Pupillometry measures such as the Neurological-Pupil-index (NPi) provide objective metrics for brainstem dysfunction. CMD refers to brain activation on fMRI/EEG to spoken commands. Both NPi and CMD are associated with long-term recovery after severe brain injury; here, we study the relationship between pupillary reactivity and CMD status. 

To assess the relationship of brainstem dysfunction and cognitive motor dissociation (CMD).

In this single-center, prospective, observational cohort-study, unresponsive patients with acute brain injury underwent serial Coma Recovery Scale-Revise (CRS-R), pupillometry, and CMD testing.  NPi-values (range 0-5) of 0 indicate unreactive and <3 poorly reactive pupils. Medical records were screened for a history of eye surgeries and eyedrops as confounders. Each CMD test was matched with the closest NPi-value obtained that day. Logistic regression was applied to identify associations between CMD and NPi-values and predictors of consciousness recovery (CRS-R³8), accounting for repeated measures. 

Amongst 96 patients, most frequent admission diagnoses were intracerebral hemorrhage (N=48,50%), subarachnoid hemorrhage (N=11,12%), and ischemic stroke (N=9,9%). 6475 pupillometry (median/patient 33[13-98]) and 373 CMD assessments were performed (median/patient 3[2-5]). CMD was detected in 13 patients(14%). NPi=0 or <3 was detected unilaterally in 48(17%) and 73(26%), and bilaterally in 29(10%) and 38(13%) instances, respectively. CMD status was not associated with NPi<3(p=0.24) or NPi=0 (p=0.48), in either or both eyes (p=0.92 and p=0.43, respectively). CRS-R<8 was associated with NPi<3 in either (p=0.005,OR=0.3[0.1-0.7]) or both eyes (p=0.003,OR=0.3[0.1-0.7) and NPi=0 in either (p=0.01,OR=0.3[0.1-0.7]) or both eyes (p=0.006,OR=0.25[0.1-0.6]).

Pupillary reactivity predicts behavioral recovery of consciousness, but not CMD. Intact arousal is a prerequisite for consciousness, including being in a CMD state; however, our findings suggest that pupillometry alone is insufficient to screen for CMD. Future studies will need to assess if more detailed assessments of brainstem dysfunction could serve as a CMD screening tool and if together they could more accurately predict functional recovery.