Why are type II focal cortical dysplasias frequently located at the bottom of sulcus? A neurodevelopmental hypothesis

Type II focal cortical dysplasias (FCD II) are highly epileptogenic brain lesions characterized by severe cortical dyslamination and by the presence of abnormal giant cells defined as dysmorphic neurons and balloon cells (typical of FCD IIb). First described by Taylor et al.,1 FCD II presents with distinct clinical features, including severe focal seizures resistant to antiseizure medication starting in childhood and frequent extratemporal location. FCD II is the third histopathological diagnosis in epilepsy surgery cohorts.2 Scalp and intracerebral neurophysiological studies identified repetitive polyspikes or bursts of fast rhythms associated with disruption of the physiological background activity as reliable FCD II biomarkers.3 Magnetic resonance imaging (MRI) revealed peculiar radiological signs characteristics of FCD II, including (1) focal blurring and T2/fluidattenuated inversion recovery (FLAIR)T2 hyperintensity at the junction between gray and white matter, (2) increased FLAIRT2 signal extending from the ventricle to the cortex (transmantle sign), (3) abnormal gyration/sulcation, and (4) increased cortical thickness.4 In addition, 18FDGPET (fluorodeoxyglucose– positron emission tomography) often shows hypometabolism.5 In small FCD lesions, these imaging abnormalities are often present in the depth of a cortical sulcus,6 leading to the introduction of the term “bottomofsulcus dysplasia” (BOSD, Figure 1A,B). Initially considered as a FCD IIb subtype,7 it is now recognized that some FCD IIa can also be defined as BOSD. Most probably, the latter has been formerly underestimated because of a minor presence of abnormal MRI findings, such as the transmantle sign (Figure 1C,D). Small BOSDs are found mainly in the frontal lobe, but have been described also in parietal, temporal, occipital, and insular lobes, and the affected sulcus is described as being deeper than its equivalent in healthy controls.6,8,9 Using quantitative morphometric analysis, Liu and colleagues9 demonstrated that the characteristic MRI abnormalities predominate in the bottom part of the sulcus, even in larger FCD lesions that extend from the bottom to the wall of the sulci. However, the real incidence of BOSD is not fully investigated in a large cohort of patients; a recent mapping of 580 FCD cases (83% FCD II, even if not specifically BOSD) clearly demonstrate that FCDs are more often observed in the superior frontal sulcus, followed by the frontal and temporal poles. Moreover, frontal FCDs were found to be smaller in comparison to those localized in the temporal and occipital lobes.10