Advancement Of Research In Age Dependent Epileptic Encephalopathy

Age Dependent Epileptic Encephalopathy(ADEE) is the most frequently refractory epilepsy in pediatrics, including Ohtahara Syndrome(OS),West Syndrome(WS) and Lennox-Gastaut Syndrome(LGS). Though different clinically and electroencephalogramically, they have the common characteristics: (1) Inclining to attack in a certain age period; (2) Special, frequent and small-scale comprehensive seizure; (3) Persistent and serious electroencephalogram anomaly;(4)Different types of etiopathogenises;(5)Often accompanied by mental underdevelopment; (6)Showing severe seizure, difficult to cure, often with developmental disorder; (7) Course of disease is progressing, and the three kinds of syntheses mutate with aging. Their epidemiology, etiopathogenisis, clinical manifestation, electroencephalogram characteristic, diagnosis, therapy and prognosis are detailed respectively in this article.The incidence of WS is relatively higher in ADEE patients, followed by LGS, while OS is relatively low. Most of OS's etiopathogenises are organic and inactive brain damage, whereas WS can be caused by many factors, such as perinatal period,neurocutaneous syndrome, inheritance metabolic disease or apomorphosis disease, central nervous system infection and developmental malformation of brain, etc; and LGS can be caused by various brain damages and inheritant metabolic diseases. It is reported in the past few years that the plasma amino acid standard and dysimmunity and abnormal glucose metabolism might have certain relation with the invasion of LGS.The beginning age of OS seizures is extremely early, all in three months after birth , 75% within 1 month, the capital type of which being the rigidity spasm, often showing front opisthotonos state, and mostly seizuring subsequently, with high frequency, One convulsion from 10 times to 300 times, or for 10~20 series. Patients suffer from the serious psychomotor developmental lag; About 85% ~90% of those with WS onset within 12 months after birth, with the crest-time of 4~8 months. When seizuring, the muscle of two sides of neck, trunk and limb symmetrically contracts suddenly, and the symptom can be roughly divided into three patterns: the flexion pattern, extended pattern, and mixed pattern. But in fact, most patients suffer from either more than one type, or three types side by side, or one after another, often accompanied by others, such as atonic seizures and tonic seizure and mero-motion seizure or atypical absences, etc. Normotrophic patients originally, after the illness, grows comparatively protruding psychomotor developmental lag; LGS generally happens between 4 months and 11 years old, mostly in 1~5 years old. Patients with LGS already have hypoevolutism and abnormal appearance of nervous system before falling ill. Mode of epileptic seizure is multiformity, Tonic seizure is very common and the most characteristic type, atonic seizures, myoclonic seizure and atypical absences also can be seen frequently. The onset mode also can change from one type to another in the course of disease. LGS is often accompanied by various levels of dysgnosia, especially before 2 years old, and often merges into behavior disorders.The major characteristic of the EEG of OS is persistent suppression-burst(S-B) EEG, namely 2-5-second suppression and 1-3-second bursting, appearing alternately, even becoming periodical. The EEG's characteristic of WS is hypsarrhythmia(HPYS),which is the most notable EEG's pattern under the awake alert and oriented state of WS early stage. Different variations of HYPS have been found in recent years. In a same patient and record, typical HYPS can co-exist with the variation. The EEG's waveform of typical LGS shows asystematic and bilateral synchronism 1.5~2.5Hz slow spikeand waves(SSW). In the changing process of OS into WS, EEG is changed into HYPS from S-B at about 3-6 months old. And then HYPS develops to SSW at about 1 years old. The three successive changes of electroencephalograms is closely related to awake and sleep cycle.According to age of onset, clinical mode of onset, specific EEC's change and psychomotor hypoevolutism, diagnosis of typical OS and WS is not difficult. LGS's clinical manifestation is relatively complex, and its diagnosis a dynamic process.OS is the most incurable among the three types of ADEE, and many drugs, such as VitB6, Valproate sodium(VPA), Benzodiazepine(BZP), Acethropan(ACTH) and steroid , etc., are used to cure this disease, and the curative effect is all not good. In the new anti-epileptic drugs, Vigabatrin(VGB) hopefully becomes the choice drug curing OS. Zonisamide(ZNS) probably play a significance role during the treatment. Thyrotropin releasing hormone(TRH) or its similar things is effective to some cases; For WS, In the hormone drug,ACTH has been constantly applied as choice drug, and the clinical practice of Adrenal cortex hormone(ACH) has gradually reduced, and TRH also certainly has the effect; In traditional anti-epileptic drugs, VPA, Nitrazepam(NZP) and Clonazepam(CZP) serve for common purposes; while in new anti-epileptic drugs, advance in research that VGB's curative effect for WS has been the most important in recent years. Felbamate(FBM), ZNS, Topiramate(TPM) and Lamotrigine(LTG) also have been reportedly applied in clinic, but the curative effect isn't definite. Moreover, VitB6, Immune globulin and Ketogenic diet shows certain effect in relieving WS's clinical seizure. Surgical operation may be used for ineffective cure with drug, but only for proper indications; In drug treatment of LGS, VPA is the choice drug. When VPA can not reducing the frequency of seizure we can add TPM or only with TPM. LTG can reduce tonic seizure and drop attack, and does not cause other serious onset at the same time. The curative effect of adding FBM has gotten approval, which can be regarded as another kind of effective cure for LGS. Moreover we still can use Gammaglobulin intravenous injection, Ketogenic diet and TRH or its similar things as adjunctive therapy of LGS. The operation of corpus callosum incised partly as palliative operation can reduce drop attack and general grandmal.There are other reports that Vagal stimulatin(VNS) has good effect on LGS.Difficult cure and prognosis mala are the common characteristics of the three types of ADEE, among which OS's prognosis is the most severe, with it's seizure difficult to control, and case fatality high, especially in the early stage of the disease; Intellect hysteresis of most patients with WS is serious, and about half of patients' seizure stop before 3 years old, and others develop into LGS or accompanied by other types of seizure; Tonic seizure of LGS probably last until adult.