Vigabatrin (VGB) proved to be effective as first-line monotherapy for treating infantile spasms (ISs) (Appleton et al., 1999; Elterman et al., 2001; Lux et al., 2005), especially in tuberous sclerosis (Chiron et al., 1997) and cortical dysplasia (Lortie et al., 2002).

Retinal toxicity of VGB raises the important question, for how long one should treat patients with ISs by using VGB, because the occurrence of peripheral visual field defects (VFDs) correlates significantly with the duration of treatment and total VGB dose (Kalviainen and Nousiainen, 2001; Vanhatalo et al., 2002).

We report four patients (Table 1) with focal cortical dysplasia (FCD; and tuberous sclerosis for one of them) that could, however, be confirmed on MRI only after age 2 years. All were first seen with asymmetric spasms and focal seizures that were easily controlled by first-line VGB therapy and benefited from normal development. VGB was discontinued after between 1 and 5 years. Spasms relapsed in all cases, were refractory to VGB, and led to severe mental retardation in the two cases with seizures persisting despite multiple medications.

Table 1. Patient data
Onset of spasmsVigabatrin startedVigabatrin stopped (yr)Relapse of spasms (yr)Recontrol of epilepsyFurther mental retardation
1 wk  1 wk2.53.9Yes (in 3 mo)No
1.5 mo  1.5 mo2.33.3Yes (in 2 mo)No
1 wk  1 wk5 5.1NoYes
2 mo  2 mo1 1.1NoYes

These cases illustrate that any decision regarding duration of VGB treatment in ISs must balance the risk of VFDs and the risk of relapse of spasms. The onset of intractable epilepsy within the first 24 months of life is a significant risk factor for the development of mental retardation (Vasconcellos et al., 2001).

ISs are among the most deleterious in early epilepsy and represent an epileptic encephalopathy (Dulac, 2001). Early spasm control might improve learning and behavioral outcome, particularly in tuberous sclerosis (Jambaque et al., 2000). When ISs relapse after a previous remission, they carry a high risk of being extremely resistant (Camfield et al., 2003), contrasting with the usually rapid response to VGB in early infancy. Despite numerous difficulties in assessing the incidence of VGB-attributable VFDs in children, the risk seems to be lower than that in adults (Kalviainen and Nousiainen, 2001); symptomatic cases are exceptional and sometimes reversible (Versino and Veggiotti, 1999); and ≥15 months treatment is required for the defect to become significant (Vanhatalo et al., 2002).

However, controlled studies concerning the optimal treatment duration with VGB in ISs are lacking. VGB seems to be stopped after 6 months without any relapse risk in patients with Down syndrome (Nabbout et al., 2001) or cryptogenic or postanoxic etiology (Capovilla et al., 2003). The same would not apply to other symptomatic causes of ISs. The present cases show that FCD increases the risk for late and severe relapse of spasms after discontinuation of VGB. Considering the difficulty of detecting such a malformation on MRI before the age of 2 years (Eltze et al., 2005), one should be aware of associated focal ictal/interictal electroclinical features suggesting a focal lesion, before discontinuation of VGB. In these patients, the risk of an epileptogenic encephalopathy developing persists in childhood, even after a favorable course of VGB in early infancy.

In view of the risks and limitations of medical treatment, epilepsy surgery should therefore be considered early in symptomatic ISs due to FCD.


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