Change In Seizure Frequency Research Articles

Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet

Objective The high-fat ketogenic diet has long been used to treat refractory childhood seizures, but whether there is a relation between the degree of ketosis and effectiveness of seizure control remains unclear. Frequent measurements of plasma ketones are difficult in children so the goal was to determine the utility of breath acetone as a marker of systemic ketosis and seizure control in children given the ketogenic diet because of seizures refractory to medication. Methods In experiment I, breath acetone and plasma ketones were assessed every 2 h during an 8-h test day in seven children. In experiment II, a preliminary assessment of the possible relation between breath acetone and seizure frequency was made over 14 d in five children and one adolescent on the ketogenic diet. Results Breath acetone was positively and curvilinearly related to plasma acetone ( r 2 = 0.99, P < 0.0001), plasma acetoacetate ( r 2 = 0.89, P < 0.0001), and plasma β-hydroxybutyrate ( r 2 = 0.94, P < 0.0001). No significant relation was found between breath acetone and seizure frequency or change in seizure frequency. Conclusions Breath acetone is indicative of systemic ketosis while on the ketogenic diet. However, owing to the wide range of seizure types and plasma acetone, more subjects will be needed to determine whether there is a clear link between breath acetone and seizure frequency or decreased seizure frequency while on the high-fat ketogenic diet.

Efficacy and tolerability of antiepileptic drugs in an Omani epileptic population

Objective The aim of this hospital-based study is to get an insight into the efficacy and tolerability of antiepileptic drugs (AED) in Omani epileptic patients. Patients and methods All Omani patients (aged 14 years and above) suffering from epileptic seizures for at least 2 years and followed-up by board-certified neurologists in Sultan Qaboos University Hospital (SQUH) were evaluated. The treatment retention rate since first visit at SQUH and over the last 2 years was used as primary efficacy measure of AED therapy. Change in seizure-frequency and side effect profiles were also assessed. Results In this population of 203 confirmed epileptic patients, generalized tonic-clonic (40%) and partial seizures (39%) were most commonly observed, idiopathic/cryptogenic origin (81%) being the most frequent encountered origin. Sixty one percent of the patients were controlled with an AED in monotherapy and overall 34% of patients could be successfully maintained on monotherapy during the whole follow-up period at SQUH (median 6 years). The treatment retention rates for carbamazepine (CBZ) at a daily dose of 400–600 mg, sodium valproate (VPA) at a daily dose of 500–1000 mg, and phenytoin (PHT) at a daily dose of 300 mg, in monotherapy over the total follow-up period was 51, 50, and 21%, respectively. In contrast, over the last 2 years these rates were highest for VPA (91%) followed by CBZ (83%) and PHT (73%). Adverse drug reactions were recorded in 67% of patients, and were most commonly encountered with VPA. Conclusions Despite a higher adverse effect profile for VPA, long-term treatment with CBZ and VPA appeared to be equally effective in terms of treatment retention rates and seizure control.

Clinical experience with levetiracetam in idiopathic generalized epilepsy according to different syndrome subtypes

Clinical experience in open‐label studies and anectodal reports suggest that levetiracetam is effective in generalized epilepsy. In this open‐label prospective study, 19 patients (3 men, 16 women) affected by idiopathic generalized epilepsy were followed for at least 6 months following the introduction of levetiracetam. Patients were categorized according to syndrome subtype: juvenile myoclonic epilepsy (8), juvenile absence epilepsy (5), childhood absence epilepsy (4), and eyelid myoclonia with absences (2). Eleven patients received levetiracetam as monotherapy, eight as add‐on therapy. Effectiveness was demonstrated in 18 patients: 13 became seizure‐free (five juvenile myoclonic epilepsy, five juvenile absence epilepsy, three childhood absence epilepsy), and five achieved significant reductions in seizure frequency (three juvenile myoclonic epilepsy, one childhood absence epilepsy, one eyelid myoclonia with absences). Only one patient experienced no change in seizure frequency (eyelid myoclonia with absences). Clinical improvement was accompanied by EEG abnormality suppression or reduction. Levetiracetam was well tolerated; no patient reported side‐effects.

Long‐term Deep Brain Stimulation for Refractory Temporal Lobe Epilepsy

dial temporal lobe onset. One patient had a bilateral regional temporal lobe onset with predominant involvement of the left side. One patient had a left-sided regional medial temporal lobe onset. Six out of the seven patients had a > 50% reduction of interictal spikes during the initial AHDBS trial period. In one patient who showed very infrequent spiking, seizure frequency that had significantly decreased was used as a criterion for implantation. All patients were implanted with an internal generator. The mean follow up in these patients was 14 months (range: 5.5‐21 months). One patient has been free of complex partial seizures (CPS) for 1.5 years and has been tapered off two antiepileptic drugs (AEDs). Three of the seven patients have a ≥50% reduction in seizure frequency: one of the three patients is seizure free during the day, and two of the three patients have been tapered off one AED. Two of the seven patients have a reduction of 25% of seizure frequency but have still been tapered off two AEDs; one of these patients had bilateral seizure onset and is currently being revised for bilateral AHDBS. In one patien,t no change in seizure frequency occurred. None of the patients report side effects. DISCUSSION

Effect of stress related to the 9/11/2001 terror attack on seizures in patients with epilepsy

Stress facilitates seizures in patients with epilepsy. The frequency with which this occurs is uncertain. Estimates range widely, from 14 to 67% of patients affected,1–5 mainly because there is no uniform definition of stress. One way of bypassing the problem of the definition of stress is to examine the effects on seizures of an event that is generally recognized as stressful. The 9/11/2001 terrorist attack was such an event in the United States. In the current study, we examined the effect of 9/11 attack-related emotional stress on seizures among patients with epilepsy in an area directly involved in one of the attacks, Washington, DC, by comparing seizure frequency before and after the attack. In addition, because we had studied the association of subjectively perceived stress with seizures in the same patients before 9/11, we compared the change in seizure frequency following 9/11 with patients' own assessment of stress as a seizure precipitant. Cognitively normal adult patients with epilepsy seen consecutively in the Georgetown University Hospital (GUH) Epilepsy Clinic between 9/12 and 12/20/01 were evaluated. GUH is 3 miles from the Pentagon, the Washington target of the 9/11/2001 attack. Greater Washington area residents present …

Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy

To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy. A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. Following a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin 600 mg/day administered twice daily (BID) or three times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing > or =50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population. Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID (p < or = 0.0001) and 44% for pregabalin BID (p < or = 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo (p < or = 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia. Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice daily or three times daily schedule with similar efficacy and tolerability results.

Group psychoeducation as treatment for psychological nonepileptic seizures

There is no consensus for the type(s) of treatment(s) that may be effective or ineffective for psychological nonepileptic seizures (PNES). We provided an open-ended group psychotherapy program to 10 patients with PNES, including a disorder-specific psychoeducation treatment component in the first 10 weeks. Seizure frequency and questionnaire responses were examined pre- and posttreatment in all 7 of 10 individuals who completed the majority of the psychoeducational sessions. Four individuals experienced no change in seizure frequency; in three of these this was due to a cessation of events at treatment initiation. Two individuals experienced a decline; and one, an increase, in seizure frequency. Significant decreases were reported in posttraumatic ( P=0.003) and dissociative ( P=0.04) symptoms and emotionally based coping mechanisms ( P=0.03). There was also a trend toward improved quality of life ( P=0.07). Experience/expression of anger remained stable. Psychoeducation may be an effective method of treating PNES and may improve coping strategies and reduce PNES-associated psychopathology in some patients. Additional controlled studies on larger samples are needed.

Vagus nerve stimulation therapy: 5-year or greater outcome at a university-based epilepsy center

Objective: This retrospective study documented long-term outcome of patients receiving vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Methods: Medical charts of 28 patients implanted for 5 years or longer were reviewed for changes in seizure frequency after 1 year of VNS therapy and at follow up, which ranged from 5 to 7 years. Numbers of antiepileptic drugs (AEDs) taken by the patients were also computed at 1 year and follow up. One patient had died and one had discontinued VNS therapy; data were available for 26 patients. Results: The median percent change in seizure frequency from baseline increased from −28% ( P=0.0053, Wilcoxon signed-rank test) at 12 months to −72% ( P<0.0001) at follow up. Some patients whose seizure frequency was not reduced during the initial 12 months of VNS therapy did experience reductions in seizure frequency during the follow-up period. Conclusion: In this retrospective study, the effectiveness of VNS therapy increased over time. Physicians should be aware that response to VNS therapy may be delayed for some patients.

Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy.

Epilepsy surgery can result in complete seizure remission rates of upto 80% in patients with mesial temporal sclerosis and unilateral seizures. The seizure-free rate after surgery for patients with extratemporal nonlesional epilepsy has ranged between 30% and 40%. Some patients with medically refractory localization-related epilepsy cannot be offered surgical resection because of inadequate localization of the epileptogenic zone, documentation of bilateral ictal onsets, or functionally important areas of cortex that prohibit resection. The short-term rate of complete remission with medications in temporal lobe epilepsy is poor. Less is known about remission rates in patients who are not surgical candidates. In this study, we evaluated the outcome of medical treatment in patients with medically refractory partial epilepsy who were evaluated for possible epilepsy surgery but deemed to be inadequate surgical candidates. A retrospective chart review and telephone survey with a self-rating questionnaire were completed for all patients who underwent epilepsy surgery evaluation but were not ultimately offered surgical treatment at the University of Michigan from 1990 through 1998. We assessed changes in seizure frequency and type, imaging characteristics, ictal recordings, interim medication history, and subjective changes in quality of life. Thirty-four subjects were available for follow-up study, at an average of >4 years after surgical evaluation. A significant reduction in seizure frequency was noted at the time of follow-up compared with that at the time of surgical evaluation. Of patients, 21% achieved seizure remission and remained seizure free for an average of 2.5 years. Four of the seven seizure-free patients attributed their remission to new antiepileptic drugs (AEDs). On a global self-rating item, 15 of 34, or 44%, felt more or much more satisfied with their lives, and 41% felt their quality of life was stable. A surprisingly large number of patients we surveyed, with refractory partial epilepsy not eligible for surgical management, reported reduced seizure frequency at follow-up, and 21% were seizure free. Our findings suggest that the long-term prognosis in patients with refractory partial epilepsy who are not surgical candidates may be more positive than might be generally expected.

Effect of vagus nerve stimulation on adults with pharmacoresistant generalized epilepsy syndromes

Introduction: Although vagus nerve stimulation (VNS) therapy is approved for the treatment of partial onset seizures, its efficacy for generalized seizures has not been fully evaluated. This Investigational Device Exemption assessed the outcome of VNS therapy among patients with generalized epilepsy syndromes. Methods: Sixteen patients with pharmacoresistant generalized epilepsy syndromes and stable antiepileptic drug (AED) regimens were implanted with the VNS therapy device and were evaluated for changes in seizure frequency and type between baseline and follow-up of 12–21 months. Results: The patients experienced a statistically significant overall median seizure frequency reduction of 43.3% ( P=0.002, Wilcoxon signed rank test) after 12–21 months of VNS therapy. Types of seizures that may involve a fall or collapse decreased with reductions in the frequency of myoclonic (60% reduction, n=9; P=0.016, Wilcoxon signed rank test), tonic (75% reduction, n=8, NS), atonic (98.6%, n=3, NS), and clonic seizures (86.7%, n=1, NS). Conclusion: The benefits of reduced seizure frequency and reduced risk of injury merit consideration of VNS therapy for patients with pharmacoresistant generalized seizure syndromes.

Quality of Life after Vagus Nerve Stimulation for Intractable Epilepsy: Is Seizure Control the Only Contributing Factor?

We assessed the impact of vagus nerve stimulation on a cohort of patients with intractable epilepsy. A 1-year prospective trial of vagus nerve stimulation for intractable epilepsy was done in 26 patients. Seizure frequency, anti-epileptic drugs, and quality of life were assessed using QOLIE-89, ELDQOL, and a Likert scale of impact of treatment. Seizures were reduced by more than 50% in 19% of the patients, by less than 50% in 46%, and were unchanged in 35% of them. Antiepileptic drugs were reduced in 43% of the patients. There was a significant improvement in the mean overall QOLIE-89 score and other measures of quality of life, but these did not correlate with changes in seizure frequency. Subjective improvement occurred in 84% of the patients. The quality of life improves in some patients following vagus nerve stimulation for intractable epilepsy. The favorable effects of this treatment may be attributable to additional factors besides seizure control which in this study was modest.

Levetiracetam monotherapy for elderly patients with epilepsy

We retrospectively identified 14 elderly patients with a history of partial seizures who received levetiracetam (LEV) monotherapy. Patients began LEV either as first line therapy ( n=5) or were converted to LEV monotherapy ( n=9) after failing prior antiepileptic medications (AEDs). Thirteen patients continued on LEV monotherapy for at least 6 months. One patient was lost to follow-up. Eight patients (61.5%) became seizure free. Four patients who began LEV as a first line therapy became seizure free, whereas the remaining four patients who converted to LEV after they failed their previous AEDs became seizure free. Four patients (30.7%) had more than a 50% seizure reduction of seizures. Only one patient had no significant change in seizure frequency after started on LEV. The total dosages used to control seizures were 500–3000 mg/day, (mean 1839.2 mg/day). LEV monotherapy can be effective and well tolerated in this group of patients. A prospective, larger, double blind monotherapy study is needed to confirm this finding.

Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy

Purpose: To evaluate the long-term clinical usefulness of levetiracetam (LEV, Keppra ® 1 Keppra is a registered trademark of UCB S.A. 1 ) as add-on therapy in patients with refractory epilepsy. Methods: Data for all 1422 patients with refractory epilepsy treated with LEV during the development program were analyzed for changes in seizure frequency per week, seizure freedom, and adverse events. Results: Median percent reduction from baseline in seizure frequency per week over the whole treatment period was 39.6%, and no decrease over time was observed within each cohort exposed to LEV for durations ranging from 6 to 54 months. The median treatment period was 399 days (range 1–8 years). The proportion of responders during the first 3 months of LEV treatment was 39.2%. This proportion remained stable at 6 months (36.1%). Overall, 38.6 and 20.1% of patients had reductions in seizure frequency of at least 50 and 75%. Sixty-five (4.6%) patients were seizure-free over their entire treatment period, compared with 167 (11.7%) and 126 (8.9%) during their last 6 and 12 months of follow-up. Ninety-seven (19.8%) of 491 patients who received only one other antiepileptic drug (AED) in addition to LEV were seizure-free during their last 6 months. The proportion of patients who reduced their number of concomitant AEDs was 14.4% (205 patients), while 5.5% (79 patients) were treated with LEV only at the end of follow-up. Accidental injury (28.0%), infection (26.6%), headache (25.8%), somnolence (23%), asthenia (22.6%), and dizziness (18.9%) were among the most common adverse events. Conclusion: LEV offers sustained efficacy in patients with refractory partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials.

Prednisone therapy in pediatric epilepsy

Steroids are often an effective treatment for the West’s syndrome. There have been few reports of steroid use in children with epilepsy outside the first year of life. I report my experience with prednisone for the treatment of older children with intractable epilepsy. Twenty-eight children (17 boys, 11 girls) aged 18 months to 10 years with intractable epilepsy were studied. Prednisone 1 mg/kg/day for 12 weeks (6 weeks daily and 6 weeks alternate therapy) was prescribed in addition to their regular antiepileptic medications. The parents kept seizure diaries, and the patients were regularly assessed for seizure frequency and side effects. The follow-up period was for 1 to 5 years. Thirteen patients (46%) became seizure free on prednisone and another 18 (40%) had a significant decrease in seizure frequency. Five patients (19%) had no change in seizure frequency. The best outcomes were seen in the absence group in which six out of seven patients became seizure free and in the Lennox-Gastaut syndrome group in which seven out of 10 became seizure free. Side effects were uncommon and included weight gain in five patients and aggression in four patients. Prednisone therapy is a safe and effective adjunctive treatment for epilepsy. It should be considered as an alternative treatment for older children with intractable generalized epilepsy who have failed conventional antiepileptic therapy.

NEUROACTIVE STEROIDS, RELAXATION, AND SEIZURE CONTROL

Neuroactive steroids alter the excitability of membrane-bound receptors in the nervous system and have a modulatory role in the stress response and in epileptogenic activity. These changes can be detected in brain as well as in plasma. The resulting rapid (<1 min) action of neuroactive steroids might explain the success of some "alternative" approaches in seizure control. Design requirements for research to adequately examine relaxation training in epileptic patients, as well as corresponding changes in neuroactive steroid levels and seizure frequency, are described.

Oxcarbazepine: a review of its use in children with epilepsy.

Oxcarbazepine (Trileptal, Timox) is structurally related to carbamazepine and has anticonvulsant activity. Studies suggest that the anticonvulsant activity of oxcarbazepine is mediated via the blocking of neuronal ion channels. In patients aged <18 years, the efficacy of oxcarbazepine monotherapy was similar to that of phenytoin in children with partial onset or generalized tonic-clonic seizures in a 48-week trial. Additional supporting findings demonstrated that 43-71% of patients with partial onset, generalized or undetermined epilepsy were seizure free after oxcarbazepine monotherapy (mean dosage 27.7-50 mg/kg/day; duration 1-5 years). In contrast, one small nonblind trial showed more patients treated with oxcarbazepine monotherapy than with carbamazepine monotherapy had recurrent seizures during 16 months of therapy (although the conclusions that can be drawn from this trial are limited). As adjunctive therapy, oxcarbazepine was significantly better than placebo at reducing seizure frequency in children and adolescents with refractory partial onset seizures with or without secondary generalization: the median percentage change in partial onset seizure frequency was 35% vs 9%, respectively, during 16 weeks of therapy. In noncomparative trials of adjunctive oxcarbazepine (mean dosage of 34.5-56.7 mg/kg/day), 7-11% of patients with partial onset or generalized seizures were seizure free during treatment, and 20-54% had seizure reductions of > or=50%. Oxcarbazepine was generally well tolerated during monotherapy and adjunctive therapy; 2.5% and 10% of patients withdrew from well controlled trials of oxcarbazepine monotherapy and adjunctive therapy. Oxcarbazepine monotherapy was better tolerated than phenytoin and events observed in oxcarbazepine-treated patients were transient. Oxcarbazepine metabolism is largely unaffected by induction of the cytochrome (CYP) P450 system. However, oxcarbazepine can inhibit CYP2C19 and induce CYP3A4 and CYP3A5, thereby interfering with the metabolism of other drugs (e.g. phenytoin). In addition, oxcarbazepine decreases plasma levels of oral contraceptives and alternative contraceptive methods should be used. In conclusion, oxcarbazepine (as both monotherapy and adjunctive therapy) has shown efficacy in the treatment of partial onset seizures in children with epilepsy. Nevertheless, the generally favorable tolerability profile and relatively low potential for drug interactions of oxcarbazepine make it a valuable option in the treatment of childhood epilepsy.

Long-term effects of 24-month treatment with vagus nerve stimulation on behaviour in children with Lennox–Gastaut syndrome

The long-term effects of vagus nerve stimulation (VNS) on behaviour were studied in 19 children with Lennox–Gastaut syndrome. We used the following stimulation parameters: output current: 1 1 2 to 2 mA; signal frequency: 30 Hz frequency; signal pulse width: 500 μs; signal ‘on and off’ time: 30 s ‘on,’ 3 min ‘off.’ The test battery consisted of cognitive tests assessing mental age and quality of life measurements assessing independency, behavioural problems, and mood. The results show relatively small changes in the behavioural outcomes, concurrent with the modest effects of VNS on seizure frequency (an average of 20.6% seizure reduction). When baseline measurements are compared with the follow-up measures, neither the cognitive measure nor the quality of life measures show any deterioration and the cognitive measure (mental age) showed mild positive changes (gain of 4.2 months mental age during the follow-up period). None of the changes were statistically significant. Treatment effect was most prominent in the group with the highest mental age at baseline, which suggests that mental retardation is a negative prognostic factor for VNS treatment. Moreover, in this specific patient group, treatment effect did not increase with treatment duration. Some evidence during follow-up suggests a direct positive effect of VNS on behavioural function, independent of changes in seizure frequency. Long-term treatment with VNS is not associated with adverse behavioural effects. Mental retardation is a negative prognostic factor for the efficacy of VNS.

Concomitant use of divalproex sodium and lamotrigine in developmentally disabled patients with epilepsy: a retrospective evaluation of efficacy and tolerability

Objective. Epilepsy in institutionalized severe developmentally disabled patients poses a therapeutic challenge. Frequently these patients have multiple seizure (sz) types that are often intractable. Both divalproex sodium (VPA) and lamotrigine (LTG) have demonstrated efficacy. We sought to examine the efficacy of this specific combination in a group of institutionalized, developmentally disabled patients with epilepsy. Methods. Medical and pharmacy records of all patients with developmental disabilities and intractable seizures were reviewed to identify those who had received VPA and LTG. This retrospective evaluation was structured with respect to time frame and outcome measure. Phase 1 consisted of baseline monotherapy with VPA. Phase 2 consisted of titration/dose escalation. Phase 3 was treatment observation period with the combination of both. Seizure frequency and adverse effect data were obtained from nursing or residential staff records. Primary outcome measures were change in seizure frequency between Phases 1 and 3. Additional measures were percentage of patients seizure-free and those with >75% reduction in seizures. A Wilcoxan signed rank test was used for statistical analysis. Results. Of 293 patients, 25 (12 M/13 F, 31.7±10.2 years) had VPA monotherapy following which LTG was added. Mean doses of VPA and LTG were 1474±728 and 165±111 mg/day, respectively. Baseline seizure frequency ranged from 1 to 25 per month. Mean seizure frequency significantly decreased ( 6.5± vs 2 .0±4.0 seizures/month, P<0.001). Sixty-four percent of these patients had ⩾75% reduction in seizures 28% became seizure-free. Conclusions. The combination of VPA and LTG appears efficacious in this group of developmentally disabled patients with intractable seizures. Rash, which has been associated with this combination, was notably absent and this may reflect the slower titration schedule used.

Cognitive behaviour therapy with adults with intractable epilepsy and psychiatric co-morbidity: preliminary observations on changes in psychological state and seizure frequency

Cognitive behaviour therapy (CBT) was undertaken with six adults with chronic, poorly controlled seizures and co-existing psychiatric and/or psychosocial difficulties. During 12 sessions of CBT from an experienced CBT Nurse Specialist, treatment focused concurrently on epilepsy-related problems, associated psychopathology and on the development of psychological strategies to reduce seizure occurrence. At the end of treatment participants rated their initial epilepsy-related problem as having less impact on their daily lives and at one-month follow-up reported less deleterious impact on everyday life in terms of their psychological difficulties. In addition participants demonstrated significant improvements in terms of their self-rated work and social adjustment, and in their decreased use of escape-avoidance coping strategies. These positive findings occurred despite the absence of a significant decrease in seizure frequency. Issues raised by the complexity and severity, both of these patients’ psychological/psychosocial difficulties and their epilepsy, are discussed in relation to the optimal length of treatment that may be required when adopting a CBT model in this patient group.

Effects of 6 Months of Treatment with Vagus Nerve Stimulation on Behavior in Children with Lennox–Gastaut Syndrome in an Open Clinical and Nonrandomized Study

The effect of vagus nerve stimulation (VNS) on behavior outcomes was studied in 16 children with Lennox–Gastaut syndrome. We used the following stimulation parameters: output current, 112 to 2 mA; signal frequency, 30 Hz; signal pulse width, 500 microseconds; signal on and off times, 30 seconds on and 3 minutes off. The test battery consisted of cognitive tests measuring mental age, attention, language, psychomotor function, and cognitive style, and quality-of-life measurements assessing independence, behavioral problems, symptoms of pervasive development disorders (PDDs) and mood. The results show relatively small changes in behavioral outcomes concurrently with modest effects on seizure frequency (an average of 26.9% seizure reduction). When baseline and endpoint measurements are compared none of the cognitive measures show any deterioration and three of five cognitive measures show slight positive changes. Among the quality-of-life measures, one measure showed a slight worsening of scores and three showed slight improvement. When the group is divided into subgroups on the basis of treatment effect the most prominent improvements are observed in the group without any effects of VNS on seizure frequency. These patients gained, on average, 9.5 months in mental age and showed more independent behavior, mood improvements and fewer PDD symptoms. This suggests an effect of VNS on behavioral function independent of changes in seizure frequency.