Optic nerve sheath diameter and eyeball transverse diameter in severe head injury and its correlation with intracranial pressure.

BACKGROUND: Gold standard for determining intracranial pressure (ICP), intraventricular catheter, is invasive with associated risks. Non-invasive investigations like magnetic resonance imaging and ultrasonography have demonstrated correlation between optic nerve sheath diameter (ONSD) and raised ICP. However, computed tomography (CT) is accessible and less operator-dependent. Literature shows variable results regarding correlations between ICP and ONSD on CT. The study aimed to investigate correlations between raised ICP and ONSD, eyeball transverse diameter (ETD), and ONSD/ETD ratios on CT scan(s) of severe head injuries. METHODS: A retrospective review of a three-year prospectively-maintained database of severe traumatic head injuries in patients who had ICP measurements and CT scans was conducted. Glasgow Coma Score (GCS), ICP, ONSD 3 mm and 9 mm behind the globe, ETD, ONSD/ETD ratios, CT Marshall Grade, and Glasgow Outcome Score (GOS) were recorded. Statistical analysis assessed correlations between ICP and CT measurements. RESULTS: Seventy-four patients were assessed; mortality rate: 36.5 %. Assault (48.6 %) and pedestrian-vehicle collisions (21.6 %) were the most common mechanisms. CT Marshall Grade correlated significantly with 3 mm and 9 mm ONSD, ONSD/ETD ratios, GCS, and GCS motor score, which correlated significantly with GOS. No significant correlation was found between ICP and ONSD, ETD or ONSD/ETD ratios. Marshall Grade was not significantly associated with ICP measurements but correlated with injury severity. CONCLUSIONS: Unlike previous studies, our study not only investigated the correlation between ICP and single variables (ONSD and ETD) but also the ONSD/ETD ratios. No correlations were observed between raised ICP and ONSD, ETD or ONSD/ETD ratio on CT in neurotrauma patients.

5-ALA localises to the autophagy compartment and increases its fluorescence upon autophagy enhancement through caloric restriction and spermidine treatment in human glioblastoma.

Glioblastoma Multiforme (GBM) is the most invasive and prevalent Central Nervous System (CNS) malignancy. It is characterised by diffuse infiltrative growth and metabolic dysregulation that impairs the extent of surgical resection (EoR), contributing to its poor prognosis. 5-Aminolevulinic acid (5-ALA) fluorescence-guided surgical resection (FGR) takes advantage of the preferential generation of 5-ALA-derived fluorescence signal in glioma cells, thereby improving visualisation and enhancing the EoR. However, despite 5-ALA FGR is a widely used technique in the surgical management of malignant gliomas, the infiltrative tumour margins usually show only vague or no visible fluorescence and thus a significant amount of residual tumour tissue may hence remain in the resection cavity, subsequently driving tumour recurrence. To investigate the molecular mechanisms that govern the preferential accumulation of 5-ALA in glioma cells, we investigated the precise subcellular localisation of 5-ALA signal using Correlative Light and Electron Microscopy (CLEM) and colocalisation analyses in U118MG glioma cells. Our results revealed strong 5-ALA signal localisation in the autophagy compartment - specifically autolysosomes and lysosomes. Flow cytometry was employed to investigate whether autophagy enhancement through spermidine treatment (SPD) or nutrient deprivation/caloric restriction (CR) would enhance 5-ALA fluorescence signal generation. Indeed, SPD, CR and a combination of SPD/CR treatment significantly increased 5-ALA signal intensity, with a most robust increase in signal intensity observed in the combination treatment of SPD/CR. When using 3-D glioma spheroids to assess the effect of 5-ALA on cellular ultrastructure, we demonstrate that 5-ALA exposure leads to cytoplasmic disruption, vacuolarisation and large-scale mitophagy induction. These findings not only suggest a critical role for the autophagy compartment in 5-ALA engagement and signal generation but also point towards a novel and practically feasible approach to enhance 5-ALA fluorescence signal intensity. The findings may highlight that indeed autophagy control may serve as a promising avenue to promote an improved resection and GBM prognosis.