No abstract

An elevation of the intracranial pressure (ICP) secondary to cerebral edema is a major contributor to morbidity and mortality in acute liver failure. In addition, invasive ICP monitoring in this setting is controversial because coagulopathy predisposes patients to hemorrhagic complications. In this case report, we describe the novel use of optic nerve sheath diameter monitoring as a noninvasive modality for checking for acute elevations in ICP in this setting. Because of the merits of rapidly evolving ultrasound technologies, this may serve as a safe method for improving patient care in this setting.

Objective: Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP. Methods: Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA-tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5 c/À ), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures. Results: Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic-ECG records on Depdc5 c/À mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event are not preceded by cardiac arrhythmia. Interpretation: Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies.

Previous studies showed that the cerebrovasodilation response to hypercapnia is attenuated with aging. The purpose of this study was to determine if normal aging attenuates increases in brain oxygenation during hypercapnia. Prefrontal cortex oxyhemoglobin (OHb) and deoxyhemoglobin (HHb) concentrations were measured in 13 healthy subjects ages 26 to 59 years using a frequency domain tissue oximeter. Measurements were obtained under the following conditions: (1) subject awake breathing spontaneously, (2) during mask ventilation with 21% oxygen, (3) mask ventilation with 100% oxygen, (4) 100% oxygen in a rebreathing circuit to increase end-tidal CO(2). Under baseline conditions breathing room air, there was a negative correlation between baseline OHb and age (r=-0.60, P<0.05). Ventilation with 100% oxygen increased OHb without a change in total hemoglobin and no affect of age. During mask rebreathing, end-tidal CO(2) increased from 39.5+/-5.0 mm Hg (millimeters of mercury) to 56.5+/-5.7 mm Hg, which produced significant increases in OHb and total blood volume that were negatively correlated with age (r=-0.67, P<0.05) and positively correlated to baseline OHb (r=0.60, P<0.05). These results indicate that OHb concentrations decreased with age, consistent with attenuated cerebral vasodilation during hypercapnia.

Intubation-related stress increased oxyhaemoglobin related to electroencephalogram and autonomic activation. Stress-induced brain stimulation may be monitored during anaesthesia using frequency domain near-infrared spectroscopy.