Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness

2021 ◽  
Vol 70 (5) ◽  
pp. 23-36
Author(s):  
Ekaterina A. Kondratyeva ◽  
Alina O. Ivanova ◽  
Maria I. Yarmolinskaya ◽  
Elena G. Potyomkina ◽  
Natalya V. Dryagina ◽  
...  

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation. AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness. MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid. RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state. CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.

2021 ◽  
Vol 11 (3) ◽  
pp. 356
Author(s):  
Anna Sontheimer ◽  
Bénédicte Pontier ◽  
Béatrice Claise ◽  
Carine Chassain ◽  
Jérôme Coste ◽  
...  

Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.


2021 ◽  
Author(s):  
Benyan Luo ◽  
Jie Yu ◽  
Qisheng Cheng ◽  
Fangping He ◽  
Fanxia Meng ◽  
...  

Abstract Intestinal microbiotas regulate brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding intestinal microbiome of patients in chronic disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the difference of intestinal microbiome and short-chain fatty acids (SCFAs) among the patients in vegetative state (VS), minimally conscious state (MCS) and emerged from minimally conscious state (EMCS), as well as the influence of antibiotics on these patients, 16S rRNA sequencing and targeted lipidomics were performed on their fecal samples and EEG signals analysis were used to evaluate their brain function. Our results showed that intestinal microbiome among the three groups differed greatly and some microbial community with its production of SCFAs were reduced in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs along with attenuated brain functional connectivity were observed in MCS patients treated with antibiotics compared to those received no antibiotic treatment, but not in the other pairwise comparisons. Finally, three genera level of microbiota, Faecailbacterium, Enterococcus and Methanobrevibacter, were considered as potential biomarkers to distinguish patients in MCS from VS with high accuracy both in the discovery cohorts and validation cohorts. Together, our findings improved the understanding of patients with chronic DoC from intestinal microbiome and provided a new reference for therapeutic targets exploration.


2019 ◽  
Vol 15 (5) ◽  
pp. 44-60 ◽  
Author(s):  
E. A. Kondratyeva ◽  
M. V. Sinkin ◽  
E. V. Sharova ◽  
S. Laureys ◽  
A. N. Kondratyev

The paper describes two patients with prolonged disorders of consciousness (PDC) because of non-traumatic brain injury, in whom a clear neurodynamic response to Zolpidem was observed.In order to illustrate systemic cerebral responses to administration of this drug in LIC patients, an analysis of clinical and electrophysiological changes has been undertaken.It has been shown that the result of Zolpidem applications in patients with prolonged disorders of consciousness (PDC) should be assessed not only by consciousness dynamics, but with the help of electroencephalogram (EEG) monitoring, too. Distinct response to Zolpidem during different periods of recovery in one patients was found.Zolpidem can render various effects in patients in vegetative state/with unresponsive wakefulness syndrome (VS/UWS) and in minimally conscious state (MCS). In one patient, sedation with EEG activation was observed, which was a sign of favorable prognosis. The other patient developed more than once local convulsions after Zolpidem administration followed by contact augmentation on the next day.The mechanism of action, necessary doses of drugs, and markers of forecasting the successful effect of that drug are yet to be further studied.


2020 ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Hu ◽  
Zhouyao Hu ◽  
Ziwei Sun ◽  
Steven Laureys ◽  
...  

Abstract Background: Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high rates of misdiagnosis by clinical consensus. The aim of this study was to investigate the proportion of misdiagnosis by clinical consensus compared to repeated behavior-scale assessments in patients with prolonged disorders of consciousness (DOC). Methods: Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical-consensus diagnosis. Trained professionals used the CRS-R to evaluate the consciousness levels of the enrolled patients repeatedly (≥5 times) within a week. Based on the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Finally, the relationship between the results of the CRS-R and the clinical consensus were analyzed. Results: In this study, 137 patients with a clinical-consensus diagnosis of prolonged DOC were enrolled. It was found that 24.7% of patients with clinical UWS were actually in MCS after a single CRS-R behavior evaluation, while the repeated CRS-R evaluation results showed that the proportion of misdiagnosis of MCS was 38.2%. A total of 16.7% of EMCS patients were misdiagnosed with clinical MCS, and 1.1% of EMCS patients were misdiagnosed with clinical UWS. Conclusions: The rate of the misdiagnosis by clinical consensus is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool in daily procedures.


Brain ◽  
2020 ◽  
Vol 143 (4) ◽  
pp. 1177-1189 ◽  
Author(s):  
Jiahui Pan ◽  
Qiuyou Xie ◽  
Pengmin Qin ◽  
Yan Chen ◽  
Yanbin He ◽  
...  

Abstract Cognitive motor dissociation describes a subset of patients with disorders of consciousness who show neuroimaging evidence of consciousness but no detectable command-following behaviours. Although essential for family counselling, decision-making, and the design of rehabilitation programmes, the prognosis for patients with cognitive motor dissociation remains under-investigated. The current study included 78 patients with disorders of consciousness who showed no detectable command-following behaviours. These patients included 45 patients with unresponsive wakefulness syndrome and 33 patients in a minimally conscious state, as diagnosed using the Coma Recovery Scale-Revised. Each patient underwent an EEG-based brain-computer interface experiment, in which he or she was instructed to perform an item-selection task (i.e. select a photograph or a number from two candidates). Patients who achieved statistically significant brain-computer interface accuracies were identified as cognitive motor dissociation. Two evaluations using the Coma Recovery Scale-Revised, one before the experiment and the other 3 months later, were carried out to measure the patients’ behavioural improvements. Among the 78 patients with disorders of consciousness, our results showed that within the unresponsive wakefulness syndrome patient group, 15 of 18 patients with cognitive motor dissociation (83.33%) regained consciousness, while only five of the other 27 unresponsive wakefulness syndrome patients without significant brain-computer interface accuracies (18.52%) regained consciousness. Furthermore, within the minimally conscious state patient group, 14 of 16 patients with cognitive motor dissociation (87.5%) showed improvements in their Coma Recovery Scale-Revised scores, whereas only four of the other 17 minimally conscious state patients without significant brain-computer interface accuracies (23.53%) had improved Coma Recovery Scale-Revised scores. Our results suggest that patients with cognitive motor dissociation have a better outcome than other patients. Our findings extend current knowledge of the prognosis for patients with cognitive motor dissociation and have important implications for brain-computer interface-based clinical diagnosis and prognosis for patients with disorders of consciousness.


2019 ◽  
Vol 9 (5) ◽  
pp. 123
Author(s):  
Elena I. Kremneva ◽  
Liudmila A. Legostaeva ◽  
Sofya N. Morozova ◽  
Dmitry V. Sergeev ◽  
Dmitry O. Sinitsyn ◽  
...  

Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.


2020 ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Hu ◽  
Zhouyao Hu ◽  
Ziwei Sun ◽  
Steven Laureys ◽  
...  

Abstract Background: Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high misdiagnosis rate for a clinical consensus. The aim of this study was to investigate the misdiagnosis rate of clinical consensus compared to repeated behavior scale assessments in patients with prolonged disorders of consciousness (DOC). Methods: Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical consensus diagnosis. Trained professionals also used the CRS-R to evaluate the consciousness levels of the enrolled patients for repeated times (≥5 times) within a week. After the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Furthermore, the relationship between the results of the CRS-R and the clinical consensus were analyzed. Results: In this study, 137 patients with a clinical consensus of prolonged DOC were enrolled. After the single CRS-R behavior evaluation, it was found that the misdiagnosis rate of clinical MCS was 24.7%, while the repeated CRS-R evaluation results showed that the misdiagnosis rate of clinical MCS was 38.2%. A total of 16.7% of EMCS cases were misdiagnosed as MCS, and 1.1% of EMCS cases were misdiagnosed as UWS. Conclusions: The current clinical consensus of the misdiagnosis rate is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool to daily procedures.


2020 ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Hu ◽  
Zhouyao Hu ◽  
Ziwei Sun ◽  
Steven Laureys ◽  
...  

Abstract Background: Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high rates of misdiagnosis by clinical consensus. The aim of this study was to investigate the proportion of misdiagnosis by clinical consensus compared to repeated behavior-scale assessments in patients with prolonged disorders of consciousness (DOC).Methods: Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical-consensus diagnosis. Trained professionals used the CRS-R to evaluate the consciousness levels of the enrolled patients repeatedly (≥5 times) within a week. Based on the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Finally, the relationship between the results of the CRS-R and the clinical consensus were analyzed.Results: In this study, 137 patients with a clinical-consensus diagnosis of prolonged DOC were enrolled. It was found that 24.7% of patients with clinical UWS were actually in MCS after a single CRS-R behavior evaluation, while the repeated CRS-R evaluation results showed that the proportion of misdiagnosis of MCS was 38.2%. A total of 16.7% of EMCS patients were misdiagnosed with clinical MCS, and 1.1% of EMCS patients were misdiagnosed with clinical UWS. Conclusions: The rate of the misdiagnosis by clinical consensus is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool in daily procedures. Keywords: Coma-Recovery Scale-Revised, Disorders of consciousness, Unresponsive wakefulness syndrome, Minimally conscious state, MisdiagnosisTrial registration: ClinicalTrials.gov ID: NCT04139239; Registered 24 October 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04139239


BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Hu ◽  
Zhouyao Hu ◽  
Ziwei Sun ◽  
Steven Laureys ◽  
...  

Abstract Background Previous studies have shown that a single Coma-Recovery Scale-Revision (CRS-R) assessment can identify high rates of misdiagnosis by clinical consensus. The aim of this study was to investigate the proportion of misdiagnosis by clinical consensus compared to repeated behavior-scale assessments in patients with prolonged disorders of consciousness (DOC). Methods Patients with prolonged DOC during hospitalization were screened by clinicians, and the clinicians formed a clinical-consensus diagnosis. Trained professionals used the CRS-R to evaluate the consciousness levels of the enrolled patients repeatedly (≥5 times) within a week. Based on the repeated evaluation results, the enrolled patients with prolonged DOC were divided into unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), and emergence from MCS (EMCS). Finally, the relationship between the results of the CRS-R and the clinical consensus were analyzed. Results In this study, 137 patients with a clinical-consensus diagnosis of prolonged DOC were enrolled. It was found that 24.7% of patients with clinical UWS were actually in MCS after a single CRS-R behavior evaluation, while the repeated CRS-R evaluation results showed that the proportion of misdiagnosis of MCS was 38.2%. A total of 16.7% of EMCS patients were misdiagnosed with clinical MCS, and 1.1% of EMCS patients were misdiagnosed with clinical UWS. Conclusions The rate of the misdiagnosis by clinical consensus is still relatively high. Therefore, clinicians should be aware of the importance of the bedside CRS-R behavior assessment and should apply the CRS-R tool in daily procedures. Trial registration ClinicalTrials.gov ID: NCT04139239; Registered 24 October 2019 - Retrospectively registered.


2018 ◽  
Vol 8 (8) ◽  
pp. 144 ◽  
Author(s):  
Sofya Morozova ◽  
Elena Kremneva ◽  
Dmitry Sergeev ◽  
Dmitry Sinitsyn ◽  
Lyudmila Legostaeva ◽  
...  

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.


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