Anne D. Ebert

Early Neurobehavioral Outcome After Stroke Is Related to Release of Neurobiochemical Markers of Brain Damage

BACKGROUND AND PURPOSE The study aimed to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to early neurobehavioral outcome after stroke. METHODS We investigated 58 patients with completed stroke who were admitted to the stroke unit of the Department of Neurology at Magdeburg University. Serial venous blood samples were taken after admission and during the first 4 days, and protein S-100B and NSE were analyzed by the use of immunoluminometric assays. In all patients, lesion topography and vascular supply were analyzed and volume of infarcted brain areas was calculated. The neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale (NIHSS) on admission, at days 1 and 4 on the stroke unit, at day 10, and at discharge from the hospital. Comprehensive neuropsychological examinations were performed in all patients with first-ever stroke event and supratentorial brain infarctions. Functional outcome was measured with the Barthel score at discharge from the hospital. RESULTS NSE and protein S-100B concentrations were significantly correlated with both volume of infarcted brain areas and NIHSS scores. Patients with an adverse neurological outcome had a significantly higher and significantly longer release of both markers. Neuropsychological impairment was associated with higher protein S-100B release, but this did not reach statistical significance. CONCLUSIONS Serum concentrations and kinetics of protein S-100B and NSE have a high predictive value for early neurobehavioral outcome after acute stroke. Protein S-100B concentrations at days 2 to 4 after acute stroke may provide valuable information for both neurological status and functional impairment at discharge from the acute care hospital.

Release of biochemical markers of damage to neuronal and glial brain tissue is associated with short and long term neuropsychological outcome after traumatic brain injury

OBJECTIVES The present study aimed at the analysis of release patterns of neurobiochemical markers of brain damage (neuron specific enolase (NSE) and protein S-100B) in patients with traumatic brain injury and their predictive value with respect to the short and long term neuropsychological outcome. METHODS Serial NSE and S-100B concentrations were analysed in blood samples taken at the first, second, and third day after traumatic brain injury. In 69 patients who fulfilled the inclusion criteria (no history of neurological or psychiatric disorder or alcohol or drug dependency, blood sampling according to the scheduled time scale, aged between 16 and 65 years) standardised neurological examinations and qualitative and quantitative evaluation of CT were performed. Comprehensive neuropsychological assessment was performed in 39 subjects 2 weeks after admission and in 29 subjects at a 6 month follow up examination. RESULTS Most patients presented with minor head injuries (GCS⩾13) at the time of admission. Six months later most patients were fully independent in activities of daily living. Two thirds of the patients, however, still had neuropsychological dysfunction. Patients with short and long term neuropsychological disorders had significantly higher NSE and S-100B serum concentrations and a significantly longer lasting release of both markers. A comparative analysis of the predictive value of clinical, neuroradiological, and biochemical data showed initial S-100B values above 140 ng/l to have the highest predictive power. CONCLUSIONS The analysis of post-traumatic release patterns of neurobiochemical markers of brain damage might help to identify patients with traumatic brain injury who run a risk of long term neuropsychological dysfunction.

Neurobehavioral Outcome Prediction After Cardiac Surgery: Role of Neurobiochemical Markers of Damage to Neuronal and Glial Brain Tissue

BACKGROUND AND PURPOSE The goal of the present study was to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to the short- and long-term neuropsychological outcomes after cardiac surgery with cardiopulmonary bypass (CPB). METHODS We investigated 74 patients who underwent elective CABG or valve replacement surgery and who showed no severe neurological deficits after surgery. Patients were investigated with a standardized neurological examination and a comprehensive neuropsychological and neuropsychiatric assessment 1 to 2 days before surgery, 3 and 8 days after surgery, and 6 months later. Serial venous blood samples were taken preoperatively and 1, 6, 20, and 30 hours after skin closure. Protein S-100B and NSE were analyzed with immunoluminometric assays. RESULTS Patients with severe postoperative neuropsychological disorders showed a significantly higher and longer release of neurobiochemical markers of brain damage. Patients who presented with a delirium according to DSM-III-R criteria 3 days after surgery had significantly higher postoperative S-100B serum concentrations. Multivariate analysis (based on postoperative NSE and S-100B concentrations and age of patients, type of operation, length of cross-clamp and perfusion time, and intraoperative and postoperative oxygenation) identified NSE and S-100B concentrations 6 to 30 hours after skin closure as the only variables that contributed significantly to a predictive model of the neuropsychological outcome. NSE, but not S-100B, release was significantly higher in patients undergoing valve replacement surgery. CONCLUSIONS Postoperative serum concentrations and kinetics of S-100B and NSE have a high predictive value with respect to the early neuropsychological and neuropsychiatric outcome after cardiac surgery. The analysis of NSE and S-100B release might allow insight into the underlying pathophysiology of brain dysfunction, thus providing a valuable tool to monitor and evaluate measures to improve cardiac surgery with CPB.

Neuropsychological sequelae of diffuse traumatic brain injury

Primary objectives: Description and analysis of neuropsychological deficits following brain trauma with diffuse lesion probably corresponding to diffuse axonal injury (DAI).Research design: A series of 111 patients suffering from traumatic brain injury could be investigated neuropsychologically within the first 4 weeks after injury and re-assessed after 5–8 months. They included 11 subjects with CT-evidence of diffuse axonal injury, but no CT-signs of focal contusions. Eleven patients with focal frontal contusions but no CT signs of DAI were matched to and compared with the DAI subjects. Seventeen TBI patients with normal CT scans served as controls.Results: When assessed within the first 4 weeks after TBI, both DAI and frontal contusion patients exhibited behavioural abnormalities and deficits in Wechsler Similarities. The DAI patients were also impaired in Digit Span backward and Stroop interference. When re-assessed, the DAI patients showed considerable deficits in the California Verbal Learning Test and in the Wisconsin Card Sorting Test.Conclusions: DAI leads to neuropsychological impairment dominated by executive and memory dysfunction.

Stroke and Cancer The Importance of Cancer-Associated Hypercoagulation as a Possible Stroke Etiology

Background and Purpose— The importance of cancer-associated hypercoagulability as a possible stroke etiology in patients with cancer has received relatively little attention to date. A recent study has suggested that cancer-associated hypercoagulation may be of special importance in the absence of conventional stroke mechanisms. Methods— We identified patients with ischemic stroke sequentially admitted to our stroke center with the additional diagnosis of active and malignant cancer from 2002 to 2011. By using our prospectively collected stroke, MRI, and laboratory data banks, the etiology and risk factors of stroke, types of cancer, deep vein thrombosis/pulmonary embolism, D-dimer levels, and diffusion-weighted imaging lesion patterns were compared to an age- and sex-matched control group. Patients with cancer with a conventional stroke etiology and patients with an unidentified and/or cancer-associated stroke etiology were analyzed separately. Results— One hundred forty patients with cancer and 140 control subjects were included. Unidentified stroke (P<0.001) and infarction in multiple vascular territories (P<0.001) were significantly more frequent and D-dimer levels significantly higher (P<0.05) in patients with cancer. Vice versa, risk factors such as hypertension (P<0.05) and hyperlipidemia (P<0.01) were more prevalent in control subjects. Deep vein thrombosis and pulmonary embolism were more frequent (P<0.01) and D-dimer levels higher (P<0.01) in the patients with unidentified and/or cancer-associated stroke etiology compared to the patients with cancer with a conventional stroke etiology. Lung and pancreatic cancer were significantly overrepresented and D-dimer levels higher in these patients compared with other patients with cancer (P<0.01). Conclusions— Our data confirm the concept of cancer-associated hypercoagulation as a widely underestimated important stroke risk factor in patients with cancer, especially in those with severely elevated D-dimer levels and in the absence of conventional risk factors.

Control of semantic interference in episodic memory retrieval is associated with an anterior cingulate-prefrontal activation pattern

Prefrontal activation is a consistent finding in functional neuroimaging studies of episodic memory retrieval. In the present study we aimed at a further analysis of prefrontal neural systems involved in the executive control of context‐specific properties in episodic memory retrieval using an event‐related fMRI design. Nine subjects were asked to learn two 20‐item word lists that consisted of concrete nouns assigned to four semantic categories. Ten items of both word lists referred to the same semantic category. Subjects were instructed to determine whether nouns displayed in random order corresponded to the first 20‐item target list. The interference evoked by the retrieval of semantically related items of the second list resulted in significantly longer reaction times compared to the noninterference condition. Contrasting the interference against the noninterference retrieval condition demonstrated an activation pattern that comprised a right anterior cingulate and frontal opercular area and a left‐lateralized dorsolateral prefrontal region. Trial averaged time series revealed that the PFC areas were selectively activated at the interference condition and did not respond to the familiarity of learned words. These findings suggest a functionally separable role of prefrontal cortical areas mediating processes associated with the executive control of interfering context information in episodic memory retrieval. Hum. Brain Mapping 13:94–103, 2001.

What does elevated high-sensitive troponin I in stroke patients mean: concomitant acute myocardial infarction or a marker for high-risk patients?

Background: Acute ischemic stroke patients may occasionally suffer from concomitant acute coronary syndrome (ACS). Troponin I and T are established biomarkers to detect ACS. Recently introduced high-sensitive cardiac troponin (hs-TNI and hs-TNT) assays are increasingly used to identify ACS in stroke patients even without signs or symptoms of ACS. These new test systems very often detect elevated values of hs-troponin, although clinical relevance and consequences of elevated hs-TNI values in these patients are unclear so far. Patients and Methods: We examined hs-TNI values in 834 consecutive ischemic stroke patients admitted to our Comprehensive Stroke Center during a 1-year period. hs-TNI was measured immediately after admission and after 3 h if initial hs-TNI was elevated above the 99th percentile of normal values (>0.045 ng/ml). Patients with elevated values were divided into two groups: (1) constant and (2) dynamic hs-TNI values. The dynamic approach was defined as a 30% rise or fall of the hs-TNI value above the critical value within 3 h. All patients received stroke diagnostic and continuous monitoring according to international stroke unit standards, including a 12-lead ECG, blood pressure, body temperature and continuous ECG monitoring, as well as regular 6-hourly neurological and general physical examination (including NIHSS scores). The cardiologists - as members of the Stroke Unit team - evaluated clinical symptoms/examination, as well as laboratory, echocardiographic and ECG findings for the diagnosis of ACS. Results: 172/834 (20.6%) patients showed elevated hs-TNI levels on admission. Patients with elevated hs-TNI values exhibited a significantly (p < 0.001) increased rate of hypertension (89 vs. 77.2%), history of stroke (24.4 vs. 14.8%), history of coronary artery disease (65.7 vs. 34.1%), history of myocardial infarction (22.1 vs. 7.6%), heart failure (12.8 vs. 5.7%) and atrial fibrillation (44.2 vs. 23.6%). 82/136 patients showed constant and 54/136 patients dynamic hs-TNI values: among the latter, 5 patients were diagnosed with ST segment elevation myocardial infarction (STEMI) and 24 with non-STEMI (NSTEMI). Conclusion: Our data demonstrate that hs-TNI was elevated in about 20.6% of acute ischemic stroke patients but therapeutically relevant ACS was diagnosed only in the dynamic group. hs-TNI elevations without dynamic changes may occur in stroke patients without ACS due to different reasons that stress the heart. Therefore, we suppose that hs-TNI is a sensitive marker to detect high-risk patients but serial measurements are mandatory and expert cardiological workup is essential for best medical treatment and to accurately diagnose ACS in acute ischemic stroke patients.

Lack of increased signal intensity in the dentate nucleus after repeated administration of a macrocyclic contrast agent in multiple sclerosis: An observational study.

AbstractRecently, several studies reported increased signal intensity (SI) in the dentate nucleus (DN) after repeated application of gadolinium-based contrast agents (GBCAs), suggesting a deposition of gadolinium in this location. Patients with relapsing–remitting multiple sclerosis (RRMS) frequently show increased permeability of the blood–brain barrier as part of the inflammatory process in the brain parenchyma, which theoretically might increase the risk of gadolinium deposition. In this retrospective study, we investigated a possible increasing SI in the DN after repeated administrations of the macrocyclic contrast agent gadoterate meglumine.Forty-one RRMS patients (33 women, mean age 38 years) with at least 6 prior gadolinium-enhanced examinations (single dose gadoterate meglumine) were identified. A total of 279 unenhanced T1-weighted examinations were analyzed.SI ratio differences did not differ between the first and last MRI examination, neither for the DN-to-pons ratio (P = 0.594) nor for the DN-to-cerebellum ratio (P = 0.847). There was no correlation between the mean DN-to-pons, or between the mean DN-to-cerebellum SI ratio and the number of MRI examinations (P = 0.848 and 0.891), disease duration (P = 0.676 and 0.985), and expanded disability status scale (EDSS) (P = 0.639 and 0.945).We found no signal increases in the DN after a minimum of 6 injections of the macrocyclic GBCA gadoterate meglumine in RRMS patients. This warrants further investigations in regard to the true pathophysiologic basis of intracerebral gadolinium deposition.

Outcome Predictors of Acute Stroke Patients in Need of Intensive Care Treatment

Background: The prognosis of stroke patients admitted to intensive care units (ICU) is commonly regarded to be poor. However, only limited data regarding outcome predictors are available. Patients and Methods: Out of 4,958 consecutive patients admitted to our stroke unit with the diagnosis of acute stroke, after analysis we identified 347 patients (164 male) in need of ICU management. In-hospital and post-rehabilitation mortality as well as functional outcome at discharge and after rehabilitation were analyzed. Results: Ischemic stroke was diagnosed in 252 patients (72.6%) and intracerebral hemorrhage occurred in 95 patients (27.4%). The mean age in our cohort was considerably high (70.8 years). One hundred patients were comatose at admission. The median NIHSS score at admission in the remaining patients was 12. Apart from stroke-related disturbances of consciousness (47.1%), the most common reasons for ICU treatment were cardiac (23.4%) and respiratory (12.1%) complications or interventional procedures requiring mechanical ventilation (11%). In all, 231/347 patients (66.6%) were mechanically ventilated (mean 84 h). In-hospital mortality (143/347; 41.2%) was associated with old age, poor NIHSS score at admission, intracerebral hemorrhage and mechanical ventilation (p < 0.001 in all). Further, admission to ICU because of stroke-related impairment of consciousness increased in-hospital mortality (p < 0.001). Similarly, poor outcome after rehabilitation was associated with old age (p = 0.029) and mechanical ventilation (p < 0.001). In patients ≥80 years with either intracerebral hemorrhage or need of mechanical ventilation, outcome was unfavorable in nearly any case. However, the overall post-rehabilitation outcome did not differ between patients with intracerebral hemorrhage and ischemic stroke (p = 0.275). Conclusion: The stroke population in our study was associated with an increased early mortality; however, given the same conditions, it was old with a high percentage of patients requiring mechanical ventilation. This did not result in increased in-hospital mortality rates compared to younger and less severely affected cohorts. Thus, ICU management is a life-saving initiative even among the elderly. However, the functional outcome was poor in older patients, thus limiting the benefits of ICU care in these patients.

Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI

Background: Advanced magnetic resonance imaging (MRI) techniques provide a window into pathological processes in multiple sclerosis (MS). Nevertheless, to date only few studies have performed sodium MRI in MS. Objectives: We analysed total sodium concentration (TSC) in hyperacute, acute and chronic lesions in MS with 23Na MRI. Methods: 23Na MRI and 1H MRI were performed in 65 MS patients and 10 healthy controls (HC). Mean TSC was quantified in all MS lesions with a diameter of >5 mm and in the normal appearing white and grey matter (NAWM, NAGM). Results: TSC in the NAWM and the NAGM of MS patients was significantly higher compared to HC (WM: 37.51 ± 2.65 mM versus 35.17 ± 3.40 mM; GM: 43.64 ± 2.75 mM versus 40.09 ± 4.64 mM). Acute and chronic MS lesions showed elevated TSC levels of different extent (contrast-enhancing lesions (49.07 ± 6.99 mM), T1 hypointense lesions (45.06 ± 6.26 mM) and remaining T1 isointense lesions (39.88 ± 5.54 mM)). However, non-enhancing hyperacute lesions with a reduced apparent diffusion coefficient showed a TSC comparable to the NAWM (37.22 ± 4.62 mM). Conclusions: TSC is not only a sensitive marker of the severity of chronic tissue abnormalities in MS but is also highly sensitive to opening of the blood–brain barrier and vasogenic tissue oedema in contrast-enhancing lesions.