Prognostic significance of pulsatile tinnitus in cervical artery dissection.

BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

Cerebral distribution of white matter lesions in migraine with aura patients.

OBJECTIVE: The objective of the study was to compare the cerebral distribution of white matter lesions (WMLs) between migraine patients with different aura symptoms. METHODS: Migraine with aura (MA) patients were consecutively enrolled as part of the Shunt-Associated Migraine (SAM) study. According to clinical symptoms, aura was classified as motor, aphasic, sensory, visual or vertebrobasilar. Standard and FLAIR (fluid attenuated inversion recovery) T(2)-weighted MRI sequences were inspected for WMLs by three independent raters blinded to clinical data. WMLs were assessed in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Schelten's scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < .0001). RESULTS: One hundred and eighty-five patients (77% women) were included. Aura symptoms were classified as visual in 172 (99%) patients, sensory in 76 (42%), aphasic in 54 (30%), motor in 39 (21%) and vertebrobasilar in 17 (9%) patients. One hundred and four patients (57%) exhibited more than one type of aura. D-WMLs were mainly detected in the frontal lobes (86%). There was no association between type of aura and the presence of WMLs in any cerebral location. CONCLUSION: Aura symptoms do not influence the cerebral distribution of WMLs associated with migraine disease.

Right-to-left shunt does not increase white matter lesion load in migraine with aura patients.

BACKGROUND: White matter lesions (WMLs) are commonly found on brain MRI of migraine patients. Migraine with aura (MA+) is associated with an increased frequency of right-to-left shunt (RLS) mostly due to patent foramen ovale. The relationship between WML load and RLS in MA+ is currently unknown. METHODS: MA+ patients were consecutively enrolled as part of the Shunt Associated Migraine (SAM) study. Patients underwent a standardized headache and vascular risk factors questionnaire, contrast-enhanced transcranial Doppler, blood coagulation tests, and brain MRI. RLS was categorized into four grades: no shunt, <10 microbubbles (mb), >10 mb single spikes pattern, and >10 mb shower/curtain pattern. Standard and fluid-attenuated inversion recovery T2-weighted MRI sequences were inspected for WMLs by three independent raters blinded to RLS grade. WML load was scored in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to excellent (kappa = 0.64 to 0.96, p < 0.0001). WML load was then correlated between patients with and without RLS. RESULTS: One hundred eighty-five patients (77% women) were included. PV-WML load was similar between patients with and without RLS. D-WML load decreased in patients with RLS (p = 0.045). On logistic regression analysis, only age was associated with WMLs (p < 0.001). CONCLUSIONS: The presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura.

Clinical importance of microbleeds in patients receiving IV thrombolysis.

BACKGROUND: Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA). METHODS: The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging. RESULTS: Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB. CONCLUSIONS: The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

Diagnostic and therapeutic impact of ambulatory electrocardiography in acute stroke.

UNLABELLED: Detection of paroxysmal atrial fibrillation (PAF) in patients with recent ischemic stroke or TIA suggests a cardioembolic etiology and leads to initiation of oral anticoagulation in suitable candidates. We assessed the diagnostic and therapeutic impact of adding ambulatory electrocardiography (24 hr ECG) to a standardised ischemic stroke workup. METHODS: We measured the frequency of detection of PAF in consecutive stroke patients who underwent 24 hr ECG that was not diagnosed clinically or on a standard 12-lead ECG. RESULTS: One hundred forty five ischemic stroke patients were included. 24 hr ECG was obtained in 136 patients (93.8%). Clinically unsuspected PAF was detected on 24 hr ECG in 7 patients (5.1%). The secondary prevention measure changed from antiplatelet agents to oral anticoagulation in 6 of 7 patients. CONCLUSION: Our findings suggest that ambulatory electrocardiography is a valuable diagnostic tool in the workup of stroke patients. Further prospective studies are needed to identify, subtypes of patients in whom the yield of ambulatory electrocardiography is higher.

Imaging strategy for acute stroke therapy.

New MR imaging methods provide us with a hitherto unimaginable wealth of information on the pathophysiologic mechanisms operative in acute stroke. The only evidence-based acute stroke therapy, thrombolysis with IV tPA, only requires a CT to exclude brain hemorrhage before treatment. In PROACT 2 (Prolyse in Acute Cerebral Thromboembolism) locoregional thrombolysis with prourokinase improved the frequency of independent outcome. The only imaging methods used in this trial were a brain CT to exclude patients with brain hemorrhage and extended early infarct signs and a classical angiogram to demonstrate the presence of an M1 or M2 segment occlusions. In principle these therapies can be applied without using sophisticated MR or CT techniques. In this brief review we discuss the potential role of these novel techniques before application of intravenous or intraarterial thrombolysis.

Relationship between severity of MR perfusion deficit and DWI lesion evolution.

OBJECTIVE: To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion. METHODS: Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion. RESULTS: Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size. CONCLUSION: Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.

Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke.

BACKGROUND AND PURPOSE: Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age. METHODS: Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)). RESULTS: The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter. CONCLUSION: Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis.

BACKGROUND AND PURPOSE: The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome. METHODS: We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis. RESULTS: Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI. CONCLUSIONS: DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

Symptomatic intracranial atherosclerosis: outcome of patients who fail antithrombotic therapy.

OBJECTIVE: To determine the prognosis of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy. BACKGROUND: The outcome of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy is unknown. These patients may represent the target group for investigation of more aggressive therapies such as intracranial angioplasty. METHODS: The authors performed a chart review and telephone interview of patients with symptomatic intracranial atherosclerosis identified in the Stanford Stroke Center clinical database. A Cox regression model was created to identify factors predictive of failure of antithrombotic therapy. The authors generated Kaplan-Meier survival curves to determine the timing of recurrent TIA, stroke, or death after failure of antithrombotic therapy. RESULTS: Fifty-two patients had symptomatic intracranial atherosclerosis and fulfilled entry criteria. Twenty-nine of the 52 patients (55.8%) had cerebral ischemic events while receiving an antithrombotic agent (antiplatelet agents [55%], warfarin [31%], or heparin [14%]). In a Cox regression model, older age was an independent predictor of failure of antithrombotic therapy, and warfarin use was associated with a decrease in risk. Recurrent TIA (n = 7), nonfatal/fatal stroke (n = 6/1), or death (n = 1) occurred in 15 of 29 (51.7%) of the patients who failed antithrombotic therapy. The median time to recurrent TIA, stroke, or death was 36 days (95% CI 13 to 59). CONCLUSIONS: Patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy have extremely high rates of recurrent TIA/stroke or death. Recurrent ischemic events typically occur within a few months after failure of standard medical therapy. The high recurrence risk observed warrants testing of alternative treatment strategies such as intracranial angioplasty.