Bilateral reductions in hippocampal volume in adults with epilepsy and a history of febrile seizures

OBJECTIVES: To examine the degree and frequency of reductions in hippocampal volume in patients with temporal lobe epilepsy with and without a history of febrile seizures. METHODS: In vivo measures of hippocampal volume were computed from three dimensional gradient echo (FLASH) images in 44 patients undergoing comprehensive evaluations for epilepsy surgery. Twenty one patients (48%) reported a history of febrile seizures. The volumes from these patients were compared with those from 23 patients without a history of febrile seizures and 34 healthy controls. RESULTS: The febrile seizure group had significant reductions in volume, both ipsilateral (30% decrease) and contralateral (15% decrease), to the EEG seizure focus. Twelve of 18 patients with febrile seizures exhibited clinically significant ipsilateral volume reductions, defined as volumes falling 2 SD below the mean obtained from the control sample. Only four of 19 patients without febrile seizures exhibited this degree of reduction. No significant correlations were found between seizure variables (for example, duration of epilepsy, seizure frequency) and ipsilateral reductions in volume. However, a significant inverse correlation (r=-0.45, P<0.05) between seizure frequency and the volume of the hippocampus contralateral to the seizure focus was found in the febrile seizure group. CONCLUSION: These results suggest that a history of febrile seizures is associated with the finding of a smaller hippocampus on the side ipsilateral to the subsequent temporal lobe focus whereas chronic factors seem to be be related to pathology contralateral to the seizure focus.     

The monolayer technique: evolution or revolution in cervico-uterine cytology]

After their first febrile seizure, 180 children were prospectively monitored to provide data for a quantitative and qualitative analysis of the factors affecting the risk of recurrence of febrile seizures and to evaluate the influence of recurrences on the outcome. Of these children, 153 had subsequent febrile episodes and were included in the risk-factor analysis. The outcome was evaluated after a 2-year follow-up in 156 children. Each febrile episode increased the risk of recurrence by 18%. Each degree of increase in temperature (Celsius) during subsequent infections almost doubled the risk of recurrence. Age, sex, the type of initial seizure, the temperature during the initial seizure, or a family history of febrile seizures or epilepsy did not influence the recurrence rate significantly. The results indicate that procedures that minimize the probability of febrile infections would decrease the risk of recurrences of febrile seizures.     

Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long-term results after two different dosage regimens

OBJECTIVE: To determine whether the recently published guidelines on neuroimaging in patients with new-onset seizures are applicable to children. METHODS: We carried out a retrospective analysis of 107 neurologically normal children (excluding children with simple febrile seizures) who had undergone neuroimaging when they presented to the emergency department with a possible "first seizure." RESULTS: Eight of the 107 children had nonepileptic events (gastroesophageal reflux, syncopal event, rigor). Of the remaining 99 children, 49 had provoked seizures (complicated febrile seizure, meningo-encephalitis, toxic or metabolic abnormalities), and 50 had unprovoked seizures. A total of 19 children had brain abnormalities identified on computed tomography (CT) scan; 7 received further investigation or intervention as a result of CT scan findings (2 with tumors, 3 with vascular anomalies, 1 with cysticercosis, and 1 with obstructive hydrocephalus). CT scan abnormalities requiring treatment or monitoring were more frequently seen in children with their first unprovoked seizure (P < .01) and in those children whose seizure onset had been focal or who had focal abnormalities identified on postictal neurologic examination (P < .04). CONCLUSION: In a child, a seizure in the setting of a fever rarely indicates the presence of an unexpected CT scan lesion requiring intervention.     

Influence of head trauma on outcome following anterior temporal lobectomy

BACKGROUND: There is controversy in the literature regarding the importance of risk factors in developing epilepsy and seizure outcome following anterior temporal lobectomy. Some of the existing studies may be biased because of patient selection and limitations in determining predisposition. OBJECTIVE: To investigate the role of risk factors for epilepsy in determining outcome following anterior temporal lobectomy. PATIENTS AND METHODS: We identified 102 patients in a consecutive surgery series for epilepsy from a tertiary center with a minimum of 1-year postoperative follow-up. Risk factors for epilepsy were determined prospectively on at least 3 occasions before anterior temporal lobectomy. Risk factors investigated were a history of febrile convulsions, family history of epilepsy, significant head trauma, history of meningitis, history of encephalitis, or significant perinatal insult. Foreign tissue lesions on magnetic resonance imaging was also included if an anterior temporal lobectomy was performed for presumed dual pathologic findings (hippocampus and lesion). Outcome was determined using Engel's classification. For statistical analysis we used successive logistic regression analysis, chi(2) test, Fisher exact test, and t test. RESULTS: Of the 102 patients, 13 had no identified risk factor for epilepsy, 49 had 1 identified risk factor, and 40 had more than 1. Frequencies were 39 febrile convulsions (15 complex febrile convulsions), 29 head trauma, 22 with lesions seen on magnetic resonance imaging, 12 history of meningitis, 2 history of encephalitis, 19 family history of epilepsy, and 4 perinatal insult. Seventy-one (70%) were classified as Engel's class I, with 56 patients continuously free of seizures at follow-up. Those without risk factor were as likely to be rendered free of seizures following anterior temporal lobectomy as those with a risk factor (P = .27). No risk factor alone or in combination was correlated with complete freedom from seizures following anterior temporal lobectomy, but the presence of head trauma, alone or in combination, was correlated with continued seizures following anterior temporal lobectomy (P = .03; odds ratio, 2.6). Better outcomes were not seen in those with head trauma before the age of 5 years (P = .57). These findings did not change if all those with lesions on magnetic resonance imaging were excluded in the analysis. Those with a history of head trauma were as likely to have pathologic evidence of mesial temporal sclerosis as others (P = .82). CONCLUSIONS: Patients with a history of significant head trauma are less likely to become free of seizures following anterior temporal lobectomy. No other risk factor correlated with a statistically significant greater or lesser chance of freedom from seizures. This information may be used in preoperative counseling of patients.     

Problematic standards: improving organizational performance through the assess and improve phases

Since 1987, we have diagnosed 10 patients, 4 males and 6 females, aged 2-11 years at the last evaluation, who all met the following criteria of severe myoclonic epilepsy in infancy (SMEI): generalized or unilateral long-lasting febrile clonic seizures in the first year of life; the subsequent appearance of myoclonic seizures and other types of seizure (partial seizures, atypical absences and convulsive status epilepticus); and neuropsychological deterioration for a certain period. Family histories of epilepsy and febrile seizures could be traced in 1 and 3 cases, respectively. None of them had previous personal history of brain insult. Electroencephalographic (EEGic) recordings in febrile seizure stage were normal; and continuous prophylaxis with phenobarbital failed to prevent the recurrence of febrile seizures. EEG studies in myoclonic stage showed generalized spike-and-waves, polyspike-and-waves, focal abnormalities and/or photosensitivity. The seizures were highly resistant to antiepileptic drugs. Our experiences suggested that comedication of valproic acid, clonazepam and carbamazepine may be most effective in treatment of the diverse seizures including myoclonic seizures, myoclonic-tonic-clonic seizures, atypical absences and partial seizures. Myoclonic seizures and atypical absences diminished in parallel to a clear-cut decrease in generalized abnormalities on EEG in 4 cases aged more than 7 years. However, the partial seizures, secondarily generalized seizures and status epilepticus were still present. Further investigations should aim to identify the underlying etiology and to search more effective treatment.     

Predictors of epilepsy in children who have experienced febrile seizures

We examined the frequency of development of afebrile seizures in 1706 children who had experienced at least one febrile seizure and were followed to the age of seven years. Epilepsy developed by seven years of age in 20 per 1000 (2 per cent), and another 10 per 1000 had at least one afebrile seizure that did not meet our definition of epilepsy. In children whose neurologic or developmental status was suspect or abnormal before any seizure and whose first seizure was complex (longer than 15 minutes, multiple or focal) epilepsy developed at a rate 18 times higher than in children with no febrile seizures (92 vs. 5 per 1000; P less than 0.001). In the largest group with febrile seizures, those previously normal with noncomplex first febrile seizures, epilepsy developed in 11 per 1000; this rate, although moderate, was greater than that for children with no febrile seizures (P = 0.027). Prior neurologic and developmental status and characteristics of the first febrile seizure are important predictors of epilepsy after febrile seizures.     

Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats

PURPOSE: Retrospective studies suggest that adult patients with intractable epilepsy may have a history of febrile seizures in childhood. Risk factors for a febrile seizure may include the rate of increase in the core temperature (T-core), its peak (Tmax), the duration of the temperature increase, or an underlying brain pathology. Recently, neuronal migration disorders (NMD) have been diagnosed with increasing frequency in patients with epilepsy, but the link between NMD, febrile seizures, and epilepsy is unclear. We studied rat pups rendered hyperthermic to ascertain the incidence of seizures, mortality, and extent of hippocampal cell loss in each group. METHODS: We exposed 14-day-old rat pups with experimentally induced NMD (n = 39) and age-matched controls (n = 30) to hyperthermia (core body temperature > 42 degrees C). RESULTS: The incidence of hyperthermia-induced behavioral seizures and mortality rate were significantly higher in rats with NMD than in controls (p < 0.05). The longer duration of hyperthermia resulted in a higher incidence of behavioral seizures and higher mortality rate (p < 0.05). In rats with NMD, hyperthermia resulted in hippocampal pyramidal cell loss independent of seizure activity; the extent of neuronal damage correlated positively with the duration of hyperthermia. In control rats, occasional neuronal loss and astrocytosis occurred only after prolonged hyperthermia. CONCLUSIONS: In immature rats, NMD lower the threshold to hyperthermia-induced behavioral seizures and hyperthermia in the presence of NMD may cause irreversible hippocampal neuronal damage.     

Treatment of febrile seizures with intermittent clobazam

Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean = 23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range = 1 to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean = 16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 degrees C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p < 0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.     

Temperature, age, and recurrence of febrile seizure

OBJECTIVE: Prediction of a recurrent febrile seizure during subsequent episodes of fever. DESIGN: Study of the data of the temperatures, seizure recurrences, and baseline patient characteristics that were collected at a randomized placebo controlled trial of ibuprofen syrup to prevent febrile seizure recurrences. SETTING: Two pediatric hospitals in the Netherlands. PATIENTS: A total of 230 children with an increased risk of febrile seizure recurrence. MAIN OUTCOME MEASURE: Seizure recurrence during a subsequent fever episode. RESULTS: A total of 509 episodes of fever were registered with 67 recurrences; 35 (52%) recurrences within the first 2 hours after fever of onset had a lower median temperature (39.3 degrees C) than 32 (48%) after more than 2 hours of fever (40.0 degrees C, P<.001). Poisson regression analysis resulted in 3 univariably significant (P<.05) predictors of a recurrence of seizure during a subsequent episode of fever. In a multivariable model, they were corrected for their correlation: interval between the last previous seizure and fever of onset less than 6 months (relative risk= 1.3 [95% confidence interval: 0.8-2.4]), age at fever of onset (relative risk=0.7 [95% confidence interval: 0.5-1.0] per year increase) and temperature at fever of onset (relative risk = 1.7 [95% confidence interval: 1.1-2.8] per degree Celsius increase). CONCLUSIONS: Half of the recurrent seizures occur in the first 2 hours after fever of onset of a subsequent fever episode. If seizure recurs at a later time, the temperature at seizure is higher compared with recurrences occurring in the first 2 hours of fever. Young age at fever of onset, high temperature at fever of onset, and high temperature during the episode of fever are associated with an increased risk of a recurrent febrile seizure at the moment that a child with a history of febrile seizures has fever again.     

The duration of febrile seizures and peripheral leukocytosis

In 203 consecutive children with febrile seizures, no clear association (odds ratio = 1.0 [95% CI, 0.9-1.1], P = .59) was found between seizure duration and blood leukocytosis (> or = 15.0 x 10(9) cells/L). Increased leukocyte counts may be misinterpreted because of seizure duration. In children with febrile seizures, leukocyte counts should be used to evaluate the underlying cause of fever.     

Low sodium levels in serum are associated with subsequent febrile seizures

Fever plays an important role in causing disturbances in fluid and electrolyte balance. Hyponatraemia has been thought to enhance the susceptibility to seizures associated with febrile illnesses in childhood. We have studied serum electrolyte levels in children with simple and complicated febrile convulsions. Sodium levels were lower in those children with complicated convulsions in comparison with those having simple convulsions (136.07 +/- 3.06 mmoll-1, mean +/- SD, n = 42, and 137.62 +/- 2.63 mmoll-1, n = 71, respectively; p < 0.01, Student's t-test). The sodium concentrations were lowest in children with repeated seizures (134.20 +/- 2.30 mmoll-1, n = 15) compared with children having simple (p < 0.01, ANOVA, Duncan's test) or other complicated types of febrile convulsions: focal seizures (137.08 +/- 3.82 mmoll-1, n = 12, p < 0.01), seizures lasting longer than 15 minutes (138.00 +/- 2.45 mmoll-1, n = 5, p < 0.05) and children over 5 years (136.70 +/- 2.06 mmoll-1, n = 10, p < 0.05). Serum potassium levels showed no statistically significant differences between the patient groups. Our results show that hyponatraemia may increase the risk for multiple convulsions during the same febrile illness.     

Pathogenic role of glutamate in hyperthermia-induced seizures

Hyperthermia induces seizures in both humans and rodents, but the underlying mechanism remains unknown. The present study showed that hyperthermia, causing rapid increase in body temperature, increases the concentration of glutamate (Glu) released into a cortical perfusate before onset of seizures in rats and that this increase in Glu concentration correlated with a decrease in seizure threshold temperature. These results indicate that increased cortical extracellular Glu induced by hyperthermia contributes to onset of seizures. The same mechanism may be involved in clinical seizures induced by fever in patients with febrile convulsions or epilepsy.     

Quantitative analysis of Epstein-Barr virus load by using a real-time PCR assay

BACKGROUND: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. OBJECTIVE: To determine whether epilepsy duration is related to HF atrophy. Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. RESULTS: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures.     

Convulsions with meningiomas: incidence and significance

In a study of a consecutive series of 127 surgically treated meningiomas, it was found that 29% of the patients had reported with convulsions as their initial symptom. In this group, surgical excision of the meningioma stopped the convulsions in about half of the patients, but the others continued to have seizures after their operations. Among those patients with meningiomas who did not have preoperative convulsions, about one-sixth (15 patients) developed postoperative seizures. Patients in both groups required prolonged anticonvulsant medication. Factors predisposing to the occurrence of postoperative seizures were the site of the tumor, faulty surgical technique, and a preoperative history of seizures.     

Rhabdomyolysis in transplant patients

In a retrospective analysis of all our patients with seizure onset prior to age 16 years, 25 patients with primary generalized tonic (n = 10) or tonic-clonic (n = 15) seizures were identified. These patients constituted 5.7% of the total seizure patient population in our institute between the ages of 1 month and 16 years. The natural history of generalized tonic-clonic seizures is known to be benign; however, that of isolated primary generalized tonic seizures is not clear. Therefore, an attempt was made to characterize the patients suffering from primary generalized tonic seizures and determine their outcome. Analysis of our patient population shows that both seizure types are characterized by early onset of generalized seizures that appear in normally developed children with a normal electroencephalographic background. The children usually respond quickly to antiepileptic drugs. A long-term follow-up (mean period of 7.6 years) was possible in 84% of the patients, and showed that 95% of them were seizure free at the end of the follow-up period. There was no significant difference between the two groups in regard to age of onset, family history, and seizures at follow-up. In conclusion, the natural history of patients with generalized tonic seizures is similar to the benign course of those with generalized tonic-clonic seizures.     

Familial resemblances in disgust sensitivity and animal phobias

We present 100 children diagnosed with epilepsy who were seizure-free for more than 1 year and still on monotherapy of antiepileptic drugs (AEDs). We matched each child with a healthy classmate and performed neuropsychological testing and EEG before and after complete withdrawal of the AEDs. The withdrawal phase lasted 3 months, but the dose decrease was individualized for each patient. Three to 4 months after complete withdrawal of the drug all patients were reassessed. Patients with seizure relapse are excluded from the study. Seventeen patients are regarded as dropout, 11 because of seizure relapse and six because of protocol violation. The remaining 83 patients were treated with carbamazepine (n = 56), valproic acid (n = 17), or phenytoin (n = 10). Serum concentrations of the AEDs were measured using peak plasma levels that were taken immediately before or after psychological testing. We used neuropsychological tests to assess psychomotor function and "central" cognitive processing such as information processing or memory function. We found significant improvement attributable to drug withdrawal on only one of the cognitive tests, namely, psychomotor speed, suggesting that the impact of AED treatment on higher-order cognitive function is rather limited. In addition, we found group differences between the epilepsy group and the control group at baseline that persisted after drug withdrawal. Subsequent analysis showed some factors that may have contributed to these group differences. First, patients with a former diagnosis of absence seizures show lower scores both at baseline and after drug withdrawal. We may assume that the seizure propensity has not disappeared completely in these patients. Some evidence is found that phenytoin may have a different cognitive profile than carbamazepine, with more impairment on tests that measure motor and mental speed. Again, this impairment persists after drug withdrawal.     

Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures

Forty children (23 boys, 17 girls) with centrotemporal spikes (rolandic focus) with and without seizures (mean age 8.4 years +/- 4.8 SD), and 40 healthy controls matched for age, sex, and socioeconomic status were assessed for their neuropsychological, intellectual, and behavioral outcome. Compared with the controls, patients were significantly impaired in their IQ, visual perception, short-term memory, in their psychiatric status and in some subtests in a fine motor performance task. No significant differences could be computed for a simple finger-motor speed exercise or a linguistic performance test. In patients, deficits in IQ were significantly correlated with frequency of spikes in the EEG, but not with frequency of seizures, lateralization of the rolandic focus, or time since rolandic focus was diagnosed. It was concluded that a rolandic focus is not as benign as once thought.     

Video game-related seizures: a report on 10 patients and a review of the literature

OBJECTIVE: To further describe the features, postulated pathophysiology, treatment, and outcome of seizures occurring while playing or watching video games (video game-related seizures (VGRS)). DESIGN: We evaluated retrospectively 10 patients with VGRS seen by us and reviewed 25 reported cases. RESULTS: The 35 patients ranged in age from 1 to 36 years (mean: 13.2); and 26 subjects (74%) were male. Eight individuals (29%) had prior infrequent nonfebrile seizures, 4 (11%) had febrile convulsions, and 2 (6%) had a family history of epilepsy. VGRS consisted of generalized tonic-clonic seizures in 22 of 35 individuals (63%); absences in 2 (6%); simple partial seizures in 6 (19%); complex partial seizures in 4 (11%); and other manifestations in 4. Neurologic examination and computed tomographic and magnetic resonance imaging scans were normal. Electroencephalograms demonstrated generalized or focal, interictal or ictal epileptic patterns in 11 of 21 patients (52%) and photoparoxysmal responses in 17 of 32 (53%). Eleven of 15 individuals (73%) treated with video game (VG) abstinence alone, 3 of 6 who received anticonvulsants but played VGs, and 7 of 12 treated with combined VG abstinence and anticonvulsants had no further seizures. CONCLUSIONS: We postulate that a special convulsive susceptibility of selected neurons in striate, peristriate, infratemporal, and posterior parietal cortices to particular visual stimuli plays a major role in VGRS. VG abstinence is the treatment of choice of VGRS. Anticonvulsant medication is suggested only for those individuals who continue to play VGs or suffer from seizures triggered by other, unavoidable visual stimuli, or from unprovoked attacks.     

Fenestration of porencephalic cysts to the lateral ventricle: experience with a new technique for treatment of seizures

BACKGROUND: Porencephalic cysts are brain cavities resulting from perinatal vascular occlusion and are commonly associated with severe neurological deficits and medically intractable epilepsy. Thirty-seven children presenting to the University of Münster with intractable seizures because of a porencephalic cyst were treated by uncapping and fenestration of these cysts to the lateral ventricle between 1978 and 1992. We conducted the following study to determine the efficacy and safety of the uncapping and fenestration procedure for the treatment of seizures. METHODS: We reviewed all cases retrospectively and assessed the outcome of these patients with regard to seizures, paresis, and perioperative complications. RESULTS: Of 37 children, 23 (62%) were seizure-free postoperatively. Nine patients (24%) had a reduction of seizures and five children (14%) remained unchanged. Of 30 patients with preoperative hemiparesis, 11 (30%) improved after the operation. The leading postoperative problem was a subcutaneous/subgaleal cushion of CSF, which affected 12 children (12 of 37). A dural patch covering the iatrogenic dural defect could not prevent or reduce postoperative CSF leakage, but prolonged the postoperative fever period. Postoperative fever occurred in 36 children (36 of 37) and was caused by an aseptic meningitis. CONCLUSIONS: Children with intractable seizures and porencephalic cysts benefit from uncapping and cyst fenestration to the lateral ventricle. Concomitant perioperative complications are mild and are easily treated.     

A meta-analytic review of the preventive treatment of recurrences of febrile seizures

OBJECTIVE: To assess the efficacy of various medications in the prevention of recurrent febrile seizures. STUDY DESIGN: A meta-analysis of all published randomized, placebo-controlled trials of the preventive treatment of febrile seizures published in English; 45 articles were found, but only 9 trials were randomized and placebo-controlled--4 using phenobarbital; 3, diazepam; 1, pyridoxine; and 1, phenytoin. In one of the phenobarbital trials, valproate was also compared with placebo. RESULTS: The risk of recurrences was significantly lower in children receiving continuous phenobarbital therapy than placebo (odds ratio 0.54, 95% confidence intervals 0.33 to 0.90, p = 0.017). The odds ratio for recurrences in the valproate group was 0.09, 95% CI 0.01 to 0.78, p = 0.011. No difference in the risk was found for recurrences between children receiving intermittent diazepam and placebo (odds ratio 0.81, 95% CI 0.54 to 1.22, p = 0.31). The risk for recurrences in children receiving pyridoxine or phenytoin did not differ from the risk among children receiving placebo. Four children would have to be treated with valproate (95% CI 2 to 11) or eight children would have to be treated with phenobarbital (95% CI 5 to 27), continuously, to prevent one febrile seizure. CONCLUSIONS: Because both agents found to be effective in prevention of recurrent febrile seizures have known adverse effects, prophylaxis of febrile seizures cannot be recommended.