Vignesh Subramanian ’24

Cortical dysplasia (CD) is a congenital disorder involving improper organization of layers of the brain, which generates pathological lesions on the organ’s surface and renders developing neurons unable to mature and connect with one another. Lesional tissue significantly increases risk of refractory epilepsy (seizures not responsive to medication) in the pediatric population, and complete surgical resection of this deformed tissue is a key predictor of seizure freedom – success at remission – following treatment or outgrowing of CD. Lesions are often visually indistinguishable from surrounding tissue and only partially detectable by preoperative magnetic resonance imaging (MRI), electrocorticography (ECoG) and intraoperative microscopy, but are characteristically stiff and structurally divergent from the normal gross brain. To overcome this clinical challenge, a study at the University of California, Los Angeles thus explored whether an intraoperative brain tonometer device could provide the tactile feedback needed to discern the borders of these dysplastic abnormalities.

Researchers deployed the Diaton Tonometer probe with minimal contact during craniotomy procedures for a sample of 24 consecutive patients with median ages of 2 years for seizure onset and 12 years at surgery. 249 stereotactic data points – an average of eight to ten per surgery – yielding four to six intraocular pressure readings apiece in high-precision spatial resolution were recorded and then correlated to MRI- and fluorodeoxyglucose positron electron tomography-registered anomalies. Separate histological analyses of biopsies of resection-targeted regions were performed to determine their individual extent of cortical dyslamination – the stratification of neurons, guided by migration and differentiation – and to correct brain stiffness measurements with mixed-effects multivariable linear regression. Subsequent receiver operating characteristic analysis determined that “normal” areas of the brain demonstrated mild cortical disorganization while higher brain stiffness correlated with age of seizure onset (with likelihood increasing with age) and duration of seizures (with likelihood increasing with length of time), among other factors. Analysis of the hypometabolism data further indicated that brain stiffness served as a better biomarker for structural rather than functional abnormalities atop the neocortex using current imaging modalities.

This research was particularly significant in its setting of precedent as the first to measure in vivo brain stiffness in patients of epilepsy surgery. The study came to conclude that the contrast between the tight range of plasticity in healthy tissue and the variability and spread of lesional stiffness makes tools that can successfully detect the latter, such as the tonometer in question, extremely viable for preoperative examination of such abnormalities.

Works Cited:

[1] A. Fallah, et al., Novel tonometer device distinguishes brain stiffness in epilepsy surgery. Nature (Scientific Reports) 10, 20978 (2020). doi: 10.1038/s41598-020-77888-0

[2] Image retrieved from: https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Epilepsy