Hydrogen inhalation promotes recovery of a patient in persistent vegetative state from intracerebral hemorrhage:A case report and literature review

BACKGROUND Persistent vegetative state(PVS)is a devastating and long-lasting clinical condition with high morbidity and mortality;currently,there are no available effective interventions.CASE SUMMARY We report the case of an 11-year-old boy with PVS caused by severe intracerebral bleeding in the left hemisphere following anticoagulation treatment.The patient’s PVS severity showed no notable improvement after 2-mo neuroprotective treatment and rehabilitation,including nerve growth factor and baclofen,hyperbaric oxygen,and comprehensive bedside rehabilitation therapies.Daily inhalation treatment(4-6 h)of high-concentration hydrogen(H2)gas(66.6%H2+33.3%O2)was provided.Surprisingly,the patient’s orientation,consciousness,ability to speak,facial expressions,and locomotor function were significantly restored,along with improvements in essential general health status,after H2 gas inhalation treatment,which was consistent with stabilized neuropathology in the left hemisphere and increased Hounsfield unit values of computed tomography in the right hemisphere.The patient finally recovered to a near normal conscious state with a Coma Recovery Scale-Revised Score of 22 from his previous score of 3.CONCLUSION Phase 1 clinical trials are needed to explore the safety and efficacy of H2 gas inhalation in patients with PVS.

Clinical application of Chinese Nanjing persistent vegetative state scale

Background:It is a challenge to characterize the consciousness level of patients with severe disturbance of consciousness and predict their prognosis effectively for Chinese doctors.We aimed to investigate the psychometric property and the diagnostic practicality of severe disturbance of consciousness by Chinese Nanjing persistent vegetative state scale(CNPVSS)which was first set up in 1996 and modified in 2001 and 2011.Methods:The concurrent validity,inter-rater consistency and diagnostic accuracy of CNPVSS and Chinese version of coma recovery scale-revised(CRS-R)were investigated by assessment of 380 patients with severe disorders of consciousness.Results:Total scores of the CNPVSS were correlated significantly with that of the CRS-R,indicating acceptable concurrent validity.Sub-scale analysis showed moderate to high inter-rater reliability and test-retest reliability.CNPVSS was superior to CRS-R on the diagnosis sensitivity.The CNPVSS was able to distinguish 65 patients in emergence from minimal consciousness state who were misclassified as in minimal consciousness state(MCS)by the CRS-R,and it could also distinguish two patients in MCS who were misclassified as in vegetative state by the CRS-R.Conclusion:The CNPVSS is an appropriate measurement and is sensitive to distinguish the MCS patients from the VS patients.

Comprehensive Proteomic Profiling of Patients'Tears Identifies Potential Biomarkers for the Traumatic Vegetative State

The vegetative state is a complex condition with unclear mechanisms and limited diagnostic, prognostic, and therapeutic methods. In this study, we aimed to explore the proteomic profile of tears from patients in a traumatic vegetative state and identify potential diagnostic markers using tears-a body fluid that can be collected noninvasively. Using iTRAQ quantitative proteomic technology, in the discovery phase, tear samples collected from 16 patients in a traumatic vegetative state and 16 normal individuals were analyzed. Among 1080 identified tear proteins, 57 were upregulated and 15 were downregulated in the patients compared to the controls. Bioinformatics analysis revealed that the differentially-expressed proteins were mainly involved in the wound response and immune response signaling pathways. Furthermore, we verified the levels of 7 differentially-expressed proteins in tears from 50 traumatic vegetative state patients and 50 normal controls （including the samples used in the discovery phase） using ELISA. The results showed that this 7-protein panel had a high discrimination ability for traumatic vegetative state （area under the curve = 0.999）. In sum- mary, the altered tear proteomic profile identified in this study provides a basis for potential tear protein markers for diagnosis and prognosis of the traumatic vegetative state and also provides novel insights into the mechanisms of traumatic vegetative state.

Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury： statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography

Background Hypoxic-ischemic brain injury （HIBI） after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state （VS） after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness （LOC） in patients with VS after post-resuscitated HIBI. Methods We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography （F-18 FDG PET） and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Results Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri （PFEw correctecd 〈0.0001 ）, and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem （PFEWcorrectecd 〈0.0001 ）. In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri （P uncorrected 〈0.005）. Conclusions Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.

Altered Protein Profiling in Tears from Patients in a Traumatic Vegetative State

Following severe traumatic brain injury .（sTBI）, patients may remain in a coma, vegetative state （VS）, or minimally conscious state （MCS）, all of which are also clinically termed disorders of consciousness. Patients in a coma show complete disability in the arousal system and fail to achieve awareness spontaneously; yet true coma represents a transient state and rarely lasts longer than a month [1]. The VS （also known as unresponsive wakefulness syndrome）, characterized as a state with spontaneous or stimulus-induced eye-opening but the patient appears totally unaware of self and environment, may persist for months or years [2]. In contrast, the MCS is evidenced by preserved and reproducible signs of awareness as well as sleep-wake cycles, suggesting better recovery than coma and VS. Considering that no signs of consciousness are detectable, patients in a VS suffer from a high rate of misdiagnosis [3].

Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule （Pcorrected 〈0.001）, and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices （Pcorrected 〈0.001）. In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices （Puncorrected 〈0.005）.Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism in patients with permanent vegetative state after acquired brain injury.

Spatial Properties of Mismatch Negativity in Patients with Disorders of Consciousness

In recent decades, event-related potentials have been used for the clinical electrophysiological assessment of patients with disorders of consciousness （DOCs）. In this paper, an oddball paradigm with two types of frequencydeviant stimulus （standard stimuli were pure tones of 1000 Hz; small deviant stimuli were pure tones of 1050 Hz; large deviant stimuli were pure tones of 1200 Hz） was applied to elicit mismatch negativity （MMN） in 30 patients with DOCs diagnosed using the JFK Coma Recovery Scale- Revised （CRS-R）. The results showed that the peak amplitudes of MMN elicited by both large and small deviant stimuli were significantly different from baseline. In terms of the spatial properties of MMN, a significant interaction effect between conditions （small and large deviant stimuli） and electrode nodes was centered at the frontocentral area. Furthermore, correlation coefficients were calculated between MMN amplitudes and CRS-R scores for each electrode among all participants to generate topographic maps. Meanwhile, a significant negative correlation between the MMN amplitudes elicited by large deviant stimuli and the CRS-R scores was also found at the frontocentral area. In consequence, our results combine the above spatial properties of MMN in patients with DOCs, and provide a more precise location （frontocentral area） at which to evaluate the correlation between clinical electrophysiological assessment and the level of consciousness.

Clinical studies on diffuse axonal injury in patients with severe closed head injury

OBJECTIVE: To discuss the clinical criteria for diagnosing diffuse axonal injury (DAI). METHODS: Clinical and computed tomographic features of 117 patients with severe closed head injury were analyzed. The authors preliminarily put forward CT diagnostic criteria of DAI, that is, 1) single or multiple small intraparenchymal hemorrhages in the cerebral hemispheres (