SUMMARYPurpose: The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin-attributed visual field loss (VAVFL) in at least 20-40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school-age children who had received VGB in infancy. Methods: Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6-12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts. Results: Vigabatrin was started at a mean age of 7.6 (range, 3.2-20.3) months. The mean duration of therapy was 21.0 (9.3-29.8) months and cumulative dose 655 g (209-1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g. Conclusions: The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age.

Epilepsy in infancy links to a significant risk of neurodevelopmental delay, calling for a better understanding of its underlying mechanisms. Here, we studied cortical activity networks in infants with early-onset epilepsy to identify network properties that could preempt infants’ neurodevelopmental course. We studied high-density (64 channel) EEG during non-REM (N2) sleep in N = 49 infants at one year of age after being diagnosed with epilepsy during their first year of life. We computed frequency-specific networks in the cortical source space for two intrinsic brain modes: amplitude-amplitude and phase-phase correlations. Cortical activity networks of all frequency bands and connectivity modes were compared between the syndrome groups, as well as between three categories of neurocognitive development. The group differences were studied at three spatial levels: global, regional, and individual connections. Cortical mechanisms related to infant epilepsy were further compared to physiological networks using an automatic spindle detection algorithm. Our results show that global connectivity does not significantly differ between epilepsy syndromes; however, it co-varies with neurocognitive development. The largest network differences were observed at the lowest (<1 Hz) and mid-range (10-15 Hz) frequency bands. An algorithmic removal of sleep spindles from the data reduced the strength of the mid-range frequency network only partially. The centrocentral and frontocentral networks at the spindle frequencies were found to be strongest in infants with a persistent age-typical neurocognitive performance, while their low-frequency (< 1 Hz) networks were weaker for both amplitude-amplitude (P = 0.008, effect size = 0.61) and phase-phase correlations (P = 0.02, effect size = 0.54) at low (< 1 Hz). However, subjects with persistent mild neurocognitive delay from 1 to 2 years of age had higher amplitude-amplitude (P = 0.02, effect size = 0.73) and phase-phase (P = 0.06, effect size = 0.59) at low frequencies than those that deteriorated from mild to severely delayed from 1 to 2 years of age. Our findings suggest that cortical activity networks reflect the underlying clinical course of infants’ epilepsy, and measures of spectrally and spatially resolved networks might become useful in better understanding infantile epilepsy as a network disease.

ABBREVIATIONS OCTOptical coherence tomography RNFL Retinal nerve fiber layer TSC Tuberous sclerosis complex VAVFD Vigabatrin-attributed visual field defect AIM To investigate the prevalence of vigabatrin-attributed visual field defect (VAVFD) in infantile spasms and the utility of optical coherence tomography (OCT) in detecting vigabatrin-related damage. METHOD We examined visual fields by Goldmann or Octopus perimetry and the thickness of peripapillary retinal nerve fiber layer (RNFL) with spectral-domain OCT at school age or adolescence. RESULTS Out of 88 patients (38 females, mean age at study 15y, SD 4y 3mo, range 6y 4mo-23y 3mo [n=65] or deceased [n=21] or moved abroad [n=2]) exposed to vigabatrin in infancy, 28 were able to perform formal visual field testing. Two had visual field defect from structural causes. We found mild VAVFD in four patients and severe VAVFD in one patient. Median vigabatrin treatment duration for those with normal visual field was 11 months compared to 19 months for those with VAVFD (p=0.04). OCT showed concomitant attenuated RNFL in three children with VAVFD, and was normal in one. The temporal half of the peripapillary RNFL was significantly thinner in the VAVFD group compared to the normal visual field group. INTERPRETATION The overall prevalence of VAVFD is lower after exposure in infancy compared to 52% which has been reported after exposure in adulthood. The risk increases with longer treatment duration. Further studies should identify infants particularly susceptible to VAVFD and clarify the role of OCT.