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J M Wild - One of the best experts on this subject based on the ideXlab platform.
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prevalence of visual field loss following exposure to Vigabatrin therapy a systematic review
Epilepsia, 2010Co-Authors: Melissa J Maguire, J M Wild, Karla Hemming, Jane L Hutton, Anthony G MarsonAbstract:Purpose: Vigabatrin is an efficacious antiepileptic drug licensed as add-on therapy in refractory epilepsy and used in infantile spasms. Eight years after licensing, there emerged a strong and possibly causative association with bilateral visual field loss. We report a systematic review ascertaining the magnitude of risk of Vigabatrin associated visual field loss (VAVFL) and any clinical predictors of risk. Methods: Electronic searches, including MEDLINE (1966-2009), EMBASE (1974-2009), and CINAHL (1982-2009), were conducted. Reports, published in full, of observational studies investigating the prevalence of visual field loss in patients with partial epilepsy treated with Vigabatrin were included. Outcomes were the proportion with visual field loss, and the relative risk of VAVFL compared to similar nonexposed patients with epilepsy. Key Findings: Thirty-two studies were identified, which included 1,678 patients exposed to Vigabatrin and 406 controls. Of the 1,678 exposed patients, 738 (44%) had visual field loss compared to just 30 (7%) among the 406 controls. The random-effects estimate for the proportion of adults with visual field loss was 52% [95% confidence interval (CI) 46-59]. The estimate for children was lower at 34% (95% CI 25-42). The relative risk for field loss in Vigabatrin-exposed patients was 4.0 (95% CI 2.9-5.5). Larger mean cumulative dose of Vigabatrin and increasing age were associated with a higher proportion of patients with visual field loss. Significance: Vigabatrin should be reserved for patients with epilepsy for whom there is no other alternative or for patients who have determined the benefit of ongoing treatment to outweigh the risk of VAVFL.
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nasal retinal nerve fiber layer attenuation a biomarker for Vigabatrin toxicity
Ophthalmology, 2009Co-Authors: Charlotte Lawthom, Philip E. M. Smith, J M WildAbstract:Purpose To investigate whether nasal peripapillary retinal nerve fiber layer (RNFL) attenuation is associated with visual field loss attributed to the anti-epileptic drug Vigabatrin. Design Prospective cross-sectional observational study. Participants Twenty-seven individuals with focal-onset epilepsy exposed to Vigabatrin and 13 individuals with focal-onset epilepsy exposed to non-GABAergic anti-epileptic drug monotherapy. Methods At one visit, suprathreshold perimetry of the central and peripheral field (3-zone, age-corrected Full Field 135 Screening Test) and threshold perimetry of the central field (Program 30-2 and the FASTPAC strategy) were undertaken using the Humphrey Field Analyzer (Carl Zeiss Meditech, Dublin, CA). At a second visit, ocular coherence tomography was undertaken for the right eye using the 3.4 RNFL thickness protocol of the StratusOCT (Carl Zeiss Meditech). Main Outcome Measures The magnitude, for each individual, of the RNFL thickness, averaged across the 4 oblique quadrants, and for each separate quadrant. Results Of the 27 individuals exposed to Vigabatrin, 11 (group I) exhibited Vigabatrin-attributed visual field loss, 15 exhibited a normal field, and 1 exhibited a homonymous quadrantanopia (group II). All 13 individuals exposed to non-GABAergic therapy had normal fields (group III). All individuals in group I exhibited abnormal average and nasal quadrant RNFL thicknesses in the presence of a normal temporal quadrant thickness. Most also exhibited additional RNFL attenuation in either the superior or inferior quadrant, or both. Four individuals in group II exhibited an identical pattern of RNFL attenuation suggesting that nasal RNFL thinning is a more sensitive marker for Vigabatrin toxicity than visual field loss. None of the 13 individuals in group III exhibited nasal quadrant RNFL attenuation. Conclusions Vigabatrin-attributed visual field loss is associated with a characteristic pattern of RNFL attenuation: nasal quadrant thinning and normal temporal quadrant thickness with, or without, superior or inferior quadrant involvement. Nasal attenuation may precede visual field loss. Ocular coherence tomography of the peripapillary RNFL should be considered in patients previously exposed to Vigabatrin. It should also be considered at baseline and follow-up in those commencing Vigabatrin for treatment of epilepsy or in trials for anti-addiction therapy. The pattern of RNFL thinning seems to be a useful biomarker to identify Vigabatrin toxicity.
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Visual field defects associated with Vigabatrin therapy
Journal of neurology neurosurgery and psychiatry, 1999Co-Authors: M. C. Lawden, T Eke, C Degg, G F A Harding, J M WildAbstract:OBJECTIVE—To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug Vigabatrin and to characterise the features of visual dysfunction found. METHODS—Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking Vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16patients with epilepsy unexposed to Vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS—Of 31 assessable patients treated with Vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12patients (39%) in whom a definite bilateral field defect was found, possibly caused by Vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with Vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking Vigabatrin, although this returned towards normal when Vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS—Treatment with Vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of Vigabatrin on the retina and seemed to persist if the drug was withdrawn.
Gregory L Krauss - One of the best experts on this subject based on the ideXlab platform.
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sabril registry 5 year results characteristics of adult patients treated with Vigabatrin
Epilepsy & Behavior, 2016Co-Authors: Gregory L Krauss, Donald W Shields, Robert C Sergott, Edward Faught, Rod Foroozan, John M Pellock, Adam Ziemann, Yekaterina Dribinsky, Deborah Lee, Sarah TorriAbstract:Vigabatrin (Sabril®), approved in the US in 2009, is currently indicated as adjunctive therapy for refractory complex partial seizures (rCPS) in patients ≥ 10 years old who have responded inadequately to several alternative treatments and as monotherapy for infantile spasms (IS) in patients 1 month to 2 years of age. Because of reports of vision loss following Vigabatrin exposure, FDA approval required a risk evaluation mitigation strategy (REMS) program. Vigabatrin is only available in the US through Support, Help, And Resources for Epilepsy (SHARE), which includes a mandated registry. This article describes 5 years of demographic and treatment exposure data from adult patients (≥ 17 years old) in the US treated with Vigabatrin and monitored in the ongoing Sabril® registry. Registry participation is mandatory for all US Sabril® prescribers and patients. A benefit-risk assessment must be documented by the physician for a patient to progress to maintenance therapy, defined as 1 month of Vigabatrin treatment for patients with IS and 3 months for patients with rCPS. Ophthalmologic assessments must be documented during and after completion of therapy. As of August 26, 2014, a total of 6823 patients were enrolled in the registry, of which 1200 were adults at enrollment. Of these patients, 1031 (86%) were naive to Vigabatrin. The majority of adult patients (n=783, 65%) had previously been prescribed ≥ 4 AEDs, and 719 (60%) were receiving ≥ 3 concomitant AEDs at Vigabatrin initiation. Prescribers submitted an initial ophthalmological assessment form for 863 patients; an ophthalmologic exam was not completed for 300 (35%) patients and thus, were considered exempted from vision testing. Of these patients, 128 (43%) were exempted for neurologic disabilities. Clinicians discontinued treatment in 8 patients because of visual field deficits (VFD) (5 patients naive to Vigabatrin and 3 patients previously exposed). Based on Kaplan-Meier survival estimates, it is estimated that approximately 71%, 55%, and 40% of adult patients naive to Vigabatrin would remain in the registry at 3, 6, and 12 months, respectively. These demographic data suggest that a proportion of adult patients remain on Vigabatrin long-term despite the risks of adverse events and significant underlying AED resistance and neurologic disease.
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registry initiated to characterize vision loss associated with Vigabatrin therapy
Epilepsy & Behavior, 2011Co-Authors: John M Pellock, Donald W Shields, Gregory L Krauss, Robert C Sergott, Edward Faught, Rod Foroozan, Gregory A Burkhart, David L Wesche, Mark A WeinbergAbstract:Abstract The Vigabatrin patient registry was implemented in August 2009 in conjunction with Food and Drug Administration approval of Vigabatrin. All US Vigabatrin-treated patients must enroll in the registry. Data on prescriber specialty/location, patient demographics, and clinical characteristics are collected. Benefit–risk assessments are required early in the course of therapy. Vision assessments are required at baseline (≤ 4 weeks after therapy initiation), every 3 months during therapy, and 3 to 6 months after discontinuation. As of February 1, 2011, 2473 patients (1500 with infantile spasms, 846 with refractory complex partial seizures, 120 with other diagnoses) had enrolled; 30.4% were previously exposed to Vigabatrin. Kaplan–Meier analysis of time in registry indicated that 83 and 97% of all enrolled patients with refractory complex partial seizures and infantile spasms remained beyond 3 and 1 month, respectively. The ongoing registry will provide visual status and other information on Vigabatrin-treated patients for both the infantile spasm and refractory complex partial seizure indications.
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Evaluating Risks for Vigabatrin Treatment
Epilepsy currents, 2009Co-Authors: Gregory L KraussAbstract:Approximately 30 to 40 percent of adults with epilepsy treated chronically with Vigabatrin develop concentric visual field constrictions. These deficits are generally mild and asymptomatic, but are usually irreversible, so risks and benefits for Vigabatrin treatment must be carefully reviewed. Infantile spasms, a particularly severe form of epilepsy, may respond to Vigabatrin; however, some infants treated with the drug develop MRI evidence of possible intramyelinic edema in subcortical structures. This article reviews the benefits of Vigabatrin treatment, the risks it poses to the retina and the developing brain, as well as possible subgroups of adults and infants with severe epilepsy for whom treatment may, nevertheless, be warranted.
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a controlled study comparing visual function in patients treated with Vigabatrin and tiagabine
Journal of Neurology Neurosurgery and Psychiatry, 2003Co-Authors: Gregory L Krauss, Mary A Johnson, S Sheth, Neil R MillerAbstract:Objective: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain γ-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, Vigabatrin, and patients treated with other AEDs. Methods: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, Vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. Results: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6° OD, 40.5° OS), while tiagabine patients had normal findings (mean 61° OD, 62° OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60° OD, 61° OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with Vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. Conclusion: Unlike Vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between Vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.
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visual dysfunction in patients receiving Vigabatrin clinical and electrophysiologic findings
Neurology, 1999Co-Authors: Neil R Miller, Mary A Johnson, S R Paul, Christopher A Girkin, Julian D Perry, M Endres, Gregory L KraussAbstract:Background: Vigabatrin is an antiepileptic drug that, although relatively well tolerated, is associated with visual field constriction and other visual disturbances of unclear origin. Methods: We performed a complete neuroophthalmologic examination and electrophysiologic studies on 39 patients receiving Vigabatrin and on 11 control patients. Results: Nearly 50% of patients receiving Vigabatrin had constricted visual fields compared with control patients. Some of the Vigabatrin patients also had reduced visual acuity and abnormal color vision. In addition, most Vigabatrin patients had abnormal electroretinographic results, the severity of which correlated strongly with the degree of visual field constriction. Conclusions: Vigabatrin can cause electrophysiologic evidence of retinal dysfunction and clinically detectable disturbances of visual sensory function.
Neil R Miller - One of the best experts on this subject based on the ideXlab platform.
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a controlled study comparing visual function in patients treated with Vigabatrin and tiagabine
Journal of Neurology Neurosurgery and Psychiatry, 2003Co-Authors: Gregory L Krauss, Mary A Johnson, S Sheth, Neil R MillerAbstract:Objective: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain γ-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, Vigabatrin, and patients treated with other AEDs. Methods: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, Vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. Results: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6° OD, 40.5° OS), while tiagabine patients had normal findings (mean 61° OD, 62° OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60° OD, 61° OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with Vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. Conclusion: Unlike Vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between Vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.
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visual dysfunction in patients receiving Vigabatrin clinical and electrophysiologic findings
Neurology, 1999Co-Authors: Neil R Miller, Mary A Johnson, S R Paul, Christopher A Girkin, Julian D Perry, M Endres, Gregory L KraussAbstract:Background: Vigabatrin is an antiepileptic drug that, although relatively well tolerated, is associated with visual field constriction and other visual disturbances of unclear origin. Methods: We performed a complete neuroophthalmologic examination and electrophysiologic studies on 39 patients receiving Vigabatrin and on 11 control patients. Results: Nearly 50% of patients receiving Vigabatrin had constricted visual fields compared with control patients. Some of the Vigabatrin patients also had reduced visual acuity and abnormal color vision. In addition, most Vigabatrin patients had abnormal electroretinographic results, the severity of which correlated strongly with the degree of visual field constriction. Conclusions: Vigabatrin can cause electrophysiologic evidence of retinal dysfunction and clinically detectable disturbances of visual sensory function.
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Vigabatrin associated retinal cone system dysfunction electroretinogram and ophthalmologic findings
Neurology, 1998Co-Authors: Gregory L Krauss, Mary A Johnson, Neil R MillerAbstract:Objective: To determine the sources of Vigabatrin-associated visual disturbances in patients treated for epilepsy. Background: Vigabatrin is an extremely effective antiepileptic drug that selectively increases brain gamma-aminobutyric acid (GABA). Several patients recently developed constricted visual fields during Vigabatrin treatment in the United Kingdom, indicating the possibility of GABA-associated retinal dysfunction. Methods: Patients with visual symptoms treated chronically with Vigabatrin at our center underwent visual evoked potentials (VEP), electroretinograms (ERG), and visual field and ophthalmologic examinations. Results: Four of 38 patients treated with Vigabatrin developed visual symptoms 2 to 40 months after starting the drug. Two patients complained of constricted visual fields and two had blurred vision. ERG demonstrated evidence of bilateral retinal dysfunction consistent with reduced inner retinal cone response in all four patients. Oscillatory potential responses were lost, suggesting impairment of the highly GABAergic amacrine cells. Two of the patients had normal VEPs and minimal findings on clinical ophthalmology examinations despite abnormal ERGs. Abnormal examination findings were narrowed retinal arteries, surface wrinkling retinopathy, and abnormal macular reflexes. One patient also had reduced rod photoreceptor function in the more symptomatic left eye. Conclusions: Visual field constriction and blurring during Vigabatrin therapy is associated with retinal cone system dysfunction. Visual symptoms may represent selective vulnerability of retinas of affected patients to GABAergic effects of Vigabatrin. The prevalence and course of retinal changes associated with Vigabatrin therapy are important to determine in a larger group of patients.
Lionel Carmant - One of the best experts on this subject based on the ideXlab platform.
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magnetic resonance imaging abnormalities associated with Vigabatrin in patients with epilepsy
Epilepsia, 2009Co-Authors: James W Wheless, Lionel Carmant, Martina Bebin, Joan A Conry, Catherine Chiron, Roy D Elterman, Michael Frost, Juliann M Paolicchi, Donald W Shields, Elizabeth A ThieleAbstract:Summary Purpose: Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with Vigabatrin for refractory complex partial seizures (CPS). Methods: Medical records and 332 cranial MRIs from 205 infants (aged ≤24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2–16 years) and adults (aged >16 years) with CPS were re-reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T2-weighted or fluid-attenuated inversion-recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with Vigabatrin were estimated. Results: Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among Vigabatrin-treated versus Vigabatrin-naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)—Vigabatrin was discontinued in four. Among adults and children treated with Vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between Vigabatrin-exposed and Vigabatrin-naive subjects. Discussion: Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on Vigabatrin therapy.
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Magnetic resonance imaging abnormalities associated with Vigabatrin in patients with epilepsy.
Epilepsia, 2008Co-Authors: James W Wheless, Lionel Carmant, Martina Bebin, Joan A Conry, Catherine Chiron, Roy D Elterman, Michael Frost, Juliann M Paolicchi, W. Donald Shields, Elizabeth A ThieleAbstract:Summary Purpose: Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with Vigabatrin for refractory complex partial seizures (CPS). Methods: Medical records and 332 cranial MRIs from 205 infants (aged ≤24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2–16 years) and adults (aged >16 years) with CPS were re-reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T2-weighted or fluid-attenuated inversion-recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with Vigabatrin were estimated. Results: Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among Vigabatrin-treated versus Vigabatrin-naive subjects (22% vs. 4%; p
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ACTH versus Vigabatrin therapy in infantile spasms: a retrospective study.
Neurology, 1999Co-Authors: Patrick Cossette, James J. Riviello, Lionel CarmantAbstract:ACTH is the standard treatment for infantile spasms (IS) in North America. Recent reports showed that Vigabatrin is a valuable treatment for IS, but comparative studies with ACTH are limited. In this study, we compare the effectiveness of ACTH versus Vigabatrin on IS. Our results support that Vigabatrin is as effective as and better tolerated than ACTH. Because of their similar efficacy, we believe that Vigabatrin should be the first intention drug for the treatment of IS.
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acth versus Vigabatrin therapy in infantile spasms a retrospective study
Neurology, 1999Co-Authors: Patrick Cossette, James J. Riviello, Lionel CarmantAbstract:Article abstract ACTH is the standard treatment for infantile spasms (IS) in North America. Recent reports showed that Vigabatrin is a valuable treatment for IS, but comparative studies with ACTH are limited. In this study, we compare the effectiveness of ACTH versus Vigabatrin on IS. Our results support that Vigabatrin is as effective as and better tolerated than ACTH. Because of their similar efficacy, we believe that Vigabatrin should be the first intention drug for the treatment of IS.
Reetta Kälviäinen - One of the best experts on this subject based on the ideXlab platform.
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Non-vision adverse events with Vigabatrin therapy.
Acta neurologica Scandinavica. Supplementum, 2011Co-Authors: S. D. Walker, Reetta KälviäinenAbstract:Walker SD, Kalviainen R. Non-vision adverse events with Vigabatrin therapy. Acta Neurol Scand: 2011: 124 (Suppl. 192): 72–82. © 2011 John Wiley & Sons A/S. Vigabatrin is an effective antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS). In clinical trials, Vigabatrin was generally well-tolerated with an adverse event profile similar to that of other AEDs. The most common treatment-related adverse events were central nervous system effects, including drowsiness, dizziness, headache, and fatigue, with adjunctive Vigabatrin in adults with rCPS, and sedation, somnolence, and irritability with Vigabatrin monotherapy in infants with IS. Vigabatrin had little effect on cognitive function, mood, or behavior in a battery of neuropsychologic tests for rCPS. In placebo-controlled clinical trials, the incidence of depression and psychosis, but not other psychiatric adverse events, was greater with Vigabatrin than placebo. Intramyelinic edema (IME) was initially identified in rats and dogs and led to a temporary suspension of clinical trials in the United States. IME was subsequently correlated with delays in evoked potential (EP) and increased T2-weighted signals on magnetic resonance imaging (MRI). Clinical trials of Vigabatrin were allowed to resume after IME was not detected by neuropathologic assessments of autopsy and neurosurgical specimens or by serial EP or MRI assessments in older children and adults receiving Vigabatrin. Subsequently, MRI abnormalities characterized by increased T2 intensity and restricted diffusion were identified in infants treated with Vigabatrin for IS. These abnormalities generally resolved with discontinuation of Vigabatrin and, in some cases, during continued therapy. The benefit of improved seizure control must be balanced against the potential risks associated with Vigabatrin, including abnormal MRI changes and other Vigabatrin-related safety issues.
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Visual field defects with Vigabatrin: epidemiology and therapeutic implications.
CNS drugs, 2001Co-Authors: Reetta Kälviäinen, Iiris NousiainenAbstract: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.
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Vigabatrin a gabaergic antiepileptic drug causes concentric visual field defects
Neurology, 1999Co-Authors: Reetta Kälviäinen, Iiris Nousiainen, Maija Mantyjarvi, Eeva Nikoskelainen, Juhani Partanen, K Partanen, Paavo J RiekkinenAbstract: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.
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Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy a randomized controlled study
JAMA Neurology, 1995Co-Authors: Reetta Kälviäinen, Marja Aikia, Anna Maija Saukkonen, Esa Mervaala, Paavo RiekkinenAbstract: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.
