Martin Müller

Differential release of interleukines 6, 8, and 10 in cerebrospinal fluid and plasma after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by a high mortality which is largely determined by the initial cerebral trauma, secondary brain injury or indirectly during a Multiple Organ Dysfunction Syndrome (MODS). Therefore, we analyzed IL-6, IL-8, and IL-10 in cerebrospinal fluid (CSF) and in plasma with respect to blood-brain barrier (BBB) integrity in 29 patients suffering from isolated TBI. IL-6 and IL-8 were significantly increased compared to baseline levels early after trauma in CSF and plasma. In all patients CSF IL-6 and IL-8 were found to be higher than corresponding plasma levels. IL-10 in plasma was significantly increased above control plasma values, however, without a significant difference to the corresponding CSF values. BBB dysfunction was temporary present in 23 patients. Significant correlations between BBB dysfunction and cytokines were not found. Thus, alterations of the BBB seems not to influence the distribution pattern of interleukines in CSF and plasma after trauma.

Prediction of Recurrent Stroke and Vascular Death in Patients With Transient Ischemic Attack or Nondisabling Stroke. A Prospective Comparison of Validated Prognostic Scores

Background and Purpose— Several predictive scores have been developed and validated for stratifying cerebrovascular patients based on the risk of future (cerebro)vascular events. We aimed to prospectively compare the predictive accuracy of the Essen Stroke Risk Score, Stroke Prognostic Instrument, Hankey score, and the Life Long After Cerebral ischemia score. Methods— Between August 2005 and December 2006, we included 2381 patients from 10 German stroke centers with an acute nondisabling ischemic stroke or transient ischemic attack and with prospective assessment of clinical variables for calculation of the predictive scores. A total of 1897 patients (79.7%) could be followed up for a median of 1 year. To evaluate the performance of each model, we calculated the area under the curve by receiver operating characteristic. In addition, we used the recommended cutoff values for calculation of sensitivity and specificity for stroke or the combined outcome of stroke or cardiovascular death. Results— The Kaplan–Meier estimate for the overall annual stroke risk was 4.8% and for recurrent stroke or cardiovascular death 6.6%. We could confirm the predictive value of all 4 previously developed scores with a marginally superior performance of the SPI-II. Conclusions— In patients with acute nondisabling ischemic stroke or transient ischemic attack, all 4 scores are able to stratify the risk of recurrent stroke or the combined outcome. Simple point scores (Essen Stroke Risk Score, Stroke Prognostic Instrument) may help to raise awareness for medical prevention in clinical routine and increase compliance with risk factor modification.

Clinical Relevance and Frequency of Transient Stenoses of the Middle and Anterior Cerebral Arteries in Bacterial Meningitis

BACKGROUND AND PURPOSE We sought to examine the frequency and clinical relevance of intracranial artery stenoses in patients with bacterial meningitis in whom the occurrence of stroke has angiographically been reported to be associated with stenoses or occlusions of the large basal cerebral arteries. METHODS Thirty-five unselected patients (24 men, 11 women; mean age, 51 +/- 18 years) with bacterial (n = 33) or fungal (n = 2) meningitis prospectively underwent serial transcranial Doppler sonography recordings of mean blood velocity (MBV) and pulsatility index in the middle (MCA) and anterior (ACA) cerebral arteries, as well as recordings of the ratio of the MBV of the MCA and internal carotid artery (MCA/ICA ratio) on days 1, 3, 5, 8, 14, and 21 after admission. The results were correlated with the Glasgow Coma Scale (days 1 to 14), the occurrence of focal cerebral signs, and the Glasgow Outcome Scale (short-term outcome, day 21). An MCA stenosis was diagnosed by an MBV of 120 cm/s or more or an MCA/ICA ratio of more than 3. An ACA stenosis was diagnosed by an MBV of 100 cm/s or more. RESULTS Transient stenoses occurred most frequently between days 3 and 5 and were detected in 18 patients (51%). Seventeen patients remained without a stenosis. Patients with stenoses showed a significantly poorer mean Glasgow Coma Scale score from day 3 (9 +/- 4) to day 14 (11 +/- 4) than patients without a stenosis (day 3: 13 +/- 4, P < .01 by t test; day 14: 14 +/- 1, P < .05). The mean Glasgow Outcome Scale score was not significantly different between both groups. The occurrence of mainly transient focal cerebral signs was significantly related to the number of narrowed vessels per patient (P < .05, chi 2 test). CONCLUSIONS Stenoses of the intracranial arteries occur frequently in bacterial meningitis and are associated with a complicated course of the disease.

The Linear Behavior of the System Middle Cerebral Artery Flow Velocity and Blood Pressure in Patients With Migraine Lack of Autonomic Control

Background and Purpose— Migraine is considered a disorder of the autonomic nervous system. We used the frequency analysis of dynamic cerebral autoregulation to assess whether blood flow regulation disturbances can be found at the frequencies at which sympathetic and parasympathetic activity is present. Methods— We measured simultaneously mean arterial blood pressure (BP) and the mean blood velocity (V) in the middle cerebral artery using transcranial Doppler ultrasound in 33 healthy controls (mean age±SD; 36±13 years) and in 22 patients with migraine (mean age; 39±7 years). Apart from assessing spectral power density for BP and V, we calculated the transfer function parameters gain, phase, and coherence at the frequency range between 0.0 and 0.25 Hz. Results— Compared with the controls, the spectral power density of BP and V exhibited a maximum magnitude of 1026 in the migraine patients, whereas the maximum magnitude of BP and V in the controls was 10−3. Coherence showed no difference between patients and controls. Gain between BP and V increased in the controls >0.01 Hz but was ≈0 or negative in the migraine patients over the whole frequency range (P<0.01). The usually observed phase lead of V against BP was absent in the migraine patients in whom BP leaded V over nearly the whole frequency range (P<0.01). Conclusions— In terms of phase and gain, dynamic cerebral autoregulation is completely different in migraine patients compared with healthy subjects. Insofar, this can be interpreted as a lack of sympathetic and parasympathetic control of cerebral blood flow.

The use of clinical scales in depicting cerebrovascular complications in bacterial meningitis.

To evaluate the utility of different scales for clinical assessment, over time, in acute bacterial meningitis, the authors investigated 53 consecutive patients (mean age 53 ± 17 years). Clinical status on days 1, 3, 5, 8, and 14 after admission was determined by the Scandinavian Stroke Scale (SSS), Glasgow Coma Scale (GCS), and Hunt and Hess Scale (HH), and, on day 21, by the Glasgow Outcome Scale (GOS). Transcranial Doppler examinations were performed serially to assess for disease‐related arterial narrowing. This was observed in 27 patients (51%) within 2 weeks of admission. All scales were observed to correlate with the 21‐day GOS. Patients with cerebral arterial narrowing had significantly decreased SSS scores between days 1 and 8 and worse GCS and HH scores between days 3 and 5. Mean blood flow velocity in the middle cerebral artery on days 5 and 8 significantly correlated with GOS (r= 0.268, P < .008; r=−0.324, P < .003, respectively). The use of such clinical scales allows standardized assessment of patients with bacterial meningitis and provides prognostic information. Cerebral arterial narrowing was observed to correlate with neurologic impairment.

Cerebral blood flow velocity and inflammatory response after severe traumatic brain injury

OBJECTIVES The cerebral blood flow velocity (CBVF) was measured by transcranial Doppler sonography in patients with severe traumatic brain injury (TBI) in order to determine, whether it depends on the posttraumatic inflammatory response. MATERIAL AND METHODS CBVF in both middle cerebral arteries (MCA) was recorded in 25 comatous TBI patients (male 20; female five; mean age +/- standard deviation (S.D.), 41 +/- 20 years) and correlated to the levels of interleukine-(IL) 6, IL-8 and IL-10 in corresponding CSF/plasma samples, to PaCO2 and to intracranial (ICP), mean arterial (MAP) and cranial perfusion pressure (CPP). RESULTS CSF IL-6 and IL-8 were clearly higher than the corresponding plasma levels (mean CSF/plasma quotient for IL-6: 159 +/- 582; for IL-8: 143 +/- 311). CBVF did not show large side-to-side differences at each examination indicating that CBFV in both MCAs was determined mostly by systemic conditions and not by severe regional abnormalities. Since all other evaluated variables including interleukines represent also systemic conditions we used the mean value (MCBFV) of both CBFVs for analysis. By stepwise regression analysis between MCBVF (mean +/- S.D., 80 +/- 26 cm/s) and the variables PaCO2 (33 +/- 4 mmHg), MAP (86 +/- 12 mmHg), ICP (20 +/- 11 mmHg), CPP (70 +/- 14 mmHg) and CSF or plasma IL-6, IL-8 and IL-10, it turned out that MCBFV correlated significantly with PaCO2 (r = 0.478; P < 0.01) and CSF IL-8 (r = -0.361; P < 0.05). CONCLUSIONS When CPP is adequate for brain perfusion, CBFV in large brain supplying arteries depends predominantly on PaCO2 and shows only a slight association to intrathecal IL-8 levels. For clinical interpretation of CBFV data, the inflammatory response seems to be of minor relevance.

Assessment of middle cerebral artery diameter after aneurysmal subarachnoid hemorrhage by transcranial color-coded duplex sonography

This study examined if vasospasm after aneurysmal subarachnoid hemorrhage could be visualized by middle cerebral artery (MCA) diameter changes in transcranial color-coded duplex sonography (TCCS). Comparative measurements between mean blood velocity (MBV) and MCA diameter were carried out in 17 patients in 76 instances. At two depth ranges (proximal, 60 55 mm: distal, 50-45 mm) two observers assessed the MCA diameter as indicated by the visualized blood flow column. At both points of measurement, the diameter differences between the two observers were within the ¿ 2 S.D. range of the mean difference indicating interobserver agreement. In 17 instances, MBV was > 120 cm/s indicating vasospasm but MBV did not correlate with absolute or relative diameter changes. MCA diameter assessment in TCCS seems reproducible. Because TCCS imaging is influenced by several factors comparative angiographic studies are necessary to clarify the TCCS findings.

Variability of velocity and duration of microembolic signals detected by bigated transcranial Doppler sonography in carotid endarterectomy

OBJECTIVE To differentiate between gaseous and particular microemboli in carotid surgery one clinical approach is the interpretation of the effective sample volume length (SVL). We investigated whether such a clinical interpretation is based on reproducible measurements. METHODS Microembolic signals (MES) recorded during carotid endarterectomy by a bigated transcranial Doppler device were analyzed off-line. In the two sample volumes, the duration and the velocity of the MES were measured by two observers independently from each other twice within 2 weeks. The SVL of the MES were calculated by multiplying duration with velocity. RESULTS In the anatomical proximal sample volume 215 MES were recorded of which 203 (94.5%) were also present in the distal. The SVL medians of the MES were 2.2-4.1 mm lower in the distal than in the proximal sample volume as a result of lower velocity and shorter duration of the MES in the distal sample volume. The median of the paired differences of the SVL was 0.2 mm (interquartile range: 0.0-1.2) in the proximal sample volume and 0.8 mm (0.2-1.8) in the distal sample volume for observer 1, and 0.6 mm (0.4-2.2) and 0.9 mm (0.5-1.6) for observer 2. The median of the paired differences of the SVL between the observers was 1.4 mm (1.2-2.9) in the proximal sample volume and 1.6 mm (1.3-3.0) in the distal. CONCLUSION The intra- and interobserver agreement on calculating SVL is good. However, the depth of insonation influences some features of embolic signals.