Objective Treatment of disorders of consciousness (DoC) remains a major clinical challenge, and noninvasive, targeted modulation of deep brain structures has emerged as a promising therapeutic strategy. We aimed to evaluate the feasibility/safety and preliminary effects of thalamic temporal interference stimulation (TIS) targeting centromedian-parafascicular (CM-PF) complex in patients with DoC.Methods We conducted a single-arm, self-controlled trial in nine patients with DoC. All patients received TIS targeting the bilateral CM-PF complex once daily for 10 consecutive days. Stimulation targets were guided by patient-specific electric field modeling to ensure precise neuromodulation. Outcome measures included adverse events, the change in Coma Recovery Scale-Revised (CRS-R) total and subscale scores from baseline to after five and 10 stimulation sessions, and alterations in EEG "ABCD" patterns and power spectral density (PSD) following the tenth session.Results No serious adverse events were reported. After 10 stimulation sessions, CRS-R total scores increased significantly, with improvements primarily observed in the auditory, visual, and motor subscales. No significant changes in CRS-R scores were detected after five stimulation sessions. EEG analyses demonstrated an increased prevalence of patterns C and D, disappearance of pattern A, and elevated global PSD in the alpha and beta frequency bands after 10 stimulation sessions.Interpretation This pilot study demonstrates that thalamic TIS is a safe and feasible noninvasive deep brain stimulation technology that may facilitate consciousness recovery in patients with DoC. Larger randomized controlled trials with longer follow-up are needed to confirm these preliminary observations.

This study aimed to assess the prevalence and prognostic value of cognitive motor dissociation (CMD) detected by active task-based electroencephalography (EEG) in a cohort of patients with disorders of consciousness (DoC). In a prospective cohort study, we enrolled 56 consecutive clinically unresponsive patients with acute or chronic brain injury. Patients underwent EEG recording during an active motor imagery task following spoken commands. Functional outcomes were assessed using the Glasgow Outcome Scale-Extended (GOS-E) at 6 months. Ten healthy volunteers served as a control group. Among the 56 unresponsive patients, 6 (10.7

BACKGROUND:Early adequate feeding reduces mortality in patients with acute severe stroke. Supplemental parenteral nutrition (SPN) may address enteral nutrition (EN) deficiency and mitigate the risk of nosocomial infection. The benefit of the EN plus early SPN strategy over the full EN strategy is unknown in acute severe stroke patients. METHODS:We retrospectively enrolled 20 patients with acute severe stroke in the SPN group who received EN plus early SPN (more than 50% of the energy target within 72 h after admission). Forty control patients in the EN group who received full EN were matched by age, sex and lesion site. The time to new-onset pneumonia or nosocomial infections was analyzed by Student's t test and the Breslow generalized Wilcoxon test. RESULTS:The baseline characteristics did not differ significantly between the SPN group and the EN group, except for higher serum leukocyte counts, neutrophil counts, and neutrophil-to-lymphocyte ratios in the SPN group (P < 0.05). Compared with that in the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days vs. 5.2 days; mean difference, 2.5 days; 95% CI, 0.65 to 4.31; P = 0.009), as was the time to new-onset nosocomial infections (7.1 days vs. 4.8 days; mean difference, 2.3 days; 95% CI, 0.46 to 4.07; P = 0.015). Kaplan-Meier analysis revealed similar cumulative probabilities of new-onset pneumonia and new-onset nosocomial infections in the two groups (P > 0.05). The rates of digestive intolerance events were similar between the two groups (40% in the SPN group vs. 52.5% in the EN group, P = 0.361). CONCLUSIONS:In patients with acute severe stroke, the application of EN plus early SPN could delay the onset of pneumonia and nosocomial infections especially in the early phase.

OBJECTIVE:The glymphatic system is a major waste clearance system in the central nervous system. We aim to investigate the glymphatic function and its prognostic values in patients with prolonged disorders of consciousness (pDoC). METHODS:We conducted a prospective and explorative cohort study including 40 patients with pDoC and 20 healthy controls. Glymphatic function was measured with the global and regional blood-oxygen-level-dependent and cerebrospinal fluid (BOLD-CSF) couplings, characterized by time-lags and strengths of the couplings. The clinical outcome was defined as improvement and no improvement in consciousness 6 months after enrollment, determined via a structured telephone follow-up based on the Coma Recovery Scale-Revised (CRS-R) score. RESULTS:Patients with pDoC exhibited significantly delayed time-lags in BOLD-CSF coupling (p < 0.05) and significantly reduced coupling strengths (p < 0.05) when compared to healthy controls. Follow-up studies indicated that shorter global BOLD-CSF coupling time-lags can predict an improved consciousness 6 months after enrollment, with an area under the receiver operating characteristic curve of 0.837, a sensitivity of 82.4%, and an accuracy of 85.7% using a cutoff point of 7.5. CONCLUSION:The glymphatic system was impaired in patients with pDoC, and its function, measured by BOLD-CSF coupling, can serve as a novel prognostic biomarker.

Disorders of consciousness (DoC) are major clinical challenges. We aimed to evaluate the effects of cerebellar intermittent theta-burst stimulation (CRB-iTBS) in the treatment of DoC. We conducted a randomized, sham-controlled, double-blind, cross-over clinical trial. Patients with vegetative state/unresponsive wakefulness syndrome or minimally conscious state within 15 days to 1 year after brain injuries were recruited. The bilateral cerebellum was targeted by iTBS for 5 consecutive days under neuronavigation. The primary outcome was the change in Coma Recovery Scale-Revised (CRS-R) total scores after five sessions. Secondary outcomes included changes in CRS-R scores after the first session, the changes in CRS-R subscales and the alterations in “ABCD” EEG patterns after the first and fifth sessions. Follow-up outcomes included six-month functional outcomes and consciousness recovery. We included 44 patients in the intention-to-treat analysis. No significant difference was observed in the change of CRS-R total scores between active and sham groups after five sessions (difference ​= ​0.428, 95 ​% CI ​= ​−0.202 - 1.057, P ​= ​0.180). However, active stimulation induced greater CRS-R improvements after the first session (difference ​= ​1.048, 95 ​% CI ​= ​0.480–1.615, P ​< ​0.001), especially in auditory, visual, oromotor/verbal, and arousal subscales. Active stimulation increased the prevalence of EEG patterns “C” and “D” after both the first and fifth sessions. Favorable six-month functional outcomes and consciousness recovery were associated with an elevation in “ABCD” EEG patterns during active treatment periods. These findings demonstrate that CRB-iTBS exhibits potential as a neuromodulation strategy to promote consciousness recovery in DoC.

意识障碍根据临床行为学评估标准主要分为三类:昏迷、无反应觉醒综合征/植物状态和微意识状态.虽然微意识状态概念的提出能够帮助临床医生鉴别无法进行功能性交流患者复杂的非反射性行为,但是不具备识别由于种种原因导致不能自我表达和运动输出但存在部分自主意识的患者,即认知运动分离(CMD).CMD可能代表了大脑通过多个功能系统整合信息的残存能力,有可能作为意识障碍患者的功能和行为恢复的替代指标.因此,在意识障碍患者的诊疗过程中识别CMD具有重要意义.本文就CMD的最新研究进展进行综述,以提高临床医生对CMD的认识以及为临床诊疗中的应用提供参考.

Purpose: To evaluate the long-term survival and functional outcomes of patients with prolonged disorders of consciousness (pDoC) 1–8 years after brain injuries. Methods: Retrospective study to assess the long-term survival and functional outcomes of patients with pDoC was conducted. We performed Cox regression and multivariate logistic regression to calculate hazard ratios (HRs) for the outcome of survival and to identify risk factors of the functional outcome. Results: We recruited 154 patients with pDoC. The duration of follow-up from disease onset was 1–8 years. The median age was 46 years (IQR, 32–59), and 65.6% (n = 101) of them were men. During the follow-up period, one hundred and ten patients (71.4%) survived; among them, 52 patients had a good outcome. From the overall survival curve, the 1-, 3-, and 8-year survival rates of patients were about 80.5%, 72.0%, and 69.7%, respectively. Cox regression analysis revealed a significant association between the lower APACHE II score (p = 0.005) (cut-off score ≥ 18) and the presence of sleep spindles (p = 0.001) with survival. Logistic regression analysis demonstrated a higher CRS-R score (cut-off score ≥ 7), and presence of sleep spindles were related to a favorable outcome among patients with pDoC. Conclusions: Sleep spindles are correlated with both long-term survival and long-term functional outcome in pDoC patients.

Background:Cryptogenic febrile infection-related epilepsy syndrome (FIRES) is a rare but catastrophic encephalopathic condition. We aimed to investigate the long-term outcome in adult cryptogenic FIRES.Methods:This was a retrospective study based on the prospective database in the neuro-intensive care unit of a tertiary hospital in China. Consecutive adult patients with cryptogenic FIRES between July 2007 to December 2021 were included. Long-term outcomes included function independence, the development of drug-resistant epilepsy (DRE), remote recurrent status epilepticus (SE), anti-seizure medications (ASMs), and changes in the brain Magnetic Resonance Imaging (MRI).Results:A total of 11 adult patients with cryptogenic FIRES were identified from 270 patients with SE. Four (36%) patients died in the hospital, with three of them withdrawing treatments, and one patient died 12 months after discharge. After the follow-up ranging from 12 to 112 months, 6 (55%) patients were still alive, and all of them achieved functional independence [modified Rankin Scale (mRS) 0-3]. 45% (5/11) patients developed DRE, 18% (2/11) had remote recurrent SE, and 55% (6/11) were on polytherapy with ASMs at the last follow-up. Most of the patients with initial normal or abnormal MRI had abnormalities in the hippocampus at follow-up, and most of the other MRI abnormalities found in the acute stage disappeared over time.Conclusion:The outcome of adult cryptogenic FIRES is daunting. More than one-third of patients die in the hospital. Survivors of cryptogenic FIRES may regain functional independence, but they usually develop DRE and receive polytherapy of ASMs for a long time.

Objective: To explore whether the EEG dynamics induced by zolpidem can predict consciousness evolu-tion in patients with prolonged disorders of consciousness (PDOC).Methods: We conducted a prospective explorative analysis on thirty-six patients with PDOC and eleven healthy controls. The EEG power spectrum was analyzed and categorized into 'ABCD' patterns at baseline and one hour after zolpidem administration at 10 mg. The clinical outcome was defined as consciousness improvement and no improvement six months after enrollment using the Coma Recovery Scale-Revised (CRS-R) score.Results: Zolpidem administration significantly increased the EEG power in the delta & theta bands and decreased EEG power in the beta bands in healthy controls. Further follow-up studies indicated that the increased EEG beta-band power induced by zolpidem can predict an improved consciousness six months after enrollment with an area under the receiver operating characteristic curve (AUC) of 0.829, the sensitivity of 94.38% and an accuracy of 81.48%.Conclusions: Our work revealed that the specific EEG responses to zolpidem can predict consciousness recovery in PDOC patients.Significance: The zolpidem-induced specific EEG responses could potentially predict the recovery of PDOC patients, which may help clinicians and patients' families in their decision-making process.& COPY; 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The management of severe neurologic infections due to multidrug-resistant (MDR) Klebsiella pneumoniae infection remains a challenge. Limited antibiotic treatment regimens make treatment of severe MDR K. pneumoniae infection more difficult. We describe a patient who developed severe meningitis and ventriculitis after craniotomy caused by MDR K. pneumoniae and was effectively treated with the administration of multichannel applications (intravenous, intrathecal and aerosol inhalation) of colistin sulfate. This case provides clinical evidence that the intrathecal, intravenous and aerosol inhalation of colistin sulfate by multichannel application can be a last resort in refractory intracranial infection by MDR K. pneumoniae.

AIMS:The prediction of outcomes in convulsive status epilepticus (CSE) remains a constant challenge. The Encephalitis-Nonconvulsive Status Epilepticus-Diazepam Resistance-Image Abnormalities-Tracheal Intubation (END-IT) score was a useful tool for predicting the functional outcomes of CSE patients, excluding cerebral hypoxia patients. With further understanding of CSE, and in view of the deficiencies of END-IT itself, we consider it necessary to modify the prediction tool.METHODS:The prediction model was designed from a cohort of CSE patients from Xijing Hospital (China), between 2008 and 2020. The enrolled subjects were randomly divided into training cohort and validation cohort as a ratio of 2:1. The logistic regression analysis was performed to identify the predictors and construct the nomogram. The performance of the nomogram was assessed by calculating the concordance index, and creating calibration plots to check the consistency between the predicted probabilities of poor prognosis and the actual outcomes of CSE.RESULTS:The training cohort included 131 patients and validation cohort included 66 patients. Variables included in the nomogram were age, etiology of CSE, non-convulsive SE, mechanical ventilation, abnormal albumin level at CSE onset. The concordance index of the nomogram in the training and validation cohorts was 0.853 (95% CI, 0.787-0.920) and 0.806 (95% CI, 0.683-0.923), respectively. The calibration plots showed an adequate consistency between the reported and predicted unfavorable outcomes of patients with CSE at 3 months after discharge.CONCLUSIONS:A nomogram for predicting the individualized risks of poor functional outcomes in CSE was constructed and validated, which has been an important modification of END-IT score.

Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive technique that allows bedside measurement of blood oxygenation level-dependent hemodynamic signals. We aimed to examine the efficacy of resting-state fNIRS in detecting the residual functional networks in patients with disorders of consciousness (DOC). We performed resting-state fNIRS in 23 DOC patients of whom 12 were in minimally conscious state (MCS) and 11 were in unresponsive wakefulness state (UWS). Ten regions of interest (ROIs) in the prefrontal cortex (PFC) were selected: both sides of Brodmann area (BA) 9, BA10, BA44, BA45, and BA46. Graph-theoretical analysis and seed-based correlation analyses were used to investigate the network topology and the strength of pairwise connections between ROIs and channels. MCS and UWS exhibited varying degrees of the loss of topological architecture, and the regional nodal properties of BA10 were significantly different between them (Nodal degree, PLeft BA10 = 0.01, PRight BA10 < 0.01; nodal efficiency, PLeft BA10 = 0.03, PRight BA10 < 0.01). Compared to healthy controls, UWS had impaired functions in both short- and long-distance connectivity, however, MCS had significantly impaired functions only in long-distance connectivity. The functional connectivity of right BA10 (AUC = 0.88) and the connections between left BA46 and right BA10 (AUC = 0.86) had excellent performance in differentiating MCS and UWS. MCS and UWS have different patterns of topological architecture and short- and long-distance connectivity in PFC. Intraconnections within BA10 and interhemispheric connections between BA10 and 46 are excellent resting-state fNIRS classifiers for distinguishing between MCS and UWS.

Cerebrovascular events, especially ischemic stroke, are common complications of essential thrombocythemia (ET). Compared to JAK2V617 F mutation, CALR mutation is considered as a lower risk factor of thrombosis in ET. Until now stroke in ET with CALR mutation has rarely been reported. We retrospectively investigated patients diagnosed with stroke and ET in Xijing hospital of Air Force Medical University, from 2015 to 2021. Clinical characteristics (including medical history, physical and auxiliary examination and prognosis) were recorded and associated literature was reviewed. Among the 19 patients diagnosed with both stroke and ET we retrieved, two cases were positive for CALR mutation. In case 1, a 71-year-old man developed the first ischemic event under the treatment of anagrelide, followed by a hemorrhagic stroke after receiving aspirin and clopidogrel for 4 months. Ischemic stroke reccurred and the neurological function deteriorated progressively. In case 2, a 44-year-old man presented with hypoxic-ischemic encephalopathy due to serious myocardial infarction and subsequent brain imaging indicated three times of ischemic stroke events. The patient gradually got improved through cytoreductive and antiplatelet therapy and rehabilitation. Literature review showed that cerebrovascular event is the most serious neurological complication of ET and may be the presenting symptom. Most of reported cases with ET accompanied by stroke were positive for JAK2 V617 F mutation, but with rare CALR mutation. ET with CALR mutation can cause both hemorrhagic and ischemic stroke. Identification of such rare causes of stroke is of great importance to provide precise and individualized prevention and therapy.

目的 探讨慢性意识障碍(pDoC)患者长期预后的影响因素并构建简易直观的列线图模型.方法 回顾性分析2014-2021年诊断为植物状态/无反应觉醒综合征(VS/UWS)或微意识状态(MCS)患者的临床资料,共计55例pDoC患者(男41例,女14例),比较预后良好组(GOSE＞3,n=15)和预后不良组(GOSE≤3,n=40)之间的差异.采用logistic回归分析方法,分析患者的临床资料对长期预后的影响,将单因素分析中P＜0.05的变量纳入多因素logistic回归模型中,基于多因素分析中P＜0.05的变量建立列线图预测模型.结果 ]研究表明,VS/UWS、MCS-和MCS+患者之间的脑电图(EEG)背景模式和大脑皮层平均标准摄取值有显著差异(均P＜0.01).意识状态、病因、昏迷恢复量表修改版评分、EEG背景模式是pDoC长期预后的独立影响因素.根据上述因素建立列线图,该列线图预测患者预后良好的曲线下面积为0.87.结论 本研究成功建立了一个预测pDoC长期预后的列线图,具有较高的预测性能和校准度,有助于指导临床医生决策.

Functional near infrared spectroscopy (fNIRS) is an emerging non-invasive technique that allows bedside measurement of blood oxygenation level-dependent hemodynamic signals. We aimed to examine the efficacy of resting-state fNIRS in detecting the residual functional networks in patients with disorders of consciousness (DOC). We performed resting-state fNIRS in 23 DOC patients of whom 12 were in minimally conscious state (MCS) and 11 were in unresponsive wakefulness state (UWS). Ten regions of interest (ROIs) in the prefrontal cortex (PFC) were selected: both sides of Brodmann area (BA) 9, BA10, BA44, BA45, and BA46. Graph-theoretical analysis and seed-based correlation analyses were used to investigate the network topology and the strength of pairwise connections between ROIs and channels. MCS and UWS exhibited varying degrees of the loss of topological architecture, and the regional nodal properties of BA10 were significantly different between them (Nodal degree, PLeft BA10 = 0.01, PRight BA10 < 0.01; nodal efficiency, PLeft BA10 = 0.03, PRight BA10 < 0.01). Compared to healthy controls, UWS had impaired functions in both short- and long-distance connectivity, however, MCS had significantly impaired functions only in long-distance connectivity. The functional connectivity of right BA10 (AUC = 0.88) and the connections between left BA46 and right BA10 (AUC = 0.86) had excellent performance in differentiating MCS and UWS. MCS and UWS have different patterns of topological architecture and short- and long-distance connectivity in PFC. Intraconnections within BA10 and interhemispheric connections between BA10 and 46 are excellent resting-state fNIRS classifiers for distinguishing between MCS and UWS.

Background To date, specialized studies focusing on status epilepticus (SE) in anti- N -methyl d -aspartate receptor (anti-NMDAR) encephalitis are limited, and the association between the occurrence of SE and clinical outcome is controversial. This study aims to investigate the differences between patients with critical anti-NMDAR encephalitis with SE and patients who experienced epileptic seizures without SE and to evaluate the long-term disease outcomes of patients with anti-NMDAR encephalitis with SE who were admitted to the neurological intensive care unit (neuro-ICU). Methods In this retrospective study based on a prospective registry, patients with anti-NMDAR encephalitis with neuro-ICU admission from 2014 to 2019 were analyzed and divided into two groups based on whether they had SE. Their clinical characteristics during the neuro-ICU stay were assessed and compared. The neurological and seizure outcomes were evaluated every 3 months. Results Of 83 patients with anti-NMDAR encephalitis, 24 required intensive care. In the SE group, 38.5% (5 of 13) of patients developed refractory SE (RSE), and 21.3% (3 of 13) of patients developed super RSE. More patients in the SE group presented with seizures as the initial symptoms (53.8% vs. 9.1%, p = 0.033) and had a strong positive NMDAR antibody titer in the cerebrospinal fluid (76.9% vs. 27.3%, p = 0.043). More patients in the non-SE group had a good neurological outcome (modified Rankin Scale (mRS) score < 2) at 3 months after disease onset (60.0% vs. 15.4%, p = 0.039), but 83.3% of patients with SE had a mRS score < 2 at 9 months after disease onset, which was similar to the rate in the non-SE group. A total of 41.7% of patients with SE had their last seizure within 1 month from disease onset, which was significantly lower than the rate in the non-SE group (90%), but all the patients with SE became seizure free after the acute phase of disease. Conclusions Patients with critical anti-NMDAR encephalitis who present with SE have a high rate of RSE/super RSE and recover more slowly than patients without SE, but most of them will eventually achieve good long-term neurological outcomes and live seizure free after the acute phase.

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by neuronal degeneration and hyperphosphorylated Tau. Magnolol is an active component isolated from Magnolia officinalis with potential neuroprotection activity. However, the function and mechanism of magnolol in AD progression is largely uncertain. In present study, the biomarkers related to AD and magnolol were predicted by bioinformatics analyses. The key biomarker levels were predicted by GSE5281 and GSE36980 using AlzData. Cell viability was detected by CCK-8 assay. mRNA and protein levels were examined by qRT-PCR and western blotting assays. Cell apoptosis was investigated by caspase-3 activity and flow cytometry analyses. The cAMP/PKA/CREB signaling was evaluated by ELISA and western blotting analyses. The results showed that CHRM1 was a key biomarker for magnolol against AD progression. Magnolol attenuated Aβ-induced viability inhibition, Tau hyperphosphorylation and apoptosis in SH-SY5Y cells by upregulating CHRM1. In addition, the cAMP signaling might be a potential pathway of CHRM1 in AD. Magnolol contributed to activation of the cAMP/PKA/CREB pathway through enhancing CHRM1 level. Inactivation of the cAMP/PKA/CREB signaling reversed the suppressive effect of magnolol on Tau hyperphosphorylation and apoptosis in Aβ-treated SH-SY5Y cells. As a conclusion, magnolol mitigated Aβ-induced Tau hyperphosphorylation and neuron apoptosis by upregulating CHRM1 and activating the cAMP/PKA/CREB pathway.

Objective: To investigate the potential prognostic value of sleep electroencephalography (EEG) pattern and serum circadian rhythm biomarkers in the recovery of consciousness in patients at the acute stage of coma. Methods: A prospective observational study which included 75 patients with coma was conducted. Twenty-four-hour continuous polysomnography (PSG) was performed to determine the sleep EEG pattern according to the modified Valente's Grade (mVG) that we proposed. Serum levels of melatonin and orexin-A at four consecutive time points during the PSG were examined. Patients were then followed for one month to determine their level of consciousness. Multivariate logistic regression analysis was performed to examine associations between demographics, aetiology, baseline clinical features (pupillary and corneal reflex, and neuron-specific enolase [NSE]), clinical scores (Glasgow Coma Scale-Motor Response [GCS-M], Full Outline of Unresponsiveness [FOUR] scale, Acute Physiology and Chronic Health Evaluation II [APACHE II] scale), mVG, serum circadian biomarkers, and recovery of consciousness within one month. Results: Within one month of enrolment, 34 patients regained consciousness and 36 patients remained non-conscious. Spearman rank correlation revealed a significant association between mVG and state of consciousness after one month. Significant variation in serum melatonin or orexin-A was not detected in either the conscious or non-conscious groups. Hypoxic aetiology, APACHE II, and mVG were independently associated with recovery of consciousness within one month. Conclusion: Sleep EEG structure, hypoxic aetiology, and APACHE II can independently predict recovery of consciousness in patients with acute coma. Taken together, we encourage neurologists to use sleep elements to assess patients with acute coma. (C) 2020 Elsevier B.V. All rights reserved.

Summary Aims To develop and validate a novel score for prediction of 3‐month functional outcome in neurocritically ill patients. Methods The development of the novel score was based on two widely used scores for general critical illnesses (Acute Physiology and Chronic Health Evaluation II, APACHE II; Simplified Acute Physiology Score II, SAPS II) and consideration of the characteristics of neurocritical illness. Data from consecutive patients admitted to neurological ICU (N‐ICU) between January 2013 and June 2016 were used for the validation. The modified Rankin Scale (mRS) was used to evaluate 3‐month functional outcomes. APACHE II scores, SAPS II scores, and our novel scores at 24 hours and 72 hours in N‐ICU were obtained. We compared the prognostic performance of our score with APACHE II and SAPS II. Results We developed a 44‐point scoring system named the INCNS score, and it includes 19 items which were categorized into five parts: inflammation (I), nutrition (N), consciousness (C), neurological function (N), and systemic function (S). We validated the INCNS score with a cohort of 941 N‐ICU patients. The 72‐hours INCNS score achieved an area under the receiver operating characteristic curve (AUC) of 0.828 (95% CI: 0.802‐0.854), and the 24‐hours INCNS score achieved an AUC of 0.788 (95% CI: 0.759‐0.817). The INCNS score exhibited significantly better discriminative and prognostic performance than APACHE II and SAPS II at both 24 hours and 72 hours in N‐ICU. Conclusion We developed an INCNS score with superior predictive power for functional outcome of neurocritically ill patients.

Mitochondrial complex I damage and oxidative stress play critical roles in the degeneration of dopaminergic (DA) neurons during the progression of Parkinson's disease (PD). Our previous study showed that NADH dehydrogenase 6 (ND6), exclusively regulated by mitochondrial myocyte enhancer factor 2D (MEF2D), was critical for mitochondrial complex I assembly. Recently, we found that Salidroside (Sal), isolated from Rhodiola rosea L., protected DA neurons by regulating oxidative stress-related mitochondrial pathways. Here, we investigated whether the mitochondrial MEF2D-ND6 pathway was involved in the neuroprotective effects of Sal. Our results showed that in 1-methyl-4-phenylpyridinium (MPP+)-injured SN4741 cells, Sal pretreatment improved cellular viability, inhibited apoptosis, and restored both the mitochondrial membrane potential and complex I activity. Similarly, the protective effects of Sal on mitochondrial complex I activity, DA neurons, and behavior were also confirmed in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned mice. Besides, Sal pretreatment restored the expression of mitochondrial MEF2D and ND6 in MPP+-injured SN4741 cells and MPTP-lesioned mice. Finally and interestingly, the protective effects of Sal were not observed in cells transfected with Mt2Ddn, a specific blocker of mitochondrial MEF2D function, suggesting that Sal protects DA neurons primarily by regulating the mitochondrial MEF2D-ND6 pathway. Our study sheds light upon the protective role of Sal through targeting the mitochondrial MEF2D-ND6 pathway in regulations of mitochondrial function and DA neuronal viability, providing novel mechanistic insights into the neuroprotective effects of Sal against PD.