癫 痫 Epilepsy

1. 癫 痫Epilepsy Shengdi Chen（陈生弟）, M.D., Ph.D. Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine

2. Epileptic seizure can be defined clinically as an intermittent, stereotyped, disturbance of consciousness; exhibiting the abnormal symptoms of behavior, emotion, motor, or sensation; It is arising from abnormal, sudden, excessive, and rapid neuronal discharges. Epilepsy is a chronic disorder, or a group of chronic disorders, in which the indispensable feature is recurrence of seizures that are typically unprovoked and usually unpredictable. Definition

3. Status epilepticus is a state of continued or recurrent seizures, with failure to regain consciousness between seizures or seizure lasts for more than 30 minutes. Prodrome refers to premonitory changes in mood or behavior-these may precede the attack by some hours. Definition

4. Aura is the subjective sensation or phenomenon that precedes and marks the onset of the epileptic seizure-it may localize the seizure origin within the brain. Ictus is the attack or seizure itself. Postictal period is the time after the ictus during which the patient may be drowsy, confused, and disoriented. Definition

5. Epidemiology In China, annual incidence rates for epilepsy range from 50-70 per 100,000. Of persons with epilepsy, 60-70% achieve remission with antiepileptic drug therapy. Mortality is increased in persons with epilepsy, higher death rates are related primarily to the underlying disease rather than epilepsy. Accidental deaths, especially drowning, are more common, in all patients with epilepsy.

6. Etiology Brain injury Cerebral vascular disease Tumors CNS inflammation Parasites Neurogenetics Neurodegenerative diseases Drugs and toxins Cortical developmental dysfunction Others

7. 发病机制 各种病因→基因表达异常→神经递质或调质异常→ 离子通道结构和功能异常→离子异常跨膜运动→神 经元异常放电→神经元间的扩布→癫痫发作

8. Pathophysiology Electrical discharges between neurons are usually restricted, and produce the normal rhythm recorded on the EEG (electroencephalogram). When a seizure occurs, large groups of neurons are activated repetitively and hypersynchronously, with dysfunction of the inhibitory synaptic contact between neurons. This produces the high-voltage spike-and-wave activity on the EEG.

9. The onset of the epileptic discharge may include the whole cortex (‘primary generalized’), may be confined to one area of the cortex(‘partial’), or may start focally and then spread to involve the whole cortex (‘secondary generalization of a partial seizure’). Pathophysiology

10. Characters of clinical manifestation General character: 发作性、短暂性、重复性、刻板性 Specific character：不同类型癫痫所具有的特征

12. The classification used today is the 1981 classification of epileptic seizures developed by the international league against epilepsy(ILAE) This system classifies seizures by clinical symptoms supplemented by EEG data. Inherent in the classification are two important physiologic principles. Classification of seizures

13. First, seizures are fundamentally of two types: those with onset limited to a part of one cerebral hemisphere(partial seizures) and those that seem to involve the brain diffusely from the beginning(generalized seizures). Second, seizures are dynamic and evolving; Clinically expression is determined as much by the sequence of spread of electrical discharge within the brain as by the area where the ictal discharge originates. Classification of seizures

14. Both generalized and partial seizures are further divided into subtypes. For partial seizures, the most important subdivision is based on consciousness, which is preserved in simple partial seizures or lost in complex partial seizures. For generalized seizures, subdivisions are based mainly on the presence or absence and character of ictal motor manifestations. Classification of seizures

15. Simple partial seizures result when ictal discharge occurs in a limited and often circumscribed area of cortex, the epitogenic focus. Almost any symptom or phenomenon can be the subjective (‘aura’)or observable manifestation of a simple partial seizure, varying from elementary motor and unilateral sensory disturbance to complex emotional, psychoillusory, hallucinatory, or dysmnesic phenomena. Clinical features(partial seizures)

16. Clinical featurespartial seizures(simple) Especially common auras include an epigastric rising sensation, fear, a feeling of unreality or detachment, déjà vu and jamais vu experiences, and olfactory hallucinations. Patients can interact normally with the environment during simple partial seizures except for limitations imposed by the seizure on specific localized brain functions.

17. Clinical featurespartial seizures(simple) In the postictal state, a focal neurologic deficit such as hemiparesis (Todd’s paralysis) that resolves over a period of 1/2 –36 hours is manifestation of an underlying focal brain lesion. Clonic movement of a single muscle group may spread to contiguous regions of the motor cortex (Jacksonian march).

19. Clinical featurespartial seizures(complex) Complex partial seizures are defined by impaired consciousness and imply bilateral spread of the seizure discharge, at least to basal forebrain and limbic areas. In addition to loss of consciousness, patients usually exhibit automatisms, such as lipsmacking, repeated swallowing, clumsy perseveration of an ongoing motor task, or some other complex motor activity that is undirected and inappropriate.

20. Clinical featurespartial seizures(complex) Postictally, patients are confused and disoriented for several minutes, and determining the transition from ictal to postictal state may be difficult without simultaneous EEG recording. 70-80% arise from the temporal lobe; foci in the frontal and occipital lobes account for most of the remainder.

21. Generalized tonic-clonic seizures (grand mal) are characterized by abrupt loss of consciousness with bilateral tonic extension of the trunk and limbs (tonic phase), often accompanied by a loud vocalization as air is forcedly expelled across contracted vocal cords (epileptic cry), followed by synchronous muscle jerking (clonic phase). Clinical featuresgeneralized seizures(grand mal)

23. Clinical featuresgeneralized seizures(grand mal) Postictally, patients are briefly unarousable, then lethargic and confused, often preferring to sleep. Many patients report inconsistent nonspecific premonitory symptoms include ill-defined anxiety, irritability, decreased concentration, and headache or other uncomfortable feelings.

24. Indicative clinical features during an attack include pupil dilation, raised blood pressure and heart rate, extensor plantar responses, and central and nail-bed cyanosis. In generalized seizures, the PO2 and pH are lowered, the creatine phosphokinase (CPK) is elevated, and there is a marked elevation of serum prolactin. Clinical featuresgeneralized seizures(grand mal)

26. Clinical featuresgeneralized seizures(absence) Absence seizures have an onset between 4 and 12 years of age. Absence seizures are momentary lapses in awareness that are accompanied by motionless staring and arrest of any ongoing activity. Absence seizures begin and end abruptly; they occur without warning and postictal period. Longer attacks may be accompanied by mild myoclonic jerks of the eyelid or facial muscles, variable loss of muscle tone, and automatisms.

28. Attempting to classify the kind of epilepsy a patient has is often more important than describing seizures, because the formulation includes other relevant clinical data of which the seizures are only a part. The other data include historical information, findings on neurologic examination, and results of EEG, brain imaging, and biochemical studies. Classification of epilepsy

29. The ILAE classification separates major groups of epilepsy first on the basis of whether seizures are partial (localization-related epilepsies) or generalized (generalized epilepsies), and second by cause(idiopathic, symptomatic, or cryptogenic epilepsy). Subtypes of epilepsy are grouped according to the patient’s age and, in the case of localization-related epilepsies by the anatomic location the presumed ictal onset zone. Classification of epilepsy

30. Classification of epilepsy Classification of the epilepsies had been less successful and more controversial than the classification of seizure types.

32. First, to determine if the patient has epilepsy; Second, to classify the type of epilepsy and identify an epilepsy syndrome; Third, if possible, to define the specific underlying cause. Diagnosis

33. Because epilepsy comprise a group of conditions and is not a single homogeneous disorder； because seizures may be symptoms of both diverse brain disorders and otherwise normal brain； it is neither possible nor desirable to develop inflexible guidelines for what constitutes a “standard” or “minimal” diagnostic evaluation. Diagnosis

34. The clinical data from the history and physical examination should allow a reasonable determination of probable diagnosis, seizure and epilepsy classification, and likelihood of underlying brain disorder. Based on these considerations, diagnostic testing should be undertaken selectively. Diagnosis

35. Diagnosis HISTORY A complete history is the cornerstone for establishing a diagnosis of epilepsy. An adequate history should provide a clear picture of the clinical features of the seizures and the sequence in which manifestations evolve; the course of the epileptic disorder; seizure precipitants, risk factors for seizures, and response to previous treatment. In children, developmental history is important.

36. HISTORY In describing the epileptic seizure, care should be taken to elicit a detailed description of any aura. Aura is actually a simple partial seizure that precede many complex partial or generalized seizures. It confirms the suspicion that the seizure begins locally within the brain and it may also provide direct clues about the location or laterality of the focus. Diagnosis

37. HISTORY Information about later events in the seizure must usually be obtained from an observer because of the patient’s impaired awareness or postictal amnesia. The nature of repetitive automatic or purposeless movements, sustained postures, presence of myoclonus, and the duration of the seizure help to delineate specific seizure types or epileptic syndromes. Diagnosis

38. HISTORY Nonspecific postictal findings of lethargy and confusion must be distinguished from focal neurologic abnormalities, such as hemiparesis or aphasia, that point to the hemisphere or seizure onset. Information about risk factors may suggest a particular cause and assist in prognosis. Age at seizure onset and course of the seizure disorder should be clarified, because these features differ in the various epilepsy syndromes. Diagnosis

39. Physical examination Findings on neurologic examination are usually normal in patients with epilepsy, but occasionally may provide etiologic clues. Focal signs indicate an underlying cerebral lesion. Diagnosis

40. Electroencephalography (EEG) EEG is the most important laboratory test in evaluating patients with seizure. It helps both to establish the diagnosis of epilepsy and to characterize specific epileptic syndromes. It may also help in management and in prognosis. Diagnosis

41. EEG Epileptiform discharges are recorded in 30-50% of epileptic patients on the first routine EEG and in 60-90% by the third routine EEG. Sleep, sleep deprivation, hyperventilation, and photic stimulation increase the likelihood of recording epileptiform discharges in some patients. Diagnosis

42. EEG Epileptiform discharges occur in 1-3% of healthy adults and children. Epileptiform discharges occur in 2.7% of adult patients with various illness,but with no history of seizures. Thus, the presence of epileptiform discharges in the appropriate clinical setting strongly supports the diagnosis of epilepsy but does not establish it unequivocally. Diagnosis

43. Long-Term Monitoring Long-term monitoring permits EEG recording for a long time, thus increasing the likelihood of recording seizures or interictal discharges. Two methods: simultaneous closed-circuit television and EEG(CCTV/EEG) monitoring and ambulatory EEG greatly improved diagnostic accuracy and the reliability of seizure classification. Diagnosis

44. CT or MRI They may reveal structural lesions that have caused the seizures or in complex partial seizures , may show hippocampal sclerosis. Diagnosis

45. It is most important to distinguish epilepsy from other causes of transient focal dysfunction or loss of consciousness. Syncope (arrhythmias, carotid sinus hypersensitivity, vasovagal attacks, postural hypotension): there is usually prodromal pallor, nausea, and sweating. Palpitations(心悸)may be experienced with arrhythmias. Differential diagnosis

46. Non-specific seizures (‘pseudoseizures’): hysterical, attention-seeking, feigned seizures are surprisingly common, especially in patients with known epilepsy. The following features help to differentiate a pseudoseizure from an epileptic seizure: pupils, blood pressure, heart rate, PO2, and pH remain unchanged; plantar response are flexor, serum prolactin levels are normal; the EEG shows no seizure activity during the episode and no postictal slowing. Differential diagnosis

47. Transient ischemic attacks (TIA): these can include transient loss of consciousness when the posterior circulation is involved. Hypoglycaemia(低血糖): this can cause behavioral disturbance and seizures. Differential diagnosis

48. Therapy of epilepsy has three goals: To eliminate seizures or reduce their frequency to the maximum extent possible. To avoid the side effects associated with long-term treatment. To assist the patient in maintaining or restoring normal psychosocial and vocational adjustment. Treatment

49. Four key principles of anticonvulsant drug treatment: To establish the diagnosis of epilepsy before starting drug therapy. Therapeutic trials of anticonvulsant drugs intended to establish or reject a diagnosis of epilepsy may yield incorrect diagnosis. To choose the right drug for the seizure type. Absence seizure does not respond to most drugs used for complex partial or generalized tonic-clonic seizures. Treatment

50. Treatment To treat the seizures, rather than the serum drug levels. Control of seizures is activated at different drug levels in different patients. To evaluate one drug at a time. In most cases, seizures can be controlled with a single drug. Therefore, beginning therapy with multiple drugs may expose patients to increased drug toxicity without added therapeutic benefit.