Serum cystatin C is correlated with mortality of traumatic brain injury patients partially mediated by acute kidney injury.

BACKGROUND: Evaluating risk of poor outcome for Traumatic Brain Injury (TBI) in early stage is necessary to make treatment strategies and decide the need for intensive care. This study is designed to verify the prognostic value of serum cystatin C in TBI patients. METHODS: 415 TBI patients admitted to West China hospital were included. Logistic regression was performed to explore risk factors of mortality and testify the correlation between cystatin C and mortality. Mediation analysis was conducted to test whether Acute Kidney Injury (AKI) and brain injury severity mediate the relationship between cystatin C level and mortality. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prognostic value of cystatin C and the constructed model incorporating cystatin C. RESULTS: The mortality rate of 415 TBI patients was 48.9%. Non-survivors had lower GCS (5 vs 8, p < 0.001) and higher cystatin C (0.92 vs 0.71, p < 0.001) than survivors. After adjusting confounding effects, multivariate logistic regression indicated GCS (p < 0.001), glucose (p < 0.001), albumin (p = 0.009), cystatin C (p < 0.001) and subdural hematoma (p = 0.042) were independent risk factors of mortality. Mediation analysis showed both AKI and brain injury severity exerted mediating effects on relationship between cystatin C and mortality of included TBI patients. The AUC of combining GCS with cystatin C was 0.862, which was higher than that of GCS alone (Z = 1.7354, p < 0.05). CONCLUSION: Both AKI and brain injury severity are mediating variables influencing the relationship between cystatin C and mortality of TBI patients. Serum cystatin C is an effective prognostic marker for TBI patients.

Ballooned neurons in semi-recent severe traumatic brain injury.

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects.

Corneal higher order aberrations by Sirius topography and their relation to different refractive errors.

PURPOSE: To compare the root mean square (RMS) of anterior corneal higher-order aberrations (HOAs) in ametropic and emmetropic eyes. METHODS: This retrospective observational study was conducted at the Department of Ophthalmology, Tishreen University Hospital, Latakia, Syria. Study eyes were divided into four groups based on refractive error: mild-to-moderate myopia, hypermetropia, myopic astigmatism, and emmetropic eyes as controls. The following anterior corneal HOAs were evaluated using the Scheimpflug-Placido Sirius (CSO, Italy) tomographer over 6 mm pupil: Root mean square (RMS) total corneal HOAs, RMS trefoil, RMS coma and RMS spherical aberrations. RESULTS: RMS values of total HOAs, trefoil and coma showed statistically significant differences in all four groups (P < 0.05, all). HOAs were noted to be lowest in the control group (0.18 ± 0.09, 011 ± 0.08 and 0.09 ± 0.08 µm, respectively) and highest in the myopic astigmatism group (0.31 ± 0.16, 0.15 ± 0.12, 0.17 ± 0.14 µm, respectively). RMS spherical aberration was lowest in the astigmatism group (0.00 ± 0.16 µm) with a statistically significant difference from that in the control group (0.05 ± 0.07 µm, P = 0.049). CONCLUSION: The mean RMS values of total HOAs, trefoil and coma were highest in the astigmatism group and lowest in the control group. However, spherical aberration was minimal in the astigmatism group. A better understanding and targeted treatment of higher-order aberrations in ametropic human eyes, and in particular eyes with astigmatism, may enhance visual quality and performance in the treatment of refractive errors. Recognising atypical HOAs may also assist in the early detection of pathological conditions such as keratoconus.

[Clinical presentation and gross appearance of diffuse axonal injury in the early post-injury period]. / Klinicheskaya i makroskopicheskaya kharakteristika diffuznogo aksonal'nogo povrezhdeniya mozga v ostrom posttravmaticheskom periode.

The objective of the study was to investigate and characterize the clinical presentation, and establish macroscopic diagnostic signs of diffuse axonal injury (DAI) in the early (up to 3 days) post-injury period. In DAI, coma develops immediately after head injury and persists for 3 days post-injury until death. The coma is accompanied by dominant primary stem neurological symptoms, hemodynamic and respiratory disturbances and does not progress to a vegetative state. Lifetime computed tomography reveals cerebral hemorrhage in 40.5% of cases. We established the macroscopic signs of head injury in DAI. For the postmortem diagnosis of DAI, a detailed macroscopic appearance of pathognomonic cerebral hemorrhages is given, which are most frequently (67.5%) localized in the corpus callosum (CC), namely in the area from its genu to the middle of the trunk (97%). A rational, improved scheme of excision of CC trunk areas for the histological study is proposed.

Recurrence of Hypoglycemic Coma in a Patient with Anorexia Nervosa.

Anorexia nervosa (AN) is occasionally complicated with hypoglycemic coma, which may cause sudden death by unknown mechanisms. We present the case of a 36-year-old woman with recurrent comas and a nineteen-year history of AN. She was found in a coma with remarkable hypoglycemia (28 mg/dL). Her BMI was 11.1 kg/m2. Endocrine workup revealed extremely low serum levels of glucagon, IGF-I and insulin. Asymptomatic hypoglycemia occurred with liver injury in the refeeding process. An aberrant glucose metabolism due to liver damage might have been involved in her susceptibility to hypoglycemia. This case suggests a possible mechanism of hypoglycemic coma in AN.

The clinical and prognostic values of optic nerve sheath diameter and optic nerve sheath diameter/eyeball transverse diameter ratio in comatose patients with supratentorial lesions.

BACKGROUND: The optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio have been proven to be correlated with intracranial pressure. This study aimed to evaluate the prognostic roles of ONSD and the ONSD/ETD ratio in comatose patients with supratentorial lesions and to determine the relationship of these two indices with the prognosis of such patients. METHODS: A total of 54 comatose patients with supratentorial lesions and 50 healthy controls were retrospectively included in this study. ONSD and ETD were measured by unenhanced computed tomography (CT). The differences in ONSD and the ONSD/ETD ratio between the two groups were compared. The prognosis of comatose patients was scored using the Glasgow Outcome Scale (GOS) at the 3-month follow-up, and these patients were classified into good (GOS score ≥ 3) and poor (GOS score < 3) prognosis groups. The differences in ONSD and the ONSD/ETD ratio were compared between comatose patients with good prognoses and those with poor prognoses. RESULTS: The ONSD and ONSD/ETD ratios in the comatose patients were 6.30 ± 0.60 mm and 0.27 ± 0.03, respectively, and both were significantly greater than those in the healthy controls (5.10 ± 0.47 mm, t = 11.426, P < 0.0001; 0.22 ± 0.02, t = 11.468, P < 0.0001; respectively). ONSD in patients with poor prognosis was significantly greater than that in patients with good prognosis (6.40 ± 0.56 vs. 6.03 ± 0.61 mm, t = 2.197, P = 0.032). The ONSD/ETD ratio in patients with poor prognosis was significantly greater than that in patients with good prognosis (0.28 ± 0.02 vs. 0.26 ± 0.03, t = 2.622, P = 0.011). The area under the receiver operating characteristic (ROC) curve, used to predict the prognosis of comatose patients, was 0.650 (95% confidence interval (CI): 0.486-0.815, P = 0.078) for ONSD and 0.711 (95% CI: 0.548-0.874, P = 0.014) for the ONSD/ETD ratio. CONCLUSIONS: The ONSD and ONSD/ETD ratios were elevated in comatose patients. The ONSD/ETD ratio might be more valuable than ONSD in predicting the prognoses of comatose patients with supratentorial lesions.

Location of Subcortical Microbleeds and Recovery of Consciousness After Severe Traumatic Brain Injury.

BACKGROUND: In patients with severe traumatic brain injury (TBI), coma is associated with impaired subcortical arousal mechanisms. However, it is unknown which nuclei involved in arousal (arousal nuclei) are implicated in coma pathogenesis and are compatible with coma recovery. METHODS: We mapped an atlas of arousal nuclei in the brainstem, thalamus, hypothalamus, and basal forebrain onto 3 tesla susceptibility-weighted images (SWI) in 12 patients with acute severe TBI who presented in coma and recovered consciousness within 6 months. We assessed the spatial distribution and volume of SWI microbleeds and evaluated the association of microbleed volume with the duration of unresponsiveness and functional recovery at 6 months. RESULTS: There was no single arousal nucleus affected by microbleeds in all patients. Rather, multiple combinations of microbleeds in brainstem, thalamic, and hypothalamic arousal nuclei were associated with coma and were compatible with recovery of consciousness. Microbleeds were frequently detected in the midbrain (100%), thalamus (83%), and pons (75%). Within the brainstem, the microbleed incidence was largest within the mesopontine tegmentum (e.g., pedunculotegmental nucleus, mesencephalic reticular formation) and ventral midbrain (e.g., substantia nigra, ventral tegmental area). Brainstem arousal nuclei were partially affected by microbleeds, with microbleed volume not exceeding 35% of brainstem nucleus volume on average. Compared to microbleed volume within nonarousal brainstem regions, the microbleed volume within arousal brainstem nuclei accounted for a larger proportion of variance in the duration of unresponsiveness and 6-month Glasgow Outcome Scale-Extended scores. CONCLUSION: These results suggest resilience of arousal mechanisms in the human brain after severe TBI.

Prolonged anesthesia alters brain synaptic architecture.

Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding ∼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.

Prolonged Unconsciousness Following Severe COVID-19.

OBJECTIVE: We report a case series of patients with prolonged but reversible unconsciousness after coronavirus disease 2019 (COVID-19)-related severe respiratory failure. METHODS: A case series of patients who were admitted to the intensive care unit due to COVID-19-related acute respiratory failure is described. RESULTS: After cessation of sedatives, the described cases all showed a prolonged comatose state. Diagnostic neurologic workup did not show signs of devastating brain injury. The clinical pattern of awakening started with early eye opening without obeying commands and persistent flaccid weakness in all cases. Time between cessation of sedatives to the first moment of being fully responsive with obeying commands ranged from 8 to 31 days. CONCLUSION: Prolonged unconsciousness in patients with severe respiratory failure due to COVID-19 can be fully reversible, warranting a cautious approach for prognostication based on a prolonged state of unconsciousness.

Functional and Structural Integrity of Frontoparietal Connectivity in Traumatic and Anoxic Coma.

OBJECTIVES: Recovery from coma might critically depend on the structural and functional integrity of frontoparietal networks. We aimed to measure this integrity in traumatic brain injury and anoxo-ischemic (cardiac arrest) coma patients by using an original multimodal MRI protocol. DESIGN: Prospective cohort study. SETTING: Three Intensive Critical Care Units affiliated to the University in Toulouse (France). PATIENTS: We longitudinally recruited 43 coma patients (Glasgow Coma Scale at the admission < 8; 29 cardiac arrest and 14 traumatic brain injury) and 34 age-matched healthy volunteers. Exclusion criteria were disorders of consciousness lasting more than 30 days and focal brain damage within the explored brain regions. Patient assessments were conducted at least 2 days (5 ± 2 d) after complete withdrawal of sedation. All patients were followed up (Coma Recovery Scale-Revised) 3 months after acute brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional and structural MRI data were recorded, and the analysis was targeted on the posteromedial cortex, the medial prefrontal cortex, and the cingulum. Univariate analyses and machine learning techniques were used to assess diagnostic and predictive values. Coma patients displayed significantly lower medial prefrontal cortex-posteromedial cortex functional connectivity (area under the curve, 0.94; 95% CI, 0.93-0.95). Cardiac arrest patients showed specific structural disturbances within posteromedial cortex. Significant cingulum architectural disturbances were observed in traumatic brain injury patients. The machine learning medial prefrontal cortex-posteromedial cortex multimodal classifier had a significant predictive value (area under the curve, 0.96; 95% CI, 0.95-0.97), best combination of subregions that discriminates a binary outcome based on Coma Recovery Scale-Revised). CONCLUSIONS: This exploratory study suggests that frontoparietal functional disconnections are specifically observed in coma and their structural counterpart provides information about brain injury mechanisms. Multimodal MRI biomarkers of frontoparietal disconnection predict 3-month outcome in our sample. These findings suggest that fronto-parietal disconnection might be particularly relevant for coma outcome prediction and could inspire innovative precision medicine approaches.

Lateral Brain Displacement and Cerebral Autoregulation in Acutely Comatose Patients.

OBJECTIVES: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurocritical care unit of the Johns Hopkins Hospital. PATIENTS: Acutely comatose patients (Glasgow Coma Score ≤ 8). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013). CONCLUSIONS: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.

Neuropathological findings in comatose patients with venoarterial extracorporeal membrane oxygenation.

We sought to describe the relation between neuropathology and clinical information including neurological examination and electroencephalogram findings in extracorporeal membrane oxygenation. We reviewed the patients who had undergone brain autopsy from November 2017 through December 2018. Four patients with neuromonitoring had post mortem examination with brain autopsy. The median age was 56, and all had venoarterial extracorporeal membrane oxygenation cannulation. There was no known acute neurologic injury prior to extracorporeal membrane oxygenation. While on extracorporeal membrane oxygenation, all were persistently comatose off sedation. Continuous encephalogram was done on all four, all of which showed delta frequency with absent reactivity. In Case 1, the pathological evaluation demonstrated small infarcts in cerebral cortices. In Case 2, it showed cortical microhemorrhages and chronic microinfarcts in basal ganglia. In Cases 3 and 4, the neuropathological assessment demonstrated diffuse hypoxic-ischemic brain injury. The clinical presentation was consistent with the widespread neuropathologic injury in two cases (Cases 3 and 4) but not in the other two (Cases 1 and 2). While "poor neurological status" was provided in the end-of-life discussion in all four, only two had significant brain injuries. There is limited understanding about brain injury in extracorporeal membrane oxygenation. Extrapolations related to prognostication from experience in other brain injury needs to be approached cautiously.

Development of a point of care system for automated coma prognosis: a prospective cohort study protocol.

INTRODUCTION: Coma is a deep state of unconsciousness that can be caused by a variety of clinical conditions. Traditional tests for coma outcome prediction are based mainly on a set of clinical observations. Recently, certain event-related potentials (ERPs), which are transient electroencephalogram (EEG) responses to auditory, visual or tactile stimuli, have been introduced as useful predictors of a positive coma outcome (ie, emergence). However, such tests require the skills of clinical neurophysiologists, who are not commonly available in many clinical settings. Additionally, none of the current standard clinical approaches have sufficient predictive accuracies to provide definitive prognoses. OBJECTIVE: The objective of this study is to develop improved machine learning procedures based on EEG/ERP for determining emergence from coma. METHODS AND ANALYSIS: Data will be collected from 50 participants in coma. EEG/ERP data will be recorded for 24 consecutive hours at a maximum of five time points spanning 30 days from the date of recruitment to track participants' progression. The study employs paradigms designed to elicit brainstem potentials, middle-latency responses, N100, mismatch negativity, P300 and N400. In the case of patient emergence, data are recorded on that occasion to form an additional basis for comparison. A relevant data set will be developed from the testing of 20 healthy controls, each spanning a 15-hour recording period in order to formulate a baseline. Collected data will be used to develop an automated procedure for analysis and detection of various ERP components that are salient to prognosis. Salient features extracted from the ERP and resting-state EEG will be identified and combined to give an accurate indicator of prognosis. ETHICS AND DISSEMINATION: This study is approved by the Hamilton Integrated Research Ethics Board (project number 4840). Results will be disseminated through peer-reviewed journal articles and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03826407.

Effects of Xingnaojing Injection on Adenosinergic Transmission and Orexin Signaling in Lateral Hypothalamus of Ethanol-Induced Coma Rats.

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.

Recurrent moderate hypoglycemia exacerbates oxidative damage and neuronal death leading to cognitive dysfunction after the hypoglycemic coma.

Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus (TIDM) patients who are under intensive insulin therapy increasing the risk for severe hypoglycemia (SH). The consequences of RH are not well understood and its repercussions on neuronal damage and cognitive function after a subsequent episode of SH have been poorly investigated. In the current study, we have addressed this question and observed that previous RH during seven consecutive days exacerbated oxidative damage and neuronal death induced by a subsequent episode of SH accompanied by a short period of coma, in the parietal cortex, the striatum and mainly in the hippocampus. These changes correlated with a severe decrease in reduced glutathione content (GSH), and a significant spatial and contextual memory deficit. Administration of the antioxidant, N-acetyl-L-cysteine, (NAC) reduced neuronal death and prevented cognitive impairment. These results demonstrate that previous RH enhances brain vulnerability to acute hypoglycemia and suggests that this effect is mediated by the decline in the antioxidant defense and oxidative damage. The present results highlight the importance of an adequate control of moderate hypoglycemic episodes in TIDM.

Quantitative analysis of relative volume of low apparent diffusion coefficient value can predict neurologic outcome after cardiac arrest.

INTRODUCTION: Predicting neurologic outcomes after cardiac arrest (CA) is challenging. This study tested the hypothesis that a quantitative analysis of diffusion weighted imaging (DWI) using the FMRIB Software Library (FSL) can predict neurologic outcomes after CA and can clarify the optimal apparent diffusion coefficient (ADC) thresholds for predicting poor neurologic outcomes. METHODS: Out-of-hospital CA patients treated with targeted temperature management (TTM) who underwent DWI were included in this study. Voxel-based analysis was performed to calculate the mean ADC value. ADC thresholds (750, 700, 650, 600, 550, 500, 450 and 400) and brain volumes below each threshold were also analyzed for their correlation with outcomes. The patients were divided into early (within 48 h after return of spontaneous circulation (ROSC)) and late group (between 48 h and 7 days after ROSC) according to the DWI scan time. The primary outcome was a poor neurologic outcome at 6 months after CA, defined as a cerebral performance category (CPC) of 3-5. RESULTS: One hundred ten DWIs were analyzed. The mean ADC values were 789.0 (761.5-826.5) × 10-6 mm2/s for the good neurologic outcome group and 715.2 (663.1-778.4) × 10-6 mm2/s for the poor neurologic outcome group (p < 0.001). All the ADC thresholds could differentiate patients with good versus poor outcomes. The ADC threshold of 400 × 10-6 mm2/s had the highest odds ratio (4.648 in the early group and 11.283 in the late group) after adjusting for initial rhythm and anoxic time. To achieve 100% specificity using an ADC threshold of 400 × 10-6 mm2/s, the sensitivity was 64% (cutoff value; >2.5% ADC threshold of 400 × 10-6 mm2/s) in the early group and 79.2% (cutoff value; >1.66% ADC threshold of 400 × 10-6 mm2/s) in the late group. CONCLUSIONS: Voxel-based analysis using FSL software can predict neurologic outcomes after CA. The ADC threshold of 400 × 10-6 mm2/s had the highest OR for predicting a poor neurologic outcome.

The inter-rater reliability and prognostic value of coma scales in Nepali children with acute encephalitis syndrome.

Background Acute encephalitis syndrome (AES) is a common cause of coma in Nepali children. The Glasgow coma scale (GCS) is used to assess the level of coma in these patients and predict outcome. Alternative coma scales may have better inter-rater reliability and prognostic value in encephalitis in Nepali children, but this has not been studied. The Adelaide coma scale (ACS), Blantyre coma scale (BCS) and the Alert, Verbal, Pain, Unresponsive scale (AVPU) are alternatives to the GCS which can be used. Methods Children aged 1-14 years who presented to Kanti Children's Hospital, Kathmandu with AES between September 2010 and November 2011 were recruited. All four coma scales (GCS, ACS, BCS and AVPU) were applied on admission, 48 h later and on discharge. Inter-rater reliability (unweighted kappa) was measured for each. Correlation and agreement between total coma score and outcome (Liverpool outcome score) was measured by Spearman's rank and Bland-Altman plot. The prognostic value of coma scales alone and in combination with physiological variables was investigated in a subgroup (n = 22). A multivariable logistic regression model was fitted by backward stepwise. Results Fifty children were recruited. Inter-rater reliability using the variables scales was fair to moderate. However, the scales poorly predicted clinical outcome. Combining the scales with physiological parameters such as systolic blood pressure improved outcome prediction. Conclusion This is the first study to compare four coma scales in Nepali children with AES. The scales exhibited fair to moderate inter-rater reliability. However, the study is inadequately powered to answer the question on the relationship between coma scales and outcome. Further larger studies are required.

Pathophysiology, clinical presentation, and treatment of coma and acute kidney injury complicating falciparum malaria.

PURPOSE OF REVIEW: Cerebral impairment and acute kidney injury (AKI) are independent predictors of mortality in both adults and children with severe falciparum malaria. In this review, we present recent advances in understanding the pathophysiology, clinical features, and management of these complications of severe malaria, and discuss future areas of research. RECENT FINDINGS: Cerebral malaria and AKI are serious and well recognized complications of severe malaria. Common pathophysiological pathways include impaired microcirculation, due to sequestration of parasitized erythrocytes, systemic inflammatory responses, and endothelial activation. Recent MRI studies show significant brain swelling in both adults and children with evidence of posterior reversible encephalopathy syndrome-like syndrome although targeted interventions including mannitol and dexamethasone are not beneficial. Recent work shows association of cell-free hemoglobin oxidation stress involved in the pathophysiology of AKI in both adults and children. Paracetamol protected renal function likely by inhibiting cell-free-mediated oxidative stress. It is unclear if heme-mediated endothelial activation or oxidative stress is involved in cerebral malaria. SUMMARY: The direct causes of cerebral and kidney dysfunction remain incompletely understood. Optimal treatment involves prompt diagnosis and effective antimalarial treatment with artesunate. Renal replacement therapy reduces mortality in AKI but delayed diagnosis is an issue.

Brain Gray Matter MRI Morphometry for Neuroprognostication After Cardiac Arrest.

OBJECTIVES: We hypothesize that the combined use of MRI cortical thickness measurement and subcortical gray matter volumetry could provide an early and accurate in vivo assessment of the structural impact of cardiac arrest and therefore could be used for long-term neuroprognostication in this setting. DESIGN: Prospective cohort study. SETTING: Five Intensive Critical Care Units affiliated to the University in Toulouse (France), Paris (France), Clermont-Ferrand (France), Liège (Belgium), and Monza (Italy). PATIENTS: High-resolution anatomical T1-weighted images were acquired in 126 anoxic coma patients ("learning" sample) 16 ± 8 days after cardiac arrest and 70 matched controls. An additional sample of 18 anoxic coma patients, recruited in Toulouse, was used to test predictive model generalization ("test" sample). All patients were followed up 1 year after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cortical thickness was computed on the whole cortical ribbon, and deep gray matter volumetry was performed after automatic segmentation. Brain morphometric data were employed to create multivariate predictive models using learning machine techniques. Patients displayed significantly extensive cortical and subcortical brain volumes atrophy compared with controls. The accuracy of a predictive classifier, encompassing cortical and subcortical components, has a significant discriminative power (learning area under the curve = 0.87; test area under the curve = 0.96). The anatomical regions which volume changes were significantly related to patient's outcome were frontal cortex, posterior cingulate cortex, thalamus, putamen, pallidum, caudate, hippocampus, and brain stem. CONCLUSIONS: These findings are consistent with the hypothesis of pathologic disruption of a striatopallidal-thalamo-cortical mesocircuit induced by cardiac arrest and pave the way for the use of combined brain quantitative morphometry in this setting.