Background: Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI. Methods: We identified 38 patients from 2008 to 2014 with NIHSS ≥8, baseline CT <6 h after stroke onset, at least 1 follow-up (FU) CT, and no parenchymal hematoma. The volumes of CSF (sulci, ventricles, and cisterns) ipsilateral (IL) and contralateral (CL) to infarct on baseline and FU CTs were quantified by manually assisted outlining with MIPAV image analysis software, as was infarct volume and MLS on FU CTs. Percentage change in CSF volumes (∆CSF) from baseline to FU scans was correlated with MLS and compared in those with vs. without malignant edema (defined as hemicraniectomy, osmotic therapy, or death/neurological deterioration with MLS ≥5 mm). Results: 11 of 38 subjects (29 %) developed malignant edema. Neither baseline NIHSS nor CSF volume differed between those with and without edema (median NIHSS 18 vs. 13, p = 0.12, CSF volume 102 vs. 124 ml, p = 0.16). Inter-rater reliability for CSF measurements was excellent (intraclass correlation coefficient 0.97). ∆CSF correlated strongly with MLS at peak edema (r = −0.75), even adjusting for infarct volume (p = 0.009). ∆CSF was also greater in those with malignant edema [−55 % (IQR −49 to −62) vs. −36 % (−27 to −45), p = 0.004]. ∆CSF was the greatest within IL sulci [−97 % (−86 to −99) vs. −71 % (−41 to −79), p = 0.002] but also significantly greater within CL sulci in those with malignant edema [−50 % (−29 to −65) vs. −25 % (0 to −31), p = 0.014]. More than half this CSF volume reduction occurred by the time of first FU CT around 24 h after stroke, while MLS rose later. Conclusions: Volumetric CSF analysis reliably quantifies CED and distinguishes those with malignant edema and MLS from those with a more benign course after LHI. ∆CSF may provide an earlier and more sensitive indicator of edema severity across a broader dynamic range than MLS.

Original languageEnglish
Pages (from-to)420-427
Number of pages8
JournalNeurocritical Care
Issue number3
StatePublished - Jun 1 2016


  • Brain edema
  • Cerebrospinal fluid
  • Neuroimaging
  • Stroke


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