*Deep tendon, plantar, Babinski reflexes if tele-examiner present Limitations of the telemedicine neurologic examination Comprehensive eye examination Cannot assess corneal reflex May be difficult to assess visual fields Neuromuscular examination Reflex testing may not be possible Difficult to fully assess peripheral strength and grade subtle strength differences between sides of the body Limited assessment of tone and rigidity May be hard to detect subtle signs of Parkinson's disease: in particular rigidity and retropulsion pull testing 44 Vestibular examination Cannot perform HINTs exam (Head Impulse, Nystagmus, Test-of-skew) for vestibular syndrome Cerebellar examination Cannot perform Dix-Hallpike test for cerebellar infarction FDA, Food and Drug Administration. *Elements of the examination that may be more difficult to perform.

Indocyanine green (ICG) is a water-soluble dye that was approved by the FDA for biomedical purposes in 1956. Initially used to measure cardiocirculatory and hepatic functions, ICG’s fluorescent properties in the near-infrared (NIR) spectrum soon led to its application in ophthalmic angiography. In the early 2000s, ICG was formally introduced in neurosurgery as an angiographic tool. In 2016, the authors’ group pioneered a novel technique with ICG named second-window ICG (SWIG), which involves infusion of a high dose of ICG (5.0 mg/kg) in patients 24 hours prior to surgery. To date, applications of SWIG have been reported in patients with high-grade gliomas, meningiomas, brain metastases, pituitary adenomas, craniopharyngiomas, chordomas, and pinealomas.The applications of ICG have clearly expanded rapidly across different specialties since its initial development. As an NIR fluorophore, ICG has advantages over other FDA-approved fluorophores, all of which are currently in the visible-light spectrum, because of NIR fluorescence’s increased tissue penetration and decreased autofluorescence. Recently, interest in the latest applications of ICG in brain tumor surgery has grown beyond its role as an NIR fluorophore, extending into shortwave infrared imaging and integration into nanotechnology. This review aims to summarize reported clinical studies on ICG fluorescence–guided surgery of intracranial tumors, as well as to provide an overview of the literature on emerging technologies related to the utility of ICG in neuro-oncological surgeries, including the following aspects: 1) ICG fluorescence in the NIR-II window; 2) ICG for photoacoustic imaging; and 3) ICG nanoparticles for combined diagnostic imaging and therapy (theranostic) applications.

Conflict of interest statement: M.A.L. is an advisory board member for Eli Lilly and Pfizer Inc., consultant to Novartis, and receives support from Pfizer for research not overlapping with the work reported here. M.R.H. has received research support, not used in the current studies, from investigator-initiated sponsored proposals from Eli Lilly & Co. and Boehringer-Ingelheim.

Circadian disruption, as occurs in shift work, is associated with metabolic diseases often attributed to a discordance between internal clocks and environmental timekeepers. REV-ERB nuclear receptors are key components of the molecular clock, but their specific role in the SCN master clock is unknown. We report here that mice lacking circadian REV-ERB nuclear receptors in the SCN maintain free-running locomotor and metabolic rhythms, but these rhythms are notably shortened by 3 hours. When housed under a 24-hour light:dark cycle and fed an obesogenic diet, these mice gained excess weight and accrued more liver fat than controls. These metabolic disturbances were corrected by matching environmental lighting to the shortened endogenous 21-hour clock period, which decreased food consumption. Thus, SCN REV-ERBs are not required for rhythmicity but determine the freerunning period length. Moreover, these results support the concept that dissonance between environmental conditions and endogenous time periods causes metabolic disruption.