Department of Neurology , 2nd affiliated hospital , College of medicine, Zhengjiang university

1. Department of Neurology , 2nd affiliated hospital , College of medicine, Zhengjiang university

2. definition: Epilepsy is a group of chronic disorders characterized by recurrent seizure, which is a transient disturbance of cerebral function caused by an abnormal neuronal discharge. That are charcterized by recurrent 、spontaneous、transient 、paroxysms.

3. Because of different position and diffuse extent of abnormal neuronal discharge, the neurologic malfunction may reflect motor, sensation, consciousness, behavior and autonomic nerve and so on. seizure Epilepsy epileptic syndromes

4. classification by etiology: 1、Idiopathic epilepsy for which most common in children and adolescent, No obviously structural change and metabolic abnormality that induce seizure are found in patients’ brain. It may be closely related to heredity. prevalence rate of close relative is high to 2-6%, which is 70% in monovular twins.

5. 2、Symptomatic epilepsy: by kinds of cerebral impairments and metabolic disorders. （1）： Congenital cerebral diseases: 脑皮质发育不全(agenesia corticalis )、先天性脑积水(congenital hydrocephalus ), 遗传代谢障碍(genetic metabolic disorders )，如卟啉病（ porphyrinopathy）、苯丙酮尿症（ phenylketonuria)等。 （2）： Cerebral trauma: 凹陷性骨折（ depressed fracture）、硬脑膜撕裂（ meninx fibrosa laceration）、脑挫裂伤（ contusion and laceration of brain）等。

6. （3） Diseases in antenatal period and perinatal diseases: are the most causes of infant epilepsy。 Hydrocephalus, intracerebral hemorrhage and infaction which caused by头吸(head aspiration )or产钳(obstetrical forceps), can make the局部脑软化(focal brain malacoma), and those may become seizure focus several。 （4） After febrile convulsion： Serious and lasting febrile convulsion can result in neuron hypoxia→impairments of neuron→proliferation of gliocyte → seizure focus. Medial temporal lobe is sensitive to hypoxia, which lead to切迹硬化(incisure sclerosis)

7. （5）Infections: meninges or encephalon is infected by kinds of bacteria、 virus、paresites, and then lead to encephalitis, meningitis, cerebral abscess. （6）Toxicosis: CO、汞（ hydrargyri,）、乙醇（alcohol）、灭鼠药（ deratization durgs）等，以及尿毒症（ uremia）、妊娠中毒症(toxenia of pregnancy )。 （7） Cerebrovascular diseases: subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, vascular malformation, et al.

8. （8） Intracranial tumors: meningothelioma, astrocytoma, metastatic tumor, lymphoma, et al. （9) Nutritional, metabolic diseases: hypocalcemia, hypoglycemia, VitB6 deficiency. （10） Degeneral, demyelinating diseases: AD, tuberous sclerosis, multiple sclerosis. Pick病等。

9. 影响癫痫发作的因素： Heredity: often involve many genes, which are only for预致性(theprediction) or 敏感性(sensitivity )of seizure. The penetrance is limited by ages. enviroments: endocrine ,如经期性癫痫(menstrual epilepsy),妊娠性癫痫(gravid epilepsy), sleep。 causative factors ，如flashing --myoclonus, overventilation--absence seizure, over hydroposia--tonic clonic seizure。 reflex epilepsy: photogenic epilepsy, chess epilepsy等。

10. pathogenesis: It caused by the neurologic disbalance between excitation and inhibition, and the abnormal stability of membrane potential. It may be increase of neuron excitation or decrease of inhibition, and abnormality of membrane.

11. 1、Change of biochemistry: excitatory amino acids (aminoglutaminic acid, aminosuccinic acid) are excitatory transmitters, which make calcium and sodium ions get in cell, destroy the stability of membrane, prolong the unpolarized time course. GABA: Cl - 2、Change of membrane potential: to show off persistent depolarization →阵发性去极化飘移( paroxysmal depolarizationshift,PDS).

12. 3、Heredity: 常染色体显性遗传夜间发作性额叶癫痫（autosomal dominant nocturnal frontal lobe epilepsy)，位于20q13.2。 少年肌阵挛癫痫已发现3个基因位点，分别被定位于6p21.3、15q14和8q24。 儿童失神癫痫的基因定位于8q24。 良性家族性婴幼儿惊厥的基因被定位于19q。 4、轴突发芽：可能是神经元异常放电的形态学基础。

13. classifications of seizure: According to that discharge originate from unilateral or bilateral (EEG), consciousness is exist or not, seizures are classified three types nine subtypes（三大类九亚型）. 单纯部分发作 （simple partial seizure） Partial seizure 复杂部分性发作 （complex partial seizure） 继发全面发作 （secondary generalized seizure）

14. 失神发作 （absence seizure） generalized seizure 肌阵挛发作（ myoclonic seizure） 阵挛性发作 （clonic seizure） 强直性发作（ tonic seizure） 强直－阵挛发作 （tonic-clonic seizure） 无张力性发作（ atonic seizure） unclassified seizure

15. simple partial seizure: Motor symptoms: focal limbs（thumb or face) ，Jacksonian epilepsy (march), Todd ,s paralysis, epilepsia partialis status。 Sensation symptoms: general sensation (numbness, pricking pain)，Jackson感觉性癫痫。特殊感觉（嗅-olfactory、味-gustateory、听-sounds、视-vision）。

16. Autonomic symptoms: nausea(呕心）,vomiting(恶吐）,烦渴（ polydipsia）、排尿欲（urination desire），sweating（出汗），cardiac arrhythmia, 等。 Psychic symptoms: amnestic disorder, sentiment abnormality(情感异常)、misconception(错觉), complicated hallucination, feelings of familiarity and unfamiliarity , et al.

17. complex partial seizure: or psychomotor seizure. The psychiatric symptoms or symptoms of special sense occur firstly, the secondary symptoms are impairments of consciousness , automatism and amnesia. Automatism: the manifestations are partially or completely poor contact with enviroments, and do repetitive actions which are aimless or unconscious. The eyes just agaze, accompany with吸吮(sucking),摸索(groping), walking, speaking, running, shouting and so on.

18. secondary generalized seizure: Begin with an aura. Simple partial seizure → secondary generalized seizure; Complex partial seizure → secondary generalized seizure; Simple partial seizure → Complex partial seizure →secondary generalized seizure. posture seizure, adversive seizure

19. absence seizure: (petit mal) Brief loss of consciousness for 5-10 seconds, no reaction to call, the eyes agazing, begin and stop abrutly. there are may be several to several hundred seizure daily. The EEG shows a characteristic 3/s spike-and-wave pattern during the seizure. The begin and stop of unconsciousness in atypical absences is slower than in typical absences. The EEG shows irregular spike-and-wave with abnormal background.

20. myoclonic seizure: Showing abrupt, transient, quick muscle contraction, which is generalized or focal. clonic seizure: Generally repetitive clonic seizure tonic seizure: The limbs straightly stretch, the head and eye deviate to one side, accompany with greater pupils.

21. tonic-clonic seizure: (grand mal) loss of consciousness and convulsions Tonic phase(强直期)： Clonic phase(痉挛期）: Postictal phase（惊厥后期）：

22. Tonic phase: • 上睑抬起(eyelids put up)，眼球上窜(eyes deviate) ，喉部痉挛(laryngeal spasm, “epileptic cry”) ，The body is stiff ,theelbows are flexed and the legs extend， limbs or handsshow a few small jerk. This stage lasts for 10-20 seconds. • Autonomic hyperactivity is prominent, such as心率加快(cardiac arrhythmia) ;blood pressure elevation; bronchial hypersecretion ; pupil dilation and the reflex to light disappear ; breathing stops, the lipsand face cyanosis (bluish).

23. Clonic phase: • The recurrent clonic muscular contractions are produced , lasting for 1 or 2 minutes. • Physiologic changes:cardiac arrhythmia ;blood pressure elevation; bronchial hypersecretion ; pupil dilation; the reflex to light disappear ; the lips and face cyanosis (bluish). Bladder and bowel funtion may be lost.

24. Postictal phase: • Breathing resumes firstly, foam(泡沫) around the mouth, urinary and fecal incontinence. • The pupil size, blood pressure, heart rate gradually return to normal level . • The patients gradually awake, headache, and muscular pain are common. • The patient does not recall the seizure itself.

25. Status epilepticus，SE: • More than 30 minutes of continuous seizure activity ，or two or more sequential seizures without full recovery of consciousness between seizures. • Usually with hyperthermia, dehydration , acidosis, WBC levations . • SEis a common life-threatening neurological disorder. It is essentially an acute, demanding immediate treatment.

26. Convulsive SE： • 强直阵挛发作状态 Tonic-clonic status epilepticus • 强直性发作状态Tonic status epilepticus • 肌阵挛性癫痫状态 Myoclonic status epilepticus • 单纯部分发作性状态 Simple partial status epilepticus • 婴儿痉挛持续状态 Infantile spasm status epilepticus • Non-convulsive SE： • 失神状态 Absence status epilepticus • 复杂部分性发作状态（颞叶癫痫持续状态） Complex partial status epilepticus

27. epileptic syndromes • 良性儿童期中央回癫痫 （ Benign childhood epilepsy with centro-temporal spike），又称sylvian or rolandic epilepsy. • West综合征（West syndrome）:又称婴儿痉挛症（infantile spasms). • Lennox-Gastaut综合征： Lennox-Gastaut syndrome

28. Benign childhood epilepsy with centro-temporal spike： An idiopathic age- and localization-related epileptic syndrome . Involving the face, pooling of saliva ,usually secondary generalized. The symptoms usually occur at night, usually have an excellent prognosis, most seizures stopped by 15 years old. EEG shows high-voltage central or temporal spike-and-wave dischargeswith normal background.

29. West syndrome（infantile spasm） The syndrome is usually symptom, may resulted by prenatal ,perinatal ，metabolic disorders. Characterized by begin with a sudden, rapid, tonic contraction of trunk and limb, such as nodding , bowing, et al. Usually occur in clusters, often several dozens, separated by several seconds. EEG shows consists of chaotic, high-voltage polymorphic delta and theta rhythms (hypsarrhythmia-高峰节律紊乱)with spike andsharp charges.

30. Lennox-Gastaut syndrome： • The age at onset is preschool stage. The syndrome is characterized by multiple types of seizures, the most common seizure types are atypic absence, tonic, myclonic and tonic-clonic seizure. • EEG show slow spike-and-wave discharges (1-2 Hz) with abnormal background. • Usually have mental retardation or regression. seizures often are resistant to therapy (refractory epilepsy).

31. Diagnosis and differentials： The diagnosis of epileptic seizures is made by analyzing the patient's detailed clinicalhistory.

32. 1、 Is it epilepsy? hysteria, syncope, migraine, TIA, sleep disorders, et al.

33. 2、classifications of seizure or epileptic syndromes?： 3. etiology： 根据history、体征、辅助检查（EEG、脑电图诱发试验、AEEG、VTMEEG、CT、MR、MRS、fMR、SPECT、PET、DSA、 lumbar puncture等）确定病因。

34. prognosis： prevention and treatment： prevention： treatable causes ： 对症治疗(pharmacologic therapy)： 身心卫生(mental health)： 外科治疗(Surgical Care)： 切除致痫灶或阻断癫痫发放传播途径

35. 对症治疗: pharmacologic therapy 发作间期的治疗(treatment during interictal phase )： 发作期的治疗： 单次发作的治疗 持续状态的治疗

36. treatment during interictal phase： （1）何时用药:原则上一旦诊断明确,就开始规范治疗. (2）合理用药:根据发作类型和癫痫综合症、不良反应、年龄、性别、经济等个体状况选药。

37. choose the appropriate drugs according to seizure type: partial epilepsy-carbamazepine, phenytoin, henobarbital. complex partial epilepsy—carbamazepine. secondary generalized epilepsy—valproic acid generalized epilepsy—valproic acid. generalized tonic-clonic seizurealso can choose phenytoin, phenobarbital. Absence epilepsy also can choose ethosuximide and clonazepam

38. TherapyDose : • Begin with small dose, use the minimum dose to get seizure free. • Carbamazepine: • therapy dose range :0.3-1.0/day. Begin with 0.2/day, increase the dose slowly if the seizure is not free. effective dose concentration is 4-12mg/L. • valproic acid: • 0.6-1.6/day,begin with 0.6/day, the effective dose concentration is 50-100mg/L. • Phenytoin: • 0.3/day,begin with 0.2/day, the effective dose concentration is 10-20mg/L.

39. Drug combination: when the epilepsy is consider refractory epilepsy, which can’t get seizure free by using mono-drug and reach effective plasma concentration, usually consider to combinate two or more anti-epilepsy drugs. It is not appropriate to combinate anti-epilepsy drugs with the same side effect and same mechanism.

40. drug side effect: • Carbamazepine: rash (Steveus-Johson syndrome), acute ataxia, agranulocytosis, et al. • Phenytoin: rash (Steveus-Johson syndrome), acute or chronic ataxia, hyperplasia of gum and hair, encephalopathy, et al. ( saturation dynamics) • Valproic acid: gastrointestinal and hepatic damage.

41. Withdraw the drugs: • The conditions withdraw drugs : • 2 to 5 years after seizure free. • Gradually decrease the drug dose. It usually need slowly withdraw the drugs when the therapy contains long duration ,large dose and much kinds of drugs • 6 to 12 months of the whole stage.

42. 卡马西平 Carbamazepine 0.1／片 得理多 Tegretol（进口）0.2／片 丙戊酸钠Sodium valproate 0.2／片 德巴金控释片( Depakine )500mg／片 德巴金糖桨、 德巴金注射液(400mg/针) 鲁米那 Luminal（苯巴比妥 phenobarbital ） 30mg/片，或0.1/针 氯硝安定: Clonazepam

43. 妥泰 Topiramax（托吡酯 Topiramate ） 25mg/片，200mg-400mg/天。 • 拉莫三嗪 Lamotrigine 50mg/片，200mg-400mg/天。 • 加巴喷丁Gabapentin:0.1/片，0.6~0.9/天。 • 奥卡西平Oxcarbazepine：0.15/片，0.6~0.9/天。 • 开普兰（左拉西坦）：500mg bid

44. treatment during seizure： Lay the patient down, prevent the drop or lingua biting, as well as the asphyxia(窒息)。 Treat the patient with high frequency and long time convulsion by intramuscular injection phenobarbital. Patient with automatism should be take care of ,in order to prevent injury.

45. treatment of status epilepticus： • Stop the seizure as quicklyer as better: • intravenous diazepam , phenytoin, clonazepam, • phenobarbital。 • Keep the open of air way, give oxygen。 • Decrease the cerebral pressure. • Infection precaution . • Keep the balance of water, salt, acid-base and allopathy.

46. 谢谢