Calvarial thickening in tuberous sclerosis complex

Introduction: Tuberous sclerosis complex (TSC)-related skeletal abnormalities are under-studied. Awareness of skull thickening in TSC patient is important from the surgical standpoint because thick skull might complicate craniotomy. This study, aimed at revealing if TSC patients are generally prone to skull thickening, had led us to retrospectively investigate the frequency and characteristics of skull thickening in these patients.

Method: TSC patients aged 10 to 60 years who underwent MRI were identified from the neurosurgery, dermatology or pediatrics clinic between 2010 and 2021. Two control groups were used for comparison: one with unruptured intracranial aneurysms to serve as control without anti-seizure medications (ASMs) exposure and another with non-TSC epilepsy as control with ASM exposure. Thickness of frontal, parietal, temporal, and occipital bones was measured at a fixed location of each bone across patients on T2-weighted axial images.

Result: 29 patients fulfilled the inclusion criteria. Frontal and temporal bones of the TSC group were significantly thicker than those of either control group. Skull thickening was significantly associated with intracerebral calcification, but not with age, sex, or ASM exposure. Focal skull thickening was associated with the presence of a subcortical calcification.

Conclusions: TSC patients have thickened skull that is often linked to intracerebral calcification. The presence of skull thickening may require modification of surgical approach during craniotomy. Skull thickening and the underlying intracerebral calcification likely share a common precipitating factor given their relationship. Future studies are warranted to clarify the genetic underpinnings of this relationship and even broader skeletal abnormalities in TSC.