Changes in electrocorticographic beta frequency components precede spreading depolarization in patients with acute brain injury.

OBJECTIVE: Spreading depolarization (SD) occurs after traumatic brain injury, subarachnoid hemorrhage, malignant hemispheric stroke and intracranial hemorrhage. SD has been associated with secondary brain injury, which can be reduced by ketamine. In this present study frequency bands of electrocorticographic (ECoG) recordings were investigated with regards to SDs. METHODS: A total of 43 patients after acute brain injury were included in this retrospective and explorative study. Relative delta 0.5-4Hz, theta 4-8Hz, alpha 8-13Hz and beta 13-40Hz bands were analyzed with regards to SD occurrence and analgesic and sedative administration. Higher frequencies, including gamma 40-70Hz, fast gamma 70-100Hz and high frequency oscillations 100-200Hz were analyzed in a subset of patients with a sampling rate of up to 400Hz. RESULTS: A close association of relative beta frequency and SD was found. Relative beta frequency was suppressed up to two hours prior to SD when compared to hours with no SD. This finding was partially explained by administration of ketamine. Even after removal of all patient data during administration of ketamine, SDs occurred predominantly during times with low relative beta frequency in a patient-independent analysis. CONCLUSION: Suppression of beta frequency by ketamine or without ketamine is associated with low SD counts. SIGNIFICANCE: Alteration of beta frequency might help to predict occurrence of SDs in acutely brain injured patients.

German Cranial Reconstruction Registry (GCRR): protocol for a prospective, multicentre, open registry.

INTRODUCTION: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established. METHODS: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty. ETHICS AND DISSEMINATION: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery. TRIAL REGISTRATION NUMBER: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425.

Is microdialysis useful for early detection of acute rejection after kidney transplantation?

INTRODUCTION: Acute rejection following kidney transplantation (KTx) is still one of the challenging complications leading to chronic allograft failure. The aim of this study was to investigate the role of microdialysis (MD) in the early detection of acute graft rejection factor following KTx in porcine model. METHODS: Sixteen pigs were randomized after KTx into case (n = 8, without immunosuppressant) and control groups (n = 8, with immunosuppressant). The rejection diagnosis in our groups was confirmed by histopathological evidences as "acute borderline rejection". Using MD, we monitored the interstitial concentrations of glucose, lactate, pyruvate, glutamate and glycerol in the transplanted grafts after reperfusion. RESULTS: In the early post-reperfusion phase the lactate level in our case group was significantly higher comparing to the control group and remained in higher levels until the end of monitoring. The lactate to pyruvate ratio showed a considerable increase in the case group during the post-reperfusion phase. The other metabolites (glucose, glycerol, glutamate) were nearly at the same levels at the end of our monitoring in both study groups. CONCLUSION: The increase in lactate and lactate to pyruvate ratios seems to be an indicator for early detection of acute rejection after KTx. Therefore, MD as a minimally invasive measurement tool may help to identify the need to immunosuppression adjustment in the early KTx phase before the clinical manifestation of the rejection.

Emergency neurosurgical care in patients treated with apixaban: report of 2 cases.

A debate has emerged regarding the safety profile of direct anticoagulants, which are increasingly prescribed for the prevention of thromboembolic events. Despite favorable safety data derived from controlled clinical trials, the absence of specific antidotes for the management of hemorrhagic complications represents a major challenge for emergency physicians. Here, we present the first report on patients treated with the direct factor Xa inhibitor apixaban and conditions requiring urgent neurosurgical intervention (intracerebral hemorrhage, n = 1; subdural hematoma, n = 1). Prothrombin complex concentrates were administered before surgery, and both patients had a favorable postsurgical course without bleeding or thromboembolic complications. Further studies are needed, but this approach seems to be suitable for the emergency management of apixaban-associated intracranial hemorrhage.

Rapid Anticoagulation Reversal With Prothrombin Complex Concentrate Before Emergency Brain Tumor Surgery.

BACKGROUND: Brain tumors may become symptomatic due to intracranial hypertension and patients may present to emergency departments in life-threatening conditions. Hence, emergency brain tumor surgery has to be considered, but sufficient hemostasis has to be present when initiating surgical procedures. Impaired hemostasis because of oral anticoagulation for the treatment of cardiovascular diseases is encountered in a growing number of patients. Here we present the first case series of anticoagulated patients receiving prothrombin complex concentrate (PCC) to rapidly restore hemostasis and facilitate emergency brain tumor surgery. METHODS: We retrospectively analyzed our institutional database of neurosurgical patients receiving PCC from February 2007 to April 2013 (n=432) and identified 5 patients who received PCC before emergency brain tumor surgery. Clinical characteristics, as well as modalities of PCC administration and parameters of hemostasis were analyzed. RESULTS: Patients had a mean Glasgow Coma Scale score of 9.4 at admission. Mean international normalized ratio was 3.75±1.98 and after administration of PCC (mean, 3260±942 IU), international normalized ratio significantly decreased to 1.19±0.07 (P<0.0001). Emergency brain tumor surgery was initiated within 5.2 hours (range, 0 to 13.5 h) after PCC administration. Diagnostic histopathology revealed metastasis (n=2), meningioma (n=2), and ependymoma (n=1). No hemorrhagic or thromboembolic events occurred and 4 patients had a good neurological outcome at hospital discharge. One patient died on the 14th postoperative day because of respiratory failure following development of pneumonia. CONCLUSIONS: In anticoagulated patients with brain tumors requiring immediate surgery due to life-threatening conditions, administration of PCC rapidly and safely restored hemostasis. PCC administration seems to be an effective option for anticoagulant reversal in this patient cohort. Further observational safety studies (eg, thromboembolic events) are warranted.

Perihemorrhagic ischemia occurs in a volume-dependent manner as assessed by multimodal cerebral monitoring in a porcine model of intracerebral hemorrhage.

BACKGROUND: Changes in the perihemorrhagic zone (PHZ) of intracerebral hemorrhage (ICH) are variable. Different mechanisms contribute to secondary neuronal injury after ICH. This multimodal monitoring study investigated early changes in the PHZ of ICH. METHODS: Twenty-four swine were anesthetized, ventilated, and underwent monitoring of vital parameters. Next to an intracranial pressure-probe (ICP), microdialysis (MD), thermodiffusion cerebral blood flow (td-CBF), and oxygen probes (PbrO2) were placed into the gray white matter junction for 12 h of monitoring. ICH was induced using the autologous blood injection model. Pre-defined volumes were 0 ml (sham), 1.5 ml ipsilateral (1.5 ml), 3.0 ml ipsilateral (3.0 ml), and 3.0 ml contralateral (3.0 ml contra). RESULTS: ICP equally increased in all groups after ICH. In the 3.0 ml group tissue oxygenation decreased to ischemic values of 9 ± 7 mmHg early after 6 h of monitoring. This decrease was associated with a significant perfusion reduction from 36 ± 8 ml/100 g/min to 20 ± 10 ml/100 g/min. MD correlated with a threefold lactate/pyruvate ratio increase. Measurements in all other groups were unchanged. CONCLUSION: Multimodal monitoring demonstrates volume-dependent changes of tissue oxygenation, blood flow, and ischemic MD markers in the PHZ independent of increased ICP suggesting early moderate ischemia. No evidence was found for the existence of a perihemorrhagic ischemia in the small hematoma groups.

Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke.

BACKGROUND: Early decompressive hemicraniectomy reduces mortality without increasing the risk of very severe disability among patients 60 years of age or younger with complete or subtotal space-occupying middle-cerebral-artery infarction. Its benefit in older patients is uncertain. METHODS: We randomly assigned 112 patients 61 years of age or older (median, 70 years; range, 61 to 82) with malignant middle-cerebral-artery infarction to either conservative treatment in the intensive care unit (the control group) or hemicraniectomy (the hemicraniectomy group); assignments were made within 48 hours after the onset of symptoms. The primary end point was survival without severe disability (defined by a score of 0 to 4 on the modified Rankin scale, which ranges from 0 [no symptoms] to 6 [death]) 6 months after randomization. RESULTS: Hemicraniectomy improved the primary outcome; the proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, as compared with 18% in the control group (odds ratio, 2.91; 95% confidence interval, 1.06 to 7.49; P=0.04). This difference resulted from lower mortality in the surgery group (33% vs. 70%). No patients had a modified Rankin scale score of 0 to 2 (survival with no disability or slight disability); 7% of patients in the surgery group and 3% of patients in the control group had a score of 3 (moderate disability); 32% and 15%, respectively, had a score of 4 (moderately severe disability [requirement for assistance with most bodily needs]); and 28% and 13%, respectively, had a score of 5 (severe disability). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group. CONCLUSIONS: Hemicraniectomy increased survival without severe disability among patients 61 years of age or older with a malignant middle-cerebral-artery infarction. The majority of survivors required assistance with most bodily needs. (Funded by the Deutsche Forschungsgemeinschaft; DESTINY II Current Controlled Trials number, ISRCTN21702227.).

Prothrombin complex concentrate facilitates emergency spinal surgery in anticoagulated patients.

BACKGROUND: Oral anticoagulants are commonly used in the ageing population and therefore, spine surgeons are increasingly confronted with anticoagulated patients requiring surgical therapy. 'Bridging therapies' with heparins are established in elective settings, but the time frame for haemostasis restoration may be too long for patients presenting with acute spinal pathology and impending disability. The goal of this study was to analyse the feasibility of prothrombin complex concentrate (PCC) administration to facilitate emergency spinal surgery in anticoagulated patients. METHOD: A retrospective analysis of the institutional database of neurosurgical patients receiving PCC from February 2007 to December 2013 (n = 485) identified 18 patients who received PCC prior to emergency spinal surgery. Clinical characteristics, as well as modalities of PCC administration and parameters of haemostasis were analysed. Furthermore, haemorrhagic complications and thromboembolic events in the further course were evaluated. RESULTS: Spinal pathologies requiring urgent neurosurgical decompression were spinal haematoma (n = 9), spinal metastasis (n = 5), vertebral body fracture (n = 2), and disc herniation (n = 2). The mean international normalized ratio (INR) on admission was 2.27 ± 1.20 and after administration of PCC (mean: 1,944 ± 953 I.U.), INR significantly decreased to 1.12 ± 0.10 (p < 0.001). Emergency surgery was initiated within 4.4 h after PCC administration (range: 0-16.6 h). Postoperatively, symptoms improved in 12 patients (66.7 %). There were two deaths (11 %), one caused by acute myocardial infarction on the fourth postoperative day. Bleeding complications occurred in two patients (epidural haemorrhage n = 1, rectal tumour haemorrhage n = 1). CONCLUSIONS: The administration of PCC facilitates emergency spinal surgery in anticoagulated patients who present with acute spinal pathology requiring urgent neurosurgical decompression. The risk of PCC-associated thromboembolic events seems to be low and justifies the use of PCC in order to avoid permanent disablement resulting from delayed surgery or non-operation.

Multiple electrode aggregometry in antiplatelet-related intracerebral haemorrhage.

As the population ages, antiplatelet agents are increasingly used in patients with cardiovascular diseases. Due to impaired platelet activity, these patients are at increased risk for bleeding complications and this is of particular importance in patients with intracerebral haemorrhage. The multiple electrode aggregometry analyser Multiplate (Roche Diagnostics, Mannheim, Germany) was introduced in 2006 to monitor the effectiveness of antiplatelet drugs in interventional cardiology. As a point-of-care device, it allows bedside assessment of platelet activity within minutes through analysis of a sample of whole blood. In patients treated with antiplatelet medication and in need of urgent cardiac surgery, these devices allow prediction of intraoperative blood loss and their use was implemented within respective guidelines to direct transfusion strategies. We used the Multiplate analyser for rapid assessment of antiplatelet activity in a patient who developed an intracerebral haemorrhage after administration of aspirin and clopidogrel. Antiplatelet activity was assessed within 10 minutes while the patient was transferred to the operating room and after transfusion of platelet concentrates and administration of desmopressin and tranexamic acid, repeated Multiplate analysis demonstrated nearly normalized platelet activity. In our view, there is great potential for this device to improve treatment in neurosurgery and especially the treatment of antiplatelet-related intracerebral haemorrhage. Instant assessment of antiplatelet activity or effectiveness of haemostatic measures is facilitated and furthermore, patients with normal platelet activity despite a positive history of antiplatelet medication intake can be identified. In these patients, empiric administration of haemostatic substances would unnecessarily increase the risk of thromboembolic events.

Initial experiences with Multiplate® for rapid assessment of antiplatelet agent activity in neurosurgical emergencies.

OBJECTIVE: As the population ages, physicians encounter a growing number of patients who are treated with antiplatelet agents and present with severe conditions requiring urgent neurosurgical therapy. Standard laboratory investigations are insufficient to evaluate platelet activity and furthermore, it is difficult to evaluate effects of haemostatic measures on platelet function. In this article we report our initial experiences with the point-of-care device Multiplate® for assessment of platelet activity in neurosurgical emergencies on patients with a reported intake of antiplatelet medication. METHODS: Multiplate® assessment of antiplatelet activity was carried out in 21 non-consecutive patients with a reported intake of antiplatelet medication (aspirin: n=21, clopidogrel: n=3, ticragrelor: n=1) and urgent admission to our hospital because of conditions such as intracranial haemorrhage requiring urgent neurosurgical therapy. Analysis was repeated in order to evaluate the effectiveness of haemostatic drugs and platelet concentrate transfusion on platelet activity in six patients. RESULTS: No technical difficulties occurred and in all cases, results were obtained within 15 min. On admission, patients' arachidonic acid induced platelet activity was reduced by 44.4±33.5% (range: -79.7% to +44.3%) compared to the lower reference limit. Two patients had a normal platelet activity despite a reported intake of aspirin. Haemostatic measures significantly increased arachidonic acid induced platelet activity by 100±66% (p<0.005). CONCLUSION: The Multiplate® device allowed rapid assessment of antiplatelet agent activity and evaluation of haemostatic measures on platelet activity. Further studies with larger patient numbers are needed, but this device may represent a valuable tool to improve treatment modalities in patients treated with antiplatelet medication and conditions requiring urgent neurosurgical therapy.

Evaluating the effects of extended cold ischemia on interstitial metabolite in grafts in kidney transplantation using microdialysis.

PURPOSE: During kidney transplantation (KTx), the length of cold ischemia time (CIT) and the subsequent changes in energy metabolism may lead to variations in interstitial metabolites. Using microdialysis (MD), we evaluated the effects of a short and long CIT on changes of these metabolites. METHODS: Sixteen pigs were randomized in two identical groups, one with a short CIT and the other one with a long CIT. Using MD in the transplanted grafts, we evaluated the parenchyma concentrations of glucose, lactate, pyruvate, glutamate and glycerol in different stages. RESULTS: We noted that during the warm ischemia time (WIT) and in the early post-reperfusion phase glucose levels increased more significantly in the long CIT group and remained high until the end of monitoring. At the end of CIT and during WIT, the long CIT group had a significantly higher glycerol level, but the level dropped gradually in the late post-reperfusion phase and reached a steady state in both groups. CONCLUSIONS: The extended CIT clearly results in considerably impaired graft metabolism. The high interstitial glucose levels within hours after KTx could be considered as a marker of primary delayed function of the graft. Furthermore, the glycerol value could reflect the extent of graft injury during the ischemia time or in case of acute impairment of graft perfusion.

Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury.

Spreading depolarizations are waves of mass neuronal and glial depolarization that propagate across the injured human cortex. They can occur with depression of neuronal activity as spreading depressions or isoelectric spreading depolarizations on a background of absent or minimal electroencephalogram activity. Spreading depolarizations are characterized by the loss of neuronal ion homeostasis and are believed to damage functional neurons, leading to neuronal necrosis or neurological degeneration and poor outcome. Analgesics and sedatives influence activity-dependent neuronal ion homeostasis and therefore represent potential modulators of spreading depolarizations. In this exploratory retrospective international multicentre analysis, we investigated the influence of midazolam, propofol, fentanyl, sufentanil, ketamine and morphine on the occurrence of spreading depolarizations in 115 brain-injured patients. A surface electrode strip was placed on the cortex, and continuous electrocorticographical recordings were obtained. We used multivariable binary logistic regression to quantify associations between the investigated drugs and the hours of electrocorticographical recordings with and without spreading depolarizations or clusters of spreading depolarizations. We found that administration of ketamine was associated with a reduction of spreading depolarizations and spreading depolarization clusters (P < 0.05). Midazolam anaesthesia, in contrast, was associated with an increased number of spreading depolarization clusters (P < 0.05). By using a univariate odds ratio analysis, we also found a significant association between ketamine administration and reduced occurrence of isoelectric spreading depolarizations in patients suffering from traumatic brain injury, subarachnoid haemorrhage and malignant hemispheric stroke (P < 0.05). Our findings suggest that ketamine-or another N-methyl-d-aspartate receptor antagonist-may represent a viable treatment for patients at risk for spreading depolarizations. This hypothesis will be tested in a prospective study.

Spreading depolarizations occur in human ischemic stroke with high incidence.

OBJECTIVE: Cortical spreading depression (CSD) and periinfarct depolarization (PID) have been shown in various experimental models of stroke to cause secondary neuronal damage and infarct expansion. For decades it has been questioned whether CSD or PID occur in human ischemic stroke. Here, we describe CSD and PID in patients with malignant middle cerebral artery infarction detected by subdural electrocorticography (ECoG). METHODS: Centres of the Co-operative Study of Brain Injury Depolarisations (COSBID) recruited 16 patients with large middle cerebral artery infarction. During surgery for decompressive hemicraniectomy, an electrode strip was placed on the periinfarct region, from which four ECoG channels were acquired. RESULTS: A total of 1,638 hours was recorded; mean monitoring time per patient was 109.2 hours. A total of 127 CSD and 42 PID events were observed. In CSD, a stereotyped slow potential change spreading between adjacent channels was accompanied by transient depression of ECoG activity. In PID, a slow potential change spread between neighboring channels despite already established suppression of ECoG activity. Most CSDs and PIDs appeared repetitively in clusters. CSD or PID was observed in all but two patients. In these two patients, the electrode strip had been placed over infarcted tissue, and accordingly, no local ECoG or recurrent transient depolarization activity occurred throughout the observation period. INTERPRETATION: CSD and PID occurred spontaneously with high frequency in this study of patients with malignant middle cerebral artery infarction. This suggests that the large volume of experimental studies of occlusive stroke that implicate spreading depolarizations in its pathophysiology can be translated, with appropriate caution, to patients and their treatment.

Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations.

Progressive ischaemic damage in animals is associated with spreading mass depolarizations of neurons and astrocytes, detected as spreading negative slow voltage variations. Speculation on whether spreading depolarizations occur in human ischaemic stroke has continued for the past 60 years. Therefore, we performed a prospective multicentre study assessing incidence and timing of spreading depolarizations and delayed ischaemic neurological deficit (DIND) in patients with major subarachnoid haemorrhage (SAH) requiring aneurysm surgery. Spreading depolarizations were recorded by electrocorticography with a subdural electrode strip placed on cerebral cortex for up to 10 days. A total of 2110 h recording time was analysed. The clinical state was monitored every 6 h. Delayed infarcts after SAH were verified by serial CT scans and/or MRI. Electrocorticography revealed 298 spreading depolarizations in 13 of the 18 patients (72%). A clinical DIND was observed in seven patients 7.8 days (7.3, 8.2) after SAH. DIND was time-locked to a sequence of recurrent spreading depolarizations in every single case (positive and negative predictive values: 86 and 100%, respectively). In four patients delayed infarcts developed in the recording area. As in the ischaemic penumbra of animals, delayed infarction was preceded by progressive prolongation of the electrocorticographic depression periods associated with spreading depolarizations to >60 min in each case. This study demonstrates that spreading depolarizations have a high incidence in major SAH and occur in ischaemic stroke. Repeated spreading depolarizations with prolonged depression periods are an early indicator of delayed ischaemic brain damage after SAH. In view of experimental evidence and the present clinical results, we suggest that spreading depolarizations with prolonged depressions are a promising target for treatment development in SAH and ischaemic stroke.

Contemporary management of aneurysmal subarachnoid hemorrhage in germany: results of a survey among 100 neurosurgical departments.

OBJECTIVE: To assess the status quo of clinical management in patients with ruptured intracranial aneurysms in Germany. In addition to preferences in vascular treatment (i.e., surgical versus endovascular), the choice of diagnostics and treatment options in the pre- and postprocedural phase is emphasized. METHODS: A standardized questionnaire was used in a postal survey. Participants were representatives of neurosurgical departments in Germany (n = 130, total number of departments). Comparisons between groups of respondents were tested using chi statistics (Fisher's exact test, two-sided). RESULTS: The overall response rate was 77% (n = 100). Preoperative assessment is standard by computed tomography and conventional angiography. Currently, endovascular treatment options are available in 71% of all responding centers. On the basis of self estimates it is projected that 63% of all ruptured aneurysms are treated surgically, whereas 37% are treated endovascularly. For anterior circulation aneurysms, a significantly higher number of respondents commit to routine or frequent use of surgical techniques compared with endovascular treatment options (93 versus 52%, P < or = 0.05). In contrast, for posterior circulation aneurysms, endovascular treatment is preferred (24 versus 94%, P < or = 0.05). Acute posthemorrhagic hydrocephalus is treated by external ventricular drainage routinely (97%). Doppler sonography, monitoring of cerebral perfusion pressure, and electrophysiology are used by a significant number of respondents. Specific treatment of subarachnoid hemorrhage (SAH) patients includes calcium antagonists (70%), glucocorticosteroids (35%), and hemorheologic agents (30%). CONCLUSION: In Germany, aneurysmal subarachnoid hemorrhage remains a disease in which standardization of clinical management is highest in preoperative diagnostics, intensive care unit monitoring, and postoperative treatment. With respect to currently published guidelines for subarachnoid hemorrhage treatment, compliance is moderate. Preferred treatment for anterior circulation aneurysms is predominantly surgical, whereas endovascular treatment options are preferentially used in aneurysms of the posterior circulation. This survey serves as a basis to analyze future developments in the management of subarachnoid hemorrhage more effectively and as an aid in finding a consensus in treatment both nationally and internationally.

Norepinephrine infusion increases interleukin-6 in plasma and cerebrospinal fluid of brain-injured rats.

BACKGROUND: Significantly increased plasma and CSF IL-6 levels reflect underlying tissue damage following clinical and experimental traumatic brain injury (TBI). Catecholamines, used under clinical conditions to maintain adequate cerebral perfusion pressure, induce a sustained IL-6 release. Thus an additional elevation in IL-6 could aggravate brain edema in the acute posttraumatic phase. We studied the changes in plasma and cerebrospinal fluid (CSF) IL-6 levels 4 and 24 hours after experimental TBI and assessed possible time-dependent effects of norepinephrine infusion on IL-6 and brain edema. MATERIAL/METHODS: Paired plasma and CSF IL-6 measured at 4 and 24 hours following TBI (n=10) were compared to levels in non-traumatized rats (n=5). In a placebo-controlled trial, 20 brain-injured male Sprague-Dawley rats were randomized to receive norepinephrine or NaCl for 90 minutes at 4 or 24 hours after TBI. Plasma IL-6 was measured before, during, and after the infusion period. One hour after stopping the infusion, CSF IL-6 and hemispheric swelling were determined. RESULTS: During the first posttraumatic day, plasma and CSF IL-6 levels were significantly increased compared to non-traumatized rats, reaching the highest values at 24 hours (p<0.05). Norepinephrine infusion significantly increased plasma IL-6 at 7 and 27 hours after TBI; IL-6 was significantly elevated in CSF only at 7 hours (p<0.05). Brain edema was not aggravated. CONCLUSIONS: The norepinephrine-induced increase in plasma and CSF IL-6 suggests that concomitant norepinephrine administration needs to be considered when interpreting systemic and local changes in IL-6 levels in TBI patients.

Focal laminar cortical MR signal abnormalities after subarachnoid hemorrhage.

In the autopsy studies of patients with delayed ischemic neurological deficits after subarachnoid hemorrhage, a predominance of cortical lesions has been observed. Similar to the autopsy descriptions in the literature, we present magnetic resonance images visualizing focal laminar cortical lesions around a fissure or sulcus in two patients, who initially did not undergo surgery, with delayed ischemic neurological deficits. This magnetic resonance imaging pattern may provide a clue to the diagnosis if the patient does not present to the emergency room with the acute hemorrhage but with delayed ischemic neurological deficits.