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Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

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.

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.

Introduction: Identifying factors associated with short term outcome following carotid endarterectomy (CEA) is important to improve patient selection. There are limited data assessing 30-day major adverse cardiac and cerebrovascular events (MACCE: stroke, myocardial infarction (MI) and death) in clinical practice. Hypothesis: We hypothesized that patients fulfilling SAPPHIRE high risk (SHR) or exclusion (SEC) criteria contribute to worse outcomes in a real-life cohort. Methods: Patients undergoing CEA at 2 centers between 1998 and 2010 were prospectively entered into a database. Baseline characteristics, comorbidities, SHR and SEC were assessed using Cox regression to determine predictors for the MACCE 30-day endpoint. Results: The analysis included 748 operations, 262 (35%) asymptomatic , 211 (28%) with previous strokes, and 278 (37%) with transient ischemic attacks (TIA). The overall MACCE rate was 6.7%, 5.0% of asymptomatic and 7.6% in symptomatic patients. SEC patients (n=137) had a MACCE rate of 14.7%; after exclusion, the MACCE rate of the remainder dropped to 4.9% (3.5% in asymptomatic and 5.4% in symptomatic patients). Hazard ratio (HR) for SEC was 3.605 (p=0.0001) after adjustment for symptomatic status. SHR patients did not show a significantly increased event rate (HR 1.714, p=0.16). In multivariate analysis diabetes (HR 2.019, p=0.02), symptomatic status (HR 2.015, p=0.049) and prior MI (HR 1.957, p=0.03) showed an independent influence on MACCE. Conclusion: High risk clinical characteristics, as defined by the SAPPHIRE study were not independently associated with 30-day increased risk of MACCE, although exclusion criteria from that study, diabetes, symptomatic status and prior MI were associated with outcomes.

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.

The phase shift between oscillations of blood pressure (BP) and Doppler middle cerebral artery flow velocity (MCAFV) reflects continuous cerebral autoregulatory action. It is not known whether a similar phase shift exists for cortical hemodynamics ('microvascular level') assessed by near infrared spectroscopy (NIRS) and what the effects are of pathological conditions. This study investigates the phase relations between oscillations of BP, MCAFV and NIRS parameters in 38 healthy older adults and 28 patients with unilateral severe obstructive carotid disease. BP was recorded noninvasively by finger plethysmography. Stable 0.1 Hz oscillations of all hemodynamic parameters were induced by regular breathing at a rate of 6/min. Basic results were that: (1) BP-induced cortical microvascular oscillations (NIRS) follow those of macrovascular oscillations (MCAFV) with a phase of 80-90 degrees (corresponding to 2-2.5 s at 0.1 Hz), most likely reflecting a transit time phenomenon; (2) oxy- and deoxyhemoglobin thereby oscillate in counterphase; (3) hemodynamic compromise in carotid obstruction leads to (a) delayed NIRS oscillations in comparison to BP which are highly correlated to a shorter phase lead of MCAFV against BP and (b) a decoupling of the oxy-/deoxyhemoglobin counterphase to 240 degrees . Cortical hemodynamic responses to BP oscillations follow specific phase relationships due to cerebral autoregulatory action and circulatory transit times. With hemodynamic impairment, as in unilateral carotid obstruction, these phases are significantly changed reflecting disturbed autoregulation.

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.

Background and Purpose— Estimation of dynamic cerebral autoregulation from spontaneous fluctuations of arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) is an attractive monitoring option for cerebral hemodynamic impairment. We evaluated the correlation coefficient index method in patients with severe obstructive carotid disease and compared it with transfer function analysis (frequency domain approach to cerebral autoregulation) and CO 2 vasomotor reactivity. Methods— In 139 patients with severe unilateral carotid stenosis (≥70%) or occlusion, CBFV (transcranial Doppler) and ABP (Finapres method) were recorded over 10 minutes. Correlations between systolic pressure, diastolic pressure, and mean ABP and CBFV oscillations over 1-minute epochs were averaged over 10 minutes to form the correlation coefficient indexes (Sx, Dx, Mx, respectively). Transfer function parameters (phase shift and gain between ABP and CBFV oscillations) were determined from the entire 10-minute period. CO 2 reactivity was assessed by inhalation of 7% CO 2 . Results— The correlation indexes Dx and Mx were significantly higher ipsilateral to stenosis and increased with degree of stenosis, indicating increasing dependence of CBFV on ABP and thus impairment of cerebral autoregulation. Dx and Mx correlated moderately but highly significantly with transfer function parameters and CO 2 reactivity and showed a good level of agreement in detecting pathological values. Patients with a small variance of the 1-minute source correlations of Dx and Mx showed clearly better correlation values. Transfer function parameters and CO 2 reactivity but not Dx and Mx were significantly poorer in patients with symptomatic stenosis or occlusion. Conclusions— The potential of the correlation coefficient indexes Dx and Mx in detecting hemodynamic impairment in patients with carotid stenosis is comparable to that of transfer function analysis and CO 2 reactivity testing. In future, a combination of various hemodynamic tests might help to identify patients at risk for ischemic events.

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.

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.

Background: The anterior communicating artery is a key collateral pathway in patients with internal carotid artery (ICA) occlusions. Diagnostic balloon or manual occlusion of the ICA is a qualified test for the collateral function of the circle of Willis. The aim of our study was to test whether transcranial Doppler sonography (TCD) with manual carotid compression is able to predict the degree of cross-over flow and tolerance of ICA occlusion. Methods: A prospective study was performed on 88 patients suffering from neck tumors or inoperable ICA aneurysms with planned ligation or permanent balloon occlusion of the ICA. Preceding a balloon occlusion lasting 20 min we performed TCD with manual carotid compression test. Insufficient cross-over flow during transient carotid occlusion was defined angiographically as missing opacification of the middle cerebral artery (MCA) after selective injection of contrast media in the contralateral ICA, and sonographically as a decrease greater than 60% in flow velocity of the MCA ipsilateral to the carotid occlusion. Results: TCD and angiography could be compared in 70 of 88 patients. Angiography showed no or insufficient collateral flow in 26%. All patients (n = 10) with a decrease in MCA velocity greater than 60% on angiography showed missing or poor cross-over flow. A greater than 50% increase in the anterior cerebral artery (ACA) predicted moderate or good cross-over flow in 98%. Clinical observation revealed 11 transient neurological deficits. Eight of them showed insufficient cross-over flow angiographically and sonographically. In 2 of 11 only TCD revealed such low collateral supply. Neither technique predicted hemodynamic ischemia in only 1 of the 11. Conclusion: TCD with carotid compression test is a valid method for predicting interhemispheric flow and clinically relevant hemodynamic compromise in cases of occlusion of the ICA.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.

Background and Purpose —Responsiveness to CO 2 is an established test of cerebrovascular reserve capacity. Arterial partial pressure of CO 2 (P co 2 ) and arterial blood pressure (BP) are key parameters for cerebral blood flow. To investigate the interaction between P co 2 and BP, we performed a study with simultaneous measurement of CO 2 and BP during CO 2 reactivity testing with transcranial Doppler sonography. Methods —Eighty-one healthy volunteers, aged 19 to 74 years, underwent examination defined by a protocol with multimodality monitoring of BP, heart rate (HR), P co 2 , and Doppler frequencies (DFs) of the left middle cerebral artery (MCA). Reproducibility was tested in a subgroup of 14 volunteers ≥65 years of age by CO 2 reactivity testing on different days. Results —Increase of P co 2 was accompanied by a parallel increase of mean±SD time values of DF (3.6±1.6%/mm Hg CO 2 ). BP levels were significantly elevated after 60-second hypercapnia (mean values, 0.5±0.55 mm Hg/mm Hg CO 2 ). A significant decrease over time was seen only for pulsatility in DF but not in BP. Analysis of variance and covariance with repeated measures revealed a highly significant effect of CO 2 on MCA Doppler shift. A less-pronounced effect on DF was seen for BP. Correlation analysis showed no significance for CO 2 reactivity, but a significant correlation between test and retest was seen in BP-related CO 2 reactivity. Conclusions —The CO 2 response curve showed the known linear increase of DF. The parallel significant increase in BP most likely results from activation of the central sympathetic nervous system. The poor reproducibility for Doppler CO 2 reactivity is to some extent explainable by variability of BP. CO 2 -induced increases in BP can have relevant influence on MCA Doppler shift and lead to misinterpretation of Doppler CO 2 test results.

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 selection of patients with cervical internal carotid artery occlusion (ICAO) for extracranial-intracranial bypass surgery is based on exhausted cerebrovascular reactivity to vasodilatory stimuli. However, a spontaneous increase in this reactivity can occur with time, questioning the ideal time for bypass surgery. In contrast, the natural course of dynamic cerebral autoregulation is not known in these patients.Patients with cervical ICAO were examined at baseline and after a mean interval of 15 months. Dynamic autoregulation was determined by transcranial Doppler sonography in both middle cerebral arteries via respiratory-induced 0.1-Hz oscillations (phase, available for n=47 patients) and correlation analysis between diastolic blood pressure and Doppler signal (index Dx, n=55 patients). Pre-defined cut-off values and repeatability measures of healthy controls were used to define significant individual changes in autoregulation.Group mean comparisons between studies were not significant for any autoregulation parameter. The intraclass correlation coefficient between studies was high for phase (ipsilateral: 0.83; contralateral: 0.74), and moderate for Dx (ipsilateral: 0.63; contralateral: 0.35). There was no clear trend for an improvement across cut-off values. A significant individual improvement/deterioration in autoregulation occurred in 6%/6% for phase and 13%/9% for Dx.Dynamic autoregulation only rarely improves during the course of ICAO. This finding should be considered when deciding for or against a policy of delaying extracranial-intracranial bypass surgery for reasons of a potentially improving hemodynamic status.

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.

Knowledge on autoregulation of cerebellar blood flow in humans is scarce. This study investigated whether cerebellar autoregulation dynamics and CO2 reactivity differ from those of the supratentorial circulation. In 56 healthy young adults, transcranial Doppler (TCD) monitoring of the posterior inferior cerebellar artery (PICA) and, simultaneously, of the contralateral middle cerebral artery (MCA) was performed. Autoregulation dynamics were assessed by the correlation coefficient method (indices Dx and Mx) from spontaneous blood pressure fluctuations and by transfer function analysis (phase and gain) from respiratory-induced 0.1 Hz blood pressure oscillations. CO2 reactivity was measured via inhalation of air mixed with 7% CO2. The autoregulatory indices Dx and Mx did not differ between the cerebellar (PICA) and cerebral (MCA) vasculature. Phase and gain, which describe faster aspects of autoregulation, showed slightly better values in the PICA compared with the MCA (higher phase, P = 0.005; lower gain, P = 0.007). Correlation between absolute autoregulation values in the PICA and the MCA was significant ( P < 0.001). The TCD CO2 reactivity was significantly lower in the PICA ( P < 0.001), which could be influenced by an assumed PICA dilation under hypercapnia. In conclusion, dynamic autoregulation in the human cerebellum is well operating and has slightly faster regulatory properties than the anterior cerebral circulation.

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.

To evaluate the accuracy of Doppler sonography compared with angiography, temporary test occlusion of the internal carotid artery (ICA) was performed as paramenter for prediction of tolerance in case of sacrifice of the ICA. The vessel occlusion was done in 67 patients by manual compression over 10 seconds and by twenty minutes lasting balloon insufflation.The results (table 1) show a good correlation between dopplersonographic and angiographic testing in terms of collateral circulation. However, Doppler sonography proved to be more indicative for predicting clinically insufficient collateral supply.

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.

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.

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.

Die medikamentose lokale intraarterielle Fibrinolyse (LIF) ist ein mittlerweile anerkanntes und etabliertes Verfahren. Ungeachtet der Wahl des Fibrinolytikums liegen die Rekanalisationszeiten allerdings bei 1–2 h, so dass zunehmend neue mechanische Techniken erprobt werden, die eine Verkurzung der Rekanalisationszeiten ermoglichen sollen. Durch eine schnellere Rekanalisation kann die Infarktgrose verkleinert werden, was zu einem besseren klinischneurologischen Outcome fuhrt. In der vorliegenden Arbeit werden die Technik der Laserlyse und erste Ergebnisse vorgestellt. Die Patienten wurden im Rahmen der „Safety and Performance Study“ bzw. der Folgestudie („Pivotal Study“) eingeschlossen. Vor der Behandlung wurden NIHSS („National Institute of Health Stroke Scale“) sowie mRS („modified Rankin Scale“) erhoben. Der Grad der Rekanalisation wurde anhand der angiographischen Ergebnisse ermittelt. Die klinischen Verlaufsuntersuchungen erfolgten 24 h, 7 Tage und 30 Tage nach Behandlung. 20 Patienten wurden eingeschlossen. 13 Patienten wurden mit Gefasverschlussen im vorderen und sieben Patienten mit Verschlussen im hinteren Stromkreislauf in die Studie aufgenommen. Entsprechend den Vorgaben der Studie wurden zwolf Behandlungen als technisch komplett mit dem EPAR-System und acht Behandlungen als inkomplett eingestuft. In funf von acht Fallen wurde der Laserkatheter eingefuhrt, aber keine Laserbehandlung durchgefuhrt. Die Rekanalisationsergebnisse im vertebrobasilaren Stromgebiet mit einer 86%igen Rekanalisationsrate bei einer mittleren Laserzeit von 7,6 min (1,3–18,9 min) sind viel versprechend, wahrend die Rekanalisationsrate im vorderen Stromkreislauf lediglich 31% betrug (mittlere Laserzeit von 5,5 min [0–15,6 min]). Neben dem Nachweis des Studienziels Sicherheit und technische Machbarkeit erwies sich diese neue Methode als effektiv in Bezug auf eine rasche Rekanalisation, so dass sie eine weitere Therapieoption zur Behandlung des akuten Schlaganfalls darstellen konnte.

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.

Dissection of the internal carotid artery (ICAD; Fig. 1) is not only widely accepted as an important component of stroke aetiology, it is also well recognised as a focal cause of lower cranial nerve palsy. In the present patient, a duplex ultrasound revealed a left, submandibular ICAD originating 3 cm distal to the ICA bifurcation. In parallel, a high-grade, long-distance stenosis was confirmed by a time-of-flight magnetic resonance angiogram. Axial T2-weighted MRI showed a crescent-like, hyperintense signal corresponding to an intramural haematoma. In addition, an asymptomatic dissecting vertebral artery (VA) aneurysm on the right V2-segment was