Increased striatal serotonin synthesis following cortical resection in children with intractable epilepsy

Abstract

Background and purpose: Serotonin is a major regulator of structural brain plasticity, which may occur following cortical resection in humans. In this study we used positron emission tomography (PET) with alpha[11C]methyl-l-tryptophan (AMT) to evaluate serotonergic alterations in subcortical structures following cortical resection in children with intractable epilepsy.

Methods: AMT uptake in the thalamus and lentiform nucleus was evaluated postoperatively (1-89 months following resection) in 19 children (mean age: 8.7 years) with a previous cortical resection due to intractable epilepsy. Ten children with partial epilepsy but without resection and seven normal children served as controls.

Results: There was an increased AMT uptake in the lentiform nucleus ipsilateral to the resection as compared to the contralateral side (mean asymmetry: 4.2+/-3.0%), and the asymmetries were significantly higher than those measured in the control groups (p<or=0.001). Post-resection asymmetry indices in the lentiform nucleus correlated inversely with postoperative time (r=-0.67; p=0.002), but not with age (p=0.29) or the extent of resection (p=0.77). In contrast, thalamic AMT uptake asymmetries were not different among the three groups (p=0.63).

Conclusions: Cortical resection results in a sustained increase of AMT uptake in the lentiform nucleus, suggesting increased serotonin synthesis. Serotonergic activation in the deafferented striatum may play a role in the functional reorganization of cortico-striatal projections in humans.

Figure 1

Increased AMT uptake (asymmetry index: 7.8%) in the ipsilateral lentiform nucleus (arrowhead) in a 8.8-year-old boy (patient 1), 1 month after a left fronto-temporal resection (see arrows on co-registered MRI and PET scans).

Figure 2

(A) PET scan showing a typical pattern of symmetric preoperative AMT uptake in a 9-year-old boy (patient 11). (B) A repeated AMT PET scan of the same patient 17 months after a right fronto-temporal resection demonstrated an increase in AMT uptake in the lentiform nucleus ipsilateral to the resection (arrow).

Figure 3

AMT uptake in the lentiform nucleus as a function of post-resection time. The asymmetry index was the highest (indicating increased uptake ipsilateral to the resection) in patients scanned early after surgery, and diminished with increasing postoperative time. The correlation could be well characterized by a logarithmic function (r = −0.69; p < 0.001).