Comparison of Different Calibration Methods in a Non-invasive ICP Assessment Model.

OBJECTIVE: Previously we described the method of continuous intracranial pressure (ICP) estimation using arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). The model was constructed using reference patient data. Various individual calibration strategies were used in the current attempt to improve the accuracy of this non-invasive ICP (nICP) assessment tool. MATERIALS AND METHODS: Forty-one patients (mean, 52 years; range, 18-77 years) with severe brain injuries were studied. CBFV in the middle cerebral artery (MCA), ABP and invasively assessed ICP were simultaneously recorded for 1 h. Recording was repeated at days 2, 4 and 7. In the first recording, invasively assessed ICP was recorded to calibrate the nICP procedure by means of either a constant shift of nICP (snICP), a constant shift of nICP/ABP ratio (anICP) or by including this recording for a model reconstruction (cnICP). At follow-up days, the calibrated nICP procedures were applied and the results compared to the original nICP. RESULTS: In 76 follow-up recordings, the mean differences (Bias), the SD and the mean absolute differences (ΔICP) between ICP and the nICP methods were (in mmHg): nICP, -5.6 ± 5.72, 6.5; snICP, +0.7 ± 6.98, 5.5, n.s.; anICP, +1.0 ± 7.22, 5.6, n.s.; cnICP, -3.4 ± 5.68, 5.4, p < 0.001. In patients with craniotomy (n = 19), the nICP was generally higher than ICP. This overestimation could be reduced by cnICP calibration, but not completely avoided. DISCUSSION: Constant shift calibrations (snICP, anICP) decrease the Bias to ICP, but increase SD and, therefore, increase the 95% confidence interval (CI = 2 × SD). This calibration method cannot be recommended. Compared to nICP, the cnICP method reduced the Bias and slightly reduced SD, and showed significantly decreased ΔICP. Compared to snICP and anICP, the Bias was higher. This effect was probably caused by the patients with craniotomy. CONCLUSION: The cnICP calibration method using initial recordings for model reconstruction showed the best results.

Practically applicable nerve ultrasound models for the diagnosis of axonal and demyelinating hereditary motor and sensory neuropathies (HMSN).

PURPOSE: To develop specific diagnostic ultrasound (US) models for hereditary motor and sensory neuropathies (HMSN) in patients with primarily demyelinating or axonal polyneuropathies (PNP) according to standard nerve conduction studies (NCS) criteria. METHODS: Single-centre, examiner-blinded cross-sectional study in acquired PNP (consecutive recruitment strategy) and HMSN patients (convenience sample). Allocation into demyelinating or axonal phenotype via easily applicable NCS criteria. Assessment of single measurements by receiver-operating curve (ROC) analysis, development of diagnostic models based on the best measurement values in ROC. RESULTS: Of 85 enrolled subjects, 53 (62%) had HMSN and 32 (38%) acquired PNPs, and 60 subjects (71%) had demyelinating and 25 (29%) axonal PNP. ROC area under the curve of means of the z-transformed 5 best measurement values was 0.87 for demyelinating and 0.99 for axonal HMSN. Diagnostic models showed high accuracy for both demyelinating (84% sensitivity, 86% specificity) and axonal HMSN (100% sensitivity and specificity). As a measure of variability of morphologic changes, standard deviations of z-transformed measurements were compared for acquired PNP and HMSN. In contrast to previous reports of more homogenous nerve enlargements in HMSN, standard deviations were higher in HMSN than in acquired PNP. Additionally, the performance of previously published models for the diagnosis of HMSN in demyelinating PNP was compared. Previously published models showed lower sensitivities (50-58%), but comparable specificities (91-100%) when applied to NCS-criteria defined demyelinating PNP group. CONCLUSION: Diagnostic ultrasound models for HMSN in patients with demyelinating or axonal neuropathies show high accuracy and can contribute to differential diagnosis in clinical routine.

Diagnostic accuracy of nerve ultrasound in hereditary and sporadic non-entrapment neuropathies.

The objective of this study is to compare the diagnostic accuracy of nerve ultrasound (US) and nerve conduction studies (NCS) for acquired non-entrapment peripheral neuropathies (PNP) and hereditary motor and sensory neuropathies (HMSN) in a routine clinical setting. The methods are based on a single-center, prospective, examiner-blinded cross-sectional study on three subject groups of healthy controls, PNP (both enrolled by a consecutive recruitment strategy), and HMSN patients (convenience sample). A clinical reference standard based on the neuropathy impairment (NIS) and neuropathy symptoms scores (NSS) was used for PNP as the external validation criterion. Diagnostic accuracy was assessed by receiver-operating curve (ROC) analyses of single-nerve measurements and logit models. Of a total of 676 consecutively screened subjects, 107 (15.8 %) were recruited, of which 36 (33.6 %) had a PNP. HMSN group consisted of 53 subjects (30 subjects (56.6 %) with genetic confirmation). AUCs of best diagnostic logit models to distinguish between controls and PNP patients were 0.86 for US and 0.97 for NCS corresponding to an equivalent specificity [US 93 % (95 % CI: 83-98 %), NCS 89 % (95 % CI: 78-95 %)], but inferior sensitivity of US [US 56 % (95 % CI: 35-74 %), NCS 97 % (95 % CI: 84-100 %)]. For differentiation between PNP and HMSN, both methods had equivalent AUCs of 0.95 corresponding to similar sensitivities/specificities. Simpler diagnostic models based on measurement protocols feasible for clinical routine revealed similar diagnostic accuracies. US has an inferior sensitivity than NCS for acquired PNP, but comparable specificity. For identification of HMSN in a PNP population, US and NCS show comparable performance.

Noninvasive Assessment of ICP: Evaluation of New TBI Data.

BACKGROUND: In a previously introduced mathematical model, intracranial pressure (ICP) was noninvasively assessed using cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP). In this study this method is evaluated using new data from patients with traumatic brain injury (TBI). MATERIALS AND METHODS: Three hundred fifteen data recordings of 137 patients (114 men; age 14-78 years, mean age 37 ± 17 years) with severe TBI were studied. CBFV, ABP, and invasively assessed ICP were simultaneously recorded for 1 h. Noninvasive ICP (nICP) was calculated and compared with ICP. RESULTS: On 315 recordings, average deviation between ICP and nICP (± standard deviation) was 4.9 ± 3.3 mmHg. The standard deviation of differences (ICP - nICP) was 5.6 mmHg. The 95 % confidence interval of ICP prediction ranged from -9.6 to 12.3 mmHg. Mean ICP was 16.7 mmHg and mean nICP was 18.0 mmHg. When nICP was adjusted by their difference 1.3 mmHg (nICPadj = nICP - 1.3), the 95 % confidence limits of ICP prediction became ±11.0 mmHg. In recordings with highly dynamic ICP signals (n = 27), ICP and nICP correlated on average with R = 0.51 ± 0.47. CONCLUSIONS: nICP assessment showed reasonable accuracy and may be used in clinical studies of patients without any indication for ICP probe implantation.

Is Impaired Autoregulation Associated with Mortality in Patients with Severe Cerebral Diseases?

BACKGROUND: Cerebral autoregulation (CA) is a mechanism that compensates for variations in cerebral perfusion pressure (CPP) by changes in cerebral blood flow resistance to keep the cerebral blood flow constant. In this study, the relationship between lethal outcome during hospitalisation and the autoregulation-related indices PRx and Mx was investigated. MATERIALS AND METHODS: Thirty patients (aged 18-77 years, mean 53 ± 16 years) with severe cerebral diseases were studied. Cerebral blood flow velocity (CBFV), arterial blood pressure (ABP) and intracranial pressure (ICP) were repeatedly recorded. CA indices were calculated as the averaged correlation between CBFV and CPP (Mx) and between ABP and ICP (PRx). Positive index values indicated impairment of CA. RESULTS: Six patients died in hospital. In this group both PRx and Mx were significantly higher than in the group of survivors (PRx: 0.41 ± 0.33 vs 0.09 ± 0.25; Mx: 0.28 ± 0.40 vs 0.03 ± 0.21; p = 0.01 and 0.04, respectively). PRx and Mx correlated significantly with Glasgow Outcome Scale (GOS) score (PRx: R = -0.40, p < 0.05; Mx: R = -0.54, p < 0.005). PRx was the only significant risk factor for mortality (p < 0.05, logistic regression). CONCLUSION: Increased PRx and Mx were associated with risk of death in patients with severe cerebral diseases. The relationship with mortality was more pronounced in PRx, whereas Mx showed a better correlation with GOS score.

Autoregulation monitoring and outcome prediction in neurocritical care patients: Does one index fit all?

Indexes PRx and Mx have been formerly introduced to assess cerebral autoregulation and have been shown to be associated with 3-month clinical outcome. In a mixed cohort of neurocritical care patients, we retrospectively investigated the impact of selected clinical characteristics on this association. Forty-one patients (18-77 years) with severe traumatic (TBI, N = 20) and non-traumatic (N = 21) brain injuries were studied. Cerebral blood flow velocity, arterial blood pressure and intracranial pressure were repeatedly recorded during 1-h periods. Calculated PRx and Mx were correlated with 3-month clinical outcome score of modified Rankin Scale (mRS) in different subgroups with specific clinical characteristics. Both PRx and Mx correlated significantly with outcome (PRx: r = 0.38, p < 0.05; AUC = 0.64, n.s./Mx: r = 0.48, p < 0.005; AUC = 0.80, p < 0.005) in the overall group, and in patients with hemicraniectomy (N = 17; PRx: r = 0.73, p < 0.001; AUC = 0.89, p < 0.01/Mx: r = 0.69, p < 0.005; AUC = 0.87, p < 0.05). Mx, not PRx, correlated significantly with mRS in patients with heart failure (N = 17; r = 0.69, p < 0.005; AUC = 0.92, p < 0.005), and in non-traumatic patients (r = 0.49, p < 0.05; AUC = 0.79, p < 0.05). PRx, not Mx, correlated significantly with mRS in TBI patients (r = 0.63, p < 0.01; AUC = 0.89, p < 0.01). Both indexes did not correlate with mRS in diabetes patients (N = 15), PRx failed in hypocapnic patients (N = 26). Both PRx and Mx were significantly associated with 3-month clinical outcome, even in patients with hemicraniectomy. PRx was more appropriate for TBI patients, while Mx was better suited for non-traumatic patients and patients with heart failure. Prognostic values of indexes were affected by diabetes (both Mx and PRx) and hypocapnia (PRx only).

[Patterns of dysfunctional parenting styles and psychological disturbances in offspring]. / Muster dysfunktionaler Erziehungsstile und psychische Storungen im Erwachsenenalter.

OBJECTIVES: Dysfunctional parenting styles represent a risk factor for the development of psychological disturbances. The present study investigated the differential validity of the German language Fragebogen zur Erfassung dysfunktionaler Erziehungsstile (FDEB; Measurement of Parental Styles, MOPS) and determined whether different forms of psychological disorders are associated with specific patterns of parenting styles. METHODS: 145 inpatients, 108 outpatients and a control group of 633 representative individuals from the general population were investigated by adapting the FDEB. RESULTS: A comparison of dysfunctional parenting styles showed different distress levels within the diagnostic groups: Patients suffering from depression reported high levels of maternal indifference and over protectiveness together with an abusive rearing behavior on the part of both parents. Patients with anxiety disorders reported having overprotective mothers. Bulimic patients as well as those with personality disorders significantly exhibited stress in almost all areas. However, anorexic patients did not differ significantly from the control group, which appeared to be the least affected of all. CONCLUSION: The FDEB showed a satisfactory differential validity. There was evidence that specific patterns of dysfunctional parenting styles were associated with different diagnostic groups.

Methodological aspects of functional transcranial Doppler sonography and recommendations for simultaneous EEG recording.

The neurovascular coupling describes a vasoregulative principle of the brain that adapts local cerebral blood flow in accordance with the underlying neuronal activity. It is the basis of modern indirect brain imaging techniques. Because of its wide availability and high tolerability the functional transcranial Doppler has been often used to assess brain function in clinical conditions. In the present paper we will give an overview of the current understanding of the coupling, explain basic principles of the Doppler technique and summarize relevant findings of functional Doppler tests in the different vascular territories of the brain. Finally, the concept of a combined functional electroencephalogram and transcranial Doppler technique will be outlined, which allows simultaneous investigation of the neuronal and vascular responses of neurovascular coupling.

Non-invasively estimated ICP pulse amplitude strongly correlates with outcome after TBI.

INTRODUCTION: An existing monitoring database of brain signal recordings in patients with head injury has been re-evaluated with regard to the accuracy of estimation of non-invasive ICP (nICP) and its components, with a particular interest in the implications for outcome after head injury. METHODS: Middle cerebral artery blood flow velocity (FV), ICP and arterial blood pressure (ABP) were recorded. Non-invasive ICP (nICP) was calculated using a mathematical model. Other signals analysed included components of ICP (n" indicates non-invasive): ICP pulse amplitude (Amp, nAmp), amplitude of the respiratory component (Resp, nResp), amplitude of slow vasogenic waves of ICP (Slow, nSlow) and index of compensatory reserve (RAP, nRAP). Mean values of analysed signals were compared against each other and between patients who died and survived. RESULTS: The correlation between ICP and nICP was moderately strong, R = 0.51 (95% prediction interval [PI] 17 mm Hg). The components of nICP and ICP were also moderately correlated with each other: the strongest correlation was observed for Resp vs. nResp (r = 0.66), while weaker for Amp vs. nAmp (r = 0.41). Non-invasive pulse amplitude of ICP showed the strongest association with outcome, with the -difference between those who survived and those who died reaching a significance level of p < 0.000001. DISCUSSION: When compared between patients who died and who survived mean nAmp showed the greatest difference, suggesting its potential to predict mortality after TBI.

Cerebral autoregulatory response depends on the direction of change in perfusion pressure.

The purpose of cerebral autoregulation is to keep cerebral blood flow constant during variations of cerebral perfusion pressure (CPP). Recently, the autoregulatory response was reported to be greater during arterial blood pressure (ABP) increase than during decrease following repeated induced changes in ABP in 14 brain-injured subjects. The goal of this study was to further investigate the asymmetry of autoregulation during spontaneous increases and decreases of CPP in a larger group of brain injury patients. Data recordings (N=727) of CPP and cerebral blood flow velocity (CBFV) in 210 subjects with traumatic brain injury (TBI) were studied. Autoregulation was assessed using moving correlation indices (Mx) between CPP and CBFV. Periods of increasing and decreasing CPP were separately correlated to corresponding CBFV in order to assess autoregulatory responses to upward (upMx) and downward (downMx) changes of CPP. These correlation indices range from -1 to +1; negative or zero values indicate intact autoregulation, whereas positive values indicate impaired autoregulation. Only data with defined strong CPP variations were evaluated. Strong CPP variations were found in 84 recordings of 53 patients. On average (+/-SD) upMx was significantly lower than downMx (0.05+/-0.49 versus 0.14+/-0.54; p < 0.005). Despite this difference, upMx and downMx were strongly correlated with each other (R=0.82; p < 0.001). In conclusion, the autoregulatory response was significantly greater during increase than during decrease in CPP. The results may indicate non-linear behavior of cerebral autoregulation.

Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial.

BACKGROUND AND PURPOSE: Patients with stroke are at substantial risk of thromboembolic complications and therefore require antithrombotic prophylaxis. To show the noninferiority of the low-molecular-weight heparin certoparin to unfractionated heparin (UFH) for the prevention of thromboembolic complications, we performed a randomized, double-blind, active-controlled multicenter trial in patients with acute ischemic stroke. METHODS: Overall, 545 patients were randomized within 24 hours of stroke onset to treatment with certoparin (3000 U anti-Xa OD; n=272) or UFH (5000 U TID; n=273) for 12 to 16 days. Patients with paresis of a leg and an National Institutes of Health Stroke Scale score of 4 to 30 points were included. The primary end point was a composite outcome of proximal deep vein thrombosis, pulmonary embolism, or death related to venous thromboembolism during treatment. Computed tomography was performed at trial entry, after 7 days, and when clinical deterioration occurred. RESULTS: The per-protocol analysis revealed 17 (7.0%) primary events in the certoparin group compared with 24 (9.7%) in the UFH group, thereby demonstrating noninferiority (P=0.0011), confirmed by intention-to-treat analysis (6.6% versus 8.8%; P=0.008). Major bleeding occurred during treatment in 3 patients allocated to certoparin (1.1%) and 5 patients allocated to UFH (1.8%). CONCLUSIONS: Certoparin (3000 U anti-Xa OD) is at least as effective and safe as UFH (TID) for the prevention of thromboembolic complications in patients with acute ischemic stroke.

[Screening and Measurement of Change of Dissociative Psychopathology: Psychometric Properties of the Short Version of the Fragebogen zu Dissoziativen Symptomen (FDS-20)]. / Screening und Veränderungsmessung dissoziativer Psychopathologie: Psychometrische Charakteristika der Kurzform des Fragebogens zu dissoziativen Symptomen (FDS-20).

Given the clinical and scientific relevance of dissociative experiences our study aimed to assess the psychometric properties of a short version of the German Dissociative Experience Scale (called FDS-20) as well as its ability to measure changes in dissociation. In a large sample (N = 1289) the FDS- 20 showed good internal consistency. A factor analysis indicated that the scale measures one single factor reflecting the general degree of dissociative psychopathology. Between-group-comparisons suggested a good discriminant validity between high and low dissociators; however, due to high standard deviations the FDS-20 is not well suited for an individual diagnosis and therefore, it should be used as a screening device. Low effect sizes (d < 0,3) between scores at the beginning and the end of inpatient treatment as well as low micro -indices pointed to a temporal stable construct and a trait scale, respectively. Alternatively to group comparisons, individual parameters of treatment success (statistical and clinical significance) were calculated. They proved to be more appropriate in measuring changes in dissociation.

Progression of early carotid atherosclerosis is only temporarily reduced after antibiotic treatment of Chlamydia pneumoniae seropositivity.

BACKGROUND: Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and cardiovascular events. There are controversial results regarding the beneficial effects of antibiotic therapy on future cardiovascular end points. METHODS AND RESULTS: We determined the long-term effect of a 30-day roxithromycin therapy on intima-to-media thickness (IMT) progression of the common carotid artery in 272 consecutive Cp-positive and Cp-negative patients with ischemic stroke in a prospective, double-blind, randomized trial with a follow-up of 4 years. Cp IgG (> or =1:64) or IgA (> or =1:16) antibodies were initially found in 125 (46%) patients. During the 3 years before antibiotic therapy, Cp-positive patients showed an enhanced IMT progression even after adjustment for other cardiovascular risk factors (0.12 [0.11 to 0.14] versus 0.07 [0.05 to 0.09] mm/year; P<0.005). The 62 Cp-positive patients given roxithromycin showed a reduced IMT progression during the first 2 years compared with the Cp-positive patients without therapy (0.07 [0.045 to 0.095] versus 0.11 [0.088 to 0.132] mm/year; P<0.01). However, IMT progression increased again during the third and fourth year to similar values as before treatment. No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up. CONCLUSIONS: The only limited positive impact of antibiotic therapy on early atherosclerosis progression in Cp-positive patients observed in our study may explain the negative results of most antibiotic trials on clinical end points.

A truly simultaneous combination of functional transcranial Doppler sonography and H(2)(15)O PET adds fundamental new information on differences in cognitive activation between schizophrenics and healthy control subjects.

UNLABELLED: Working memory deficits are a cardinal feature of the pathophysiology of schizophrenia. Lesion studies and functional blood flow-dependent imaging methods with coarse temporal resolution, such as PET and functional MRI (fMRI), tend to paint a fairly static picture of the cortical regions involved. In contrast, functional transcranial Doppler sonography (fTCD) provides a high temporal resolution. Truly simultaneous fTCD-fMRI is not yet possible for technical reasons, but H(2)(15)O PET and fTCD can be used really simultaneously. However, this combination has not yet been used for cognitive activations in schizophrenia. We therefore investigated the extent to which there are both spatial (PET) and temporal changes (fTCD) in the activation patterns of schizophrenic patients. METHODS: Eleven clinically stable chronic schizophrenic, right-handed patients and 10 healthy, right-handed control subjects, matched for age, sex, education, and intelligence quotient, participated in the study. We selected stable chronic schizophrenic patients who could perform a working memory task (N-back task) as well as healthy volunteers to exclude the possibility of imaged artifacts due to poor performance. All subjects were examined with a truly simultaneous fTCD-H(2)(15)O PET combination under cognitive activation. RESULTS: Schizophrenic patients activate a significantly larger cortical volume for adequate task performance (P < 0.05), but with a significantly lower blood flow increase in this volume (P < 0.01), than do control subjects. Furthermore, they cannot significantly increase blood flow velocity during the time course of cognitive activation as control subjects do. There were only significant correlations between neuropsychologic performance and imaging parameters (fTCD changes, PET blood flow changes) in control subjects (all r >or= /0.65/; P < 0.05), but no significant correlations in schizophrenics (all r < /0.3/; P > 0.4). CONCLUSION: We demonstrated that schizophrenic patients exhibit qualitative differences in the spatial and temporal resolution of cognitive processing. All facts could be interpreted as a sign of alternative, less efficient problem-solving strategies in schizophrenia that lead to the working memory deficits observed during the further course of this disease. Truly simultaneous fTCD-PET can be used in neuroscience to add fundamental new information on spatial and temporal cognitive activation behavior to understand the true physiologic nature of the disease-specific differences of mental illnesses that are seen as disorders of the mind arising in the brain.

Adaptive noninvasive assessment of intracranial pressure and cerebral autoregulation.

BACKGROUND AND PURPOSE: A mathematical model has previously been introduced to estimate noninvasively intracranial pressure (nICP). In the present multicenter study, we investigated the ability of model to adapt to the state of cerebral autoregulation (SCA). This modification was intended to improve the quality of nICP estimation and noninvasive assessment of pressure reactivity of the cerebrovascular system. METHODS: We studied 145 patients after severe head injuries or stroke. All patients had direct ICP, arterial blood pressure (ABP), and transcranial Doppler middle cerebral artery blood flow velocity (FV) monitored. The SCA was assessed by moving correlation (Mx index) of cerebral perfusion pressure (CPP=ABP-ICP) and cerebral blood flow velocity and correlation of ABP and ICP (PRx index). nICP was calculated from ABP and FV waveforms. When nICP was used instead of ICP, the SCA was continuously estimated, and the model was dynamically adapted to the SCA. RESULTS: High and moderate correlations between invasively (Mx, PRx) and noninvasively (nMx, nPRx) estimated autoregulation indexes were observed (Mx: R=0.90, P<0.001; PRx: R=0.62, P<0.001). Values of Mx and nMx indicated contradictory SCA in 4 of 167 evaluated recordings; values of PRx and nPRx were contradictory in 27 recordings. When the model was adapted to the SCA, the mean error of ICP estimation decreased significantly (P<0.005). CONCLUSIONS: Continuous adaptation of the model to SCA improves the accuracy of noninvasive estimation of ICP and ICP dynamics. The same model provides a noninvasive and continuous assessment of SCA.

Clinical applications of a non-invasive ICP monitoring method.

BACKGROUND AND PURPOSE: Until now the assessment of intracranial pressure (ICP) requires invasive methods. A previously introduced mathematical model allowed the non-invasive estimation of ICP (nICP) from arterial blood pressure (ABP) and blood flow velocity (FV). In various studies we have investigated the accuracy of this method and possible clinical applications. METHODS AND RESULTS: Selected hemodynamic parameters, calculated from the cerebral blood FV and the ABP curves, were used to express the relationship between ABP input and ICP output by linear transformation rules. In several clinical studies the accuracy and possible benefits of this method of non-invasive ICP (nICP) assessment were investigated. ASSESSMENT OF ICP PLATEAU WAVES: In 17 severely head injured patients we verified this model by comparison of nICP and measured ICP during generation of plateau waves, recorded in seven of these patients. In all simulations plateau elevations of ICP were well replicated. The correlation coefficient between increase of nICP and real ICP was R=0.98; P<0.001. LUMBAR INFUSION TESTS: Twenty one hydrocephalic patients were studied. Parallel increases in real ICP and nICP during lumbar infusion tests were evidently visible. Resistance of cerebrospinal fluid outflow (Rcsf) was computed using nICP and compared with Rcsf computed from real ICP. The mean error between real and non-invasive Rcsf was 4.1+/-2.2 mmHg min/ml. CEREBRAL AUTOREGULATION: One hundred and forty five patients were studied after severe head injuries. The state of autoregulation was assessed by moving correlation of cerebral perfusion pressure (CPP=ABP-ICP) and FV (Mx index). nICP instead of ICP was used to continuously estimate the state of autoregulation and to dynamically adapt the nICP procedure to this state. A median error between ICP and nICP of 6.0 mmHg was observed. Directly and non-invasively assessed Mx indices correlated highly significantly (R=0.9; P<0.001). CONCLUSIONS: The results demonstrate that the nICP assessment model constitutes a reliable method to monitor ICP and may therefore provide various useful clinical applications.

Reduced progression of early carotid atherosclerosis after antibiotic treatment and Chlamydia pneumoniae seropositivity.

BACKGROUND: Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis, and a beneficial effect of antibiotic therapy on future cardiovascular events was described. METHODS AND RESULTS: We evaluated the effect of roxithromycin therapy (150 mg twice daily for 30 days) on the progression of the intima-to-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective and randomized trial with a follow-up of 2 years in 272 consecutive patients with ischemic stroke aged over 55 years in whom the first IMT measurement and Cp testing (IgG and IgA) were performed at least 3 years before the roxithromycin treatment. Cp IgG antibodies (> or =1:64) were initially found in 123 (45%) patients and IgA antibodies (> or =1:16) in 112 (41%) patients. During the 3 years before antibiotic therapy, Cp-positive patients showed an enhanced IMT progression, even after adjustment for other cardiovascular risk factors (0.12 [95% CI, 0.11 to 0.14] versus 0.07 [0.05 to 0.09] mm/year; P<0.005). The 62 Cp-positive patients given roxithromycin showed a significantly decreased IMT progression after 2 years compared with the Cp-positive patients without therapy (0.07 [0.045 to 0.095] versus 0.11 [0.088 to 0.132] mm/year; P<0.01). No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up. No change of IMT was observed in Cp-negative patients given roxithromycin (n=74) compared with those without therapy (0.06 [0.03 to 0.09] versus 0.07 [0.05 to 0.09] mm/year). CONCLUSIONS: Our findings suggest a positive impact of antibiotic therapy on early atherosclerosis progression in Cp-seropositive patients with cerebrovascular disease.

Elevated C-reactive protein is associated with an increased intima to media thickness of the common carotid artery.

In this study, we analyzed the relationship between serum C-reactive protein (CRP) and the intima to media thickness (IMT) of the common carotid artery in 411 consecutive neurological inpatients (215 males, mean age 64.1 years). The CRP concentration was determined within 12 h and patients were subdivided according to the CRP level. Patients with an elevated CRP (n = 149) showed a significantly larger IMT [1.05 mm (95% confidence interval (CI) 1.02-1.09) vs. 0.92 mm (95% CI 0.89-0.94)]. Multivariate linear regression analysis revealed that an elevated CRP level, age, pack-years of smoking, body mass index, incidence of diabetes mellitus and ischemic stroke were independently associated with an increased IMT (p < 0.05).