Clinical characteristics and outcomes of patients with antibody-related autoimmune encephalitis presenting with disorders of consciousness: A prospective cohort study.

OBJECTIVE: To explore the clinical characteristics, short- and long-term functional outcomes, and risk factors for antibody-related autoimmune encephalitis (AE) in patients with disorders of consciousness (DoC). METHODS: Clinical data were collected from AE patients admitted to Xuanwu Hospital of Capital Medical University from January 2012 to December 2021, and patients were followed up for up to 24 months after immunotherapy. RESULTS: A total of 312 patients with AE were included: 197 (63.1%) with anti-NMDAR encephalitis, 71 (22.8%) with anti-LGI1 encephalitis, 20 (6.4%) with anti-GABAbR encephalitis, 10 (3.2%) with anti-CASPR2 encephalitis, 10 (3.2%) with anti-GAD65 encephalitis, and 4 (1.3%) with anti-AMPAR2 encephalitis. Among these patients, 32.4% (101/312) presented with DoC, and the median (interquartile range, IQR) time to DoC was 16 (7.5, 32) days. DoC patients had higher rates of various clinical features of AE (p < .05). DoC was associated with elevated lumbar puncture cerebrospinal fluid (CSF) pressure, CSF leukocyte count, and specific antibody titer (p < .05). A high percentage of patients in the DoC group had a poor prognosis at discharge and at 6 months after immunotherapy (p < .001), but no significant difference in prognosis was noted between the DoC group and the non-DoC group at 12 and 24 months after immunotherapy. Dyskinesia (OR = 3.266, 95% CI: 1.550-6.925, p = .002), autonomic dysfunction (OR = 5.871, 95% CI: 2.574-14.096, and p < .001), increased CSF pressure (OR = 1.007, 95% CI: 1.001-1.014, p = .046), and modified Rankin scale (mRS) score ≥3 at the initiation of immunotherapy (OR = 7.457, 95% CI: 3.225-18.839, p < .001) were independent risk factors for DoC in AE patients. CONCLUSION: DoC is a relatively common clinical symptom in patients with AE, especially critically ill patients. Despite requiring longer hospitalization, DoC mostly improves with treatment of the primary disease and has a good long-term prognosis after aggressive life support and combination immunotherapy.

Clinical manifestations and outcomes associated with a high 2HELPS2B score in patients with acute impaired consciousness.

PURPOSE: The 2HELPS2B score is an invaluable tool for assessing seizure risk in critically ill patients with unconsciousness. However, this can be challenging for non-epileptologists to use owing to its reliance on electroencephalogram (EEG) analysis. Thus, identifying clinical manifestations associated with high 2HELPS2B scores is crucial. METHODS: We examined patients who underwent EEG for acute impaired consciousness in the emergency department between 2020 and 2022. We evaluated the clinical manifestations immediately prior to the EEG tests and identified those associated with a 2HELPS2B score ≥ 2. Additionally, we investigated clinical outcomes in accordance with these manifestations and the 2HELPS2B score. RESULTS: A total of 78 patients were included in this study. While the median 2HELPS2B score was 1 (range: 0-6), 13 patients (16.6%) showed electrographic/electroclinical seizures or status epilepticus and 16 patients (20.5%) showed ictal-interictal continuum in their EEGs. Abnormal muscle tonus (p = 0.034) and eye deviation (p = 0.021) were Significantly associated with a 2HELPS2B score ≥ 2. The presence of these manifestations (p < 0.001) and a 2HELPS2B score ≥ 2 (p < 0.001) were both significantly associated with a favorable response to anti-seizure medication. Conversely, patients with a 2HELPS2B score ≥ 2 who exhibited these clinical manifestations were more likely to be non-dischargeable (p = 0.053), have prolonged intensive care unit stays (p = 0.002), or require extended ventilator use (p = 0.082). CONCLUSION: Abnormal muscle tonus and eye deviation were significant manifestations compatible with a 2HELPS2B score ≥ 2 and may indicate an increased risk of seizures or the severity of the epileptic condition.

Prognosis of patients with prolonged disorders of consciousness after brain injury: a longitudinal cohort study.

Background: The findings regarding the prognosis of prolonged disorders of consciousness (PDOC) vary widely among different studies. This study aims to investigate the mortality, consciousness recovery and disabilities of patients with PDOC after brain injury. Methods: A total of 204 patients with PDOC were included in a longitudinal cohort study, including 129 males and 75 females. There were 112 cases of traumatic brain injury (TBI), 62 cases of cerebral hemorrhage (CH), 13 cases of cerebral infarction (CI) and 17 cases of ischemic hypoxic encephalopathy (IHE). The status of consciousness at 1, 2, 3, 6, 12, 18, 24, 36, 48 months of the disease course was assessed or followed up using the Revised Coma Recovery Scale (CRS-R). If the patients were conscious, the disability Rating Scale (DRS) was also performed. The prognosis of different PDOC including coma, vegetative state (VS) and minimal conscious state (MCS) was analyzed. The survival patients were screened for variables and included in multivariate binary Logistic regression to screen the factors affecting the recovery of consciousness. Results: The mortality rates at 12, 24, 36, and 48 months were 10.7, 23.4, 38.9, and 68.4%, respectively. The median time of death was 18 months (8.75, 29). The probability of MCS regaining consciousness was higher than VS (p < 0.05), with the degree of disability left lower than VS (p < 0.05). There was no significant difference between MCS- and MCS+ groups in terms of the probability of regaining consciousness, the extent of residual disability, and mortality rates (p > 0.05). The mortality rate of coma was higher than that of other PDOC (p < 0.05). The mortality rate of MCS was lower than that of VS, but the difference was not statistically significant (p > 0.05). The probability of consciousness recovery after TBI was the highest and the mortality rate was the lowest. The possibility of consciousness recovery in IHE was the least, and the mortality rate of CI was the highest. The cause of brain injury and initial CRS-R score were the factors affecting the consciousness recovery of patients (p < 0.05). Conclusion: The prognosis of MCS is more favorable than VS, with comparable outcomes between MCS- and MCS+, while comatose patients was the poorest. TBI has the best prognosis and IHE has the worst prognosis.

Cognitive Motor Dissociation in Disorders of Consciousness.

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

Subcortical white matter differences according to presence of disorders of consciousness in hypoxic-ischemic brain injury: a tract-based spatial statistics study.

We investigated differences in subcortical white matter according to the presence disorders of consciousness (DOC) in patients with hypoxic-ischemic brain injury (HI-BI), using tract-based spatial statistics (TBSS). Thirty-two consecutive patients with HI-BI were recruited. The patients were assigned in group A [preserved consciousness (Glasgow Coma Scale: 15 and Coma Recovery Scale-revised (CRS-R): 23, 9 patients)] or group B [DOC present (Glasgow Coma Scale <15 and CRS-R < 23, 20 patients)]. Voxel-wise statistical analysis of fractional anisotropy data was performed by using TBSS as implemented in the FMRIB Software Library. We calculated mean fractional anisotropy values across the white matter skeleton and within 48 regions of interest (ROIs) based on intersections between the skeleton and the probabilistic Johns Hopkins University white matter atlases. Among the 48 ROIs examined, the fractional anisotropy values of two ROIs (the left superior corona radiata, and left tapetum) were significantly lower in group B than in group A ( P  < 0.05). No significant differences were observed, however, in the other 46 ROIs ( P  > 0.05). Our results suggest that abnormalities of the superior corona radiata and tapetum may be critical for DOC presence in patients with HI-BI.

[Diagnostic criteria for prolonged and chronic disturbances of consciousness after aneurysmal subarachnoid hemorrhages]. / Diagnosticheskie kriterii prodlennykh i khronicheskikh narushenii soznaniya posle anevrizmaticheskikh subarakhnoidal'nykh krovoizliyanii.

BACKGROUND: In recent years, prolonged states of impaired consciousness became widespread among patients with aneurysmal subarachnoid hemorrhage. Treatment and maintenance of vital functions in such patients represent a complex medical, economic and social problem. In this regard, searching for the causes of prolonged states of impaired consciousness and predicting the outcomes are important. OBJECTIVE: To analyze available literature data on prevention and treatment of prolonged states of impaired consciousness after aneurysmal subarachnoid hemorrhage. RESULTS: We reviewed the PubMed database using the keywords «unresponsive wakefulness syndrome¼, «persistent vegetative state2, «minimal consciousness state¼ and «outcome of subarachnoid hemorrhage¼. Only 4 reports devoted to the causes and treatment outcomes in patients with prolonged impairment of consciousness after aneurysmal subarachnoid hemorrhage were found. At the same time, patients with aneurysmal subarachnoid hemorrhage comprise up to 11% among all cases of prolonged states of impaired consciousness. Examination, management and treatment of patients with prolonged impairment of consciousness after aneurysmal subarachnoid hemorrhage are carried out according to general principles without taking into account specific etiological and pathogenetic factors. CONCLUSION: Increased number of patients with prolonged impairment of consciousness after aneurysmal subarachnoid hemorrhage necessitates analysis of etiopathogenesis and outcomes of these disorders based on modern clinical, instrumental and laboratory assessment of the brain.

Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol.

INTRODUCTION: Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. METHODS AND ANALYSES: The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current's frequency targets alpha brain oscillations (8-13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8-13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers' burden. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l'Île-de-Montréal (Project ID 2021-2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial's results will be published on a public trial registry database (ClinicalTrials.gov). TRIAL REGISTRATION NUMBER: NCT05833568.

Natural course and predictors of consciousness recovery in children with prolonged disorder of consciousness.

Prolonged disorder of consciousness (DoC) is a rising challenge. Pediatric data on diagnosis and prognosis of prolonged DoC were too limited and heterogeneous, making it difficult to define the natural course and evaluate the prognosis. The present study explored the emergence from the Minimally Conscious State (eMCS) incidence at different months postinjury drawing the natural course, and detected the predictors of the incidence in children with prolonged DoC. A hospital-based prospective cohort study was conducted. Kaplan-Meier curves, as well as univariate and multivariate COX regression analysis, were performed. The study enrolled 383 pediatric DoC individuals, including 220 males (57.4%), with an average age of 3.9 (1.9-7.3) years. The median duration between onset and rehabilitation is 30.0 (21.0-46.0) days. At enrollment, the ratio of vegetative state/unresponsive wakefulness syndrome (VS/WUS) to MCS is 78.9%-21.1%. Traumatic brain injury and infection are the major etiologies (36.8% and 37.1%, respectively), followed by hypoxia cerebral injury (12.3%). For children with prolonged DoC, the cumulative incidence of eMCS at months 3, 6, 12, and 24 was 0.510, 0.652, 0.731, 0.784 VS 0.290, 0.418, 0.539, 0.603 in the traumatic VS non-traumatic subgroup, respectively. For children in a persistent vegetative state (PVS), the cumulative incidence of emergence at months in 3, 6, 12, 24, 36 and 48 was testified as 0.439, 0.591, 0.683, 0.724, 0.743 and 0.743 in the traumatic subgroup, and 0.204, 0.349, 0.469, 0.534, 0.589 and 0.620 in the non-traumatic subgroup. Participants who exhibit any of the following four demographical and/or clinical characteristics-namely, older than 4 years at onset, accepted rehabilitation within 28 days of onset, remained MCS at enrollment, or with etiology of traumatic brain injuries-had a significantly positive outcome of consciousness recovery (eMCS). Moreover, both prolongation of the central somatosensory conductive time (CCT) (level 2) and absence of N20 (level 3) independently predict a negative outcome. In children with prolonged DoC, we found that 12 months postinjury was critical to eMCS, and a preferred timepoint to define chronic vegetative state (VS). The characteristics including age, etiology, time before rehabilitation, consciousness state, and SEP results were useful predictors of conscious recovery.Trial registration Registered 06/11/2018, the registration number is chiCTR1800019330 (chictr.org.cn). Registered prospectively.

Anti-NMDAR encephalitis in a child with long impaired consciousness and persistent antibodies: a case report and mini review.

We described a challenging case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in a young girl. Despite enduring months of reduced consciousness with ongoing antibody presence, she ultimately exhibited remarkable improvement within a 5-year follow-up period. Additionally, we conducted a concise review of relevant literature on anti-NMDAR encephalitis, with a specific focus on anti-NMDAR antibodies. Our findings enhance the clinical comprehension of anti-NMDAR encephalitis and offer valuable insights to clinicians for its management.

Disorders of Consciousness.

This article reviews the definition, assessment, neuroimaging, treatment, and rehabilitation for disorders of consciousness after an acquired brain injury. It also explores special considerations and new neuromodulation treatment options.

Short-term outcomes of early intensive neurorehabilitation for prolonged disorders of consciousness: A prospective cohort study.

BACKGROUND: Advances in medical care have increased survival in people with severe brain injuries and with that the number of survivors with prolonged disorders of consciousness (PDOC) has increased. In the literature, early intensive neurorehabilitation (EIN) for people with PDOC is recommended to achieve the best possible outcomes. OBJECTIVES: To evaluate the frequency and extent of recovery of consciousness, mortality, complications, pain and discomfort, and medication during a nationwide EIN programme in people with PDOC after acquired brain injury. We hypothesized that level of consciousness would improve in half of people with PDOC. METHODS: Prospective cohort study. People with PDOC aged 16 years and older admitted to the EIN department centralized in a single rehabilitation centre in the Netherlands (Libra Rehabilitation & Audiology) were included. The EIN delivers a subacute medical level of care and rehabilitation for a maximum duration of 14 weeks. The outcome measures were level of consciousness (CRS-R), mortality, number of complications, medication and pain/discomfort (NCS-R). RESULTS: Of the 104 people included, 68 % emerged to a minimal conscious state with command-following or higher during EIN and 44 % regained consciousness. Mortality during EIN was 6 %, and 50 % of deaths followed a non-treatment decision or withdrawal of life-sustaining treatment. Almost all participants had at least 1 medical complication, leading to hospital readmission for 30 %. 73 % showed no pain or discomfort. During EIN, cardiovascular medication and analgesics were reduced by 15 %. CONCLUSIONS: During the EIN programme, a large percentage of people with PDOC regained at least a minimal conscious state or even consciousness. These outcomes and the frequent medical complications in these people suggest that intensive specialized care should be offered to all people with PDOC. The outcomes of this study might help health professionals to better inform the families of people with PDOC about the short-term prognosis of PDOC. PROTOCOL REGISTRATION NUMBER: The Dutch Trial Register, NL 8138.

Resting state networks in patients with acute disorders of consciousness after severe traumatic brain injury.

OBJECTIVES: This study aims to describe resting state networks (RSN) in patients with disorders of consciousness (DOC)s after acute severe traumatic brain injury (TBI). METHODS: Adult patients with TBI with a GCS score <8 who remained in a coma, minimally conscious state (MCS), or unresponsive wakefulness syndrome (UWS), between 2017 and 2020 were included. Blood-oxygen-level dependent imaging was performed to compare their RSN with 10 healthy volunteers. RESULTS: Of a total of 293 patients evaluated, only 13 patients were included according to inclusion criteria: 7 in coma (54%), 2 in MCS (15%), and 4 (31%) had an UWS. RSN analysis showed that the default mode network (DMN) was present and symmetric in 6 patients (46%), absent in 1 (8%), and asymmetric in 6 (46%). The executive control network (ECN) was present in all patients but was asymmetric in 3 (23%). The right ECN was absent in 2 patients (15%) and the left ECN in 1 (7%). The medial visual network was present in 11 (85%) patients. Finally, the cerebellar network was symmetric in 8 patients (62%), asymmetric in 1 (8%), and absent in 4 (30%). CONCLUSIONS: A substantial impairment in activation of RSN is demonstrated in patients with DOC after severe TBI in comparison with healthy subjects. Three patterns of activation were found: normal/complete activation, 2) asymmetric activation or partially absent, and 3) absent activation.

[A Case of Consciousness Disorder Due to Hyperammonemia Induced by Modified FOLFOX6 for Multiple Liver Metastasis from Rectal Cancer].

A 74-year-old man underwent laparoscopic-assisted high anterior resection with D3 lymph node dissection for rectal cancer, which was simultaneously accompanied by multiple liver metastases. The patient received mFOLFOX6 therapy for liver metastases 1 month after the surgery. Anorexia, nausea, and vomiting appeared on the second day of treatment. On the third day of treatment, impaired consciousness(JCS Ⅱ-20)and flapping tremors appeared. Blood tests revealed hyperammonemia, and the patient was diagnosed with impaired consciousness due to hyperammonemia, which was inferred to be caused by 5-fluorouracil(5-FU). Intravenous infusion and branched-chain amino acids were administered, and the patient recovered. The underlying disease of renal dysfunction, constipation, and dehydration due to chemotherapy might have induced the hyperammonemia. It is important to note that hyperammonemia can lead to a disturbance of consciousness during chemotherapy including 5-FU.

Analysis of the efficacy of hyperbaric oxygen therapy for disorders of consciousness: A retrospective cohort study.

OBJECTIVE: To analyze the efficacy and associated factors affecting the prognosis in patients with disturbance of consciousness after hyperbaric oxygen (HBO) treatment. METHODS: A retrospective study was carried out on patients with disorders of consciousness (DOC) receiving HBO treatment from January to January 2022 in the Second Department of Rehabilitation Medicine of the Second Hospital of Hebei Medical University, China. RESULTS: HBO therapy improved the Glasgow Coma Scale (GCS) and Chinese Nanjing Persistent Vegetative State Scale (CNPVSS), as well as the clinical efficacy in patients with DOC. The comparison of GCS and CNPVSS scores in patients with DOC before and after HBO treatment was all statistically significant, with 325 patients (67.1%) showing effective results and 159 patients (32.9%) having unchanged outcomes. Univariate analysis indicated that there were statistically significant differences in age, HBO intervention time, HBO treatment times, pre-treatment GCS score, and etiology and underlying diseases between the good and poor prognoses groups. Multivariate regression analysis showed that HBO intervention time ≤7 days, HBO treatment ＞ times, high GCS score before HBO treatment, and brain trauma were independent influencing factors in achieving a good prognosis for patients with DOC. Low pre-treatment GCS scores were an independent risk factor for a poor prognosis in patients with brain trauma while being male, late HBO intervention time, fewer HBO treatment times, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after a stroke. Being ≥50 years of age, late HBO intervention time, and low pre-treatment GCS scores were independent risk factors for a poor prognosis in patients with DOC after hypoxic-ischaemic encephalopathy. CONCLUSION: HBO therapy can improve the GCS, CNPVSS scores and clinical efficacy in patients with DOC, and the timing of HBO intervention ≤7 days, times of HBO treatment, high pre-treatment GCS score, and brain trauma were the independent influencing factors of good prognosis in patients with DOC.

[Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury]. / K probleme individualizatsii neiromodulyatornoi farmakoterapii pri prolongirovannykh i khronicheskikh narusheniyakh soznaniya vsledstvie tyazheloi cherepno-mozgovoi travmy.

One of the most probable causes of effective therapy for post-comatose disorders of consciousness is the lack of individualization of drug prescriptions. In this observational study, we analyzed 48 courses of neuromodulatory therapy in 28 patients with prolonged and chronic disorders of consciousness following severe traumatic brain injury. Comparison of 24 effective and 24 ineffective courses demonstrated higher effectiveness of pharmacotherapy through its individualization, i.e. the choice of a drug whose neuromodulatory spectrum would correspond to neurological syndromes of neurotransmitter dysfunction. In this approach, 74% of therapy courses were effective while opposite management resulted only 34% of effective courses.

Neurobehavioral Progress and Signs of Transition in Children With Prolonged Disorders of Consciousness: A Retrospective Longitudinal Study With the Coma Recovery Scale-Revised.

BACKGROUND: Research on disorders of consciousness in children is scarce and includes disparate and barely comparable participants and assessment instruments and therefore provides inconclusive information on the clinical progress and recovery in this population. This study retrospectively investigated the neurobehavioral progress and the signs of transition between states of consciousness in a group of children admitted to a rehabilitation program either with an unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS). METHODS: Systematic weekly assessments were conducted with the Coma Recovery Scale-Revised (CRS-R) until emergence from MCS, discharge, or death. RESULTS: Twenty-one children, nine admitted with a UWS and 12 admitted in an MCS, were included in the study. Four children with a UWS transitioned to an MCS with a CRS-R of 10 (9.2 to 12.2) by showing visual pursuit, visual fixation, or localization to noxious stimulation. Twelve children emerged from the MCS with a CRS-R of 20.5 (19 to 21.7). Children who emerged from the MCS had had a shorter time postinjury and higher CRS-R at admission, compared with those who did not emerge. CONCLUSIONS: Almost half of the children who were admitted with a UWS transitioned to an MCS, and almost all who were admitted in an MCS emerged from this state. Children who emerged had shorter times since injury and higher scores on the CRS-R at admission, compared with those who did not emerge.