Vigabatrin for childhood partial-onset epilepsies.
ABSTRACT To determine vigabatrin's effectiveness and the prevalence of symptomatic visual impairment (i.e., impairment affecting the ability to perform everyday activities) associated with its therapy in pediatric epilepsy, we retrospectively reviewed medical records of 156 patients receiving vigabatrin at Cincinnati Children's Medical Center from 1998-2010. In addition to demographics and vigabatrin dosing information, data included seizure type/frequency at presentation and subsequent follow-up. Of 156 patients, we excluded 35 because their medical records were insufficient to permit verification of the exact duration or timing of vigabatrin treatment. To evaluate efficacy (n = 121/135), we used a 5-point scale (0-4) to compare seizure frequency at several time points. To evaluate visual impairment (n = 63), we reviewed serial ophthalmologic evaluations at baseline and during treatment for patients in whom they were clinically indicated. Mean age at treatment initiation was 1.8 years (range, 0.1-29.2 years). Treatment duration ranged from 0.7-101.0 months, with an estimated average daily dose of 79 mg/kg/day. Tuberous sclerosis complex was the commonest seizure etiology (83%). Partial-onset seizure, alone or with infantile spasms, was the commonest seizure type (84%). Seizure frequency decreased from 3.7 ± 0.6 S.D. at baseline to 1.8 ± 1.7 S.D. at 6 months (P < 0.001). Responses to vigabatrin did not differ by tuberous sclerosis complex or nontuberous sclerosis complex etiology, and were sustained for 5 years. Sixty-three patients (∼50% of all patients evaluated) underwent clinically indicated ophthalmologic assessments during the review period. In our clinical judgment, no cases of clinically relevant vigabatrin-associated visual impairment occurred. Vigabatrin was effective for refractory childhood partial-onset epilepsy, and was not associated with symptomatic vision loss.
- SourceAvailable from: Darcy A Krueger[Show abstract] [Hide abstract]
ABSTRACT: Historically, before the advent of modern imaging and genetic testing, Tuberous Sclerosis Complex (TSC) was more of a diagnostic challenge and less of a treatment challenge. This is because the natural history of TSC was poorly understood and TSC-specific treatments were non-existent. In the current era, diagnosis is more straightforward but management is much more complex. Disease manifestations vary by age, severity, and organ system. Management issues in the first few months of life, including neurologic manifestations, are very different than late childhood, adolescence, and adulthood. With increasing numbers of TSC diagnoses being made prenatally or shortly after birth, the opportunity for interventions that may improve long-term developmental and epilepsy outcomes now may precede the onset of neurological clinical symptoms. Familiarity and anticipation of these neurologic complications and rapid response to their emergence is crucial. Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1-3 years, is now standard of care. Early SEGA detection provides opportunity to initiate pharmacologic treatment with everolimus if appropriate, thereby negating the need for invasive surgery. Routine electroencephalography (EEG) in asymptomatic infants for the first year or two of life is becoming increasingly accepted, with treatment initiation of vigabatrin dependent on concerning EEG findings instead of waiting until onset of clinical seizures, the traditional approach. Effective SEGA treatment and optimal seizure control remain principal during the first few decades of life for the clinical neurologist involved in the management of TSC. However, during the same period and extending through adulthood, assessment of TSC-associated neuropsychiatric disorder (TAND) is also key to the best clinical outcome and quality of life for affected individuals and their surrounding family and caregivers.Current Treatment Options in Neurology 07/2013; · 2.18 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Tuberous sclerosis complex (TSC) is a genetic disorder that can affect multiple organ systems, including the brain, heart, skin, kidney, and lung, by formation of benign hamartomas. It can be associated with autism, epilepsy, and other neurocognitive and behavioral disabilities. The incidence of TSC is approximately 1 in 6,000 live births, but it may be underdiagnosed. Mutations to either the TSC1 (coding for hamartin) or TSC2 (coding for tuberin) genes are present in 85% of patients with TSC. The TSC1/TSC2 protein dimer complex is a crucial inhibitory element in the mammalian target of rapamycin (mTOR) complex 1 pathway that regulates cell growth and proliferation. The manifestations of TSC usually require management over the entire life of the patient. Until recently, there were few options, other than surgical removal, for treating the symptoms of TSC related to growth of hamartomas. Increased understanding of the genetic cause of the disease and the underlying dysregulation of the mTOR pathway has led to clinical trials of mTOR inhibitors including sirolimus and everolimus. This article will review the various manifestations of TSC and describe treatment strategies, recommendations for surveillance, and use of mTOR inhibitors in their management.The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses. 08/2013; 45(4):223-239.
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ABSTRACT: To evaluate the predominant pattern of brain injury and the anatomic areas of injury in children with infantile spasms following neonatal hypoxic-ischemic encephalopathy. A nested case-control study of infantile spasms in children with term neonatal hypoxic-ischemic encephalopathy was performed. All patients had T1/T2-weighted magnetic resonance imaging with diffusion-weighted imaging performed on the third day of life. Using a validated scoring system, the magnetic resonance imaging was classified as: normal, watershed, basal ganglia/thalamus, total, or focal-multifocal. Two study investigators scored additional anatomic areas of injury (cortical extent, levels of the brainstem, hypothalamus) on T1/T2-weighted magnetic resonance imaging and diffusion-weighted imaging blinded to the outcome. The predominant pattern of brain injury and anatomic areas of injury were compared between patients who developed infantile spasms and randomly selected controls. Eight patients who developed infantile spasms were identified among a cohort of 176 term newborns with hypoxic-ischemic encephalopathy (4.5%). There were no significant differences in the perinatal and neonatal course between newborns who developed infantile spasms and controls who did not. The development of infantile spasms after neonatal hypoxic-ischemic encephalopathy was significantly associated with basal ganglia/thalamus and total brain injury (P = 0.001), extent of cortical injury greater than 50% (odds ratio = 11.7, 95% confidence interval = 1.1-158.5, P = 0.01), injury to the midbrain (odds ratio = 13, 95% confidence interval = 1.3-172, P = 0.007) and hypothalamic abnormalities (P = 0.01). The development of infantile spasms after hypoxic-ischemic encephalopathy is associated with injury to the basal ganglia and thalami on neonatal magnetic resonance imaging, particularly when extensive cortical injury and/or injury to the midbrain is present.Pediatric Neurology 10/2013; · 1.50 Impact Factor
Vigabatrin for Childhood Partial-Onset Epilepsies
Hansel M. Greiner MD, Elizabeth R. Lynch MS, Steve Fordyce BA, Karen Agricola FNP-CP,
Cynthia Tudor PNP, David Neal Franz MD, Darcy A. Krueger MD, PhD*
Division of Neurology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
Received 18 August 2011
Accepted 29 November 2011
To determine vigabatrin’s effectiveness and the prevalence of symptomatic visual impairment (i.e.,
impairment affecting the ability to perform everyday activities) associated with its therapy in pediatric
epilepsy, we retrospectively reviewed medical records of 156 patients receiving vigabatrin at Cincinnati
data included seizure type/frequency at presentation and subsequent follow-up. Of 156 patients, we
excluded 35 because their medical records were insufficient to permit verification of the exact duration or
seizure frequency at several time points. To evaluate visual impairment (n ¼ 63), we reviewed serial
ophthalmologic evaluations at baseline and during treatment for patients in whom they were clinically
from 0.7-101.0 months, with an estimated average dailydose of 79 mg/kg/day. Tuberous sclerosis complex
was the commonest seizure etiology (83%). Partial-onset seizure, alone or with infantile spasms, was the
commonest seizure type (84%). Seizure frequency decreased from 3.7 ? 0.6 S.D. at baseline to 1.8 ? 1.7 S.D.
at 6 months (P < 0.001). Responses to vigabatrin did not differ by tuberous sclerosis complex or non-
tuberous sclerosis complex etiology, and were sustained for 5 years. Sixty-three patients (w50% of all
patients evaluated) underwent clinically indicated ophthalmologic assessments during the review period.
In our clinical judgment, no cases of clinically relevant vigabatrin-associated visual impairment occurred.
Vigabatrin was effective for refractory childhood partial-onset epilepsy, and was not associated with
symptomatic vision loss.
? 2012 Elsevier Inc. All rights reserved.
Vigabatrin is a potent g-aminobutyric acid transaminase inhib-
itor approved for use as adjunctive treatment in adult patients with
refractory, complex partial seizures who inadequately respond to
other treatment, and for whom the potential benefit outweighs the
risk of vision loss. Vigabatrin is also used as monotherapy for
infantile spasms in pediatric patients aged 1 month to 2 years .
However, clinical indications for vigabatrin in other settings,
Vigabatrin was demonstrated to be effective in the treatment of
infantile spasms [1-7], particularly when infantile spasms were
associated with tuberous sclerosis complex [8,9]. A Cochrane Data-
base review of 11 prospective studies of vigabatrin vs placebo for
patients with refractory partial seizures revealed that ?50% seizure
reduction was achieved by significantly more vigabatrin-treated
patients . However, the majority of patients included in that
analysis were adults, and only short-term benefits were evaluated.
Furthermore, patients with partial-onset seizures in association
with other seizure types, such as infantile spasms, and those with
tuberous sclerosis complex were specifically excluded. In a recent
retrospective analysis of vigabatrin use in pediatric patients, the
control of refractory partial seizures after treatment for 6 months
was observed in 20 (34%) of 59 patients with partial seizures .
The identification of peripheral visual field defects as a potential
its use . Because of substantial variations in methodology,
patient selection, and population size, estimates for peripheral
visual field defects range from 19-92% for adults , and from
9-62% for pediatric patients . The actual incidence of vigabatrin-
associated visual field loss remains unknown. Permanent, bilateral,
concentric visual field constriction was first reported with vigaba-
trin use in 1997 . Although data regarding visual field loss from
randomized, controlled trials are not available, several cross-
sectional, observational studies reported peripheral visual field
defects ranging from mild to severe in 30-50% of patients [15-21].
* Communications should be addressed to: Dr. Krueger; Division of Neurology;
Department of Pediatrics; Cincinnati Children’s Hospital Medical Center; 3333
Burnet Avenue, ML #2015; Cincinnati, OH 45229.
E-mail address: email@example.com
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/pnu
0887-8994/$ - see front matter ? 2012 Elsevier Inc. All rights reserved.
Pediatric Neurology 46 (2012) 83e88
With concern regarding potential vigabatrin-associated visual
field loss, determining which patients may benefit the most from
vigabatrin therapy is critical. Despite the proven efficacy of
vigabatrin, fear of vigabatrin-associated visual field loss is a major
consideration when prescribing it for patients with refractory pedi-
atric epilepsy. The functional consequences of vigabatrin-associated
visual field loss for patients with tuberous sclerosis complex and
other conditions associated with refractory epilepsy are not clear,
especially when weighed against the morbidity of uncontrolled
epilepsy and coexisting associated developmental delays, cognitive
impairment, and behavioral difficulties [12,22].
and long-term (?5 years) efficacy of vigabatrin in a large, mostly
pediatric cohort with partial-onset epilepsies, including patients
defects during a 12-year time span for this patient population.
Materials and Methods
We performed a retrospective chart review of patients who were treated with
vigabatrin and followed in the pediatric neurology clinics at Cincinnati Children’s
Hospital between January 1, 1998, and June 1, 2010. We obtained permission to
perform this study from the Institutional Review Board at Cincinnati Children’s
age, sex, the etiologies, frequencies, and descriptions of seizures, clinical course,
if applicable, the reason for discontinuation. Seizure type was identified according to
clinical descriptions and physicians’ diagnoses at the initiation of treatment and
during follow-up. In the present analysis, we included only those patients for whom
the initiation and discontinuation (or continuation as of June 1, 2010) of vigabatrin
could be verified. Before vigabatrin was commercially available in the United States
(late 2009), it was obtained through a source in the United Kingdom.
We obtained seizure frequency data for three time points: baseline (initiation of
vigabatrin), 6 months, and end of therapy (or most recent evaluation before June 1,
2010, for patients continuing therapy). Seizure frequency was recorded by several
practitioners through various methods during the 12-year analysis period. To address
the variability of seizure quantification by various practitioners, we developed
a 5-point scale and applied it uniformly to each case. This scale reflects seizure
frequency regardless of the recording methodology originally used (Table 1). Via this
5-point scale, a change of1 pointwould conservatively representa ?50% reduction or
increase in seizure frequency. For the purposes of this analysis, the original seizure
was converted to this scale. Treatment response was defined as improvement by at
least one category in the scale.
Seizure scores at baseline and 6 months were compared to evaluate the short-
term efficacy of vigabatrin. We considered patients treated with vigabatrin for less
of vigabatrin, we stratified patients treated for more than 1 year according to treat-
ment duration, and compared seizure scores at each time point with baseline values.
We performed analyses for statistical significance in terms of individual treatment
response using Wilcoxon rank-sum tests. For correlative analyses, the Spearman
rank-order correlation was used to assess statistical significance.
Peripheral visual function was typically assessed informally (and not by formal
visual perimetry) because of the patients’ ages and the high incidence of cognitive
impairment. We assessed visual signs according to serial pediatric ophthalmologic
assessments performed as part of our standard clinical practice. We determined the
method of assessment (e.g., patient complaint, formal or informal visual perimetry,
electroretinography, or clinical examination) and classified ophthalmologic findings
as either normal or abnormal. We further subdivided abnormal findings by type:
abnormal, related to tuberous sclerosis complex; abnormal, related to underlying
disease (e.g., cortical visual loss); abnormal because of refractive errors; abnormal,
related to treatment; and abnormal, but unable to classify further.
Patient demographics and vigabatrin-treatment characteristics
We evaluated 156 patients previously or currently treated with
vigabatrin at Cincinnati Children’s Hospital during the analysis
period (Table 2). Of these 156, we excluded 35 patients from the
analyses because their medical records were insufficient to permit
verification of the exact duration or timing of vigabatrin treatment.
Of the 121 patients included in the analyses, 63 (52%) were male.
The majority (83%) were diagnosed with tuberous sclerosis
complex, as was expected given the consensus recommendations
 for the treatment of tuberous sclerosis complex-associated
infantile spasms with vigabatrin, long before the compound
became commercially available in the United States in 2009. The
mean age was 1.8 years (range, 0.1-29.2 years). Only one patient
was more than 21 years of age at the time of initiating vigabatrin,
and 61% of patients were ?2 years of age.
Treatment duration ranged from 0.7-101.0 months, with an
average estimated daily dose of 79 mg/kg/day (Table 2). Partial-
onset seizure was the most common seizure type treated (105 of
121 patients). However, 41 of these patients had a history of
infantile spasms occurring before or concurrent with partial-onset
seizures, whereas four patients manifested additional seizures
types (e.g., generalized onset, myoclonic, tonic, or atonic). Twelve
patients weretreated for infantile spasms only, and four manifested
other seizure types alone.
Effects of vigabatrin on seizure frequency
To evaluate the initial response to vigabatrin treatment, we
examined seizure frequency after treatment with vigabatrin for 6
months. Baseline and 6-month seizure frequency data were avail-
able for 89 of the 121 patients. The mean baseline seizure score was
Table 1. Definitions for seizure frequency severity scores
Seizure-free status >3 months
?1 seizure/month, but <1 seizure/week
?1 seizure/week, but <1 seizure/day
Table 2. Patient demographics and characteristics of vigabatrin treatment
Patients included in analysis (n)
Sex, n (%)
Seizure etiology, n (%)
Tuberous sclerosis complex
Nontuberous sclerosis complex
Age at time of initiating vigabatrin, n (%)
Seizure type treated with vigabatrin, n (%)
Infantile spasms alone
Partial-onset in association with infantile
Other seizure types alone
Partial-onset in association with other
Vigabatrin treatment duration, n (%)
H.M. Greiner et al. / Pediatric Neurology 46 (2012) 83e88
3.7 ? 0.6 S.D., indicating that most patients were experiencing daily
seizures before the initiation of vigabatrin, and all were experi-
encing at least one seizure per month (Fig 1). After treatment with
vigabatrin for 6 months, the mean seizure score decreased to 1.8 ?
1.6 S.D. (P < 0.001 vs baseline). Overall, 61 of 121 patients (50%)
responded to treatment, as indicated by an improvement in seizure
score by at least one category. Of patients with initial daily seizures
(n ¼ 73), 24 (33%) were seizure-free and another eight (11%)
manifested, on average, less than 1 seizure/month after 6 months of
To evaluate whether treatment response was sustained for more
than 6 months, we examined seizure frequency in patients treated
with vigabatrin for ?1 year (n ¼ 55). The median treatment dura-
tion for this subset of patients was 2.5 years. The seizure score at
each time point up to 5 years revealed a significant decrease in
seizure frequency compared with baseline (Fig 2). At 5 years of
vigabatrin treatment, the seizure frequency severity score was 2.4
? 1.6 S.D., compared with a baseline seizure score of 3.7 ? 0.7 S.D.
(P ¼ 0.002). Five patients received vigabatrin for an initial period of
1-4 years with good response, after which vigabatrin was dis-
continued and seizuresreemergedwithin 1.5 months to3 years. For
four of the five patients, good treatment response was regained
with vigabatrin within 6 months after reinitiating it.
Treatment response at 6 months did not differ significantly
between tuberous sclerosis complex and nontuberous sclerosis
complex etiologies (Table 3). Upon examining seizure type and
treatment response, we determined that the mean decrease in
seizure score was significant for partial-onset seizures alone,
infantile spasms alone, and partial-onset seizures in association
the onset of partial seizures constituted a significant predictor of
improved treatment efficacy at the 6-month time point (P < 0.05;
Table 4). Age and vigabatrin dose did not demonstrate a significant
Patients treated for shorter periods of time (i.e., <6 months)
generally discontinued vibabatrin for lack of efficacy or because
their spasms had ceased.
Ophthalmologic findings for patients treated with vigabatrin
A total of 63 patients underwent ophthalmologic assessments,
as clinically indicated according to consensus guidelines spon-
sored by the National Institutes of Health , during the study
period available for review. The mean age in this cohort when
vigabatrin was initiated was 3.7 years (range, 0.1-29.2 years). The
average duration of treatment was 30.6 months, and the most
recent ophthalmologic evaluation was performed, on average,
after 18.5 months of therapy (range, 0.2-95.1 months). For the
majority of patients, ophthalmologic examinations consisted of
clinical functional assessments and dilated funduscopic examina-
tions only. Only four patients received formalized testing with
electroretinography, and age-related and cognitive-related diffi-
culties were cited as reasons to limit formalized testing with
electroretinography. Thirty-one of the 63 patients (49%) with
ophthalmologic assessments manifested visual abnormalities
(Table 5). The most common abnormalities were related to
tuberous sclerosis complex (n ¼ 13), and retinal hamartomas
comprised the most common single finding in this group.
Refractive errors (n ¼ 9) and cortical visual loss (n ¼ 5) repre-
sented the next most common abnormalities. Only one patient
exhibited findings that raised concern for possible vigabatrin-
associated visual field loss. This patient was an 8-year-old white
boy with tuberous sclerosis complex and an onset of infantile
spasms at age 6 months. The initiation of vigabatrin at that time
resulted in an immediate cessation of seizure activity. However,
the patient subsequently developed daily partial seizures, and his
vigabatrin therapy was continued. The medication seemed to
provide benefit by decreasing the number and severity of seizures,
but seizures continued to occur on a daily basis. When the patient
was 7 years of age, visual fields according to confrontation were
normal. The patient was too inattentive for formal visual field
perimetry. Moreover, the patient manifested a retinal hamartoma
in his right eye and bilateral refractive abnormalities. Electroreti-
nography revealed abnormal scotopic responses and reductions in
photopic flicker in both eyes (Fig 3). Therefore, we could not
determine definitively if the patient’s visual abnormalities were
attributable to vigabatrin, but the medication was discontinued
Figure 1. Seizure frequency severity scores at baseline and after 6 months of vig-
abatrin treatment. Numbers of patients in each category are indicated above each
Figure 2. Seizure frequency severity scores, stratified according to duration of vig-
abatrin treatment. Error bars indicate standard errors of the means.
Table 3. Response to vigabatrin treatment according to seizure etiology
Score (Mean ? S.D.)
3.8 ? 0.6
Score (Mean ? S.D.)
1.8 ? 1.6
complex (n ¼ 78)
complex (n ¼ 11)
S.D. ¼ Standard deviation
* P values were based on Wilcoxon rank-sum tests to compare seizure frequency
severity scores at baseline and after 6 months of vigabatrin treatment.
3.5 ? 0.92.0 ? 1.70.031
H.M. Greiner et al. / Pediatric Neurology 46 (2012) 83e88
We observed a significant decrease in seizure score with vig-
abatrin treatment in a pediatric population, regardless of seizure
etiology (tuberous sclerosis complex or nontuberous sclerosis
complex) or type (infantile spasms or partial seizures). The sample
was medically refractory, and most patients experienced daily
seizures. This study indicates, despite the limitations of its retro-
spective design, that vigabatrin was efficacious for epilepsy outside
of its current Food and Drug Administration-approved indications
for partial-onset seizures in infants, older children, and patients
with conditions of tuberous sclerosis complex and nontuberous
sclerosis complex etiologies.
Ourresults are similartothoseof previousprospectivestudies of
the researchers observed 50% seizure reductions for 43-67% of
patients [2,25-28]. In the present cohort, 50% demonstrated an
vigabatrin therapy. Moreover, vigabatrin appeared to provide
a durable effect on seizure frequency, which was sustained through
5 years of treatment. We obtained end-of-treatment data for chil-
similar to those in the 6-month data. This finding may reflect the
unique responsethat many patients achievewith vigabatrin, even if
they have not responded to several other anticonvulsants.
In our practice, we have observed that vigabatrin is usually
tolerated at doses up to 150 mg/kg/day, and can be titrated rapidly
to determine efficacy. The efficacy and safety of vigabatrin at 150
mg/kg/day were reported in several other studies [29-31]. Disor-
dered sleep, somnolence, and behavioral disturbances are the most
frequently encountered adverse effects. These reactions are
generally dose-dependent and respond to decreasing the dosage
and reintroducing the medication more gradually [8,12,22].
Given the efficacy and tolerability of vigabatrin, vigabatrin-
associated visual field loss constitutes the primary obstacle to
initiating treatment. Recently, several authors attempted to address
the prevalence and severity of vigabatrin-associated visual field
loss, its relationship to total cumulative vigabatrin dose, and most
importantly, the functional visual outcomes of children who
experience this adverse effect as part of their treatment. Electro-
retinography has been used for early diagnoses of vigabatrin-
associated visual field loss, but this test typically requires
sedation or anesthesia in pediatric patients, and results can be
abnormal or poorly reproducible because of intercurrent neuro-
logic disease or anticonvulsant treatment. Furthermore, baseline
tuberous sclerosis complex-associated retinal abnormalities may
affect the results, such that comparisons with standard normative
values may not yield accurate interpretations of findings in this
specific patient sample . In our report, only four of 63 patients
(6%) with ophthalmologic evaluations available had undergone
electroretinography. One patient exhibited findings consistent with
but not conclusive for vigabatrin-associated visual field loss.
The incidence of functionally significant vigabatrin-associated
visual field loss and how best to screen for it remain unclear
[12,13]. Visual field perimetry is noninvasive but often infeasible for
the young or cognitively impaired. In the largest cross-sectional
study to date in adults, Sergott et al.  analyzed visual field
perimetry data from 359 patients, of whom 258 had been exposed
tovigabatrin. Sixteenpercent of patients manifested bilateralvisual
field constriction, most of which was mild to moderate. A ques-
tionnaire about visual signs indicated a weak correlation between
visual field constriction and functional visual signs such as bump-
ing into objects. In another study of 16 children aged 6-12 years
treated with vigabatrin for infantile spasms in infancy, only one
manifested mild vigabatrin-associated visual field loss . The
authors suggested that children treated in infancy may run a lesser
risk of vigabatrin-associated visual field loss.
In our clinical practice, we routinely perform clinical ophthal-
mologic evaluations every 6-12 months for patients treated with
vigabatrin. The extremely low incidence of visual signs or ophthal-
mologic abnormalities we observed in our cohort, with treatment
extending well beyond 5 years in many patients, suggests that this
approach is reasonable. Indeed, most families do not choose elec-
troretinographic surveillance, even when offered, after they
understand the steps involved in testing and the limited applica-
bility of results. Diagnostic alternatives to electroretinography, as
well as the underlying mechanisms of vigabatrin-associated visual
field loss, are undergoing evaluation.
Optical coherence tomography, which measures the thickness of
electroretinography, and could emerge as a less invasive adjunctive
test for vigabatrin-associated visual field loss . Recent evidence
indicates that taurine deficiency may play a role in vigabatrin-
associated visual field loss, and that such loss is preventable with
taurine supplementation . Based on these promising results and
the lack of adverse effects of taurine supplementation, we now offer
taurine supplementation to patients being treated with vigabatrin.
Further trials are necessary to determine if this supplementation can
prevent vigabatrin-associated visual field loss in humans.
This study was limited by its retrospective nature. Seizure scores
represent a range of seizure frequency based on available chart data
Table 5. Visual abnormalities according to type
Complex (n ¼ 53)
Complex (n ¼ 10)
Mean age (years)
Mean duration (months)
Abnormal, refractive only (n)
Abnormal, tuberous sclerosis
Abnormal, cortical (n)
Abnormal, vigabatrin (n)
Abnormal, other (n)
* Subretinal bleeding and exudate.
yOptic hypoplasia (n ¼ 1) and retinal coloboma (n ¼ 1).
Table 4. Response to vigabatrin treatment according to seizure type
Seizure Type Baseline Seizure Frequency Severity
Score (Mean ? S.D.)
3.6 ? 0.7
3.8 ? 0.6
3.3 ? 1.2
3.9 ? 0.4
4.0 ? 0.0
6-Month Seizure Frequency
Severity Score (Mean ? S.D.)
2.4 ? 1.6
1.3 ? 1.6
2.0 ? 1.7
1.4 ? 1.6
2.7 ? 2.3
Partial-onset alone (n ¼ 37)
Partial-onset with infantile spasms (n ¼ 38)
Partial-onset and other (n ¼ 3)
Infantile spasms alone (n ¼ 8)
Other alone (n ¼ 3)
¼ Not significant
S.D. ¼ Standard deviation
* P values were based on Wilcoxon rank-sum tests to compare seizure frequency severity scores at baseline and after 6 months of vigabatrin treatment.
H.M. Greiner et al. / Pediatric Neurology 46 (2012) 83e88
and are, we think, inferior to seizure diaries as an outcome
measurement. This scale is not a validated measurement tool for
use in clinical trials, but rather a tool we used to standardize the
reporting of seizure results in this analysis. Nonetheless, this report
provides additional evidence of the anticonvulsant efficacy of vig-
abatrin for children of various ages and seizure types. In addition,
the methodology of ophthalmologic assessment varied by clinician
and over time during the 12-year period included in this analysis.
Baseline ophthalmologic assessments were not available for
comparisons. Electroretinography was performed in only four
patients. However, this is consistent with standard practice in this
population, because electroretinographic results are of limited
value . In addition, few patients were evaluated through formal
vision testing (e.g., perimetry or optical coherence tomography).
Responses to vigabatrin did not differ by tuberous sclerosis
complex or nontuberous sclerosis complex etiology, and were
sustained for 5 years. However, approximately one sixth of the
patients in this analysis manifested a nontuberous sclerosis
complex etiology, which limits comparisons to those with tuberous
The possibility of vigabatrin-associated visual field loss should
not prevent the consideration of vigabatrin for treating refractory
epilepsy in pediatric patients. We observed that clinical benefit is
usually evident during the early course of treatment, when the
relativeriskof vigabatrin-associatedvisual fieldlossislower.Tothis
point, vigabatrin studies involving infantile spasms demonstrate
that response may be achieved very quickly (<2 weeks, in general,
majority of peripheral visual field defects during vigabatrin therapy
occur ?1 year of treatment . A 3-6-month trial of vigabatrin
with refractory partial epilepsy [36-38], except when such seizures
occur in associationwith Dravet syndrome or Angelman syndrome,
where vigabatrin is specifically contraindicated [39,40]. Treatment
should not be withheld because of concerns about vigabatrin-
fieldloss.The assessment of
associated visual field loss remains difficult, but functionally
significant retinal toxicity in pediatric patients appears to be rare.
All authors report that the analyses in this study were funded through an unre-
stricted medical education grant from Lundbeck, Inc. (Deerfield, IL). None of the
authors have additional conflicts of interest to disclose. The manuscript was drafted
by H.M.G. and D.A.K. All authors reviewed and approved the final manuscript for
submission to this Journal. Editorial support during preparation and revision of the
manuscript was provided by Robin L. Stromberg, PhD, of JK Associates, Inc. (Con-
shohocken, PA), and Michael A. Nissen, ELS, of Lundbeck, Inc. (Deerfield, IL). This
support was funded by Lundbeck, Inc.
 Lundbeck, Inc. Sabril [package insert]. Deerfield, IL: Lundbeck, Inc., 2010.
 French JA, Mosier M, Walker S, Sommerville K, Sussman N. A double-blind,
placebo-controlled study of vigabatrin three g/day in patients with uncon-
trolled complex partial seizures: Vigabatrin Protocol 024 Investigative Cohort.
Figure 3. Photopic flicker response (A) and maximal scotopic response (B) in electroretinograms of a 7-year-old patient with suspected vigabatrin-associated toxicity. Courtesy of
Larry Baitch, OD, PhD. OD, right eye; OS, left eye.
H.M. Greiner et al. / Pediatric Neurology 46 (2012) 83e88
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