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Effect of Lesion Burden on Recovery and on Response to Amantadine in Patients with Disorders of Consciousness after Traumatic Brain Injury (P7.184)

OBJECTIVE: To assess the effect of lesion burden by CT on recovery and response to amantadine treatment in patients with prolonged traumatic disorders of consciousness (DoC).
BACKGROUND: Amantadine improves the pace and quality of recovery after traumatic DoC but it is uncertain how injury characteristics such as lesion burden affect recovery and the benefit of amantadine.
DESIGN/METHODS: Retrospective analysis of a randomized controlled trial dataset on 184 patients (87 amantadine; 97 placebo) with non-penetrating post-traumatic DoC, 4-16 weeks post-injury from 11 neurorehabilitation centers (USA, Denmark, and Germany). CT scans were visually coded against standard templates in 117 cortical and subcortical regions. Outcome measures: Disability Rating Scale (DRS) and Coma Recovery Scale-Revised (CRS-R) scores, 4 and 6 weeks post-randomization.
RESULTS: In the placebo group, higher lesion burden was significantly associated with worse outcome at 6 weeks post-randomization (cortical: n=89, DRS P=.0124, CRS-R P=.0324; subcortical: n=91, DRS P=.0067, CRS-R P=.0256). Follow-up regional analyses, controlling for time post-injury and initial level of consciousness, demonstrated a strong relationship of lesion burden to outcome in thalamus, striatum, medial prefrontal, dorsolateral prefrontal, parahippocampal, sensorimotor, auditory and temporoparietal association areas but not in precuneus/posterior cingulate, visual or brainstem areas. There was no significant interaction of lesion burden and treatment group (amantadine or placebo) at 4 weeks, however, inspection of the 4wk slope of recovery suggested that amantadine-treated patients with highest lesion burden recovered more slowly, similar to the placebo group, while patients in the placebo group with lowest lesion burden recovered faster, similar to the amantadine group.
CONCLUSIONS: Higher lesion burden on routine CT imaging is associated with worse recovery in patients with traumatic DoC, but does not conclusively limit the response to amantadine treatment. Damage in specific regions of interest was associated with functional outcome although the influence of regional versus global lesion burden remains unclear. Disclosure: Dr. Katz has nothing to disclose. Dr. Whyte has nothing to disclose. Dr. Chang has nothing to disclose. Dr. Eshkar has nothing to disclose. Dr. Kalmar has nothing to disclose. Dr. Long has nothing to disclose. Dr. Yablon has received personal compensation for activities with Medtronic, Inc. and Allergan, Inc. Dr. Bagiella has nothing to disclose. Dr. Giacino has nothing to disclose.