The ketogenic diet improves recently worsened focal epilepsy

Aim  We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet.
Method  From the 70 patients who received the ketogenic diet during a 3-year period at our institution, we retrospectively selected patients with focal epilepsy. There were 22 children, 13 females and nine males, aged from 5 months to 18 years 6 months (mean 6y 9mo, SD 5y 11mo). Fifteen had symptomatic and seven had cryptogenic focal epilepsy. Seizure frequency 1 week before initiating the ketogenic diet was compared with that at 1 month and at the last visit on the diet.
Results  Eleven patients were responders (defined as reduction of seizures by more than 50%) at 1 month. Responders were higher ( p =0.046) in the group with a recent worsening of seizures than in those with stable seizure frequency. Seven patients were still seizure-free at 6 months on the diet. Tolerability was excellent in 10 patients. Five patients stopped the diet because of early side effects.
Interpretation  The ketogenic diet may be a valuable therapeutic option for children with pharmacoresistant focal epilepsy, particularly those with a recent deterioration of seizure control and neurological status. Because of its rapid effect, the ketogenic diet may be a useful support to intravenous emergency drugs in such a situation.     

Efficacy of the ketogenic diet: Which epilepsies respond?

We report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty-four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty-nine (48%) of 61 patients were responders at 3 months. Two children became seizure-free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic-atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet.     

Ketogenic diet in patients with myoclonic-astatic epilepsy.

For more than 80 years, the ketogenic diet has been used as an alternative to antiepileptic drugs for patients with refractory epilepsy. Myoclonic-astatic epilepsy in early childhood is one of the malignant epilepsy syndromes that often proves refractory to antiepileptic drugs treatment. Objective. In this prospective study we assess the efficacy and tolerability of the ketogenic diet in patients with myoclonic-astatic epilepsy. Material and methods. Between March 1, 1990 and August 31, 2004, 30 patients who met diagnostic criteria of myoclonic-astatic epilepsy were seen at our department. Eleven of them were placed on the ketogenic diet using the Hopkins protocol and were followed for a minimum of 18 months. Results. The children had previously received a mean of 5.2 different antiepileptic drugs and were on a mean of 2.2 antiepileptic drugs when the diet was started. Eighteen months after initiating the diet, six of the patients (54.5%) remained on the diet. Two patients (18%) were seizure-free, two (18%) had a 75-99% decrease in seizures, and the remaining two children (18%) had a 50% to 74% decrease in seizures. The first two patients were tapered off the diet after remaining seizure-free, without antiepileptic drugs for several years. In the two patients who had sporadic seizures, antiepileptic drugs were reduced to one, and in the last two the seizure frequency was significantly reduced. No differences in seizure control were found when compared for age, sex, or seizure type. Five of our patients discontinued the ketogenic diet in less than 3 months (four because of lack of effectiveness and one because of persistent vomiting). Conclusion. The ketogenic diet is a promising therapy for patients with myoclonic-astatic epilepsy, with over half the children showing a > 50% reduction in seizures, and seizure-freedom in 18%. In drug resistant cases of myoclonic-astatic epilepsy, the diet should be considered early in the course of this syndrome and not as a last resort.     

Ketogenic diet in adolescents and adults with epilepsy

PurposeThe ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy.MethodTwenty-nine adult and adolescent patients (mean age 32 years, range 11–51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet.ResultsFifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13–35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects.ConclusionThe ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment.     

Focal ictal beta discharge on scalp EEG predicts excellent outcome of frontal lobe epilepsy surgery

PURPOSE: To determine whether a focal beta-frequency discharge at seizure onset on scalp EEG predicts outcome of frontal lobe epilepsy (FLE) surgery. METHODS: We identified 54 consecutive patients with intractable FLE who underwent epilepsy surgery between December 1987 and December 1996. A blind review of EEGs and magnetic resonance images (MRIs) was performed. Lesional epilepsy is defined as presence of an underlying structural abnormality on MRI. RESULTS: Overall, 28 (52%) patients were seizure free, with a mean follow-up of 46.5 months. Presence of a focal beta-frequency discharge at seizure onset on scalp EEG predicted seizure-free outcome in lesional (p = 0.02) and non-lesional (p = 0.01) epilepsy patients. At least 90% of patients who had either lesional or non-lesional epilepsy were seizure free if scalp EEG revealed a focal beta discharge at ictal onset. Moreover, logistic regression analysis showed that focal ictal beta pattern and completeness of lesion resection were independently predictive of seizure-free outcome. Ictal onset with lateralized EEG activity of any kind and postresection electrocorticographic spikes did not predict surgical outcome (p > 0.05). CONCLUSIONS: Only about 25% of FLE surgical patients have a focal beta-frequency discharge at seizure onset on scalp EEG. However, its presence is highly predictive of excellent postsurgical seizure control in either lesional or non-lesional FLE surgical patients.     

Efficacy of the ketogenic diet in focal versus generalized seizures

Most reports of the ketogenic diet have focused on its efficacy for generalized seizures. Few data are available regarding its effect on focal seizures. We retrospectively studied patients (mean = 7.5 years of age) with medically intractable epilepsy treated by the ketogenic diet. The predominant seizure types in each patient were classified as generalized (100 patients) or focal (34 patients) based on ictal electroencephalograms (EEGs) or seizure semiology and interictal EEG. A seizure reduction of more than 50% compared with baseline was seen in nine patients (27%) with focal seizures and 46 patients (46%) with generalized seizures at 3 months, in 10 patients (30%) with focal seizures and 46 patients (46%) with generalized seizures at 6 months, and in eight patients (24%) with focal seizures and 42 patients (42%) with generalized seizures at 12 months. Differences were not significant. Outcome tended to be better in patients younger than 12 years of age compared with the older age group, but the difference was significant at 6 months only. Our results suggest that some patients with intractable focal epilepsy may respond favorably to the ketogenic diet and that this option should be considered if epilepsy surgery is not possible.     

A population‐based study of long‐term outcome of epilepsy in childhood with a focal or hemispheric lesion on neuroimaging

Purpose: To evaluate long‐term seizure outcome in children with epilepsy and a focal or hemispheric neuroimaging abnormality. Methods: All children (<18 years and residing in Olmsted County, Minnesota) with new‐onset epilepsy diagnosed between 1980 and 2004 and a single focal lesion on neuroimaging were identified by review of the Rochester Epidemiologic Project database. Outcomes were divided into three categories: (1) seizure freedom for 1 or more years at last follow‐up, (2) ongoing seizures but not medically intractable epilepsy, and (3) medically intractable epilepsy or undergoing epilepsy surgery. We also evaluated the proportion who achieved seizure control without surgical intervention and whether lesion type predicted intractability. Key Findings: Of the 359 children with newly diagnosed epilepsy, 37 (10%) had a focal or hemispheric lesion on neuroimaging. Median age of diagnosis was 89 months (25th percentile 26 months, 75th percentile 142 months) and at follow‐up was 137 months (25th percentile 95 months, 75th percentile 211 months). Eighty‐three percent of children with malformations of cortical development, 67% with mesial temporal sclerosis, 33% with encephalomalacia, and 50% with vascular malformations had intractable epilepsy at follow‐up or underwent resective surgery for medically intractable epilepsy. Among the different etiologies, presence of encephalomalacia predicted the lowest likelihood of medical intractability or undergoing surgery (p < 0.01). At final follow‐up, 24 (65%) of our entire cohort was seizure free. Following surgery, seizure freedom was achieved in 80% with mesial temporal sclerosis, 67% with encephalomalacia, 67% with vascular malformation, and 50% with malformations of cortical development. There was no statistically significant difference between the different etiologies on neuroimaging and seizure freedom after surgery. Twelve children (32%) achieved seizure freedom with medical management alone. Significance: Focal lesions on neuroimaging confer a high risk of medical intractability among children with new‐onset epilepsy. However, 32% of this cohort achieved seizure remission with medical management alone, including 58% with encephalomalacia and 33% with mesial temporal sclerosis.     

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial

BACKGROUND: The ketogenic diet has been widely and successfully used to treat children with drug-resistant epilepsy since the 1920s. The aim of this study was to test the efficacy of the ketogenic diet in a randomised controlled trial. METHODS: 145 children aged between 2 and 16 years who had at least daily seizures (or more than seven seizures per week), had failed to respond to at least two antiepileptic drugs, and had not been treated previously with the ketogenic diet participated in a randomised controlled trial of its efficacy to control seizures. Enrolment for the trial ran between December, 2001, and July, 2006. Children were seen at one of two hospital centres or a residential centre for young people with epilepsy. Children were randomly assigned to receive a ketogenic diet, either immediately or after a 3-month delay, with no other changes to treatment (control group). Neither the family nor investigators were blinded to the group assignment. Early withdrawals were recorded, and seizure frequency on the diet was assessed after 3 months and compared with that of the controls. The primary endpoint was a reduction in seizures; analysis was intention to treat. Tolerability of the diet was assessed by questionnaire at 3 months. The trial is registered with ClinicalTrials.gov, number NCT00564915. FINDINGS: 73 children were assigned to the ketogenic diet and 72 children to the control group. Data from 103 children were available for analysis: 54 on the ketogenic diet and 49 controls. Of those who did not complete the trial, 16 children did not receive their intervention, 16 did not provide adequate data, and ten withdrew from the treatment before the 3-month review, six because of intolerance. After 3 months, the mean percentage of baseline seizures was significantly lower in the diet group than in the controls (62.0%vs 136.9%, 75% decrease, 95% CI 42.4-107.4%; p<0.0001). 28 children (38%) in the diet group had greater than 50% seizure reduction compared with four (6%) controls (p<0.0001), and five children (7%) in the diet group had greater than 90% seizure reduction compared with no controls (p=0.0582). There was no significant difference in the efficacy of the treatment between symptomatic generalised or symptomatic focal syndromes. The most frequent side-effects reported at 3-month review were constipation, vomiting, lack of energy, and hunger. INTERPRETATION: The results from this trial of the ketogenic diet support its use in children with treatment-intractable epilepsy. FUNDING: HSA Charitable Trust; Smiths Charity; Scientific Hospital Supplies; Milk Development Council.     

Prognostic factors in neocortical epilepsy surgery: multivariate analysis

PURPOSE: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery. METHODS: One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status >or=2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors. RESULTS: The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p<0.05). Multivariate analysis revealed that a focal lesion on MRI (p=0.003), correct localization by FDG-PET (p=0.007), and localized ictal onset on EEG (p=0.01) were independent predictors of a good outcome. CONCLUSIONS: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.     

The ketogenic diet: a review of the experience at Connecticut Children's Medical Center

We undertook a retrospective analysis of epilepsy patients referred and treated for more than 6 months with the ketogenic diet during 1994-1999 at Connecticut Children's Medical Center. Outcome measures included antiepileptic drug number, seizure frequency, electroencephalogram background/paroxysmal activity, and adverse effects at 6 months and 1 year on the ketogenic diet. The final cohort included 24 of 48 referred patients (mean age, 6.5 years; range = 1-15 years of age). The etiology of epilepsy was equally divided between idiopathic and cryptogenic epilepsy and symptomatic epilepsy. Intention to treat analysis revealed that 35% (17 of 48) achieved more than 50% reduction in seizure frequency, and 8.5% (four of 48) were seizure-free by 6 months. A sustained 50% or greater reduction at 1 year was observed in 23% (11 of 48), and the same 8.5% (four of 48) remained seizure-free. None of these improvements were statistically related to age (P = 0.97), sex (P = 0.78), or epilepsy etiology (P = 0.80). The number of antiepileptic drugs used per patient decreased. Electroencephalogram at 1 year demonstrated an improvement in background in 31% (five of 16 patients) and a reduction in paroxysmal features in 37.5% (6 of 16 patients). Most adverse effects were mild, self-limited, and occurred early. Hyperuricemia (more than 6 mg/dL) was more persistent in three patients.     

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.     

Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?

It has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less-restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information was obtained from 27 patients who made this dietary change from four different institutions. Ten (37%) patients had ≥10% additional seizure reduction with the KD over the MAD, of which five became seizure-free. The five children who did not improve on the MAD failed to improve when transitioned to the KD. A higher incidence of improvement with the KD occurred for those with myoclonic-astatic epilepsy (70% vs. 12% for all other etiologies, p = 0.004), including all who became seizure-free. These results suggest that the KD probably represents a "higher dose" of dietary therapy than the MAD, which may particularly benefit those with myoclonic-astatic epilepsy.     

Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet

Aim. We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Methods. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Results. Two of the three children responded well to the ketogenic diet. One of these patients became seizure‐free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Conclusion. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.     

Surgical treatment for epilepsy

Nearly one-third of patients with newly diagnosed epilepsy will develop medically refractory seizure disorders. The initial response to antiepileptic drug therapy is highly predictive of long-term outcome. Patients with intractable epilepsy may have a progressive disorder that is medically, physically, and socially disabling. Surgical resection of the epileptogenic zone or lesional pathology, or both, may significantly reduce seizure tendency in selected patients. The present review supports the position that early and effective epilepsy surgery may not only render the patient with intractable partial epilepsy seizure-free, but also allow the individual to become a participating and productive member of society. Patients with surgically remediable epileptic syndromes should be identified early in the evaluation and treatment of their seizure disorders. Favorable candidates for focal cortical resection include individuals with medial temporal lobe epilepsy and partial seizures related to selected lesional pathology, e.g. primary brain tumor or vascular anomalies. In conclusion, surgical treatment of intractable partial epilepsy has been shown to compare favorably to antiepileptic drug therapy. Individuals rendered seizure-free may experience a significant improvement in quality of life. Patients who fail to respond to initial antiepileptic drug therapy should be “triaged” to a presurgical evaluation. Ictal semiology combined with structural magnetic resonance imaging and the electroclinical correlation may permit identification of candidates for early and effective surgical treatment.     

The ketogenic diet for intractable epilepsy in adults: preliminary results

PURPOSE: Little is known concerning the efficacy and adverse effects of the ketogenic diet in adults with refractory epilepsy. This review reports preliminary results in 11 adults prospectively treated with the diet who had previously failed to gain seizure control with two or more medications and/or surgery. METHODS: Eleven patients nine women, two men), median age, 32.2 years (range, 19-45 years) were treated with the ketogenic diet with a 4:1 ratio with fluid restriction. Six patients had symptomatic partial epilepsy, and five had symptomatic generalized epilepsy. The diet was administered in addition to antiepileptic medication by a multidisciplinary team geared exclusively to adult patients. Medications were not changed while on the diet. Seizure frequency at 8-month follow-up was compared with frequency during a baseline period. RESULTS: At 8 months of follow-up, three patients had a 90% seizure decrease, three patients had a 50-89% decrease in seizure frequency, one patient had <50% seizure decrease, and four patients discontinued the diet. Of the four patients who discontinued the diet, two had no appreciable change in their seizures despite high ketone levels. Two patients were unable to maintain persistent ketosis at home, despite having done so in the hospital. All seizure types responded to the diet. Common adverse effects included constipation and menstrual irregularities in women. Most patients reported a subjective improvement in concentration. Serum cholesterol and triglycerides increased while on the diet as well as cholesterol high-density lipoprotein (HDL) ratios. CONCLUSIONS: The ketogenic diet shows promise in both adult generalized and partial epilepsy. Persistent ketosis was possible in adults, and the diet was tolerable for most patients. Further study assessing the efficacy of the ketogenic diet, and the cognitive and long-term effects is ongoing.     

Tuberous sclerosis complex and the ketogenic diet

PURPOSE: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early-onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described. METHODS: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5-year period at Johns Hopkins Hospital and Massachusetts General Hospital. RESULTS: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a >50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a >90% response. Five children had at least a 5-month seizure-free response. Diet duration ranged from 2 months to 5 years (mean, 2 years). CONCLUSIONS: In this limited-duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC.     

Role of EEG as a monitoring tool in patients with glucose transporter type I deficiency syndrome (GLUT1-DS) on ketogenic diet

Rationale

Glucose transporter type I deficiency syndrome (GLUT1-DS) is the fourth most frequent single-gene epilepsy refractory to standard antiepileptic drugs. Multiple seizure types and variable electrographic findings are reported. Ketogenic diet is expected to result in the complete resolution of the epileptiform activity.

Methods

A retrospective chart review of patients with GLUT1-DS on ketogenic diet between December 2012 and February 2022 was done. Analysis of the EEGs prior to and during the ketogenic diet was done.

Results

34 patients on ketogenic diet were reviewed. Ten had clinical diagnosis of GLUT1-DS, and seven of them had genetic confirmation. 71% were female. The average age at seizure onset was 13.85 m.o. (range: 3–60, SD ±20.52), at diagnosis was 44.57 m.o (range: 19–79), and at the onset of ketogenic diet was 46.43 m.o. (range: 20–83). 29 months (range: 13–38) delay between symptoms onset until diagnosis was noticed. At the diagnosis 100% reported seizures: 71% myoclonic, 57% generalized motor, 57% absence, 28% atonic, and 14% focal motor. Also, 71% abnormal eye movements, 57% ataxia, and 28% intolerance to fasting. 86% had normal brain MRI. 71% had abnormal EEG. All were on ketogenic diet, and four on classical (1.75:1–2.25:1 ratio). Six were clinically seizure-free after the ketogenic diet. EEG features included notch delta, focal spike and wave, and generalized spike/polyspike and wave. One patient had bilateral independent centrotemporal spikes. Spikes showed high and very high amplitude in all of them (>200 μV). The variation of the spike index decreased in three patients but increased in two.

Conclusion

Ketogenic diet is the choice treatment for patients with GLUT1-DS. Electrographic features could show worsening after initiation of the ketogenic diet even with seizure control. EEG did not prove to be a reliable tool for adjusting KD in our cohort. Centrotemporal spikes have not been reported in patients with GLUT-1 DS.     

Discontinuation of antiepileptic drugs after successful epilepsy surgery

OBJECTIVE: To evaluate the frequency and risk factors for seizure recurrence subsequent to antiepileptic drug (AED) withdrawal in patients who underwent surgical treatment for intractable partial epilepsy and were rendered seizure-free. METHODS: The outcome of discontinuation of AED medication was studied retrospectively in 210 consecutive patients who were rendered seizure-free after epilepsy surgery performed between 1989 and 1993. RESULTS: Medical therapy was reduced in 96 patients and discontinued in 84 patients. The seizure recurrence rate after complete AED withdrawal was 14% and 36% at 2 and 5 years. In contrast, only 3% and 7% of the 30 patients who did not alter AED treatment after surgery had recurrent seizures in the same time intervals. After AED discontinuation, seizures tended to recur more often in patients with normal preoperative MRI studies compared with those with focal pathology. However, this difference did not reach significance. Intraoperative electrocorticography, extent of surgical resection, postoperative EEG, and seizure-free duration after surgery were not predictive of seizure outcome after AED withdrawal. CONCLUSIONS: AED withdrawal was associated with seizure recurrence in a significant portion of patients rendered seizure-free by epilepsy surgery. Patients with a normal preoperative MRI study showed a tendency for higher seizure recurrence, whereas the duration of seizure-free postoperative AED treatment interval did not significantly influence the seizure recurrence rate. These results will prove useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.     

How long does it take for epilepsy to become intractable? A prospective investigation

OBJECTIVE: To determine prospectively when in the course of epilepsy intractability becomes apparent. METHODS: Data are from a prospective cohort of 613 children followed for a median of 9.7 years. Epilepsy syndromes were grouped: focal, idiopathic, catastrophic, and other. Intractability was defined in two ways: (1) 2 drugs failed, 1 seizure/month, on average, for 18 months (stringent), and (2) failure of 2 drugs. Delayed intractability was defined as 3 or more years after epilepsy diagnosis. RESULTS: Eighty-three children (13.8%) met the stringent and 142 (23.2%) met the two-drug definition. Intractability depended on syndrome (p < 0.0001): 26 (31.3%) children meeting stringent and 39 (27.5%) meeting the 2-drug definition had delayed intractability. Intractability was delayed more often in focal than catastrophic epilepsy (stringent: 46.2 vs 14.3%, p = 0.003; two-drug: 40.3 vs 2.2%, p 相似文献   

Cognitive function in preschool children after epilepsy surgery: rationale for early intervention

PURPOSE: The detrimental effect of frequent early seizures on the cognitive potential of children is a significant clinical issue. Epilepsy surgery in childhood offers a good prognosis for seizure control and improved developmental outcome. We studied the postoperative outcome and the developmental velocity after surgery and analyzed risk factors for developmental delay in 50 consecutive preschool children treated surgically for severe epilepsy at ages 3 to 7 years. METHODS: Pre- and postoperative developmental quotients (DQs) were analyzed with analysis of variance; stepwise linear regressions were performed on preoperative DQs and on a difference score between post- and preoperative DQs to determine risk factors for preoperative development and factors influencing postoperative development. RESULTS: Of the 50 patients, 70% were retarded, with IQ < 70; 16% were of average intelligence, with IQ ranging from 85 to 115. Age at seizure onset and extent of lesion were predictive variables for preoperative cognitive development. Six to 12 months after surgery (early postoperative phase), 66% were seizure free (Engel outcome class I), 26% had substantial to worthwhile seizure reduction (classes II and III), and 8% were unchanged (class IV). Forty-one (82%) children showed stable velocity of development; three children showed gains of >/=15 IQ points; three had developmental decline (loss of >/=10 IQ points), which was transient in two children; and three children moved from not assessable to assessable. At last follow-up (6 months to 10 years after surgery), 11 children showed IQ/DQ gains of >/=15 IQ points. Gains in IQ were observed only in seizure-free children and were stable over time. Shorter duration of epilepsy was significantly associated with a postoperative increase in DQ. CONCLUSIONS: (a) Substantial global mental delay is common in young children treated for epilepsy with surgery; (b) In most patients, postoperative development proceeded at a stable velocity; (c) Catch-up development may occur but only in seizure-free patients; (d) Substantial cognitive losses were noted in only one child. and (e) Early seizure control stabilized developmental velocity in this patient cohort.