Vigabatrin-Induced Peripheral Visual Field Defects in Patients With Refractory Partial Epilepsy

Purpose: Vigabatrin can cause retinopathy, resulting in bilateral visual field constriction. Previous analyses of results from a prospective, observational study assessing vigabatrin-induced visual field constriction (described below) employed a partially subjective interpretation of static perimetery. In an effort to affirm these previous findings through more objective, quantitative methodology, we now report data from a subset analysis of refractory partial epilepsy patients in the study who underwent Goldmann kinetic perimetry. Methods: Patients aged ≥8 years with refractory partial seizures were enrolled and grouped: those receiving vigabatrin for ≥6 months (Group I); those who had received vigabatrin for ≥6 months and then had discontinued for ≥6 months (Group II); and those naïve to vigabatrin (Group III). Patients underwent static or kinetic perimetry or both every 4–6 months for ≤3 years. For kinetic perimetry, the temporal and nasal visual fields were measured along the horizontal meridian with the largest (V4e, IV4e) and smallest (I2e, I1e) isopters, respectively. Results: Of 735 patients enrolled, 341 had Goldmann perimetry data. Of these, 258 received vigabatrin. Sixteen percent of vigabatrin-exposed patients had moderate visual field defects (30°–60° retained temporal vision), and 3% had severe defects (\u3c30° retained temporal vision). Visual function questionnaire results indicated a weak correlation between visual field constriction severity and visual symptoms. Conclusions: These results affirm both an analysis of the same study based primarily on static perimetry and findings from cross-sectional studies. The present analysis verifies that visual field constriction, when it occurs, is most often mild or moderate and is not associated with symptoms of abnormal visual function. The clinical decision to prescribe vigabatrin should be based on a benefit-risk analysis for each individual patient

Three-dimensional neurorehabilitation: a different perspective

The authors have narrated their perspective on rehabilitation of neurological disabilities based upon their experiences in three different regions of the globe, hence the word three dimensional . It also reflects the need of holistic approach in neurorehabilitation. The article emphasizes the significance of impact of socio-cultural factors on disability and the way different challenges can change outcomes of the same neurological impairment in different health care systems. The understanding, perception and management of disability secondary to any neurological impairment varies greatly from one region to another across the world. Hence treatment guidelines applicable in one socioeconomic setup may not be applicable in another setting, making neurorehabilitation a very unique specialty of medicine. Conventionally, in the field of medicine, popular treatment guidelines usually originate in high income countries, which are considered standards of practice even by developing health systems regardless of the feasibility of their application. Neurorehabilitation guidelines need to be unique to health systems having socio-economic and cultural similarities. The general perception of disability and cultural needs should be given high consideration while dealing with neurological impairments; rendering the need of tailored guidelines specific to each population. This idea is new to medical education and disability care. It deserves more attention among health care providers dealing with functional limitations secondary to neurological impairments

Does the Swedish Interactive Threshold Algorithm (SITA) accurately map visual field loss attributed to vigabatrin?

Purpose Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. Methods The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years ± 14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. Results SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots , defect area and defect severity. Conclusions Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients

The right and the wrong with epilepsy and her science

This is a commentary and an opinion paper attempting a critical reassessment of the methods and practices of epilepsy research as we see it. The enormous progress in the field of epilepsy in recent years is a cause of celebration. Advances have been made on most fronts, and the position of patients with epilepsy in society has greatly improved. However, there have also been culs‐de‐sac and dead ends of modern science and clinical practice which are also intriguing. It may be true that we can learn more from our mistakes than from our successes. In this opinion paper, we have listed some of the successes and some of the failures of past epilepsy practice, and also areas of current practice and theory which we feel are likely to prove mistaken. The underlying reasons for misdirected practices and theories include, in our view, the influence of fashion, bad science, and the bureaucracies of practice and academic medicine. As a result, some findings are far from objective. Recognition is the first step to remediation, and hopefully future research will minimize some of the pitfalls mentioned in this article and bring the “End of Epilepsy,” as defined and predicted by Oswei Temkin, closer than it is today

Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review.

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases

Treatment of refractory complex partial seizures: role of vigabatrin

Vigabatrin (VGB) is an antiepileptic drug that was designed to inhibit GABA-transaminase, and increase levels of γ-amino-butyric acid (GABA), a major inhibitory neurotransmitter in the brain. VGB has demonstrated efficacy as an adjunctive antiepileptic drug for refractory complex partial seizures (CPS) and for infantile spasms (IS). This review focuses on its use for complex partial seizures. Although VGB is well tolerated, there have been significant safety concerns about intramyelinic edema and visual field defects. VGB is associated with a risk of developing bilateral concentric visual field defects. Therefore, the use of VGB for complex partial seizures should be limited to those patients with seizures refractory to other treatments. Patients must have baseline and follow-up monitoring of visual fields, early assessment of its efficacy, and ongoing evaluation of the benefits and risks of VGB therapy

Vigabatrin and Visual Field Defects in Pediatric Epilepsy Patients

We studied the prevalence, type and severity of vigabatrin (VGB)-attributed visual field defects (VFDs), and used these data to assess the associated risk factors in pediatric patients. Medical records were retrospectively reviewed for 67 pediatric patients who received VGB alone or in combination with other antiepileptic drugs, and who had undergone visual field examinations using a Humphrey visual field analyzer. Of the 67 patients, 15 had VGB-attributed VFDs: 13 had nasal arcuate type, 1 had nasal and temporal constricted type and 1 had nasal constricted type. In terms of severity, 7 patients had Grade I VGB-attributed VFDs, 5 had Grade II, 2 had Grade III, and 1 had Grade IV. Although there were no significant differences between the VFD and non-VFD groups with regards to all tested parameters, there were no cases of VGB-attributed VFDs in patients with total treatment durations <2 yr and cumulative doses <10 g/kg. In conclusion, the prevalence of VGB-attributed VFDs in VGB-treated pediatric epilepsy patients was 22%. The high frequency of VGB-attributed VFDs indicates that physicians should inform all patients of this risk prior to VGB treatment and perform periodic visual field examinations

Peripapillary retinal nerve fibre layer thickness in individuals with epilepsy exposed to vigabatrin

Background: The antiepileptic drug vigabatrin (VGB) is associated with the development of visual field loss in around 50% of exposed individuals. The mechanisms of VGB retinotoxicity are unknown, and there is continued debate as to the best methods of assessing visual function in VGB-exposed individuals, particularly in those unable to perform perimetry. Methods: 204 VGB-exposed individuals, 90 non-exposed individuals with epilepsy and 90 healthy controls participated. Individuals underwent visual field testing using Goldmann kinetic perimetry and peripapillary retinal nerve fibre layer (ppRNFL) imaging using optical coherence tomography (OCT). Results: A retrospective analysis of the evolution of vigabatrin associated visual field loss (VAVFL) in individuals continuing VGB showed progression of VAVFL in all individuals over a ten-year period. More VGB-exposed individuals were able to perform OCT compared to perimetry. Measures of ppRNFL thickness were found to be highly repeatable in this population. There was a strong correlation between ppRNFL thickness and visual field size suggesting that irreversible VAVFL may be related to loss of retinal ganglion cells (RGCs). Duration of VGB exposure, maximum daily VGB dose, male gender and the presence of a homonymous visual field defect were associated with ppRNFL thinning. The pattern of ppRNFL thinning suggested that ppRNFL loss progresses with increasing VGB exposure. Subtle ppRNFL thinning may occur in discrete areas after exposure to small amounts of VGB, whilst other ppRNFL areas appear to be resistant to large cumulative VGB exposure. The ppRNFL was significantly thinner in non-exposed individuals with epilepsy compared to healthy controls. Factors that may be associated with ppRNFL thinning included the presence of learning disability, MTLE with HS and longer duration of epilepsy. Conclusions: ppRNFL imaging using OCT provides a useful tool to assess VGB-exposed individuals, and can provide an accurate estimate of the extent of VAVFL in the absence of a reliable direct measure of the visual field. Understanding patterns of ppRNFL thinning associated with cumulative VGB-exposure may aid in the early detection of VGB toxicity. Pathophysiological mechanisms of VAVFL are unknown; however, pathology of RGC apparatus is evidently implicated