Cerebrospinal fluid neuron-specific enolase following seizures in children: role of etiology

Neuron-specific enolase, a marker for neuronal injury, is elevated following seizures in adults, but relatively few data exist on postictal neuron-specific enolase levels in children. This study measured cerebrospinal fluid (CSF) neuron-specific enolase levels after seizures in 49 consecutive pediatric patients and investigated the role of seizure type, duration, and etiology in influencing neuron-specific enolase. Overall, there was no significant difference in neuron-specific enolase levels between patients with seizures and a control group. However, 4 of the 49 seizure patients (8%) had neuron-specific enolase levels clearly above the normal range. Seizure patients with symptomatic etiologies had significantly increased neuron-specific enolase compared to cryptogenic/idiopathic or febrile seizures. The four individual patients with elevated cerebrospinal fluid neuron-specific enolase all had identified metabolic or genetic etiologies and presented with medically refractory status epilepticus. No individuals with cryptogenic/idiopathic or febrile seizures had abnormal neuron-specific enolase. There was no significant effect of seizure duration or type on cerebrospinal fluid neuron-specific enolase. In contrast to adults, acute seizure-induced neuronal injury in children as detected by neuron-specific enolase is rare and may occur primarily with severe symptomatic etiologies. Children with cryptogenic, idiopathic, or febrile seizures, including status epilepticus, are at relatively low risk for neuronal damage following seizures.     

Cerebrospinal Fluid and Serum Neuron-Specific Enolase Levels After Febrile Seizures

PURPOSE: Neuron-specific enolase (NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizures (FS) cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE. METHODS: Fifty-three patients aged from 6 months to 7 years were enrolled. Among them, 36 patients had generalized seizures, and 17 had partial seizures. The maximal seizure duration was 90 min. Blood and CSF samples for measurement of NSE were obtained immediately after the seizure. NSE was measured using an enzyme immunoassay (EIA). RESULTS: Serum and CSF levels of NSE ranged up to 10 ng/mL, but very high levels were not observed. In patients with partial seizures, the NSE level in the CSF and the ratio of the CSF to serum NSE levels showed a strong correlation with seizure duration. Conversely, there were no correlations between NSE levels and seizure duration in the patients with generalized seizures. CONCLUSIONS: These results indicate that FS seldom cause severe neurologic damage, but prolonged partial seizures may cause slight neuronal injury.     

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997

PURPOSE: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. METHODS: This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. RESULTS: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). CONCLUSIONS: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.     

Cerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure

PurposeWhether repeated brief seizures can cause neuronal damage is controversial. Cerebrospinal fluid (CSF) total tau (T-tau) and phosphorylated tau (P-tau) measurements have been suggested for the diagnosis of Alzheimer's disease, and T-tau may also be a marker of axonal damage and neuronal degeneration. We studied T-tau and P-tau levels and P-tau/T-tau ratio in CSF after epileptic seizures in order to determine whether they are increased after seizures.MethodsA total of 54 patients with tonic–clonic or partial secondarily generalized seizures due to various etiologies were studied and CSF obtained within 48 h after the seizure.ResultsThere were no statistical differences in the levels of T-tau (p = 0.09, ANOVA) or P-tau (p = 0.60) between different etiologic groups or controls. No patients with epilepsy of unknown origin had abnormal CSF T-tau whereas 11 patients with acute or remote symptomatic seizures had abnormal T-tau levels and the P-tau/T-tau ratio showed significant differences between the groups and controls (p = 0.003).ConclusionsEpileptic seizures with unknown etiology did not increase CSF tau levels. Abnormal tau levels were associated with either acute or remote symptomatic seizures with known etiology. The presence of elevated CSF tau increases the probability of symptomatic cause in a patient with a seizure.     

Nonfebrile Illness Seizures: A Unique Seizure Category?

PURPOSE: To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. METHODS: This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.     

Serum and CSF neuron-specific enolase in patients with West syndrome

OBJECTIVE: To determine whether frequent seizures and/or hypsarrhythmia may cause neuronal injury in West syndrome. BACKGROUND: West syndrome is an age-related epileptic syndrome of infancy characterized by clusters of epileptic spasms, a peculiar interictal EEG pattern of hypsarrhythmia, and mental deterioration. Recent clinical studies demonstrated that serum and CSF neuron-specific enolase (NSE)-a marker of neuronal injury-were increased after status epilepticus. METHODS: The authors examined serum and CSF NSE levels in 18 newly diagnosed infants (8.4 +/- 2.2 months) with West syndrome (3 cryptogenic, 15 symptomatic). In patients who showed complete resolution of spasms and disappearance of hypsarrhythmia (responders), additional serum NSE levels were determined several weeks after cessation of seizures. Serum NSE levels were obtained from 28 age-matched infants with normal neurologic development (control group), and 10 infants with an acute neurologic insult. RESULTS: There were no significant differences (p > 0.05) in serum NSE levels between the group with West syndrome (12.9 +/- 3.4 ng/mL) and the control group (13.2 +/- 3.1 ng/mL). The serum NSE value in the group with an acute insult (100.3 +/- 67.4 ng/mL) was significantly higher (p < 0.0001) than that for the West syndrome and the control groups. The mean +/- SD CSF NSE level was 7.3 +/- 3.6 ng/mL, which is similar to the reported CSF NSE levels of Japanese infants without neurologic disease. Thirteen responders showed no significant (p > 0.05) change in serum NSE after cessation of epileptic spasms. CONCLUSION: Normal serum and CSF neuron-specific enolase levels provided no evidence that seizures and/or hypsarrhythmia induced neuronal injury in West syndrome.     

Clinical correlations of occipital epileptiform discharges in children.

OBJECTIVES: To determine the frequency of different causes of occipital epileptiform discharges (OEDs) in children and to analyze the EEG features that help predict epilepsy type and prognosis. METHODS: We identified children with OEDs in the absence of other focal discharges using an EEG database at our center; the presence of generalized spike-wave discharges (GSW) or slowing was not an exclusion criterion. Diagnosis, neurologic status, seizure semiology, and seizure remission status were recorded. RESULTS: Of 90 patients with OEDs, 50 (56%) had symptomatic seizures (18 with cerebral palsy, 11 with cerebral dysgenesis, 8 with genetic abnormalities); 31 (34%) had idiopathic seizures, including 6 with benign childhood epilepsy with occipital paroxysms (BCEOP), 8 (9%) had no seizures; and 1 (1%) had febrile seizures. Only two reported ictal visual symptoms. Eighty-seven percent with background slowing had symptomatic seizures, and 87% with normal backgrounds had idiopathic seizures (p < 0.001). Of 72 children with seizures and adequate follow-up, 28 of 45 (62%) with a normal background experienced seizure remission compared with 10 of 27 (37%) with background slowing (p = 0.04). Twenty of 81 patients with epilepsy had GSW. Twelve (60%) of the 20 GSW-positive patients had idiopathic epilepsy compared with 19 of 61 (31%) without GSW (p = 0.02). CONCLUSIONS: Most epilepsy in referred children with OEDs is symptomatic; syndromes such as BCEOP are rare. Visual ictal symptoms are rare. The presence of GSW or a normal background rhythm correlates with idiopathic seizures and a better prognosis.     

Cerebrospinal fluid somatostatin levels in febrile seizures and epilepsy in children

We analysed the level of cerebrospinal fluid (CSF) somatostatin in children with febrile seizures and epilepsy. In the febrile seizure group (n = 23), the somatostatin level was 83.9 +/- 11.2 pg/ml, which was significantly higher than that of age-matched controls. CSF samples obtained within 3 h of the last seizure had higher somatostatin levels (106.1 +/- 12.4 pg/ml;n = 14) than did the CSF obtained after 3 h (49.4 +/- 15.6 pg/ml;n = 9). The mean somatostatin level in the epilepsy group was 35.3 +/- 4.3 pg/ml (n = 34), and was distributed as follows: 27.6 +/- 3.6 pg/ml in the idiopathic generalized epilepsy group (n = 16), 44.0 +/- 9.4 pg/ml in the symptomatic generalized epilepsy group (n = 13), and 37.2 +/- 10.1 pg/ml in the partial epilepsy group (n = 5). The levels in each group were significantly higher than those in age-matched controls. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons in children with febrile seizures and epilepsy. The finding that patients with convulsive disease had elevated levels of CSF somatostatin suggests that somatostatin release is somehow related to seizure activity. It remains to be determined whether this is due to increased release from over-active excitatory neurons or leakage from damaged or anoxic neurons, secondary to seizure activity.     

戊四氮致痫大鼠脑脊液神经元特异性烯醇化酶的水平测定

目的通过测定戊四氮致痫大鼠脑脊液中的神经元特异性烯醇化酶(NSE)水平的变化,探讨痫性发作与脑损伤之间的关系。方法110只Wistar大鼠分为实验组和对照组。实验组给予戊四氮(PIZ)腹腔注射。根据痫性发作的强度分为轻度组和重度组。用酶联免疫吸附法(ELISA)测定不同痫性发作强度、不同时间点大鼠脑脊液中NSE水平的变化,并与对照组进行对比。结果重度组脑脊液NSE水平在1h、2h、4h、6h均显著高于轻度组和对照组(P<0.01);轻度组脑脊液NSE含量在1h高于对照组(P<0.05),在2h、4h、6h显著高于轻度组;脑脊液NSE水平在痫性发作后1h迅速升高。4h达到高峰,24h恢复到正常水平。结论痫性发作可对大鼠神经细胞造成明显的损害。损害的程度与痫性发作的程度有关。痫性发作后4h可能是进行早期干预、防止脑细胞损伤的时间窗。     

Aborted and refractory status epilepticus in children: a comparative analysis

PURPOSE: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. METHODS: Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications.     

In Whom Does Status Epilepticus Occur: Age-Related Differences in Children

: Purpose: Status epilepticus (SE) is an uncommon but potentially life-threatening seizure. It is most common in children. Little is known about the differences within the pediatric age group in terms of the type of patient seen with SE. Methods: We analyzed the records of 394 children aged 1 month to 16 years who were part of two large studies of pediatric SE conducted in Bronx, New York, and Richmond, Virginia. The 394 children had a mean age of 4.4 years and included 349 (89%) with an initial episode of SE. Results: Status epilepticus was most common in younger children with > 40% of cases occurring in those younger than 2 years. The distribution of causes was highly age dependent. More than 80% of children younger than 2 years had SE of febrile or acute symptomatic origin, whereas cryptogenic and remote symptomatic causes were most common in older children (p <0.001). One hundred fifty-eight (40%) of the cases were known to be previously neurologically abnormal, including 35 (21%) of 169 younger than age 2 years and 123 (55%) of 225 older than 2 years (p <0.001). One hundred seventy-seven (45%) children had a history of seizures including 142 (41%) of the 349 children with a first episode of SE. A history of seizures was present in 34 (20%) of those younger than 2 years and 143 (64%) of those older than 2 years (p < 0.001). The effect of age remained significant even when the analysis was limited to those with SE of cryptogenic or remote symptomatic origin. Conclusions: There is a strong effect of age on the frequency and etiology of SE, as well as on the type of child who has SE. In young children, SE occurs primarily in children who are neurologically normal and with no history of unprovoked seizures. In older children, SE occurs primarily in those who are known to have prior unprovoked seizures and who are often also neurologically abnormal.     

Cognitive outcomes in children who present with a first unprovoked seizure

Purpose: To determine the long‐term cognitive and educational outcomes in children prospectively identified at the time of a first unprovoked seizure. Methods: A cohort of children with a first unprovoked seizure was enrolled and followed for a mean of 15 years. Cognitive function and educational outcomes were determined 10 or more years after the first seizure via standardized neuropsychological tests, school records, and structured interviews. Children with symptomatic etiology were excluded from the analysis. When available, siblings of study subjects were recruited as normal controls. Primary educational outcome was defined as enrollment into special education services or grade repetition. Results: Twenty‐eight percent of (43 of 153) of children with a single seizure and 40% (42 of 105) of children with epilepsy received special education service or repeated a grade (p = 0.05). There was a statistically significant trend in which the children with more seizures tended to require special education or repeat a grade more often (28% in single seizure group vs. 34% in 2–9 seizure group vs. 64% in ≥10 seizure group; p = 0.004). Of 163 subjects who completed neuropsychological testing, children with single seizures tended to score higher than children with epilepsy on Wide Range Achievement Test‐3 (WRAT) reading (p = 0.08), Test of Non‐Verbal Intelligence‐II (TONI‐II) (p = 0.02), and Wechsler Intelligence Scale for Children (WISC)/Wechsler Adult Intelligence Scale (WAIS) (p = 0.07). There was no statistically significant difference between children with a single seizure and sibling controls. Conclusion: The results suggest that children with a single seizure represent a group that is distinctly different from children with epilepsy and are more similar to sibling controls. In contrast, even children with very mild epilepsy have significantly worse educational outcomes.     

Cerebrospinal Fluid Lactate Levels and Prognosis in Status Epilepticus

Despite recent advances in the treatment of status epilepticus (SE), the mortality and morbidity associated with this condition remains high. Although the reasons for this excessive mortality are not known, several factors are suspected, including cerebral ischemia, cardiovascular collapse, toxic stimulation by neurotransmitters and hormones, or toxic products of intermediary metabolism. Cerebral lactic acidosis can cause cortical injury and has been shown to occur with seizures in experimental animals and in a limited number of human studies. We determined cerebrospinal fluid (CSF) and plasma lactate in 29 patients with generalized SE of diverse etiology. CSF was obtained within 12 h of termination of clinical seizure activity. The mean CSF lactate for all SE patients was elevated (3.74 +/- 0.31 mM) as compared with that of normal controls (1.60 +/- 0.10 mM) from non-neurologic patients undergoing spinal anesthesia. In patients who died or had a poor neurologic recovery, CSF lactate level was 5.36 +/- 0.58 mM (9 patients), whereas in 20 patients who showed good recovery CSF lactate level was 3.01 +/- 0.22 mM (p less than 0.005). The results demonstrate that SE causes a significant increase in CSF lactate and suggest that the magnitude of lactate elevation may serve as a predictive indicator of morbidity and mortality.     

Childhood absence epilepsy requiring more than one medication for seizure control

INTRODUCTION: Absence epilepsy is the most common primary generalized epilepsy syndrome encountered in pediatric practice. Treatment is pharmacologically specific and usually successful with a single medication. The objective of this study was to identify any clinical or electroencephalographic features at initial presentation in a consecutive cohort of children with absence epilepsy that may be associated with the need for a second medication. METHODS: A computerized pediatric neurology database (1991-2007 inclusive) was retrospectively searched for all patients with typical absence seizures, 3 Hz spike and wave on EEG and no apparent symptomatic etiology who were over the age of two years at seizure onset with at least one year of follow-up. All such children were then divided into two groups; a) those requiring a single medication for seizure control (Group 1), and b) those requiring two medications for seizure control despite optimal management with the initial medication as determined by serum drug monitoring (Group 2). Clinical and electrographic features evident at diagnosis were then contrasted between Group 1 and 2. RESULTS: Seventy-five children with absence seizures were initially identified with 52 meeting the study's inclusion and none of the exclusion criteria. Of these 52 children, 43 required a single medication for seizure control (Group 1), while 9 required two or more medications for seizure control (Group 2). A significant difference (p < 0.05) was apparent between Group 1 and 2 with respect to gender (16/43 males vs 8/9 males) and mean age of diagnosis (8.19 years +/- 3.00 vs 6.06 years +/- 2.22). Age of onset of seizures, interval duration of seizures prior to treatment initiation, duration of seizures, presence of automatisms, family history, presence of co-morbid conditions and EEG findings were not found to be significantly different between the two Groups. CONCLUSIONS: Male gender and an earlier age of diagnosis is associated with the need for two medications for seizure control in children with absence epilepsy. This observation may suggest the need for more intensive early programmatic follow-up for young male children with newly diagnosed absence epilepsy to effect more rapid attainment of seizure control.     

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.     

Kinetics of Serum Neuron-Specific Enolase and Prolactin in Patients After Single Epileptic Seizures

PURPOSE: To investigate and compare the temporal profile of serial levels of neuron-specific enolase (NSE) and prolactin in serum from patients after single epileptic seizures. METHODS: Measurement of NSE and prolactin by sensitive immunoassays in 21 patients with complex partial seizure (CPSs: n = 11) and secondarily generalized tonic-clonic seizures (SGTCSs; n = 10) during continuous video-EEG monitoring at four different time points (1, 3, 6, and 24 h after ictal event). Statistical analysis was performed by using a repeated-measures analysis of variance (ANOVA) model. RESULTS: Mean+/-SD values for NSE levels (ng/ml) were 12.5 +/-4.4 (1 h), 10.8+/-3.8 (3 h), 11.1+/-4.9 (6 h), and 8.2+/-1.9 (24 h). The corresponding prolactin levels (mU/L) were 1,311+/-1,034, 232+/-158, 237+/-175, and 251+/-98. There was a significant decrease of NSE and prolactin levels over time (p < 0.001). The pair-wise comparison of NSE levels showed significant differences between the time points 1 vs. 24 h (p < 0.001), 3 vs. 24 h (p = 0.007), and 6 vs. 24 h (p = 0.009). In contrast, serum prolactin levels showed a significant difference between 1 vs. 3 h (p < 0.001) only. Most of the NSE levels remained normal after CPSs and SGTCSs. At 1 h after the seizure, only 33% of the subjects had increased NSE, whereas abnormal prolactin levels occurred with a sensitivity of 80%. CONCLUSIONS: In contrast to prolactin, serum NSE is not a sensitive marker of individual seizures. Only some individuals showed an increase of NSE beyond the prolactin-sensitive time frame after a single seizure, and mean NSE levels were not significantly increased compared with those of normal controls.     

PTZ致痫大鼠海马区神经元损伤的研究

目的:为了解癫痫(Epilepsg,EP)发生后大脑海马区的损害情况,本文采用戊四氮诱导建立大鼠癫痫模型, 采用酶标免疫吸附法(EIA)和免疫组化染色法检测NSE的改变,使用电子显微镜研究超微结构的改变,探讨EP后脑组织的损坏情况。方法:雄性SD大鼠54只,随机分为对照组(A=13)及实验组(41只)。实验组腹腔注射(IP)PTZ 50mg/ kg体重1次,对照组IP生理盐水。根据EP发作分级,0-1级7只,视为B组,立即取脑:2级以上发作34只,随机抽样于EP发作后0h(C=10);6h(D=14);24h(E=10)断头。取脑前抽取躯干血,分离海马。A、D组随机抽取3只进行电镜观察。采用EIA法测试血清和海马NSE-值;以S-P免疫组化染色法染色,观察各组大鼠海马的NSE表达。结果:实验组海马和血清的NSE均明显高于对照组:即使无EP大发作,但有兴奋症状的大鼠,NSE亦高于对照组,表明也有脑组织损害。免疫组化染色显示:对照组海马组织几乎未见NSE的表达,即大发作后海马的NSE表达明显增加,但随时间推移而降低。电镜观察发现EP后大鼠海马CA1区的神经元细胞出现水肿、基质密度变淡、微丝溶解消失、细胞器减少、毛细血管周围间隙扩大等明显改变。结论:EP发作对大鼠海马区神经细胞造成了明显的损害。     

Distribution of Epilepsy Syndromes in a Cohort of Children Prospectively Monitored from the Time of Their First Unprovoked Seizure

PURPOSE: To assess the distribution of epilepsy syndromes and their stability in children. METHODS: A cohort of 407 children with a first unprovoked seizure was prospectively recruited and followed up for a mean of 9.4 years. Etiology and epilepsy syndromes were classified by using the International League Against Epilepsy (ILAE) guidelines in the 182 children with two or more seizures. Classification was done both at time of second seizure and at last follow-up. Two-year terminal remission also was analyzed by etiology and epilepsy syndrome. RESULTS: Etiology of epilepsy syndromes was idiopathic in 45 (25%), cryptogenic in 89 (49%), and remote symptomatic in 48 (26%). In the initial classification, 114 (63%) children had a localization-based epilepsy syndrome including idiopathic in 26, cryptogenic in 34, and symptomatic based on localization or etiology in 54. Twenty-one (12%) children had a generalized epilepsy syndrome, including 19 with primary generalized epilepsy. Forty-seven (26%) cases were in the category of undetermined if focal or generalized. At last follow-up, there was a change in either etiology (n = 16) or the final epilepsy syndrome classification (n = 33) or both (n = 15) in 34 (19%) cases. At time of last follow-up, 144 (79%) of the children with epilepsy were in 2-year terminal remission, and 108 (59%) were in 2-year terminal remission without medications. Factors associated with a favorable prognosis included an idiopathic or cryptogenic etiology and having a localization-based idiopathic epilepsy syndrome. CONCLUSIONS: After two seizures, childhood-onset epilepsy can be classified by etiology and epilepsy syndrome. Prognosis is favorable in the majority of cases. However, the apparent syndrome may change with longer follow-up. The ability to classify these cases early in the clinical course is important if they are to be used for prognostic purposes.     

Predictive clinical factors for the differential diagnosis of childhood extratemporal seizures

PURPOSE: To describe predictive clinical factors for the differentiation between childhood frontal lobe epilepsy (FLE) and posterior cortex epilepsy (PCE). METHODS: Two independent, blinded investigators analyzed 177 seizures from 35 children (aged 11 months to 12 years) with extratemporal epilepsy selected by postoperative seizure-free outcome. Semiologic seizure components and different periictal signs were observed. Age at onset, auras, seizure frequency, and nocturnal dominance, as well as surgical and histopathologic data, were collected from medical charts. RESULTS: Twenty patients had FLE, and 15 had PCE. Patients from both groups had daily seizures without significant differences in frequency but with higher nocturnal dominance in children with FLE (p < 0.05). Visual aura, nystagmus, and versive seizure were observed exclusively in the PCE group, whereas somatosensory aura and hypermotor seizures appeared only in FLE. Tonic seizures were significantly more frequent in FLE (p < 0.01), whereas the presence of clonic seizure (FLE; p = 0.07) and postictal nose-wiping (PCE; p = 0.05) showed only a trend to localize the seizure-onset zone. Myoclonic seizures, epileptic spasms, psychomotor seizures, atonic seizures, oral and manual automatisms, as well as vocalization and eye deviation appeared in both groups without significant differences in their frequency. CONCLUSIONS: Characteristic features described in adults' extratemporal epilepsies were frequently missing during childhood seizures, especially in infants and preschool children. Ictal features help only a little in differentiating childhood FLE from PCE. Nocturnal appearance and the type of aura have high localizing value; therefore an accurate history taking is still an essential element of pediatric presurgical evaluation.     

Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study

PURPOSE: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new-onset seizures. METHODS: Subjects were 224 children with new-onset seizures (aged 4-14 years) and 159 siblings (4-18 years). Caregiver's ratings of the behavior were collected 4 times: at baseline, and at 6, 12, and 24 months. During the 2-year period, 163 (73%) children had at least one additional seizure, and 61 (27%) had none. Data were analyzed by using repeated measures analysis of variance both with and without covariates [site, age, gender, race, caregiver education (years), and seizure medications]. RESULTS: On average, children had higher CBCL Total and Internalizing Behavior Problems scores across all times when experiencing recurrent seizures than when not experiencing recurrent seizures (Total Problems, p = 0.041, controlling for demographics and seizure medications). Siblings had significantly lower Total and Internalizing Problems scores than both children experiencing (Total Problems adjusting for covariates, p = 0.0001) and not experiencing recurrent seizures (p = 0.0004). Externalizing Problems scores were not significantly different among children with recurring seizures, children without recurring seizures, and siblings. CONCLUSIONS: Recurrent seizures significantly predicted behavior problems very early in the course of a seizure condition, even when key child, demographic, and seizure variables were controlled. Explanations for these findings include the possibilities that both seizures and behavior problems are caused by an underlying neurological disorder, that seizures per se disrupt behavior, or that children have negative psychological responses to seizure activity.