Long‐term outcome in children with infantile spasms treated with vigabatrin: A cohort of 180 patients

Abstract

SUMMARYObjective: Evaluation of efficacy of vigabatrin as the first drug in infants with previously untreated infantile spasms (IS) and reporting the long-term outcome. Methods: We analyzed a cohort of 180 infants with infantile spasms treated with vigabatrin as the first drug. Following initial evaluation and a 48-h basal period for counting the spasms, vigabatrin was administered using the same protocol in all. After 14 days all infants were assessed for therapeutic response (primary outcome). Psychomotor development was evaluated by a psychologist and neurologist prior to the initiation of treatment and during the follow-up. Seizure outcomes were followed prospectively, by seizure types and epilepsy syndromes. Long-term (secondary) outcomes included neurologic status, occurrence of late epilepsy, and developmental/cognitive status. Results: Vigabatrin terminated the spasms in 101 patients (56.9%) at a mean period of 5 days. Patients with normal psychomotor development prior to the onset of spasms responded best. After follow-up of 2.4 to 18.9 years (mean 10.64; standard deviation [SD] 4.40), 38.1% of responders, treated with vigabatrin, had severe neurologic dysfunction, 42% had epilepsy, and 42.2% had unfavorable intellectual outcome. The group with symptomatic etiology and abnormal neurologic status at presentation demonstrated a significantly worse prognosis and a more unfavorable outcome than cryptogenic or idiopathic cases (85.1% and 81.6% versus 14.9% and 0%-p = 0.001). Idiopathic patients treated with vigabatrin were all intellectually normal, except the youngest patient who had borderline cognitive function. Significance: The most important prognostic factors were the underlying etiology and preexisting developmental profile. Long-term outcome in the patients treated with vigabatrin was similar to the outcome in patients treated with adrenocorticotropic hormone (ACTH) or corticosteroids, as reported in earlier studies. The long-term prognosis of idiopathic cases treated with vigabatrin was favorable.

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

“…Other studies have demonstrated improved outcomes with initiation of treatment within 4 weeks of spasms present as well as early response to treatment. 6,[35][36][37][38][39] Cohen et al 37 have reported improved seizure and cognitive outcome with early initiation of ACTH. The majority of these studies have cohorts that are exclusively "cryptogenic children," who have no prior developmental delay and no identifiable etiology.…”

Preclinical tissue distribution and metabolic correlations of vigabatrin, an antiepileptic drug associated with potential use‐limiting visual field defects

“…VGB is currently used as adjuvant therapy for refractory epilepsies, complex partial seizures, secondarily generalized seizures, infantile spasms, and is under active investigation in tuberous sclerosis complex . However, an extensive body of literature suggests that VGB is associated with peripheral visual field defects (pVFD), but others have suggested that VGB ocular toxicity correlates with pre‐existing anomalies, both structural and genetic .…”

“…The differences in dosepool size correlations for the S and R isomers in PFC, VC, and less Figure 6 was employed complex. 2,[22][23][24] However, an extensive body of literature suggests that VGB is associated with peripheral visual field defects (pVFD), 25 but others have suggested that VGB ocular toxicity correlates with pre-existing anomalies, both structural and genetic. 26 The occurrence of permanent visual field constriction in patients receiving VGB is 6-7%).…”

Long‐term outcome in children with infantile spasms treated with vigabatrin: A cohort of 180 patients

“…I have read with great interest the article of Djuric et al., “Long‐term outcome in children with infantile spasms treated with vigabatrin: A cohort of 180 patients.”…”

“… The numbers have been misquoted. In the Discussion “comparing the results of with ACTH‐treated in a Finnish study, 51/88 patients (58%) versus 48/147 (33%) (48% is an error) were seizure‐free, and 48/83 of patients (57.8%) versus 36/147 (24.5%) showed favorable intellectual outcome.” These figures presented in the article of Djuric et al. concerned responders (Table 4) and not the whole group.…”