Disorders of consciousness : clinical and ethical perspective

Disorders of consciousness are among the main consequences of severe brain injury. They are characterised by the disruption of the relationship between the quantitative (arousal, wakefulness) and the qualitative (awareness of the self and environment) aspects of consciousness. This includes conditions where a high level of arousal is not accompanied with retained awareness (and vice versa). An accurate diagnosis of patients with severe brain injuries who present with various forms of disorders of consciousness still poses a real clinical, scientific and ethical challenge. This paper describes those conditions as well as diagnostic criteria and behavioural tools commonly used for their discrimination. The authors discuss brain death, coma, vegetative state, minimally conscious state and locked-in syndrome. Ethical and prognostic issues associated with the diagnosis and treatment of such patients are also discussed. Moreover, a clear classification of disorders of consciousness is proposed, which is intended to eliminate some ambiguities in Polish nomenclature concerning this type of neurological disorders. Behavioural scales are standard clinical tools for bedside assessment of patients with disorders of consciousness. In this paper, we review several behavioural scales, and describe their diagnostic advantages and shortcomings. The JFK Coma Recovery Scale–Revised (CRS-R) appears to present high sensitivity and specificity of diagnosing disorders of consciousness. The use of scales, such as the CRS-R, along with neuroimaging approaches (which have been developing intensively in the recent years) may provide a way to obtain a complete and accurate diagnosis of disorders of consciousness. That is why translation of the CRS-R and its validation in Polish conditions might play an important role in the diagnosis of such patients in our country

The newest research concerning consciousness of people in a vegetative state. A work based on results of fMRI imaging.

Diagnosis of the vegetative state is a highly subjective process, depending on the interpretation of overt behavior and the clinical experience of the examiner. Currently the decision-making process is based mostly on the behavioral evaluation, which is sometimes insufficient due to the severe peripheral motor dysfunction in some patients. The rate of misdiagnosis is very high (about 40%). There is a general agreement that new techniques which can provide some evidence of patient awareness and don't require any motor abilities, should be used during the diagnosis. One of those techniques is the functional magnetic resonance imaging (fMRI). This method proved that some patients who were not able to move, could perform imaginary tasks (this performance is accompanied with changes in activation in some specific brain regions) and thus demonstrate their awareness. Some scientists claim that using fMRI together with behavioral assessment would decrease the rate of misdiagnosis. fMRI can also be used as a communication between the physician and patient and thus improve quality of life in severely disabled patients.Diagnoza stanu wegetatywnego jest bardzo subiektywna i zależy od interpretacji zachowania pacjenta oraz doświadczenia klinicznego diagnostyka. Obecnie diagnoza opiera się przede wszystkim na ocenie zachowania, co często jest niewystarczające z powodu dysfunkcji motorycznych u części pacjentów, dlatego liczba nieprawidłowych diagnoz jest bardzo wysoka (wynosi ok. 40%). Powszechnie uważa się, że w procesie diagnostycznym powinno stosować się techniki, które nie wymagają od badanych żadnych zdolności motorycznych. Jedną z takich technik jest funkcjonalny rezonans magnetyczny (fMRI). Metoda ta pozwala na wykazanie, że część pacjentów, która nie ma możliwości ruchu, potrafi wykonać zadania wyobrażeniowe (co jest związane ze zmianami w aktywacji określonych rejonów mózgu) i wykazać, że jest świadoma. Część naukowców uważa, że zastosowanie fMRI razem z oceną behawioralną zmniejszyłoby liczbę nieprawidłowych diagnoz. fMRI może być również użyte w komunikacji pomiędzy pacjentem a lekarzem i przez to poprawić jakość życia pacjentów ze znaczną niepełnosprawnością

Diagnosis of disorders of consciousness based on EEG- use of correlates of motor intention

StreszczenieDiagnoza zaburzeń świadomości jest obecnie oparta głównie na obserwacji zachowania pacjentów. Uważa się, że osoba jest świadoma, jeżeli wykona dane polecenie lub adekwatnie odpowie na zadane pytanie. Możliwe jednak, że całkowicie lub częściowo świadomi pacjenci są sparaliżowani i nie można u nich zaobserwować żadnej wolicjonalnej aktywności motorycznej. Użycie nowoczesnych narzędzi (fMRI, PET, EEG) pozwala na wykrycie świadomych działań pacjentów, bez opierania się na ich możliwościach motorycznych. Cel: Zbadanie za pomocą EEG możliwości wykrycia wykonywania poleceń przez grupę kontrolną (osoby zdrowe ) i pacjentów z diagnozą zaburzeń świadomości.Metody: Osoby zdrowe oraz pacjenci z dwóch ośrodków w Toruniu zostali poddani częściowo zmodyfikowanej procedurze EEG, opracowanej przez Gugera i wsp. oraz Cruse i wsp. (Guger i wsp., 2003; Cruse i wsp., 2011, 2012a, 2012b). Zaraz po usłyszeniu dźwięku badani mieli wykonać jeden z dwóch typów zadań: 1) zgięcie palców prawej ręki i wyprostowanie ich 2) zaciśnięcie palców stopy i wyprostowanie ich. Zastosowano analizę czasowo-częstotliwościową oraz analizę pojedynczych prób eksperymentalnych z zastosowaniem naiwnego klasyfikatora bayesowskiego.Wyniki: U 6 zdrowych osób badanych obie zastosowane analizy statystyczne wykazały, że wykonali oni polecenia w obu lub przynajmniej w jednym warunku. 3 pacjentów uzyskało niejednoznaczne wyniki, na podstawie których nie można wyciągnąć wniosków na temat stopnia świadomości badanych. Wnioski: Nie udało się w jednoznaczny sposób potwierdzić użyteczności zastosowanej procedury w diagnozie zaburzeń świadomości. Powodem mogą być czynniki proceduralne lub etiologia zaburzeń u pacjentów.AbstractDiagnosis of disorders of consciousness is mainly based on the observation of patient's behaviour. It is claimed, that a person is conscious if he or she follows commands or in adequate manner answers questions given to him or her. However, it is also possible that fully or partially conscious patients are paralysed and no volitional external motor activity can be observed. Using modern tools (fMRI, PET, EEG) researchers can detect conscious efforts of patients, without having to rely on their motor abilities. .Objective: To determine the possibility of detection of command-following in control group (healthy volunteers) and patients with the diagnosis of disorders of consciousness analyzing the recorded EEG signal. Methods: Healthy volunteers and patients from two patient care centers in Toruń underwent partially modified procedure developed by Guger et al. and Cruse et al. (Guger et al., 2003; Cruse et al., 2011, 2012a, 2012b). The subjects were asked to perform one of the two types of tasks as soon as they heard a sound: 1) to squeeze the right hand and then relax it 2) to wriggle all of the toes on both feet, and then relax them. EEG signal was examined using time-frequency analysis and single-trial analysis with the naive Bayes classifier method.Results: In 6 healthy volunteers both statistical analysis (time-frequency analysis and single-trial classification) correlates of command-following were observed either in both, or one condition. 3 patients had mixed pattern of results, so it is impossible to draw any firm conclusions about their level of consciousness. Conclusion: The usefulness of this procedure in the diagnosis of disorders of consciousness was not univocally confirmed. The factors of procedure and etiolology of disorders of consciousness had to be taken into account

"Effect of selected exogenous factors on pregnant women, on pregnancy process and the biological status of the offspring"

Celem niniejszej pracy była ocena wpływu czynników egzogennych na kobiety w czasie ciąży, na jej przebieg oraz stan biologiczny ich potomstwa. Badanie miało charakter ankietowy i zostało przeprowadzone w grupie 180 kobiet posiadających potomstwo, zamieszkujących województwo Małopolskie. Zakres pracy obejmował wpływ dwóch czynników: spożywania alkoholu oraz palenia tytoniu. Dokonano charakterystyki badanych kobiet. Przeprowadzona analiza zachowań kobiet w czasie ciąży wykazała wiele nieprawidłowości: ok. 30% przyznało się do picia alkoholu w tym okresie. Palenie czynne potwierdziło 20% badanych, a narażenie na działanie dymu tytoniowego z otoczenia 60% respondentek. Powikłania okołoporodowe częściej dotyczyły kobiet wykazujących niebezpieczne zachowania w tym okresie. Komplikacje w czasie ciąży stwierdzono u kobiet, z których 40% sięgała po alkohol, 50% paliła tytoń, a w przypadku 56% narażone były na działanie dymu tytoniowego. Kobiety te częściej rodziły przez cesarskie cięcie oraz w terminach poprzedzających planowaną datę rozwiązania. Ocena stanu biologicznego potomstwa oparta została na: masie urodzeniowej, długości ciała, dojrzałości w skali Apgar, częstotliwości występowania zaburzeń rozwojowych oraz wad wrodzonych. Wyniki badań ukazały negatywny wpływ używek na stan dzieci oraz matki. Noworodki matek spożywających alkohol częściej rodziły się z niską, a nawet bardzo niską masą urodzeniową, mniejszą długością ciała. Częściej występował u nich także zaburzenia rozwojowe. U noworodków grupy matek pijących w ciąży najczęściej pojawiły się zaburzenia pracy serca, układu krążenia, rozwoju kończyn, rozszczepienie warg i podniebienia. U noworodków matek palących czynnie i biernie wystąpiły zaburzenia pracy układu oddechowego oraz układu krążenia. Do innych powikłań zaliczono: zaburzenia układu nerwowego oraz moczowego. Wyniki dojrzałości dzieci w skali Apgar nie wykazały różnic istotnych statystycznie. Badania wykazały różnicę między deklarowaną świadomością negatywnego oddziaływania używek w okresie ciąży, a ich stosowaniem. Koniec badań przyniósł jednak pozytywne wyniki. Znaczna większość zadeklarowała, że gdy ponownie zajdzie w ciążę wyeliminuje zachowania zagrażające jej oraz dziecku.The point of this research was a judgement of influences exogenous factors on women during pregnancy, on course of a pregnancy and biological condition their offspring. The research had a questionnaire character and was conducted in a group of 180 women who has children, and lives in a Małopolskie province. Scope of work included influence of two factors: drinking alcohol and smoking. It was made a characteristic of this woman. Carried out analysis showed many irregularities. Approximately 30% admitted to drinking alcohol in this period. Active smoking confirmed about 20% surveyed people and exposure to tobacco smoke from surroundings 60% respondents. Perinatal complications more often affected women exhibiting dangerous behaviour in this period. Complications in time of pregnancy found in women with whom 40% took the alcohol, 50% was smoking and in case 56% exposed to tobacco smoke. This group of women more often was boring with caesarean earlier than planning term. The judgement of biological condition of the offspring was based on: birth weight, body length, maturing in Apgar scale and frequency appearing developmental disorders and birth defects. Results of the researches showed a negative impact of stimulants on children’s and mother’s conditions. The newborns’ drinking mothers more often were boring with low and even very low birth weight, smaller body length. More often developmental disorders was appearing. The newborns from group of drinking mothers, mostly there were heart work disorders, circulatory system, limb development, cleft palate and lips. Newborns from active and passive smoking mothers’ group appeared disorders in working of respiratory system and with heart. To another complications included: disorders central nervous and urinary system. The results of the maturing in Apgar scale didn’t show any important differences statistically. The results of the researches showed the difference between declared awareness of the negative influence of stimulants in pregnancy period and using them. The end of the researches, however, brought the positive conclusions. The vast majority of women declared that if they get pregnant once again, they will eliminate behaviours which threaten her and her child

Disorders of consciousness in view of neuroimaging

Patients after severe brain injury are often unable to communicate, move on their own or show evidence of a purposeful behaviour, yet at the same time they may remain conscious. Such states are referred to as disorders of consciousness. Their clinical diagnosis, as based on complex behavioural criteria, is still prone to error and may lead to ambiguous cases. This article is an overview of the recent experimental approaches aimed at the assessment of the structure and function of the central nervous system, based on neuroimaging and employing the current knowledge regarding the mechanisms of consciousness. All these approaches are aimed at identifying the most efficient measure to enable a reliable diagnosing. The first approach is based on structural imaging that provides information on the organisation and state of neural connections within the brain. Other approaches are functional studies divided into passive and active ones. Passive paradigms evaluate the ability of the neural networks in the patient’s brain to sustain consciousness without them having to take part in an experimental task, while the active ones enable the assessment of the state of consciousness on the basis of neural correlates of volitional activities recorded as the patient performs mental tasks. The latter approach rests on an assumption that volitional activity requires conscious processing and cannot be explained in terms of stereotypic reaction to stimulation. While a significant number of approaches presented herein works quite well with respect to differentiating the states on the group level, still only a few of them allow such differentiation on the level of an individual patient. On the latter level, the most important challenge (when it comes to choose a particular care for a patient) could be carried out by a complementary use of several methods at the same time or the evaluation of brain function based on various neuroimaging techniques (EEG and fMRI)

Contributions of dopaminergic and non-dopaminergic neurons to VTA-stimulation induced neurovascular responses in brain reward circuits

Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together. We further used electrical stimulation to non-selectively activate neurons in the VTA. All three stimulation conditions effectively activated the mesolimbic dopaminergic system and triggered dopamine releases into the NAcc as measured by in vivo fast-scan cyclic voltammetry. Furthermore, both optogenetic stimulation paradigms led to indistinguishable self-stimulation behavior. In contrast to these similarities, however, the BOLD response pattern differed greatly between groups. In general, BOLD responses were weaker and sparser with increasing stimulation specificity for dopaminergic neurons. In addition, repetitive stimulation of the VTA caused a progressive decoupling of dopamine release and BOLD signal strength, and dopamine receptor antagonists were unable to block the BOLD signal elicited by VTA stimulation. To exclude that the sedation during fMRI is the cause of minimal mesolimbic BOLD in response to specific dopaminergic stimulation, we repeated our experiments using CBF SPECT in awake animals. Again, we found activations only for less-specific stimulation. Based on these results we conclude that canonical BOLD responses in the reward system represent mainly the activity of non-dopaminergic neurons. Thus, the minor effects of projecting dopaminergic neurons are concealed by non-dopaminergic activity, a finding which highlights the importance of a careful interpretation of reward-related human fMRI data

Matching stimulation paradigms resolve apparent differences between optogenetic and electrical VTA stimulation

BACKGROUND: Optogenetic stimulation has grown into a popular brain stimulation method in basic neuroscience while electrical stimulation predominates in clinical applications. In order to explain the effects of electrical stimulation on a cellular level and evaluate potential advantages of optogenetic therapies, comparisons between the two stimulation modalities are necessary. This comparison is hindered, however, by the difficulty of effectively matching the two fundamentally different modalities. OBJECTIVE:Comparison of brain-wide activation patterns in response to intensity-matched electrical and optogenetic VTA stimulation. METHODS: We mapped optogenetic and electrical self-stimulation rates in the same mice over stimulation intensity and determined iso-behavioral intensities. Using functional 99mTc-HMPAO SPECT imaging of cerebral blood flow in awake animals, we obtained brain-wide activation patterns for both modalities at these iso-behavioral intensities. We performed these experiments in two mouse lines commonly used for optogenetic VTA stimulation, DAT::Cre and TH::Cre mice. RESULTS: We find iso-behavioral intensity matching of stimulation gives rise to similar brain activation patterns. Differences between mouse lines were more pronounced than differences between modalities. CONCLUSIONS: Previously found large differences of electrical and optogenetic stimulation might be due to unmatched stimulation intensity, particularly relative electrical overstimulation. These findings imply that therapeutic electrical VTA stimulation might be relatively specific if employed with optimized parameters