Olfactory sniffing signals consciousness in unresponsive patients with brain injuries.

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious1, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions2,3. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries4,5. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal6, and we therefore hypothesized that it may serve as a biomarker for consciousness7. Here we use a non-verbal non-task-dependent measure known as the sniff response8-11 to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function10-15. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury.

BACKGROUND: The prognosis of long-term severe disorders of consciousness due to traumatic brain injury is discouraging. There is little definitive evidence of the underlying mechanisms, but a deficiency of the dopaminergic system may be involved. METHODS: In a prospective open-labelled clinical study, the feasibility, relative efficacy and safety of continuous subcutaneous (s.c.) administration of apomorphine in Vegetative State (VS) or Minimally Conscious State (MCS) patients due to severe traumatic brain injury (TBI) was tested. Apomorphine was administered to eight patients. Outcome measures were the Coma Near-Coma Scale (CNCS) and Disability Rating Scale (DRS). RESULTS: Drug management was implemented without any problems. There was improvement in the primary outcomes for all patients. Awakening was seen as rapidly as within the first 24 hours of drug administration and as late as 4 weeks. Seven of the patients had completely recovered consciousness. All improvements were sustained for at least 1 year, even after apomorphine was discontinued. Drug-related adverse events were all anticipated and resolved after the dose was reduced. CONCLUSION: Based on this open-label pilot study, continuous s.c. apomorphine infusion appears to be feasible, safe and potentially effective in improving consciousness in patients in VS and MCS due to severe TBI.

Fast awakening from minimally conscious state with apomorphine.

BACKGROUND: Traumatic brain injury (TBI) can induce long-term severe disorders of consciousness. Evidence suggests an underlying dopaminergic deficit. Dopamine agonists may therefore play an important role in recovery of consciousness. OBJECTIVE: To explore the response to continuous subcutaneous administration of apomorphine in a patient who had remained in minimally conscious state for 104 days and to evaluate the anatomical substrate of the effect. DESIGN: A prospective, open-label, daily treatment, dose-escalation single case clinical study, with retrospective diffusion tensor image (DTI) evaluation. RESULTS: On the fist day of treatment, the patient was able to move his limbs on command and answer yes/no questions which had not been the case prior to apomorphine administration. Subsequently there was a full recovery of consciousness and substantial functional recovery that was sustained even after apomorphine discontinuation. At the highest dose, mild dyskinesias were observed. These resolved with a lowering of the dose. DTI demonstrated a decrease of thalamocortical and corticothalamic projections in this MCS patient compared to normal volunteers. CONCLUSION: Although this is an open-label single-patient case report, the data are consistent with the theory that a dopaminergic deficit underlies MCS and that it may be overcome with apomorphine administration.

Vegetative state.

Nowadays more and more patients survive severe brain injury, whether due to traumatic or other causes, owing to the technological advances in medicine. Added to this is a better understanding of pathophysiologic processes, the quality and availability of emergency medicine, and increased medical knowledge in the field. More patients are regaining consciousness than previously. Recovery of functional ability ranges from those still requiring significant nursing care to those able to function independently in activities of daily living. These changes in the levels of consciousness and function can also occur after very long periods of vegetative state. In our personal experience in the hospital, in 2004, 81% of patients in a post-traumatic vegetative state recovered some level of consciousness.

Differential time and related appearance of signs, indicating improvement in the state of consciousness in vegetative state traumatic brain injury (VS-TBI) patients after initiation of dopamine treatment.

OBJECTIVE: The goal of the study was to look for the response of treatment with increasing doses of dopaminergic medication on the recovery of vegetative state patients post-TBI. DESIGN: A prospective study of eight patients aged 25-50 years in vegetative state (VS) of mean duration of 104 days following traumatic brain injury (TBI) was performed by investigating changes of their state of consciousness while they were treated with levodopa/carbidopa. RESULTS: Initial improvement was observed in all patients within a mean of 13 days after onset of treatment. Seven patients recovered consciousness after a mean time of 31 days of treatment. The remaining patient showed only slight improvement to minimally conscious state. The sequence of symptoms leading to recovery was the same in all patients; the first to appear was moving a limb on a request, which appeared at a mean time of 13 days. Gradual increase of dose leads to the appearance of better-organized responses like reacting to more than one command, than opening the mouth and appearance of a reciprocal contact. The only side effect was visual hallucinations in one patient, which disappeared after decreasing the dosage. CONCLUSIONS: Clinical awareness to the structured order of responses and to the effect of dosage can help clinicians in early assessment of response to dopaminergic treatment in VS patients.