclusions
Pharmacological Study
Mice of Kunming strain were given Li's Prescription No.5 Capsule in the dosage of 4g/kg of body weight for 10-18 days. (8) It was demonstrated experimentally that the medicine has the following effects:
1. Promoting the mice's learning and memory capacities
(1) The medicine was found to be highly effective in improving the acquired disorder caused by scopolamine, disturbance of memory repetition caused by ethanol, and disturbance of memory consolidation caused by sodium nitrite in the mice.
(2) The medicine improved mice's ability to find way, leading to a significant learning achievement in maze.
(3) The medicine accelerated significantly the acquirement of conditioned reflex and raised obviously the positive initiative reflex avoidance rate in young mice. In the conditioned reflex training, the RNA content in the brain of the mice was significantly higher in those which had been given Li's Prescription No.5 than in the controls which had received no drug.
2. Improving energy metabolism of the brain
(1) It prolonged both the breathing time when the mice were killed and the survival time in an environment where there was a shortage of oxygen under normal pressure.
(2) In the presence of acute incomplete shortage of brain oxygen, Li's Prescription No.5 reduced water content both in the brain tissue and in brain tissue protein, and alleviated both the increased protein amount in the brain tissue (a reflection of oozing plasma protein) and cerebral edema in the presence of ischemia, indicating that the medicine has the effect of anti-anoxia.
(3) With ischemia in the brain, it reduced the formation of the product of lipid peroxide－malondialdehyde (MDA)－in the brain tissue, suggesting that it inhibits the formation of free radicals and alleviates cell injury.
(4) In mice with ischemia in the brain, it reduced both the consumption of APT and the formation of lactic acid in the brain tissue, indicating that it can improve energy metabolism of the brain.
3. Promoting development of the brain and the body.
(1) It accelerated weight gain of mice in developmental stage.
(2) It elevated RNA level in the brain of young mice, stimulated the synthesis of brain protein in young mice with deficiency of the kidney, showing that it promotes development of the brain.
(3) Li's Prescription No.5 also caused proliferation of cells in the liver, spleen and thymus gland of mice with deficiency of the kidney. It increased not only the synthesis of protein in the liver and thymus gland of mice but also the Hb content in normal rats. Moreover, it accelerated the animal's weight gain. These effects, similar to those produced by growth hormones, might be related to the increase of dopaminergic nervous function and of release of growth hormone.
4. Improving cerebral microcirculation and reducing blood viscosity
5. Li's Prescription No.5 enhanced levodopa-induced mechanical movement in the mice, indicating that it has the action of enhancing dopaminergic nervous function
Toxicological Study
1. Mice of Kunming strain were given Li's Prescription No.5 by intubation feeding in the maximum daily dosage of 40 g/kg of body weight, which was about 200 times the human clinical dosage. The results showed that the medicine is safe and non-toxic.
2. Rats were given Li's Prescription No.5 by intubation feeding in the daily dosages of 3 g/kg of body weight and 9 g/kg of body weight respectively for 120 successive days. No toxic or side effects were observed as compared with the control group. (9-12)

Discussion

The rapid development of modern medicine in recent years has brought about such new techniques in the diagnosis of encephalopathy as CT, MRI, DSA and RGBF. The brain can be recognized anatomically, biochemically, pathologically and from other aspects. This results in the improvement of accuracy of diagnosis of encephalopathy and the direct understanding of the location, size, morphology and nature of pathological change. With the development of the diagnosis and treatment of encephalopathy, some drugs such as brain activator and nerve growth factor have been developed in recent years which are promising in improving brain function. In the treatment of encephalopathy, the theory of traditional Chinese medicine lays stress on balance of yin and yang and coordination of visceral functions and pays attention to the concept of wholism in treatment. The successful treatment of various diseases that affect the functioning of the brain with Li's Prescription No.5 is an example.
Compared with the functional disorders of other organs of the human body, diseases that affect the functioning of the brain have their own peculiarities. They affect both activities of thought and consciousness and cause dysfunction of other organs of the organism, greatly lowering the life quality of the sufferers. There are many factors causing diseases that affect the functioning of the brain and manifestations of the diseases differ greatly but, in the final analysis, structural damage or functional inhibition of neurons is the fundamental cause of the diseases. How to improve the function of neurons and how to promote regeneration of residual neurons have been the field of serious study by scholars all over the world. Earlier studies held that nerve cell had no power of regeneration; recent studies, however, believe that neuron does have some plasticity, however limited that may be. (13) The pathogenesis of various diseases that affect the functioning of the brain differs greatly, and in some of the diseases the pathogenesis is still unknown; therefore, there exists certain blindness in the treatment and curative effect is also uncertain, especially mongolian idiocy (21-trisomy syndrome) for which no specific therapy is available. Even in cerebral infarction and encephalomalacia commonly encountered in department of neurointernal medicine, the damaged neurons cannot be made to regenerate, only by means of combined treatment can the brain compensation be improved and the symptoms ameliorated.
In view of this situation, the author has, based on his more than 20 years' research with great concentration and repeated practices, successfully developed Li's Prescription No.5 which is effective in treating various diseases that affect the functioning of the brain. Li's Prescription No.5, absorbing the quintessence of traditional Chinese medicine and using the achievements of modern medical scientific researches for reference, has yielded unexpected results in clinical application. It has blazed a new path for treating encephalopathy with traditional Chinese medicine, enriched the theories of traditional Chinese medicine, and demonstrated the huge potentiality contained in treatment of diseases with traditional Chinese medicine. Li's Prescription No.5 was first used in the treatment of MR. All MR patients treated with Li's Prescription No.5 had marked improvement in intelligence, speech and physical development. What is more, dyskinesia of extremities and dysaudia got highly improved, and, in varying degrees, strabismus was corrected, vision of blind persons and hearing of deaf persons were regained. The medication is particularly effective in treating concomitant epilepsy. Sixteen vegetables due to brain trauma have regained their consciousness and 2 of them even returned to normal social life. Satisfactory results were also obtained in treating MR patients with concomitant strabismus. Findings of pharmacological and toxicological studies have fully demonstrated the clinical value of Li's Prescription No.5. The medicine has the following significances: (1) It is a new breakthrough in the history of modern medical treatment; (2) it enriches the theories of traditional Chinese medicine and demonstrates the tremendous potentialities contained in traditional Chinese medicine; (3) it finds a new way for traditional Chinese medicines to treat encephalopathy in a scientific and systematic way, thus providing a useful frame of reference for studying treatment of other somatic diseases with Chinese medicines; (4) it breaks down barriers of treatment of hereditary diseases, traditional ideas hold that heredity determines trait and that somatic defects caused by chromosome or gene abnormalities are irreversible; however, the distinctive therapeutic effectiveness of Li's Prescription No.5 on encephalopathy due to chromosome abnormalities reflects the huge plasticity that exists in human body and the possibility of acquired redevelopment, this remaining to be confirmed by molecular biological study; (5) the therapeutic effectiveness of Li's Prescription No.5 in treating many diseases that affect the functioning of the brain has challenged conventional therapeutic ideas that stress specific drugs for specific diseases; and (6) the successful clinical application of Li's Prescription No.5 will inevitably shed new light on the development of central nervous system and the regeneration of nerve cells and update some of the conventional neurobiological and neurophysiological viewpoints. Therefore, the development and application of Li's Prescription No.5 and the approach to its mechanism of action have a triple social, economic and academic value.
In an attempt to explain the encephalic and somatic development as well as their normal functioning, the author boldly puts forward a new hypothesis (called Li's theory for short), the main point of which is that there might exist in the brain an "adjusting point" which controls the normal development and functioning of the central nervous system, just as the central nervous system governs the development and functioning of the whole organism. The hypofunction of the "adjusting point" will make an impact on the development and functioning of the central nervous system, followed by the occurrence of disturbances of perception, cognition and thinking of human brain, manifested as feeblemindedness and affective disorder and/or structural and functional abnormalities of cerebral cortex, which will lead to extremity dyskinesia, hypoacusis and blindness. The hyperfunction of the "adjusting points" will lead to the occurrence of over-excitation of central nervous system, thus developing different types of psychonosema such as affective disorder and the somatic manifestation epilepsy. It is, therefore, reasonable to regard the "adjusting point" as the center of the central nervous system. The definition of the "adjusting point" is functional and not anatomical, it may be a high-energy magnetic field in the brain which interferes with all the activities of the brain in the form of electromagnetic wave and maintains electric potential gradient inside and outside neurolemma. Advancing the hypothesis is based on the following facts: Firstly, the activities of human brain, whether those of higher thinking or those of controlling the body, are based on bioelectric activity, the production and transmission of which necessarily form electromagnetic field in the ambient space and thus makes an impact on the function and metabolism of adjacent neurons; secondly, despite the deep thorough studies on the formation and metabolism of the brain in modern science, the structural complexity of human brain and the limitations of research impose restrictions on the understanding of the cerebral functions, or rather, the cerebral latent energy; and despite the fact that the one-position sign governing somatic movement can easily localize the functional position of human brain, the domain of the higher thinking activities of human brain cannot be accurately localized because of the involvement of extensive synergism of the brain, this bringing about some difficulties in research and remaining to be explored further; thirdly; the fact that central nervous system has some plasticity, namely, power of regeneration, suggests that regulation of the function and development of neurons by "adjusting point" has some material base; and fourthly, lack of marked abnormality in cerebral morphology in many patients with hereditary mental retardation indicates that there may be neuronal hypometabolism and hypofunction only and that there exists possibility of further improving such hypometabolism and hypofunction. According to this hypothesis, the author is of the opinion that various diseases that affect the functioning of the brain, whether congenital or acquired, all lead to dysfunction of neuronal membrane with resultant transport blockade of ions on the membrane and other metabolites, difficulty in maintaining electrostatic potential inside and outside the membrane, influence on the occurrence and transmission of electric excitation of nerves, then interference with the function of the "adjusting point", and, finally, the occurrence of neuronal dysfunction and hypometabolism (such as circulatory disturbance of hormone, pathological enhancement of free radical reaction and reduced cytotrophic supply). It is, therefore, the key to the treatment of various diseases that affect the functioning of the brain to restore and improve the function of neuronal membrane, which undertakes the ingestion of nutrients and the excretion of product of metabolism. Drug ingredients of Li's Prescription No.5, upon entering the organism, undergo transformation and the available compositions bind with and activate the receptors on nerve cell membrane, then promote metabolism of nerve cells, enhance transport function of nerve cell membrane, and accelerate the entry of nutrients into nerve cell membrane and the completion of effective concentration difference of ions inside and outside the membrane, thus increasing on whole basis the intensity of magnetic field ("adjusting point") in the brain. The restoration of function of "adjusting point" to normal conversely promotes redevelopment and functioning of central nervous system by the following routes: (1) perfecting the function of blood-brain barrier and increasing both quantity of entry of such nutrients as amino acids and phospholipids and levels of ribonucleic acid (memory molecule), protein and neurotransmitters (such as acetylcholine, dopamine, etc.) to make the residual neurons regenerate and function; (2) regulating microcirculation of the brain, raising the energy metabolism and utilization rate of the brain, increasing oxygen content, and enhancing the activity of nerve cells and their sensitivity to external stimulation to make the nerve cells in dormant state and the damaged nerve cells revive and to mobilize the latent energy of the brain; (3) promoting synthesis of neurotrophic factors to strengthen regeneration of nerve cells; (4) eliminating noxious substances (such as free radicals, lipofuscin, etc.) in the brain and restoring the function of nerve cell membrane; and (5) mobilizing pituitary function to increase the synthesis or release of growth hormone and facilitate physical development. The above-mentioned mechanism of drug action is only a hypothesis, remains to be demonstrated clinically and experimentally and needs joint studies in the fields of neurophysiology, neuroanatomy, neurobiochemistry, neuroradiology and molecular biology to make a great contribution to the prevention of hypophrenia, the improvement of population quality and bringing benefit to mankind.
References
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(2) Scott H. Outcome of very severe birth asphyxia. Arch Dis Chil, 1976, 51: 712.
(3) Mulligan JC, et al. Neonatal asphyxia.Ⅱ.Neonatal mortality and long-term sequelae. J Paediat, 1980,96: 903.
(4) Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics, 1981, 68: 36.
(5) American Psychiatric Association. DSM-Ⅳ: Diagnostic and statistical manual of mental disorders, 4th ed. Washington: American Psychiatric Association, 1994: 92-94.
(6) Chinese Psychiatric Association and Affiliated Hospital of Encephalopathy of Nanjing Medical University (ed.). The classification scheme and diagnostic criteria for Chinese mental diseases. 1st ed; Nanjing: Southeast University Publishing House, 1995.
(7) Gong Yaoxian, Lin Chuanding, Zhang Houcan, et al. The Concise Chinese-revised Wechsler Intelligence Scale Manual Changsha: Hunan Medical College, December 1986: 3-4.
(8) Wu Yongjie. A comprehensive report on pharmacological and toxicological studies for clinicians' reference. J Modern Encephalopath Med, 1997, special issue: 23-26.
(9) Wu Yongjie. Acute toxicity test data of Li's Prescription No.5 J Modern Encephalopath Med, 1997, special issue: 26.
(10) Meng Fumin, Wu Yongjie, Li Wenguang. Pathological observations Prescription No.5 J Modern Encephalopath Med, 1997, special issue 30-31.
(11) Chen Tiejiang. Peroral acute rat toxicity test report of Li's Prescription No.5 (Naolizhibao) Capsule. J Modern Encephalopath Med, 1997, special issue: 32.
(12) Deng Lixia, Wu Dawei. A report on mice marrow cell micronucleus test of Li's Prescription No.5 (Naolizhibao) Capsule. J Morden Encephalopath Med, 1997, special issue: 32-33.
(13) Wu Yongjie. The principal pharmacodynamic test data and references of Li's Prescription No.5. J Modern Encephalopath Med, 1997, special issue: 34-49.

　 ·Original Articles·

Observations on Therapeutic Effectiveness of
Li's Prescription No.5 in Treatment of Cerebral Palsy and Mental Retardation (Dementia) and an Approach to Its Mechanism of Action

Li Zizhong

[Abstract] Objective The importance of control of hypophrenia and the lack of effective remedies for the disease at present prompted the author to make a thorough study on this problem and developed a traditional Chinese medicinal prescription－ "Li's Prescription No.5". Very satisfactory results were obtained with clinical application of the prescription. Reported herein are the results of therapeutic observation and an approach to mechanism of action of Li's Prescription No.5. Method Xu's ten-item oral-answer test was used to test intelligence. Part of the patients were subjected to EEG, CT and chromosome examinations before and after treatment to compare therapeutic effectiveness. Only preparation of Li's Prescription No.5 was given to all the patients without any other drugs. Results Of the 1 396 patients with mental retardation, 1 253 showed marked effectiveness after 2-4 courses of treatment and 143 showed effectiveness, the effective rate being 100% and markedly effective rate being 89.8%. In no case was toxic or side effect observed. Conclusions Clinical application showed that Li's Prescription No.5 might be the ideal therapy for mental retardation at present. The author advances the theory of "adjusting point" on the development and functioning of human brain (Li's theory) and discusses the mechanism of action of Li's Prescription No.5.
[Key words] Li's Prescription No.5 Cerebral palsy Mental retardation Hypophrenia Li's theory

The prophylaxis and treatment of hypophrenia is one of the leading problems of improving population quality. The morbidity rate of child hypophrenia is about 3% abroad, 2%-3% in rural areas and 1% in cities of this country. According to a preliminary investigation, there are about 24 million people suffering from mental retardation (MR) in the 1 100 million people (1). The disease is characterized mainly by developmental retardation of intelligence, with intelligence quotient (IQ) below 70 points in most cases. Patients with the disease are unable to adapt themselves to the objective requirements in study, life and behaviors and bring about a heavy burden to the family and society. At present, no satisfactory therapy is available. For more than ten years, we have explored and studied the problem and made some

Author's unit: Guangdong Gaoming Medical and Medicinal Institute of Encephalopathy, 2 Heping Lane, Cangjiang Road, Hecheng District, Gaoming, Guangdong 528500.
progress by using traditional Chinese medicine to treat hypophrenia. This demonstrated that the intelligence of children with hypophrenia still has the possibility to improve. By using self-made capsule of Li's Prescription No.5 we have treated 1 396 MR children and achieved unexpected results. Reported herein are the results of treatment.

Clinical data
General Data
Of the 1 396 MR children, aged 3-24 years, mean 15.6 years, 833 were males and 563 were females; 92 were of mild type (dull-wittedness), 380 were of moderate type (dementia) and 924 were of severe type (idiocy). Part of the affected children had concomitant dysopia (27 cases), dyskinesia (including paralysis, stiffness and ataxia, 382 cases) and epilepsy (264 cases). The vast majority of the affected children had been treated in different places in many ways but they failed to respond to medical treatment. One thousand and thirty cases had a history of difficult labor, delivery suffocation, premature delivery, forceps delivery, 285 had a history of high fever, convulsion and diarrhea, 4 cases had chromosome abnormalities, and 77 cases had unknown causes.
Psychometric Method
The more complexity of the revised Wechsler Intelligence Scale for Children (WISC-R) prompted us to use the simple and easy Xu's oral-answer test (2), the items of which are as follows: (1) count backwards from 30 to 1 and record the state of completeness and the speed; (2) recite in order numerals, starting with five-digit number till nine-digit number, and record the digit number recited; (3) conduct continued subtraction, for children aged less than 8 years, use 30-3……, for those aged more than 8 years, use 100-7……, and record the state of completeness and the speed; (4) differentiate things, make the children differentiate a chicken from a duck, and record the state of completeness; (5) make the affected children tell the kinds of colour they know and record them; (6) describe things, let the affected children describe the contour of an elephant and record the accuracy and totality; (7) do mathematical exercises, for example, a pencil costs 13 cents, what's the money for 2 pencils? For children aged 10 years or over, they may be asked: Fifty-nine apples are distributed to 5 little friends, how many apples does everybody have? And how many apples are left over? They are asked to do sums in their head. Record the right or wrong answers; (8) explain uses, make the children explain the uses of wood and record how many kinds of uses he can tell; (9) test logic memory, let the children retell a about story and record the degree of accuracy of retelling; and (10) making test of "shooting birds", the children are asked how many birds are left over if one of the ten birds on the tree is shooted to death.
The above-mentioned 10-items test had been tested in 200 school-age children aged 7-13 years. Except the items 7 and 10 which should be evaluated according to the correct or wrong answer, the remaining items are evaluated according to the average value. If an affected child comes up to the level of average value, he (she) is said to pass the test and given 10 points. If the total score is below 40 points, the patient can be regarded as having oligophrenia by taking his (her) case history into account. The total scores of the 1 396 children in this series were all below 40 points. Follow-up study was made on several items of the test during the course of treatment to judge, with reference to the school record and the parent's report, whether there was improvement or not.
Accessory Examinations
Electroencephalography (EEG): Of the 530 patients in this series who received EEG examination, 236 showed moderate-to-severe abnormality, with asymmetrical bilateral waves. Spike and ware waves were found in patients with concomitant epilepsy.
Skull CT scanning: Two hundred and twenty-three patients were subjected to pretreatment CT scanning. Eighty-five of them showed different degrees of pathological changes, including focal low density of the brain, widened cerebral sulci, narrowed cerebral gyri, enlarged ventricles, and cystic degeneration. Patients with concomitant monoparesis and cerebral hemiplegia all showed abnormal CT findings.
Chromosome examination: Six affected children suspected of having a history of genetic diseases were subjected to chromosomal karyotype analysis. Four of them had chromosome abnormalities.

Method of Treatment and Results
Method of Treatment
All the patients were treated with Li's Prescription No.5 capsule only, without any other medicines. Three to five capsules each time, three times a day, oral administration for three successive months constitutes one course of treatment. Follow-up study was made after two courses of treatment to interpret therapeutic effectiveness. Some of the patients were given EEG and CT reexamination. For those who had some but not satisfactory results, additional one or two courses of treatment were given.

Results
Criteria for interpreting therapeutic effectiveness: (1) Notable effect: Noticeable improvement in nervous dysfunction. Affected children who had made marked progress in learning, school records, psychometry, and social adaptability based on the feedback from teachers and parents fell into this category; (2) effectiveness: showing improvement in behavior and learning capacity without resulting in a huge hike in school work; and (3) failure: showing no change in behavior and learning capacity after treatment.
Of the 1 396 cases undergoing 2-4 courses of treatment, 1 253 had notable effectiveness and 143 had some effectiveness, the effective
rate being 100% and the notably effective rate being 89.8% (Table 1). Treatment with the drug has the following characteristics: (1) a better curative effect on congenital MR; (2) a good curative effect for patient aged less than 18 years; (3) a wonderful curative effect on MR caused by chromosome abnormalitics; (4) promoting growth and development of the organism and correcting abnormal physical signs, such as gain in body height, enlargement of head circumference, correction of strabismus and improvement in looks; (5) visual recovery of blindness due to optic atsophy; (6) recovery of limb functions in patients with cerebral palsy; and (7) correction of concomitant epilepsy and dysaudia.
Reexamination of EEG and CT made on part of the patients showed that 236 cases, especially those with concomitant epilepsy, had marked improvement in EEG, with diminution or disappearance of spike and ware wave after treatment and that 23 of the 85 cases showing abnormal CT findings had some improvement after treatment, as manifested by reduction or disappearance of focal low density of the brain, shallow cerebral sulci and widened cerebral gyri (Table 2). In none of the cases did toxic reaction occur.

Table 1 Therapeutical analysis of children with MD
Patient's condition No.of cases No.of cases showing No.of cases showing No.of
No table effectiveness some effectiveness failures
Mild type (dull-wittedness) 92 92 0 0
Moderate type (dementia) 380 344 36 0
Severe type (idiocy) 924 817 107 0
Total 1 396 1 253 143 0

Table 2 Changes in EEG and CT before and after treatment
Item No.of cases No.of positive cases No.of improved cases Improvement
Examined before treatment after treatment rate (%)
EEG 530 236 151 64
CT 223 85 23 27.4

Typical cases
Case 1 Liao, a boy aged 5 years, had a history of high fever and convulsion at 3, followed by hypophrenia, abnormal behavior and dyskinesia. The patient had previously been diagnosed as having encephalopathic sequela, epilepsy, etc. and treated with pyrithioxine hydrochloride, glutamic acid and cytidine diaphosphate choline at several hospitals in xi'an and Lanzhou with no response. On

examination, he looked dull with binocular strabismus, lockjaw and speech problem. He could only utter mono-syllabic sounds now and then. Other symptoms included: lack of response, inability to lift his head due to weak neck, upper limb spasm, tight fists, adducted thumbs, flexed wrists, inability to stand up due to weak lower limbs, intorsive feet with scissor's gait, weakened knee reflex and positive bilateral Babinski's sign. EEG showed moderate abnormality, CT scanning showed decreased white matter density in bilateral parieto-occipital regions, and magnetic resonance imaging (MRI) showed abnormal signal of bilateral lenticular nucleus, Liao was diagnosed as having demyelinating disease. He was given Li's Prescription No.5 capsule, 3 capsules each time, three times a day, for 1 successive year. Follow-up study found that he had had remarkable improvement in intelligence, his strabismus had been corrected, jaws loosened, neck muscles strengthened, upper limb spasm had disappeared, fingers had been flexible, and myodynamia of lower limbs had been recovered. Walking steadily, he could move up and down the stairs without stumble and ride a tricycle unaided for a few li's distance. Having restored his linguistic function, he was able to speak fluently and articulately and count numbers within 100. He could do simple arithmetic, eat and dress without help, and play ball games and skip rope with other children. EEG and CT reexamination showed no marked abnormalities.
Case 2 Zhang, a 7-year-old boy, born 6 weeks premature weighed only 1.4 kg at birth, had contracted neonatal jaundice and neonatal pneumonia on day 7 after birth. Ten months after birth he still had no tooth eruption and could neither creep nor raise his head because of the weak limbs and maldevelopment. When he was 3 years old, he could neither speak nor walk, and had poor comprehension. When he was 4 years and 6 months old, he could only utter such monosyllabic sounds as Pa and Ma and still could not walk alone. When first seen at the hospital, the patient made hoarse monosyllabic sounds and sometimes screamed. Though hyperactive, he could not coordinate his action well and had unstable gait. He was irritable, wilful and sialotic with his tongue often hanging outside his mouth. He could not respond to the call of nature and could not tell when he was hungry or full. Neuropsychiatric examination showed a dull appearance, microcephaly, a head circumference of 38 cm and a tower-shaped skull, depressed occiput, flat temporo-occiput, obliquely upward ocular hypertelorism, bilateral paropsis, relatively broader nose ala, and smaller, disarranged teeth. His four limbs had involuntary movement. His upper limbs were intorted, muscular tension increased, both thumbs adducted, and wrists flexed, with hyperreflexia of brachial biceps and positive Hoffmann's sign. He showed scissors gait with intorted feet. The muscle strength of the right lower limb was 2nd degree, that of the left lower limb 3rd degree. He had hyperreflexia of knee jerk, hypermyotonia, patellar and ankle clonus and positive bilateral Babinski's sign. EEG showed mild abnormality. CT showed slightly broadened cerebral sulci. Chromosome examination confirmed that the patient had 21-trisomy syndrome. He was diagnosed as having extremely severe MR complicated with cerebral palsy. After one year's treatment with Li's Prescription No.5 the affected child had marked improvement in his intelligence, awareness and understanding. He could do two-digit addition and subtraction. At ordinary times he liked singing and watching TV programs for children and could retell the central content of the story he had seen. He became enunciative and fluent. His head circumference increased to 48 cm, the morphological development of his head and facial organs became as normal as that of normal children. Involuntary movement of the extremities disappeared, and gait and posture returned to normal. He moved his hands freely, walked almost steadily. His muscular tension was reduced and his myodynamia was restored. Babinski's sign (+) was restricted only to his right side. CT reexamination showed cerebral sulci and fissures shrunk. EEG reexamination was basically normal.
Case 3 Yang, a 6-year-old boy, a premature infant of 206 days, weighed 1.6 kg at birth, could smile ten months after birth, raised his head at one year of age, had closure of bregmatic fontanel at two years and six months of age, could not stand up alone. His parents were healthy and denied history of familial hereditary disease and consanguineous marriage. At the time of examination the affected child was found to be unable to take care of himself at all, hyporeactive to external stimulation, unaware of hungry or full, cold or warm, unclear in enunciation with hoarse monosyllabic sounds, unable to express a complete idea, hyperactive, irritable, sialotic with his tongue often hanging outside his mouth, and non-responsive to the call of nature, and he was often found to bite his finger nails and dirty things to eat, to be unable to stand up alone and often to imitate and repeat some simple actions. The affected child didn't cooperate with the doctor during physical examination. Neuropsychiatric examination showed no response, apathy, presence of pain, head circumference 35.5 cm, orbital hypertelorism, low and flat nose root, a protruding tongue with laceration on its surface and salivation, smaller and disarranged teeth, deformity of ear, ear margin 2.3 cm, involuntary movement of the extremities, torsion spasm of both upper limbs, showing "airplane-shaped muscle" backwards, chicken's-claw type of both hands, hypermyotonia, flexed wrists, hyperreflexia of brachial biceps and positive Hoffmann's sign. His hands were short and broad, thumbs 2.0 cm, index fingers 2.6 cm, middle fingers 2.8 cm, ring fingers 2.6 cm and little fingers 1.8 cm. His body height was 97 cm, both hands were one-line palms, both feet had plantar flexion and intorsion, with hyperreflexia of knee jerk, hypermyotonia and positive bilateral Babinski's sign. He was diagnosed as having (1) extremely severe MR and (2) 21-trisomy syndrome. After six month's treatment, the affected child grew and developed rapidly, his intelligence improved notably, he was quick in action and active in nature. Having restored his linguistic function, he was able to speak fluently and articulately. Such symptoms as protruding tongue, salivation and biting nails had disappeared. His answer kept to the point and could count numbers within 100. He could sing children's songs and do simple arithmetic. His motor function of extremities was restored to normal, involuntary movement of the extremities and torsion spasm of the upper extremities had disappeared with resultant free action. His body height was 110 cm., head circumference 48 cm, right ear margin 6.3 cm, left ear margin 6.2 cm, thumb 4.1 cm, middle finger 5.2 cm, index finger 4.7 cm and ring finger 4.6 cm, the increase of fingers being significant.
Case 4 Zhou, male, aged 18 years, had had high fever (41.2℃) due to common cold at 6 months of life, followed by frequent episodes of epilepsy one month later, which had been treated in many ways but failed to respond to medical treatment. At the time of examination, the patient showed a physiognomy of dementia with right strabismus and poor vision. He had rightward obliquity, chicken-claw type of both hands without power of gripping, hypermyotonia, torsion spasm, rightward-abduction gait of lower limbs with both heel failing to touch the ground, bilateral hyperreflexia of knee jerk, and positive Babinski's sign which was manifest on the right side. CT scanning showed broaden cerebral sulci and fissures, and EEG examination showed moderate abnormality. He was diagnosed as having severe type of MD complicated with cerebral palsy and was given Li's Prescription No.5. According to the parent's report, this medicine began to produce effect after oral administration for two successive months, and six months later intelligence and functions of extremities and speech recovered. One year later strabismus was corrected, and vision was restored to 1.5 (both eyes). He became articulate and fluent. His torsion spasm disappeared, muscular tension decreased, gait stabilized, and pathologic sign disappeared. The patient had a bright and cheerful disposition, was initiative and liked singing and dancing. He has started school and got good school record. He often initiatively helped his parents in doing housework, he could go shopping alone just as a normal person. CT scanning showed cerebral sulci and fissures shrunk, and EEG reexamination showed normal findings.
Case 5 Yang, a six years old girl, had been diagnosed as having (1) arachnoid cyst, (2) obstructive hydrocephlus, and (3) functional cerebral palsy at Beijing Medical University. On examination she was found to be unable to walk by changing step, to have no linguistic function, no cognitive ability and no faculty of understanding. She had a large malformed head, a head circumference of 58 cm, a markedly leftwards oblique face, strabismus and diminution of vision (left eye 0.2, right eye 0.3), and irregular features. After treatment with Li's Prescription No.5 for three successive months, functions of extremities, speech and consciousness got notable restoration, and it was unimaginable that her head circumference had reduced to 51 cm, that she had had a regular face and features and that her strabismus had been corrected with improved vision.

Discussion
Mental retardation (MR) or hypophrenia is internationally defined as the state of those whose intellectual powers fall significantly below the level of the same age on a standardized intelligence test with accompanying defect in adaptive capacity (WHO, 1985). (3) In accordance with the above-mentioned definition, the diagnostic criteria for MR should correspondingly include three aspects: (1) the fall of intellectual powers significantly below the level of the same age is that IQ is lower than the mean by 2 standard deviations, with an IQ below 70; (2) the adaptive capacity is lower than the social normal values, there are marked defects in one's own life and in practising social duties; (3) MR occurs in the stage of developmental age, namely, under 18 years of age. (4) It is evident that the diagnosis of MR should consider the following three aspects: (1) Only in the cases whose conditions conform to the three diagnostic criteria can the diagnosis of MR be mode. Simple low IQ with good adaptive capacity cannot be diagnosed as MR. Decline in intelligence after adult stage is not known as MR but as dementia. (2) The diagnosis of MR is chiefly psychological and behavioral and not simple medical evaluation. (3) MR is not a permanent intellectual disturbance in all cases, and the IQ is changeable. The vast majority of patients in this series were under 18 years of age, a small number of patients, though aged over 18 years, had their disease in childhood; therefore, their diagnosis of MR is in keeping with the criteria.
Intelligence is a multifactorial genetic trait and the result of interaction of heredity and environment. Heredity determines the attainable level of intelligence under the optimum conditions, namely, latent energy. Environment determines the extent to which the latent energy can really be developed, improvement of environment facilitates the development of intelligence. (5) There is no consistent idea on definition of intelligence. Intelligence is a power, behaviors that reflect intelligence are manifested by the following aspects: capacity of learning, capacity of acquiring knowledge and benefiting from it, capacity of thinking and reasoning, and ability to solve problems and adapt environmental changes, these belonging in the field of cognition. Adaptive capacity (behavior) is assessed on the basis of people of the same age and cultural background to interpret the extent to which one is able to attain his own life and practise social duties. Adaptive behavior does not simply take medicine as the index but takes the requirements made on oneself by social environment in which he lives as standard. Full understanding of the implications of intelligence and adaptive capacity is highly helpful to the interpretation of therapeutic effectiveness as well as to the diagnosis of disease.
MR, a symptom, has many etiologic factors including, according to the international standardized etiologic classification of MR (WHO, 1985), (1) infection and poisoning, (2) injury and physical factors, (3) metabolic and nutritional factors (including hereditary metabolic disease), (4) macroscopically detected encephalopathy (including hereditary degeneration), (5) congenital factors of unknown causes (deformity, congenital idiocy syndrome, neural tube defect), (6) chromosome disease, (7) perinatal factors, (8) concomitant mental diseases, (9) adverse environmental factors, social mental damage, social deprival, etc. , and (10) others. It can be seen from above that, other than the bio-medical factors, about 20%-35% of MR patients can be found to have medical abnormalities, which are severe type in most cases, with chromosome disease accounting for 15%-20% of the total, the most common being 21-trisome syndrome. Those without medical abnormal findings account for about 65.8% of the total, and about 50% are due to social environmental factors. In addition, part of MR patients are of unknown causes. It has also been reported (4) that in the etiological factors of MR definite genetic defect makes up about 37%, environmental factors constitute 20%, and the remaining 43% are of unknown causes. In this series of patients, 1 030 cases (73.8%) were found to have had a history of difficult labor, delivery suffocation,
premature labor or forceps delivery; 285 cases (20.4%) were found to have had a history of high fever, convulsion or diarrhea; and the remaining cases (5.5%) were of unknown causes. As condition is limited, it is impossible to make chromosome analysis in all cases; in the six cases examined, however, 4 were found to have chromosome abnormalities, two of them had 21-trisome syndrome (cases 2, 3). It is obvious that chromosome abnormalities are a key factor in the pathogenesis of MR. Moreover, MR caused by prenatal and perinatal factors accounts for vast majority of the cases, indicating that prevention of MR should be focused on perinatal health care.
In addition to abnormalities of intelligence and social adaptive capacity, MR has some concomitant somatic diseases, the most important are the three kinds of diseases: (1) Sensory disturbance In this series of patients, 251 (18%) had dysopia with optic atrophy. (2) Dyskinesia In addition to the common clumsiness in movement, MR has rigidity, ataxia and other disturbances. In this series of MR patients, cerebral palsy was seen in 382 (27.4%) cases. (3) Epilepsy Epileptic attack is very common in the disease, especially in severe cases. It is reported that about one third of patients have epileptic attack. It is more frequently encountered in MR due to brain injury. In our series of patients, there were 264 cases (18.9%) of concomitant epilepsy, slightly lower than the figure reported in literature, and among the factors inducing epilepsy, the most common is the high fever caused by "common cold", "pneumonia" and "toxic dysentery". No sufficient attention was devoted to the morphology and electrophysiology of the brain of the affected children. The author made CT and EEG observation on part of the cases and found that no marked abnormalities were detected in the vast majority of the affected children but that in extremely severe MR children, especially in those with concomitant cerebral palsy, shallowed cerebral gyri, deepened cerebral sulci and fissures, local cerebromalacia and hydrocepalus were observed in CT scanning and in the affected children with concomitant epilepsy pathological spike and ware wave were detected in EEG examination.
The diagnosis of MR should be carried out at the same time of treatment or intervention, this being the process of comprehensive multidiscipline diagnosis and treatment. The purpose of treatment is to make, as far as possible, the affected child take care of himself, to improve his intelligence to the maximum limit, and to learn the skills of communicating with people and of adapting social life. Method of treatment includes pharmacotherapy and psychological education. Because MR patients are, for the most part, of unknown causes and even if the cause of disease is known, the symptoms that have developed cannot usually be treated by the method of removing etiologic factors. Therefore, no specific therapy is available at present. In Western medicine, drugs with action of promoting cerebral metabolism such as vitamin B6, pyrithioxine hydrochloride, glutamic acid and cytidine diphosphate choline are commonly used but they have no notable therapeutic effectiveness. For some accompanying symptoms of MR, the Western medicine can only give expectant treatment, for examples, behavior abnormalities, restless leg syndrome and hypoprosexia are treated with nervous stimulants, epilepsy with antiepileptics and mental symptoms with tranquilizers. Treatment of MR with traditional Chinese medicine seems to have its distinctive qualities. In this aspect, scholars at home have done large quantities of research work and obtained encouraging results. It must be, however, noted that treatment of the disease remains in the stage of clinical observation at present. The use of decoction in the form of prepared drugs is inconvenient for long-term use. Other forms of prepared drugs convenient for administration, carry and storage such as granule preparation, syrut, tablet, pill, etc. must be used for the affected child's persistent administration. Methods of treatment include (6) a special prescription for a particular disease, treatment with syndrome differentiation, acupuncture and moxibustion, point-injection therapy, ear needling and auricular-plaster therapy. A special prescription for a particular disease refers to a special prescription or fixed form of prepared drugs composed of effective drugs screened according to experience through the ages and clinical data and from different angles for treatment of disease,
this being the method more frequently used at present. According to various reports in literature, (6,7,8) treatment starts mainly with (1) tonifying the kidney, replenishing vital essence and marrow, (2) tonifying the heart, invigorating the spleen and inducing resuscitation, (3) tonifying the viscera with viscera and (4) promoting blood circulation by removing blood stasis, restoring consciousness and dispelling phlegm. Treatment with syndrome differentiation, though it can be directed against the patient's condition and can be individualized in treatment, is difficult to systematize, scientize and popularize. In view of this restriction of treating MR with traditional Chinese medicine at the moment, the author has, based on many years' research with great concentration and repeated practices, successfully developed "Li's Prescription No.5" capsule which is easy to be administered for treating MR. This drug, absorbing the quintessence of traditional Chinese medicine and using the achievements of modern medical scientific researches, has yielded unexpected results in clinical application. It has broken a fresh path for treating MR with traditional Chinese medicine, enriched the theories of traditional Chinese medicine, and demonstrated the huge potentiality contained in treatment of disease with traditional Chinese medicine. In our series of patients, the notably effective rate was 89.8% and the effective rate was 100%, with all the patients highly improved in intelligence, speech and physical development. Moreover, dyskinesia of extremities and hypoacusis were markedly improved, strabismus was corrected, blindness due to optic atrophy regained its vision. The medication was particularly effective for those patients with concomitant epilepsy, with a consolidation rate of 100%. What is more, the marked effectiveness of the medication is also reflected in the morphology and electrophysiology of the brain, with EEG improvement rate reaching 64%, CT improvement rate reaching 27.4%. The author also found that a better therapeutic effectiveness was obtained in MR caused by congenital factors than by acquired factors. It is worth mentioning that this drug was highly effective in treating MR due to chromosome abnormalities as well (case 2 and case 3) and promoted physical development, as seen in case 3 in which after treatment the affected child not only regained his motor function of extremities and linguistie function and improved his intelligence but also had great changes in physical signs, as was observed in follow-up study in which the head circumference was found to be 48 cm, an increase by 12.5 cm; ear margin 6.3 cm in length, an increase by 2.7 cm; body height 118 cm, an increase by 22 cm; and fingers were found to have an average increase of 2.3 cm. In addition, those aged under 18 years had a significant therapeutic effectiveness. This breaks through the age limit in MR treatment, differing from the reports of many domestic scholars. Wang et al. (7) reported that of the 70 children with atelencephalia treated by differentiation of symptoms and signs, 23 were notably effective and 37 were effective, the total effective rate being 85.8% and that the smaller the age and the earlier the treatment, the more notable the effect in treating MR due to congenital factors and with dyskinesia as the dominant manifestation. Zhou et al. (8) also reported similar findings. The author is of the opinion that the present medication has blazed new trails in three aspects: (1) The therapeutic effectiveness is unexpected, the effective rate being 100%; (2) it breaks through the age limit in MR treatment, those aged under 18 years all had a better therapeutic effectiveness; and (3) in addition to the redevelopment of the central nervous system, it promotes the redevelopment of the whole organism.
The miraculous effectiveness of Li's Prescription No.5 defies any explanation using existing theories. In an attempt to explain the encephalic and body development as well as their normal functioning, the author boldly puts forward a new hypothesis (called Li's theory for short), the main point of which is that there might exist in the brain an "adjusting point" which controls the normal development and functioning of the central nervous system, just as the central nervous system governs the development and functioning of the whole organism. The hypofunction of the "adjusting point" will make an impact on the development and functioning of the central nervous system, followed by the occurrence of disturbances of perception and thinking of human brain, manifested as feeblemindedness and affective disorder and loss of control of cerebral domain governing somatic movement, resulting in extremity dyskinesia, hypoacusis and blindness. The hyperfunction of the "adjusting point" will lead to the occurrence of over-excitation of central nervous system, thus developing different types of psychonosema such as affective disorder and epilepsy. It is, therefore, reasonable to regard the "adjusting point" as the center of the central nervous system. The definition of the "adjusting point" is functional and not anatomical, it may be a high-energy magnetic field in the brain which interferes with all the activities of the brain in the form of electromagnetic wave and maintains electric potential gradient on both sides of neurolemma. Advancing the hypothesis is based on the following facts: Firstly, the activities of human brain, whether those of higher thinking or those of controlling the body, are based on bioelectric activity, the production and transmission of which necessarily forms electro-magnetic field in the ambient space and thus makes an impact on the function and metabolism of adjacent neurons(9) ; secondly, despite the deep thorough studies on the formation and metabolism of the brain in modern science, the structural complexity of human brain and the limitations of research methods impose restrictions on the understanding of the cerebral functions, or rather, the cerebral latent energy, such as the extraordinary powers and the phenomenon of deep breathing exercises of man; and despite the fact that the one-position sign governing somatic movement can easily localize the functional position of human brain, the domain of the higher thinking activities of human brain cannot be accurately localized because of the involvement of extensive synergism of the brain, this bringing about some difficulties and remaining to be explored further; thirdly, the fact that central nervous system has some plasticity, (10) namely, power of regeneration, suggests that regulation of the function and development of neurons by "adjusting point" has some material base; and fourthly, lack of marked abnormality in cerebral morphology in many patients with mental retardation, especially in those having chromosome abnormalities, indicates that there may be neuronal hypometabolism and hypofunction only and that there exists possibility of further improving such hypometabolism and hypofunction. According to this hypothesis, the author is of the opinion that MR, whether congenital or acquired, all leads to anion-cation imbalance in the brain, thus interferes with the function of the "adjusting point", with development of abnormalities of neuronal function and metabolism (such as microcirculatory disturbance, pathological enhancement of free radical reaction, and reduction of cytotrophic supply). Those with accompanying somatic symptoms (such as cerebral palsy, strabismus, blindness, etc) have particular nerve mass and the organic lesion of fiber yet. It is, therefore, the key to treating MR to correct the anion-cation imbalance in the brain, the wonderful therapeutic effectiveness of Li's Prescription No.5 in treating MR in turn confirms this. This elevation of anion-cation index by Li's Prescription No.5 leads to enhancement of potential gradient, functional improvement of the "adjusting point", and acceleration of transformation and transmission of electromagnetic field, thus directly promoting the regeneration and functioning of the central nervous system. The routes by which Li's Prescription No.5 takes effect are: (1) opening the blood-brain barrier and increasing quantity of entry of such nutrients as amino acids, peptides and phospholipids to make the residual neurons regenerate and function; (2) regulating microcirculation of the brain, raising the energy metabolism of the brain, increasing oxygen supply, and enhancing the activity of nerve cells and their sensitivity to external stimulation to make the nerve cells in dormant state and the damaged nerve cells revive and to mobilize the latent energy of the brain; (3) promoting synthesis of neurotrophic factors to strengthen regeneration of nerve cells; (4) regulating ions (such as Ca, Na, K, etc.) transport in the brain and restoring the bioelectric activity of nerve cells and its transmission: (5) eliminating noxious substances such as free radicals in the brain and restoring the function of nerve cell membrance; and (6) mobilizing the pituitary function to increase the synthesis and release of growth hormone and facilitate physical development. This hypothesis might explain the patients' post-treatment rise of intelligence, enhancement of social adaptive ability, restoration of extremity and speech function, correction of strabismus, improvement of hearing, regaining vision in those with optic atrophy, surpassing normal level in intelligence in individual patients, physical development, and the return to normal of physical signs. This drug has a dual-directional regulation: skull exceeding normal size shrinks (case 5) and that smaller than normal size enlarges (case 2), this being a strong evidence.
To sum up, the author used "Li's Prescription No.5" to treat MR and obtained wonderful therapeutic effectiveness, the notably effective rate being 89.8% and the effective rate being 100%. Patients aged less than 18 years all had therapeutic effectiveness. The medication was highly effective for those with concomitant blindness and epilepsy. More notably, the medication was able to promote redevelopment of the organism of affected children with microsoma due to chromosome abnormalities. In addition, the notable therapeutic effectiveness was also reflected in the anatomy and electrophysiology of the affected children's brain, with CT improvement rate reaching 27.4% and EEG improvement rate reaching 64%. The author advances the theory of "adjusting point" on the development and functioning of human brain (Li's theory). The occurrence of MR is related to the hypofunction of the "adjusting point". Li's Prescription No.5 makes intelligence of child with fe4eblemindedness recover or even exceed the normal level, it certainly makes normal persons more clever by developing the latent function of the brain. This fully suggests a vast range of prospects for developing "Li's Prescription No.5" to serve the whole society. In addition, Li's theory might be used as theoretical guidance or for reference in the diagnosis and treatment of other diseases of the central nervous system and somatic diseases, and this remains to be jointly explored by people of the same profession.

Reference

(1) Li Pu. Foreign Medicine, Series Genetics, 1990, (4): 169.
(2) Xu Junmian. J of Traditional Chin Med, 1985, (1): 38.
(3) Zuo Qihua. J of Appl Pediat, 1989, (1): 31.
(4) Wang Xiaoyun. Tianjin Medicine, 1992, (8): 494.
(5) Xia Zhenjun, et al. Applied Psychiatry. 1st ed; Shanghai, Shanghai Scientific and Technological Publishing House, 1990, pp 355-371.
(6) Qian Dayu. J of Traditional Chin Med, 1990, (7): 53.
(7) Wang Lie, et al. J of New Traditional Chin Med, 1984, (4): 27.
(8) Zhou Xiting, et al. Shanghai J of Traditional Chin Med, 1988, (1): 10.
(9) Su Zhufei. Foreign Medicine, Series Pediatrics, 1982, (1): 1.
(10) Xiao Xiaming, et al. Foreign Medicine, series Pediatrics, 1981, (1): 16.

　 ·Original Articles·

A Retrospective Survey of Treatment of
Various Encephalic Diseases With Li's Prescription No.5

Li Zizhong 1, Bu Dingfang 2, Mu Ying 3, Qu Chuanyan 4,
Liu Shenru 2, Li Zhihuai 5, Wu Yuwei 6, Pan Yanlai 7

[Abstract] Objective In order to confirm the curative effect of Li's Prescription No.5 in treatment of various encephalic diseases, a follow-up study was carried out on 1 164 patients for three successive months. Method Criteria for case selection and for interpreting curative effect were established. A retrospective therapeutic analysis was made on the basis of reexamination. Results After treatment with Li's Prescription No.5, 641 (55.1%) cases showed notable effect and 452 (38.8%) cases showed general effect, the total effective rate being 93.9%. Those with protracted course of seqelae or retrograde affection also showed improvement in varying degrees after treatment. Conclusions Li's Prescription No.5 does have curative effect on encephalopathy. There isn't any direct connection between curative effect and the cause and kind of the disease and the patient's age, this suggests that the mechanism of the drug action is nonspecifically promoting restoration of damaged brain functions.
[Key words] Li's Prescription No.5 Encephalopathy Retrospective survey

Wound and disablement of nervous system caused by such factors as abnormal development, genetic disease, perinatal injury, trauma, vascular disease, infection, degeneration or retrograde affection are frequently encountered in clinical practice. At present, no specific remedies for such diseases are available. In foreign countries, treatment relies mainly on physical therapy and dirigation and in this country on acupuncture and moxibustion, massage, pharmacotherapy and dirigation. For more than 10 years, we have used Li's traditional Chinese medicinal prescription to treat various diseases that affect the functioning of the brain and got satisfactory results. In 1994, a follow-up study had

Authors' units: 1. Guangdong Gaoming Medical and Medicinal Institute of Encephalopathy. 2. Department of Pediatric Neurology, Beijing Medical University. 3. Department of Genetic Diseases, Beijing Medical University. 4. Center for Maternity and Infant Health, Beijing Medical University. 5. Guangdong Institute of Geriatrics. 6. Department of Neurointernal Medicine, the People's Hospital of Guangdong Province. 7. The People's Hospital of Guangdong Province.
been carried out on 1 864 patients with encephalopathy seen in Gansu Province. During the period May-August 1997, a retrospective therapeutic survey was made on patients treated previously in provinces of Zhejiang, Jiangxi, Yunnan and Guangdong. Reported herein are the results of the second survey.
Subjects and Methods
Subjects
Case Selection All patients who had been treated previously were informed of their going back to the follow-up survey spots for a follow-up study by telephone or by sending off letters. All return-visit patients served as subjects of therapeutic survey without selection, except those taking Li's Prescription No.5 for less than three months; receiving acupuncture and moxibustion, massage, breathing exercises and other traditional Chinese or Western medicines at the same time, or receiving radicotomy of back or orthopedic therapy within a recent year; and having infection or injury of nervous system for less than a year, or showing improvement in symptoms in recent 6 months though the disease lasted for over a year.
Methods
Methods of Investigation A repeated inquiry about cause of disease and a repeated physical examination were made with consulting films of both CT scanning and MRI and relevant laboratory findings including EEG to check the diagnosis. Detailed inquiries were made of patients and their families about changes in the following aspects before and after treatment: (1) motor function including function and posture of lifting head, standing, sitting, walking, running and hands, myodynamia, muscular tension, involuntary movement, coordinate movement and stiff joint; (2) linguistic function including the number of words and phrases, the length of sentences, the ability to express clearly, the degree of enunciation, and the comprehension and response to speech; (3) learning and cognition including the awareness of the name, form of address, age and occupation of oneself and his (her) family members, numeral and counting ability, attention, school records, and memory; (4) social adaptive capacity including the ability to take care of oneself in daily life, housework, the ability to communicate with others, sense of shame, risk consciousness, and status of attending school and working; (5) mental symptoms including restlessness, excitation, aggressive and destructive behavior, or timidness, shrink and eccentric behavior; and (6) development of body height, body weight and head circumference, strabismus and hearing ability.
Interpretation of Curative Effect Notable effect: A significant improvement in at least 3 of the above items(1)-(6) with increased social adaptive capacity. General effect: An improvement in at least 2 of the above items (1)-(6) with partially increased motor function or social adaptive capacity. Failure: Showing no change or improvement in only 1 item. In a small number of patients who had only one abnormality (such as limb paralysis, deafness, etc.), the interpretation of curative effect was based on the change of the symptom before and after treatment.
Results
Cases and Status of Treatment
Cases followed up accounted for 85% of the total number of cases that should be followed up. There were 1 164 cases in all that satisfied the criteria for case selection. All the patients selected took Li's Prescription No.5 only. Of the 1 164 patients, 436 had taken the medicine for 3-6 months, 504 for 6-12 months, 128 for 12-18 months, and 72 for more than 18 months. There were 596 patients who had been taking the medicine, 261 patients had withdrawal of the medicine for less than a year, and 283 patients had withdrawal of the medicine for a year or over. No adverse reaction to Li's Prescription No.5 was found during the follow-up study.
Curative Effect
Curative Effect on Mental Retardation and Cerebral Palsy
As shown in Table 1, of the 590 cases of mental retardation (MR), 386 had concomitant cerebral palsy. Simple cerebral palsy was seen in 178 cases. MR patients in this series had IQ<50 in most cases, their cerebral palsy was mostly spastic and in a small number of cases it was extrapyramidal or mixed type. EEG showed diffused inactive echoes in most cases and spike wave, sharp wave and spike and ware complex in a small number of cases. Disseminated low-density change of cerebral hemisphere and peripheral hydrocephalus were commonly found in skull CT scanning. Acquired factors such as perinatal suffocation, anoxia, ischemia, nuclear jaundice, brain infection in early infancy, and severe general infection were, for the most part, the contributing factors in the development of disease, and in a small number of cases the cause of disease was unknown. For treatment of encephalopathy due to congenital factors, see Table 2.
After treatment with Li's Prescription No.5, the vast majority of cases showed marked improvement in cerebral palsy and feeblemindedness, epilepsy was controlled, and visuoauditory function got improved. Of the 590 MR cases, 524 showed progress in speech, as manifested by increased number of words and phrases, increased length of sentences, and clear enunciation as well as awareness of family members' names. Thirty-eight patients who had had unclear enunciation could sing "Ma ma is the best in the world" or could even recite some Tang poems. Two hundred and sixty-four patients showed highly increased ability to take care of themselves in daily life and to do housework. Forty-one patients had a desire to go to school or to work on a job. One hundred and eighty-nine patients had their restlessness, aggressive behavior, catalepsy or timidness basically controlled and became obedient and active in getting in touch with others. Of the 564 patients with cerebral palsy, 79 who had been unable to stand were able to walk, and 126 who had walked unsteadily were able to walk steadily for a longer distance. Disappearance or abatement of scissors' gait was observed in cases showing effectiveness. One hundred and ninety-two patients had reduced muscular tension of upper limbs with fingers stretched out. In short, the total effective rate of treating MR or cerebral palsy was over 90%.



Table 1 The curative effect of treating MR and cerebral palsy
No.of Notable General Failure
cases effectiveness effectiveness
Mental retardation (MR) 204 110 84 10
MR with concomitant cerebral palsy 386 217 150 19
Simple cerebral palsy 178 93 79 6
Total 768 420 313 35

Typical Cases
Case 1 Cui ×× was a boy of seven year and six months of age. No obvious abnormalities were found during gestational, perinatal and neonatal period. When he was 8 months old, he was found to stretch his upper limbs backward when putting forth his strength. He started to walk independently at 4 and speak at 5. Physical examination showed restlessness, strabismus of both eyes, increased muscular tension of extremities, 70°abduction angle of both thighs and positive ankle-clonus. Skull MRI showed negative findings. He was diagnosed as having mental retardation with concomitant cerebral palsy. After oral administration of Li's Prescription No.5 for seven successive months, he could walk steadily, go upstairs and downstairs alone and run and could catch a rubber ball with hands. Before treatment he could only utter a few words and hum a tune and now could say "Grandfather eats orange with his mouth arching repeatedly" and sing the song "Ma ma is the best in the world". He could take care of himself in daily life and started to attend first grade of primary school.
Case 2 Zhao××，male, aged 19 years. No obvious abnormalities were found during gestational,

perinatal and neonatal period. Only at the age of 2 could he sit and only at the age of 3 could he speak. He had hypophrenia. Physical examination showed sluggish expression, strabismus of both eyes, basically normal muscular tension, and tendon reflex (++), no pathologic sign was elicited. Skull CT scanning showed mildly enlarged ventricles. He was diagnosed as having mental retardation and was given Li's Prescription No.5 for oral administration. Eight months later he made marked progress in speech and other aspects. He could only utter a few words with unclear enunciation before treatment. After treatment he could say "I cherish the memory of maternal grandfather. If he were alive, I would call at his home." Before treatment he could only carry a pail of water and after treatment he could not only carry a pail of water, make a fire and feed pigs but also buy some things in shop according to parents' request. He became more lively than he had been before and active in getting in touch with others. He actively asked his parents to take him to the hospital of Director Li to buy medicine.
Curative Effect on MR Caused by Congenital Deformity Syndrome See Table 2. Deformity syndrome included chromosome abnormalities, diseases of gene mutation, environmental teratogenesis, and congenital deformities of unknown causes. In our series of patients, 49 patients were found to have had trisomy 21 syndrome and 39 patients to have had Gillian Turner-type X-linked mental deficiency syndrome, Prader-Willi's syndrome, Cohen's syndrome, hypothyroidism (cretinism) and phenylketonuria, respectively. Patients with trisomy 21 syndrome all had typical appearance, one-line palm and separation of the first and the sencond toes, all of which were confirmed by chromosome examination in part of the patients. The clinical manifestations of Gillian Turner-type X-linked mental deficiency syndrome in many patients were testicular enlargement, large ears with prominence, and prominent forehead and chin, all of which were demonstrated by chromosome examination. Prader-Willi's syndrome was manifested as hypomyotonia, obesity and small hands and feet. The clinical manifestations of Cohen's syndrome were maldevelopment of incisor protuberance, obesity and hypomyotonia. Phenylketonuria, caused by hereditary phenylalanine metabolic disturbance, was manifested as urinous odor, positive FeCl3 reaction, and elevated blood phenylalanine. Cretinism was characterized by dwarf, pachycheilia, macroglossia, and low levels of T4 and TSH. No manifestations of paralysis were observed in hypophrenia caused by chromosomal aberration or gene mutation. Of the 49 patients with trisomy 21 syndrome, 36 showed increased and fluent talk and responded quickly to conversation after treatment. Twenty-four patients had learned to entertain a guest warmly and to do housework actively. Seventeen patients showed an increased ability to take care of themselves in daily life and began to pay attention to hygiene and clothing, they also gave increased points in IQ test. The other 39 patients with deformity also showed marked improvement in ability to take care of themselves in daily life, speech and adaptive capacity. Typical cases are as follows:
Case 1 Mr.Yang, aged 22 years, had typical trisomy 21 syndrome and showed a karyotype of 47XY+21. After taking the medicine for 7 successive months he showed an increased and fluent talk and liked to talk about television and movie with his family members. He poured a cup of tea and gave a cigarette to a guest, being very warm. He could keep in mind the guest whom he had contacted with once. He liked to do housework seriously and orderly. He grew taller by 2 cm in the recent year.
Case 2 He××，a boy aged 12 years, was fat with small palpebral fissure, downwards oblique external canthus of both eyes, protuberance on upper incisor teeth, mild thoracic kyphosis and hypophrenia. He was diagnosed as having Cohen's syndrome. After taking the medicine for 19 successive months, he had learned addition and subtraction within two digits. He could distinguish banknotes of different denominations, make a phone call, know and write some words, and recite some children's songs, his enunciation was more clear than before. His hands were more nimble than before and the posture of camptocormia and rotation in moving disappeared.


Table 2 Curative effect on MR caused by congenital deformity syndrome
No.of cases Notable effectiveness General effectiveness Failure
Trisomy 21 syndrome 49 13 27 9
Other deformities 39 26 12 1
Total 88 39 39 10

Curative Effect on Sequelae of Infection of the Brain, Cerebrovascular Diseases and Brain Trauma (Table 3)


Table 3 Curative effect on sequelae of infection of the brain, cerebrovascular diseases and
brain trauma
No.of Notable General Failure
cases effectiveness effectiveness
Sequela of encephalitis 48 26 15 7
Sequelae of toxic encephalopathy 52 30 22 0
due to infection and meningitis
Brain injury due to convulsion and epilepsy 21 5 13 3
Sequelae of cerebrovascular diseases 35 14 18 3
Sequela of brain trauma 19 6 9 4
Sequela of brain operation 3 3 0 0
Fish bile poisoning 2 2 0 0
Others 15 9 6 0
Total 195 95 83 17

Included in this series were hypophrenia and dyskinesia caused by brain injury, cerebrovascular diseases, inflammation and other etiological factors after infancy. The diagnosis was based mainly on medical history, physical examination and data of accessory examinations. Preschool children and school-age children predominated in patients of this series, 13 patients were less than 3 years of age and 92 patients more than 18 years of age. Dyskinesia was found in 176 cases, intellectual disturbance in 92 cases, complicated epilepsy in 56 cases, and complicated behavior disorder in 40 cases.
Treatment with Li's Prescription No.5 led to improvement in symptoms and signs in varying degrees. Satisfactory results, especially the promotion of intelligence, were obtained in treating sequelae due to viral encephalitis, toxic encephalopathy due to infection and meningitis. Even better curative effect can be expected if this medication is combined with acupuncture and moxibustion, massage and rehabilitation training. Typical case is as follows:
Case Mr.Shang, aged 31 years, had encephalitis in March 1993 and experienced coma for more than a month, which was followed by hemiplegia on the right side, mental and reactive retardation, stubbornness, involuntary laugh, and choke and cough in drinking water. He failed to respond to medical treatment in many ways. Six months after treatment with Li's Prescription No.5, he could walk some 50 metres alone, understand what other persons said, and say complete sentences. Only 3 months after oral administration of the medicine could he sell good in his own shop and work out accounts with electronic calculator. Such symptoms as involuntary laugh disappeared basically.
Curative Effect on Retrograde Encephalopathy (Table 4)


Table 4 Curative effect on retrograde encephalopathy
No.of Notable General Faliure
cases effectiveness effectiveness
Senile dementia 32 23 9 0
Extrapyramidal diseases 45 27 17 1
Cerebellar and spino-cerebellar degeneration 16 9 6 1
Others 8 0 5 3
Total 101 59 37 5

Senile dementia in this series included Alzheimer's disease, vascular dementia and mixed type dementia. Extrapyramidal diseases included Parkinson's disease, Parkinson's syndrome and torsion dystonia. Cerebellar diseases included cerebellar atrophy caused by arteriosclerosis and cerebral infarction, olivo-ponto-cerebellar atrophy, cerebellar cortical degeneration and Friedreich ataxia. Other cases included demyelinating disease, leukodystrophy, mitochondrial encephalomyopathy, etc.
Li's Prescription No.5 has notable curative effect on dementia as manifested by improvement in memory, affective disorder, psychonosema, and personal care. Curative effect is, of course, related to such factors as duration of illness, age, type of dementia and the degree of support enjoyed from society and family. Li's Prescription No.5 is effective in controlling tremor and hypermyotonia. It controls the advance of illness, reduces the dosage of dopamine preparation or even stops the use of dopamine preparation. It is less effective in treating torsion dystonia and athetosis. Cerebellar degeneration belongs to retrograde affection of nervous system, many cases of cerebellar degeneration are concerned in heredity and are in progressive development. At present, no specific remedy for cerebellar degeneration is available in modern medicine. Of the 16 cases treated with Li's Prescription No.5 and followed up, 9 showed notable effectiveness, and 6 showed general effectiveness. The effect of the treatment varied with the individual. Typical cases are as follows:
Case 1 Mrs. Zheng, age 74 years, had hypomnesis 6 years ago, with unclear enunciation and eccentric behavior. In the recent two years, she could neither recognize any of her family members nor recollect the past. She always defecated and urinated anywhere without the sense of shame, and always stuck out her tongue. Skull CT scanning showed encephalatrophy. She was diagnosed as having Alzheimer's disease and was given Li's Prescription No.5 for oral administration. Three months later her memory got highly improved, she could recognize her family members and call their names, could understand what other persons said, and could talk with others on her own initiative. She now kept her tongue within her mouth and no longer defecated and urinated anywhere.
Case 2 Mr.Ai, aged 63 years, had cerebral infarction three years ago. When discharged from hospital, he had weakness of right limbs, slurred speech with an irrelevant answer, and expressional sluggishness. One month later he had tremor of fingers, bradypragia, festinating gait and marked hypomnesis. Skull CT scanning showed lacunar cerebral infarction and mild encephalatrophy. He was diagnosed as having lacunar cerebral infarction and Parkinson's syndrome and was given oral administration of Li's Prescription No.5. Forty days later tremor of fingers disappeared, and he became articulate, could step forward, and felt clearheaded.
Curative Effect on Visuoauditory Disturbance and Autism (Table 5)


Table 5 Curative effect on visuoauditory disturbance and autism
No.of Notable General Failure
cases effectiveness effectiveness
Sound perception nerve deafness 5 2 3 0
Optic atrophy 6 1 1 4
Autism 7 1 5 1
Total 18 4 9 5

The curative effect of Li's Prescription No.5 on sound perception nerve deafness, optic atrophy and autism warrants further observation and study. Two patients had deafness due to streptomycin poisoning. One, aged 3 years and 6 months, had his hearing improved after taking the medicine for three successive months, could learn to speak following his parents, and could say "I want to eat something ," "I want to have a bowel movement." His eyes could trace the direction of a sound. The other, aged 16 years, had an account in his own words after taking the medicine for 17 successive months: " My right ear can hear you, my left ear is ringing but also can hear a little." The patient could hear you if you spoke loudly behind him. The treatment also led to improved hearing in the other three cases. One of the 6 MR children with concomitant cerebral palsy and optic atrophy in Table 1 had his naked visual acuity increased from 0.1-0.2 to 0.6-0.8 after taking the medicine, and another patient had his visual acuity improved after taking the medicine for a year and could get out of the obstacle when walking. Seven affected children with autism showed improvement in intelligence and in dystropy after treatment.
The Total Curative Effect of Li's Prescription No.5 on Various Encephalic Diseases (Table 6)

Table 6 Total curative effect of Li's Prescription No.5 on various encephalic diseases
Notable General Failure
effectiveness effectiveness
No.of cases 641 452 71
Percentage (%) 55.1% 38.8% 6.1%



The total effective rate was as high as 93.9%. It is evident that Li's Chinese medicinal prescription does have curative effect on diseases of central nervous system regardless of the site (cerebral cortex, basal ganglion, brain stem or cerebellum) of pathologic change, the nature (trauma, vascular disease, inflammation, degenerative disease or congenital disease) of lesion and the length of duration of illness. This is the conclusion drawn from treatment of several ten thousand patients over ten years and has been demonstrated by this retrospective survey.
Discussion
Li's Prescription No.5 consists mainly of tortoise plastron, wolfberry fruit, Siberian solomonseal rhizome, grassleaved sweetflag rhizome, bitter cardamon, Chinese angelica root, polygala root and safflower and has the efficiency of tonifying the kidney and marrow, promoting qi circulation and activating collaterals, promoting the production of blood and strengthening the bone, and promoting blood circulation by removing blood stasis. This retrospective survey made on 1 164 cases of encephalopathy has demonstrated that Li's Prescription No.5 has notable therapeutic effect on various diseases that affect the functioning of the brain. What is the mechanism of its action? The serial experimental studies which we have carried out for

years may help to elucidate the mechanism. In 1995, Wu Yongjie, a pharmacological professor of Lanzhou Medical College, demonstrated by animal experiments that Li's Prescription No.5 promoted the mice's learning and memory capacities; increased the effect of anti-ischemia and anti-anoxia, inhibited the formation of free radicals, improved energy metabolism of the brain; enhanced levodopa-induced mechanical movement in the mice, indicating that it has the action of enhancing dopaminergic nervous function; and promoted development of the brain and the body. (1) Wu later demonstrated that Li's Prescription No.5 markedly decreased cell apoptosis of in vitro cultured mesencephalic neurons of rat embryo; made the cell bodies of dopaminergic neruons of dense area of black substance of rats in study group larger than those in control group, the extent of the increase being related to the dosage of Li's Prescription No.5; and had nerve protective effect on striate body of black substance of experimental Parkinson's disease model. (2) The in vitro culture of nerve cells is an ideal extracorporeal model for studying mechanism of neuronal injury and drug action. PC12 cell is the clone formed by pheochromocytoma of adrenal medulla of rat and has the characteristics of typical neuroendocrine cells. (3) A study in collaboration with professor Liu Guoqing of China Pharmaceutical University and professor Li Rui of Guangzhou University of Traditional Chinese
Medicine and Materia Medica showed that decoction (containing volatile oil ingredient ) of Li's Prescription No.5 and medicated serum of Li's Prescription No.5 do promote the proliferation of PC12 cells, the proliferation rate being 63.9% and inhibit ischemic and anoxic injury, the inhibition rate being as high as 93%. (4) The experimental studies demonstrated that Li's Prescription No.5 has the effects of improving metabolism of brain cells, inhibiting apoptosis of brain cells, facilitating development of brain cells, and improving functioning of brain cells. It is, therefore, applicable to clinical treatment of mental retardation, cerebral palsy, retrogressive diseases (senile dementia, Parkinson's disease), brain trauma, cerebrovascular disease, sequela of encephalitis and congenital brain diseases caused by chromosomal aberration, gene mutation and hereditary metabolic disease.
According to the theory advanced based on clinical and experimental study that there might exist a functional adjusting point in the brain, Li's Prescription No.5 is easy to permeate blood-brain barrier, improves the metabolism of brain cells, regulates the anion-cation imbalance in the brain, maintains a high-energy magnetic field, and interferes with and improves the brain function in the form of electromagnetic wave.
The discovery of the plasticity of central nervous system after injury in the 1950s demonstrated the axonal growth after neuronal injury and the relationship between axonal regeneration and neuronal type and control of axonal microenvironment (5), thus overthrowing the conclusive statement in the beginning of the 20th century that damaged brain cells had no power of regeneration. In November 1998, Peter S.Eriksson of Sahlgrenska University Hospital, Goteborg; Sweden, Fred H.Gage of Salk Biological Institute, California, U.S.A. and their colleagues published the astonishing news: the human adult brain does routinely produce neurons in at least one part－hippocampus. (6) Like bone marrow, the cerebrum also has stem cells. These stem cells exist only in certain parts of the brain such as hippocampus. Researchers are looking for regulatory factors to make the stem cells proliferate, then migrate and differentiate, and finally restore the structure and function of the brain. This will be an arduous and long-term effort. Li's Prescription No.5 produced on the basis of long standing and well established traditional Chinese medicine provides good micro-environment for the axonal regeneration of neurons and the proliferaiton and differentiation of cerebral stem cells, greatly enhances the plasticity of central nervous system, and facilitates regeneration of central nerve cells. Gratifying dawn emerges in the treatment of encephalopathy.

References

1. Wu Yongjie. The principal pharmacodynamic test data and references of Li's Prescription No.5. J Modern Encephalopath Med, 1997, special issue: 34-49.
2. Li Zizhong. Studies on treatment of nerve retrograde affection with Naokang Capsule (originally Li's Prescription No.5). Symposium of 98' Seminar on Traditional Medicine of Asia-Pacific Region, May 1998; 5.
3. Peruche B, Krieglstein J. Neuroblastoma cells for testing neuroprotective effects. J. Pharmacol Meth, 1991, 23:63.
4. Liu Guoqing, Li Rui, Jiang Xuehua, et al. Protection on ischemia-like injury and improving effects on proliferation of Lishi No.5 on neuron. Pharmacol and Clin of Chin Materia Medica, 1999, 15 (2):32.
5. Lund RD (1978). Development and plasticity of the brain, New York; Oxford University Press.
6. Gerd kempermann and Fred H Gage. New nerve cells of human adult brain. Scientific American, May 1999; 48-53.

　
·Original Articles·

Abnormal Psychology and Personality

Li Zizhong

[Abstract] Abnormal psychology and personality disorder are the common mental diseases and highly harmful to human health. According to statistics, mentally induced diseases account for more than 70%. Previously, the poor understanding of their pathogenesis and the lack of effective control measures led to poor clinical curative effect. With the development of immunology in recent years, scientists now have greatly improved knowledge on allergic diseases and personality disorder. But this discipline of science is just in its beginning, there remain a lot of aspects to be explored.
[Key words] Abnormal psychology Personality Psychological diseases


Abnormal Psychology
Abnormal psychology refers to unhealthy mental activities which deviate from normal scope. The word "abnormal" differs from "normal" in relative significance. Abnormal psychology is affected by a variety of factors including social environment, habits and customs, culture, sense of value and religious mode. No absolute or definite demarcation line can, therefore, be drawn between normal psychology and abnormal psychology.
Abnormal psychology in a broad sense refers to irrealizable, irrational or unhealthy psychologic development that happens in normal persons, such as contrary psychology, day dream, sexual hallucination, self-love, idolum, projective psychology, anagogy and so on.
Abnormal psychology in a narrow sense refers to all types of abnormal personality, sexual perversion, dependence on alcohol, opium, heroin or other drugs, neuroses, psychonosema caused by brain trauma, epilepsy or somatic disease and various mental diseases.
Abnormal Personality or Personality Disorder
Personality disorder in a narrow sense refers only to moral or antisocial personality and that in a broad sense includes all personality disorders.

Author's unit: Guangdong Gaoming Medical and Medicinal Institute of Encephalopathy, Gaoming, Guangdong 528500.

Personality is an enduring disposition to act and feel in particular ways that differentiate one individual from another. These patterns are sometimes conceptualized as different categories and sometimes as different dimensions. Normal personality also differs from abnormal personality relatively. No absolute demarcation line can be drawn between abnormal personality and normal personality and between abnormal personality and nervous disease or mental disease. Only when an individual's personality defect is so severe that his social adaptive capacity is highly affected and gives much trouble to people around him can the individual be regarded as having abnormal personality.
Abnormal personality can be attributed to the following three factors:
1. Organic or biologic factors
Genetic factors play a certain role in the formation of abnormal personality. It has been shown by relevant data that the incidence of criminal offence, nervous disease, suicide, getting drunk and creating a disturbance, mental disease, intellectual maldevelopment, personality defect or abnormal personality in families with abnormal personality far exceeds that in families with normal personality. In addition, abnormal personality can often be found in sequelae of brain injury due to brain trauma and encephalitis and sequela state of chronic epilepsy and schizophrenia. Persons with sex chromosome abnormalities can also have concomitant abnormal personality or antisocial criminal impulse. An electroencephalogram screening made in a larger part of patients with abnormal personality showed that the abnormality rate of electroencephalogram in these patients is by far higher than that in the control group consisting of normal persons. These data suggest that organic factor of the brain plays a certain role in part of patients with abnormal personality.
2. Psychological factors
The psychological factors refer mainly to psychic trauma in infancy, improper upbringing, particularly the maternal deprivation and being maltreated in infancy, the effect of a broken-up family on child's psychology, over-spoiling a child (particularly the only son or daughter) of parents, inconsistent or incoherent family education of parents, and the bad examples of degenerated parents. In view of the fact that the most important period for an individual's personality to form is before 5-6 years of age, carelessness in the psychologic development of children in this period is liable to cause some type of mental disease or to commit a crime or both after growing up.
3. Harmful effects of social environment
Harmful society will create contrary psychology or spiritual contamination derived from direct environment. A most striking example is the poison and destroyment of the so-called "great proletarian cultural revolution" to young people's ideology, this "revolution" brought about quite a lot of people with abnormal psychology or personality. In addition, some unhealthy tendencies and irrational phenomena in real society, various spiritual contaminations and such actual problems as educational deprivation, unemployment and disappointment in a love affair are liable to evoke great indignation, resistance, repression, faith crisis, pessimism, giving oneself up as hopeless and drifting with the tide, thus developing personality disorder.
Classification of Abnormal Personality
1. Antisocial Abnormal Personality
It is also called "grim abnormal personality" and is the type of being most liable to have criminal or illegal activities. Various bad behaviors and habits start often with childhood, including telling lies, cutting class, stealing, coming to blows, roaming the streets and disturbance of sexual behavior. This is the origin of "problem child", who will finally become an individual typical of this abnormal personality after growing up.
A thorough investigation and study has shown that individuals with this type of abnormal personality have the following 16 characteristics: (1) having good intelligence and being superficially likable; (2) lack of delusion and other mental manifestations of irrational thought; (3) lack of clinical manifestations of neurosis; (4) putting no trust in others; (5) dishonesty; (6) shamelessness and regretlessness; (7) having antisocial behaviors of harbouring evil intentions or doing a mischief without particular purpose; (8) morallessness and lack of correct judgement between good and evil and between right and wrong, and not drawing a lesson; (9) extreme selfishness and self-centredness; (10) unfeelingness, not loving others, showing indifference to the sufferings of others; (11) lack of self-knowledge; (12) being not amenable to reason and not responsible for interpersonal relationships; (13) being fond of fantasy, addicted to drink or not; (14) having abnormal or disturbed sexual life; (15) rarely having a real suicide unless being put in a hopeless situation or committing suicide to escape punishment; and (16) often accomplishing nothing in the program for life.
Those who have this type of abnormal personality often act impetuouly on impulse, thus bringing about sufferings of others and not themselves. However, they are, in fact, not real psychotics and according to the stipulation of Article 15 of Chinese Corporal Punishment they have complete ability to bear responsibility for their own behaviors.
No specific drugs for correcting or treating antisocial abnormal personality are available at present. Education and prevention remain the methods of first choice. Great attention should be paid to mental health of childhood, and behavioral problems and abnormal psychological tendencies exposed during childhood should be solved by the method of patient education and instruction.
2. Paranoid Personality Disorder
It is a personality distinguished by such traits as excessive sensitivity to rejection by others, subjectivity, stubbornness, suspiciousness, hostility, and self-importance. This type of personality disorder, though it may be premorbid personality basis of paranoid psychosis, differs from the latter in lack of such mental symptoms as true pathologic delusion.
No specific drugs for this type of personality disorder are available, psychotherapy and nerve block therapy are generally used.
3. Schizoid Personality Disorder
It is a personality characterized by solitariness, emotional coldness to others, excessive introspection, and eccentricity of behavior. Generally speaking, persons who have schizoid personality may have good intelligence, some may achieve great successes in natural science, philosophy, literature or art. Some schizophrenics have this personality before their illness, but most schizoid personalities do not become schizophrenic. Schizoid personality differs from schizophrenia in two main points: (1) lack of particular symptoms seen in schizophrenia, including hallucination, delusion, apathy or affective ambivalence, thought incoherence and behavioral disturbance, and possessing some adaptive capacity of real life; (2) relative stability of schizoid personality disorder throughout one's life with rare development of mental deterioration.
There are no specific remedies for this type of personality disorder. Care must be taken to avoid mental stimulation and to prevent the development of schizophrenia under malignant stimulation.
4. Affective Personality
Affective personality can be divided into the following three subtypes:
(1) Depressive Personality It is a mental state characterized by excessive sadness, emotional coldness to others and apathy. Activity can be agitated and restless or slow and retarded. Behavior is governed by pessimistic or despairing beliefs, and sleep, appetite, and concentration are disturbed. Depressive personality is liable to develop reactive depression under harmful effects.
(2) Manic Personality It is a state of mind characterized by excessive cheerfulness and increased activity. The mood is euphoric and changes rapidly to irritability. Behavior is overactive and extravagant.
(3) Cycloid Affective Personality It is characterized by a circular affective fluctuation and manifested as manic personality in mood elevation and as depressive personality in mood depression but the affective fluctuation is not so severe as to develop manic-depressive psychosis. An investigation made on the above-mentioned three subtypes of affective personality showed that the incidence of similar personality manifestations or of manic-depressive psychosis in families of persons who have affective personality disorder is significantly higher than that in normal population. Therefore, affective personality disorder may be related to the imbalance of catecholamine in the brain and to genetic factors. There are also no specific remedies for these above-mentioned personalities. It is important to avoid mental stimulation to prevent the development of reactive depression or accident of suicide under harmful stimulations. Small doses of anti-manic or anti-depressive drugs may also be tried.
5. Obsessive-compulsive Personality
It is manifested as overcautiousness, stubbornness, following rules, orders, etc. docilely, setting excessively strict demands on oneself and on others, demanding perfection, excessive frugality or even stinginess, fear of contamination and so on. There is no obvious obsession or compulsive behavior in obsessive-compulsive personality. It can be treated with behavior therapy and also with psychotherapy.
6. Hysterical Personality
It is more commonly found in females, characterized by instability and shallowness of feelings, by vulnerability to suggestion and by superficiality and a tendency to manipulate in personal relationships, and also called "dramatic personality". Patients with such symptoms are usually treated with psychotherapy and behavior therapy.
7. Delicate Personality
It can be divided into subtypes of dependence personality, passive personality and energy-vigour deficiency personality. Its features are lack of initiative, deficiency of energy vigour, being dependent on others and highly sensitive to mental stimulation, emotional instability and lack of joys of life. Persons with this personality are liable to suffer from neurasthenia, anxiety, hypochondria, depression, etc. The main point of control is to pay attention to mental health of children in addition to psychotherapy.
8. Explosive Personality
It includes aggressive personality, excitable personality, agitating personality, emotional instability-type personality, argumentative-type personality, and paranoid personality. It is characterized by explosion of very strong anger and impulse due to minor mental stimulation which is difficult to control by oneself and liable to evoke violent aggressive behavior. It is also known as episodic dyscontrol syndrome. Generally speaking, persons with this type of personality do not necessarily have antisocial tendency but may, under harmful effects, commit an offence against the law and usually have a certain responsibility for a crime. Psychotherapy is usually the method of choice, adequate amount of psychosedative may also be used in stage of attack.
9. Infantilism-type Personality
It is characterized by emotional immaturity and behavioral infantilism and sometimes accompanied by mild oligophrenia. No specific remedies are available for this type of personality.
10.Organic Personality Disorder
It is also called organic abnormal personality, refers to changes in personality due to organic changes of the brain, and is generally manifested as degenerated morals and ethics and some moral antisocial behaviors. Such diseases as craniocerebral trauma, encephalitis, meningitis, presenile encephalatrophy, brain tumor, birth trauma and cerebral lesion syndrome can all lead to the development of organic personality disorder. In addition, epileptic personality and schizoid personality disorder also belong to this category.
Epileptic personality disorder found in epileptics with long-term grand mal epilepsy is characterized by too long-winded and repetitious speech, a suspicious frame of mind, strong retaliation, liability to be irritated, hot-temperedness, and sometimes violent behavior due to minor problem. Sometimes, patients with epileptic personality disorder may fall into pathological affect state under strong mental stimulation (with concomitant obvious disturbance of consciousness), thus evoking severe impulses and harmful acts. Antiepileptics and tranquilizers are indicated.
Schizoid personality disorder is characterized by solitariness, emotional coldness to others, excessive introspection, and eccentricity of behavior. Some schizophrenics have this personality before their illness, but most schizoid personalities do not become schizophrenic. Patients with schizoid personality disorder should be followed up, re-examined and treated promptly to prevent development or relapse of schizophrenia.
In the presence of illegal activities, patients with the above-mentioned organic personality disorder generally have part of responsibility for a crime.
11.Other Psychopathic Behaviors
Principally, there are the following three kinds:
(1) Munchhausen's syndrome It is a mental disorder in which the patient persistently tries to obtain hospital treatment for an illness that is nonexistent, an extreme form of malingering. The disease may be described in vivid detail, and in some cases injury may be deliberately self-inflicted in an attempt to give the appearance of authenticity to the claims being made.
(2) Kleptomania It is a pathologically strong impulse to steal, often in the absence of any desire for the stolen object(s). It is sometimes associated with depression. This abnormal behavior differs from both "psychiatric collection", which is seen in senile dementia and chronic schizophrenia, and general hardened thief, but, generally speaking, persons with kleptomania have part of responsibility for a larceny.
(3) Pyromania It is an excessively strong impulse to set things on fire, often in the absence of any desire for retaliation, destroyment, frame-up or other motives. If there is special sexual pleasant sensation in setting things on fire, the pyromania is known as "pyroerotomania". It should be differentiated from general arsonists. Persons with pyromania or pyroerotomania should have part of responsibility for committing arson.
Psychotherapy is indicated to the above-mentioned three psychopathic behaviors.
Sexual Perversion or Parasexuality
It refers to any abnormal sexual behavior. The abnormality may be in the sexual object or in the activity engaged in. The activity is sexually pleasurable. The definition of what is normal varies with different cultures. Treatment is necessary only when the perversion causes suffering.
1. Homosexuality
Homosexuality refers to the condition of being sexually attracted, covertly or overtly, by members of one's own sex, it can affect either sex. The cause of homosexuality remains unclear, although explanations in terms of either a deviant family structure or an environment with limited opportunities for heterosexual contacts are increasingly accepted. The vast majority of homosexuality is due to lopsided development of sexual psychology except that a minority of it (less than 5%) may have morphological abnormality of sex chromosome, true or false hermaphroditism or cryptorrhea. Therapy may be offered to individuals wishing to change their sexual orientation. There are no drugs available for changing sexual orientation, although it is possible to depress the sexual drive. Treatment consists of psychotherapy or specific behavior therapy designed to eliminate homosexual behavior and fantasy and to increase heterosexual behavior.
(1) Clinical Classification
Homosexuality is clinically divided into three main types:
(a) Active and Passive Type In homosexuality the one who plays the part of a husband is called active type and the other who plays the part of a wife is called passive type. The male passive type (e