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).

Objective: 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. Methods: 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 pCi <20% increase. Results: 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; p < 0.0001). 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; p < 0.0001) 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. Conclusions: 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.

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 48h) 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.

OBJECTIVETo compare the impact of initial corticosteroid treatment on high-resolution MRI and colour-coded duplex sonography (CCDS) findings in patients with GCA (temporal).METHODSSensitivity 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 and >4 days. In 41 patients, imaging results were compared with findings of temporal artery biopsy (TAB).RESULTSSixty-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% and >4 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% and >4 days 50% and 56%, respectively.CONCLUSIONSensitivity 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.

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.

OBJECTIVES: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.METHODS: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.RESULTS: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.DISCUSSION: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.

Purpose 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. Methods 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). Results 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. Conclusions 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.

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.

Background: Natalizumab inhibits adherence of leukocytes to the cerebral endothelium. Since leukocytes play a role in regulating vascular tone, natalizumab may also affect cerebral vasoregulation. The aim of this observational study was to investigate whether neurovascular coupling and cerebral autoregulation are altered following routine clinical infusion of natalizumab in patients with relapsing-remitting multiple sclerosis. Methods: In 18 patients receiving regular infusion of 300 mg natalizumab, neurovascular coupling to visual stimulation and dynamic cerebral autoregulation (phase and gain of 0.1-Hz oscillations) were measured by transcranial Doppler ultrasound (before, and 2 h and 2 days after the infusion). A repeated examination 28 days after infusion served as a control situation. Results: Neurovascular coupling was altered 2 h 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. Conclusion: 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.

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% CO2. 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.

BACKGROUND:By mapping the dynamics of brain reorganization, functional magnetic resonance imaging MRI (fMRI) has allowed for significant progress in understanding cerebral plasticity phenomena after a stroke. However, cerebro-vascular diseases can affect blood oxygen level dependent (BOLD) signal. Cerebral autoregulation is a primary function of cerebral hemodynamics, which allows to maintain a relatively constant blood flow despite changes in arterial blood pressure and perfusion pressure. Cerebral autoregulation is reported to become less effective in the early phases post-stroke. This study investigated whether any impairment of cerebral hemodynamics that occurs during the acute and the subacute phases of ischemic stroke is related to changes in BOLD response. We enrolled six aphasic patients affected by acute stroke. All patients underwent a Transcranial Doppler to assess cerebral autoregulation (Mx index) and fMRI to evaluate the amplitude and the peak latency (time to peak-TTP) of BOLD response in the acute (i.e., within four days of stroke occurrence) and the subacute (i.e., between five and twelve days after stroke onset) stroke phases.RESULTS:As patients advanced from the acute to subacute stroke phase, the affected hemisphere presented a BOLD TTP increase (p = 0.04) and a deterioration of cerebral autoregulation (Mx index increase, p = 0.046). A similar but not significant trend was observed also in the unaffected hemisphere. When the two hemispheres were grouped together, BOLD TTP delay was significantly related to worsening cerebral autoregulation (Mx index increase) (Spearman's rho = 0.734; p = 0.01).CONCLUSIONS:The hemodynamic response function subtending BOLD signal may present a delay in peak latency that arises as patients advance from the acute to the subacute stroke phase. This delay is related to the deterioration of cerebral hemodynamics. These findings suggest that remodeling the fMRI hemodynamic response function in the different phases of stroke may optimize the detection of BOLD signal changes.

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.

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.

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.

HomeStrokeVol. 38, No. 2Response to Letter by Gerriets et al Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Letter by Gerriets et al Matthias Reinhard Thomas Els Andreas Hetzel Matthias ReinhardMatthias Reinhard Department of Neurology, University of Freiburg, Freiburg, Germany Thomas ElsThomas Els Department of Neurology, University of Freiburg, Freiburg, Germany, Department of Neurology, Marien Hospital Bergisch Gladbach, Bergisch Gladbach, Germany Andreas HetzelAndreas Hetzel Department of Neurology, University of Freiburg, Freiburg, Germany Originally published14 Dec 2006https://doi.org/10.1161/01.STR.0000254443.78965.10Stroke. 2007;38:252Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: December 14, 2006: Previous Version 1 Response:We greatly appreciate the thoughtful comments by Dr Gerriets and coworkers. Our finding of blood-brain barrier disruption after 300 kHz insonation in a 62-year-old man with cerebral small-vessel disease1 is substantiated by their remarkable animal study demonstrating vasogenic edema on MRI after 20 kHz insonation.2 Mechanical and not thermal effects3 thus seem to be responsible for the possibly deleterious side effects of low-frequency ultrasound. The dilemma is that the better bone penetration and thus recanalizing efficacy of low-frequency ultrasound in vitro is apparently foiled by a higher rate of mechanical side effects in vivo. In a randomized clinical study, 2 MHz sonothrombolysis was safe and resulted in a higher rate of recanalization,4 whereas an in vitro skull model could not demonstrate any sonothrombolytic efficacy of 1.8 MHz insonation.5 The only sonothrombolysis study in humans using low-frequency ultrasound of 300 kHz6 showed hemorrhagic, most probably mechanical side effects but (unlike in vitro studies) not a higher recanalization rate compared with recombinant tissue plasminogen activator alone. In the light of these conflicting results between in vitro and in vivo studies, there is a sincere need for in vivo animal studies balancing different ultrasound frequencies (between 300 kHz and 2 MHz), powers and target volumes against optimal clinical efficacy and lowest side effects. We fully agree with Dr Gerriets and colleagues that an extensive preclinical evaluation of this topic is needed before future clinical studies in humans.DisclosuresNone.1 Reinhard M, Hetzel A, Kruger S, Kretzer S, Talazko J, Ziyeh S, Weber J, Els T. Blood-brain barrier disruption by low-frequency ultrasound. Stroke. 2006; 37: 1546–1548.LinkGoogle Scholar2 Schneider F, Gerriets T, Walberer M, Mueller C, Rolke R, Eicke BM, Bohl J, Kempski O, Kaps M, Bachmann G, Dieterich M, Nedelmann M. Brain edema and intracerebral necrosis caused by transcranial low-frequency 20-kHz ultrasound: a safety study in rats. Stroke. 2006; 37: 1301–1306.LinkGoogle Scholar3 Fatar M, Stroick M, Griebe M, Alonso A, Hennerici MG, Daffertshofer M. Brain temperature during 340-kHz pulsed ultrasound insonation: a safety study for sonothrombolysis. Stroke. 2006; 37: 1883–1887.LinkGoogle Scholar4 Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moyé LA, Hill MD, Wojner AW. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med. 2004; 351: 2170–2178.CrossrefMedlineGoogle Scholar5 Pfaffenberger S, Devcic-Kuhar B, Kollmann C, Kastl SP, Kaun C, Speidl WS, Weiss TW, Demyanets S, Ullrich R, Sochor H, Woeber C, Zeitlhofer J, Huber K, Groeschl M, Benes E, Maurer G, Wojter J, Gottsauner-Wolf M. Can a commercial diagnostic ultrasound device accelerate thrombolysis? An in vitro skull model. Stroke. 2005; 36: 124–128.LinkGoogle Scholar6 Daffertshofer M, Gass A, Ringleb P, Sitzer M, Sliwka U, Els T, Sedlaczek O, Koroshetz WJ, Hennerici MG. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke. 2005; 36: 1441–1446.LinkGoogle Scholar eLetters(0) eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate. Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page. Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails February 2007Vol 38, Issue 2 Advertisement Article Information Metrics https://doi.org/10.1161/01.STR.0000254443.78965.10 Originally publishedDecember 14, 2006 PDF download Advertisement

Objectives: Cerebral autoregulation is a key protective mechanism for regular brain function. Despite the functional importance of the cerebellum, its autoregulatory ability has not been systematically studied in humans so far. This study simultaneously investigates cerebellar and cerebral autoregulation using transcranial Doppler (TCD) monitoring.

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.

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 rnacrovascular 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. degrees 2006 Elsevier B.V. All rights reserved.

204 ies and 50% basilar artery stenosis confi rming the thrombotic nature of the stroke. No cardiac source of embolism was found. Therefore, given the initial evidence of right vertebral artery occlusion by magnetic resonance angiography, we suspect that the progression to bilateral involvement was due to occlusion of a penetrating branch, although unfortunately the autopsy report did not focus on the origins of the anterior spinal arteries and no cerebral angiogram was performed. MMS accounted for less than 0.5% of all cerebral infarcts in one series [1] and a similar number was reported in a 700-autopsy report [7] . Up to 1996, only 40 well-documented cases were reported [6] , and this condition still remains a diagnostic challenge because of the heterogeneous clinical presentations [6] . In our patient the presence of upbeat nystagmus was an important diagnostic clue. It is thought to be secondary to medial longitudinal fasciculus involvement, although others proposed the involvement of the nucleus intercalatus of Starderini [8] . However, previous reports underemphasized the diagnostic importance of the upbeat nystagmus [1] , including the largest case series of MMS published in 1995 and 2004 [9, 10] because of the heterogeneous clinical presentation of the MMS. In summary, we present the fi rst concomitant DWI and autopsydocumented case of progression of right to bilateral anteromedial medullary ischemia. It also points to the need of early suspicion of peritonitis or other abdominal infection in patients with bilateral brainstem ischemia and unexplained fever. Similar to patients with spinal cord injury, they may develop threatening abdominal infections without the classical signs of peritoneal irritation [11] .

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 <0.9 mm and DC ≥24×10 −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 <24 were lower (46.3%, 41.1%; respectively), but they also increased in combination (54.3%). 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.