(Kiosk 4) Profound Verbal Function Improvements After Single-dose Zolpidem in Two Minimally Conscious Patients with Severe Traumatic Brain Injuries

Case Diagnosis: Two young patients with severe traumatic brain injuries

Case Description or Program Description: Two patients presented with disorders of consciousness secondary to severe TBIs. On initial Coma Recovery Scale-Revised (CRS-R), patient 1, a 24-year-old woman, scored 12 consistent with a minimally conscious state (MCS). Her neurostimulant regimen included amantadine, modafinil, and methylphenidate. The second patient, a 23-year-old man, also scored 12 on the initial CRS-R consistent with MCS. He was started on amantadine. Despite both patients improving on CRS-R, they remained in MCS and were deemed candidates for zolpidem trials.

Setting: Acute inpatient rehabilitation facility (IRF)

Assessment/Results: For patient 1, her trial was 8 weeks post-TBI and 4 weeks into inpatient rehabilitation. On CRS-R 1-hour after 10mg zolpidem administration her score improved from 14 to 17, notably demonstrating functional object use indicating emergence from MCS. She returned to MCS on repeat CRS-R an hour later. She had another zolpidem trial 10 days later again with emergence as well as intelligible verbalizations for the first time but no functional communication.
For patient 2, his zolpidem trial was conducted approximately 6 weeks post-TBI and 3 weeks into inpatient rehabilitation. One hour after 10mg zolpidem administration, his CRS-R score improved from 14 to 19 which included functional object use and communication indicating emergence. On repeat CRS-R at the 2-hour mark, his CRS-R continued to increase in auditory and visual function scales. Both patients were continued on zolpidem 10mg daily upon discharge to a subacute rehabilitation facility specialized in brain injury during which they fully emerged.

Discussion (relevance): Incidence of “zolpidem-responders” is low with research findings ranging from 4.8-6.7%. The mesocircuit model for zolpidem-induced improvements in impaired consciousness postulates zolpidem, a GABA-A agonist, inhibits globus pallidus internus. This releases central thalamus from inhibition and increases activation of the prefrontal cortex. The effect of zolpidem is transient however these effects are reproducible with no development of tolerance. The similarities between these cases, such as age and MCS at trial, suggests further research is needed to elucidate prognostic factors of zolpidem response.

Conclusions: Zolpidem trials should be considered in patients with disorders of consciousness and can lead to profound behavioral improvements in the rare responder.