Vigabatrin-associated brain abnormalities on magnetic resonance imaging in the treatment of infantile spasms: a case report / 中华神经科杂志

Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) is a relatively rare side effect of vigabatrin, most of which are asymptomatic. However, there will be extremely rare cases with hyperkinetic disorders, myoclonus, tremor, and acute encephalopathy under certain circumstances. VABAM is often underappreciated by physicians and its accurate incidence remains unclear. A female infant who was diagnosed with infantile spasms and required adrenocorticotropic hormone therapy accompanied by various antiseizure medicines was reported. Unfortunately, she became lethargic and her spasm deteriorated gradually after vigabatrin exposure. Her brain magnetic resonance imaging revealed abnormal signals bilaterally in the dorsal midbrain, thalamus, and rostral part of the pallidum. She had a seizure amelioration and became lively as a result of vigabatrin withdrawal. In the meanwhile, magnetic resonance imaging returned to normal. Attempts were made to discover the risk factors of VABAM and potential pathogenesis. Further understanding of the disease should contribute to decreasing misdiagnosis and making precise decisions.

Progress in efficacy and safety of vigabatrin in treatment of epilepsy associated with tuberous sclerosis complex in children / 国际儿科学杂志

Tuberous sclerosis complex(TSC)is an autosomal dominant skin-nerve syndrome with diverse clinical manifestations.Epilepsy is the most common neurological manifestation.Vigabatrin(VGB)is an inhibitory neurotransmitter γ-aminobutyric acid(GABA)analogue.It reduces the degradation of GABA by irreversibly binding to GABA transaminase, thereby increasing the level of GABA in the central nervous system and exerting anti-epileptic effects.It is suitable for the treatment of various types of epilepsy related to TSC.In recent years, the preventive effect of VGB in TSC-related epilepsy has attracted wide attention.There is a certain degree of adverse reactions during the use of VGB, the most noteworthy of which is the visual field and central nervous system changes.This article reviews the efficacy and safety of VGB in the treatment of TSC-related epilepsy.

Vigabatrina comparado con hormona adrenocorticotrópica para el tratamiento de espasmos infantiles y Síndrome de West / Vigabatrin compared with adrenocorticotropic hormone for the treatment of infantile spasms and West Syndrome

OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.

OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.

Efectos Adversos del Tratamiento con Vigabatrina en Síndrome de West: reporte de 2 casos / Adverse Effects of Vigabatrin Use for West Syndrome treatment: a report of 2 Clinical Cases

El síndrome de West (SW) es un síndrome epiléptico de la infancia temprana. Dentro de los fármacos de primera línea utilizados para su tratamiento se encuentran la hormona adrenocorticotropa (ACTH) y Vigabatrina. Estudios sugieren igual efectividad en el uso a largo plazo de ambos para controlar el SW. En Chile, el uso de Vigabatrina ha aumentado dada su mayor disponibilidad, facilidad de uso y menor costo. Se describen 2 casos clínicos presentando complicaciones agudas infrecuentes secundarias a su uso. Ambos pacientes con antecedentes de SW y trisomía 21. Primer caso: Lactante de 11 meses que inicia tratamiento con 100 mg/kg/día de Vigabatrina a los 7 meses, aumentando a 150 mg/kg/día por mala respuesta. Evolucionó con un síndrome extrapiramidal, con alteraciones radiológicas características. Segundo caso: Lactante de 7 meses, que tras iniciar tratamiento con vigabatrina (100 mg/kg/día) desarrolla rash facial sugerente de hipersensibilidad a fármacos antiepilépticos (FAEs), sin compromiso mucoso ni alteraciones sistémicas. Ambas regresan a su basal luego de suspensión o disminución de dosis del medicamento. Destaca la importancia de la monitorización de efectos adversos en el uso de FAEs y atender la aparición de reacciones poco conocidas. Las alteraciones imagenológicas por Vigabatrina son conocidas, no así el síndrome extrapiramidal asociado (primer caso). Por otra parte, las reacciones cutáneas están ampliamente descritas para múltiples FAEs, pero no para Vigabatrina (segundo caso). Dado el uso frecuente de Vigabatrina para tratar SW y otras epilepsias, es fundamental conocer y manejar reacciones adversas poco conocidas como las aquí presentadas. Palabras claves: Síndrome de West, Síndrome de Down, espasmos infantiles, vigabatrina, reacciones adversas, toxicidad, alergia, rash.

West Syndrome is an epileptic syndrome which typically presents in early childhood. In regard to treatment, the first line includes adrenocorticotropic hormone (ACTH) and Vigabatrin. Studies suggest similar response in the long term to both treatments. In Chile, Vigabatrin is being used more frequently as it is more available, of easier administration and lower cost. We present in the following report 2 clinical cases that presented acute infrequent complications secondary to its use in patients with both Down and West Syndrome. First case: 11-month-old infant who was initially treated with 100mg/kg/day of Vigabatrin at 7 months of age and increased to 150mg/kg/day due to lack of response. She evolved with an extrapyramidal syndrome with radiological manifestations. The second case: 7-month old toddler who initiated treatment with 100mg/kg/day of Vigabatrin and developed a facial rash, suggestive of hypersensitivity to antiepileptic drugs, with no mucosal or systemic involvement. Both patients returned to their previous condition shortly after Vigabatrin was decreased or discontinued. We emphasize the importance of the early monitorization of adverse effects in the use of antiepileptic drugs and awareness of less common reactions. Radiological findings associated with the use of Vigabatrin are well known, but not the clinical evolution with symptomatic extrapyramidal symptoms, as in the first case. Allergic reactions to the use of antiepileptic drugs have also been reported to several drugs, but not to Vigabatrin (second case). As Vigabatrin is being used more frequently to treat WS and other epilepsies it is important to know and manage uncommon adverse reactions as the ones presented in this report. Keywords: West Syndrome, Down Syndrome, infantile spasms, vigabatrin, adverse reactions, toxicity, allergy, rash

Síndrome transicional: del síndrome de West al síndrome de Lennox-Gastaut / Transional syndrome: from West to Lennox-Gastaut syndromes

El síndrome de West o espasmos infantiles, es una encefalopatía epiléptica clasificada como epilepsias y síndromes generalizados. Hay múltiples informes de la evolución de síndrome de West a síndrome de Lennox-Gastaut de un 25 hasta 60%, sin reconocerse una causa específica. Se ha comunicado que pueden ser solo una entidad epiléptica dependiente de la edad y que estaría en relación con el grado de inmadurez cerebral. En esta revisión retrospectiva de 130 casos de espasmos infantiles, solo 14 (10.7%) evolucionaron a Lennox-Gastaut. El haber recibido en todos los casos vigabatrina como tratamiento nos hace suponer que la baja incidencia podría estar relacionada con el uso de este fármaco. Dado que la vigabatrina tiene una acción gabaérgica y aumenta los niveles de ACTH podría explicar esta relación, pero esto deberá confirmarse con el mejor conocimiento de los mecanismos íntimos de estas graves encefalopatías.

West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.

Progress in the treatment of infantile spasms / 中华实用儿科临床杂志

Infantile spasms constitutes an unique,age-specific epilepsy syndrome of early infancy characterized by epileptic spasms often accompanied by neurodevelopmental regression and an electroencephalograph finding of hypsarrhythmia.For the complex and various etiologies,the pathogenesis remains unclear.Although the relevant guidelines and consensuses are being updated all the time,but proven therapies are still limited because of efficacy,tolerability,at times even availability.In this paper,the current findings regarding up-to-date advances in the treatment of infant spasms were reviewed,especially in use of the corticosteroid and vigabatrin as well as the quality-of-care indicators for infantile spasms.

Newer Anti-epileptic Drugs.

Need and Purpose of review: A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children. Methods used for locating, selecting, extracting and synthesizing data: MEDLINE search (1966-2013) was performed using terms “newer anti-epileptic drugs”, “Oxcarbazepine”, vigabatrin”, topiramate”, “zonisamide”, “levetiracetam”, “lacosamide”, “rufinamide”, “stiripentol”, “retigabine”, “eslicarbazepine”, “brivaracetam”, “ganaxolone” and “perampanel” for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children. Main conclusions: Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine , levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.

Vigabatrina aumenta atividade da superóxido dismutase no corpo estriado de ratos após crises convulsivas induzidas pela pilocarpina / Vigabratine increases superoxide dismutase activity in striatum of rat after pilocarpine-induced seizures

CONTEXTO: Tem sido sugerido que durante as crises convulsivas induzidas pela pilocarpina pode ser observado aumento no estresse oxidativo cerebral. Estudos sugerem que compostos com atividade antioxidante podem fornecer certo grau de proteção contra a neurotoxicidade induzida pelas crises convulsivas. OBJETIVOS: O presente estudo investigou as ações farmacológicas da vigabatrina nas alterações comportamentais e na atividade enzimática da superóxido dismutase (SOD) no corpo estriado de ratos adultos. MÉTODOS: Ratos Wistar adultos (2 meses de idade) foram usados nos experimentos e divididos em quatro grupos. O primeiro foi tratado com solução salina 0,9 por cento (grupo controle). O segundo grupo foi tratado com pilocarpina (400 mg/kg, i.p., grupo P400). O terceiro grupo foi tratado com vigabatrina (500 mg/kg, i.p., grupo VGB) e o quarto grupo foi tratado com vigabatrina (500 mg/kg, i.p.) e 30 minutos depois com pilocarpina (400 mg/kg, i.p., grupo VGB + P400). Os animais que apresentaram crises convulsivas, estado de mal epiléptico e não morreram durante o período de 24 horas de observação foram sacrificados para dissecação do corpo estriado para realização da determinação da atividade da SOD. RESULTADOS: Os estudos comportamentais revelaram que, após administração de pilocarpina, todos os animais apresentaram sinais colinérgicos periféricos, movimentos estereotipados e tremores. No mesmo grupo, foram observados, em 75 por cento dos animais, crises convulsivas e o estado de mal epiléptico. Por sua vez, o pré-tratamento com vigabatrina produziu redução significativa de 50 por cento nas crises convulsivas. Com relação aos estudos neuroquímicos, não foram observadas alterações na atividade da SOD no corpo estriado do grupo P400, em comparação aos valores do grupo controle. No entanto, no grupo VGB + P400 foi visto aumento significativo na atividade da SOD de 34 por cento e 35 por cento, quando comparado aos grupos controle e P400, respectivamente. ...

BACKGROUND: Pilocarpine-induced seizures have been suggested to be mediated by increases in oxidative stress. Current studies have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures. OBJECTIVES: This study investigated the pharmacological actions of vigabatrin on behavioral changes and superoxide dismutase (SOD) activity in striatum of adult rats. METHODS: Adult rats (2 months old) were used in the experiments and divided into four groups. The first was treated with 0.9 percent saline (control group). The second group was treated with pilocarpine (400 mg/kg, i.p., P400 group). The third group received vigabatrin alone (500 mg/kg, i.p., VGB group) and the fourth group was treated with vigabatrin (500 mg/kg, i.p.) and 30 minutes later received pilocarpine (400 mg/kg, i.p., VGB + P400 group). The animals which had seizures and status epilepticus (SE) and did not die within 24 hours of observation were sacrificed to perform the neurochemical studies. RESULTS: Behavioral studies showed that the administration of pilocarpine produces peripheral cholinergic signs, tremors and stereotyped movements in all animals. An amount of 75 percent of those rats developed to seizures and SE. In turn, the pre-treatment with vigabatrin produced a 50 percent reduction in the rate of seizures and SE. Regarding the neurochemical studies, there were no changes in the striatal SOD activity in P400 group as compared to the control group. However, in the VGB + P400 group it was verified significant increases in SOD activity of 34 percent and 35 percent as compared to control and P400 group, respectively. DISCUSSION: Our results indicate that behavioral changes occur during seizures, but SOD activity remained unaltered during the acute phase of the convulsive crisis. Our findings suggest that the anticonvulsant effect of vigabatrin may be the result of modulation of this enzyme, in an attempt to protect ...

Incontinentia pigmenti: presentación neonatal: a propósito de un caso clínico / Incontinentia pigmenti: neonatal presentation: a purpose of clinical case

La incontinentia pigmenti (IP) también conocida como síndrome de Bloch-Sulzberger, es una genodermatosis infrecuente ligada al cromosoma X que afecta tejidos derivados del neuroectodermo: piel, faneras, ojos, sistema nervioso central y dientes. En la etapa neonatal se plantean diagnósticos diferenciales como el impétigo ampollar, herpes neonatal, citomegalovirus, mastocitosis, epidermólisis ampollar hereditaria. El diagnóstico temprano permite detectar las posibles patologías asociadas, que son determinantes para el pronóstico del paciente.

Incontinentia pigmenti, also known as Bloch-Sulzberger syndrome, is a rare congenital X-linked genodermatosis with variable involvement of tissues derived from neuroectoderm and mesoderm skin, hair, nails, eyes and central nervous system. Differential diagnoses are manifested in the neonatal period, such as bullous impetigo, neonatal herpes, cytomegalovirus, mastocytosis and hereditary epidermolysis bullosa. Early diagnosis allows detection of associated diseases which determine the patients prognosis.

Study of Clinical Course of Epilepsy in Children with Tuberous Sclerosis Complex / 대한간질학회지

PURPOSE: The aim of this study is to investigate the incidence, clinical features and outcome in pediatric tuberous sclerosis complex(TSC) patients with epilepsy. METHODS: Fifty seven of 74 patients (77.0%) were included in the study, who were diagnosed with epilepsy associated with TSC from 1991 to 2008. Clinical data were obtained from medical records retrospectively. RESULTS: Of the 57 patients, initial seizure types were infantile spasms (n=25, 43.8%), complex partial seizure (n=24, 42.1%), generalized tonic seizure (n=5, 8.7%), simple partial seizure (n=2, 3.4%), and atonic seizure (n=1, 1.7%), respectively. Seventeen patients (29.8%) had changes of their seizure types during the clinical course. Excluding the five patients with insufficient data, 52 patients were treated with antiepileptic drugs and four of them underwent epilepsy surgery. Twenty-six of 52 patients (50.0%) with medical treatment and two patients (50.0%) with epilepsy surgery became seizure free. Among the patients with infantile spasms, vigabatrin induced seizure freedom in 13 of 14 patients (92.8%) within four weeks, and five of them maintained seizure remission with vigabatrin monotherapy. CONCLUSIONS: Half of epileptic patients showed good responses to medical treatment, especially vigabatrin for infantile spasms. Epilepsy surgery can be treatment option for selected patients.

El pretratamiento agudo y subcrónico con farmacos anticonvulsivantes modifica las crisis generalizadas inducidas por el pentilenetetrazol en el ratón / The acute and subchronic pretreatment with antiepileptic drugs modifies the pentylenetetrazol- induced generalized seizures in mice

Objetivo: El incremento en el contenido de GABA cerebral o la administración de un agente GABA-mimético se emplea como un tratamiento antiepiléptico eficaz. Sin embargo, se sugiere que el empleo de farmacos que alteran continuamente la transmisión sinoptica puede afectar al sistema nervioso. En el presente estudio se evaluaron los efectos del pretratamiento agudo (una administración) y subcrónico (administraciones diarias por 7 días) de diazepam (DZP; 10 mg/kg, ip), gabapentina (GBP, 100 mg/kg, vo) y vigabatrina (VGB, 500 mg/kg, vo) en las crisis generalizadas inducidas por pentilenetetrazol (PTZ, 80 mg/kg ip). Materiales y métodos: Ratones macho de la cepa taconic (20-25 g) recibieron tratamiento agudo y subcrónico de DZP, GBP o VGB y 24 h después de la última administración se aplicó PTZ. Se evaluaron las latencias a la primera crisis clónica, a la fase tónica así como la incidencia de muerte. Resultados: El pretratamiento agudo con DZP protegió 100 por ciento a los animales de los efectos del PTZ, mientras que su administración subcrónica redujo la latencia a la crisis clónica (21 por ciento; p<0.05), la fase tónica (27 por ciento, p<0.05) y muerte (37 por ciento, p<0.05). La aplicación aguda de VGB protegió 100 por ciento a los animales de los efectos del PTZ, mientras que su aplicación subcrónica aumentó la latencia a las crisis clónicas (32 por ciento, p<0.05), aunque facilitó la aparición de la crisis tónica (55 por ciento, p<0.05) y la muerte (58 por ciento, p<0.05). La administración aguda de GBP elevó la latencia a la crisis clónica (52 por ciento, p<0.05), mientras que su administración subcrónica no modificó el efecto producido por PTZ. Conclusiones: Estos resultados sugieren que el pretratamiento agudo y subcrónico de farmacos que incrementan la transmisión GABAérgica modifican diferencialmente la susceptibilidad a las crisis por PTZ y que su administración repetida puede facilitar la producción de crisis convulsivas.

Objetives: The increased GABA content or administration of a centrally active GABA-mimetic agent have been used as a efficacious anticonvulsant therapeutic approach. However, it has been suggested that the use of drugs that continually and noncontingently alter synaptic transmission could alter at the nervous system. The present study was carried out to investigate the effects of acute (one administration) and subchronic (7 daily administrations) treatments with Diazepam (DZP; 10 mg/kg, ip), Gabapentin (GBP, 100 mg/kg. vo) and Vigabatrin (VGB, 500 mg/kg, vo) on pentylenetetrazol-induced generalized seizures (PTZ, 80 mg/kg, ip). Materials and methods: Male Taconic mice (20-25 g) received acute or subchronic treatment with DZP, VGB or GBP and 24 h after the last administration, the effects of PTZ (latency to the clonus, forelimb extension and death incidence) were evaluated. Results: Acute DZP protected all animals (100 percent) to the convulsant effects of PTZ, whereas subchronic DZP decreased the latency to the clonic (21 percent; p<0.05), tonic (27 percent, p<0.05) and death (37 percent, p<0.05). The acute treatment with VGB protect all animals (100 percent) to the effects of PTZ, whereas its subcronic administration enhanced the latency to clonus (32 percent, p<0.05), but facilitated the appearance of tonic seizures (55 percent, p<0.05) and death (58 percent, p<0.05). The acute administration of GPB increased the latency to clonus (52 percent, p<0.05), whereas its subchronic treatment did not modify the PTZ-induced effects. Conclusions: The present results indicate that the acute pretreatment with drugs enhancing GABAergic transmission differently modifies the seizure susceptibility, and that the subchronic administration may facilitate the seizure activity.

Visual Field Changes in Pediatric and Adolescent Patients Treated with Vigabatrin

PURPOSE: To investigate perimetric changes in pediatric and adolescent patients treated with vigabatrin and to assess the relationship between the visual field defect and the cumulative dose, the duration of treatment, or the age when vigabatrin was first taken. METHODS: Pediatric and adolescent patients treated with vigabatrin for seizure for at least 6 months were examined with Goldmann perimetry. The cumulative dose, the duration of treatment, the age when vigabatrin was first taken, and whether a combination of anticonvulsants and vigabatrin was taken were recorded. Mean radial degree (MRD) determination from the right eye was used to compare the amount of constriction. RESULTS: Visual field constriction developed in 19 (27.1%) out of 70 patients and MRD decreased by 22.7% a mean duration of 86.7+/-27.4 months of treatment. The visual field significantly decreased in the superior, nasal, and inferior field with temporal and central sparing (p<0.001). There was a statistically significant correlation between the average MRD and the cumulative dose (r2=0.1772, p<0.001), and the duration of treatment (r2=0.1713, p<0.001), but no correlation between the average MRD and either the age when vigabatrin was first taken, or the combination of anticonvulsants with vigabatrin. CONCLUSIONS: Visual field constriction developed in one quarter of pediatric and adolescent patients treated with vigabatrin, which significantly correlated with the cumulative dose and the duration of treatment. Therefore, a regular examination of the visual field is warranted for pediatric and adolescent patients treated with vigabatrin.

Déficit de succínico semialdehído deshidrogenasa: Primer caso de aciduria 4 OH butírica en Uruguay

Resumen El déficit de succínico semialdehído deshidrogenasa es una enfermedad rara cuya alteración en la vía catabólica del ácido aminobutírico (principal neurotransmisor del sistema nervioso central) impide el paso de ácido succínico semialdehído a ácido succínico, condicionando un aumento de ácido 4 hidroxibutírico en líquido cefalorraquídeo y plasma, lo que permite la detección de la enfermedad. La clínica es muy inespecífica, pudiendo presentar desde retraso psicomotor, hipotonía, convulsiones y ataxia no progresiva, hasta trastornos de conducta con crisis de ansiedad y rasgos autistas. Los hallazgos a nivel electroencefalográfico incluyen enlentecimiento del ritmo de base, con descargas epileptiformes focales o generalizadas. En la neuroimagen, en tanto, pueden hallarse frecuentemente hiperintensidades bilaterales y simétricas en T2, a nivel del núcleo pálido. Si bien el tratamiento con vigabatrina teóricamente inhibe la formación de succínico semialdehído con la consecuente reducción de los niveles de ácido 4 hidroxibutírico, no existe al momento actual un tratamiento efectivo para todos los casos. El principal objetivo de este artículo es presentar un paciente con deficiencia de succínico semialdehído deshidrogenasa, debido a su excepcionalidad, con solamente 350 casos identificados en el mundo, siendo el primer caso diagnosticado en Uruguay.

Summary Succinic semialdehyde dehydrogenase deficiency is a rare disorder of the catabolic pathway of gamma-aminobutyric acid, the major central nervous system inhibitory neurotransmitter. Because of such deficiency, transamination of gamma-aminobutyric acid to succinic semialdehyde is shunted towards the production of 4-hydroxybutyric acid, a neurotoxic metabolite which becomes abundant in physiologic fluids which allows the detection of the disorder. Clinical features are not specific and consist of psychomotor retardation, seizures, hypotonia and non progressive ataxia. Electroencephalographic finding include background slowing and generalized or focal epileptiform discharges. Magnetic resonance imaging reveals in most of the cases, increased T2-weighted signal of the globus pallidi bilaterally and symmetrically. Eventhough vigabatrin should theoretically inhibit the formation of succinic semialdehyde and therefore 4-hydroxybutyric acid, to date there is no effective treatment for succinic semialdehyde dehydrogenase deficiency. Due to its uniqueness, the main objective of this article is to present a patient with succinic semialdehyde dehydrogenase deficiency, with only 350 cases identified worldwide.

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.

Visual Field Changes in Children with Vigabatrin Treatment

PURPOSE: Recently, several reports have documented persistent visual field changes associated with long-term use of Vigabatrin, an antiepileptic drug. Epilepsy is a common disease in children, therefore we investigated perimetric changes in children who were on Vigabatrin treatment. METHODS: Total 36 eyes of 18 patients who had been treated with Vigabatrin were tested with Humphrey Field Analyzer. The visual fields were assessed using central 30-2 threshold test and peripheral 60-4 threshold test. RESULTS: In central 30-2 threshold tests, 13 eyes(40.6%) showed mild visual field constrictions and 4 eyes(12.5%) showed severe visual field constrictions. In peripheral 60-4 threshold tests, 23 eyes(71.8%) showed visual field changes. CONCLUSIONS: Asymptomatic visual field loss may develop in Vigabatrin-treated children. Regular examinations of the visual field is warranted for Vigabatrin-teated children.

Assessment of the Relationship between Vigabatrin and Visual Field Defect in Children

PURPOSE: The authors carried out this study to determine the relationship between vigabatrin (VGB) and visual field defect. METHODS: Seventy eight patients older than 8 years who had epilepsy which had developed and been diagnosed, and were receiving add-on therapy, were the subjects of this study. If suspicious results were obtained from the initial test with the Humphrey automatic perimeter, the patient was tested again with the Goldman perimeter. Follow-up examinations were performed on these patients after 6 months. RESULTS: In this study, five of the 78 patients had suspicious primary test results, but upon the second examination they were all found to be normal. Thus there were no patients with visual field defects. CONCLUSIONS: VGB is a drug which may cause visual field defects, but in this study no patients presented with this symptom. Instead of limiting the use of VGB due to the adverse effect of visual field defect in the initial treatment of partial seizure and infantile spasm untreatable with other medication, if used with care it may not cause serious problems. Screening for visual defect is recommended, and in patients taking VGB regular examination is necessary.

Visual Field Defect in the Vigabatrin-treated Pediatric Patients / 대한소아신경학회지

PURPOSE: Vigabatrin has proved to be a successful and well tolerated drug used for the treatment of epilepsy of partial onset and for infantile spasms(West's syndrome). It is a selective and irreversible inhibitor of gamma-aminobutyric acid transaminase that is associated with visual field defect. We performed this study to investigate visual field defects in children treated with Vigabatrin. METHODS: We performed a complete neuroophthalmologic examination and electrophy siologic studies on 28 patients receiving Vigabtrin. They underwent static perimetry using either full field 81 points or central 30-2 threshold screening program on the Humphrey visual field analyser, followed by the ophthalmic examination to rule out ocular causes for visual field defects. RESULTS: The patients had a mean age of 11.9+/-3.1 years and the mean treatment duration with Vigabatrin was 14.9 months. 11 of 28 patients were abnormal on static perimetry. Among them, four were false negative, one was false positive and two had fixation loss, which were suggestive of poor cooperation. Four of them had visual field defects including right homonymous inferior quadrantanopia, left incongruous incomplete hemianopsia, bilateral right homonymous hemianopsia, bilateral left homonymous hemianopsia. CONCLUSION: Visual field examination in children is more difficult than in adults because of a lack of cooperation. Although we could not find any patients with visual field defect from Vigabatrin, vigilance and close follow up are necessary when the drug is prescribed.

Factors Related to Weight Changes in Epileptic Children Treated with Vigabatrin

PURPOSE: This study was undertaken to investigate factors related to weight changes in children treated with vigabatrin(VGB). METHODS: We have analyzed mean weight standard deviation scores(SDS) retrospectively and interviewed 35 childhood epileptic patients attending Pusan National University Hospital on VGB monotherapy followed over 36 months. Putative risk factors including sex, age, duration of VGB administration, mean weight SDS score at diagnosis, dose of VGB administration, seizure type (generalized or partial), and etiology(idipathic or symptomatic) were statistically analyzed. RESULTS: Thirty five children(21 boys, 14 girls) were treated with VGB monotherapy. The mean age of patients at diagnosis was 3.21 +/- 4.13 years, and the mean weight SDS at diagnosis was -0.19 +/- 1.09. After the administration of VGB, the mean weight SDS was significantly increased (P0.05). CONCLUSIONS: VGB monotherapy significantly affects weight gain of patients treated for epilepsy. Strategies, such as optimizing diet and establishing an exercise routine, should be devised to help patients avoid weight gain when starting on VGB. It may be prudent to avoid, where possible, combinations of VGB with other antiepileptic drugs(such as valproate, carbamazepine gabapentin) which can lead to weight gain.

Effects of Vigabatrin on Pilocarpine-Induced Seizures in Immature Rats

PURPOSE: Vigabatrin is a widely used antiepileptic drug that greatly increases whole brain gamma- aminobutyric acid(GABA). But little is known about the anticonvulsant effect of vigabatrin on pilocarpine-induced seizures in the immature rats. This study was conducted to determine the effects of vigabatrin on pilocarpine-induced seizures in the immature rats. METHODS: Six to eight day old Sprague-Dawley rats were classified into control(n=5) and vigabatrin-treated(n=5) groups that were pretreated with 30mg/kg of vigabatrin. Animals received vigabatrin or saline, intraperitonealy, for 6 days, once a day. And on the 5th day, right and left cortical electrodes were placed in 10-14 day old animals using stereotaxic instrument. The following day 2.5-hour EEG recordings were obtained to monitor the latency to first electrographic seizures and to first status epilepticus induced by intraperitoneal injection of pilocarpine(200mg/kg). Data were analyzed using the log-rank test. RESULTS: Electrographic seizures and status epilepticus were seen in 80% of vigabatrin-treated group, and in 100% of control group rats. And the latency to first seizure was 8.8+/-2.0 minutes in control group and 20.5+/-5.2 minutes in vigabatrin-treated animals(P<0.02), and to status epilepticus was 12.2+/-1.2 minutes in control group and 29.3+/-6.3 minutes in vigabatrin-treated group(P<0.03). CONCLUSION: It was confirmed that 30mg/kg of vigabatrin administration for 6 days did not affect the body weight gain and behavior of immature rats and had an anticonvulsant effect. These findings might demonstrate that the prolonged latency to seizure, and to status epilepticus, was a time to reduce GABA that was elevated in the brain by vigabatrin administration below the seizure threshold, by pilocarpine.

A Case of Vigabatrin Induced Symptomatic Visual Field Defect

Vigabatrin (VGB) is one of the most frequently prescribed new anti-epileptic drugs in the world since 1989. It has minimal side effects and fewer drug interactions with other anti-epileptic drugs. Recently, concern of the prevalence and pathophysiology of visual impairment with VGB has been increased since the reports of visual field constriction in patients treated with VGB. We report a 46-year-old man with a visual field defect who has been suffering from complex partial seizures for 29 years. Brain magnetic resonance image (MRI) and electroencephalogram (EEG) were non-specific. The frequency of seizures was about 5 times a month for the past 5 years. VGB, in a dose of 1500 mg/day, was prescribed as an add on drug in addition to carbamazepine. 19 months after VGB treatment, the patient complained of visual dimness especially in the lower half of the visual field. He expressed it as "waving". He had no metabolic derangement. Fundus examination, visual evoked potential, and electroretinogram showed normal findings. A visual field analysis showed a bilateral field defect in the lower half. A follow up visual field analysis, 6 months after the withdrawal of VGB, revealed a slight improvement of visual field defects which were noted without significant clinical improvement. This case implicates that visual field defects due to VGB may be partially reversible.