A Controlled Study of Oral Vigabatrin (ɣ-Vinyl GABA) in Patients with Cerebellar Ataxia

Bonnet, Anne Marie; Esteguy, M.; Tell, G.; Schechter, Paul J.; Hardenberg, J.; Agid, Yves

doi:10.1017/s0317167100036672

Cited by 16 publications

(10 citation statements)

References 9 publications

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“…It was seen to have a beneficial effect on tardive dyskinesias induced by neuroleptics, and there was conflicting evidence as to whether it ameliorated ataxia in degenerative cerebellar diseases. [9][10][11][12][13] There was one report of it having a positive effect on spasticity in metachromatic leukodystrophy. 14 There have been equivocal results in its use as a treatment of dyskinesias in Parkinson disease and spasticity in multiple sclerosis.…”

Section: Discussionmentioning

confidence: 99%

An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms

Fong

Osborne

Edwards

et al. 2013

Develop Med Child Neuro

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AIM We aimed to investigate the relationship between movement disorders, changes on brain magnetic resonance imaging (MRI), and vigabatrin therapy in children with infantile spasms. METHOD Retrospective review and brain MRI analysis of children enrolled in the InternationalCollaborative Infantile Spasms Study (ICISS) who developed a movement disorder on vigabatrin therapy. Comparisons were made with controls within ICISS who had no movement disorder. RESULTSTen of 124 infants had a movement disorder and in eight it had developed on vigabatrin therapy. Two had a movement disorder that resolved on dose-reduction of vigabatrin, one had improvement on withdrawing vigabatrin, two had resolution without any dose change, and in three it persisted despite vigabatrin withdrawal. The typical brain MRI changes associated with vigabatrin therapy were noted in two infants. Ten control infants were identified. Typical MRI changes noted with vigabatrin were noted in three controls.INTERPRETATION It is possible that in two out of eight cases, vigabatrin was associated with the development of a movement disorder. In six out of eight cases a causal relationship was less plausible. The majority of infants treated with vigabatrin did not develop a movement disorder. MRI changes associated with vigabatrin do not appear to be specifically related to the movement disorder.Infantile spasms are an age-related epileptic encephalopathy that occurs in children, usually between the ages of 3 months and 18 months. The seizures manifest typically as clusters of either flexor or extensor epileptic spasms, which are often coincident with an arrest or regression of neurodevelopment. The electroencephalograph characteristically, but not always, shows a chaotic high voltage interictal pattern known as hypsarrhythmia. Many underlying aetiologies, such as tuberous sclerosis complex, trisomy 21, neuronal migration disorders, and hypoxic-ischaemic encephalopathy, have been associated with infantile spasms but in a significant minority of cases no cause is found. There has been much debate about the most effective treatment modality for these patients but there appears to be a relatively wide consensus that the two most effective therapies are either the GABA-ergic anticonvulsant, vigabatrin, or hormonal therapies (prednisolone, adrenocorticotrophin hormone [ACTH], or synthetic ACTH). 1It has been known since the 1980s that vigabatrin usage in animals was associated with the development of intramyelinic oedema in the central nervous system, most notably in the cerebellum, reticular formation and optic tracts in rats, and columns of the fornix and the optic tracts in dogs. 2,3 Recently reports have surfaced in the literature linking vigabatrin usage in humans with characteristic magnetic resonance imaging (MRI) changes in the globus pallidus, thalamus, brain stem, and dentate nuclei of the cerebellum. 4,5 These changes appear to be dose-dependent

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Section: Discussionmentioning

confidence: 99%

An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms

Fong

Osborne

Edwards

et al. 2013

Develop Med Child Neuro

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“…There was either little change or a deterioration in the Parkinsonism symptoms associated with neuroleptic administration. In the degenerative ataxia syndromes including Huntington's disease, Friedreich's ataxia and idiopathic familial generalised ataxia, vigabatrin has not been shown to be efficacious (Bonnet et al 1986;Carella et al 1986;Scigliano et al 1984).…”

Section: Use In Other Neurological Disordersmentioning

confidence: 99%

A Risk-Benefit Assessment of Vigabatrin in the Treatment of Neurological Disorders

Srinivasan

Richens

1994

Drug Safety

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Vigabatrin was designed to increase the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. It does this by replacing GABA as a substrate for the action of the catabolic enzyme GABA-transaminase. As a result of this inhibition, neuronal GABA levels are elevated, resulting in enhanced endogenous GABA transmission. A number of clinical trials assessing the effect of vigabatrin in epilepsy have been completed. Vigabatrin is of proven benefit in partial seizures and secondarily generalised tonic clonic seizures, and it is licensed for use as adjunctive therapy in these conditions in several European countries. It has been shown to be effective in some epilepsy syndromes in children including West's syndrome, infantile spasms and cryptogenic partial seizures. Its effect on primary generalised tonic clonic seizures is variable, while there is considerable evidence that it has a deleterious effect on myoclonic and absence seizures. There have been a few reports of the benefits of vigabatrin in other neurological disorders including tardive dyskinesia, degenerative ataxias and GABA metabolism disorders. The adverse effects associated with vigabatrin are similar to those seen with other anticonvulsants, with a predominance of CNS effects including somnolence, fatigue, irritability, dizziness and headache. Psychiatric symptoms including depression and psychosis are seen in a small number of patients and cause the most problems. These often necessitate discontinuation of vigabatrin, which usually results in resolution of symptoms.

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“…Botez et al did not find improvement in ataxia when treating a group of 27 patients with FRDA with amantadine hydrochloride (90). The same result was reported by Filla et al, in a double-blind cross-over trial using amantadine hydrochloride in 12 patients with FRDA (115).…”

Section: Spinocerebellar Atrophiesmentioning

confidence: 59%

Neurochemistry and Neuropharmacology of the Cerebellar Ataxias

Gazulla¹,

Hermoso-Contreras²,

Tintoré³

2012

Spinocerebellar Ataxia

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A Controlled Study of Oral Vigabatrin (ɣ-Vinyl GABA) in Patients with Cerebellar Ataxia

Cited by 16 publications

References 9 publications

An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms

An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms

A Risk-Benefit Assessment of Vigabatrin in the Treatment of Neurological Disorders

Neurochemistry and Neuropharmacology of the Cerebellar Ataxias

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