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.

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.

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.

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 µg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

Chronic subdural haematoma associated with disturbance of consciousness: significance of acute-on-chronic subdural haematoma.

OBJECTIVE: Detailed features of chronic subdural haematoma (cSDH) associated with disturbance of consciousness and acute-on-chronic subdural haematoma (a/cSDH), in which acute subdural haematoma overlaps cSDH, remain poorly understood. The object of this study was to clarify both characteristics of cSDH associated with disturbance of consciousness and the significance of a/cSDH. METHODS: Clinical factors and computed tomography (CT) findings were retrospectively investigated in 349 consecutive patients admitted between 2006 and 2013 and diagnosed with cSDH. RESULTS: Glasgow Coma Scale (GCS) was ≤ 8 in 21 patients (6.0%) and 9-14 in 29 patients excluding aphasia and/or dementia (8.3%). Multiple logistic regression analysis indicated that a/cSDH, female sex and haemodialysis were significantly related to severe disturbance of consciousness (GCS ≤ 8). Predictors for a/cSDH observed in 29 patients (8.3%) were trauma history within 7 days before admission, high prothrombin time-international rate, and use of anticoagulants and/or antiplatelets. Unfavourable outcomes were observed in 29 of 299 patients (9.7%) without consciousness disturbance, compared to 27 of 50 patients (54%) with consciousness disturbance. Predictors of unfavourable outcome were consciousness disturbance, increase in age, malignancy, trauma history within 7 days and haemodialysis. DISCUSSION: Disturbance of consciousness associated with cSDH, often caused by either a/cSDH or concomitant disease, frequently resulted in unfavourable outcomes. As a result, in cSDH patients associated with disturbance of consciousness, underlying conditions, especially a/cSDH, which is often caused by haemostatic abnormality, should be clarified and managed.

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

OBJECTIVE: The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). METHODS: This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. RESULTS: There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). CONCLUSION: The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most fundamental warning signs in the clinical monitoring of comatose patients.

The impact of lymphopenia on delirium in ICU patients.

BACKGROUND: Immunosuppressed states may predispose patients to development of acute brain injury during times of critical illness. Lymphopenia is a non-specific yet commonly used bedside marker of immunosuppressed states. METHODS: We examined whether lymphopenia would predict development of acute brain dysfunction (delirium and/or coma) in 518 patients enrolled in the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study in medical and surgical ICUs of a tertiary care, university-based medical center. Utilizing proportional odds logistic regression and Cox proportional hazards survival analysis, we assessed the relationship between pre-enrollment lymphocytes and subsequent cognitive outcomes including delirium- and coma-free days (DCFDs) and 30-day mortality. RESULTS: There were no statistically significant associations between lymphocytes and DCFDs (p = 0.17); additionally, the relationship between lymphocytes and mortality was not statistically significant (p = 0.71). Among 259 patients without history of cancer or diabetes, there was no statistically significant association between lymphocytes and DCFDs (p = 0.07). CONCLUSION: lymphopenia, a commonly used bedside marker of immunosuppression, does not appear to be a marker of risk for acute brain injury (delirium/coma) or 30-day mortality in general medical/surgical ICU patients.

[The current conceptions of non-pharmacological therapeutic methods capabilities and mechanism of their action].

The current conceptions of non- pharmacological therapeutic methods capabilities and mechanism of their action. The current article demonstrates the modern capabilities of non-pharmacological therapeutic methods on the example of effective use of infrared-terahertz radiation and acupuncture in cases when the standard treatments failed. The first clinical presentation describes the case of successful intervention in the stroke patient on his 18 day of staying in coma. The second presentation dedicates to rehabilitation of a post-stroke patient with hemiparesis and wheelchair use for five years. Then the modern approaches to understanding the employed methods are proposed. The developing concept is based on the idea that the applied therapeutic modalitiy forms an afferent matrix-challenge in the central nervous system to which the latter elaborates the reciprocal efferent matrix-response. In the process of reaction the central nervous system performs a kind of reboot of its system functional connections thus eliminating stagnant pathological dominants and inhibitions. It is proposed to employ the accumulated experience in the conditions of increasing restriction of drugs and medical devices import.

Coma from wall suction-induced CSF leak complicating spinal surgery.

A 72-year-old woman was admitted for elective L4/L5 laminectomy. The operative procedure was extradural, and a Jackson-Pratt (JP) drain was placed in the tissue bed and set to wall suction during skin closure. During closure, the patient developed a 15 s period of asystole. The patient was haemodynamically stable, but was comatose for 3 days postoperatively. Cardiac enzymes and EEG were unrevealing. Head CT showed traces of subarachnoid haemorrhage and signs suggestive of cerebral anoxia. JP drain at the incision produced 170-210 mL/day of fluid, positive for ß-2 transferrin, indicating cerebrospinal fluid (CSF). The patient fully returned to baseline on hospital day 10. MRI on hospital day 8 normalised. The reversible coma and radiographic findings were most consistent with acute intracranial hypotension relating to acute loss of CSF. Because radiographic findings can mimic hypoxic-ischaemic injury, acute intracranial hypotension should be considered in the differential diagnosis of postoperative coma after cranial or spinal surgery.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings.

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings / Bolhas do coma pós-intoxicação por depressores do sistema nervoso central: relato de caso incluindo achados histopatológicos

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Sudden intraaqueductal dislocation of a third ventricle ependymoma causing acute decompensation of hydrocephalus.

The authors report an unusual sudden intraaqueductal dislocation of a third ventricle ependymoma causing acute loss of consciousness, and they detail its neuroendoscopic treatment. This case is unique and has never been described in the literature before. The patient suffered from headache and recurrent nausea. Admission MR images revealed a contrast-enhancing lesion within the posterior part of the third ventricle. During the course of the day of admission, the patient suddenly became comatose. Emergency MR imaging demonstrated a deeply intraaqueductal dislocation of the pedicled tumor, with complete obstruction of the aqueduct and ventricular dilation. Immediate surgical intervention with endoscopic third ventriculostomy and complete tumor removal was performed. After surgery, the patient made a rapid recovery. In this case, the authors presume a sudden intraaqueductal dislocation of the ependymoma caused by aspiration of the tumor as a result of the caudal CSF flow.

Congenital ataxia, mental retardation, and dyskinesia associated with a novel CACNA1A mutation.

The CACNA1A gene encodes the pore forming alpha-1A subunit of neuronal voltage-dependent P/Q-type Ca( 2+) channels. Mutations in this gene result in clinical heterogeneity, and present with either chronic progressive symptoms, paroxysmal events, or both, with clinical overlap among the different phenotypes. The authors describe a seven year-old boy with mental retardation and congenital cerebellar ataxia that developed dyskinesia at the age of a few months, and recurrent episodes of coma following mild head trauma associated with motor and autonomic signs, from the second year of life. An extensive metabolic evaluation, interictal electroencephalography (EEG), and muscle biopsy were normal. Brain magnetic resonance imaging (MRI) during one of these episodes revealed edema of the right hemisphere and cerebellar atrophy. Genetic testing revealed a R1350Q mutation in the CACNA1A gene. This is a novel de novo mutation.Congenital cerebellar ataxia can be a result of CACNA1A mutations, especially when associated with recurrent unexplained coma.

Hemorrhagic colloid cyst with sudden coma.

BACKGROUND: Third ventricle colloid cysts are regarded as benign lesions. They may, however, present with dramatic and rapidly deteriorating neurological signs, leading to sudden death. Although the exact cause of this clinical course is unknown, acute hydrocephalus caused by occlusion of Monro's foramina has been suggested. This, in turn, may be the result of acute cyst swelling, which can exceptionally be due to an intralesional hemorrhage. CASE REPORT: This report illustrates the case of a young patient who deteriorated to sudden coma and was found to have a hemorrhagic colloid cyst of the third ventricle. This was removed via a purely endoscopic technique. Although the radiological results were excellent, the clinical outcome was poor. CONCLUSIONS: This case suggests once again the importance of the early recognition of colloid cysts of the third ventricle for appropriate treatment before potentially irreversible neurological deterioration sets in.

Endotoxemia produces coma and brain swelling in bile duct ligated rats.

UNLABELLED: This study explores the hypothesis that the inflammatory response induced by administration of lipopolysaccharide (LPS) exacerbates brain edema in cirrhotic rats; and if so whether this is associated with altered brain metabolism of ammonia or anatomical disturbance of the blood-brain barrier. Adult Sprague-Dawley rats 4 weeks after bile duct ligation (BDL)/Sham-operation, or naïve rats fed a hyperammonemic diet (HD), were injected with LPS (0.5 mg/kg, intraperitoneally) or saline, and killed 3 hours later. LPS administration increased brain water in HD, BDL, and sham-operated groups significantly (P < 0.05), but this was associated with progression to pre-coma stages only in BDL rats. LPS induced cytotoxic brain swelling and maintained anatomical integrity of the blood-brain barrier. Plasma/brain ammonia levels were higher in HD and BDL rats than in sham-operated controls and did not change with LPS administration. Brain glutamine/myoinositol ratio was increased in the HD group but reduced in the BDL animals. There was a background pro-inflammatory cytokine response in the brains of cirrhotic rats, and plasma/brain tumor necrosis factor alpha (TNF-alpha) and IL-6 significantly increased in LPS-treated animals. Plasma nitrite/nitrate levels increased significantly in LPS groups compared with non-LPS controls; however, frontal cortex nitrotyrosine levels only increased in the BDL + LPS rats (P < 0.005 versus BDL controls). CONCLUSION: Injection of LPS into cirrhotic rats induces pre-coma and exacerbates cytotoxic edema because of the synergistic effect of hyperammonemia and the induced inflammatory response. Although the exact mechanism of how hyperammonemia and LPS facilitate cytotoxic edema and pre-coma in cirrhosis is not clear, our data support an important role for the nitrosation of brain proteins.

Fatal intratumoral hemorrhage immediately after gamma knife radiosurgery for brain metastases: case report.

Radiosurgical treatment of brain tumors is sometimes considered to be free from significant acute complications or adverse effects. A rare case of fatal intratumoral hemorrhage immediately after gamma knife radiosurgery (GKR) for brain metastasis is reported. A 46-year-old woman with lung cancer complicated by systemic dissemination experienced an acute episode of headache, speech disturbances, and right-side hemiparesis. She had no history of arterial hypertension or coagulation disorders. CT and MRI disclosed multiple brain metastases. The largest tumor, which was located in the left frontal lobe and caused a significant mass effect, was removed microsurgically without any complications. GKR for nine residual metastases was done on the fourth postoperative day. The marginal dose, which corresponded to the 50% prescription isodose line, constituted 20 Gy. No complications were noticed during frame fixation, treatment itself, or frame removal. Fifteen minutes after the end of the GKR session the patient acutely fell into a deep coma. Urgent CT disclosed a massive hemorrhage in the left cerebellar hemisphere in the vicinity of the radiosurgically treated lesion. The patient died 4 days later and autopsy confirmed the presence of intratumoral hemorrhage. In conclusion, GKR for metastatic brain tumors should not be considered as a risk-free procedure and, while extremely rare, even fatal complications can occur after treatment.