Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy

Abstract

SUMMARYPurpose: 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 T 2 -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.

Abnormal Axial Diffusivity in the Deep Gray Nuclei and Dorsal Brain Stem in Infantile Spasm Treated with Vigabatrin

“…Previous studies have shown that children younger than 2 years of age were more likely to demonstrate abnormal signal intensity in the deep gray nuclei and dorsal brain stem compared with older children or adults when exposed to vigabatrin. 5,7,16 The observed abnormal signal intensity in the deep gray nuclei and dorsal brain stem in infants with relatively immature myelin exposed to vigabatrin may not be related to myelin vacuolationhence, the lack of significant alteration of D Ќ in the globi pallidi, thalami, and dorsal brain stem in our cohort of patients.…”

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…Hyperintensities in basal ganglia, thalamus, brainstem and dentate nucleus have, very recently, been shown in approximately one-third of those exposed to vigabatrin [76][77][78][79]. These MRI abnormalities may occur as early as 3 months after the initiation of therapy.…”

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…[85] Alternatively, electrophilic metabolites can react with nucleophilic groups on proteins without covalent binding. [86] The drug-peptide + [50] Haematological abnormalities + [40] MRI abnormalities + [72][73][74] a The list is assembled by anatomophysiological systems (CNS, gastrointestinal system, skin, and renal system). This material is the copyright of the original publisher.…”

“…Symmetric magnetic resonance imaging (MRI) hyperintensities (T2 and DWI sequences) and magnetic resonance spectroscopy (MRS) abnormalities have been described in the globus pallidi, thalami, dentate nuclei and cerebral peduncles of patients with infantile spasms treated with GVG. [72][73][74] MRI abnormalities, which are supposed to depend on both high GVG dosage and younger age, are transient and disappear after GVG withdrawal. [72,73] MRS changes, in contrast, persist after GVG discontinuation; this might indicate that these changes are related to seizure activity rather than a direct drug effect.…”

“…[72][73][74] MRI abnormalities, which are supposed to depend on both high GVG dosage and younger age, are transient and disappear after GVG withdrawal. [72,73] MRS changes, in contrast, persist after GVG discontinuation; this might indicate that these changes are related to seizure activity rather than a direct drug effect. [74] However, the potential pathogenic mechanisms remain unclear.…”