Next to grey and white matter atrophy, cerebrospinal fluid (CSF) volume and ventricular dilation may be surrogate biomarkers for brain atrophy in spinal cord injury (SCI). We therefore aimed to track brain atrophy by means of CSF volume changes and ventricular enlargements over two years following SCI. Fifteen SCI patients and 18 healthy controls underwent a series of T1-weighted scans during five time-points over two years. Changes of CSF/ Intracranial volume (CSF/ICV) ratio and ventricular enlargement rate over time were determined. Sample sizes with 80% power and 5% significance were calculated to detect a range of treatment effects for a two-armed trial. There was a significant cross-sectional increased CSF/ICV ratio in patients compared with controls at each time point (P<0.02). However, the rate of CSF/ICV changes was not significantly different between groups over time. CSF volume increased linearly over bilateral sensorimotor cortices (left: P=0.002, right: P=0.042) and in the supracerebellar space (P<0.001) within two years. An acceleration of the enlargement within the third (P=0.017) and the fourth (P=0.006) ventricles was observed in patients. Sample size estimation for six-month trials with CSF volume requires 25 patients per treatment arm to detect a hypothetical treatment effect in terms of slowing of atrophy rate of 30%. This study shows that SCI-induced changes in CSF/ICV ratio and ventricular expansion rate provide additional information on the neurodegenerative processes following injury. The sensitivity to scoring treatment effects speaks to its potential to serve as a sensitive biomarker in addition to local atrophy measures.