The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Promoting the process of determining brain death through standardized training.

Objective: This study aims to explore the training mode for brain death determination to ensure the quality of subsequent brain death determination. Methods: A four-skill and four-step (FFT) training model was adopted, which included a clinical neurological examination, an electroencephalogram (EEG) examination, a short-latency somatosensory evoked potential (SLSEP) examination, and a transcranial Doppler (TCD) examination. Each skill is divided into four steps: multimedia theory teaching, bedside demonstration, one-on-one real or dummy simulation training, and assessment. The authors analyzed the training results of 1,577 professional and technical personnel who participated in the FFT training model from 2013 to 2020 (25 sessions), including error rate analysis of the written examination, knowledge gap analysis, and influencing factors analysis. Results: The total error rates for all four written examination topics were < 5%, at 4.13% for SLSEP, 4.11% for EEG, 3.71% for TCD, and 3.65% for clinical evaluation. The knowledge gap analysis of the four-skill test papers suggested that the trainees had different knowledge gaps. Based on the univariate analysis and the multiple linear regression analysis, among the six factors, specialty categories, professional and technical titles, and hospital level were the independent influencing factors of answer errors (p < 0.01). Conclusion: The FFT model is suitable for brain death (BD) determination training in China; however, the authors should pay attention to the professional characteristics of participants, strengthen the knowledge gap training, and strive to narrow the difference in training quality.

To Accelerate the Process of Brain Death Determination in China Through the Strategy and Practice of Establishing Demonstration Hospitals.

BACKGROUND: Our objective was to explore whether a brain death determination (BDD) strategy with demonstration hospitals can accelerate the process of BDD in China. METHODS: We proposed the construction standards for the BDD quality control demonstration hospitals (BDDHs). The quality and quantity of BDD cases were then analyzed. RESULTS: A total of 107 BDDHs were established from 2013 to 2022 covering 29 provinces, autonomous regions, and municipalities under jurisdiction of the central government of the Chinese mainland (except Qinghai and Tibet). A total of 1,948 professional and technical personnel from these 107 BDDHs received training in BDD, 107 quality control personnel were trained in the quality control management of BDD, and 1,293 instruments for electroencephalography, short-latency somatosensory evoked potential recordings, and transcranial Doppler imaging were provided for BDD. A total of 6,735 BDD cases were submitted to the quality control center. Among the nine quality control indicators for BDD in these cases, the implementation rate, completion rate, and coincidence rate of apnea testing increased the most, reaching 99%. CONCLUSIONS: The strategy of constructing BDDHs to promote BDD is feasible and reliable. Ensuring quality and quantity is a fundamental element for the rapid and orderly popularization of BDD in China.

Assessment of disease severity and patient prognosis in anti-GABABR encephalitis with and without comorbid tumors.

Purpose: This study aimed to analyze the severity of the condition and prognosis of patients with anti-gamma-aminobutyric-acid type B receptor (anti-GABABR) encephalitis with tumors. Methods: Patients with anti-GABABR encephalitis admitted to one of two hospitals from 2020 to 2022 were enrolled and divided into tumor and non-tumor groups. The clinical characteristics, condition severity, treatment options, and prognosis of the two groups of patients were compared and analyzed. Results: Eighteen patients with anti-GABABR encephalitis were included, ten of whom had tumors. The comparison of clinical characteristics showed that rates of status epilepticus and coma were significantly higher in the group with tumors (P = 0.013 and P = 0.025, respectively); the incidences of pulmonary infection, respiratory failure, hyponatremia, and hypoproteinemia were also substantially more frequent in the tumor group (P = 0.054, P = 0.036, P = 0.015, and P = 0.025, respectively). The laboratory test result comparison showed that serum neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) were present only in the group with tumors (P = 0.036 and P = 0.092, respectively), but there was no significant difference in the occurrence of elevated CEA between the two groups. Conversely, the percentage of serum systemic autoimmune antibodies was higher in the group without tumors than in the group with tumors (P = 0.043). Patients with tumors tended to have poor outcomes (P = 0.152, OR: 7.000). Conclusion: Severe brain damage and complications occur in patients with anti-GABABR encephalitis and comorbid tumors. Early screening for serum NSE and CEA helps in the early diagnosis and treatment of tumors. The prognosis is much worse for anti-GABABR encephalitis with tumors.

Quantitative EEG and brain network analysis: predicting awakening from early coma after cardiopulmonary resuscitation.

OBJECTIVE: For patients in early coma after cardiopulmonary resuscitation (CPR), quantitative electroencephalogram (EEG) and brain network analysis was performed to identify relevant indicators of awakening. METHODS: A prospective cohort study was conducted on comatose patients after CPR in the neuro-critical care unit. The included patients received clinical evaluation. The bedside high-density (64-lead) EEG monitoring was performed for visual grading and calculation of power spectrum and brain network parameters. A 3-month prognostic assessment was performed and the patients were dichotomized into the awakening group and the unawakening group. RESULTS: A total of 25 patients were included. The awakening group had higher GCS score, more slow wave pattern and reactive EEG than the unawakening group (P = 0.003, P < 0.001, P < 0.001, respectively). Compared with the unawakening group, (1) the awakening group had significantly higher absolute and relative θ power and slow/fast band ratio of the whole brain (P < 0.05), (2) the awakening group had stronger connection based on coherence, phase synchronization, phase lag index and cross-correlation (P < 0.05), (3) the awakening group had higher small-worldness, clustering coefficient and average path length based on graph theory (P < 0.05). CONCLUSIONS: The power spectrum and brain network characteristics in patients in early coma after CPR have predictive value for recovery.

Long-term follow-up of phenobarbital versus valproate for generalized convulsive status epilepticus in adults: A randomized clinical trial.

OBJECTIVE: Intravenous phenobarbital is frequently offered to patients with generalized convulsive status epilepticus (GCSE) in China, but its long-term benefits are unclear. We aimed to evaluate the long-term effects of intravenous phenobarbital on adult patients with GCSE. METHODS: This randomized clinical trial with a 12-month follow-up was performed in Xuanwu Hospital, Capital Medical University (Beijing, China) between February 2011 and December 2021. After the failure of intravenous diazepam treatment, adult patients with GCSE were randomized to receive either intravenous phenobarbital or valproate. Neurological outcome within 12-month was dichotomized as good (modified Rankin scale, mRS 0-2) or poor (mRS 3-6). Cognitive function was measured by mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) were tested for mood disorders. RESULTS: We consecutively recruited 166 patients with GCSE. After excluding individuals with termination after intravenous diazepam (n = 61), and with other exclusion criteria (n = 7), 98 patients were included and 88.0% (66/75) of survivors achieved seizure freedom at 12-month. Forty-five patients (45.92%) had good outcomes at 3-month and 57 patients (58.16%) had good outcomes at 12-month. And 46.67% (35/75) of survivors showed mRS improvement at 12-month (phenobarbital group, n = 17 vs. valproate group, n = 18, P = 0.321). Despite there was no significant difference with respect to good outcomes at 3-month (54.0% vs. 37.5%, P = 0.101), the rate of good outcomes in phenobarbital group was higher than valproate group at 12-month (68.0% vs. 47.92%, P = 0.044). A total of 43 patients successfully participated cognitive and emotional tests. Mild cognitive impairment was found in 7.14% of phenobarbital group and 50.0% in valproate group (P = 0.026). In addition, there were no significant differences with respect to anxiety (36.36% vs. 38.10%) and depression (31.82% vs. 47.62%) between the phenobarbital and valproate groups. CONCLUSIONS: Combined with long term conventional therapy, intravenous phenobarbital group had more good outcomes than intravenous valproate group in Chinese adult patients with GCSE up to 12-month follow-up. This finding may prompt the option of intravenous phenobarbital especially in patients with limited access to new antiseizure drugs.

The development of neurocritical care in China from the perspective of evaluation and treatment of critical neurological diseases.

Objective: To understand the varieties, evaluation, treatment, and prognosis of severe neurological diseases using the third NCU survey in China. Design: A cross-sectional questionnaire study. The study was completed in three main steps: filling in the questionnaire, sorting out the survey data, and analyzing the survey data. Results: Of 206 NCUs, 165 (80%) provided relatively complete information. It was estimated that 96,201 patients with severe neurological diseases were diagnosed and treated throughout the year, with an average fatality rate of 4.1%. The most prevalent severe neurological disease was cerebrovascular disease (55.2%). The most prevalent comorbidity was hypertension (56.7%). The most prevalent complication was hypoproteinemia (24.2%). The most common nosocomial infection was hospital-acquired pneumonia (10.6%). The GCS, APACHE II, EEG, and TCD were the most commonly used (62.4-95.2%). The implementation rate of the five nursing evaluation techniques reached 55.8-90.9%. Routinely raising the head of the bed by 30°, endotracheal intubation and central venous catheterization were the mostprevalent treatment strategies (97.6, 94.5, and 90.3%, respectively). Traditional tracheotomy, invasive mechanical ventilation and nasogastric tube feeding (75.8, 95.8, and 95.8%, respectively) were more common than percutaneous tracheotomy, non-invasive mechanical ventilation and nasogastric tube insertion (57.6, 57.6, and 66.7%, respectively). Body surface hypothermia brain protection technology was more commonly used than intravascular hypothermia technology (67.3 > 6.1%). The rates of minimally invasive hematoma removal and ventricular puncture were only 40.0 and 45.5%, respectively. Conclusion: In addition to traditional recognized basic life assessment and support technology, it is necessary to the use of promote specialized technology for neurological diseases, according to the characteristics of critical neurological diseases.

Status dystonicus in adult patients with anti-N-methyl-D-aspartate-acid receptor encephalitis.

OBJECTIVE: Status dystonicus (SD) is a severe movement disorder (MD) and has rarely been recognized in anti-N-methyl-D-aspartate-acid receptor (NMDAR) encephalitis, particularly in adult patients. We aim to explore the clinical characteristics and outcome of SD in anti-NMDAR encephalitis. METHODS: Patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital from July 2013 to December 2019 were prospectively enrolled. SD was diagnosed based on the patients' clinical manifestations and video EEG monitoring. Outcome was evaluated 6 and 12 months after enrollment using the modified Ranking Scale (mRS). RESULTS: A total of 172 patients with anti-NMDAR encephalitis, including 95 males (55.2%) and 77 females (44.8%) with a median age of 26 years (interquartile range 19 to 34) were enrolled. Eighty patients (46.5%) presented with movement disorder (MD), 14 of whom suffered from SD, which manifested as chorea (14/14, 100%), orofacial dyskinesia (12/14, 85.7%), generalized dystonia (8/14, 57.1%), tremor (8/14, 57.1%), stereotypies (5/14, 35.7%), and catatonia (1/14, 7.1%) of the trunk and limbs. All SD patients exhibited disturbed consciousness and central hypoventilation, requiring intensive care. SD patients also had high cerebrospinal fluid NMDAR antibody titers, a higher proportion of ovarian teratoma, higher mRS scores upon enrollment, longer duration to recover, and poorer outcomes at 6 (P < 0.05) but not at 12 months as compared to non-SD patients. CONCLUSION: SD is not uncommon in anti-NMDAR encephalitis patients and relates to the severity and worse short-term outcome of the anti-NMDAR encephalitis. Early recognition of SD and timely treatment is important to shorten the time needed for recuperation.

Clinical characteristics and prognosis of paroxysmal sympathetic hyperactivity in patients with severe nontraumatic brain injury.

OBJECTIVE: This prospective study investigated and analyzed the clinical characteristics and prognosis of paroxysmal sympathetic hyperactivity (PSH) in patients with severe nontraumatic brain injury. METHODS: Patients presenting with severe nontraumatic brain injury with PSH from July 2018 to June 2019 were enrolled. A PSH assessment measure ≥ 8 points was used as the criterion for PSH. Clinical data, indicators related to PSH, treatment effects and the prognosis were prospectively collected and analyzed. RESULTS: A total of 220 patients with severe nontraumatic brain injury were analyzed, and PSH occurred in 8 patients (3.6%).     The primary neurological diseases included acute cerebral infarction, anti-N-methyl-D-aspartate receptor encephalitis, hypoxic encephalopathy and acute disseminated encephalitis. The Glasgow Coma Scale score was lower than 8 in the 8 patients with PSH. Seven of these eight patients had a Glasgow outcome scale (GOS) score of 3 or less than 3, and one patient had a GOS of 5 after 6 months. The medicines that effectively controlled PSH included dexmedetomidine, clonazepam, midazolam and diazepam. CONCLUSIONS: Although the incidence was lower for nontraumatic brain injury complicated with PSH than for traumatic brain injury, patients with PSH had a more severe disease state and poorer prognoses. Dexmedetomidine might effectively control PSH.

Ion channel P2X7 receptor in the progression of cancer.

P2X7 receptor (P2X7) is a non-selective and ATP-sensitive ligand-gated cation channel. Studies have confirmed that it is expressed in a variety of cells and correlates with their function, frequently in immune cells and tumor cells. We found increased expression of this receptor in many tumor cells, and it has a role in tumor survival and progression. In immune cells, upregulation of the receptor has a double effect on tumor suppression as well as tumor promotion. This review describes the structure of P2X7 and its role in the tumor microenvironment and presents possible mechanisms of P2X7 in tumor invasion and metastasis. Understanding the potential of P2X7 for tumor treatment, we also present several therapeutic agents targeting P2X7 and their mechanisms of action. In conclusion, the study of P2X7 is an important guideline for the use of clinical tumor therapy and may be able to provide a new idea for tumor treatment, but considering the complexity of the biological effects of P2X7, the drugs should be used with caution in clinical practice.

Comatose Patients After Cardiopulmonary Resuscitation: An Analysis Based on Quantitative Methods of EEG Reactivity.

Objective: Every year, approximately 50-110/1,00,000 people worldwide suffer from cardiac arrest, followed by hypoxic-ischemic encephalopathy after cardiopulmonary resuscitation (CPR), and approximately 40-66% of patients do not recover. The purpose of this study was to identify the brain network parameters and key brain regions associated with awakening by comparing the reactivity characteristics of the brain networks between the awakening and unawakening groups of CPR patients after coma, thereby providing a basis for further awakening interventions. Method: This study involved a prospective cohort study. Using a 64-electrode electroencephalography (EEG) wireless 64A system, EEG signals were recorded from 16 comatose patients after CPR in the acute phase (<1 month) from 2019 to 2020. MATLAB (2017b) was used to quantitatively analyze the reactivity (power spectrum and entropy) and brain network characteristics (coherence and phase lag index) after pain stimulation. The patients were divided into an awakening group and an unawakening group based on their ability to execute commands or engage in repeated and continuous purposeful behavior after 3 months. The above parameters were compared to determine whether there were differences between the two groups. Results: (1) Power spectrum: the awakening group had higher gamma, beta and alpha spectral power after pain stimulation in the frontal and parietal lobes, and lower delta and theta spectral power in the bilateral temporal and occipital lobes than the unawakening group. (2) Entropy: after pain stimulation, the awakening group had higher entropy in the frontal and parietal lobes and lower entropy in the temporal occipital lobes than the unawakening group. (3) Connectivity: after pain stimulation, the awakening group had stronger gamma and beta connectivity in nearly the whole brain, but weaker theta and delta connectivity in some brain regions (e.g., the frontal-occipital lobe and parietal-occipital lobe) than the unawakening group. Conclusion: After CPR, comatose patients were more likely to awaken if there was a higher stimulation of fast-frequency band spectral power, higher entropy, stronger whole-brain connectivity and better retention of frontal-parietal lobe function after pain stimulation.

Minimum Criteria for Brain Death Determination: Consensus Promotion and Chinese Practice.

BACKGROUND: Brain death (BD), the irreversible cessation of function in the whole brain, is a well-known condition in most countries. The criteria and practical guidelines for brain death determination (BDD) in China were issued by the Brain Injury Evaluation Quality Control Center (BQCC) of the National Health and Family Planning Commission in 2013. Thereafter, we proposed a plan called the three-step quality control plan (three-step QCP) to ensure the safety and consistency of the clinical judgments regarding BD. By retrospectively reviewing this plan, we aimed to identify problems during its implementation and to provide suggestions for future work on quality control for BDD. METHODS: Data were retrieved from the BQCC database. The characteristics and test results of physicians undergoing a BDD training course and the BD case records submitted by hospitals before and after receiving accreditation were analyzed. RESULTS: In the first step of the plan, the error rate for physicians undergoing the BDD paper test was highest for limb movement discrimination (26.29%); this error rate was correlated with age (per 10-year increase) (odds ratio = 1.262, 95% confidence interval 1.067-1.491, P = 0.007) but was nonsignificantly associated with sex, specialty category, professional level, and hospital level (P > 0.05). During the second step of the plan, the highest percentage of problems was associated with apnea testing (22.75%), followed by ancillary testing of BDD (16.17%). In the last step, the highest percentage of problems in the case records was associated with apnea testing (41.73%). CONCLUSIONS: The three-step QCP is of significant utility for ensuring accuracy and appropriateness in BDD. Simultaneously, this study provides important evidence for advancing quality control for BDD in the next stage.

Characteristics and Outcomes of Paroxysmal Sympathetic Hyperactivity in Anti-NMDAR Encephalitis.

Background: To explore the clinical characteristics and prognosis of autonomic dysfunction and paroxysmal sympathetic hyperactivity (PSH), and evaluate the efficacy of drugs used to suppress PSH episode in anti-NMDAR encephalitis patients. Methods: Patients who met the diagnostic criteria of anti-NMDAR encephalitis were enrolled from January 2012 to August 2018 and followed up for 2 years. PSH was diagnosed according to the PSH-Assessment Measure. The demographics data, clinical features, auxiliary tests results, treatments, and outcomes were prospective collected and analyzed. Results: A total of 132 anti-NMDAR encephalitis patients were enrolled, of which 27.3% and 9.1% experienced autonomic dysfunction and probable PSH respectively. Cardiac autonomic dysfunction was the most common subtype (77.8%). Patients with a higher incidence of ovarian teratoma, mechanical ventilation, neurological intensive care unit admission, and elevated glucose and NMDAR antibody titer in the CSF were more likely to exhibit autonomic dysfunction or PSH. Episodes of PSH can be suppressed by monotherapy in patients without prior sedative drug use with an efficacy of 90%. No significant difference was observed between the prognosis of patients with or without autonomic dysfunction, or between the PSH versus non-PSH groups after 6 months and even during long-term follow-up. However, patients with cardiac autonomic dysfunction had poor prognosis at 6 months. Conclusion: PSH is a common clinical condition in patients with anti-NMDAR encephalitis, especially in severe cases, and can be effectively managed by several drug monotherapies. Despite necessitating longer hospital stay, autonomic dysfunction or PSH do not seem to compromise the neurological recovery of patients.

The Combination of N60 with Mismatch Negativity Improves the Prediction of Awakening from Coma.

BACKGROUND: Our objective was to evaluate the use of event-related potentials and the middle-latency somatosensory evoked potential (MLSEP) for the prediction of awakening in coma, determine the evaluation day that evoked potentials (EPs) best predict an awakening outcome, and determine whether the mismatch negativity (MMN) combined with the MLSEP, when recorded at 7 days after coma, improved the prediction of awakening from coma. METHODS: Design prospective blinded cohort study. Setting neurointensive care unit of a university hospital. Patients 113 consecutive patients who were severely comatose, whose etiologies of coma included stroke (65 patients), hypoxic-ischemic encephalopathy (28 patients), intracranial infection (6 patients), and other (14 patients). Interventions none. Measurements we gathered Glasgow Coma Scale scores and recorded EPs for all patients who were comatose at 7, 14, and 30 days after coma onset, unless the patients returned to consciousness. The EPs examined included the MLSEP, the middle-latency auditory evoked potential, the N100, and the MMN. With telephone follow-up after 3 months, the patients were classified as awakening or nonawakening according to Glasgow Outcome Scale. RESULTS: When predicting an awakening outcome, at least the unilateral presence of the N60 had the highest sensitivity (82.7%), whereas the presence of the MMN showed the highest specificity (82.0%). The area under the receiver operating characteristic curve for the EPs were high at 7 days after coma onset. At 7 days after coma onset, the combination of the N60 and MMN offered good predictive performance for awakening (area under the receiver operating characteristic curve = 0.852, 95% confidence interval 0.765-0.940), with increased sensitivity (70.0%) and improved specificity (91.7%). CONCLUSIONS: The N60 and MMN were the strongest prognostic factors for an awakening outcome. Furthermore, at 7 days after coma onset, the combination of the N60 and MMN improved the prediction of an awakening outcome in patients who were comatose.

Presence of Anti-Thyroid Antibodies Correlate to Worse Outcome of Anti-NMDAR Encephalitis.

Objective: To investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs). Methods: The clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months. Results: A total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026]. Conclusion: ATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.

Phenobarbital versus valproate for generalized convulsive status epilepticus in adults (2): A multicenter prospective randomized controlled trial in China (China 2-P vs. V).

OBJECTIVE: A multicenter study of phenobarbital versus valproate (i.e., the China 2-P vs. V study) was conducted to compare the efficacy and safety of phenobarbital and valproate for generalized convulsive status epilepticus (SE) in a multicenter trial design. METHODS: Three improvements (uniform intravenous pumping, pump speed adjustment according to adverse events and blood drug level monitoring) over a previous study were made regarding an intravenous regimen of phenobarbital and valproate in a multicenter, prospective, randomized, controlled study. Long-term electroencephalography (EEG) monitoring was performed after initial drug treatment. Termination, relapse, adverse event and poor prognosis rates in patients with generalized convulsive status epilepticus (GCSE) were compared. RESULTS: The rate of GCSE termination within one hour were significantly higher in the phenobarbital group (33 cases) than in the valproate group (36 cases) (84.8 % vs. 63.9 %, P = 0.048), but the rates of nontermination of EEG epileptic discharge within one hour were similar between the two groups (12.1 % vs. 8.3 %, P = 0.702). The relapse and adverse event rates were not significantly different between groups, but 3 hypoventilation events and 1 hypotension event occurred in the phenobarbital group compared to 0 in the valproate group. There were no cases of epileptiform EEG discharge relapse in the phenobarbital group, compared to 1 case in the valproate group. CONCLUSIONS: The phenobarbital regimen evaluated in this study has a higher GCSE termination rate than the valproate regimen, indicating that the former is suitable for countries, regions and individuals with limited access to new antiepileptic drugs or limited economic means.

Clinical efficacy of plasma exchange in patients with autoimmune encephalitis.

OBJECTIVE: To determine the clinical and antibody response after therapeutic plasma exchange (TPE) in patients with severe refractory antibody-associated autoimmune encephalitis (AE). METHODS: This single-center prospective cohort included all patients consecutively admitted to our hospital because of severe refractory AE over the period from July 2014 to June 2019. All patients received immunotherapy (steroids, intravenous immunoglobulin (IVIG), and/or TPE). The primary outcome was evaluated at 1- and 2-month postenrollment, and the long-term outcome was followed up at 6 and 12 months. AE antibody titers in the cerebrospinal fluid and plasma were evaluated before and after TPE/IVIG. RESULTS: This study enrolled 57 patients with severe refractory AE, including anti-NMDA receptor encephalitis (n = 51), anti-GABAb receptor encephalitis (n = 3), anti-LGI 1 encephalitis (n = 2), and anti-AMPA receptor encephalitis (n = 1). Of all 57 patients, 33 patients received TPE for a total of 193 procedures, and 24 patients with contraindications or refusal of TPE were in the non-TPE group. Compared with the non-TPE group, the TPE group exhibited greater clinical improvement: 21 (37%) versus 8 (14%) after 1 month (P = 0.03) and 31 (54%) versus 16 (28%) after 2 months (P = 0.01), respectively. Complications and adverse events associated with TPE occurred in 91 procedures (47%) without serious adverse events associated with the use of TPE. INTERPRETATION: TPE might be an effective rescue therapy associated with rapid functional improvement in patients with severe steroid/IVIG refractory antibody-associated AE from this nonrandomized control trial.

Clinical Value of Detecting Anti-Mutated Citrullinated Vimentin, Anti-Cyclic Citrullinated Peptide, Red Cell Distribution Width and 25-Hydroxyvitamin D in the Diagnosis of Rheumatoid Arthritis.

OBJECTIVES: To investigate the clinical value of detecting anti-mutated citrullinated vimentin (anti-MCV), anti-citrullinated peptide (anti-CCP), red-blood-cell distribution width (RDW), and 25-hydroxyvitamin D (25-[OH]D) in the diagnosis of rheumatoid arthritis (RA). METHODS: We enrolled 119 patients with RA, 114 control individuals without RA (disease controls), and 40 healthy controls in our study (Han Chinese). Anti-CCP and anti-MCV were detected by enzyme-linked immunosorbent assay (ELISA), 25-(OH)D was detected by electrochemical luminescence, and RDW was calculated by erythrocyte parameters detected via the electric resistance method. RESULTS: The serum levels of anti-CCP and anti-MCV in RA were higher than those in disease controls and healthy controls (P <.01). The areas under the curve (AUCs) of anti-MCV, anti-CCP, RDW, and 25-(OH)D were 0.857, 0.890, 0.611, and 0.569 respectively (P <.05). In various combinations of indicators, when RDW, 25-(OH)D, and anti-CCP; or RDW, 25-(OH)D, anti-CCP, and anti-MCV were connected in parallel, the sensitivity was the highest (all 94.1%). Also, when RDW, 25-(OH)D, anti-CCP, and anti-MCV were connected in series, the sensitivity was the lowest (13.4%). CONCLUSIONS: Anti-CCP and anti-MCV are ideal indices for RA diagnosis. Also, in combination with RDW and 25-(OH)D, the diagnostic level will be improved, as well as the sensitivity and specificity, which is significant for the differential diagnosis of RA.

Early Consciousness Disorder in Acute Large Hemispheric Infarction: An Analysis Based on Quantitative EEG and Brain Network Characteristics.

BACKGROUND: Large hemispheric infarction (LHI) is an ischemic stroke affecting at least two-thirds of the middle cerebral artery territory, with or without involvement of the anterior cerebral artery or posterior cerebral artery, and approximately 77% of LHI patients have early consciousness disorder (ECD). We constructed a functional brain network for LHI patients with an acute consciousness disorder to identify new diagnostic markers related to ECDs by analyzing brain network characteristics and mechanisms. METHODS: Between August 1, 2017, and September 30, 2018, patients with acute (< 1 month) LHI were admitted to the neurocritical care unit at Xuanwu Hospital of Capital Medical University. Electroencephalography (EEG) data were recorded, and the MATLAB platform (2017b) was used to calculate spectral power, entropy, coherence and phase synchronization. The quantitative EEG and brain network characteristics of different consciousness states and different frequency bands were analyzed (α = 0.05). EEG data were recorded 38 times in 30 patients, 25 of whom were in the ECD group, while 13 patients were in the conscious group. RESULTS: (1) Spectral power analysis: The conscious group had higher beta relative spectral power across the whole brain, higher alpha spectral power in the frontal-parietal lobe on the infarction contralateral side, and lower theta and delta spectral power in the central-occipital lobe on the infarction contralateral side than the ECD group. (2) Entropy analysis: The conscious group had higher approximate entropy (ApEn) and permutation entropy (PeEn) across the whole brain than the ECD group. (3) Coherence: The conscious group had higher alpha coherence in nearly the whole brain and higher beta coherence in the bilateral frontal-parietal and parietal-occipital lobes than the ECD group. (4) Phase synchronization: The conscious group had higher alpha and beta synchronization in nearly the whole brain, particularly in the frontal-parietal and parietal-occipital lobes, than the ECD group. (5) Graph theory: The conscious group had higher small-worldness in each frequency band than the ECD group. CONCLUSION: In patients with LHI, higher levels of consciousness were associated with more alpha and beta oscillations and fewer delta and theta oscillations. Higher ApEn, PeEn, total brain connectivity, and small-worldness and a wider signal distribution range corresponded to a higher consciousness level.

EEG signal varies with different outcomes in comatose patients: A quantitative method of electroencephalography reactivity.

BACKGROUND: Electroencephalographic reactivity (EEG-R) is a major predictor of outcome in comatose patients; however, the inter-rater reliability is limited due to the lack of homogeneous stimuli and quantitative interpretation. NEW METHODS: EEG-R testing was employed in comatose patients by quantifiable electrical stimulation. Reactivity at different frequency bands was computed as the difference between pre- and post-stimulations in power spectra and connectivity function (including magnitude squared coherence and transfer entropy). The clinical outcomes were dichotomized as good and poor according to the recovery of consciousness. Signal discrimination of EEG-R was compared between the two groups. RESULTS: A total of 18 patients (43%) regained consciousness at a 3-month follow-up. In the patients who regained consciousness, the EEG power increased significantly (P < 0.05) at the Alpha and Beta frequency bands after stimulation as compared to those with no behavioral awakening. Also, connectivity enhancement (including linear and nonlinear analysis) in the Beta and Gamma bands and connectivity decrease (nonlinear transfer entropy analysis) in the Delta band after stimulus were observed in the good outcome group. COMPARISON WITH EXISTING METHOD(S): In this study, the combined use of quantifiable stimulation and quantitative analysis shed new light on differentiating brain responses in comatose patients with good and poor outcomes as well as exploring the nature of EEG changes concerning the recovery of consciousness. CONCLUSIONS: The combination of quantifiable electrical stimulation and quantitative analysis with spectral power and connectivity for the EEG-R may be a promising method to predict the outcome of comatose patients.