The clinical criteria are:

-No evidence of awareness of self or environment; no interaction with others

-No evidence of sustained, reproducible, purposeful or voluntary behavioral responses to visual, auditory, tactile or noxious stimuli.

-No evidence of language comprehension or expression

-Return of sleep-wake cycles, arousal, even smiling, frowning, yawning

-Sufficient hypothalamic and brainstem autonomic functions to survive if given medical or nursing care.

-Bowel and bladder incontinence-Variably preserved cranial nerve and spinal reflexes

 

In 2000 Clauss & Nel et al were the first to publish a report on the unexpected arousal after zolpidem in a patient categorized to the Vegetative State (3). This was followed by another publication, 2006 in NeuroRehabilitation, describing similar cases (4). Two motor vehicle accident patients and one near drowning patient, all of them classified to the Vegetative State for at least three years, were transiently aroused every morning after zolpidem. Glasgow Coma Scale scores ranged from 6-9/15 before to 10-15/15 after zolpidem. Rancho Los Amigos Cognitive scores ranged from I-II before to V-VII afterwards. Drug efficacy did not decrease and there were no long term side effects after 3-6 years daily use. In these patients brain function increased within 30 minutes after oral application of zolpidem with a maximum effect after 1 hour, lasting 2-3 hours (4). Imaging studies using ^99mTc HMPAO Brain SPECT or ¹⁸F FDG PET  scans show that non-functioning areas start to function again after zolpidem in such patients (3, 4, 5). In 2008 Du et al reported arousal in seven Vegetative State patients after zolpidem. The patients had significant improvements in their cerebral state index, electromyographic index, burst suppression and cerebral perfusion (6).

Zolpidem’s proposed  mode of action is the modulation of ‘abnormal’ GABA receptors that are responsible for Brain dormancy in the Vegetative State, neurodormancy (4). Neurodormancy is the manifestation of a re-modulated GABA receptor status that occurs in areas of the brain after injury. A previous study has shown that certain types of brain suppression are associated with an altered composition of GABA(A) receptor subunits (7). In another study, this suppression was associated with reorganisation of GABA mediation in the cerebellum (8). With normal or borderline GABA levels, GABA receptors remain functioning normally, but in depleted regions such receptors presumably undergo molecular modifications or changes in abundance, possibly due to gene expression, as found in other ischaemic brain conditions (9).

 

For further information on neurodormancy, please click on -Brain dormancy theory- in the main menu. 

References

4          Clauss RP and Nel HW, Drug induced arousal from permanent Vegetative State, Neurorehabilitation 2006, 21: 23-8.