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Background and purpose External counterpulsation improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non-acute) at-risk patients with high-grade carotid artery disease may benefit from counterpulsation needs to be validated. Methods Twenty-eight patients (71 ± 6.5 years, five women) with asymptomatic unilateral chronic severe internal carotid artery stenosis (>70%) or occlusion were randomized to receive 20 min active counterpulsation followed by sham treatment or vice versa. Cerebral blood flow velocity (CBFV) (measured bilaterally by transcranial middle cerebral artery Doppler), tissue oxygenation index (TOI) (measured over the bilateral prefrontal cortex by near-infrared spectroscopy) and cerebral hemodynamic parameters, such as relative pulse slope index (RPSI), were monitored. Results Ipsilateral mean CBFV (ΔVmean +3.5 ± 1.2 cm/s) and tissue oxygenation (ΔTOI +2.86 ± 0.8) increased significantly during active counterpulsation compared to baseline, whilst the sham had little effect (ΔVmean +1.13 ± 1.1 cm/s; ΔTOI +1.25 ± 0.65). On contralateral sides, neither counterpulsation nor sham control had any effect on either parameter. During counterpulsation, early dynamic changes in ΔRPSI of the ipsilateral CBFV signal predicted improved tissue oxygenation during counterpulsation (odds ratio 1.179, 95% confidence interval 1.01-1.51), whilst baseline cerebrovascular reactivity to hypercapnia failed to show an association. Conclusions In patients with high-grade carotid disease, ipsilateral cerebral oxygenation and blood flow velocity are increased by counterpulsation. This is a necessary condition for the stimulation of regenerative collateral artery growth and thus a therapeutic concept for the prevention of cerebral ischaemia. This study provides a rationale for further clinical investigations on the long-term effects of counterpulsation on cerebral hemodynamics and collateral growth.

Background Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. Methods SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. Findings It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. Interpretation The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Background The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS). Methods Patients with anterior AIS, baseline NIHSS 7–20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients. Results Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001). Conclusion The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236). CA extern

To assess the usefulness of transcranial Doppler CO2 reactivity (CO2R) for prediction of ipsilateral ischemic stroke in carotid artery stenosis and occlusion with a meta-analysis of prospective studies based on individual patient data.We searched Medline, Biosis Previews, Science Citation Index, The Cochrane Library, and EMBASE for studies in which patients with severe carotid artery stenosis or occlusion underwent Doppler CO2R testing (inhalation of CO2 or breath-holding) and were prospectively followed for ipsilateral ischemic stroke. Individual data from 754 patients from 9 studies were included. We used percentage cerebral blood flow velocity increase (pCi) during hypercapnia as the primary CO2R measure, and defined impaired reactivity as pCi20% increase.In a multiple regression model, impaired CO2R was independently associated with an increased risk of ipsilateral ischemic stroke (hazard ratio [HR] 3.69; confidence interval [CI] 2.01, 6.77; p0.0001). Risk prediction was similar for recently symptomatic vs asymptomatic patients. Using continuous values of pCi, a significant association between decreasing pCi and increasing risk of ipsilateral stroke was found: HR of 1.64 (95% CI 1.33, 2.02; p0.0001) per 10% decrease in pCi. For patients with asymptomatic internal carotid artery stenosis only (n = 330), a comparable stroke risk prediction was found: increasing HR 1.95 (95% CI 1.26, 3.04; p = 0.003) per 10% decrease in pCi.This analysis supports the usefulness of CO2R in risk prediction for patients with severe carotid artery stenosis or occlusion, both in recently symptomatic and asymptomatic patients. Further studies should evaluate whether treatment strategies in asymptomatic patients based on CO2R could improve patient outcomes.

Post-traumatic growth (PTG) is the experience of positive changes that can follow a traumatic event. The current study examined the factorial as well as the discriminant validity of the German version of the Post-traumatic Growth Inventory (PTGI-G) in stroke patients. A total of 188 adult stroke patients (63.3% male; median age 69 years) completed the PTGI-G and the German version of the Hospital Anxiety and Depression Scale (HADS-D) at the end of their inpatient rehabilitation. Confirmatory factor analyses indicate an acceptable model fit of both the original five-factor solution as well as a second-order factor model of the PTGI-G (CFI > .95; RMSEA < .01). Small and non-significant correlations between the PTGI-G subscales and the depression scale of the HADS-D support the discriminant validity of the PTGI-G. The PTGI-G appears to be a valid tool in the context of stroke research.

Summary Cerebral autoregulation is particularly challenged in acute ischemic stroke. In this review we summarize the data of our previous studies on autoregulation regarding the effect of rtPA on autoregulation after stroke. A pooled analysis of two studies (45 patients) has shown a worsening of the autoregulatory index Mx between an early (first 48 h) and late (days 5–7) measurement. This increase was more pronounced on affected sides than on unaffected sides. Poor ipsilateral Mx was associated with a greater volume of MCA infarction at a late measurement and related to poor clinical outcome. Overall, autoregulatory impairment tends to increase mainly in large infarction and generalize to the contralateral side during the first days after ischemic stroke. As a limitation, transcranial Doppler sonography does not allow to detect focal areas of dysautoregulation in smaller strokes. To better understand the temporal and spatial dynamics of dysautoregulation in acute stroke in relation to the type and size of infarction, new bedside hemodynamic monitoring techniques (like multi-channel near-infrared spectroscopy) are needed.

The controversy as to whether Doppler ultrasonic methods should play a role in clinical decision-making in the prevention of stroke is attributable to reported disagreement between angiographic and ultrasonic results and the lack of internationally accepted ultrasound criteria for describing the degree of stenosis. Foremost among the explanations for both is the broad scatter of peak systolic velocities in the stenosis, the criterion that has so far received most attention. Grading based on a set of main and additional criteria can overcome diagnostic errors. Morphological measurements (B-mode images and color flow imaging) are the main criteria for low and moderate degrees of stenosis. Increased velocities in the stenosis indicate narrowing, but the appearance of collateral flow and decreased poststenotic flow velocity prove a high degree stenosis (≥70%), additionally allowing the estimation of the hemodynamic effect in the category of high-degree stenosis. Additional criteria refer to the effect of a stenosis on prestenotic flow (common carotid artery), the extent of poststenotic flow disturbances, and derived velocity criteria (diastolic peak velocity and the carotid ratio). This multiparametric approach is intended to increase the reliability and the standard of reporting of ultrasonic results for arteriosclerotic disease of the carotid artery.

Reinhard M, Rutsch S, Lambeck J, Wihler C, Czosnyka M, Weiller C, Hetzel A. Dynamic cerebral autoregulation associates with infarct size and outcome after ischemic stroke. Acta Neurol Scand: 2012: 125: 156–162. © 2011 John Wiley & Sons A/S. Objectives – Cerebral autoregulation is particularly challenged in acute ischemic stroke. We investigated (1) clinical and radiological factors related to dynamic cerebral autoregulation (DCA) in acute stroke and (2) the relationship between DCA and clinical outcome of stroke. Methods – A total of 45 patients with middle cerebral artery (MCA) stroke were analyzed pooling two previous studies. DCA was measured by transcranial Doppler in both MCAs early (within 48 h from onset) and late (day 5–7) using low-frequency phase and correlation analysis (index Mx). Outcome was assessed by modified Rankin scale after a mean period of 4 months. Results – Mx increased (i.e. autoregulation worsened) between the early and late measurement, more so on affected (P = 0.005) than on unaffected sides (P = 0.014). Poorer autoregulation as indicated by lower ipsilateral phase (early and late) and higher Mx (late measurement) were significantly related to larger infarction. More severe stroke was significantly related to poorer ipsilateral Mx and phase. Ipsilateral phase in the early (P = 0.019) and Mx in the late measurement (P = 0.016) were related to poor clinical outcome according to univariate analysis. Conclusions – Impairment of DCA ipsilateral to acute ischemic stroke is associated with larger infarction. Dysautoregulation tends to worsen and spread to the contralateral side over the first days post-stroke and is associated with poor clinical outcome.

In internal carotid artery occlusion (ICAO), a spontaneous increase of cerebral vasoreactivity (CVR) may occur over time. Statins are known to increase CVR. We analyzed the influence of statin treatment and other cofactors on CVR improvement in patients with ICAO. Sixty-six patients with ICAO were reexamined after 15 ± 6 months. CVR in both middle cerebral arteries was assessed by transcranial Doppler and inhalation of 7% CO(2). Pre-defined cut-off values were used to define exhausted CVR. Cofactors analyzed were: age, sex, hypertension, diabetes, statin treatment, degree of contralateral stenosis, quality of intracranial collateral flow, duration of ICAO. Mean CVR did not differ between the two studies. Twenty patients had exhausted CVR at baseline, 11 of them improved above the cut-off at follow-up (55%). Factors significantly associated with this improvement were good collateral pattern at baseline (p = 0.0065) and statin treatment (p = 0.0179). Odds ratios for improving CVR were 36.0 [95% CI 2.7-476.3] for good collateral flow and 20.0 [95% CI 1.7-238.6] for statin treatment. In conclusion, exhausted CVR frequently improves during the course of ICAO. Good collateral function and statin treatment are significantly associated with improving CVR.

Blood pressure management in acute intracerebral hemorrhage (ICH) relies on functioning cerebral autoregulation. The time course of autoregulation in acute ICH and its relation with clinical outcome are not known.Twenty-six patients with spontaneous ICH were studied on days 1, 3 and 5 after ictus. Autoregulation was noninvasively measured from spontaneous fluctuations of blood pressure and middle cerebral artery flow velocity (assessed by transcranial Doppler) using the correlation coefficient index Mx. From the same signals, non-invasive cerebral perfusion pressure was calculated. Results were compared with 55 healthy controls and related with clinical and radiological factors and 90-day outcome (modified Rankin scale).Average Mx values of all patients did not differ across days or from controls. Higher Mx (i.e., poorer autoregulation) on day 5 was significantly related with lower Glasgow coma score, ventricular hemorrhage (both sides) and lower noninvasive cerebral perfusion pressure (ipsilateral). Increasing ipsilateral Mx between days 3 and 5 was related with lower Glasgow coma score and ventricular hemorrhage. In a multivariate analysis controlling for other hemodynamic factors, higher ipsilateral Mx on day 5 (p = 0.013) was a significant predictor for poor 90-day outcome.Cerebral autoregulation is primarily preserved in acute ICH, but a secondary decline mainly ipsilateral to the ICH can occur. This is associated with poor clinical status, ventricular hemorrhage, lower cerebral perfusion pressure and worse clinical outcome.

In a prospective study the results of 238 consecutive ultrasound examinations of the carotid artery were correlated with angiography to test the reliability of colour coded duplex sonography in preocclusive carotid artery disease. This series was compared with a series of 611 vessels with angiographically controlled conventional duplex sonography. In 61 resp. 84 cases stenoses > or = 90% or occlusions of the internal carotid artery were found. The reliability of colour coded duplex sonography for the diagnosis of > or = 90% stenoses was extremely high (sensitivity and specificity 98%), as well as in preocclusive, > 95% stenoses (100% and 98%), and for the diagnosis of occlusion, after exclusion of angiographic false positive diagnosis of occlusion (95% and 99%). Statistically colour coded flow imaging failed to increase significantly the high diagnostic sensitivity or specificity of conventional duplex sonography, especially in preocclusive carotid artery disease. However, the remarkable increase in frequency of the diagnosis preocclusive stenosis with the introduction of colour coded Duplex Sonography probably reflects a higher sensitivity of this method. In addition the direct comparison of both ultrasound techniques showed a better image of the vessel wall abnormalities and the residual lumen with colour coded duplex sonography.

A b s t r ac t BACKGROUND Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age. This association has not been established in patients 55 years of age or older. METHODS We prospectively examined 503 consecutive patients who had had a stroke, and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause. We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients, using transesophageal echocardiography. We also compared data for the 131 younger patients (

Background and Purpose— We hypothesized that for the prediction or exclusion of aortic thrombi or plaques ≥4 mm, the combination of intima-media thickness (IMT) and distensibility (DC) of the common carotid arteries would be superior to the measurement of IMT alone. Methods— We prospectively included 208 stroke patients (mean age, 60 years) undergoing transesophageal echocardiography for screening of aortic plaques. IMT and DC were determined by ultrasound, and DC was quantified by measuring blood pressure and the common carotid arteries diameter change on M-mode ultrasound during the cardiac cycle. Results— Negative predictive values of IMT −3 /kPa for the exclusion of aortic atheroma ≥4 mm were similar (92.0% and 91.7%, respectively). However, negative predictive values increased to 98.2% and to 100.0% for the exclusion of aortic thrombi when both parameters were combined. Positive predictive values of IMT ≥0.9 mm and DC Conclusions— Our findings suggest that IMT and DC represent different vessel wall properties and that measuring both parameters provides optimized characterization of carotid atherosclerosis. Combining IMT and DC increases the predictive power of carotid ultrasound, making transesophageal echocardiography dispensable for assessment of the aorta for those with normal carotid arteries and indispensable for those patients with carotid atherosclerosis.

This study investigated (a) the hypothesis that stroke patients with aortic atheroma would show comparable atherosclerotic changes in the carotid arteries, which are easily accessible for ultrasound evaluation and (b) the possibility of carotid duplex sonography as a replacement for transoesophageal echocardiography (TEE) for the exclusion or prediction of relevant aortic plaques.In 301 consecutive patients (mean age 62 years) with acute cerebral ischaemia, two dimensional ultrasound measurements were taken of common carotid artery intima media thickness (IMT) and maximal plaque area (PA) and the local degree of internal carotid artery (ICA) stenosis were determined. Maximal aortic wall thickness (AWT) was assessed by TEE.An IMTor =0.9 mm yielded a negative predictive value (NPV) of 95.8% for exclusion of aortic atheromasor =4 mm and an NPV of 100% for the exclusion of aortic thrombi. However, positive predictive value of IMT0.9 mm was low (29.6%), increasing only slightly in the presence of carotid plaques (33%). Incidence of aortic thrombi was significantly higher withor =50% compared with50% ICA stenosis (11.3% v 3.9%, respectively). IMT and PA correlated moderately with AWT (r = 0.47, r = 0.53, respectively; p0.001). Systolic blood pressure, coronary heart disease and peripheral artery disease, increased IMT, and ICA stenosisor =50% were independently related to AWTor =4 mm.A high NPV of normal carotid ultrasound does not support routine TEE for the exclusion of complex aortic plaques as a high risk source of cerebral embolism. However, in patients with carotid atherosclerosis, particularly in those with ICA stenosisor =50%, TEE should be performed to exclude an additional high risk source for stroke.

Background and Purpose— This study investigates dynamic cerebral autoregulation assessed from spontaneous blood pressure (ABP) and cerebral blood flow velocity (CBFV) fluctuations and its time course in acute ischemic stroke. Methods— Forty patients admitted with acute ischemic stroke in the territory of the middle cerebral artery (MCA) were enrolled. Admission National Institutes of Health Stroke score was 6±4. Study 1 was performed within 22 (±11) hours and study 2 was performed within 134 (±25) hours of ictus. The final analysis comprised 33 and 29 patients for study 1 and study 2, respectively. Twenty-five age- and sex-matched controls were studied. ABP (Finapres method) and CBFV in both MCAs (transcranial Doppler) were recorded over 10 minutes. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged, yielding the correlation coefficient indices (Dx, Mx). Transfer function analysis was applied to obtain phase shift and gain between ABP and CBFV oscillations. Results— No disturbance of autoregulation was indicated by all parameters at study 1. Separate analyses for clinical severity, stroke side, and size did not reveal significant differences for the various autoregulatory indices at study 1 and 2. At study 2, MCA flow velocity was significantly increased on both sides, the autoregulation index Mx was slightly but significantly ( P Conclusions— Dynamic cerebral autoregulation assessed from spontaneous blood pressure fluctuations does not seem to be relevantly disturbed in early minor MCA stroke. At the subacute stage, slight autoregulatory disturbance may be present.

Background and Purpose— Analysis of dynamic cerebral autoregulation (DCA) from spontaneous blood pressure fluctuations might contribute to prognosis of severe internal carotid artery stenosis, but its response to carotid recanalization has not been investigated so far. This study investigates the effect of carotid endarterectomy or stenting on various DCA parameters. Methods— In 58 patients with severe unilateral stenosis undergoing carotid endarterectomy (n=41) or stenting (n=17), cerebral blood flow velocity (CBFV, transcranial Doppler) and arterial blood pressure (ABP, Finapres method) were recorded over 10 minutes before and on average 3 days after carotid recanalization. Nineteen patients were additionally examined after 7 months. Correlations between diastolic and mean ABP and CBFV fluctuations were averaged to form the correlation coefficient indices (diastolic [Dx] and mean values [Mx]). Transfer function parameters (low-frequency phase and high-frequency gain between ABP and CBFV oscillations) were calculated over the same 10 minutes. CO 2 reactivity was assessed via inhalation of 7% CO 2 . Results— Before recanalization, all DCA parameters were clearly impaired ipsilaterally compared with contralateral sides. Phase, Dx, and Mx indicated early normalization of DCA after both endarterectomy and stenting. By multiple regression, the degree of DCA improvement was highly significantly related to the extent of impairment before recanalization. No significant change in DCA was found at follow-up. Ipsilateral gain and CO 2 reactivity increased significantly less after endarterectomy than after stenting ( P Conclusions— Dynamic cerebral dysautoregulation in patients with severe carotid obstruction is readily and completely remedied by carotid recanalization.

OBJECTIVE: To evaluate findings for patients with carotid cavernous fistulae or dural arteriovenous fistuiae (AVFs) who underwent transvenous embolization via different transvenous approaches. METHODS: Retrospective analysis of data for 31 patients (age range, 17-81 yr; mean age, 59.3 yr) with carotid cavernous fistulae (n = 6) or dural AVFs [cavernous sinus [CS], n = 11; transverse/sigmoid sinus, n = 14) was performed. The AVFs were treated with coils via different transvenous approaches, in 56 procedures. Doppler ultrasonography and time-resolved, two-dimensional, magnetic resonance projection angiography were performed to confirm the treatment. The mean clinical follow-up period was 32.5 months. RESULTS: A total of 34 transvenous procedures were performed for 17 AVFs of the CS. Eleven patients with AVFs of the CS (63%) were cured with respect to clinical symptoms, and six patients experienced improvement (37%). The approach via the internal jugular vein and inferior petrosai sinus (n = 15) was possible in 60% of cases, with complete occiusion of the fistula in 78% of cases. With the approach via the facial vein (n = 8), there was a 50% success rate. The superior ophthaimic vein approach (n = 5) was associated with a high rate of technical success (100%), with a rate of complete fistula occlusion of 80%. We encountered complications, with transient morbidity, in four cases (23.5%). For 14 dural AVFs of the transverse/sigmoid sinus, 22 transvenous procedures were performed; 12 patients were cured (85.7%) and 2 experienced improvement (14.3%). The technical success rate was 86%, with complete occlusion in 42% of cases. Minor complications occurred in six cases (42.9%) but did not lead to permanent morbidity. CONCLUSION: Transvenous treatment of CS and transverse/sigmoid sinus AVFs can be effective if all transvenous approaches, including combined surgical/endovascular approaches, are considered.

Eclampsia is frequently associated with brain edema, cerebral infarction or hemorrhage. Its underlying cerebrovascular pathophysiology is still poorly understood. We examined cerebral autoregulation by a non-invasive multimodal assessment in a 28-year-old primaparous woman with postpartal eclampsia. Transcranial Doppler sonography showed considerably increased cerebral blood flow velocity (CBFV) of all basal cerebral vessels. Magnetic resonance imaging demonstrated multifocal vasogenic brain edema. Using transfer function analysis, a severely decreased phase shift between respiratory-induced 0.1-Hz oscillations of arterial blood pressure and CBFV was observed, indicating substantial disturbance of dynamic cerebral autoregulation (DCA). In contrast, CO2-vasomotor reactivity of the right middle cerebral artery was only slightly reduced. We therefore assume that the cerebral arteriolar dysfunction in eclampsia leads primarily to an impairment of the autoregulatory mechanism that is followed by different degrees of arteriolar vasodilation. Because of its probably high sensitivity to hemodynamic disturbances, assessment of DCA might be of great value in early pre-eclampsia for risk prediction of cerebral arteriopathy and eclampsia. Copyright © 2003 ISUOG. Published by John Wiley & Sons, Ltd.

Background: Amplitude responsiveness of cerebral blood flow velocity (CBFV) to CO2 is an established test of cerebrovascular reserve capacity. We aimed to analyze the time course of CBFV during CO2 reactivity testing in patients with severe carotid stenosis. Methods: 87 patients were assigned to three different groups according to the degree of stenosis (A 75–89%, B 90–94%, C 95–100%) and CBFV dynamics was assessed by transcranial Doppler sonography during hypercapnia induced by inhalation of 7% CO2. Time constants for the duration of CBFV and the end-tidal CO2 partial pressure (PetCO2) increase and decrease were calculated. In addition, time delays between subsequent changes of PetCO2 and CBFV during on- and offset of hypercapnia were determined. Results: There was a significant reduction of conventional CO2 reactivity on the side ipsilateral to the stenosis in all groups. Time constants of CBFV showed no major differences between ipsi- and contralateral sides or between different groups. The off delay between the decrease in PetCO2 and the consequent decrease in CBFV was the only out of 6 different dynamic parameters which significantly differentiated critical stenosis and occlusion from severe stenosis. Retest variability showed a highly significant correlation. Conclusions: Analysis of the dynamic CBFV response during the applied CO2 inhalation protocol revealed a significant and reproducible delay parameter which has power to detect cerebral hemodynamic compromise in patients with carotid artery stenosis similar to the conventional CO2 reactivity parameter.

Giant cell arteritis (GCA) is known to affect the extracranial part of the vertebral arteries. Bilateral vertebral artery occlusion (BVAO) is a rare but serious neurologic condition. We report 3 patients with autopsy-proven (2 patients) or clinically diagnosed (1 patient) GCA causing BVAO. A review of the literature concerning BVAO revealed 5 other cases of BVAO resulting from GCA and 110 cases with underlying arteriosclerotic disease. Our 3 patients (mean age, 66 yr; range, 60-78 yr) with BVAO resulting from GCA all had initial severe headache followed by the onset of stepwise progressive, partly side-alternating neurologic deficits due to bilateral infarctions in the vertebrobasilar circulation territory. This course, more accelerated in BVAO due to GCA than in BVAO of arteriosclerotic origin, seems to be a typical, if not particular, clinical syndrome. BVAO was the first clinical manifestation of GCA in 1 of our patients and in 1 published case. From a clinical view, BVAO resulting from GCA differs from BVAO of arteriosclerotic origin by the much higher mortality rate (75% versus 19%, respectively), the presence of headache (100% versus 22%), fever (50% versus 0%), and elevated erythrocyte sedimentation rate (ESR in all GCA cases >45 mm/h; no data in the arteriosclerotic patient group), but not by the neurologic signs themselves. Therapy of BVAO resulting from GCA is purely empiric. In view of the serious prognosis, we propose treatment with intravenous high-dose glucocorticoids and additional immunosuppression with cyclophosphamide; the use of anticoagulation depends on the individual patient's estimated risk-benefit profile. Although BVAO due to GCA is rare, physicians and especially rheumatologists or neurologists should be aware of this entity because of its high mortality in patients without immediate introduction of a high-dose immunosuppressive therapy. Suspicion of GCA should arise in a patient aged over 50 years with no other vascular risk factors suffering from bilateral symptoms of ischemia in the vertebrobasilar territory, with a quickly progressing stepwise course and with headache, fever, or history of myalgia. ESR and temporal artery biopsy should be performed without delay. Early diagnosis of GCA is necessary for immediate initiation of intensive antiinflammatory and immunosuppressive treatment, without which progressive deterioration and systemic involvement are likely to be fatal.

In three patients with acute occlusion of the basilar artery intra-arterial fibrinolysis resulted in only partial recanalization and revealed severe stenosis as the underlying cause. Application of micro-stents without previous dilatation resulted in vessel re-opening. Two patients had an excellent clinical outcome. One patient died 10 days after the stroke due to brainstem infarction. Emergency primary stent application may improve the outcome in acute basilar artery occlusion, if intra-arterial thrombolysis fails to re-establish a sufficient flow.

Arterial blood pressure (ABP) shows polyphasic changes during the Mueller manoeuvre (voluntary negative intrathoracic pressure). The aim of the present study was to investigate (1) whether these changes could lie applied to detect impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2) whether the degree of indicated impairment correlates with transfer function phase as another current measure for dCA (deep breathing method) and CO 2 -reactivity. We examined 13 patients with severe unilateral carotid artery stenosis and 16 age-matched controls during 15-s Mueller manoeuvres (MM) at -30 mmHg using bilateral transcranial Doppler sonography and non-invasive ABP recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to below baseline. CBFV reincreased in controls and on contralateral sides in patients 6.0 s (3.8-9.5 s, median and range) after the onset of the decrease, despite a further fall in ABP. CBFV over the affected side revealed a significantly delayed reincrease (8.0 (5.6-10.3) s; P

Sirs: Spinal subarachnoid hemorrhage (SAH) acounts for less than 1% of SAHs. Cerebral complications are uncommon and moderate in severity. We report on a 30year old woman suffering from severe cerebral vasospasms, without subarachnoid blood in successive cranial CT scans, due to spinal SAH caused by a ruptured solitary spinal aneurysm of unknown etiology. The patient suffered from a graft-versus-host reaction of her transplanted kidney. Under immunosuppression, she developed recurrent pneumonias and a septicemia with unknown germ that were treated by intravenous antibiotics. In the further course, she suddenly presented with headache, back pain and progressive behavioural disturbances. Cranial CT at this time was normal. Three lumbar punctures revealed a hemorrhagic CSF that was considered to be artificially bloody. Because of increasing paraparesis and rectal incontinence, the patient was referred to our clinic one week later. On admission, she was in poor clinical condition with reduced consciousness, no speech production, nuchal rigidity and paraplegia lasting for more than 24 hours. Cranial CT was normal, whereas cranial MRI showed bilateral MCA-infarction on diffusionweighted MRI (Fig. 1A). Spinal MRI revealed a ventrally located intraspinal circular tumour at the level of the twelfth thoracic vertebra with an intradural T1-hyperintensive signal in the thoracolumbar canal (Fig. 1B). Suboccipital puncture yielded a hemorrhagic CSF (2540 cells per ll). Conventional panangiography revealed a solitary aneurysm (8 · 15 mm) originating from the descending branch of the anterior spinal artery at the level of the twelfth thoracic vertebra (Fig. 1C) as well as generalised, severe cerebral vasospasms. Despite immediate triple-Hand nimodipine-therapy, CT 12h later demonstrated large bilateral MCAinfarction, but was still without any cerebral SAH (Fig. 1D). Because of the infavorable prognosis, palliative treatment was carried out until death due to a pneumogenic sepsis 23 days later. To date, 20 cases of spinal SAH due to a rupture of isolated spinal aneurysms have been reported [1–2, 4–16]. Of the eight reported patients with thoracolumbar aneurysms, all had an acute onset of pain in the thoracolumbar region [1, 8, 11, 13, 15]. Three also had paraparesis [1, 8]. Six of the eight patients were treated surgically [8, 11, 13, 15] whilst the other two had a conservative treatment [1]. All patients recovered either without or with minor neurological deficits. The authors found two dissecting aneurysms [8], an inflammation within the vessel wall in two cases [1, 11] and no evident etiology in the other four reports [1, 8, 13, 15]. In our patient, general autopsy did not reveal any underlying systemic (e.g. polyarteriitis nodosa, connective tissue disorder, syphilis), cerebral or further spinal vascular pathology. Since the SAH was related in timing to systemic infection in the context of immunosuppression, the aneurysm may result from a local inflammation. Morphologically, inflammatory aneurysms are characterised by proliferation of the tunica intima and media as well as inflammatory infiltrates. Infectious agents may be detected within the vessel wall [4, 11]. However, the aneurysm in our patient only yielded a prominent fibroblastic proliferation without inflammatory infiltrates (Fig. 2). Additional analysis of blood and CSF samples did not contain any germs and all serological tests were negative. Thus the inflammatory etiology remains speculative. In summary, we present the case of a young woman who suffered from symptomatic cerebral vasospasms due to spinal SAH caused by a ruptured solitary spinal aneurysm. Pathogenesis of cerebral vasospasm is unclear, but is most probably due to a distant inflammatory response caused by the subarachnoid blood [3]. Although there have been a few R. Surges AE M. Schubert AE C. Weiller A. Hetzel AE W.-D. Niesen (&) Dept. of Neurology University Clinics of Freiburg Breisacherstr. 64 79106 Freiburg, Germany Tel.: +49-761/270-5157 Fax: +49-761/270-5328 E-Mail: wolf-dirk.niesen@uniklinikfreiburg.de

In vivo studies selectively assessing preganglionic and central autonomic nervous system activity in patients with autonomic failure have so far been limited to testing pituitary function. In animal experiments carbon dioxide (CO2) selectively stimulates central sympathetic nuclei in the ventrolateral medulla and preganglionic sympathetic neurons in the cervical trunk. This central stimulation seems to overrule less pronounced peripheral vasodilatatory effects. This study addressed the question of whether hypercapnea is a suitable challenge procedure to test preganglionic and central autonomic activity in healthy subjects and in patients with autonomic failure of preganglionic and central origin. Seven patients with multiple system atrophy (MSA) and 30 age-matched healthy volunteers underwent a protocol including a Valsalva manoeuvre (VM) under normo- and hypercapnic conditions and exposure to hypercapnea under supine resting conditions. Blood pressure (BP), heart rate (HR) and end-tidal CO2 partial pressure were measured continuously and non-invasively. In normal controls hypercapnea induced significantly higher BP values in phases II, IIe, III and IV of the VM compared to the normocapnic VM and a significant increase in BP during steady-state supine exposure compared to normocapnic baseline. HR increased significantly only after 40 s of steady-state hypercapnea during the latter challenge. In patients with MSA and autonomic failure, in whom a predominantly preganglionic lesion of the autonomic nervous system is established, no significant effects of hypercapnea on the cardiovascular parameters were found. Although this non-invasive challenge procedure cannot differentiate between pre- and postganglionic autonomic failure, exposure to hypercapnea enables the investigation of efferent autonomic activity to vasoconstrictors generated from autonomic centres in the brainstem and cervical trunk.

The objective of the present study was to identify predictors of left atrial spontaneous echocardiographic contrast (SEC) or thrombus in patients with stroke with sinus rhythm and left ventricular dysfunction. Of 500 consecutive patients with stroke, 48 with sinus rhythm and reduced left ventricular ejection fractions (EFs)or =45% were examined. Ten patients presented with SEC or thrombus. The patients with SEC or thrombus had larger left atrial diameters (47 +/- 4 vs 42 +/- 6 mm, p0.05), smaller EFs (30 +/- 9% vs 38 +/- 8%, p0.01), and slower left atrial appendage (LAA) flow velocities (42 +/- 13 vs 61 +/- 17 cm/s, p0.01). Multivariate analysis identified EFor =35% and LAA flow velocityor =55 cm/s as predictors of SEC or thrombus (p0.05). Patients with stroke with sinus rhythm and moderate- to high-grade reduction of the left ventricular EF represent a risk group for a left atrial source of embolism and should undergo transesophageal echocardiography.

To compare the impact of initial corticosteroid treatment on high-resolution MRI and colour-coded duplex sonography (CCDS) findings in patients with GCA (temporal).Sensitivity and specificity of CCDS and high-resolution contrast-enhanced MRI studies of 59 patients with suspected GCA were retrospectively analysed. Patients were grouped according to the duration of steroid treatment before imaging: 0-1 day, 2-4 days and4 days. In 41 patients, imaging results were compared with findings of temporal artery biopsy (TAB).Sixty-one per cent (36/59) of patients were diagnosed with GCA. TAB findings were positive in 59% (24/41). The compared results of TAB sensitivity of CCDS and MRI under steroid treatment of 0-1 day were 92% and 90%, 2-4 days 80% and 78% and4 days 50% and 80%, respectively. The compared results of the final clinical diagnosis sensitivity of CCDS and MRI under steroid treatment of 0-1 day was 88% and 85%, 2-4 days 50% and 64% and4 days 50% and 56%, respectively.Sensitivity of a first-time CCDS or an MRI for detection of GCA rapidly decreases under corticosteroid treatment. Therefore imaging of patients with suspected GCA should be performed as soon as possible, preferably within the first days of treatment.

Aims: Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Leukocytes play a role in regulating the vascular tone. Natalizumab may thus also affect cerebral vasoregulation. This observational study investigates whether neurovascular coupling and cerebral autoregulation are altered after routine clinical infusion of natalizumab in patients with relapsing remitting multiple sclerosis. Methods: In eighteen patients receiving a regular infusion of 300mg natalizumab, neurovascular coupling to visual stimulation (control system approach) and dynamic cerebral autoregulation (phase and gain of 0.1Hz oscillations) were serially measured by transcranial Doppler ultrasound (before, 2 hours and 2 days after the infusion). A repeated examination 28 days after infusion served as a control situation. Results: Neurovascular coupling was altered 2 hours and 2 days after infusion with an overshooting initial hemodynamic response. After 28 days, neurovascular coupling was similar to values before the infusion. Dynamic cerebral autoregulation, cerebral blood flow velocity and pulsatility index in the middle and posterior cerebral artery were unaltered. Neurovascular coupling was not related to age, sex, disease duration, time since last relapse, clinical severity, number of previous natalizumab infusions and occurrence of new headaches after the infusion. Conclusions: Natalizumab infusion is associated with a temporarily increased initial hyperemia to functional activation. Such a hyperreactivity suggests an increased bioavailability of nitric oxide during functional activation. This is perhaps caused by altered leukocyte concentration in the cerebral microcirculation. Hemodynamic effects of immunosuppressive agents acting at the cerebral microcirculation should be considered in future research. Ideally, they could play a role in noninvasively monitoring the direct biological effects of such drugs at their site of action. A placebo-controlled trial is thus warranted to confirm the results of this observational study.

Neurovascular coupling and cerebral autoregulation are two brain intrinsic vasoregulative mechanisms that rapidly adjust local cerebral blood flow. This study examined if stenotic disease affects both mechanisms in the posterior cerebral artery. Ten patients with altogether 13 stenosed (≥50%) posterior cerebral artery (PCA) sides were studied. In addition, 6 control persons without a PCA stenosis were examined. Cerebral blood flow velocity was assessed from both PCAs with transcranial Doppler sonography; blood pressure was measured noninvasively via fingerplethysmography. Neurovascular coupling was assessed by a control system approach using a standard visual stimulation paradigm. Cerebral autoregulation dynamics were measured from spontaneous oscillations of blood pressure and cerebral blood flow velocity by transfer function analysis (phase and gain). The parameters of neurovascular coupling and cerebral autoregulation did not show relevant differences between controls, nonstenosed sides, and stenosed sides. The 3 severely stenosed PCA sides showed a trend to a minor functional flow velocity change and attenuation of the neurovascular coupling mechanism in relation to sides with moderate stenosis. Phase and gain were not altered on sides with PCA stenosis. We conclude that in a group of patients with mainly moderate stenosis of the PCA neurovascular coupling and dynamic autoregulation dynamics seem to be unaltered.

Objective To compare the diagnostic performance of high-resolution magnetic resonance imaging (MRI) and color-coded duplex sonography (CCDS) in patients with giant cell (temporal) arteritis (GCA). Methods Results of high-resolution MRI and CCDS in 59 patients with suspected GCA were compared with the final clinical diagnosis (based on the American College of Rheumatology GCA criteria and a 6-month followup study). Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method. In 41 of the patients, imaging results were also compared with the findings of a temporal artery (TA) biopsy. Results Thirty-six of the 59 patients (61%) were ultimately diagnosed as having GCA. Sensitivity of high-resolution MRI and CCDS was 69% and 67%, respectively, specificity was 91% and 91%, PPV was 93% and 92%, and NPV was 66% and 64%, respectively. TA biopsy findings were positive in 24 of the 41 biopsied patients (59%). Sensitivity of high-resolution MRI and CCDS compared with TA biopsy was 83% and 79%, respectively, specificity was 71% and 59%, PPV was 80% and 73%, and NPV was 75% and 67%, respectively. The differences between high-resolution MRI and CCDS were not significant. Conclusion The diagnostic power of high-resolution MRI and CCDS in detecting GCA was comparable. Either of these noninvasive techniques may have value in the evaluation of patients with suspected GCA, and decisions regarding which technique to use may depend on the clinical setting.

Cerebral autoregulation (CAR) is a control machanism of the brain keeping cerebral blood flow constant albeit the arterial blood pressure varies. Impaired CAR may be associated with an increased risk of cerebral ischemic events in patients with obstructive cerebrovascular disease. Spontaneous blood pressure oscillations are analyzed using a nonparametric and two parametric transfer function estimators, i.e. the autoregressive-moving-average model with exogenous inputs or the vector-autoregressive model. Performance of the methods was compared using data from patients with unilateral stenosis or occlusion. We also analyzed reproducibility by comparing partitions of the data an with data from other patients which have been measured twice. Results show that there is no significant difference between methods (ANOVA, p > 0.27), and that CAR measurements can be performed reproducibly (Kendall’s τ, p < 0.0016) by all three methods. In conclusion, CAR measurements by means of spontaneous oscillations can be obtained stably and the presented parametric approaches can serve for future online application of CAR measurement.

The combination of morphologic and hemodynamic information can help in assessing the risk of embolic stroke associated with thrombi and plaques in the descending aorta. For two acute stroke patients, the determination of individual embolic pathways using flow-sensitive four-dimensional (4D) MRI are reported. 3D visualization of local flow patterns, i.e., retrograde flow channels originating at the site of the atheroma, in conjunction with exact plaque localization, suggested potential embolization of high-risk plaques in the descending aorta although they are located downstream from the supraaortic arteries. Our findings indicate that taking plaques of the descending aorta into consideration may help improve the spectrum of pathologies considered as high-risk sources for brain ischemia. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc.

Objectives: To evaluate a new three dimensional (3D) MRI protocol for the reliable detection of aortic high risk plaques compared with transoesophageal echocardiography (TOE) and to test the reliability of additional MRI in stroke of undetermined aetiology. Methods: 74 acute stroke patients were examined by both TOE and MRI at 3 Tesla with special regard to aortic high risk plaques (ie, ⩾4 mm, superimposed thrombi). ECG synchronised pre- and post-contrast T1 weighted 3D imaging (spatial resolution ∼1 mm3) covering the thoracic aorta was employed. In plaques ⩾3 mm, additional two dimensional T2 imaging and time resolved (CINE) imaging sequences were performed. Aetiology of brain ischaemia was classified according to modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Aortic high risk embolic sources detected by MRI in patients with cryptogenic stroke were evaluated. Results: Differences in maximum aortic wall thickness for TOE and MRI were not statistically significant for all aortic segments. The overall number of high risk plaques detected by MRI (n = 74) was substantially higher compared with TOE (n = 47). Most noticeably, MRI identified aortic high risk pathologies in 8/26 (30.8%) patients with cryptogenic stroke after standard diagnostics, including TOE (n = 2: dissection or thrombus; n = 6: plaques ⩾4 mm). Conclusions: Our results demonstrate the feasibility of this 3D MRI protocol for the reliable detection of aortic high risk plaques in acute stroke patients. Because of improved visualisation of the aortic arch and the detection of additional embolic sources not seen by standard diagnostics, this novel technique may become a valuable tool for future patients with cryptogenic stroke.

Background: To investigate whether there is: (1) a specific temporal course of cerebral dysautoregulation in acute ischemic stroke, and (2) a separate detrimental effect of recombinant tissue plasminogen activator (rtPA) on autoregulation dynamics in this situation. Methods: We studied 16 patients with acute middle cerebral artery (MCA) occlusion and rtPA thrombolysis (intra-arterial or intravenous application, or both). Controls were 71 healthy adults and 11 patients with minor stroke not receiving rtPA. Dynamic autoregulation was recorded from spontaneous fluctuations of blood pressure and MCA flow velocity (transcranial Doppler) using two well-described approaches (index Mx, phase shift). Three measurements were performed (study 1: 20 ± 9 h of ictus; study 2: 64 ± 10 h; study 3: 112 ± 7 h). Results: Two groups of clinical outcome were identified: good (modified Rankin scale ≤2, n = 9, MCA infarct volume = 14 ± 16%), poor (modified Rankin scale >2, n = 7, MCA infarct volume = 62 ± 21%). In the good outcome group, no relevant changes in Mx and phase were observed on both MCA sides compared with controls. In the poor outcome group, the index Mx deteriorated over studies 1–3 on affected sides, with worse values compared to the controls (p < 0.05). Phase was already impaired on affected sides of poor outcome patients in study 1 (p < 0.01 vs. controls) and tended to decrease further until study 3. Phase also decreased moderately on contralateral sides in poor outcome patients from studies 1 to 3 (p < 0.05, nonsignificant compared with controls). Conclusions: Cerebral autoregulation is increasingly impaired, mainly on the affected side, over the first 5 days of major ischemic stroke after unsuccessful rtPA thrombolysis. It is bilaterally preserved in minor stroke after successful rtPA thrombolysis, indicating no separate detrimental effect of rtPA on the cerebral autoregulatory mechanism.

Dynamic cerebral autoregulation assessed from blood pressure transients can be considerably impaired in severe internal carotid artery (ICA) obstruction. It is unknown whether impaired autoregulation indicates an increased risk of subsequent ischemic events in this situation. 165 patients with ICA stenosis (> 70 %) or occlusion were prospectively followed until anterior circulation stroke, transient ischemic attack, carotid recanalization without prior event, death or study end. Transcranial Doppler sonography was used to determine autoregulation in both middle cerebral arteries from spontaneous blood pressure fluctuations (correlation coefficient indices Dx and Mx) and respiratory- induced 0.1 Hz oscillations (phase). Standard CO(2) reactivity (CO(2)R) was additionally assessed. All indices were classified as impaired vs. preserved according to reference values from 79 agematched controls. During median follow-up of 24.5 months, there were 16 ischemic events over ipsilateral sides. Competing risk analysis revealed a significant predictive effect on ipsilateral ischemic events for impaired Dx (rate ratio 8.2 [95 % confidence interval 1.7-39], p = 0.0079), phase (5.0 [2-13], p = 0.0007) and CO(2)R (9.4 [2.2-40], p = 0.0025). Restricting analysis to severe stenosis alone (n = 103), only impaired phase (rate ratio 8.6 [1.6-45], p = 0.01) remained as a significant predictor. In a continuous statistical model, only Dx and Mx were significant predictors of ischemic events (p = 0.012 and p = 0.016). In conclusion, impaired dynamic cerebral autoregulation indicates an increased risk of subsequent ischemic events in severe obstructive ICA disease. Its clinical application might thus be of help in identifying higher risk patients.

Das Von-Hippel-Lindau-Syndrom ist eine hereditare Tumorerkrankung. Die interdisziplinare Versorgung der Patienten ist von zentraler Bedeutung, weil die Erkrankung nicht nur die Augen, sondern zahlreiche weitere Zielorgane betrifft. Klassische Veranderungen sind Hamangioblastome von Kleinhirn, Medulla oblongata und Ruckenmark, Nierenkarzinome, Phaochromozytome, Pankreaszysten und Inselzelltumoren sowie Tumoren des Endolymphsacks des Innenohrs. Das Untersuchungsprogramm umfasst die augenarztliche Untersuchung, MRT von Kopf, Ruckenmark und Abdomen. Jahrliche Kontrollen werden empfohlen. Die Durchfuhrung der Untersuchungen, die die Grundlage einer rechtzeitigen und meist erfolgreichen Therapie darstellen, ist eine organisatorische Herausforderung.

Migraine affects the autonomous nervous system and a recent investigation has also proposed a severe disturbance of dynamic cerebral blood flow regulation in the middle cerebral artery during spontaneous blood pressure oscillations. This study investigates whether dynamic cerebral autoregulation is impaired in persons with migraine among a normal cohort. Out of 94 adults studied to establish normal values for dynamic autoregulation, 19 suffered from migraine according to IHS criteria (10 of them with aura). Transcranial Doppler sonography and fingerplethysmography were used to determine dynamic autoregulation of both middle cerebral arteries following spontaneous low frequency (0.06-0.12 Hz) blood pressure fluctuations (phase and gain of transfer function, correlation coefficient indices Dx and Mx). No significant differences were found for the low frequency variability of blood pressure (power spectral density) and various indices of dynamic cerebral autoregulation between persons with and without migraine. Moreover, no differences were observed between persons with migraine, with and without aura. This study based on a normal cohort does not support the presence of generally impaired cerebral autoregulation dynamics in persons with migraine. Future studies should focus on posterior circulation and particular cerebellar autoregulation.

Background and Purpose— A recent study showed a dramatic increase in cerebral hemorrhage comprising atypical locations with low-frequency ultrasound–mediated recombinant tissue plasminogen activator–thrombolysis in humans. Here, we provide a possible explanation for this phenomenon by a side effect observed in a study using the similar ultrasound device. Methods— The study was originally undertaken to investigate by transcranial Doppler sonography, positron emission tomography and perfusion MRI whether transcranial application of wide-field low-frequency ultrasound (300 kHz) improves cerebral hemodynamics in patients with cerebral small vessel disease. Results— Showing no clear positive effect on cerebral hemodynamics in 4 patients and on cerebral perfusion (positron emission tomography) in 2 patients, the study has been terminated early because of a remarkable side effect in the first patient (a 62 year-old man) undergoing perfusion-MRI: detection of frontoparietal extravasation of Gadolinium contrast agent (applied during MRI perfusion imaging preinsonation) on MRI immediately postinsonation. Conclusions— Abnormal permeability of the human blood-brain barrier can be induced by wide-field low-frequency insonation. The observed excessive bleeding rate with low-frequency sonothrombolysis might thus be attributable to primary blood-brain barrier disruption by ultrasound.

Background and Purpose— Transesophageal echocardiography (TEE) is the gold standard in detecting high-risk (ie, aortic thrombi) and potential sources (ie, patent foramen ovale [PFO]) of cerebral embolism. We sought to evaluate the additional information and therapeutic impact provided by TEE in stroke patients and to characterize patients in whom TEE is indispensable. Methods— We included 503 consecutive patients (mean age 62.2 years) with acute brain ischemia. Each patient received TEE and the following routine diagnostics: ultrasound of brain supplying arteries, ECG or Holter-ECG, transthoracic echocardiography, and brain imaging (computed tomography or MRI). Stroke etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. High-risk sources in TEE were: aortic thrombi or plaques ≥4 mm, thrombi in left atrial cavity/left atrial appendage, spontaneous echo contrast, and left atrial flow velocity Results— Stroke etiology was determined by routine diagnostics in 276 of 503 patients (54.9%). Of the remaining 227 patients (undetermined etiology), 212 (93.4%) were candidates for oral anticoagulation (OA). TEE revealed a high-risk source, with indication for OA in 17 of them (8.0%). A potential source leading to OA was found in an additional 48 patients (22.6%). The remaining 147 patients (69.3%) were treated by platelet inhibitors or statins. Conclusions— TEE strongly influenced secondary prevention and led to OA in one third of our patients with stroke of undetermined etiology. TEE is indispensable in all patients being candidates for OA when routine diagnostics cannot clarify stroke etiology.

Hemostasis in the left atrial (LA) appendage (LAA) is an important cause in the formation of thrombi. Determination of the LAA flow velocity (LAAV) could be a quantitative parameter for estimating thromboembolic risk. The objective of this study was to: (1) determine the relationship between LAAV and qualitative parameters with elevated thromboembolic risk (thrombus/spontaneous echocontrast [SEC]); and (2) define factors that influence LAAV.In all, 500 patients with stroke were examined consecutively by transesophageal echocardiography. In addition to measurement of the LAAV, the atrial appendage was examined for the presence of thrombi or SEC.LAAV differed significantly among patients with sinus rhythm (71 +/- 16 cm/s), paroxysmal atrial fibrillation (AF) and in sinus rhythm during transesophageal echocardiography (46 +/- 13 cm/s), paroxysmal AF and AF during transesophageal echocardiography (32 +/- 12 cm/s), and chronic AF (27 +/- 9 cm/s, P.001). Independent of the rhythm, the risk of thrombus/SEC increased significantly at an LAAV less than 55 cm/s. At an LAAV 55 cm/s or more there is only a minimal risk of thrombus/SEC (negative predictive value 100% and 99%, respectively). Multivariate analysis showed that LAAV is the strongest predictor for the occurrence of thrombus/SEC (P.0001). Further multivariate analysis showed that left ventricular ejection fraction, LA size, (paroxysmal) AF, age, and sex are independent parameters influencing LAAV.Independent of the basic rhythm, there is a close relationship between LAAV and qualitative parameters of elevated thromboembolic risk. LAAV could, therefore, be a quantitative surrogate parameter for risk stratification. It is influenced by both cardiac and extracardiac factors.

Background and Purpose— Impaired cerebrovascular reserve capacity (CVC) is a risk factor for ischemic events in patients with high-grade carotid stenosis and occlusion. In this study, the CVC in response to a CO 2 challenge was evaluated with blood oxygen level–dependent (BOLD) MRI and the results compared with those of a transcranial Doppler CO 2 tests. Methods— A T 2 *-weighted single-shot multigradient echo-planar imaging sequence was used to determine cerebral CO 2 reactivity. T 2 * values were calculated for each pixel at rest and during a challenge with 7% CO 2 , and a reference function was fitted to the T 2 * time courses. Whole-brain color-coded ΔT 2 * parameter maps were calculated and visually evaluated for regional differences. Additionally, a region-of-interest analysis was undertaken. Average values for ΔT 2 * normalized to changes in end-tidal P co 2 were calculated. Results were correlated with a transcranial Doppler CO 2 tests in 20 patients with high-grade stenosis or occlusion of the carotid artery. Results— Color parameter maps showed areas of decreased BOLD effect within the internal carotid artery territory in 12 of 13 hemispheres with impaired CVC in transcranial Doppler CO 2 test. Regional normalized ΔT 2 * was highly correlated with changes of middle cerebral artery blood flow velocity in transcranial Doppler CO 2 test. Normalized ΔT 2 * was significantly reduced in hemispheres with impaired CVC in transcranial Doppler ( P Conclusions— BOLD MRI can easily be included in routine MRI exams. The technique is robust and yields diagnostic information concerning the cerebrovascular reserve.

The aim of this study is to analyze the work of the interdisciplinary Brain Tumor Board (BTB) which was established at Freiburg University Hospital in 1998.From January 1998 to December 2003, a total of 1,516 patients were discussed in 259 meetings of the BTB. The protocols of the BTB were analyzed retrospectively.In 79% of the patients, the diagnosis was based on histological findings or a typical radiological appearance of a lesion, or both. This group was composed of 4 subgroups: 28% benign skull base tumors (19% meningiomas, 4% pituitary adenomas, 3% acoustic schwannomas, 2% others), 24% primary brain tumors of glial origin (8% glioblastomas, 12% gliomas other than glioblastomas, 5% oligoastrocytomas or oligodendrogliomas), 19% brain metastases, and 8% other brain or skull base tumors. In 13% of the cases, the exact diagnosis was still unknown when the patient was presented. 8% of the presentations were motivated by nontumorous interdisciplinary problems (e.g. arterio-venous malformations). The recommendations given by the BTB included: 23% further diagnostic procedures (11% non-invasive examinations, 12% stereotactic biopsies), 57% active antitumoral therapy (22% resection, 17% fractionated radiotherapy, 13% radiosurgery, 5% chemotherapy,1% embolization), 20% no treatment (14% watchful waiting, 6% supportive care). 91% of the BTB recommendations were realized within 3 months.Interdisciplinary care seems to be particularly necessary in patients with benign skull base tumors, gliomas and brain metastases. Decisions made in a small interdisciplinary group of experts have a high potential of subsequently being realized.

Introduction: Both for hemicraniectomy and for hypothermia, several reports describe a beneficial effect in patients with malignant supratentorial cerebral ischemia. We compared the safety and the clinical outcome in patients with a malignant supratentorial infarction who were treated with hemicraniectomy alone (HA) or received a combination therapy with hemicraniectomy and hypothermia of 35°C (HH), respectively. Methods: In a prospective and randomized study, 25 consecutive patients were treated after an ischemic infarction of more than two thirds of one hemisphere by HA (n = 13 patients) or the HH combination therapy (n = 12 patients). Safety parameters were compared between both treatment groups, the clinical outcome was assessed during treatment and after 6 months. Results: Age, cranial CT or MRI findings, initial National institutes of Health Stroke Scale Score (NIHSSS) and level of consciousness were not significantly different between both groups. Hemicraniectomy was performed within 15 ± 6 h after the ischemic event. Hypothermia was induced immediately after surgery. Overall mortality was 12% (2/13 vs. 1/12 in the two groups), but none of these 3 patients died due to treatment-related complications. There were no severe side effects of hypothermia. Duration of need for intensive care or for mechanical ventilation and infectious status did not differ significantly between both groups, but the need for catecholamine application was increased in the HH group. The clinical outcome showed a tendency for a better outcome in the HH compared with the HA group with respect to status after 6 months, as assessed by the NIHSSS (10 ± 1 vs. 11 ± 3, p < 0.08). Discussion: The present study suggests that a combined therapy of mild hypothermia and hemicraniectomy in malignant brain infarction does not imply additional risks by side effects and improves functional outcome as compared with hemicraniectomy alone.

The quality of collateral blood supply in carotid disease is pivotal for the resulting hemodynamic compromise. However, the interrelation between different patterns of collateral blood flow and actual impairment of cerebral autoregulation (CAR) has not been analyzed so far. Dynamic CAR was assessed noninvasively by the phase shift between respiratory-induced 0.1-Hz oscillations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in 101 patients with severe unilateral carotid stenosis (> or = 75%) or occlusion. CO(2)-vasomotor reactivity was assessed via inhalation of 7% CO(2). Spontaneously activated collaterals via primary (anterior/posterior communicating artery, type I, n = 65) and secondary (ophthalmic artery / leptomeningeal with or without primary pathways, group II, n = 24) pathways were assessed by transcranial Doppler/duplex sonography. Signs of functional stenosis in the anterior collateral pathways were subsumed under type III (n = 12). Best dynamic CAR (phase shift) on affected sides was observed for type I (n = 65), in which values did not differ significantly from contralateral sides. Reduced phase shift values were present in type II; poorest values were observed for type III. CO(2)-reactivity differed mainly between type I and the other types. A less distinct differentiation of autoregulatory impairment was found when dividing patients into groups of different degrees of stenosis. Symptomatic patients (previous TIA/stroke) were significantly less frequent in the group with type I collateral flow and had significantly lower phase shift and CO(2)-reactivity values. In conclusion, we found that dynamic CAR is substantially impaired if secondary collateral pathways are activated or if functional stenosis in the activated anterior collateral pathway is present. These hemodynamic constellations are also associated with a higher proportion of clinically symptomatic patients. Determination of dynamic CAR by transfer function analysis represents a convenient, sensitive method for detection of cerebral hemodynamic compromise in obstructive carotid disease.

Increased pulsatility of blood flow in the basal cerebral arteries recorded with the use of transcranial Doppler sonography (TCD) corresponds to increased intracranial pressure (ICP) to near the level of the diastolic arterial blood pressure. We describe the case of a 39-year-old woman who developed acute reduction in consciousness, anisocoria, gaze deviation, and right-sided hemiparesis 2 days after resection of a relapsed astrocytoma. MRI revealed only a moderate enlargement of the ventricles, but TCD revealed highly pulsatile waveforms of all basal cerebral arteries, showing a biphasic pattern with diastolic backflow. This pattern was interpreted as a massive increase in ICP with imminent danger of cerebral circulatory arrest corresponding to acute malresorptive hydrocephalus. External cerebrospinal fluid drainage was immediately undertaken, revealing excessive ICP of more than 50 cm H2O. Twenty-four hours after this intervention, both the ICP and the Doppler waveforms had returned to normal. This case illustrates the usefulness of TCD for diagnosing a critical but potentially reversible acute increase in ICP with imminent cerebral circulatory arrest. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:324–327, 2003

Intact cerebral autoregulation is essential to prevent cerebral hypoperfusion during pronounced changes in arterial blood pressure (ABP) in patients with autonomic failure (AF). It is still a matter of debate whether and to what extent cerebral autoregulation is disturbed in these patients. This study evaluates the interaction between cerebral blood flow velocity (CBFV) and ABP during Valsalva maneuver (VM) and tilt-table testing in nine patients with multiple system atrophy including AF and in 14 age-matched controls. CBFV and ABP were recorded noninvasively using transcranial Doppler sonography and the Finapres device. Responses to VM were graded by the autoregulation slope index (ASI). Cerebrovascular resistance changes were estimated by the conventional ratio ABP/CBFV and by the dynamic pressure-velocity relationship. To challenge cerebral autoregulation further, tests were repeated under hypercapnic predilation of cerebral arterioles. During VM, CBFV reincreased in patients despite a pronounced ABP drop and showed an overshoot after the strain, thus, being similar to controls. The ASI was higher in patients than in controls ( p0.05). During 70 degrees head-up tilt, ABP dropped markedly, but the decrease in CBFV was small and did not differ significantly from controls. In patients, both tests were associated with a substantial decrease of the dynamic but not of the conventional pressure-velocity relationship. Under hypercapnia, the CBFV response in patients remained unchanged. We conclude that 1). cerebral arterioles have the capacity for adequate vasodilation during ABP drops in patients with AF and that this ability is still present under hypercapnic predilation. 2). The mechanism of cerebral autoregulation in itself does not seem to be affected by the AF but is rather well exercised. 3) The VM presents, in addition to tilt-table testing, a simple test for clinical evaluation of cerebral autoregulation in patients with AF.

BackgroundBilateral severe obstruction of the internal carotid artery is a hemodynamically critical state. We aimed to (1) analyze dynamic cerebral autoregulation (DCA) in affected patients, and (2) to correlate DCA data with different collateral flow patterns.MethodsDCA was assessed noninvasively by transfer function analysis (phase shift) of respiratory-induced oscillations at 0.1 Hz of arterial blood pressure (Finapres method) and cerebral blood flow velocity (transcranial Doppler) in 30 patients with severe bilateral carotid stenosis (> or =75%) or occlusion. CO(2)-reactivity was measured via inhalation of 7% CO(2). 30 patients with unilateral stenosis were recruited as controls.ResultsPatients with bilateral 75-89% stenosis had a virtually preserved phase shift. A pronounced reduction was found in bilateral critical stenosis or obstruction (90-100%). Patients with ipsilateral 90-100% and contralateral 75-89% stenosis had a significantly less severe reduction of phase shift on the ipsilateral side. CO(2)-reactivity showed a less marked reduction in patients with bilateral critical stenosis or occlusion. Phase shift was best if "Willisian" collaterals were present. Significantly reduced values were found if only secondary collaterals (ophthalmic artery, leptomeningeal flow) were detected. Poorest values occurred with recruitment of functionally stenosed "Willisian" collaterals. CO(2)-reactivity showed poor values with sole recruitment of secondary collaterals, whereas functionally stenosed primary collaterals did not show values as poor as for phase shift. Clinically symptomatic patients had significantly lower phase shift and CO(2)-reactivity values.ConclusionsDCA is severely impaired in bilateral critical carotid stenosis or occlusion. Sole recruitment of secondary collaterals and signs of a functional stenosis in primary ("Willisian") collaterals reflect insufficient collateral supply with a poor hemodynamic status. CO(2)-reactivity assessing the vasodilatory reserve and DCA represent different information for characterizing cerebral hemodynamic impairment. Determining transfer function phase might be a physiologically well supported approach for analysis of cerebral hemodynamic compromise.