Thoughts and Consciousness     twitter    Louis' awakening    neurotransmitters     donations

 

The Minimally Conscious State (MCS) is distinguished from Coma and the Vegetative State by the presence of behaviours associated with conscious awareness. In MCS, cognitively mediated behaviour occurs inconsistently, but is reproducible or sustained long enough to be differentiated from reflexive behaviour. The reproducibility of such evidence is affected by the consistency and complexity of the behavioural response (1).

Limited but clearly discernible evidence of self or environmental awareness must be demonstrated on a reproducible or sustained basis by one or more of the following behaviours:

-Following simple commands.

-Gestural or verbal yes/no responses (regardless of accuracy).

-Intelligible verbalization.

-Purposeful behavior, including movements or affective behaviors that occur in contingent relation to relevant environmental stimuli and are not due to reflexive activity.

 

Over the last few years, zolpidem (ambien) was shown to improve clinical features encountered in the Minimally Conscious State. It can increase brain function within 30 minutes after oral application with a maximum effect after 1 hour, lasting 2-3 hours (2, 3). Imaging studies using ^99mTc HMPAO Brain SPECT or ¹⁸F FDG PET in patients after brain damage have shown that non-functioning areas start to function again after zolpidem (2,4). One case showed that zolpidem was effective in a minimally conscious patient after hanging and another showed that the medicine is effective in relieving symptoms in long standing brain anoxia after cardiac arrest (2, 5). In a study by Whyte et al on 15 patients, a marked improvement was reported in an MCS patient (6).

Zolpidem’s proposed  mode of action is the modulation of ‘abnormal’ GABA receptors that are responsible for Brain dormancy, also called the neurodormant state (7). The neurodormant state 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 (8). In another study, this suppression was associated with reorganisation of GABA mediation in the cerebellum (9). 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 (10).

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

 

 

References

1          J.T. Giacino, PhD, S. Ashwal, MD, N. Childs, MD, R. Cranford, MD, B. Jennett, MD, D.I. Katz, MD, J.P. Kelly, MD, J.H.Rosenberg, MD, J. Whyte, MD PhD;, R.D. Zafonte, DO and N.D. Zasler, MD. The Minimally Conscious State Definition and criteria. Neurology 2002,   58: 349-353.

2          Brefel-Courbon C, Payoux P, Ory F, Sommet A, Slaoui T, Raboyeau G, Lemesle    B, Puel M, Montastruc JL, Demonet JF and Cardebat D, Clinical and Imaging evidence of zolpidem effect in hypoxic encephalopathy, Ann Neurol.2007, 62: 102.

3          Shames JL, Ring H. Transient reversal of anoxic brain injury after zolpidem administration: a case report. Arch Phys Med Rehabil. 2008, 89: 386-8.

4          Clauss RP and Nel HW, The effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO Brain SPECT in humans, Arzneim.-Forsch./Drug Res. 2004, 54: 641-646.

5          Shadan FF, Poceta JS and Kline LE, Zolpidem for Postanoxic Spasticity. Southern Medical Journal 2004, 97: 791-792.

6          Whyte J and Myers R, Incidence of clinically significant responses to zolpidem among patients with Disorders Of Consciousness: A preliminary placebo controlled trial. American Journal of Physical Medicine and Rehabilitation. 2009, 88: 410- 418.

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

8         Niimura K, Chugani DC, Muzik O and Chugani HT, Cerebellar reorganization following cortical injury in humans: effects of lesion size and age, Neurology. 1999, 10: 792-797.

9         Witte OW and Stoll G, Delayed and remote effects of focal cortical infarctions:secondary damage and reactive plasticity, Adv Neurol. 1997, 73: 207-227.

10        Aviles-Reyes RX, Angelo MF, Villarreal A, Rios H, Lazarowski A and Ramos  AJ, Intermittent hypoxia during sleep induces reactive gliosis and limited neuronal death in rats: Implications for sleep apnea, J Neurochem 2010, 112: 854-69.