An oncology-directed history, with particular attention to a detailed medication history, is critical to narrowing the differential diagnosis Physical examination should look for other findings such as papilledema or focal neurologic findings that may also narrow the differential diagnosis Laboratory evaluation should be carried out as recommended in Chapter 97 Neurologic Emergencies If a drug-related cause is suspected, specific drug levels when available may be helpful If a lumbar puncture is planned to look for malignant cells or an infectious etiology, the risk of herniation should be assessed Imaging studies may be appropriate if an intracranial lesion is suspected or when the diagnosis is unclear A CT scan without contrast can be useful to identify midline shift, increased ventricular size, or a hemorrhagic stroke A CT scan with contrast can identify likely carcinomatous meningitis or a supratentorial mass lesion MRI can identify mass lesions anywhere in the CNS including below the tentorium, ischemic stroke, hypertensive encephalopathy, or encephalitis Management of drug-related altered mental status usually involves withholding the offending agent and supporting the patient until return to baseline If narcoticrelated, avoid rapid and complete reversal with standard doses of naloxone, which could cause excruciating pain that will be unresponsive to further narcotics for to hours Supportive care such as stimulation should be tried prior to reversal If reversal is required, the appropriate dose of naloxone (0.1 mg/kg) should be diluted in 10 mL of normal saline and then administered in 1-mL aliquots while titrating to effect Alternatively, dosing can be initiated at µg/kg for mild respiratory depression and 10 µg/kg for reversal of moderate to severe respiratory depression as needed Laboratory evaluation of hepatic and renal function may identify contributing factors to increased drug effect If ifosfamide neurotoxicity is suspected, many recommend methylene blue treatment using dosages that have been extrapolated from other settings The usual dose for adolescents and adults is 50 mg administered orally or by slow IV push There is no clear dosage for younger children but there are case reports using to mg/kg as in the treatment for methemoglobinemia For management of hypertensive encephalopathy, see Chapter 37 Hypertension