Decompressive hemicraniectomy prolongs short-term survival in patients with poor-grade aneurysmal subarachnoid hemorrhage with associated intracerebral hemorrhage; however, this trend is not statistically significant, and the overall QoL experienced by survivors is poor. Decompressive hemicraniectomy may be indicated if performed early in a select subset of patients. On the basis of our preliminary data, large prospective studies to investigate this issue further may not be warranted.

Pain relievers containing N-acetyl-para-aminophenol, also called APAP, acetaminophen or paracetamol, in combination with opioid narcotics are top-selling pharmaceuticals in the U.S. Individuals who abuse these drugs for as little as sixty days can develop tinnitus and progressive bilateral sensorineural hearing loss. Recently published studies indicate that APAP and its metabolic product N-acetyl-p-benzoquinoneimine (NAPQI) are the primary ototoxic agents in this type of pain relievers. However, the mechanisms underlying the deleterious effects of these drugs on auditory cells remain to be fully characterized. In this study, we report cellular, genomic, and proteomic experiments revealing that cytotoxicity by APAP and NAPQI involves two different pathways in Immortomouse™-derived HEI-OC1 cells, implicating ROS overproduction, alterations in ER morphology, redistribution of intra-cisternal chaperones, activation of the eIF2α-CHOP pathway, as well as changes in ER stress and protein folding response markers. Thus, both oxidative and ER stress are part of the cellular and molecular mechanisms that contribute to the cytotoxic effects of APAP and NAPQI in these cells. We suggest that these in vitro findings should be taken into consideration when designing pharmacological strategies aimed at preventing the toxic effects of these drugs on the auditory system.

Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and antimalarial medications. Because their benefits in combating certain life-threatening diseases often outweigh the risks, the use of these ototoxic drugs cannot simply be avoided. In this review, the authors discuss some of the most frequently used ototoxic drugs and what is currently known about the cell and molecular mechanisms underlying their noxious effects. The authors also provide suggestions for the clinical management of ototoxic medications, including ototoxic detection and drug monitoring. Understanding the mechanisms of drug ototoxicity may lead to new strategies for preventing and curing drug-induced hearing loss, as well as developing new pharmacological drugs with less toxic side effects.

These data demonstrate a correlation between soluble ICAM-1 levels and functional outcome following aneurysmal SAH that appears to be, at least in part, independent of the initial hemorrhage.