The Spectrum of Headache in Leptomeningeal Metastases: A Comprehensive Review with Clinical Management Guidelines.

PURPOSE OF REVIEW: Headaches are a common, oftentimes debilitating symptom in patients with leptomeningeal metastases. RECENT FINDINGS: The third edition of the International Classification of Headache Disorders provides a useful diagnostic framework for headaches secondary to leptomeningeal metastases based on the temporal relationship of headache with disease onset, change in headache severity in correlation with leptomeningeal disease burden, and accompanying neurologic signs such as cranial nerve palsies and encephalopathy. However, headaches in patients with leptomeningeal metastases can be further defined by a wide range of varying cancer- and treatment-related pathophysiologies, each requiring a tailored approach. A thorough review of the literature and expert opinion on five observed headache sub-classifications in patients with leptomeningeal metastases is provided, with attention to necessary diagnostic testing, recommended first-line treatments, and prevention strategies.

Interactions of DEET and Novel Repellents With Mosquito Odorant Receptors.

The carboxamide N,N-di-ethyl-meta-toluamide (DEET) is the most effective and widely used insect repellent today. However, drawbacks concerning the efficacy and the safety of the repellent have led to efforts to design new classes of insect repellents. Through quantitative structure-activity relationships, chemists have discovered two chemical groups of novel repellents: the acylpiperidines and the carboxamides, with the acylpiperidines generally more potent in biological assays. Although the exact mechanism of action of DEET and other repellents has not yet been thoroughly elucidated, previous research shows that the activity of insect odorant receptors are inhibited in the presence of repellents. The present electrophysiological study employs two-electrode voltage clamp with Xenopus laevis oocytes expressing AgOR2/AgOrco and AgOR8/AgOrco receptors to assess the effects of the novel repellents on Anopheles gambiae Giles (Insecta: Diptera: Culicidae) mosquito odorant receptors. The novel acylpiperidines and carboxamides reversibly inhibited (12-91%) odorant-evoked currents from both AgOR2/AgOrco and AgOR8/AgOrco receptors in a dose-dependent manner at all tested concentrations (30 µM to 1 mM). Furthermore, all the novel agents were more potent inhibitors of the receptors than DEET, with the acylpiperidines producing on average greater inhibition than the carboxamides. Interestingly, there was a correlation (r2 = 0.72) between the percentage inhibition of AgOR2/AgOrco receptor currents and protection times of the acylpiperidines. Our results add to existing evidence that the repellency of a compound is linked to its ability to disrupt the insect olfactory system and that the acylpiperidines could represent a class of more effective alternatives to the current gold standard, DEET.