Predictions of Therapeutic Effects of Zolpidem in Disorders of Consciousness Patients

Project: A - Government Institutionb - National Science and Technology Council

Project Details


Unresponsive wakefulness syndrome or vegetative state (UWS/VS) and minimally conscious state (MCS)—Disorders of Consciousness—are debilitating neurological conditions that affect patients’ awareness of self and of the external environment. Over the last decade, DOC patients have attracted more and more attention in clinics worldwide. According to Taiwan’s 創世基金會(personal communication; November 18, 2015), they care for 1,700 UWS patients locally, and they estimate that this is only about 5% of Taiwan’s total. In other words, Taiwan’s UWS patients total in the 10s of thousands. Nevertheless, in Taiwan too little attention has been given to the most recent methods of diagnosis, prognosis, and treatment. This is especially unfortunate since much progress has been made in recent years, on all fronts. For patients with DOC, the importance of early prognosis and effective therapy is self-evident, but markers of therapeutic recovery and effective interventions are still inadequate. Furthermore, previously published studies have reported that up to 41% of patients with DOC (UWS/VS and MCS) are erroneously assigned a diagnosis of vegetative state. If this figure reflects the case in Taiwan, and if 創世基金會’s estimates are correct, then Taiwan likely has thousands of misdiagnosed patients. Recently researchers have used the neuroimaging methods (fMRI, FDG-PET, MRS and so on) to investigate the residual brain functions of these patients, in order to begin developing reliable markers for diagnosis or prognosis marker. Moreover, some promising results have been observed using the GABAergic drug, zolpidem (also known as, ambien). Only a subset of patients, however, show this therapeutic response to the drug, suggesting that a particular mode of remaining brain function is required for the intervention to be effective. What these neural properties may be remains to be investigated, so it is currently not possible to predict which patients will and which will not respond to zolpidem intervention. This study is using multimodal neuroimaging (fMRI, MRS and PET) in a large cohort of DOC patients. First, we will combine the results of the multimodal neuroimaging to evaluate the residual brain functions, and then to investigate the relationship between the residual brain functions and diagnosis/prognosis. This will be helpful to develop markers for diagnosis or prognosis that are more accurate. Second, the patients will be treated with zolpidem. The neural properties (residual brain functions) of those who do respond to the treatment will then be compared to those of the patients who do not. This will allow the identification of potential biomarkers of zolpidem efficacy in DOC treatment. And, third, discovering the differences between responders and non-responders will provide key insights into the neural mechanisms involved in DOC, indeed in consciousness itself.
Effective start/end date8/1/167/31/17


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