Transcranial Doppler detection of cerebral fat emboli and relation to paradoxical embolism: a pilot study.

BACKGROUND: The fat embolism syndrome is clinically characterized by dyspnea, skin petechiae, and neurological dysfunction. It is associated mainly with long bone fracture and bone marrow fat passage to the systemic circulation. An intracardiac right-to-left shunt (RLS) could allow larger fat particles to reach the systemic circulation. Transcranial Doppler can be a useful tool to detect both RLS and the fat particles reaching the brain. METHODS AND RESULTS: We prospectively studied patients with femur shaft fracture with RLS evaluation, daily transcranial Doppler with embolus detection studies, and neurological examinations to evaluate the relation of RLS and microembolic signals to the development of fat embolism syndrome. Forty-two patients were included; 14 had an RLS detected. Seven patients developed neurological symptoms; all of them had a positive RLS (P=<0.001). The patients with an RLS showed higher counts and higher intensities of microembolic signals (P=<0.05 and P=<0.01, respectively) compared with those who did not have an RLS identified. The presence of high microembolic signal counts and intensities in patients with RLS was strongly predictive of the occurrence of neurological symptoms (odds ratio, 204; 95% confidence interval, 11 to 3724; P<0.001) with a positive predictive value of 86% and negative predictive value of 97%. CONCLUSIONS: In patients with long bone fractures, the presence of an RLS is associated with larger and more frequent microembolic signals to the brain detected by transcranial Doppler study and can predict the development of neurological symptoms.

High-dose atorvastatin enhances impaired cerebral vasomotor reactivity.

The influence of statin therapy on cerebral vasomotor function has not been fully characterized. We report the effects of high-dose atorvastatin therapy on cerebral vasomotor reactivity (VMR) in patients with controlled hypertension and dyslipidemia. We prospectively enrolled 36 patients with controlled hypertension and a low-density lipoprotein (LDL) cholesterol concentration >100 mg/dL. Atorvastatin 80 mg was given daily for 6 months and then discontinued. VMR was assessed by hypercapnic and hypocapnic transcranial Doppler challenge in both the right and left middle cerebral artery (MCA) at baseline, and after 3 and 6 months of therapy. Forty-five days after statin cessation, a repeat VMR was performed. VMR impairment was defined as ≤70%. Blood pressure, lipid levels, liver function, and creatine kinase level were monitored. Mean patient age was 60 years, 16 were men, and 13 had a previous history of subcortical infarction. Mean LDL cholesterol level before treatment was 154 ± 30 mg/dL. Atorvastatin lowered LDL by 53% at 3 months and by 46% at 6 months. Baseline VMR was 71% ± 21% in the right MCA and 70% ± 19% in the left MCA. No significant effect of atorvastatin on VMR was seen at 3 months and 6 months in the study population as a whole. In the subgroup of patients with baseline VMR impairment, atorvastatin therapy was associated with significantly improved VMR at both 3 and 6 months. This effect persisted for at least 45 days after discontinuation of therapy. Our findings indicate that high-dose atorvastatin therapy can significantly improve impaired cerebral VMR, and that the effects of atorvastatin on VMR persist for 1.5 months after discontinuation of therapy. We found no benefit of atorvastatin therapy in patients with preserved baseline vasoreactivity.

Cerebral fat microembolism and cognitive decline after hip and knee replacement.

BACKGROUND AND PURPOSE: Intra-operative cerebral microembolism may be a factor in the etiology of cognitive decline after orthopedic surgery. We here examine the impact of intra-operative microembolism on cognitive dysfunction after hip and knee replacement surgery. METHODS: We enrolled 24 patients, at least 65 years old, requiring elective knee or hip replacement surgery. A transcranial Doppler shunt study was done to determine study eligibility so that the final study population consisted of 12 consecutive patients with and 12 consecutive patients without a venous-arterial shunt. A standard neuropsychological test battery was administered before surgery, at hospital discharge and 3 months after surgery. All patients were monitored intra-operatively for microemboli. Quality of life data were assessed at 1 year. RESULTS: The mean age of patients was 74 years. All patients had intra-operative microemboli. The mean number of emboli was 9.9+/-18. Cognitive decline was present in 18/22 (75%) at discharge and in 10/22 (45%) at 3 months, despite improved quality of life measures. There was no correlation between cognitive decline and intra-operative microembolism. CONCLUSIONS: Cognitive decline was seen frequently after hip and knee surgery. Intra-operative microembolism occurred universally but did not significantly influence postoperative cognition. Quality of life and functional outcome demonstrated improvement in all cases in spite of cognitive dysfunction.

In-hospital delays to stroke thrombolysis: paradoxical effect of early arrival.

OBJECTIVE: To determine the causes of in-hospital delays for thrombolysis. METHODS: We performed a 4 year retrospective chart analysis of i.v. tPA-treated patients at an academic medical center. Data collected included age, stroke severity by the National Institutes of Health Stroke Scale (NIHSS) and the following time points: symptom onset, hospital arrival, computed tomography (CT), i.v. tPA order and i.v. tPA initiation of infusion. RESULTS: Thirty-one cases with sufficient information for analysis were identified. Mean time from onset to arrival was 58 minutes, from arrival to brain CT was 32 minutes, and from onset to i.v. rtPA infusion was 169 minutes. The mean delay between i.v. tPA order and infusion was 32 minutes. Delay between order and administration of i.v. tPA resulted in treatment after 3 hours in 9/31 cases. An inverse relationship between early hospital arrival and delayed thrombolysis was noted. Age and stroke severity did not impact treatment times. CONCLUSION: An unexpected delay between order and actual initiation of i.v. tPA infusion resulted in almost one-third of patients receiving thrombolytics after 3 hours from symptom onset. The cause of this delay could not be discerned by this study. The paradoxical effect between early arrival to hospital and delayed treatment may be related to a sense of urgency in those arriving close to 3 hours after onset. Critical reviews such as this permit identification of hospital delays in stroke treatment, thus allowing institution of appropriate strategies to ensure prompt treatment.

MR imaging after hip and knee replacement.

BACKGROUND: Diffusion-weighted (DW) imaging abnormalities often develop in patients after invasive procedures associated with cerebral microembolism. Cerebral microembolism has recently been shown during orthopedic surgery. We here examine the effects of intraoperative microembolism on acute magnetic resonance(MR) imaging in patients undergoing hip and knee replacement. METHODS: We enrolled 24 patients, at least 65 years old, requiring elective knee or hip replacement surgery. MR with DW and axial fluid-attenuated inversion recovery (FLAIR) imaging was performed pre- and postoperatively. All patients were monitored intraoperatively for microemboli. RESULTS: The mean age of patients was 74 years. All patients had intraoperative microemboli. The mean number of emboli detected was 9.9 +/- 18 per surgery. MR imaging was obtained a mean of 3.5 days postoperatively. No DW imaging abnormalities were found after surgery. One patient had new findings on postoperative FLAIR imaging. CONCLUSION: Intraoperative microembolism occurred universally, but did not lead to acute DW imaging abnormalities following knee and hip replacement. Acute imaging abnormalities on FLAIR imaging are rare but may occasionally occur after joint surgery.

Signs and symptoms of sleep apnea and acute stroke severity: is sleep apnea neuroprotective?

BACKGROUND: In animal models, brief periods of hypoxemia render the brain tolerant to subsequent ischemic insults. Sleep apnea leads to frequent episodes of nocturnal hypoxemia and may induce ischemic tolerance. Snoring and daytime sleepiness are cardinal symptoms of sleep apnea. We undertook this study to determine differences in stroke severity and early neurologic course in patients at risk for sleep apnea as determined by a sleep questionnaire. METHODS: Patients admitted with acute ischemic stroke completed the Berlin questionnaire. The Berlin questionnaire examines habitual snoring, daytime sleepiness, presence of hypertension, and body mass index (BMI) and classifies patients into a high or low risk for sleep apnea group. National Institutes of Health Stroke Scale (NIHSS) score was determined on admission and day 5 of hospitalization. Age, sex, cardiovascular risk factors, BMI, and stroke mechanism were determined prospectively. RESULTS: We enrolled 190 patients with a mean age of 60 years and 53% were men. The Berlin questionnaire classified 103 patients (54%) at high risk for sleep apnea. The median NIHSS score on admission and day 5 of hospitalization did not differ between the two groups after multivariate analysis. Examined separately, we found no effect of snoring, daytime sleepiness, or BMI on acute stroke severity and outcome. CONCLUSION: We found that a large number of patients admitted with acute ischemic stroke were at high risk for having sleep apnea. We were not able to show that a constellation of symptoms and features highly suggestive of sleep apnea influenced stroke severity or early neurologic course after acute ischemic stroke.

Acute Thyrotoxicosis of Graves Disease Associated with Moyamoya Vasculopathy and Stroke in Latin American Women: A Case Series and Review of the Literature.

OBJECTIVE: Moyamoya disease is a cerebral vasculopathy characterized by stenosis of the terminal internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery. There is an association between moyamoya vasculopathy and Graves disease, primarily in Asian populations. Here, we present the largest series of non-Asian, predominantly Latino patients with moyamoya vasculopathy in the setting of Graves thyrotoxicosis, as well as the largest review of the literature to date. METHODS: We retrospectively analyzed patients presenting with stroke in the setting of clinical Graves disease to our institution from 2004 to 2014. Moyamoya vasculopathy was diagnosed by magnetic resonance angiography in all patients. RESULTS: Eight patients with Graves disease thyrotoxicosis and moyamoya vasculopathy were identified. Six patients were effectively managed with aggressive medical management using antithyroid and antiplatelet medications. No recurrent strokes were noted once thyrotoxicosis was controlled. Intracranial bypass was necessary in 2 patients who failed medical management. Seventy-nine additional cases were reported from the literature. There was no significant difference in clinical improvement between medical therapy alone and medical therapy with neurosurgical prophylaxis (87.0% vs. 88.0%, respectively; P = 0.94). CONCLUSIONS: Moyamoya vasculopathy associated with Graves disease thyrotoxicosis in non-Asian women may be more common than previously thought. In addition, our series suggests that thyrotoxicosis promotes the progression of vasculopathy. Based on our review, there is no significant difference in clinical improvement between proper medical and surgical therapies. Aggressive medical therapy should be considered first-line treatment for moyamoya vasculopathy with Graves thyrotoxicosis, with neurosurgical rescue reserved for medically refractory cases.

Diffusion-weighted magnetic resonance imaging in symptomatic vertebrobasilar atherosclerosis and dissection.

BACKGROUND: Acute multiple brain infarction (AMBI) pattern on diffusion-weighted imaging (DWI) is associated with arterial and cardiac sources of embolism. The DWI characteristics of patients with stroke due to vertebrobasilar arterial dissection and atherosclerotic disease have not been reported in detail. OBJECTIVE: To describe the DWI stroke patterns in patients with posterior circulation occlusive disease to determine mechanisms of ischemia. DESIGN: Retrospective analysis of infarct patterns in patients with symptomatic vertebrobasilar disease. SETTING: Large community-based teaching hospital. PATIENTS: Patients admitted with stroke due to vertebrobasilar disease were identified retrospectively. Patients were included if DWI was obtained within 7 days of symptom onset. MAIN OUTCOME MEASURE: Infarct patterns were analyzed according to established templates of vascular territories. RESULTS: Eleven patients with vertebral dissection and 39 patients with atherothrombosis were identified. An AMBI pattern was present in 8 (72%) of 11 patients with arterial dissections and 25 (64%) of 39 patients with atherosclerotic disease (P = .48). Distal embolism to the terminal branches of the basilar artery occurred with equal frequency in both groups and was found in half of all cases. Isolated thalamic infarction did not occur. Pontine infarction was noted in 2 (18%) of 11 patients with dissections and 18 (46%) of 39 patients with atherosclerosis (P = .09). Cerebellar border zone involvement was found in 14 (36%) of 39 patients with atherosclerosis and 4 (37%) of 11 patients with dissections (P = .6). CONCLUSIONS: Large arterial disease is frequently associated with AMBI in the posterior circulation. The incidence of AMBI was comparable to that reported in the anterior circulation. This DWI study supports the importance of embolism as the main mechanism of infarction in patients with vertebrobasilar occlusive disease. On the basis of our experience, large-vessel vertebrobasilar disease rarely causes isolated small-vessel thalamic infarction.

Diffusion-weighted magnetic resonance imaging in internal carotid artery dissection.

BACKGROUND: Acute multiple brain infarction pattern on diffusion-weighted imaging is associated with arterial or cardiac sources of embolism. OBJECTIVES: To review the diffusion-weighted imaging characteristics of patients with strokes secondary to internal carotid artery (ICA) dissection and to gain further insights into the mechanisms of cerebral ischemia. DESIGN: Patients with ICA dissection and ischemic stroke were identified by review of an angiographic database and hospital discharge codes. Patients were included if the diagnosis of ICA dissection was confirmed and diffusion-weighted imaging was obtained within 10 days of symptom onset. Infarct patterns were analyzed according to established templates of vascular territories. RESULTS: Inclusion criteria were met by 14 patients. Internal carotid artery occlusion was present in 10. Acute multiple brain infarction was found in 10 (71%) of the 14 patients. Cortical involvement was found in 8 patients, while the infarct was restricted to the subcortical region in 6. In 9 (64%) of the 14 patients, ischemic lesions were located in 1 of the 3 border zones. CONCLUSIONS: Acute multiple brain infarction pattern with border zone involvement is frequently found in ICA dissection-related strokes. This finding may further support an interaction of hemodynamic and embolic mechanisms as a cause of cerebral ischemia in this condition.

Endovascular closure of a patent foramen ovale in the fat embolism syndrome: changes in the embolic patterns as detected by transcranial Doppler.

BACKGROUND: The posttraumatic fat embolism syndrome (FES) is characterized by petechiae and pulmonary and cerebral dysfunction. A patent foramen ovale (PFO) could worsen the prognosis of FES by allowing larger emboli to reach the systemic circulation. Transcranial Doppler ultrasonography can be used to diagnose and monitor cerebral microembolism in FES. OBJECTIVE: To describe a case of successful percutaneous closure of PFO in a patient with posttraumatic FES with excellent clinical outcome. PATIENT AND METHODS: A 17-year-old girl presented with a posttraumatic long-bone fracture complicated by typical severe FES. Transcranial Doppler disclosed multiple microembolic signals over both middle cerebral and basilar arteries. A large PFO was diagnosed by transesophageal echocardiogram. A brain magnetic resonance image with diffusion-weighted sequences showed multiple bilateral areas of abnormal diffusion in watershed territories. Percutaneous PFO closure with a buttoned device was successfully performed. RESULTS: Closure of PFO was associated with marked reduction in the number and intensity of microembolic signals. Subsequent surgical repair of the fracture with the patient under transcranial Doppler monitoring was uneventful. There was excellent correlation between clinical course and microembolic signal load by transcranial Doppler. CONCLUSIONS: Cerebral fat embolism after long-bone fractures can be detected in vivo and monitored over time with the use of transcranial Doppler techniques. If a PFO is present, its closure before surgical manipulation of the fracture is feasible and could have important protective effects against massive systemic embolization.

Detection of microemboli by transcranial Doppler ultrasonography in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the frequency and characteristics of microembolic signals (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the presence of MES and vasospasm. Each middle cerebral artery was monitored for 30 minutes three times each week. Patients were excluded if they had traumatic SAH or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1-16 d) after SAH and lasted 6.6 days (1-13 d). Eleven individuals without SAH or other cerebrovascular diseases who were treated in the same unit served as control subjects. Each patient underwent monitoring of both middle cerebral arteries a mean of three times; therefore, 46 vessels were studied (a total of 138 observations). Control subjects underwent assessment of each middle cerebral artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16 of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with 2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P < 0.05). MES were observed for 83% of patients with clinical vasospasm and 54% of those without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138 vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of those without vasospasm. Aneurysms proximal to the monitored artery were identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were common in SAH, occurring in 70% of cases of SAH and one-third of all vessels monitored. Although MES were more frequent among patients with clinical vasospasm, this difference did not reach statistical significance. We were unable to demonstrate a relationship between ultrasonographic vasospasm and MES, and the presence of a proximal secured or unsecured aneurysm did not alter the chance of detection of MES. Further studies are required to determine the origin and clinical relevance of MES in SAH.

Subclavian steal and a persistent trigeminal artery.

A persistent trigeminal artery (PTA) has been found in a number of cerebrovascular diseases. A 73-year-old asymptomatic woman was noted to have a left PTA and left subclavian steal by catheter angiography. Carotid duplex revealed a peak systolic flow velocity of 294 cm/s in the internal carotid artery (ICA) and an ICA to common carotid artery ratio > 4, suggestive of a high-grade stenosis. Only a low-grade stenosis was identified by catheter angiography. The elevated flow velocities in the left ICA were attributed to increased collateral blood flow across the stenosis to the left PTA, which compensated for the subclavian steal. Transcranial Doppler found an alternating flow pattern in the basilar artery (mean flow velocity [MFV] = 18 cm/s) and left vertebral artery (MFV = 43 cm/s). During brachial hyperemia, the MFV increased by 178% in the basilar artery and 102% in the left vertebral artery. The data suggest that a PTA may compensate for subclavian steal and may have a protective hemodynamic role in this setting.

Rapidly progressive dementia due to bilateral internal carotid artery occlusion with infarction of the total length of the corpus callosum.

The authors report a patient with rapidly progressive cognitive decline due to bilateral internal carotid artery occlusion (ICAO) resulting in multiple pathologically proven cerebral infarctions including the entire length of the corpus callosum. The gradual evolution of the deficits was suggestive of hemodynamic ischemia. Bilateral ICAO should be considered in the differential diagnosis of patients with rapidly cognitive decline. Although ICAO commonly spares the splenium, complete callosal infarction is possible in the presence of bilateral ICAO.

Brain microembolism.

PURPOSE: To alert clinicians about the occurrence of a subtype of brain infarction, its suspected etiology, and its detection by specific neuroimaging techniques. METHODS: The article presents 5 nonconsecutive patients admitted to the stroke services of 2 tertiary care hospitals, who presented with acute or subacute symptoms suspicious, but at times atypical, of brain ischemia. FINDINGS: Each patient had evidence of 3 to > 20 small areas of recent brain infarction detected by diffusion-weighted imaging (DWI). When available, brain computerized tomography images were not helpful for the diagnosis of these recent infarcts. Most lesions were present on magnetic resonance imaging fluid-attenuated inversion recovery sequences, but the diffusion-weighted images allowed the determination of their acuity. Further evaluation revealed a potential source of embolism in each patient. Brain microembolism was suspected in all cases. CONCLUSION: Small and multiple areas of acute or subacute brain infarction occasionally present with clinical features atypical for brain embolism. They can be detected by magnetic resonance DWI studies.

Cerebral vasomotor reactivity monitoring in posterior reversible encephalopathy syndrome.

A 25-year-old woman was admitted for vomiting, hypertension and seizures. Magnetic resonance imaging was compatible with posterior reversible encephalopathy syndrome and a transcranial Doppler/vasomotor reactivity study (TCD/VMR) demonstrated loss of vasomotor reactivity. The clinical recovery was concomitant to improvement in the TCD/VMR.

Ultrasound velocity criteria for vertebral origin stenosis.

BACKGROUND: Despite remaining an important cause of posterior circulation stroke, the non-invasive diagnosis of vertebral artery origin (VAo) stenosis is problematic. We here examine peak systolic velocity (PSV) criteria for the diagnosis of VAo stenosis and assess if the PSV ratio at the origin to the distal segments improves diagnostic accuracy. METHODS: We performed a retrospective analysis of patients studied by catheter cerebral angiography and extracranial Duplex ultrasonography. The angiographic degree of stenosis, PSV at the VAo, proximal vertebral artery (VA1), and intra-foraminal (VA2) segment were recorded. We calculated the VAo/VA1 and VAo/VA2 PSV ratio. A receiver operator curve was obtained (ROC) and the area under the curve (AUC) was compared for three different diagnostic criteria: PSV VAo, VAo/VA1, and VAo/VA2 PSV ratio. RESULTS: A total of 386 vertebral arteries were angiographically examined and VAo stenosis 50-99% was found in 36 (9%) vessels. The PSV VAo was the most accurate diagnostic parameter with an AUC .821 +/- .052 (SE) (CI: .72, .92). A PSV of 114 cm/second maximized sensitivity (71%) and specificity (90%). CONCLUSION: Our results support the use of PSV as a diagnostic criterion for VAo stenosis compared to a PSV ratio of VAo/V1 and VAo/V2.

Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety.

BACKGROUND: The optimal blood pressure (BP) for treating acute intracerebral hemorrhage remains (ICH) uncertain. High BP may contribute to hematoma growth while excessive BP reduction might precipitate peri-hemorrhage ischemia. We examine here the feasibility and safety of reducing BP to lower than presently recommended levels in patients with acute ICH. METHODS: Patients with ICH were prospectively randomized to standard BP treatment (mean arterial BP [MAP] 110-130 mmHg) or aggressive BP lowering (MAP < 110 mmHg) within 8 h of symptom onset. MAP was managed during the 48 h treatment period. NIHSS was obtained at baseline, 24, and 48 h. Brain CT was done 24 h after symptoms. A modified Rankin Scale (mRs) was obtained at 90 days. A clinical decline (NIHSS drop > or = 2 points) within the first 48 h was the primary endpoint. Hematoma enlargement at 24 h was a secondary endpoint. RESULTS: We enrolled 21 patients into each group. Mean age was 60.6 +/- 12.3 years and MAP on presentation was 147.6 +/- 18.2 mmHg. Treatment was started on average 3.2 +/- 2.2 h after symptom onset. Baseline clinical variables were identical between the 2 treatment groups. Target blood pressure was achieved within 87.1 +/- 59.6 min in the standard group and 163.5 +/- 163.8 min in the aggressive BP treatment group. There were no significant differences in early neurological deterioration, hematoma and edema growth, and clinical outcome at 90 days. CONCLUSION: A more aggressive reduction of acute hypertension after ICH does not increase the rate of neurological deterioration even when treatment is initiated within hours of symptom onset. Lowering BP aggressively did not affect hematoma and edema expansion but this possibility deserves further study.

Microemboli in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The determinants of ischemic complications in subarachnoid hemorrhage (SAH) are not well defined. The objective of this study is to evaluate the role of microemboli in SAH-related cerebral ischemia. METHODS: Forty patients with aneurysmal SAH were monitored with transcranial Doppler (TCD) for the presence of embolic signals (ES) and vasospasm, and followed clinically for the development of cerebral ischemic symptoms, from the time the aneurysm was secured until day 14 posthemorrhage or discharge. RESULTS: Microembolic signals were detected in 15/40 patients, appeared at a mean of 6.7 days after hemorrhage, and were often noted bilaterally. There was a close association between ES and cerebral ischemic symptoms (P= .003), and ES were commonly present in the distribution of the vessel with ischemic symptoms. Ultrasonographic vasospasm did not correlate with ischemia and there was no relationship between microembolic signals and vasospasm. CONCLUSIONS: In this study, ES detected in over a third of SAH victims, were associated with the development of cerebral ischemic symptoms, and were not related to vasospasm, but rather appeared to be an independent risk factor for the development of ischemic symptoms in SAH.