Acute brain injury and nanomedicine: sex as a biological variable.

Sex as a biological variable has been recognized for decades to be a critical aspect of the drug development process, as differences in drug pharmacology and toxicity in female versus male subjects can drive the success or failure of new therapeutics. These concepts in development of traditional drug systems have only recently begun to be applied for advancing nanomedicine systems that are designed for drug delivery or imaging in the central nervous system (CNS). This review provides a comprehensive overview of the current state of two fields of research - nanomedicine and acute brain injury-centering on sex as a biological variable. We highlight areas of each field that provide foundational understanding of sex as a biological variable in nanomedicine, brain development, immune response, and pathophysiology of traumatic brain injury and stroke. We describe current knowledge on female versus male physiology as well as a growing number of empirical reports that directly address sex as a biological variable in these contexts. In sum, the data make clear two key observations. First, the manner in which sex affects nanomedicine distribution, toxicity, or efficacy is important, complex, and depends on the specific nanoparticle system under considerations; second, although field knowledge is accumulating to enable us to understand sex as a biological variable in the fields of nanomedicine and acute brain injury, there are critical gaps in knowledge that will need to be addressed. We anticipate that understanding sex as a biological variable in the development of nanomedicine systems to treat acute CNS injury will be an important determinant of their success.

Self-Trephination in Cranial Excoriation Disorder.

BACKGROUND AND IMPORTANCE: Trephination is a procedure in which a small hole is made in the skull. Rare cases of self-trephination by individuals seeking medical benefit have been reported. Excoriation disorder is a compulsive skin-picking condition in which an individual self-inflicts cutaneous lesions. Left untreated, severe excoriation disorder can pose significant health risks. CLINICAL PRESENTATION: Here, we describe 5 patients who presented with self-trephination due to a severe form of compulsive cranial excoriation at 2 neighboring academic medical centers over a 4-year period. We review the clinical presentation of self-trephination in cranial excoriation disorder and associated risk factors, surgical and nonsurgical interventions, complications of the disease, treatments, and mortality. Defining clinical characteristics include repetitive self-induced destruction of the scalp and skull with entry into the intracranial compartment, frequent psychiatric comorbidities, infection or injury of the brain with consequent neurological morbidity or mortality, and frequent treatment failures because of poor adherence. CONCLUSION: Self-trephination in cranial excoriation disorder is a severe neuropsychological disorder and neurosurgical emergency that exposes the brain and is often life-threatening. Appropriate therapy requires antibiotics, surgical debridement and repair of the wound, and concomitant effective psychiatric management of the underlying compulsion, including the use of antidepressants and behavioral therapy.