Abstracts

Rationale: Patients who have malformations of cortical development (MCD) experience an increased incidence of epilepsy. MCDs may arise from disruptions in neuronal migration or cortical organization, resulting in misplaced or malformed gray matter. While prior research has focused on the epileptogenicity of the abnormal gray matter, there is also evidence of important microstructural abnormalities in white matter as well. We hypothesized that the white matter thalamocortical projections which mediate sleep spindles would be disrupted by MCDs. Since acquired lesions that affect these projections have been associated with alterations in spindle characteristics, we sought to investigate whether such abnormalities are also present in MCDs.Methods: Electroencephalographic recordings of 10 subjects with neuroimaging-confirmed diagnoses of a cortical malformation (6 bilateral, 4 unilateral) were compared to those of 10 age- and gender-matched controls with normal brain imaging and no epilepsy. Sleep spindles were evaluated in the most recent routine or long-term EEG study obtained. Spindles were defined as waveforms distinct from the background with a frequency between 12-16 Hz and duration between 0.5-2 seconds. For each subject, a 30-second epoch beginning with the first noted spindle was analyzed by visual inspection for maximum spindle frequency, spindle density, laterality and location (anterior, central, posterior or diffuse). All analyses were performed independently by two electroencephalographers, who resolved differences by consensus. The spindle characteristics of malformation subjects and controls were compared using appropriate statistical tests.Results: Malformation subjects and controls were well-matched in age, gender, EEG study type and medication usage. Malformation subjects demonstrated a significantly lower proportion of bilateral spindles (48% vs. 80%, Χ²=6.02, p=0.01). While the sample size was small, unilateral malformations exhibited fewer ipsilateral than contralateral spindles (Figure 1). Spindle location also differed significantly between the two groups, with malformation subjects having a greater proportion of anterior and diffuse spindles (Χ²=4.19, p=0.04). There was no significant difference in the mean spindle density or the mean maximum spindle frequency between the two groups. Conclusions: Our findings demonstrate that patients with MCDs have an altered expression of sleep spindles, with a decrease in bilateral spindles and an increased proportion of anterior and diffuse spindles. In addition, we noted a decrease in ipsilateral spindles with unilateral malformations. These results imply that malformations disrupt the normal thalamocortical projections that mediate spindle generation. The potential relationship between the disrupted sleep architecture and the medically refractory epilepsy seen in many patients with MCDs deserves further study.