TUMORAL VASOGENIC EDEMA

Pathogenesis:  production of VEGF, glutamate, leukotrienes (increases permeability of tumor vessels) and absence of tight endothelial cell junctions in tumor blood vessels (respond to VEGF and basic fibroblast growth factor)

Gliomas, meningiomas, metastatic tumors à secretes VEGF à binds to VEGFR1 and VEGFR2 (surface of endothelial cells à formation of gaps in endothelium à fluid leakage into brain parenchyma à vasogenic edema à spreads more in white matter (lower resistance than gray matter) à disrupts synaptic transmission, alters neuronal excitability à HA, seizures, focal deficits, encephalopathy, herniation

DEXAMETHASONE

Advantages:  Lack of mineralocorticoid activity, less fluid retention; lower risk of infection and cognitive impairment

Mechanism:  Upregulates Ang-1 (BBB-stabilizing factor) and downregulates VEGF in astrocytes and pericytes; increases clearance of peritumoral edema by facilitating transport of fluid into ventricular system

Dosage:

  • Severe symptoms: 10mg IV loading dose then 4mg QID or 8 mg BID
  • Lower doses (1-2mg QID) may be as effective and less toxic if without impending herniation
  • Long half life to allow BID dosing
  • Improves within hours, maximum benefit within 24-72 hours, neuroimaging may not confirm until at least 1 week
  • If 16mg/day insufficient, may increase up to 100mg/day

Taper:  once improved, taper by 50% every 4 days

Guidelines: 16mg/d or more if severe symptoms due to inc ICP and edema due to brain mets; for milder symptoms, start 4-8mg daily; if asymptomatic, steroids not recommended; taper over 2 week period or longer

Complications:

  • insomnia, essential tremor, hiccups
  • GI complications
  • Steroid myopathy – prox weakness in week 9-12
  • PCP infection – risk increases while tapering steroids; fever and dyspnea and dry cough but can be subtle and nonspecific

Novel treatments: bevacizumab (anti-VEGF monoclonal antibodies); corticotrophin-releasing factor, COX-2 inhibitors?

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