Declining trend in valproate use in Finland among females of childbearing age in 2012-2016 - a nationwide registry-based outpatient study.

BACKGROUND AND PURPOSE: Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus on women. METHODS: We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses. RESULTS: Between 2012 and 2016, the prevalence of VPA use among women aged 15-44 years decreased by 19%, from 50/10 000 to 40/10 000 (prevalence rate ratio, 0.81; 95% confidence intervals, 0.77-0.91; P < 0.001). The use of VPA due to epilepsy decreased significantly in females aged 15-24 and 25-34 years and that due to bipolar disorders decreased significantly in females aged 25-34 and 35-44 years. The use of VPA in the miscellaneous indication group decreased by 32% after 2014 in females aged 15-44 years and, most strikingly, by 56% among those aged 15-25 years. In women with epilepsy, the use of VPA increased among those over the age of 44 years. CONCLUSIONS: The rates of female VPA users with childbearing potential have decreased in all three major indication groups in Finland during recent years, especially after the European Medicines Agency restrictions were published in 2014. However, it still remains open to question as to whether the practice of VPA use follows current guidelines. A special concern is the relatively high prevalence of off-label use of VPA in fertile-aged females.

Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

Pregabalin in partial seizures: a pragmatic 21-week, open-label study (PREPS).

BACKGROUND AND PURPOSE: Pregabalin has demonstrated efficacy in controlled trials as adjunctive treatment in patients with refractory seizures. METHODS: This open-label, 21-week study in adults with at least two partial seizures in the last 2 months, who were inadequately controlled with one to three antiepileptic drugs, evaluated pregabalin 150-600 mg/day (dosed twice daily). The study comprised a prospective or retrospective 8-week baseline phase, and 9-week dose optimization and 12-week maintenance periods. The primary assessment was the mean percentage change in 28-day seizure frequency between baseline and end-point (last 12 weeks of treatment, last observation carried forward, modified intention-to-treat population). RESULTS: Four hundred and seventy-six patients from Europe were included in this study (51% men; mean age/epilepsy duration 40.1/24.1 years). The median baseline seizure frequency was 5.5/28 days. Amongst the patient population, 78% completed the 21-week treatment period; 7% discontinued for lack of efficacy and 12% because of adverse events (AEs). The mean last pregabalin dose was 359 mg/day. The mean (95% CI) reduction in seizure frequency was 36% (31%; 41%). The median reduction was 33%, and 39% of patients had a >or=50% reduction in seizure frequency. There were 19% and 8% of patients free of seizures during their last 4 and 12 weeks of treatment, respectively. The three most common AEs were dizziness (17%), somnolence (13%) and weight increase (13%). CONCLUSIONS: This open-label study of pregabalin demonstrated efficacy that was consistent with that observed in previous controlled epilepsy trials. Pregabalin was well tolerated. The AE profile was also consistent with that reported in previous trials.

Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiency.

Accurate diagnosis, especially in progressive hereditary diseases, is essential for the treatment and genetic counseling of the patient and the family. Neuronal ceroid lipofuscinoses (NCL) are amongst the most common groups of neurodegenerative diseases. Infantile, juvenile, and adult-onset types with multiple genotype-phenotype associations have been described. A fluorimetric enzyme assay for palmitoyl protein thioesterase (PPT) from leukocytes and fibroblasts has been previously developed to confirm the diagnosis of infantile NCL. We describe a patient with juvenile-onset NCL phenotype with a new CLN1 mutation and deficient PPT activity. Over 40 different mutations have been found in patients with PPT deficiency, indicating that screening for known mutations is not an efficient way to diagnose this disorder. Therefore, PPT enzyme analysis should precede mutation analysis in suspected PPT deficiency, particularly in patients with granular osmiophilic deposits (GROD) or in patients who have negative ultrastructural data. The use of enzyme assay led to the diagnosis of this patient with juvenile-onset Finnish variant NCL with PPT deficiency, and we expect that greater awareness of the utility of the enzymatic assay may lead to identification of other similar cases awaiting a definitive diagnosis.

Long-term efficacy and cognitive effects of vigabatrin.

Vigabatrin is effective as add-on therapy in about 50% of patients with partial epilepsy refractory to drugs. Furthermore, at least half of the original responders maintain the response over several years. As monotherapy, both vigabatrin and carbamazepine seem to be successful in a similar proportion of newly diagnosed patients with epilepsy, but carbamazepine monotherapy fails more often due to side-effects and vigabatrin more often due to lack of efficacy. However, vigabatrin monotherapy seems to be extremely well tolerated, particularly in relation to cognitive function.

Long-term study with gabapentin in patients with drug-resistant epileptic seizures.

OBJECTIVE: To study the efficacy and safety of gabapentin in long-term treatment. DESIGN: A 4-year follow-up study of 25 patients with visits at 3-month intervals. SETTING: The patients were followed up in the outpatient unit of the University Hospital of Kuopio (Finland). PATIENTS: We treated 25 patients with drug-resistant complex partial seizures and secondarily generalized seizures in an open-label long-term study, using gabapentin as an additional means of therapy after a 3-month double-blind, placebo-controlled phase. Thirteen patients showed no benefit from gabapentin; the study medication was discontinued after 4 to 6 months of treatment. Of the 12 patients who responded enough to continue treatment, five were withdrawn due to different reasons, one because of loss of response. MAIN OUTCOME MEASURES: The number of patients receiving the study drug in the follow-up and reduction of seizure frequency from baseline level as analyzed by the Wilcoxon test. RESULTS: Seven patients received gabapentin therapy for more than 4 years. The median follow-up time was 54 months. There was a significant reduction in seizure frequency throughout the follow-up period. Five of seven patients had a greater than 50% seizure frequency reduction at 4 years, representing 20% of the 25 patients who entered the study. CONCLUSIONS: Gabapentin possesses good efficacy in long-term treatment of patients with partial and secondarily generalized epileptic seizures. It is safe to use, and it is fairly well tolerated even in long-term treatment.

Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study.

OBJECTIVE: To evaluate the efficacy, safety, and cognitive effects of initial vigabatrin monotherapy compared with initial carbamazepine monotherapy in patients with newly diagnosed epilepsy. DESIGN: Open, randomized, controlled design. Follow-up period of 12 months. SETTING: University hospital with an epilepsy center. PATIENTS: A total of 100 patients, aged 15 to 64 years, classified as suffering from partial seizures and/or generalized tonic-clonic seizures were randomized to either vigabatrin or carbamazepine monotherapy. Fifty-nine patients with a single epileptic seizure and no antiepileptic drug treatment served as a control population for objective safety measures. OUTCOME MEASURES: To evaluate the comparative efficacy and toxicity of vigabatrin and carbamazepine, the drug success rate (ie, the proportion of patients continuing successful treatment with the randomly assigned drug) after 12 months of steady-state treatment was used. To evaluate the safety of the drugs in addition to reported side effects, visual evoked potential recordings and neuropsychological evaluation were performed during follow-up. RESULTS: During the 12-month follow-up period, 60% of patients receiving vigabatrin and carbamazepine were treated successfully. Vigabatrin caused fewer side effects that required discontinuation of therapy. However, vigabatrin had to be discontinuated more often owing to lack of efficacy, and fewer of the successfully treated patients receiving vigabatrin achieved total freedom from seizures. Vigabatrin had no detrimental effects on cognitive functions. Retrieval from both episodic and semantic memory and flexibility of mental processing improved significantly in patients successfully treated with vigabatrin. CONCLUSION: Vigabatrin seems to be an effective and safe antiepileptic drug as primary monotherapy for epilepsy with fewer cognitive side effects than carbamazepine.

[18F]FDG-PET reveals temporal hypometabolism in patients with temporal lobe epilepsy even when quantitative MRI and histopathological analysis show only mild hippocampal damage.

BACKGROUND: The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([(18)F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. OBJECTIVE: To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. PATIENTS AND METHODS: Sixteen patients with drug-resistant temporal lobe epilepsy underwent [(18)F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. RESULTS: Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [(18)F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. CONCLUSIONS: [(18)F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD.

No reversion in vigabatrin-associated visual field defects.

Sixty adult patients with partial epilepsy who have been treated with vigabatrin for 7 months to 14 years as mono- or add-on therapy were examined with repeated kinetic Goldmann perimetries to evaluate the prevalence, risk factors, and long-term outcome of vigabatrin-associated visual field defects. A follow-up examination was performed after 4 to 38 months (mean, 15 +/- 7) in 55 patients, 29 of whom had discontinued vigabatrin therapy. Neither reversion nor progression in visual field constriction was observed.

Newer antiepileptic drugs as monotherapy: data on vigabatrin.

Studies examining the use of vigabatrin as monotherapy for the treatment of epilepsy are relatively scarce, and of the few that have been reported, only two were of sufficient size to provide definitive data. In both trials, vigabatrin was compared with carbamazepine for efficacy and safety. In one of these studies, carbamasepine was found to be more effective than vigabatrin in reducing seizure frequency, and the two were found to be comparably efficacious in the other study. What differed significantly, however, was vigabatrin's favorable safety profile. Vigabatrin appears to be a reasonable choice for single-drug therapy in the treatment of certain types of seizures. In other patients, it remains useful as an adjunct to other antiepileptic drugs.

Sweat gland vacuoles in Unverricht-Lundborg disease: a clue to diagnosis?

There has been no reported pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease (ULD). We report membrane-bound vacuoles with clear contents in eccrine clear cells and dark cells in five of seven patients with ULD, as well as in one clinically unaffected sibling. Vacuoles were not seen in the biopsies of two patients and of eight controls with Lafora's disease. These findings, though not entirely specific, suggest that skin biopsy may serve as a diagnostic aid to give supportive evidence for ULD.

Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field defects.

OBJECTIVE: To determine whether there is a causal link between vigabatrin treatment and concentric visual field defects and to evaluate the prevalence of these visual field constrictions. BACKGROUND: While the GABAergic antiepileptic drug (AED) vigabatrin was being clinically developed, only rare cases (less than 1:1000) of symptomatic visual field constriction and retinal disorders were reported. During 1997 to 1998, concentric visual field constrictions were described in case reports of mostly drug-resistant epilepsy patients receiving vigabatrin concurrently with other AEDs. METHODS: Ophthalmologic tests including Goldmann perimetry were performed on 32 adult patients on long-term successful vigabatrin monotherapy (treatment duration 29 to 119 months) and on 18 patients on carbamazepine monotherapy (treatment duration 32 to 108 months). Eighteen healthy adults served as controls. RESULTS: None of the patients complained about vision problems when asked to participate into the study. Thirteen out of the 32 (40%) epilepsy patients treated with vigabatrin monotherapy had concentrically constricted visual fields (9% severely, 31% mildly constricted), whereas none of the carbamazepine monotherapy patients or normal controls presented with a visual field defect (chi-square test, p = 0.0001). The extents of the visual fields were significantly constricted in vigabatrin group as compared with the visual fields of the patients in carbamazepine group or healthy controls (analysis of variance, Scheffe F-test, significant at 99%). CONCLUSIONS: The use of vigabatrin seems to increase the risk of a unique and specific pattern of bilateral, mainly asymptomatic visual field constriction. This risk should be considered when using vigabatrin. Visual field testing should also be performed before treatment and during routine follow-up for patients on vigabatrin.

Recurrent seizures may cause hippocampal damage in temporal lobe epilepsy.

OBJECTIVE: To investigate whether recurrent seizures cause hippocampal damage in temporal lobe epilepsy (TLE). PATIENTS: Eighteen patients with newly diagnosed cryptogenic TLE, 14 patients with chronic well-controlled cryptogenic TLE, 32 patients with chronic drug-resistant cryptogenic TLE, and 25 healthy subjects were studied. MEASUREMENTS: Hippocampal MRI volumetry and T2 relaxometry were used. RESULTS: Chronic drug-resistant patients with seizure focus in the left temporal lobe had an 18% smaller left hippocampus and chronic drug-resistant patients with seizure focus in the right temporal lobe had a 14% smaller right hippocampus than did the control group (p < 0.05). Chronic drug-resistant patients with seizure focus on the left side had longer T2 relaxation times in the body of the left hippocampus than did the control group (p < 0.001) and chronic drug-resistant patients with seizure focus on the right side had longer T2 relaxation times in the body of the right hippocampus than did the control subjects (p < 0.01). In all patients with a left seizure focus, the left hippocampal volume correlated inversely with the estimated total number of partial (r = -0.391, p < 0.01) or generalized (r = -0.312, p < 0.05) seizures the patient had experienced. The prolongation of the left T2 relaxation time in the body of the hippocampus correlated with the total number of both partial (r = 0.670, p < 0.001) and generalized (r = 0.481, p < 0.001) seizures and with the duration of TLE symptoms (r = 0.580, p < 0.001). CONCLUSIONS: In patients with cryptogenic epilepsy, recurrent seizures may cause damage to the hippocampus throughout the lifetime of the patient.

Severity of hippocampal atrophy correlates with the prolongation of MRI T2 relaxation time in temporal lobe epilepsy but not in Alzheimer's disease.

We analyzed hippocampal volumes and T2 relaxation times by MRI from 78 control subjects, 24 patients with temporal lobe epilepsy, and 55 patients with Alzheimer's disease (AD). In the epilepsy group, the hippocampal volumes were 27% smaller than in control subjects (p < 0.001). The T2 relaxation times were prolonged (8 to 20 ms compared with control subjects) in the head, body, and tail portions of the hippocampus on the focal side (p < 0.01) and also on the contralateral side (p < 0.05) compared with control subjects. In the epilepsy group, the prolongation of T2 relaxation time correlated inversely with the hippocampal volume (p < 0.05). In the AD group, the hippocampal volumes were 35% smaller than in control subjects (p < 0.01). The T2 relaxation times were slightly prolonged (5 to 6 ms) in the head and tail portions of the right hippocampus (p < 0.01), but the T2 relaxation times did not correlate with the hippocampal volumes. These data show that the degree of prolongation of T2 relaxation time is associated with severity of hippocampal atrophy in temporal lobe epilepsy but not in AD.

High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit.

The authors studied prospectively the effects of thiopental anesthesia on seizure control, hemodynamics, and the course of intensive care in 10 patients with refractory status epilepticus. Clinical and electrophysiological seizures were terminated in every patient. Hemodynamically, thiopental was well tolerated, but slow recovery from anesthesia prolonged the need for intensive care.

[11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology.

OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

Place of newer antiepileptic drugs in the treatment of epilepsy.

There are several new antiepileptic drugs undergoing extensive clinical investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and oxcarbazepine--appear to be the most widely tested and promising agents. Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is also effective in infantile spasms, but seems to have negative effects on myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition, lamotrigine and felbamate seem to have efficacy in idiopathic generalised epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine, but less toxic. Gabapentin has few adverse effects and has efficacy in some patients with drug-resistant partial epilepsy. Some of the new antiepileptic drugs modify excitatory or inhibitory amino acid transmission, but some of them may employ new, still unknown mechanisms of action. Depending on the mechanism of action, the therapeutic effectiveness of the antiepileptic drugs may differ in specific epileptic syndromes. Future antiepileptic drugs may thus give us the possibility to design rational polypharmacy for individual patients by combining agents with different spectra of effectiveness. Considering the goal of good tolerability in the development of the new antiepileptic drugs, polypharmacy with these agents is not expected to increase adverse effects significantly.

Do seizures cause neuronal damage? A MRI study in newly diagnosed and chronic epilepsy.

It is a matter of dispute whether or not recurrent epileptic seizures cause neuronal damage in the human brain. We approached this question by measuring the volumes of the amygdala, hippocampus and parahippocampal gyrus with magnetic resonance imaging in 15 controls, 13 unmedicated patients with newly diagnosed epilepsy and 16 patients with chronic drug-refractory epilepsy. In all patients, the seizure origin was in the temporal lobe region and the seizure aetiology was unknown. Newly diagnosed epilepsy patients with seizure lateralization on the left had increased hippocampal right-left difference (p < 0.01) and right/left ratio (p < 0.05) compared with controls. Patients with chronic epilepsy and lateralization on the left had increased hippocampal right-left difference (p < 0.05) and right/left ratio (p < 0.05) compared with controls. In this patient group, the volume of the left hippocampus was 16% smaller than in controls (p < 0.01). The rostral portion of the parahippocampal gyrus was 12% smaller than in controls (p < 0.01). In chronic epilepsy patients with lateralization on the right, we found a statistically non-significant decrease (13%) in the right hippocampal volume compared with controls. In this patient group, the amygdaloid right-left difference (p < 0.05) and right/left ratio (p < 0.05) were decreased compared with controls. The present cross-sectional study provides evidence that mild hippocampal damage is already present in the early stages of epilepsy. Hippocampal damage is more severe in patients with a long history of recurrent generalized seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced N-acetylaspartate concentration in temporal lobe epilepsy by quantitative 1H MRS in vivo.

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

Visual field defects with vigabatrin: epidemiology and therapeutic implications.

Vigabatrin is an antiepileptic drug (AED) that acts as a selective irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase. In 1997, 3 cases of severe symptomatic and persistent visual field constriction associated with vigabatrin treatment were described. During 1997 to 1998, similar concentric visual field constrictions were described in patients with drug-resistant epilepsy who were receiving vigabatrin concurrently with other AEDs. However, a study of patients treated with vigabatrin monotherapy alone showed that there was a causal relationship between vigabatrin treatment and the specific bilateral concentric visual field constriction. The Marketing Authorisation Holders survey (involving 335 vigabatrin recipients aged >14 years) indicated that 31% of patients [95% confidence interval (CI) 26 to 36%] had a visual field defect attributable to vigabatrin, compared with a 0% incidence of visual field defects (upper 95% CI 3%) in an unexposed control group. Other studies in adults have given similar overall prevalences, with a total of 169 of 528 patients diagnosed with vigabatrin-associated field defects (32%, 95% CI 28 to 36%). Male gender seems to be associated with an increase in the relative risk of visual field loss of approximately 2-fold. The pattern of defect is typically a bilateral, absolute concentric constriction of the visual field, the severity of which varies from mild to severe. Data gathered so far suggest that the cumulative incidence increases rapidly during the first 2 years of treatment and within the first 2 kg of vigabatrin intake, stabilising at 3 years and after a total vigabatrin dose of 3 kg. The prevalence of vigabatrin-associated field defects seems to be lower in children, but there are also methodological problems and greater variability in the assessment of visual fields in children. There is particular concern that the increased risk of the visual field defects will outweigh the benefit of the drug in patients who could be controlled with other AEDs. Vigabatrin should currently be used only in combination with other AEDs for patients with resistant partial epilepsy when all other appropriate drug combinations have proved inadequate or have not been tolerated. Regular visual field testing should be performed before the start of treatment and at regular intervals during treatment. Patients with pre-existent visual field defects due to other causes should not be treated with vigabatrin. Currently, the benefits of treating infantile spasms with vigabatrin monotherapy seem to outweigh the risks, but further prospective studies and follow-up of children receiving treatment are needed to evaluate the place of vigabatrin in this indication.