Antonio Carolei

To reveal covert abilities in a minimally conscious state (MCS) through an innovative activation paradigm based on olfactory imagery. Case study. A patient in MCS was asked to 'imagine an unpleasant odour' or to 'relax' in response to the appearance on a screen of a downward pointing arrow or a cross, respectively. Electrophysiological responses to stimuli were investigated by means of an 8-channel EEG equipment and analysed using a specific threshold algorithm. The protocol was repeated for 10 sessions separated from each other by 2 weeks. Accuracy, defined as the number of successes with respect to the total number of trials, was used to evaluate the number of times in which the classification strategy was successful. Analyses of accuracy showed that the patient was able to activate and to relax himself purposefully and that he optimized his performances with the number of sessions, probably as a result of training-related improvements. Subtle signs of consciousness may be under-estimated and need to be revealed through specific activation tasks. This paradigm may be useful to detect covert signs of consciousness, especially when patients are precluded from carrying out more complex cognitive tasks.

Background: Several studies have assessed the associations between migraine and underweight, pre-obesity or obesity, with conflicting results. To assess the consistency of the data on the topic, we performed a systematic review and meta-analysis of the available observational studies. Methods: Multiple electronic databases were systematically searched up to October 2014 for studies assessing the association between migraine and body mass index categories (underweight, pre-obesity, or obesity). Results: Out of 2,022 records, we included 15 studies. When considering the 11 studies following the World Health Organization BMI cutoffs, we found an increased risk of having migraine in underweight subjects (pooled adjusted effect estimate [PAEE] 1.21; 95% CI, 1.07-1.37; P = 0.002) and in obese women (PAEE 1.44; 95% CI, 1.05-1.97; P = 0.023) as compared with normal weight subjects; additionally, pre-obese subjects had an increased risk of having chronic migraine (PAEE 1.39; 95% CI, 1.13-1.71; P = 0.002). When considering all the 15 studies, we additionally found an increased risk of having migraine in obese as compared with normal weight subjects (PAEE 1.14; 95% CI, 1.02-1.27; P = 0.017); additionally, obese subjects had an increased risk of having chronic migraine (PAEE 1.75; 95% CI, 1.33-2.29; P < 0.001). The pooled analysis did not indicate an increased risk of having migraine in pre-obese subjects. Conclusions: The meta-analysis of the available observational studies suggested an association between migraine and obesity likely mediated by gender and migraine frequency. Further studies taking into account gender, migraine type, frequency, activity, and duration could provide more robust evidence.

The neurobiological approach to consciousness moves from the assumption that all phenomenal experiences are based on neuronal activity in the brain. Consciousness has two main components: wakefulness and awareness. While it may be relatively easy to determine the neuronal correlates of wakefulness, it is not the same for awareness, of which the neural correlates are poorly understood. Knowledge of the circuitry and the neurochemistry of the sleep/wake condition is necessary but not sufficient to understand the circuitry and neurochemistry of consciousness. Disorders of consciousness (DOCs) include coma, vegetative state and minimally conscious state. The study of DOCs and of the electrophysiological changes underlying general anaesthesia-induced loss of consciousness may help in understanding the neuronal correlates of consciousness. In turn, the understanding of the neural bases of consciousness may help in designing interventions aimed at restoring consciousness in DOC patients. Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.). This review provides an overview of such drugs, which are from various and diverging classes but can be grouped into two main categories: CNS stimulants and CNS depressants. The available data seem to suggest an awakening effect obtained with CNS depressants rather than stimulants, the latter being more effective at improving functional cognitive and behavioral recovery in patients who have spontaneously regained an appreciable level of consciousness. There is a need for more rigorous systematic trials and further investigation of the above treatments, with particular attention paid to their mechanisms of action and the neurotransmitters involved.

The growing diffusion of life support procedures, including cardiopulmonary resuscitation (CPR) and advanced cardiac life support (ACLS), allows physicians to keep a person alive almost indefinitely when the person's heart has stopped beating autonomously or spontaneous breathing is precluded. However, in some cases patients are brought back to life but remain in a vegetative state (VS) or in a minimally conscious state (MCS). This prompts reflections on the 'pros and cons' of life support procedures and on the recommended conduct to be adopted for the general management of patients who survive in a VS or MCS. Important issues to be debated include the choice of therapeutic management which guarantees for the patient the maximum possible physical and mental well-being; the distinction between 'worthwhile' and 'disproportionate' treatments; the patient's right to make decisions concerning his or her own health status; the possibility to make 'advance directives' when still healthy or when a life-threatening illness has been diagnosed; the role of relatives and caregivers in the choice of the best treatment for unconscious patients and the identification of ethically and scientifically valid criteria for the inclusion of unconscious patients in studies investigating experimental therapies.

Cases of recovery from vegetative and minimally conscious state after the administration of various pharmacological agents have been recently reported. These agents include CNS depressants (zolpidem, baclofen, lamotrigine) and CNS stimulants (tricyclic antidepressants, selective serotonin reuptake inhibitors, dopaminergic agents, methylphenidate). The action of CNS depressants as awakening agents sounds paradoxical, as they are commonly prescribed to slow down brain activity in the management of anxiety, muscle tension, pain, insomnia and seizures. How these drugs may improve the level of consciousness in some brain-injured patients is the subject of intense debate. Here we hypothesize that CNS depressants may promote consciousness recovery by reversing a condition of GABA impairment in the injured brain, restoring the normal ratio between synaptic excitation and inhibition, which is the prerequisite for any transition from a resting state to goal-oriented activities (GABA impairment hypothesis). Alternative or complementary mechanisms underlying the improvement of consciousness may include the reversal of a neurodormant state within areas affected by diaschisis (diaschisis hypothesis) and the modulation of an informative overload to the cortex as a consequence of filter failure in the injured brain (informative overload hypothesis). A better understanding of how single agents act on neural networks, whose functioning is critical for recovery, may help to advance a tailored pharmacological approach in the treatment of severely brain injured patients.